Anatomy & Physiology for Midwives 3: Third Edition

Chapter 13. Physiology of parturition

Learning objectives

• To describe uterine changes in pregnancy and its preparation for labour.

• To discuss theories of the initiation and timing of parturition in humans.

• To relate factors thought to be involved with initiation of labour to methods for inducing labour, possible causes and treatment of preterm labour.

• To describe the effects of labour on maternal and fetal physiology.

• To outline the physiology of pain in relation to childbirth and the rationale for choice of pain relief.


The success of pregnancy and, ultimately, the survival of the species, depend on the baby being born healthy and mature enough to survive. In pregnancy and labour, the uterus has to fulfil two very different functions. It has to grow but remain quiescent during pregnancy to allow fetal development and then, at the appropriate time, commence the powerful and coordinated contractions which result in the birth of the infant. However, parturition also requires the maturation of the fetal systems essential for extrauterine survival. The mother also needs to be physiologically prepared for lactation. Therefore, the maturation of the fetus and the onset of labour need to be synchronized. Asynchrony leads to preterm birth (≤37 weeks gestation).

Most human infants are capable of surviving birth and are born at term (defined as between the end of the 37th week and 42 weeks of pregnancy). Preterm birth rates are increasing and in 2005, 9.6% of all births (12.9 million) worldwide were preterm (Beck et al., 2010). 85% of preterm births occurred in Africa and Asia. The highest rates of preterm births occur in Africa (11.9% of all births) and North America (10.6%); Europe has the lowest rates (6.2%). Modern practices such as women giving birth at a later age and fertility treatment (and subsequent multiple gestation) have increased the incidence of preterm birth (Lawn et al., 2009). Low socioeconomic status, being of certain ethnicities or having low body mass index, bacterial vaginosis or other infections including periodontal disease, inflammation, vascular disease, uterine overdistension, stress, smoking and a history of preterm delivery and abortion are all risk factors for spontaneous preterm birth (Goldenberg et al., 2008). The causes of preterm birth are not well understood which limits effective obstetric and neonatal care. Therapeutic approaches currently focus on arresting established preterm labour; early diagnosis, treatment or primary prevention of preterm birth are surprisingly unsuccessful.

Chapter case study

While working in Africa, Zara had been able to assist several of her African friends during childbirth, all of which had occurred at home and attended by mostly female relatives who had informed Zara that they would only call the local midwife if they felt things were going wrong. All her friends had had uncomplicated deliveries and Zara felt quite privileged to have witnessed childbirth in such a different way to how it is presented within most modern Western societies.

Zara is keen to have a waterbirth at home and wants to avoid all forms of pain relief. She also wants her sister and some of her close friends who are also heavily pregnant to be present if possible. As Zara has had all her antenatal care from her midwife, she particularly wants her midwife to care for her in labour, especially as her midwife has extensive experience of waterbirth.

• What factors do you think will be a positive influence on enabling Zara to have a normal birth?

Preterm birth is the predominant cause of perinatal morbidity and mortality in developed countries. Most early neonatal deaths, that are not associated with a lethal deformity, are associated with prematurity and preterm infants have an increased risk of complications not just in the neonatal period but in the long-term (Saigal and Doyle, 2008). Long-term consequences include cognitive and motor neurodevelopment disabilities that include cerebral palsy, mental retardation, deafness, blindness, learning disabilities, chronic lung disease and possibly an increased risk of disease in adult life. The shorter the gestation, the poorer the prognosis is. Even though very low-birth-weight babies (i.e. those born below 1000 g) may now survive, it is generally associated with rates of morbidity and much emotional stress for their parents, as well as a high financial burden on neonatal intensive care units. There are also long-term health and education costs associated with physical and mental handicap and neurodevelopmental complications. It can be argued that one of the principal objectives of obstetrics is to reduce preterm labour. The survival rate of premature infants born alive with borderline viability has improved over the last decade (Field et al., 2008), however improved survival rates have not been matched by a proportional decrease in the incidence of disability (Stephens and Vohr, 2009).

There are three categories of causes of preterm birth: iatrogenic or indicated, where complications of pregnancy such as eclampsia, pre-eclampsia or intrauterine growth retardation, enforce obstetric intervention and the deliberate induction of premature delivery (30–35% of cases); preterm premature rupture of (fetal) membranes (PPROM), which may be associated with infection (25–30% of cases); and spontaneous or idiopathic preterm labour (40–45% of cases; Goldenberg et al., 2008). The failure of spontaneous labour is also not well understood; prolonged pregnancy (gestation >42 weeks or 294 days) is also associated with increased fetal morbidity and mortality.

The factors controlling the transition from one state to the other are not well understood but are very important both in determining the possible causes of preterm labour and in understanding how to induce labour successfully without eliciting fetal distress. The control of the onset of human (and primate) parturition remains elusive. There are marked differences between human and other mammalian species in the cascade of factors leading to parturition. Humans have a very high rate of premature birth compared with other species. For most domestic and laboratory animals the duration of gestation is remarkably constant; for example, there is less than 1% variation in sheep (Jenkin and Young, 2004). Theoretically, the length of gestation does not matter to the mother. The crucial aspect is that the baby can survive from birth. It seems plausible, therefore, that the fetus controls the length of gestation. Certainly, in some experimental animals, for example sheep, there is proven fetal involvement in the timing of labour but it is difficult to obtain such evidence in humans.

In other species, it seems that the same signal controls fetal maturation and triggers the onset of labour so parturition is synchronized. In humans, the two pathways seem to be separable (Fig. 13.1). The human fetus appears to undergo lung maturation 4–6 weeks before labour, unlike other species in which the signals initiating labour also stimulate fetal organ maturity. It is not clear why the events leading to parturition should be so complex in the human; however, it seems plausible that a variable length of gestation is advantageous. The complexity of control of parturition in humans might allow a transfer of control from mother to fetus. Thus, in early pregnancy, it may be physiologically expedient for the mother to terminate the pregnancy if it is harmful for her long-term health to continue. Spontaneous termination of a pregnancy that is unlikely to be completed, for example because maternal nutrient intake is insufficient, prevents needless maternal investment. Later in gestation, once the fetus is mature enough to survive, fetal control of parturition would allow the fetus to remain in the uterus if the environment was favourable. The fetus could respond to stress by switching from cell division and growth to accelerated maturation and earlier initiation of parturition. This would suggest that intrauterine growth restriction is part of an adaptive response to fetal stress which increases survival as long as the stressor is not too early or too severe. It is not surprising, therefore, that many of the signals involved in parturition are also involved in physiological stress responses. Midwifery and obstetric management of women in labour is often interventionist. This chapter covers the physiology of parturition; for information about clinical management, readers are referred to midwifery texts in the list of further reading.

B9780702034893000307/f13-01-9780702034893.jpg is missing

Fig. 13.1

The two distinct pathways controlling parturition and fetal development in the human.

Stages of labour

From a clinical point of view, labour is often divided into three stages (Fig. 13.2). However, physiologically there is no abrupt transition between stages. The events leading to the onset of labour are gradually and inconspicuously initiated earlier in the pregnancy, and the three stages overlap. The first stage is that of progressive cervical dilatation, timed from the onset of regular coordinated contractions accompanied by progressive effacement (thinning) and dilatation of the cervix. The end of this stage is marked by the full dilatation of the cervix as the uterine contractions pull the entire tissue of the cervix upwards until it becomes incorporated into the lower uterine segment, continuous with the uterine walls. This stage lasts an average of 12–14 h in primigravidae, but tends to be shorter in multigravidae. The second stage is fetal expulsion, from full cervical dilatation until the delivery of the baby. The contractions are strong and aided by the respiratory muscles. The second stage may take over an hour in primigravidae and as little as a few minutes in multigravidae. The third stage of labour involves separation and complete expulsion of the placenta and membranes, and control of bleeding from the uteroplacental circulation. The return to the prepregnant state is described as the puerperium (see Chapter 14).

B9780702034893000307/f13-02-9780702034893.jpg is missing

Fig. 13.2

Stages of labour.

From a physiological point of view, it is useful to think of labour being related to phases of uterine myometrial activity. For most of pregnancy, the uterus is in phase 0, the quiescent phase. Under the influence of progesterone (the literal meaning of progesterone is ‘pro-gestation’, i.e. promoting and sustaining pregnancy), the uterus is relatively quiet and non-responsive to stimuli. Other factors involved in quiescence are prostacyclin, nitric oxide, relaxin, parathyroid hormone-related peptide, calcitonin gene-related peptide and vasoactive intestinal peptide (Terzidou, 2007). All these factors act to increase cAMP (or cGMP) and thus inhibit the release of intracellular calcium that is required for myometrial activity. In late pregnancy, the uterus changes from being quiescent (having a low level of muscle activity) to being activated; this is known as phase 1, the activation phase. This transition to activation is the initiation of labour; labour results from activation and then stimulation of the myometrium. The receptors and signalling pathways are modulated so they respond to contractile stimuli. Activation is partially stimulated by mechanical stretch of the uterus together with changes in signalling via endocrine and paracrine pathways, possibly resulting from an increased activity of the fetal hypothalamic–pituitary–adrenal (HPA) axis. Increased levels of oestrogen and CRH lead to an up-regulation of genes involved in contraction including genes for connexin 43, prostaglandins and oxytocin receptors. The increased production of oestrogen may be due to increased availability of fetally derived precursors. In the third phase of parturition, phase 2 - stimulation, the activated uterus is spontaneously excitable and responsive to uterotonins such as prostaglandins, oxytocin and CRH; it develops coordinated, effective and forceful contractions. The activation of the uterus in this stimulation phase is the start of a positive feedback loop whereby the initial signals become further amplified and the uterus becomes fully stimulated allowing progression of the first and second stages of labour. This phase is accompanied by inflammatory-like biochemical changes. There is increased synthesis of prostaglandins and cytokines and an influx of neutrophils which produce proteases which are involved in remodelling and ripening of the cervical tissue. The uterus is able to perform a remarkable mechanical effort to expel its contents – the baby, placenta and associated membranes and fluids – through the birth canal (Fig. 13.3). The final phase is the uterine involution phase.

B9780702034893000307/f13-03-9780702034893.jpg is missing

Fig. 13.3

Expulsion through the birth canal.

The uterus at term

Uterine growth in pregnancy

The uterine muscle undergoes exceptional growth throughout pregnancy to accommodate the growing fetus. The prepregnant weight of the uterus is about 50 g in a nulliparous woman and about 60–70 g in a multiparous woman with a capacity of about 10 mL. During pregnancy, uterine size increases 20-fold, to about 800–1200 g and a capacity of about 5 L. Initially, the uterus grows by hyperplasia (increasing cell number). This is under the influence of oestrogen and, unlike later growth, occurs regardless of the site of implantation. By the 4th month, the uterine wall has thickened from 10 to 25 mm. Subsequent growth is due to hypertrophy and stretch stimulated by uterine distension. The uterine wall thins and the smooth muscle cells increase markedly in length (from 50 to 500 μm long and from 5 to 15 μm wide) as they accumulate contractile proteins. The increased overall size is accompanied by a change in uterine shape from a sphere to a cylinder. By term, the organization of the myometrial cells allows coordinated, strong and effective contractions to develop. The uterine muscle is innervated by adrenergic, cholinergic and peptidergic fibres, which are more abundant in the cervix and uterine tubes. The uterus also has many sensory nerves. By the third trimester, the uterine wall is thin, about 5–10 mm by term; the fetal movements are visible and the fetus can be palpated through the uterine wall (Blackburn, 2007). The uterus almost reaches the liver and displaces the stomach and intestine. The blood vessels in the non-pregnant uterus are extremely tortuous and coiled (see Chapter 2); this allows them to adapt to the increased requirements of the expanding uterine tissue. Uterine blood flow increases in pregnancy as the blood vessel diameter increases and resistance to flow decreases.

Uterine muscle organization

The uterus is predominantly comprised bundles each of 10–50 myometrial (smooth muscle) cells separated by connective tissue, formed of collagen and elastin. The distribution of the smooth muscle varies throughout the length of the uterus. The smooth muscle density is highest in the fundus of the uterus (an approximate ratio of smooth muscle fibres:connective tissue of 90:10) and gradually declines until the cervix where the ratio is 20:80. Associated with the myometrium are leukocytes which produce cytokines. Pro-contractile proteins such as oxytocin receptors and connexin 43 are preferentially expressed in the fundal region of the uterus. The isthmus, which forms the lower segment of the uterus, has lower smooth muscle content. The lower segment forms at about weeks 28–30 of pregnancy. Caesarean sections late in gestation are usually via the lower segment of the uterus (lower-segment caesarean section, LSCS), whereas the incision in an emergency ‘classic’ caesarean section earlier in pregnancy usually is on the midline of the uterus and is likely to dictate the method of delivery in future deliveries. Contractile strength is related to the proportion of smooth muscle (Petersen et al., 1991). Therefore, the upper part of the uterus contracts strongly and the lower segment, which has a diminishing proportion of muscle, contracts weakly and passively (see Fig. 13.10, p. 338).

The uterine muscle forms three distinct anatomical layers, which are more evident with the hypertrophy of the uterus that occurs in pregnancy (Fig. 13.4). The innermost layer has muscle mostly in a longitudinal orientation. The myometrium has more muscle fibres in the inner layer than it does in the outer layers (Terzidou, 2007). The outermost layer has longitudinal and circular fibres. The middle layer of uterine muscle has spiralling fibres and is particularly well vascularized. It is this middle layer that ensures the blood vessels in the uterus are occluded in the third stage of labour as the spiralling fibres contract around the blood vessels. The lower uterine segment has a high expression of CRH receptor type I which is involved in relaxation and of the enzymes involved in cervical ripening.

B9780702034893000307/f13-04ab-9780702034893.jpg is missing

Fig. 13.4

Uterine muscle layers: (A) the inner and outer muscle layers; (B) spiral organization of central smooth muscle fibres.

(Reproduced with permission from Sweet and Tiran, 1996.)

The myometrium

The myometrium is formed of myometrial cells embedded in a collagen-rich connective tissue matrix which has blood vessels interspersed within it. The cytoplasm of the myometrial cells or myocytes is packed with long random bundles of actin and myosin. Compared with skeletal muscles, the concentration of actin is higher and the myosin has longer filaments, which increases the maximum shortening of the contractile cells. Myosin is both a structural protein and an Mg-ATPase, an enzyme that can hydrolyse ATP and utilize the energy for movement. When ATP is hydrolysed (broken down), actin and myosin cross-bridges form so actin and myosin slide past each other, shortening the cell so that the muscle contracts (Fig. 13.5). Myosin is made up of two heavy chains forming the ATPase and two light chains, which bind calcium and undergo phosphorylation. Phosphorylation is the incorporation of a phosphate group catalysed by a kinase, in this case myosin light-chain kinase (MLCK) which effectively activates the protein. Factors that negatively affect myometrial contractility may be important in maintaining uterine quiescence through pregnancy; those that increase contractility may be important in facilitating the progression of labour.

B9780702034893000307/f13-05-9780702034893.jpg is missing

Fig. 13.5

Cell shortening and myosin contractile elements in myometrial muscle contraction: (A) relaxed; (B) contracted.

The role of calcium

Muscle contraction is triggered by a rise in the intracellular concentration of calcium ions. Electrical activity, calcium ion influx and development of myometrial tension are precisely synchronized (López Bernal, 2003). Calcium ions bind to the calcium-binding protein calmodulin (CAM) which regulates the activity of many of the intracellular enzymes generating a cascade of reactions leading to binding of actin and myosin (Wray et al., 2003). Binding of calcium to CAM forms a Ca–CAM complex which activates MLCK. MLCK is inhibited when calcium levels are low. The activated MLCK undergoes a conformational change which exposes the catalytic site so the MLCK can be phosphorylated and will interact with actin, initiating contractions. Removal of calcium results in dephosphorylation of myosin by myosin light-chain phosphatase and causes muscle relaxation. Smooth muscle contraction can therefore be increased either by activating MLCK or by inhibiting myosin phosphatase.

Calcium enters the myometrial cell from the extracellular fluid or is released from intracellular binding sites and organelles including the sarcoplasmic reticulum of the myometrial cells. Calcium released from the sarcoplasmic reticulum can prime contractions that need to be sustained by calcium influx. Voltage-operated calcium channels regulate contractility by allowing calcium entry. Calcium-activated potassium channels set the threshold of activation of the cell membrane. There is a good correlation between intracellular calcium concentration and the muscular force developed with ionized calcium (Ca2+) concentration increasing from approximately 100–500 nm during contraction. Uterotonins (substances that stimulate myometrial contractility), such as prostaglandins and oxytocin, increase calcium influx and mobilize intracellular calcium stores, therefore increasing intracellular calcium concentrations and MLCK phosphorylation and increasing myometrial activity. Agents that inhibit myometrial activity, such as progesterone, β-mimetics, relaxin and prostacyclin, decrease intracellular Ca2+ by promoting calcium uptake into the intracellular stores such as the sarcoplasmic reticulum so free calcium levels decrease and the uterine muscle relaxes. Calcium channel blockers, such as nifedipine, prevent calcium entry into the cells promoting relaxation of the uterus.

The control of myometrial contractions

Intracellular calcium levels (and myometrial activity) are controlled by various receptors on the myometrial cell surface. Most hormones that affect myometrial contractility bind to receptor sites that are coupled to one of two G-proteins: Gαs or Gαq (see Chapter 3Bernal et al., 1995). The G-proteins act as transducers between the receptor and the effector regulating the cellular response by coupling the receptor to different signal-generating enzymes within the cell. These enzymes, in turn, generate an amplifying cascade of second messengers. The G-proteins allow the myometrial tissue to respond to a large number of agonists with a limited number of effects, either relaxation or contraction (Fig. 13.6). One of the G-protein pathways (Gαq) is linked to the inositol phosphate pathway. Binding of agonists (uterotonins) to receptors coupled to this G-protein activates phospholipase C (PLC), generating inositol triphosphate and diacylglycerol. Inositol trisphosphate stimulates the release of calcium ions from the sarcoplasmic reticulum and diacylglycerol activates the enzymes protein kinase C and phospholipase A. The latter releases arachidonic acid from membrane phospholipids; arachidonic acid is the precursor of prostaglandins. The result is a rise in intracellular calcium and therefore smooth muscle contraction. The other G-protein pathway (Gαs) activates adenylate cyclase, an enzyme that generates cyclic adenosine monophosphate (cAMP) and inhibits release of calcium. Agonists that stimulate this pathway, such as β-adrenergic receptor agonists and prostacyclin, will cause decreased release of Ca2+ from intracellular Ca2+ stores and dephosphorylation of myosin (so MLCK cannot bind Ca–CAM) and thus uterine relaxation (Yuan and López Bernal, 2007).

B9780702034893000307/f13-06-9780702034893.jpg is missing

Fig. 13.6

The regulation of muscle contraction by G-proteins.

Gap junctions

The onset of regular uterine contractions is gradual. As pregnancy progresses, the resting potential of the myometrial cells falls so that action potentials are generated with greater ease. Initially spontaneous uterine contractility is inhibited but becomes significant by mid-gestation. At about 20–24 weeks, hardening (or ‘tightening’) of the uterus can be felt as muscle contractions start. Initially, uterine activity is mostly of low amplitude and high frequency, with peak activity at night. This circadian rhythm stops at about 3 weeks before delivery, and may be mediated by cortisol (Germain et al., 1993). At first, small groups of myometrial cells contract together causing small fluctuations in intrauterine pressure. As pregnancy progresses, adjacent cells begin to contract synchronously so the contractions become more coordinated. This increased coordination results from cell–cell coupling and is due to the formation of intercellular gap junctions.

Gap junctions are formed from bundles of proteins, called connexins, that align forming pore-like symmetrical channels protruding through adjacent cells, so allowing contact and communication. Gap junctions exist in other tissues that act together in a coordinated fashion, such as cardiac muscle and pancreatic islets. In the open state, gap junctions allow rapid transmission of signals such as electrical stimuli and second messengers such as calcium and inositol trisphosphate (Fig. 13.7). This means that depolarization and smooth muscle contraction in one cell are quickly communicated to adjacent cells so there is a spread of excitation and a synchrony of contractions.

B9780702034893000307/f13-07-9780702034893.jpg is missing

Fig. 13.7

The gap junction.

There is an increase in the synthesis of gap junctional protein connexin 43 and the number of gap junctions increases during gestation to about 1000 per myometrial cell. Physiological regulation of connexins and formation of gap junctions is by prostaglandins and steroid hormones; oestrogen and some prostaglandins increase and progesterone and nitric oxide suppress gap junction formation (Garfield et al., 1988). Gap junction density can be determined by measuring electrical resistance of tissue. The resistance of human myometrium at term is about half of that in the non-pregnant uterus and much less than that in other smooth muscle (for instance bladder and stomach), which indicates that the cells of the pregnant myometrium are very well coupled. Gap junction formation increases prior to spontaneous labour, resulting in synchronization and coordination of high-amplitude high-frequency myometrial contractions so increased intrauterine pressure is generated (Neulen and Breckwoldt, 1994). This is why palpation especially near to term, can stimulates uterine tightening; palpation initiates the first stimulation of the uterus which then spreads throughout the myometrium. Often fetal movements will trigger uterine tightening for the same reasons. Suppression of gap junctions may be important at the time of implantation and in early pregnancy (Grummer and Winterhager, 1998).

Uterine contractions and quiescence

The uterus exhibits spontaneous contractility. A biopsy specimen of uterine tissue, placed in a physiological solution, will contract involuntarily every 2–5 min without stimulation. During the menstrual cycle, three patterns of uterine contractility have been described (De Ziegler et al., 2001). At the beginning of the cycle (menstruation), all layers of the myometrium contract exerting anterograde (from fundus to cervix) expulsive forces; these contractions may be associated with painful cramps (dysmenorrhoea). During the receptive window, in the late follicular phase, uterine contractility involves only the inner layers of the myometrium and is gentle and not perceived by women; this facilitates retrograde (cervix to fundus) transport of sperm towards the uterine tubes where fertilization usually takes place (see Chapter 7). As progesterone levels rise after ovulation, the uterus reaches a stage of quiescence. In pregnancy, progesterone continues to increase and to suppress the rhythmic activity of the uterus. Progesterone decreases the expression of genes for contraction-related proteins, stimulates the relaxant pathways and suppresses the stimulatory pathways of the myometrium and inhibits the binding of oxytocin to its receptors (Mitchell and Taggart, 2009). Other inhibitors of uterine contractions early in pregnancy include relaxin, prostacyclin and nitric oxide, all of which increase intracellular cAMP and/or decrease intracellular calcium levels. It is also suggested that human chorionic gonadotrophin (hCG) inhibits myometrial contractility (Slattery et al., 2001).

However, the uterus is never completely quiescent. From about 7 weeks, the contractions, or ‘contractures’, are irregular, not synchronized and focal in origin; they have a very high frequency and a very low intensity (Wray, 1993). From mid-gestation, the contractions increase gradually in intensity and frequency until about 6 weeks before term when their intensity increases more markedly. The early Braxton Hicks contractions can be perceived but, although strong, they are not normally painful as the cervix remains closed. In labour, the contractions become synchronized, regular and more intense with increased duration. In primate models, in the few days before delivery, uterine contractions become synchronized during the night and disappear during the day until delivery. This pattern has not been observed in humans but women do have periods of active contractions which then cease suggesting there is also a degree of reversibility in the early stages of human labour (Smith, 2007).

The characteristics of the myometrium change markedly during pregnancy (Shynlova et al., 2009). In early pregnancy, there is a proliferative phase when the expression of IGF proteins is increased and an anti-apoptotic pathway is up-regulated. This is followed by a synthetic phase of growth and remodelling involving cellular hypertrophy and increased synthesis of extracellular matrix proteins. In the third phase the myometrial cells develop a contractile phenotype exhibiting increased excitability and sensitivity to calcium, spontaneous activity and enhanced responses to agonists. In the final phase of pregnancy, the myometrial cells are highly active and committed to labour. The cells are more excitable, there is increased connectivity between the cells and there are changes in the contractile proteins. In this phase, the myometrial cells actively participate in the inflammatory process by producing pro-inflammatory cytokines. There is a further stage of postpartum uterine involution (see Chapter 14).

The cervix

The consistency of the cervix changes in pregnancy to become softer and compliant in preparation for labour. For most of pregnancy, the cervix is a rigid cylindrical structure about 4–7 cm long which forms a closed canal (Mitchell and Taggart, 2009) though in women who have had a previous vaginal delivery, the cervix may be slightly shorted with an internal diameter of about a centimetre. The cervix consists mostly of collagen fibrils, elastic connective tissue and blood vessels with some smooth muscle fibres. Connective tissue changes affect the whole uterus but are more evident in the cervix. The uterine contractions imposed on the softened cervix result in it changing shape. During the pregnancy, the role of the cervix is to act as a closure for the uterus containing its contents and protecting them from ascending infection. Prior to the delivery of the baby, the cervix loses its structural rigidity and is pulled by the uterine contractions so it changes from being a tubular closure to becoming a wide-funnelled canal with very thin edges that is continuous with the rest of the uterine structure. In primigravida women, this shape change occurs in two distinct stages.

The first stage of cervical change is effacement, where the cylindrical shape is transformed into a funnel, but the internal sphincter, or os, is still patent and closed. The longitudinal muscle fibres of the cervix shorten. The differential localization of the fibres means that the outer margins of the cervix develop more tension so maximum uptake of the cervix occurs at the lower end and the external os and softer cervical tissue move upwards into the lower uterine segment (Gee and Olah, 1993). During vaginal examination, a midwife might feel an ‘effacement ridge’ of the cervical tissue undergoing effacement (Fig. 13.8) the ridge is the dissipating form of the external os.

B9780702034893000307/f13-08-9780702034893.jpg is missing

Fig. 13.8

The differential movement of tissue planes at the time of cervical effacement and early dilatation. M, direction of movement of collagen bundles; T, differential tension across the myometrium.

(Reproduced with permission from Sweet and Tiran, 1996.)

The second stage begins when full dilatation is reached (the edges of the internal os can no longer be felt); the uterus and vagina form one continuous ‘sleeve’ opening for the exit of the fetus. In multiparous women, the transition from one stage to the other is far less abrupt so effacement and dilatation occur simultaneously. Dilatation is due to the retraction or shortening of the upper part of the uterus, rather than pressure from the descending presenting fetal part. Therefore, if there is no effective presenting part, as in a transverse lie, cervical dilatation still occurs. The dramatic changes in the cervix result from a combination of structural changes in the tissue and forces exerted by the uterine contractions.

The cervix is predominantly composed of fibrous connective tissue plus some smooth muscle and fibroblasts together with blood vessels, epithelium and mucus-secreting glands. The rigidity of the cervix is related to its high content of collagen, particularly type I and type III collagen. There are two elements to cervical softening: increased vascularity and water content, and structural changes in the connective tissue. At term, 90% of the weight of the cervix is water. Connective tissue is formed of collagen fibres and elastin held together by an extracellular matrix, or ground substance. The ground substance is predominantly composed of proteoglycans, which coat the collagen fibres and modify their physical properties, determining the water content of the tissue. Hormones that promote cervical softening affect the composition of the ground substance. Prior to the onset of labour, there is increased expression and activity of matrix metalloproteinases (MMP) which leads to a progressive breakdown of the collagen matrix; the composition of the proteoglycans changes so that dermatan sulphate decreases and hyaluronic acid and glycosaminoglycans increase. Dermatan sulphate binds collagen fibrils tightly, whereas hyaluronic acid has a lesser affinity for collagen and attracts water. Although the proteoglycans are a minor constituent of the cervix, they have an amazing ability to bind water: 1 g of hyaluronic acid can bind about 1 L of water (Uldbjerg and Malstrom, 1991). The increased level of hyaluronic acid may act as a signal to activate resident macrophages and neutrophils to secrete interleukins. Interleukins increase prostaglandin activity and neutrophil migration and degranulation (releasing collagenase and elastase). Two other glycoproteins are also involved in cervical changes. Decorin binds and immobilizes the collagen fibres thus stabilizing the structure of the extracellular matrix in early pregnancy. Concentrations of decorin fall in late gestation. Fibronectin binds dermatan sulphate and collagen, protecting collagen from collagenase and stabilizing the extracellular matrix. Hyaluronic acid weakens the interaction of collagen with fibronectin.

The mechanical strength of the ground substance changes as the water content increases and the number of cross-links between elements of the connective tissue diminishes. The collagen increases in solubility and becomes disorganized and weakened (like a fraying rope) so it is more vulnerable to enzymatic digestion. Collagen is resistant to most proteases except collagenase from fibroblasts and neutrophil elastase. Amounts of neutrophil elastase in the cervix significantly increase at term. The association between intrauterine infection and premature labour may be linked to neutrophil infiltration and activation. The effects of oestrogen on cervical ripening are suggested to be mediated by insulin-like growth factor I (IGF-I; Stjernholm et al., 1996). Collagenolysis is a complex balance between availability of free collagenase and the inhibitory proteins. Connective tissue in the body of the uterus also changes at term altering uterine compliance. The level of elastin increases throughout the pregnancy. It provides the elastic recoil that coordinates the contraction–retraction cycle and is important in the return of the uterus to its normal shape after delivery.

Although the cervix has relatively little smooth muscle tissue, it may have an important functional role as a sphincter. The cervix constricts with uterine contractions in early labour (Olah, 1994). It is suggested that this coordinated muscular activity is important in the maintenance of cervical integrity during Braxton Hicks contractions before labour (Steer and Johnson, 1998).

Cervical ripening is predominantly an inflammatory process. Macrophages and neutrophils infiltrate the cervical tissue towards term. They produce cytokines and elastases and collagenases which digest the extracellular matrix proteins.

Assessment of cervical effacement

In practice, the cervix can be assessed by using a simple scoring system, the Bishop's score (Table 13.1). This is particularly useful prior to induction of labour and for monitoring the changes in the cervix as the induction progresses.

Table 13.1 Bishop's Score

Bishop's Score




Station of presenting part




Position of cervix







Very soft


3–4 cm

1–2 cm

<1 cm

Dilation of cervix


1–2 cm

>2 cm


(Bishop's score)

If the cervix is soft, effaced and has started to dilate, induction may be implemented by artificial rupture of the membranes, which augments endogenous prostaglandin production. If the cervix is less favourable, prostaglandin E2(PGE2) is administered into the posterior fornix of the vagina to facilitate effacement. However, PGE2 should be used with caution in multiparous women because they have a greater sensitivity to it.

The cause of these structural changes in the cervix is not clear. It is thought to be hormonally controlled. Relaxin has been shown to be important in cervical ripening in rodents and has been used clinically to promote cervical ripening in humans. However, the levels of endogenous relaxin in pregnant women seem to be highest at the beginning of the second trimester. Oestrogen affects the synthesis of connective tissue components in vitro but has limited success when used pharmacologically as an induction method. PGE2 causes cervical softening or ‘ripening’ and is produced naturally by both the cervix and the fetal membranes. PGE2 appears to act by increasing collagenolytic activity rather than by changing the composition of the ground substance, which probably precedes prostaglandin use in successful induction of labour. Following delivery, glycoproteins that bind strongly to collagen are re-formed so the rigidity of the cervix is re-established; however, it never completely regains its original form (see Chapter 14). Damage to the cervix may have long-term consequences (Box 13.1).

Box 13.1

Clinical issues relating to the cervix

Longitudinal fibres allow full dilatation of the cervix to be achieved without the pressure of a presenting part, for instance in the case of a transverse lie. Artificial dilatation of an unprepared cervix may damage the collagen fibres. This can result in the cervix failing to remain intact during subsequent pregnancies, resulting in habitual spontaneous abortion, usually in mid-trimester. Preoperative preparation to avoid this involves the administration of a prostaglandin derivative, which induces cervical softening and aids artificial dilatation of the cervix. This method is used prior to procedures involving exploration of the uterine cavity such as termination of pregnancy, evacuation of retained products of conception, surgical ablation of the endometrium and investigation of infertility.

Initiation of parturition

Animal models of parturition

Parturition in sheep has been studied in detail. Based on the assumption that mammals are likely to share similar physiological mechanisms for the onset of labour, clinical procedures derived from understanding the mechanisms of parturition in sheep were developed, both for inducing labour and for inhibiting preterm labour in humans. Progesterone is essential for pregnancy maintenance in sheep and the fetal lamb plays a crucial role in the timing of labour. Initiation of labour in sheep is driven by the maturation of the fetal brain; the effect is that progesterone falls resulting in increased uterine activity. Expression of pro-opiomelanocortin (POMC), the precursor of adrenocorticotrophic hormone (ACTH), progressively increases in the pituitary from mid-gestation as the fetal brain matures (Challis et al., 2000). Regulation of secretion of pituitary ACTH in the fetal lamb is by antidiuretic hormone (ADH, also known as vasopressin) and corticotrophin-releasing hormone (CRH). Thus, the first indicator of impending labour in sheep is a sharp rise in fetal cortisol levels due to mature secretion of ACTH from the pituitary gland and increased adrenal sensitivity to ACTH. Removal or abnormal development of the fetal lamb pituitary gland prevents the onset of labour. Infusion of ACTH, cortisone or dexamethasone (a cortisol analogue, frequently used as an anti-inflammatory drug) into the sheep fetus induces labour. Fetal stress such as hypoxia and undernutrition can stimulate preterm birth in sheep (Warnes et al., 1998) by increasing fetal HPA maturation.

The effects of raised cortisol levels are naturally efficient and both promote fetal organ maturity (functional maturation of the fetal lungs and other systems) and initiate labour. Cortisol induces 17α-hydroxylase activity in the placenta that promotes the conversion of C21 steroids to C18 steroids. Thus 17α-hydroxylase converts progesterone to oestrogen so that the progesterone:oestrogen ratio alters in favour of oestrogen. This increases prostaglandin (PGF) synthesis by the placenta and myometrium. The alteration in oestrogen and progesterone levels can be measured prior to the onset of labour. Exogenous oestrogen induces labour and infusion of progesterone inhibits labour in the sheep. Increasing oestrogen or decreasing progesterone levels stimulates the synthesis of PGF. Prostaglandins increase myometrial sensitivity to oxytocin. PGF is important in cervical softening and increases uterine contractility. A positive feedback mechanism, known as the Ferguson reflex, amplifies the signals. The pressure of the fetal presenting part on the cervix activates a neurohumoral reflex whereby afferent nerves from the cervix impinge on the hypothalamus and increase oxytocin release from the posterior pituitary gland. Oxytocin stimulates uterine contractions and causes further release of PGF from the uterus. However, initiation of labour in the human is different in a number of respects from that in the sheep. Note that pregnancy in some species, such as goats, rabbits and rodents, depends on progesterone secretion from the corpus luteum because the placenta is not the source of progesterone. Luteolysis, mediated by PGF, causes a fall in progesterone and initiation of parturition in these species. The fetus does not seem to play such an important role in the timing of parturition in these species as it does in sheep.

Initiation of parturition in humans

The mean length of human gestation is 39.6 weeks and the majority of births occur between 38 and 42 weeks (Steer and Johnson, 1998). Such a wide range of gestation times in normal pregnancy suggests the timing mechanism is not precise, possibly because it is affected by a number of factors including external influences. The fetus seems to maintain the pregnancy actively. Labour invariably ensues after fetal death has occurred, although it might be delayed by a few weeks (and therefore be pre-empted by mechanical removal of the products of conception). Labour occurs sooner if placental damage has occurred. The critical events permitting extrauterine survival are adequate maturation of the fetal lung and nervous system. The fetal brain may monitor this maturation and control the timing mechanism. Mothers of fetuses with brain abnormalities still progress into labour spontaneously but with a much wider range of gestation (see below). This suggests the fetal brain affects the precise timing of labour in humans, rather than controlling the exact length of gestation.

Hormonal changes associated with parturition in humans

The role of the fetal pituitary–adrenal axis

In sheep, maturation of the fetal HPA initiates parturition. Human fetal malformations such as anencephaly (no cerebrum), malformed pituitary glands or hypoplasia of the adrenal glands are associated with an increased range of gestation length (both longer and shorter) but women still undergo spontaneous labour (Steer and Johnson, 1998). In sheep, similar fetal malformations, either accidental or deliberate, result in significantly prolonged gestation which adversely affects the fetus. This implies that the fetal–adrenal axis has a supportive rather than a direct role in parturition, acting to fine tune the gestational length in humans, rather than functioning as the ‘on–off switch’ for the initiation of labour, as seen in sheep.


It is evident that the human fetal anterior pituitary gland undergoes maturational changes in the last weeks of gestation as the profile of hormonal release changes. However, there are no defined changes measurable in the maternal circulation prior to the onset of labour. The raised cortisol levels in the cord blood of infants, who have experienced a spontaneous delivery rather than an induced one, or delivery by caesarean section, are maternally derived and are secondary to maternal pain. Labour itself, whether spontaneous or induced, causes stress and therefore an increased production of cortisol, which can cross the placenta. It is possible to differentiate between cortisol of maternal origin and cortisol of fetal origin by comparing the levels in umbilical cord arterial blood with those in the cord vein. Blood in the vein flows from the placenta to the fetus so if cortisol levels are higher in the vein than in the arteries this suggests the source of cortisol is maternal.

Exogenous corticosteroids (such as dexamethasone and betamethasone) given to a pregnant woman at 24–34 weeks to promote fetal lung maturity (see Chapter 15) do not initiate parturition, although oestrogen and cortisol levels fall. Pharmacological doses of glucocorticoids introduced into the amniotic fluid increase uterine activity and induce labour; however, this effect is not observed with physiological doses. Most researchers have not been able to measure an increase in cortisol prior to the onset of labour, nor an effect on placental hormone production. Therefore, it now seems unlikely that cortisol is important in initiating labour in humans, although it has a vital role in the maturation of fetal lungs and other organs. Several factors may affect physiological responses to cortisol; these include corticosteroid-binding protein (CBP) which would influence the relative concentration of free cortisol, metabolism of cortisol to inactive cortisone by 11β-hydroxysteroid dehydrogenase and modification of corticosteroid receptor expression.

Progesterone:oestrogen ratio

In most animal models, progesterone withdrawal is the trigger for parturition. In the sheep, fetal cortisol affects steroidogenesis so progesterone levels fall and oestrogen levels increase. This is a result of increased expression and activity of placental 17α-hydroxylase (see above). Across almost all species, the fall in plasma progesterone concentration is a common endocrine event leading to parturition. However, progesterone levels do not fall prior to labour in humans. In humans, the placenta does not express inducible 17α-hydroxylase activity and therefore cannot convert progesterone to oestrogen. However, increases in free oestriol levels have been observed in saliva of women before the onset of labour, both preterm and at term (Goodwin, 1999).

High progesterone levels inhibit myometrial activity during implantation and favour uterine quiescence throughout the pregnancy. This suppression of myometrial activity is essential to the maintenance of pregnancy, although parturition begins without a measurable decrease in maternal peripheral progesterone levels. Large doses of progesterone are relatively unsuccessful in inhibiting preterm labour in humans. However, mifepristone, the progesterone receptor antagonist previously known as RU-486, inhibits progesterone so it blocks the effect of progesterone and induces labour (Thong and Baird, 1992). Mifepristone is used clinically as an effective abortifacient. It also has anti-glucocorticoid activity and can cause ripening of the cervix and increase sensitivity to contractile prostaglandins.

It is possible in humans that there could be a functional progesterone withdrawal such as local changes in progesterone concentration or receptor binding which, even in the absence of a fall in progesterone concentration in peripheral blood, may affect myometrial activity. As the uterus enlarges during the pregnancy, the part of the uterine wall distal to the site of implantation, and therefore furthest away from the major source of progesterone production, may re-establish uterine contractions and trigger the onset of labour (Challis et al., 2000). Measurement of absolute progesterone levels may therefore be misleading as the biological effects will be altered by receptor density, levels of binding proteins or postreceptor changes. The fetal membranes and maternal decidua can both metabolize progesterone and produce cortisol. Cortisol is antagonistic to progesterone and can increase the synthesis of CRH (Karalis et al., 1996). Fetal membranes, therefore, offer a mechanism for local control of progesterone concentration. Alternative mechanisms have been suggested for the apparent lack of progesterone withdrawal prior to human parturition. These include sequestration of progesterone, another progesterone-like steroid being involved as a natural antagonist or local inactivation of progesterone, for instance progesterone is converted into an inactive metabolite that competes for receptor sites (Challis et al., 2000). For instance, before labour, the major products of the paracrine steroid hormone synthesis could be progesterone and oestrone (a weak oestrogen) and following the onset of labour the major products could be less active progesterone metabolites and biologically active oestradiol (Mitchell and Wong, 1993). It has also been suggested that in humans there is a regionalization of uterine activity and high progesterone levels are important in promoting relaxation of the lower uterine segment while contractions in the fundal area facilitate the descent of the fetus (Challis et al., 2000). Changes in progesterone receptor expression could potentially act as a functional progesterone block and thus control myometrial progesterone responsiveness (Mesiano, 2004). The altered progesterone receptor profile is postulated to modulate oestrogen effects (and hence oxytocin responses) via expression of oestrogen receptors. The human progesterone receptor exists in several isoforms produced from a single gene. PR-B is the full-length isoform which is the major mediator of progesterone effects whereas PR-A lacks the N-terminal part of the protein that contains one of the functional domains so it tends to have effects that oppose those of PR-B. There are also PR-C and two other truncated isoforms. It seems that the expression of PR-A may increase significantly before the onset of labour at term so that the ratio of the two forms changes during gestation thus affecting the response of the uterine tissue and the ability of progesterone to suppress myometrial activity (Goldman and Shalev, 2007). The increased synthesis of PR-A may be mediated by inflammatory factors and Toll-like receptors (Smith et al., 2007); this pathway may be increased in some cases of preterm labour associated with infection.

The interaction of progesterone with its receptors requires specific co-activators; these co-activators are less abundant towards the onset of labour (Smith, 2007). Progesterone metabolites may also interact with the progesterone receptors in a different way to progesterone (Mitchell and Taggart, 2009). Progesterone bioactivity could also be regulated at the post-receptor level.

Human placental production of oestrogen increases throughout labour and the rate seems to increase in the latter part of gestation. In sheep, increased oestrogen causes increased contraction-associated proteins (CAPs) and up-regulation of prostaglandin synthase and consequent increased synthesis of PGE2, promoting a positive feedback on myometrial contractility. However, spontaneous labour in humans can occur in the absence of measurable changes in oestrogen concentration. Exogenous oestrogen infusion in humans causes a transient increase in uterine activity and decreases the oxytocin threshold of the uterus but does not induce premature delivery or fetal membrane changes (Challis et al., 2000).

Synthesis of placental oestrogen depends on fetal cooperation in the provision of the precursors, and could thus potentially provide an opportunity for the human fetus to manipulate the progesterone:oestrogen ratio and uterine activity. The fetal adrenal gland in humans and higher primates is a relatively large percentage of body mass compared with the adult and has three zones: the outer adult zone produces mostly aldosterone, the unique fetal zone produces dehydroepiandrosterone sulphate (DHEAS) and the transitional zone produces mostly cortisol. This large fetal zone of the adrenal gland disappears in the neonatal period and may be regulated by hCG levels. DHEAS is the fetal adrenal C19 steroid precursor for placental oestradiol-17α and oestrone synthesis, which are implicated as having a role in labour. DHEAS is converted to oestrogens by placental sulphatase, aromatase and other enzymes (see Chapter 3). Production of DHEAS is controlled by ACTH from the anterior pituitary, which is itself regulated by hypothalamic CRH. CRH of placental origin can also stimulate production of DHEAS from the fetal zone (see below). However, women who have placental sulphatase or aromatase deficiencies and produce very little placental oestrogen can have normal pregnancy and labour (López Bernal, 2003). Thus, the changing ratio of oestrogen to progesterone may facilitate effective uterine contractions but is probably not critical for the induction of labour (Steer and Johnson, 1998).

Corticotrophin-releasing hormone

Hypothalamic CRH controls the function of the pituitary–adrenal axis in response to stress. CRH stimulates the anterior pituitary gland to produce corticotrophin which then stimulates the cortex of the adrenal gland to release cortisol. However, even in the presence of significant stress, levels of CRH are relatively low compared to the levels reached in pregnancy. CRH is expressed abundantly in the syncytiotrophoblast cells of the human placenta (but not in non-primate placentas) and CRH-receptors are expressed in the primate placenta and myometrium. Placental CRH seems to have an important role in the initiation of parturition in higher primates and humans. CRH is synthesized by the placenta predominantly into the maternal circulation though some enters the fetal circulation (Smith, 2007). Levels of CRH steadily increase in the maternal circulation from mid-term (about 90 days before the onset of labour) until about 35 weeks when levels sharply rise and are usually particularly high in pregnancies ending with premature labour (Wolfe et al., 1990) and those complicated by pre-eclampsia (Smith and Nicholson, 2007). CRH activity is attenuated by CRH-binding protein (CRH-BP), which is synthesized by the liver, placenta and brain so most CRH is in the bound (inactive) form during pregnancy. However, towards term, when levels of CRH increase, levels of CRH-BP simultaneously fall and the capacity of the CRH-BPO is saturated so circulating levels of physiologically active, free CRH markedly increase. The maternal adrenal CRH receptors are down-regulated so the ACTH response to CRH is blunted in late pregnancy; this protects the maternal pituitary-adrenal axis from over-stimulation.

The stress hormone, cortisol, normally has a negative feedback effect to inhibit CRH secretion and thus ACTH and cortisol secretion as part of the HPA axis. The opposite situation occurs with placental CRH where cortisol has a positive feedback effect to further increase CRH release by the placenta. This positive feedback is further augmented by increased prostaglandin production (Petraglia et al., 1995), which also increases placental synthesis of CRH. Fetal stresses such as hypoxia and hypoglycaemia result in increased CRH concentrations. CRH is a vasodilator in the placental vascular bed (Clifton et al., 1994) so increased CRH should result in increased blood flow and abrogation of the fetal insult. However, if the insult persists, then CRH would increase fetal ACTH secretion and increase DHEAS production thus increasing oestrogen synthesis which leads to myometrial activation. Thus, CRH appears to be a mechanism by which a compromised fetus can precipitate labour when intrauterine life becomes unfavourable. The pathway by which CRH in the fetal circulation increases pituitary corticotrophin production which subsequently stimulates cortisol secretion by the fetal adrenal gland is important in the maturation of the fetal lungs and other organs particularly the central nervous system and gut (see Chapter 15). The maturing fetal lungs increase their production of surfactant proteins which can then enter the amniotic fluid; these surfactant proteins together with phospholipids and inflammatory cytokines are thought to stimulate inflammation in the fetal membranes and underlying myometrium and contribute to the amplification of the signals leading to labour (Smith, 2007).

It has been suggested that the ratio of placental CRH and CRH-BP acts as a placental ‘clock’ which controls the length of gestation and allows a distressed fetus to ‘wind-on’ the clock to initiate premature labour (Smith, 2007). CRH receptors can couple to different G-proteins in different tissues and at different stages of pregnancy (Karteris et al., 1998). So for most of pregnancy, CRH is coupled to the G-protein (Gαs) involved in increasing cAMP levels. It therefore has a ‘protective’ role and promotes myometrial quiescence via the generation of cAMP and cGMP, and up-regulation of nitric oxide synthase expression. Near term, the expression of CRH receptors changes to the form that couples to the other G-protein pathway (Gαq) so that CRH now activates PLC and mobilizes Ca2+ from intracellular calcium stores thus promoting increased myometrial contractility and labour (Hillhouse and Grammatopoulos, 2002). The involvement of a physiological stress pathway in the onset of labour could explain the relationship between maternal stress and reproductive failure (Nakamura et al., 2008) and the interesting possible relationship between maternal periconceptional nutritional status and the timing of parturition (MacLaughlin and McMillen, 2007). Maternal stress would stimulate the maternal pituitary-adrenal axis resulting in increased maternal cortisol production which would stimulate placental CRH release (Smith et al., 2007). Myometrial contractility is also enhanced by up-regulation of oxytocin receptor expression and cross-talk between the oxytocin and CRH receptors.

Other factors

It is argued that an alternative pathway for initiation of labour is the switching off of mechanisms that cause relaxation (see above; López Bernal, 2003). Cyclic nucleotides (cAMP, etc.) promote myometrial relaxation and β2-adrenergic agonists are effective tocolytic agents (see Table 13.2). The enzyme adenylyl cyclase catalyses the production of cAMP from ATP. Coupling of receptors to adenylyl cyclase may be responsible for uterine quiescence. As progesterone inhibits activity of the phosphodiesterase which breaks down cAMP, thus terminating its action, progesterone sustains the effect of cAMP and promotes uterine relaxation during pregnancy.

Table 13.2 Intervention in labour




Treatment of preterm labour (tocolytic agents)

Progesterone and related compounds

May relax uterus or block inflammatory pathways

Possibly reduce late preterm birth but not associated with reduced perinatal mortality or morbidity

β-Adrenergic agonists (betamimetics or ‘β-agonists’), for example ritodrine, terbutaline, fenoterol

Inhibit uterine contractions

Effects often short-lived; unpleasant side-effects (cardiovascular, metabolic and neuromuscular)

Magnesium sulphate

Inhibits myometrial contractility by competing with calcium entry and inhibiting actomyosin interaction

Limited usefulness as a tocolytic agent but useful as cerebroprotective agent

Oxytocin receptor antagonists, for example atosiban,barusiban

Competitive inhibition of oxytocin

Clinical trials taking place; potentially useful as oxytocin receptors have limited distribution. Some side effects as acts on vasopressin receptors

Prostaglandin synthase inhibitors, for example indomethacin

Inhibit preterm contractions

Serious neonatal complications in infants born <30 weeks

Reduce connectivity between myocytes

Adverse effects on fetal renal function, associated with oligohydramnios

Calcium-channel blockers, for example nifedipine

Decrease intracellular calcium, cause uterine relaxation

May affect placental and uterine blood flow; cardiovascular side-effects (hypotension and tachycardia); nonsteroidal anti-inflammatory agents



Risk of aspiration, intoxication, depression and incontinence

Treatment of post-term labour (methods of induction)


Used to augment labour; oxytocin has little effect on unripe cervix

Production of endogenous oxytocin can be increased by nipple stimulation

PGF2 agonists, for example dinoprostone, Cervidil, Prepidil

Cervical ripening, induction of labour

Effects depend on expression of receptors

Misoprostol (Cytotec)

Synthetic PGE1 analogue; used to reduce acid in the stomach

Can cause the uterus to contract; nausea and diarrhoea

Mifepristone (RU-486; Mifegyne)


Primarily used to induce first trimester abortion

Labour is an inflammatory process but the relationship between the immune system and parturition is not clear. It is clear that significant intrauterine infection can trigger parturition and cause preterm birth. Proinflammatory cytokines such as interleukin 1β (IL-1β), IL-6 and tumour necrosis factor-α (TNF-α), may have an important role in parturition (Mitchell and Taggart, 2009).

Signal amplification

Once labour has been initiated and the myometrium is activated, there is a positive feed-forward stimulation of myometrial activity. This signal amplification is mediated by prolabour factors, known as CAPs or uterotonins. These include prostaglandins and prostanoid receptors, oxytocin and oxytocin receptors, gap junctions and ion channels. It has not been easy to discriminate between those hormones and signals that initiate labour and those that amplify the triggering signals.


Prostaglandins (PGs) of the 2-series are known to be important in the feed-forward signal amplification and progression of labour; they promote myometrial contractions, cervical dilatation and membrane rupture. Prostaglandins are present in the circulation in low concentrations and are cleared in the pulmonary circulation so they are difficult to measure as they have paracrine activity and a short half-life. Prostaglandins can be formed as a consequence of tissue trauma (including labour itself and any manipulative or tactile stimuli). In late pregnancy, prostaglandin synthesis is readily stimulated by minor local stimuli, such as coitus, vaginal examination, sweeping the membranes or amniotomy, which are associated with inducing labour. Exogenous prostaglandins can be used therapeutically to ripen the cervix and to induce uterine contractions and labour. Mid-trimester abortion can be induced by procedures, such as intra-amniotic injection of hypertonic saline, that result in the increased synthesis and release of prostaglandins. Increasing DHEAS or oestrogen concentration and decreasing progesterone concentration increase production of prostaglandins (Challis et al., 2000). An increase is myometrial expression of prostaglandins receptors, particularly the receptor of PGF, is implicated in the causes of some preterm labour (Olson et al., 2003).

Prostaglandins are synthesized in the fetal membranes, decidua, myometrium and cervix; levels fall abruptly following placental separation. The rate-limiting step of prostaglandin production may be important in initiating labour. Activity of phospholipase A2 (PLA2) may regulate the level of arachidonic acid, which is the precursor of prostaglandins (see Chapter 3). Increased oestrogen (or decreased progesterone) stimulates the release of PLA2 from decidual lysosomes and therefore increases free arachidonic acid and subsequent prostaglandin synthesis. Arachidonic acid can also be produced indirectly via phospholipase C activity. Alternatively, the activity of cyclooxygenase (COX) may be rate-limiting (Aitken et al., 1990). The chorion produces prostaglandin dehydrogenase (PGDH), the enzyme which inactivates prostaglandins (Smith, 2007). In late pregnancy, chorionic PGDH activity decreases so the levels of PGE2 rises.

The two most important prostaglandins in labour appear to be PGF and PGE2. At term, concentrations of PGE2 and PGF are higher in the decidua and myometrium (but these tissues are subject to tissue trauma so some authors believe raised prostaglandin levels are caused by increased uterine activity). PGE2 is involved in cervical ripening, by mediating the release of MMP, and is metabolized by the myometrium to produce PGF. However, women with extrauterine pregnancies go into labour at term and experience painful uterine contractions even though there are no fetal membranes in contact with the uterus.

Maintenance of human pregnancy may depend on the synthesis of PGE2 being inhibited and this inhibition of prostaglandin synthesis being attenuated at the onset of labour. Prostaglandin concentrations in the pregnant uterus are very low (about 200 times lower than at any stage in the menstrual cycle), but increase sharply in the maternal circulation from 36 weeks' gestation probably in response to the increasing level of CRH (Hertelendy and Zakar, 2004). Arachidonic acid, the precursor, is plentiful but synthesis of prostaglandins is inhibited, even if the pregnancy is extrauterine. Progesterone or the fetus may directly or indirectly moderate synthesis or metabolism of prostaglandins. Endogenous inhibitors of prostaglandin synthesis have been identified in maternal plasma; levels fall towards the end of gestation. Inhibitors of the COX enzymes, such as aspirin and indomethacin, block prostaglandin synthesis and are used therapeutically to treat preterm labour. Prostaglandin synthesis is up-regulated by cortisol (and dexamethasone), oestradiol, CRH and the inflammatory cytokines interleukin 1β (IL-1β) and tumour necrosis factor α (TNFα; Bowen et al., 2002).

Low doses of prostaglandins, particularly PGF, increase myometrial responsiveness to prostaglandins and oxytocin possibly by increasing the formation of gap junctions. In vitro, PGE2 has a biphasic effect, stimulating at nanomolar concentrations and inhibiting at micromolar concentrations. It also has a dual action: when its effects are mediated by the EP1 and EP3 receptors, PGE2 increases intracellular calcium concentration, but the EP2 receptor is coupled to adenylate cyclase so PGE2 acting at this receptor decreases intracellular calcium and favours relaxation. Variations in regional prostaglandin synthesis may occur (Wilmsatt et al., 1995).

Prostacyclin (PGI2) is synthesized in the myometrium and cervix. It promotes myometrial quiescence. It has an important role in maintaining uterine blood flow in labour; it causes vasodilation of smooth muscle and inhibits platelet aggregation, potentially inhibiting thromboembolic complications. Myometrial relaxation between uterine contractions in labour prevents occlusion of the uterine vessels and hypoxia which could lead to uterine dystocia (Hertelendy and Zakar, 2004). Placental thromboxane (TxA2) has opposing effects to PGI2 and is important in the closure of the fetal ductus arteriosus and haemostasis after delivery. In pre-eclampsia, levels of prostacyclin are low and levels of thromboxane are high. This is the rationale for aspirin treatment of pre-eclampsia. Aspirin-like drugs, by inhibiting the COX enzymes and thereby prostaglandin synthesis, restore thromboxane levels in pre-eclampsia. Trials using aspirin caused a slight prolongation of gestation and diminution of uterine contractions, but also increased the risk of premature closure of the ductus arteriosus and postnatal bleeding problems in the mother.

Prostaglandins are metabolized by the enzyme PGDH which is located in the fetal membranes. Deficiency of PGDH is associated with preterm labour. Expression of PGDH is up-regulated by progesterone and IL-10 and suppressed by cortisol (and dexamethasone), oestradiol, CRH, IL-1β and TNFα. Parturition is, therefore, essentially an inflammatory process. The association between infection and preterm labour is thought to be due to the release of phospholipases from bacterial organisms (Romero et al., 2003), which cause an increase in arachidonic acid release and so prostaglandin synthesis. Decidual macrophages respond to bacterial products by releasing pro-inflammatory cytokines. Bacterial endotoxins, such as lipopolysaccharide, can either increase prostaglandin release directly or further stimulate release of cytokines which then increase prostaglandin synthesis. Lipopolysaccharide also contributes to premature rupture of the membranes.

Prostaglandins also have an important role in the establishment of a neonatal circulatory pattern (see Chapter 15). Respiratory distress syndrome is associated with high levels of PGF in the infant's circulation, and patent ductus arteriosus with high PGE2 levels. PGE2 can prevent the ductus arteriosus from closing and inhibitors of prostaglandin synthesis can promote its closure. There is indirect evidence (i.e. fetal breathing movements, FBM, stop) that PGE2 increases in the fetal circulation 48–72 h before the onset of labour (Thorburn, 1992). It is possible that this is mirrored by a local increase in PGE2concentration in uterine tissue, which initiates labour.


Oxytocin is a peptide synthesized by the hypothalamus and released from the posterior pituitary gland (see Chapter 3). A synthetic form (Oxytocinon or Syntocinon) is used extensively for induction and augmentation of human labour and can prevent postpartum bleeding or haemorrhage. Endogenous oxytocin production can also be stimulated, for instance by nipple stimulation, with a favourable outcome. However, it is not certain whether oxytocin is important in the initiation of labour. As oxytocin receptors are generally localized to the uterus, mammary glands and pituitary, oxytocin antagonists and agonists have few systemic effects. Maternal oxytocin levels are very low and do not change very much before labour. Maternal pituitary production of oxytocin dramatically increases in the first stage of labour. However, focusing on circulating levels of oxytocin may be misleading. The concentration of oxytocin receptors in the myometrium and decidua rise dramatically (by 100–200 times) during late pregnancy so the sensitivity of the uterus increases (Fuchs et al., 1984). This means the uterus can be stimulated by low concentrations of maternal oxytocin levels that previously had no effect. Therapeutic doses adequate to augment labour are very variable, which probably reflects individual differences in receptor number. If used to augment labour infusions of Oxytocinon should commenced on low dosage which is gradually increased until regular, strong contractions (around 3 in every 10 min time period) are present to ensure hyperstimulation of the myometrium is reduced. The pattern of oxytocin release changes at the onset of labour, with an increased frequency of pulses (Fuchs et al., 1991). It may be important that maternal oxytocin levels stay low during the pregnancy so the sensitivity of the uterus to oxytocin is maintained. Oxytocin antagonists, such as atosiban, have been used to inhibit uterine contractility in preterm labour (see Table 13.2) but not always effectively. Atosiban is useful in slowing down preterm labour so that steroids can be administered to facilitate fetal lung maturity however it can also cause raised blood glucose levels so should be used with caution with diabetic women (Berkman et al., 2003). Note that all tocolytic medications have side effects some of which can be extreme and potentially life-threatening (Blumenfeld and Lyell, 2009).

Exposure of decidual cells to oxytocin increases the release of prostaglandins. Vaginal examination in late pregnancy stimulates the Ferguson reflex so oxytocin is released from the posterior pituitary, which stimulates uterine prostaglandin production. Earlier in pregnancy, this response does not occur, presumably because there are inadequate oxytocin receptors. Women who go into preterm labour seem to have an increased expression of oxytocin receptors and higher myometrial sensitivity to oxytocin. Failed induction of labour is associated with a reduced number of oxytocin receptors. Therefore the initiation of labour depends on mechanisms that induce the expression of oxytocin receptors in the myometrium rather affect the oxytocin level itself. Both oestrogen and prostaglandins increase uterine responsiveness to oxytocin.

Oxytocin is also synthesized by the decidua and may act locally (Miller et al., 1993). The fetal posterior pituitary produces both oxytocin and ADH (vasopressin). Exogenous Oxytocinon can cause uterine contractions in sheep and women carrying an anencephalic fetus (Honnebier et al., 1974); however, the physiological relevance of this is not clear as maternal oxytocin secretion does not rise until labour has been initiated. In spontaneous labour, fetal secretion of oxytocin is high and transferred across the placenta at levels comparable to those used to induce uterine activity (Husslein, 1985). The increment in oxytocin levels is greater in the umbilical arteries than in the umbilical vein and is much higher than maternal levels, suggesting it is synthesized by the fetus and transferred across the placenta. Initiation and maintenance of human labour may therefore be influenced by fetal oxytocin production. ADH (vasopressin) is produced at even higher concentrations than oxytocin and may regulate prostaglandin production.


Relaxin is a polypeptide hormone produced by the corpus luteum, and decidua and placenta in pregnancy, which promotes tissue remodelling during reproduction (Bani, 1997). It has been found to inhibit myometrial contractility and promote vasodilation, via nitric oxide synthesis, until late pregnancy. It also appears to promote cervical ripening at parturition. Concentrations of relaxin appear to be highest in the first trimester and then fall. A very early fall is associated with preterm labour. Histologically, the number of cells staining positively for relaxin is much less after spontaneous delivery compared with caesarean section. Relaxin may inhibit PGE2 production during pregnancy but favours its production in labour. It may act synergistically with progesterone during the pregnancy, maintaining uterine quiescence and inhibiting oxytocin release.

The maternal endocrine system

Ovaries are not necessary for the initiation of labour. Hypophysectomized women (who have no pituitary glands) and women with diabetes insipidus (a posterior pituitary defect) go into labour at term. However, the posterior pituitary stores oxytocin, which is synthesized in the hypothalamus. In the absence of a functional pituitary gland, oxytocin is probably secreted directly by the hypothalamus. Adrenalectomized women on corticosteroid maintenance therapy go into labour spontaneously but women with Addison's disease tend to have prolonged pregnancy.

The maternal nervous system

There is a higher density of adrenergic and cholinergic innervation towards the cervix. The non-pregnant uterus contracts in response to both adrenaline and noradrenaline but, at term, noradrenaline increases uterine contractions and adrenaline causes relaxation. α-Receptor antagonists, such as phentolamine, decrease uterine activity and inhibit the response to noradrenaline so adrenergic drugs are used to suppress contractions in preterm labour; β-receptor antagonists, such as propranolol, increase uterine activity. Catecholamines both stimulate and inhibit uterine activity, acting via the α2-receptors and β2-receptors respectively. The α1-receptors increase intracellular calcium concentrations and promote contractile activity. However, labour occurs normally in paraplegic women (who have no nervous input to the uterus), suggesting that the onset and progress of labour is under hormonal, rather than nervous, control. Neural control appears to modulate uterine activity but is subordinate to hormonal control.


In a normal pregnancy, growth of the uterus keeps pace with the growth of its contents and the limit of stretchability is probably not reached. In fact, mechanical stretching of the uterine wall by the growing fetus induces smooth muscle hypertrophy and increases its tensile strength. However, overstretching, for instance with multiple pregnancy and polyhydramnios, is associated with a shorter gestation period. The probable mechanism is that stretching of the muscle fibres increases their excitability and that mechanical stress can increase responsiveness to uterotonins. In most smooth-muscle containing tissues in the body, stretching leads to reflex contraction. Multiple gestation and polyhydramnios are associated with over-distension of the uterus and a higher incidence of preterm labour. Distension of the uterus causes myometrial stretching and also stretching of the fetal membranes which line the inner surface of the uterus.

The timing of parturition

In some mammalian species there is a clear seasonal influence on ovulation and delivery. There are obvious advantages to ensuring the young are born at the optimal time of year when there is a plentiful food supply and less threat from predators. In these species, the length of the daylight period, mediated by night-time secretion of melatonin, appears to play an important role. The human fetus possibly has the potential to survive birth as early as the 24th week of gestation. Most babies are delivered after the 37th week of gestation. However, there is a range of gestational periods producing healthy babies capable of survival. It is suggested that this variation in apparently normal gestation could allow changing environmental conditions to influence the precise timing. One suggestion is that the time of the lunar month could affect the timing after 37 weeks. Other suggestions are that gestational length may be linked to the length of the individual woman's ovarian cycle or may have a familial pattern. Women with longer menstrual cycles may have a lower level of oestrogen, which could affect the initiation of parturition (see above).

Mammals tend to labour most effectively during the period of the day in which they normally rest. They usually seek isolation and privacy and protection from terrestrial predators. Nocturnal species tend to give birth during the day and diurnal species tend to give birth at night (Rosenberg and Trevathan, 2002). This timing may be because the effect of the parasympathetic nervous system is then dominant; labour is inhibited by sympathetic stimulation. Both the start of labour and the actual time of delivery occur more frequently at night and in the early hours of the morning (Honnebier and Nathanielsz, 1994). Circadian rhythms occur in several variables including pregnancy-associated hormones and prelabour myometrial activity. Uterine activity and oxytocin levels are higher at night until about 3 weeks before delivery. The maternal circadian system probably entrains fetal cooperation. Circadian rhythms do not occur in sheep (Apostolakis et al., 1993).

The evolutionary context of human labour

Humans have large and complex brains and are the only living mammal that habitually walks on two legs. They have a complicated mechanism of labour and routinely seek assistance when they give birth. The development of bipedal locomotion has resulted in a changed pelvic structure and physiology. One suggestion is that eye contact in sexual intercourse has led to the vagina forming a right-angle with the brim of the pelvis and uterus, presenting a laborious passageway in childbirth (Stewart, 1984). The relatively straight cylindrical pelvis of our forebears has evolved into a tilted conical birth canal. Pelvic size has decreased to enhance adaptation to the upright posture and swift movement.

It is thought that the upright stance of human ancestors led to thickening and lengthening of the pelvic bones and the forward curvature of the sacrum (Stewart, 1984); this stance imposes extra pressure on the pregnant cervix. Humans have a particularly high concentration of cervical collagen compared with other species. Unlike most other animals, where the cervix remains firmly closed until just before delivery, there is usually some degree of cervical softening relatively early in human pregnancy (Fig. 13.9); partial dilatation of the cervix occurs much earlier in gestation (Leppert, 1995). Because there is such a wide variation in the cervical changes among pregnant women, cervical assessment in isolation of other signs is an unreliable indicator of the imminence of labour. Towards the end of the first stage of labour, the changing shape of the cervix means that its tissue becomes integrated with the rest of the uterus (Fig. 13.8; see below).

B9780702034893000307/f13-09-9780702034893.jpg is missing

Fig. 13.9

(A) Prior to lightening: the fundus is in close proximity to the diaphragm and the lower uterine segment is still firm so the fetal head remains high. (B) After lightening (2–3 weeks before the onset of labour): the lower uterine segment has softened and dilated so the fetal head descends and the fundus sinks below the diaphragm, easing breathing.

(Reproduced with permission from Bennett and Brown, 1999.)

The evolution of the human brain resulted in cephalization, the marked enlargement of head size in relation to overall body mass (Stewart, 1984). This creates the potential problem of obstructed labour, which occurs at a much higher rate in humans compared to other animals. The fetus has to negotiate rather than simply pass through the pelvic cavity. It seems that humans have adapted by the fetus completing in utero development at a relatively early stage, and being born at a much smaller proportion of the adult weight. Cephalization has resulted in secondary altriciality, the infant being born at an immature and helpless state of development. Human infants are born with a smaller proportion of adult brain size than other primates. This has significant implications for parental behaviour and social relationships as well as placing a higher emphasis on the importance of nutrition in providing for development of the nervous system in the postnatal year.

Humans are not the only animals that have difficulty in childbirth (Rosenberg and Trevathan, 2002). The smaller bodied primates, such as monkeys and gibbons, have similar cephalopelvic constraints; the neonate at birth has a head size that is close to the size of its mother's birth canal. Monkeys usually deliver in a squatting position away from other members of the social group, who may observe from a distance. The mother monkey may wipe mucus from the infant's mouth and nose and guide the infant, who is usually dexterous with developed motor skills, out of the birth canal towards the nipples (Rosenberg and Trevathan, 2002). Because of mechanical differences in the birth process, however, the human fetus has to rotate within the pelvic cavity and is usually born in an occipitoanterior position (head facing away from the maternal pubic bones, in the opposite direction from the mother). In this position, it is difficult for the mother to reach to clear a breathing passage or remove the umbilical cord from the infant's neck. Thus, human mothers actively seek assistance in childbirth and birth is a social rather than a solitary occurrence.

Whereas most primates squat during delivery, unless women are used to squatting, the semi-upright positions of kneeling and sitting are thought to be optimal (Rosenberg and Trevathan, 2002). The upright position (standing, squatting or sitting) results in a shortened second stage of labour and more favourable maternal and infant outcomes. Being upright allows maternal effort to be aided by gravity. The presenting part bears the force of the neonate. The occiput has well developed cranial plates and is best able to withstand the stress (Rosenberg and Trevathan, 2002).

It is suggested that the physiological control of birth is mediated by hormones that are derived from archaic brain structures such as the hypothalamus and pituitary gland (Odent, 2001) and that labour is facilitated by an environment that promotes these primitive pathways. The neocortex, on the other hand, is thought to inhibit the primitive pathways. The neocortex responds to bright light and to language. Thus, it is suggested that bright lights, feelings of being observed (and use of cameras and monitoring equipment) and use of language which stimulate neocortical activity might interfere with the primitive physiological processes and impede the progress of labour. This may explain why relaxation techniques may progress labour. Often women appear to become detached from their surroundings indicating that neocortex activity is suppressed as they inwardly focus on their body activity and dampening down their responses to external stimuli. Fear is an archaic emotional response; women often cry out and express emotional fear in advanced labour suggesting the archaic brain activity is dominant. Maternal levels of catecholamines peak towards the end of labour which increases maternal awareness and alertness as the baby is born. This is suggested to be an evolutionary advantage, promoting maternal behaviour and protectionism, even aggressiveness (Odent, 2001).

The first stage of labour

Uterine contractions in labour

If softening of the cervix has taken place, the coordinated uterine contractions exert a steady pull thus stretching the cervix. This effacement of the cervix often takes place before the contractions become completely regular so it may occur a week or so before labour. As the cervix effaces, the presenting part of the fetus, usually the head, descends into the cavity of the pelvis. The fetal position alters so that it fits well; this is described as engagement.

Contractions are involuntary and will therefore occur in an unconscious woman. However, they can be temporarily abolished by emotional disturbances (including moving from home to hospital and by a change in staff shifts). The frequency and strength of the contractions can be increased by enemas, prostaglandins and oxytocin preparations, and by stretching of the cervix or pelvic floor by the presenting part. Contractions are regular and intermittent. The intermittent nature is important as it allows recovery of both the uterus and the labouring woman and a resumed oxygen supply to the fetus.

Contractions begin to feel painful once the cervix starts to dilate. Backache often precedes cervical dilation. The pain is due to ischaemia in the muscle during the contraction because the uterine blood vessels are compressed. Similar pain occurs for the same reason in spasmodic dysmenorrhoea. Uterine pain is analogous to myocardial pain in angina when blood flow in the coronary arteries supplying the cardiac muscle is restricted. Baseline tone in labour is about 10–12 mmHg (Blackburn, 2007). An increase in intrauterine pressure of about 10–20 mmHg can be palpated abdominally and perceived by the women at 15–20 mmHg. Pain is often perceived when the pressure rises above 25 mmHg. Pressures may rise to 50 mmHg in the first stage and to 75–100 mmHg in the second stage. Weak contractions have a shorter duration with longer intervals between each contraction. The sensation of pain is related not just to the strength of contraction and the interval between each contraction but also to the well-being of the mother and position of the fetus. An anxious or tired woman experiences pain at lower uterine pressure intensity (see below). Maternal position and use of analgesics may influence the strength and timing of contractions. A woman whose baby is in a posterior position which commonly presents with a deflexed head (often described as an abnormal attitude or military position) also tends to have greater backache as there is increased pressure on the sacral bones and posterior joints of the pelvis.

Contraction waves

The uterus is also analogous to the heart in another respect in that it appears to exhibit pacemaker activity, although specific pacemaker cells have not been localized. Specific areas that depolarize more rapidly have not been identified, although it was believed that they were each side of the fundus, near the uterotubal junctions or cornuae. All myometrial cells have spontaneous pacemaker activity. The contractions tend to originate from cells near the fundus and spread as a wave, as the electrical activity moves through the gap junctions of the muscle fibres (Fig. 13.10). The waves are strongest at the fundus, which has the highest density of muscle fibres, and take about 15–30 s to travel down the length of the uterus (Blackburn, 2007). There is a polarity of wave contraction with rhythmic coordination between the upper segment, which contracts for longer and retracts, and the lower segment, which contracts slightly later, to a less extent and dilates. This is described as fundal dominance; it is similar to the peristaltic waves generated by smooth muscle in other viscera. If the wave pattern is abnormal, for instance if the lower part contracts first or more strongly, the waves become erratic and uncoordinated and labour does not progress efficiently. This is described as ‘incoordinate uterine activity’.

B9780702034893000307/f13-10-9780702034893.jpg is missing

Fig. 13.10

Contraction and retraction of uterine muscle cells.

(Reproduced with permission from Sweet and Tiran, 1996.)

The uterus relaxes between contractions, which is important for oxygenation of the fetus and myometrium. The upper part of the uterus does not relax fully between contractions but retracts instead. This means that the muscle fibres do not return fully to the original length but progressively and gradually get a little bit shorter and thicker with each contraction (Fig. 13.11). This means that the less active lower segment is pulled up towards the shortening upper part of the uterus. (If the uterine muscle relaxed completely following each contraction, the uterus would remain the same size and labour would not progress.) The weakest points are the os and cervix which are effaced and dilated, enlarging the opening of the uterus.

B9780702034893000307/f13-11-9780702034893.jpg is missing

Fig. 13.11

Uterine muscle contraction. Rather than the uterine myometrial cells relaxing fully (as in A), during labour the myometrial cells in the upper segment of the uterus retract getting progressively shorter (as in B). The lower uterine segment and the cervix dilate in response to the forces of contraction generated by the shortening upper segment thus the fetus is expelled.

Formation of hindwaters and forewaters

As the lower segment stretches and the cervix starts to efface and change its position, the chorion becomes detached from the uterine wall. The operculum tends to become dislodged from the receding cervical canal. The loss of this mucus closure (or ‘show’), which may be blood-streaked (caused by the rupture of tiny superficial blood vessels during detachment of the mucous plug), indicates the external os has started to dissipate and that active dilatation of the internal os is imminent. The membranes are extruded through the opening cervix by the pressure of the amniotic fluid (Fig. 13.12). The head of the fetus tends to act as a ball-valve separating the amniotic fluid pushing through the cervix (forewaters) from the remainder of the fluid (hindwaters). The forewaters transmit the pressure generated from the waves of contraction, spreading the force evenly over the cervix, which aids its further effacement and dilatation. The hindwaters help to cushion the fetus from the contraction pressures. As the fundus presses on the upper aspect of the fetus (usually breech) during contractions, the pressure is transmitted through the fetal body to the lower segment and cervix (this is known as the fetal axis pressure). As uterine contractions progress, the pressure of the fluid in the forewaters rises and the membranes tend to rupture. When the fetus is in an abnormal position (for example in a breech or posterior and deflexed cephalic position), the pressure of the forewaters is not as great because the presenting part does not plug the cervix as effectively. This explains why a ‘soft and floppy bag’ of forewaters is associated with abnormal presentations.

B9780702034893000307/f13-12-9780702034893.jpg is missing

Fig. 13.12

Effacement and dilatation of the cervix: (A) in a primigravidae; (B) occurring simultaneously in a multigravidae.

(Reproduced with permission from Sweet and Tiran, 1996.)

Membrane rupture

As well as an increase in the pressure of the forewaters, the fetal membranes may also rupture when the contractions cause the presenting part to distend them. There is a loss of lubricant between the chorion and amnion leading to increased shear force and cell rupture (Blackburn, 2007). In 5–10% of pregnancies, premature rupture of the membranes (PROM) occurs spontaneously before the onset of uterine contractions as the earliest sign of labour (Duff, 1996); about 60% of these are classified as term gestation. Spontaneous rupture of the membranes before 37 weeks' gestation often culminates in premature labour and delivery. Early rupture of the membranes as the first event in the course of labour is a cause for concern as it may indicate an ill-fitting presentation or high head at term in a primigravida, polyhydramnios or chorioamnionitis (a local infection which may be due to chlamydia or streptococcus).

Rupture of the amniotic membrane is associated with collagen degradation in the membrane (Hampson et al., 1997). Usually coordinated contractions and dilatation of the cervix follow rupture of the membranes but if there is a delay the fetus is at risk from ascending infections so clinical intervention may be necessary if labour has not followed within 24 h. There is controversy about artificial rupture of membranes and the effect it has on speeding up labour; it is thought that labour may progress more abruptly and painfully (Barret et al., 1992).

Size changes in the uterus and cervix

As the size of the upper segment of the uterus gradually diminishes because of the repeated cycles of contraction and retraction, the fetus is pushed into the lower segment so its presenting part (Box 13.2) exerts pressure on the obstructing maternal tissues. This results in increased oxytocin release from the posterior pituitary gland, which increases uterine activity by positive feedback mechanisms (see Chapter 1). Later in labour, when the baby has been born and the placenta has been expelled, retraction aids the uterine walls to come together so the cavity is obliterated as the uterine walls lie in apposition. A physiological retraction ring forms at the junction between the thick retracted segment of the upper segment and the thin distended wall of the lower segment. Under normal conditions, this ring is not visibly evident or palpable by abdominal examination. A pathological visible ‘Bandl's ring’ is the consequence of failure to recognize and manage obstructed labour appropriately and is a sign of imminent uterine rupture.

Box 13.2

Terms used for fetal presentation

• Attitude: relationship between fetal head and limbs and fetal trunk

• Lie: relationship of fetus to long axis of uterus

• Presentation: part of fetus presenting in lower aspect of uterus

• Presenting part: part of presentation immediately inside internal os

• Position: relationship of presentation, or presenting part, to maternal pelvis

• Denominator: part of presenting part marking position

The rate of cervical dilatation is not constant; initially the cervix dilates slowly, but early changes are reinforced by positive feedback mechanisms and the rate accelerates. The latent phase of the first stage is slower and can take up to 12 h (Box 13.3Fig. 13.13). It is during this stage, when dilatation to 3–4 cm is achieved, that the cervix positively contracts in response to oxytocin (Olah et al., 1993). This probably facilitates effacement. After a transition stage of about 15 min when the cervix does not contract, the cervix then dilates in response to myometrial contractions during the faster active phase.

Box 13.3

Progression of labour

The medical model of care in labour has defined an acceptable rate of progress in labour. Failure of labour to progress at this rate is described as abnormal and used as the rationale for medical intervention. Progress in labour is assessed through the use of a partogram. Cervical dilatation at the rate of 0.5 cm/h is accepted as normal. Intervention (such as amniotomy or use of Oxytocinon) is usually recommended if the rate of progress falls below 2 cm of the expected progress in 4 h. If in a further 4 h, following the use of Oxytocinon, if further progress is less than a further 2 cm then surgical intervention should be considered (NCCWCH, 2007).

B9780702034893000307/f13-13-9780702034893.jpg is missing

Fig. 13.13

The partogram is a complete visual record of measurements made during labour and delivery.

(Reproduced with permission from Symonds and Symonds, 1997.)

Case study 13.1 is an example of the first stage of labour.

Case study 13.1

Martha is a para 3; her previous pregnancies and labour were uneventful. She was admitted to the labour ward and confirmed to be in labour as her cervix was 6 cm dilated at 13:00 h. Four hours later on a repeat vaginal examination there was no further dilation, the membranes were intact, and cephalic presentation at the spines was judged to be in a direct occipito-anterior position. Martha was coping well and there were no concerns raised over the fetal condition.

• Should the midwife refer Martha for an obstetric opinion?

• Is the fact that Martha has made no progress enough to justify intervention?

• How could the midwife justify her decision to leave Martha alone, if she felt that this were appropriate?

• What physiological processes/influences may be contributing to this situation?

Table 13.2 details the possible types of intervention in labour.

The second stage of labour

By the end of the first stage of labour, the lower uterine segment, the cervix, the pelvic floor and the vulval outlet form one continuous dilated birth canal. The forces required to expel the fetus are both from the uterine muscle activity and from the secondary muscles of the abdomen and diaphragm, which augment the contractions of the uterus. The forces generated by the uterus can be described as the primary power and the complementary force from the voluntary movement of the respiratory muscles as the secondary power. By this stage, the uterus is markedly retracted and undergoing a pattern of strong, regular and repetitive contractions. The mother is compelled involuntarily to bear down or push. As she inspires before pushing, the diaphragm is lowered and the abdominal muscles contract, augmenting the contractile forces of the uterus. Bearing down by the mother helps to overcome the resistance of the soft tissues of the vagina and the pelvic floor. The fetal attitude (see Box 13.2) extends as it is directed through the birth canal, which aids the efficiency of the uterine contractions. The pain experienced in the second stage of labour is often less as cervical dilatation is complete and the woman is aware that progress is more rapid.

As the fetal head passes through the pelvis, the pressure on the sacral nerves may be associated with cramp in the legs and pain from the trauma to the tissue. The fetus distends the vagina and displaces the pelvic floor. The anterior part of the pelvic floor is drawn up causing the urethra to elongate and become compressed. The bladder is therefore repositioned within the protective environs of the abdomen. Posteriorly, the pelvic floor is stretched forward in relation to the presenting part and the rectum is compressed, which may lead to defecation (which is often a sign the second stage has commenced). The perineum is flattened, lengthened and thinned by the presenting part of the fetus.

During a contraction, the presenting part (usually the fetal head) advances forward and, if not in a direct anterior position, rotates forwards facilitated by the shape and resistance of the pelvic floor. If the fetal head is completely flexed, then the top of the head (the flexion point) meets the resistance of the pelvic floor optimising rotation. In the interval between contractions, the presenting part recedes slightly and may rotate back but, as the uterine muscle retracts with each contraction, progression in the forward direction is maintained. This progression has been likened to taking two steps forward and one step back. Once the flexion point is positioned over the uretogenital hiatus, the fetal head starts to distend the perineum and vaginal opening. When the widest part of the fetal head (the biparietal diameter) distends the vulva, the stretching is at its maximum, hence pain may be severe if not managed effectively with analgesia. This is described as ‘crowning’ of the head. The severity of the pain may cause a labouring woman to gasp and inhale sharply. The momentary break in the bearing-down movement has an important role in protecting the perineum from too much trauma, which can cause tearing of the tissue. Once the head is delivered, it realigns itself with the original internal position of the fetal body (so the baby's head moves from facing the maternal anus to facing one of the maternal buttocks); this is called restitution. Following restitution, the next contraction forces the anterior shoulder to contact the perineum and therefore further external rotation of the head occurs with the fetus facing at right angles with the maternal midline. The birth of the baby is usually accomplished with the next contraction following ‘crowning’ with the posterior shoulder leading. A gush of amniotic fluid escapes. The fetus undergoes a pattern of passive corkscrew movements as it follows the shape and curvature of the pelvis (curvature of Carus). The gutter shape of the pelvic floor facilitates the rotation of the presenting part enabling the widest diameters of the pelvis to accommodate the largest dimensions of the fetal head and shoulders (Fig. 13.14). In breach presentations, the anterior buttock of the fetus contacts with the perineum first and so rotates forward and once the anterior buttock lies over the uretogenital hiatus the breech will distend the perineum and vaginal opening as it is born.

B9780702034893000307/f13-14-9780702034893.jpg is missing

Fig. 13.14

Rotation of the presenting part: (A) delivery of the head; (B) restitution; (C) external rotation.

(Adapted with permission from Bennett and Brown, 1999.)

Influences of pelvic and pelvic floor morphology and parturition

The passage of the fetus through the pelvis is described in practice as the mechanism of labour. Engagement describes the descent of the presenting part into the true pelvic cavity; the term relates to the widest transverse diameter of the fetal skull having negotiated the pelvic brim or inlet. If the baby has a cephalic (head-first) presentation, this is described in terms of number of fifths palpable (Fig. 13.15). Verification of the degree of engagement can be achieved through vaginal examination. With a cephalic presentation, the level of the biparietal prominences is judged in relation to the pelvic brim and the pelvic outlet at the level of the ischial spines. Engagement may occur long before the onset of labour, or may occur during, or even late on in, labour (more common in multiparous women). In a primigravida, engagement usually occurs at about 36 weeks' gestation in response to effacement of the cervix. Engagement does not indicate cavity and outlet measurements.

B9780702034893000307/f13-15-9780702034893.jpg is missing

Fig. 13.15

(A) Flexion and descent of the presenting part into the pelvic cavity; (B) engagement of the head. (A, reproduced with permission from Bennett and Brown, 1999; B, reproduced with permission from Sweet and Tiran, 1996.)

The third stage of labour

During the third stage, the placenta separates from the wall of the uterus and is expelled. Before separation, the placental extracellular matrix is thought to be weakened by proteases including MMP produced by the decidua and fetal membranes (Weiss et al., 2007). The uterus retracts markedly and bleeding from the placental wound site is constrained. Following the safe delivery of a healthy baby, the third stage of labour still presents a number of potential hazards. Should part of the placenta be retained, control of bleeding is impaired and a life-threatening postpartum haemorrhage could ensue. Immediately after delivery, the uterus markedly decreases in size. The pattern of contractions is interrupted for a minute or so, until contractions resume at a slow rate. As the uterus retracts, the placental site is greatly diminished. The placenta is not elastic, thus it tends to wrinkle and buckle and be sheared off the elastic uterine wall (like a paper label coming away from a deflating balloon). It is at this stage that some fetal blood from the placental circulation can enter the maternal circulation, potentially causing problems if there is Rhesus incompatibility (see Chapter 10). The marked retraction of the uterus impedes the venous drainage of the maternal intervillous spaces. Separation usually begins in the centre of the placenta and the extravasculated blood forms a haematoma or retroplacental clot between the placenta and decidua aiding its separation as the clot adds to the placental weight peeling the membranes from the uterine wall. As the uterus retracts, its progressively shortening muscle fibres tighten around the maternal vessels, forming ‘living ligatures’, which impede blood flow. This restricts the flow of maternal blood to the uterus and placental wound site, preventing excessive blood loss.

It is the commencement of spontaneous or stimulated uterine contractions following the completion of the second stage of labour that causes the placenta to separate from the uterine wall. The weight of the placenta completes the detachment of the membranes, which peel off and are expelled (Fig. 13.16). The site of placental implantation determines the speed of separation and the method of placental expulsion. The fetal membranes are expelled with the maternal or fetal surface prominent. The Schultze method of expulsion whereby the fetal side presents is most common and is associated with a fundal site implantation and the Matthews-Duncan expulsion (whereby the placenta slips out sideways like a button through a button-hole) is more likely with a lateral implantation. In some cultures, the placenta has important significance and women keep it for ritual ceremonies.

B9780702034893000307/f13-16ae-9780702034893.jpg is missing

Fig. 13.16

The mechanism of placental separation and expulsion: (A) uterine wall partially retracted but not sufficiently to cause placental separation; (B) further contraction and retraction thicken uterine wall, reduce placental site and aid placental separation; (C) complete separation and formation of retroplacental clot (note: the thin lower segment has collapsed like a concertina following the birth of the baby); (D) Schultze method of expulsion; (E) Matthews-Duncan method of expulsion.

Active management

The third stage of labour can be physiologically managed (passive management), taking about 20–30 min to complete, but active management is widely practised by midwives, shortening the time of placental delivery to a few minutes. Active management involves the injection of an anti-tocolytic agent such as Syntometrine (see below) at the birth of the anterior shoulder or shortly after the delivery of the baby and delivering the placenta and membranes by controlled cord traction (CCT; also known as the Brandt–Andrews manoeuvre). The sheared-off placenta is extracted rather than expelled if active management of the third stage of labour is implemented. The use of CCT is subject to some discussion and is not practised in all countries. The placenta should be separated and the uterus should be well contracted before CCT to ensure that it does not cause uterine inversion. The woman may be asked to bear down to assist expulsion of the placenta.

Syntometrine is a combination of oxytocinon (also called syntocinon; synthetic oxytocin) and ergometrine which is used to reduce the risk of postpartum haemorrhage. Oxytocinon acts within 2–3 min following intramuscular injection, by causing intermittent contractions. These effectively continue the retraction process behind the placental site, thus encouraging separation and early expulsion. Ergometrine becomes effective about 5–7 min after administration. By this time, aided by CCT (commenced as soon as the uterus contracts down), the placenta has been expelled. The midwife applies cord traction by gripping the umbilical cord with one hand and applying a downward traction (Fig. 13.17). The other hand is placed on the lower abdomen, thumb and index finger stretched out to provide a line of contact) applying pressure to avoid inversion of the uterus. Ergometrine produces a sustained uterine contraction, which promotes the haemostatic action of the living ligatures. It is essential, therefore, to deliver the placenta before ergometrine stimulates closure of the cervix as this could result in a retained placenta. The third stage of labour can also be managed using intramuscular injections of Oxytocinon only following delivery as it has fewer side effects. Oxytocinon should not be used if there is a history of hypertension as ergometrine can increase blood pressure further.

B9780702034893000307/f13-17-9780702034893.jpg is missing

Fig. 13.17

Controlled cord traction (Brandt–Andrews method).

(Reproduced with permission from Bennett and Brown, 1999.)

Physiological management of the third stage of labour involves no routine use of anti-tocolytic drugs, not clamping the umbilical cord until pulsations cease, no uterine manipulation or controlled cord traction, and delivery of the placenta and membranes solely by maternal effort should be completed within 1 h of birth. Skin-to-skin contact and early breast feeding may facilitate the delivery of the placenta in the third stage by stimulating endogenous maternal oxytocin release. Women should be encouraged to empty their bladders and adopt an upright position as gravity will aid delivery of the placenta. During this time, palpation of the uterus should be avoided but careful observation is required especially of vaginal blood loss to identify haemorrhage. As placental separation occurs, there is usually an increase in blood loss but this is reduced as the uterus contracts down and the presence of the placenta in the upper part of the birth canal stimulates the mother to bear down. This may stimulate more oxytocin release due to Ferguson's reflex. Division of the umbilical cord should not be rushed unless the baby needs attention and ideally the cord should not be cut until it is pulse-less. Many practitioners advocate not clamping the maternal end of the cord to facilitate spontaneous delivery of the placenta as the free draining of the blood softens the placental body making it easier to pass through the birth canal.

The effects of labour on maternal physiology

Cardiovascular system

The stress of labour prepares the woman for the inevitable blood loss at delivery and limitation of bleeding after placental separation. Dehydration and muscle activity increase the haemoglobin concentration. Erythropoiesis and white blood cell number also increase as part of the normal response to stress. Concentrations of clotting factors increase, clotting times shorten and fibrinolytic activity is decreased on completion of the third stage of labour. The placenta and decidua are very rich sources of thromboplastin which can activate coagulation (see Chapter 1). About 5–10% of the total body fibrin is deposited as a haemostatic endometrial mesh over the placental wound site (Blackburn, 2007). This hypercoagulable state is further developed in the puerperium (see Chapter 14).

The cardiovascular system is affected by pain, anxiety, apprehension, position and anaesthesia, as well as by the muscular activity of the uterus itself and the dramatic increase in catecholamine production during labour. Uterine contractions progressively increase cardiac output as venous return and circulating volume are increased. Each contraction can contribute 300–500 mL of blood to the circulation (Sullivan and Ramanathan, 1985), which significantly increases cardiac output and blood pressure. In the supine position, stroke volume and cardiac output tend to be lower and heart rate raised.

Catecholamines affect vascular tone and increase blood pressure; this effect is reduced with anaesthetics. Pain and anxiety result in tachycardia (increased heart rate) and affect blood pressure. During a contraction, systolic blood pressure increases by at least 35 mmHg and diastolic blood pressure may increase between 25 and 65 mmHg (Blackburn, 2007). The increment in blood pressure precedes each contraction and falls to baseline between contractions. The greatest haemodynamic changes occur in women delivering their baby vaginally, which is an important consideration for women who have cardiac disease.

The respiratory system

Labour affects the respiratory system as the muscular work increases metabolic rate and oxygen consumption. Respiratory rate and depth of respiration increase. Anxiety, drugs and use of a gas mask mouthpiece can all affect respiratory rate. There is a tendency for a labouring woman to hyperventilate. Hyperventilation is a natural response to pain. Contractions occurring at high frequency can affect oxygenation causing muscular hypoxia and acidosis. Hypoxia can increase the amount of pain experienced.

The increased ventilation causes a progressive and marked decrease in partial pressure of carbon dioxide (to about 25 mmHg) particularly if the contractions are painful. In early labour, hyperventilation can cause respiratory alkalosis and increased blood pH. This can result in the woman experiencing dizziness and tingling of her fingers and toes, and possibly developing muscle spasms. At extremely low PaCO2, blood flow can be affected and the oxygen–haemoglobin dissociation curve (see Chapter 1) shifts to the left so release of oxygen is impaired. The remedy of breath counting to slow respiratory rate, especially if the woman counts them with her partner or a midwife who deliberately slows down counting, can prevent or correct hyperventilatory effects.

By the end of the first stage, maternal acidosis due to isometric muscle contractions is likely and is compensated for, to a degree, by the respiratory alkalosis. The muscle contractions reduce blood flow to the uterine muscle, which becomes hypoxic and undergoes anaerobic metabolism. Flow to the intervillous space also decreases so fetal levels of carbon dioxide increase and the fetus tends to become acidotic. During bearing down, when the mother's accessory respiratory muscles are involved, mild respiratory acidosis is likely. In the second stage of labour lactate levels increase, thus pH falls. This metabolic acidosis is not compensated for.

The renin–angiotensin system

Labour and delivery affect the renin–angiotensin system of both fetus and mother. Levels of renin and angiotensinogen increase, which are important in maintaining blood flow, but can also affect handling and excretion of drugs. Glomerular filtration rate, renal blood flow and sodium excretion are also affected by raised catecholamine levels or general anaesthetic. Oxytocin has structural similarities with ADH and has inherent antidiuretic properties; therefore fluid retention is increased in labour. Women in labour can be at risk of iatrogenic water intoxication due to loss of electrolytes, use of Oxytocinon, or intravenous fluid administration.

Metabolic rate

Maternal glucose consumption markedly increases in labour to provide energy required by the uterus and skeletal muscles. Glucose and triacylglycerides are used as energy sources. Oxytocin has some insulin-like properties. An increased body temperature during labour may indicate dehydration or infection. It is common for women to experience a transient postpartum chill about 15 min after the birth of the baby or delivery of the placenta. In the following 24 h, postpartum women frequently have a slightly raised temperature secondary to dehydration.

Nutrition in labour

Food and drink consumption in labour is controversial. There are two conflicting arguments. The first is that a woman in labour might possibly require a general anaesthetic and therefore should be treated as a preoperative patient at risk of gastric aspiration. Pulmonary aspiration of gastric acid (Mendelson's syndrome) or particulate food matter, although rare, is a major cause of morbidity and mortality for women in labour. The risks of gastric aspiration are thought to be greatly reduced if oral intake is limited (Rowe, 1997). Pregnant women have a slower gastric emptying rate (see Chapter 11), which is further delayed by labour (Carp et al., 1992), and decreased tone of the lower oesophageal sphincter but it is not known whether this delayed gastric emptying predisposes to gastric aspiration.

The opposing view is that a more liberal policy is more beneficial and that women are being needlessly deprived of food. It is argued that general anaesthesia is relatively rare now and that techniques have improved, which make aspiration of gastric contents unlikely. It is argued that prolonged fasting could have detrimental psychological and physiological effects, including increased anxiety and stress.

Pregnant women are predisposed to ketosis, particularly in labour. Pregnancy is a ketotic state and fasting in pregnancy is invariably associated with ketonuria (Scheepers et al., 2001). It is estimated that a woman in labour has an energy requirement of 700–1100 kcal/h. When glycogen stores are exhausted, adipose tissue is mobilized. Fatty acid oxidation increases ketosis, an excess of ketone bodies in the plasma, which are excreted into the urine. Lipolysis provides fatty acid substrates for maternal energy needs and spares glucose for the fetus. The critical question is whether ketosis is detrimental to the progress of labour. Ketones can increase acidity, cause excessive renal excretion of sodium and cross the placenta to the fetus. Although the length of labour is correlated with the degree of ketosis, it is not clear whether longer labour results in increased ketosis or whether ketosis prolongs labour.

It is suggested that fasting in labour can increase the need for medical intervention. Allowing women to eat in labour reduces the plasma level of ketones, which may aid the progress of labour (Scutton et al., 1996). Ketonuria can be treated by administration of intravenous dextrose but this is associated with fluid and electrolyte imbalance. A number of women experience nausea and vomiting in labour. But, in practice, more maternity units are cautiously adopting a liberal policy offering a non-particulate diet while using antacids and H2-antagonists to reduce gastric pH and decrease volume of gastric contents, thus minimizing the risk of aspiration and lung damage.

The effects of labour on the fetus

Labour has profound effects on the fetus and is important in aiding the adaptation to extrauterine life (see Chapter 15). Understanding the effects of labour on the fetus is important in differentiating between normal healthy responses and diagnosing fetal distress.

Behaviour of the fetus during pregnancy

The use of ultrasound led to the observation that, after 36 weeks, the fetus exhibits a number of clearly definable behavioural states, which are analogous to the neonatal states (see Chapter 15). These states have characteristic patterns of fetal heart rate (FHR), FBM, eye movements, voiding and mouthing movements (Table 13.3). The patterns of fetal behaviour change with gestational age and are assumed to reflect the activity of the fetal central nervous system and can potentially be used to recognize a compromised fetus (Nijhuis, 2003). The movements evidently demonstrate fetal ability to respond to external stimuli. Many factors such as time of day, meals, smoking, etc. affect fetal behaviour. Most of the movements that are discernible in the third trimester can be traced back to the first trimester. Both the movements and the periods of quiescence between them are important.

Table 13.3 Fetal behavioural states

State 1F (1 fetal); quiet sleep

Fetal quiescence with brief gross startles; high-voltage electrocortical activity; no eye movement; FHR accelerations; minimal heart rate variability; isolated fetal heart rate

State 2F (2 fetal); active sleep

Paradoxical/irregular sleep; frequent and periodic stretches; retroflexion and movements of extremities; low-voltage electrocortical activity; continuous eye movements; increased FHR variability with frequent accelerations

State 3F (3 fetal); quiet awake

Absence of gross movements; continuous rapid eye movements; stable, but widely oscillating FHR, no accelerations

State 4F (4 fetal); active awake

Vigorous and continual movements; rapid eye movement; unstable heart rate – large, long accelerations and tachycardia

FBM can be detected from the end of the first trimester (Nijhuis, 2003). FBM are more regular in state 1F than in state 2F, they occur more frequently in state 2F and are present but irregular in states 3F and 4F. It has been suggested that FBM are more likely to be state-dependent when maternal glucose levels are lower (Mulder et al., 1994). There is a postprandial increase in FBM and smoking diminishes them. Fetal voiding movements are inhibited in state 1F but occur at the transition to state 2F. Sucking and swallowing can be seen from the end of the first trimester. Regular or rhythmic mouthing movements are most often observed in state 1F, when they occur in bursts of 10–20 min, whereas powerful sucking movements can be seen in state 3F. Both regular mouthing and sucking can entrain FHR patterns which can bewilder clinical interpretation.

States 1F and 2F account for about 90% of fetal life in late gestation. FHR patterns during these four behavioural states may mimic fetal distress. The fetal behavioural states and the transitions between them can be observed throughout labour. States 1F and 2F predominate as they do before labour. It is thought that diminished FHR variability and absent accelerations in a healthy term fetus probably represent fetal sleep rather than fetal distress. In the deep sleep state 1F, FHR pattern is usually unaffected even by strong uterine contractions. A period of low fetal heart variability (FHV) or tachycardia may indicate that fetal oxygenation is being compromised. In the second stage of labour, the length of the behavioural cycles decreases; this is related to the gamut of sensory stimuli and head compression incurred during this stage of labour.

FBM increase in frequency and in length of episode as gestation progresses. By the third trimester, FBM occur for 30% of the time and are closely associated with behavioural state, especially active sleep (2F). A few days before the onset of labour, FBM are depressed, probably because increased levels of prostaglandin, especially PGE2, inhibit the fetal respiratory centre. During the latent stage of labour, FBM occur for about 10% of the time but almost cease in the active stage. In preterm labour, the decrease in FBM is less acute. FBM may be affected by changes in oxygenation and pH. FBM require energy so the fetus decreases FBM in response to hypoxia as an adaptive response to conserve oxygen. The hypoxia-induced decrease in FBM is more marked near term possibly because the responses to hypoxia have become more sensitive as the respiratory centre becomes more mature.

Although hypoxia normally decreases FBM, deeper, sustained inspiration or gasping is stimulated synergistically by raised carbon dioxide levels in the presence of hypoxia. In perinatal aspiration, this gasping can cause meconium inspiration. Paradoxically, maternal hyperventilation decreases FBM. Hypoglycaemia and central nervous system depressants, such as ethanol, barbiturates and diazepam, decrease FBM. Theophylline increases FBM and is used to treat postnatal apnoea in premature infants. Prostaglandin inhibitors, such as indomethacin, stimulate FBM but have to be used with caution because of their effects on fetal vascular function.

Changes in fetal behaviour over the course of pregnancy are summarized in Box 13.4.

Box 13.4

Changes in fetal behaviour during pregnancy

First trimester

• Specific sequence of movements

• Continual activity

• Coordinated and graceful quality

Second trimester

• Body movements diminish

• Breathing movements increase

• Quiescence increases

• Rest–activity cycles develop

Third trimester

• Clear fetal behavioural states

• Specific combination of variables

• Stable with state transitions

• Breathing is state-dependent

Changes during labour

The stress of labour causes a reflex increase in maternal catecholamine levels well above those seen in non-pregnant women or pregnant women before labour. The physiological stress and hypoxia associated with the pain and anxiety increase adrenaline secretion. The physiological work of labour, which is highest in the second stage of labour, increases noradrenaline release. Placental metabolism of maternal catecholamines reduces the transfer to the fetus. However, maternal catecholamines can affect placental blood flow and affect the fetus in labour. Animal studies show that adrenaline is associated with vasoconstriction and a reduction in uterine blood flow. As the rise in adrenaline level is associated with maternal stress in labour, there is a clear advantage to limiting maternal psychological distress and pain.

Normal labour and delivery are associated with increased physiological stress resulting in raised cord levels of catecholamines in the neonate (Gluckman et al., 1999). This increase in fetal catecholamines may be a response to fetal compression, mild acidosis and other stimuli experienced during the birth. It is suggested that this is an adaptive response that facilitates extrauterine adaptation. The increased catecholamines stimulate breathing, increase fluid absorption from the lungs, stimulate surfactant release, enhance irritability, and play a role in metabolism by mobilizing glucose and fatty acids (Gluckman et al., 1999).

Fetal tissues are metabolically active; heat dissipation is via the placenta to the mother. Cord exclusion in animals results in an increase in fetal temperature. It seems likely that uterine contractions affecting uterine blood flow will impair heat transfer, particularly in active labour. At delivery, there is a transition from a heat-producing fetus to a neonate dependent on heat generation. In utero, PGE2 and adenosine derived from the placenta may have a role in suppressing the activity of brown adipose tissue and therefore minimizing heat production by the fetus. Occlusion of the umbilical cord is the signal to increase heat generation. Non-shivering thermogenesis by brown adipose tissue is under the control of noradrenaline (see Chapter 1) released during labour.

A healthy term fetus has good energy stores and a normal base excess so it can tolerate temporary reductions in uterine perfusion in labour. There is a marked increase in fetal glycogen storage in the last month of gestation. The fetus also has the enzymes required for glycogenolysis. However, under normal uterine conditions, placental transfer of maternal glucose means that the fetal glucose pool is of maternal origin. Until labour, the fetus still depends on maternal sources of glucose. The changes in catecholamine secretion boost neonatal metabolism.

The placenta also provides the route of oxygen transfer and carbon dioxide removal. Maternal hyperventilation in labour increases carbon dioxide diffusion across the placenta, therefore increasing respiratory alkalosis (increasing pH). However, respiratory depression caused by oversedation or magnesium sulphate could have the opposite effect. In the presence of a reduced oxygen supply, anaerobic metabolism will cause metabolic acidosis. Lactate diffusion across the placenta is slow and the fetal kidney is not efficient at clearing organic acids. It seems likely that the respiratory alkalosis related to maternal hyperventilation compensates for at least some of the metabolic acidosis, owing to anaerobic glycolysis, thus restoring fetal pH to a normal range. Normal labour nevertheless will cause a gradual decrease in fetal pH, oxygen and bicarbonate ions and a corresponding rise in partial pressure of carbon dioxide.

Uterine blood flow is largely determined by maternal blood pressure, cardiac output and uterine muscular tone. Labour compromises uterine blood flow. The maternal spiral arteries, which perfuse the intervillous spaces, are occluded and venous drainage of the spaces is obstructed during uterine contractions. Doppler measurements show that blood flow through the uterine arteries is gradually reduced during a contraction and gradually returns when the uterus relaxes. Most animal models demonstrate that the placenta has an anatomical redundancy; over 70% of the placental capillary bed must be occluded before impedance to gas exchange rises significantly. If placental reserve is reduced, uterine contractions may have a significant effect on fetal hypoxia and acidosis. Even with a healthy placenta and normal uterine blood flow, contractions with excessive strength of frequency can cause fetal hypoxia and bradycardia. Maternal conditions may exacerbate this by reducing uterine perfusion; supine posture can reduce venous return, therefore cardiac output and regional anaesthesia can cause vasodilation so decreasing maternal cardiac output.

Labour promotes the clearance of fetal lung fluid. Transient tachypnoea, caused by residual lung fluid, is more common in babies born by elective caesarean section than in those experiencing a vaginal delivery. Chest compression mechanically expels a small volume of fluid. Late in gestation, the pulmonary epithelial cells actively secrete chloride ions, which create a gradient maintaining adequate lung volume in utero. Before birth the lung epithelial cells change from being predominantly chloride-secreting to being sodium-absorbing, which draws fluid into the interstitial spaces. The sodium-pumping activity is increased in spontaneous labour; this may be related to the catecholamine surge.

A mature sucking pattern is evident from 36 weeks of gestation. Although fetal swallowing can be observed as early as 11 weeks' gestation, near-term discrete episodes of swallowing occur, probably triggered by ‘thirst’, gastric emptying or changed composition of amniotic fluid (Boyle, 1992). This swallowing may be important for gut development and maturation. In labour there is some evidence that swallowing increases. Meconium passage is rare until about 38 weeks when the control of intestinal peristalsis is more mature. Early meconium passage is associated with listeriosis. Meconium-stained amniotic fluid occurs in about a third of pregnancies beyond 42 weeks. Hypoxia induces vasoconstriction of the fetal gut, hyperperistalsis and anal sphincter relaxation, so passage of meconium has been associated with fetal distress (Houlihan and Knuppel, 1994). However, it has been argued that meconium-stained fluid could reflect normal maturity of the fetal gut function (Katz and Bowes, 1992). Less than 2% of babies born with meconium-stained fluid go on to develop severe meconium aspiration syndrome. It has been suggested that the primary cause of this syndrome is pulmonary epithelial damage or airway obstruction, which results in ineffectual clearance of meconium. The residual meconium can interfere with surfactant dispersal and increase the severity of the respiratory problems.

The fetal skull and fetal presentation

The dimensions of the fetal head correlate well with those of the maternal pelvis. Examination of the shape of the baby's head soon after delivery shows how it passed through the pelvis (Fig. 13.18). The bones of the fetal skull are relatively mobile and mould under compression during labour. The sutures and fontanelles (Fig. 13.19) allow the skull bones to overlap partially so the dimensions of the presenting part can be reduced by about 0.5–1 cm. Diameters that are not compressed elongate to compensate for those that are reduced. If the pressure generated against the cervix impedes the circulation in the scalp then oedema may occur forming a caput or swelling. The area of the caput and the degree of moulding indicate the degree of head compression endured in labour. The caput is usually absorbed within a few days of delivery and requires no treatment. If the head is compressed in an abnormal diameter, or if the moulding is too excessive or rapid, the dura mater forming the falx cerebri may be pulled from the tentorium cerebellum resulting in rupture of the venous sinuses and intercranial haemorrhage (Fig. 13.20).

B9780702034893000307/f13-18-9780702034893.jpg is missing

Fig. 13.18

The relationship between the shape of the baby's head and the moulding of the fetal skull.

B9780702034893000307/f13-19-9780702034893.jpg is missing

Fig. 13.19

Sutures and fontanelles of the fetal skull.

B9780702034893000307/f13-20-9780702034893.jpg is missing

Fig. 13.20

Coronal section through the fetal head to show intracranial membranes and venous sinuses.

(Reproduced with permission from Bennett and Brown, 1999.)

The position of the fetus (see Box 13.2, for an explanation of terms) is determined on abdominal examination in later pregnancy and early labour (Fig. 13.21). The midwife can gently palpate the pregnant woman's abdomen to determine how the fetus is lying and how the presenting part of the fetus relates to the pelvis. The degree of engagement of the fetal head into the brim of the pelvis can also be ascertained. Auscultation of the fetal heart confirms the initial findings. The lie of the fetus describes the relative position of the long axis of the fetus to the long axis of the uterus. Usually the lie is longitudinal, rather than oblique or transverse, particularly in the last weeks of pregnancy. The attitude is the degree of flexion of the fetus. In the fully flexed attitude, the fit of the fetus in the uterus is comfortable. The presentation describes the presenting part of the fetus. Cephalic presentation occurs in most pregnancies. The fetal position is described by the relationship of the denominator (the presenting part) to areas of the maternal pelvis. The pelvic areas are: left and right, anterior, lateral or posterior areas. The occiput (the bone at the back of the fetal skull) is the denominator of a cephalic position so the fetus could, for instance, be described to be in a right occipitoanterior position. Anterior positions are more common because the fetal spine is against the mother's abdominal wall. Occipitoposterior positions tend to result in the fetus assuming a deflexed attitude, which can result in less-effective contraction, prolonged labour, uneven cervical dilatation, increased risk of trauma to the perineum and unfavourable compression of the fetal head.

B9780702034893000307/f13-21-9780702034893.jpg is missing

Fig. 13.21

(A) Attitude and (B) presentation of the fetus.

(Reproduced with permission from Sweet and Tiran, 1996.)

Pain in labour

Many women experience severe pain in labour. Pain is a complex and personal phenomenon. Although it is easier to understand the neurophysiological aspects of tissue damage, the experience of pain is always subjective and is related to psychological state and past experience. Pain can be defined as a sensation (sensory and emotional experience) usually evoked by tissue damage or inflammation that stimulates the activity of specific receptors transmitting information to pain centres in the brain. Although pain can often be considered to be part of a protective mechanism (a rapid warning system) against tissue damage, there are some exceptions. For instance, pain associated with radiation (as in sunburn) or tumour growth tends to occur well after the tissue damage has occurred so it does not function as a warning. Chronic pain associated with degenerative diseases, such as arthritis, also cannot be regarded as a protective reflex. In labour, some aspects of pain experienced can be protective, such as the pain due to stretching of the soft tissue as the baby's head is crowned, which causes the woman to gasp.

The perception of pain depends on a number of physiological factors. The location and intensity of the stimuli affect the quality and severity of the perceived pain; generally, the higher the intensity of the stimuli, the greater is the pain experienced. However, psychological and cultural factors are important in the perception of pain (Box 13.5). Mood and personality type are important; generally, anxious or tired people are less able to tolerate pain but emotional arousal limits pain perception. In certain primitive cultures, the father has the ‘labour pains’ and the mother quietly gives birth.

Box 13.5

Factors affecting pain perception

• Anatomy

• Physiology

• Psychology

• Sociology

• Culture

• Cognition

• Learning

Pain receptors

Pain or nociceptive receptors respond to stimuli that cause tissue damage. They are specific, responding to chemical mediators of tissue damage, such as plasmakinins, acetylcholine, histamine and substance P. Pain receptors are distributed unevenly with a higher density in skin, dental pulp, some internal organs, periosteum, meninges, arterial walls and joint surfaces. Pain receptors are free nerve endings that form part of small afferent myelinated Aδ fibres and larger (but unmyelinated) C fibres (Table 13.4). There is controversy over the pain being caused by overstimulation of other receptor types such as those that respond to temperature and pressure (Box 13.6).

Table 13.4 Fast and slow pain receptors

Fast Pain

Slow Pain

Bright, sharp, localized sensation

Dull, intense, diffuse unpleasant feeling

C fibres

2–5 μm diameter

0.4–1.2 μm diameter



Conduct at 12–30 m/s

Conduct at 0.5–2 m/s

Terminate on neurons laminars I and II

Terminate on neurons in laminars I and V

Spinothalamic tract

Spinorecticular tract

Somatic pain

Visceral pain

Box 13.6

Pain receptors


• Aα (Ia and Ib) (myelinated): position proprioception, touch, pressure, vibration

• Aβ (II) (myelinated): fine discriminative touch, pressure, vibration

• Aγ (myelinated): burning sensation


• Aδ (III) (myelinated): well-localizable sharp pain, temperature

• C (IV) (unmyelinated): dull aching pain, temperature

Pain transmission

Transmission of pain depends on the type of fibre in which the nerve ending triggers the impulse. In general the speed of transmission is faster in larger fibres and those that are myelinated (see Chapter 1). Sharp stabbing sensations are thought to be conducted by Aδ fibres and dull aching or burning pain by the slower unmyelinated C fibres. Myelinated fibres are more sensitive to ischaemia. Small unmyelinated fibres are more susceptible to local anaesthetics such as procaine, which is effective at blocking aching pain.

The nerve fibres enter the spinal cord and terminate in the grey matter of the dorsal horn (Fig. 13.22). Aδ fibres have a relatively direct route of transmission, synapsing with neurons in the dorsal horn to the brain stem and via the spinothalamic tract to the thalamus and cerebral cortex. Therefore the pain is perceived as sharp and is easy to localize. The unmyelinated C fibres synapse in the grey matter of the spinal cord as well but are routed through the spinoreticular tract and reticular formation to the thalamus and cortex. Within the reticular formation, a number of physiological processes take place, stimulating the nervous system and affecting electrical activity in the brain, wakefulness and attention. The state of excitement that is generated means the pain is difficult to localize and produces unpleasant symptoms. The limbic system (which includes the hypothalamus and the amygdala) at the base of the brain is stimulated, which affects emotional responses such as fear, anger, pleasure and satisfaction. The thalamus integrates the sensation of pain and relays the information that tissue damage has occurred. The somatosensory cortex discriminates and identifies the precise position of the tissue damage and the parietal cortex is involved in interpreting the information and relating the learned meaningfulness to past experience. The main excitatory neurotransmitter in pain perception is glutamate.

B9780702034893000307/f13-22-9780702034893.jpg is missing

Fig. 13.22

Pathways of pain transmission.

(Reproduced with permission from Bennett and Brown, 1999.)

The gate control theory

There is a relationship between the pain receptors and the touch receptors at the level of the spinal cord. The pain gate control theory, proposed by Melzack and Wall (1965), suggests that interneurons in the substantia gelatinosa of the dorsal horn of the spinal cord can regulate the conduction of the ascending afferent nerve (Fig. 13.23). So input from the large-diameter myelinated fibres from the touch receptors can inhibit the impulses on the smaller-diameter fibres from the pain receptors, acting as a gate. This means that touch, like massage, can inhibit transmission from the pain receptor unless activity along the smaller fibres markedly increases. Descending fibres from the brain can also modify transmission of pain signals, thus ‘opening’ or ‘closing’ the gate. This explains the relationship between psychological factors and pain perception. If a labouring woman is feeling relaxed and confident, the descending inhibition is high so less pain is perceived. If she becomes tired or anxious, the descending inhibition is reduced. Transcutaneous electrical nerve stimulation (TENS) acts both to stimulate the large-diameter touch afferent nerves and possibly to stimulate powerful descending inhibitory pathways.

B9780702034893000307/f13-23-9780702034893.jpg is missing

Fig. 13.23

The gate control theory of pain.

Pain from muscle contractions

Both visceral pain from the uterus and somatic pain from trauma to the soft tissues of the birth canal are experienced in labour. Visceral pain tends to predominate in the first stage of labour when the uterus is contracting and the cervix is stretching and dilating. Rhythmic muscle contraction in the presence of an adequate blood flow does not usually cause pain. In labour, uterine contractions compress blood vessels and reduce flow; the ischaemic pain persists until the flow is restored. It is hypothesized that a chemical mediator reaches critical levels when flow is limited and stimulates the pain receptors. When flow is restored, the chemical mediator is diluted or metabolized. This is similar to exertion causing myocardial ischaemia and angina pain, which is relieved by rest and decreased myocardial oxygen requirements. Initially, pain is transmitted by the afferent fibres entering the spinal cord at T11 and T12, spreading to T10 and L1.

Referred pain

In referred pain, damage from one part of the body is experienced as though it had occurred in another part of the body. The pain fibres from the damaged area enter the spinal cord at the same level as the afferent nerves from the referred area. Usually the pain is referred to another tissue or structure that developed from the same embryonic structure or dermatome in which the pain originates. So, for instance, development of the diaphragm begins in the neck but, as the lungs develop, the diaphragm and the phrenic nerve migrate towards the abdomen. The afferent fibres in the phrenic nerve enter the spinal cord with the afferent fibres from the tip of the shoulder. Irritation of the diaphragm is therefore referred as a pain in the shoulder. However, previous experience is important in referred pain. Pain from the abdominal viscera including the uterus is usually referred to the midline. But in patients who have experienced abdominal surgery, such as a caesarean section, the pain is referred to the scar site. Pain during this stage arising from the uterus and cervix may be referred. A labouring woman may experience pain over her abdominal wall, between the naval and pubic bone, radiating down her thighs and in the lumbar and sacral regions.

Somatic pain

Somatic pain caused by the presenting part impinging on the birth canal, vulva and perineum tends to occur in the transition and in second stage of labour. Pain is transmitted by the pudendal nerves S2, S3 and S4. The conscious sensation of pain is accompanied by a number of physiological responses including increased ventilation and cardiac output, inhibition of gastrointestinal function, increased oxygen demand and metabolic rate and increased catecholamine release. The increased catecholamine release may detrimentally affect placental perfusion and uterine contractions. Non-pharmacological methods of pain relief, such as imagery, relaxation techniques and provision of information about the progress of labour, probably decrease anxiety and stress and responses mediated by the sympathetic nervous system. Women with epidurals in situ may experience pain during the second stage of labour even if the epidural has been effective earlier. This is because epidurals are more effective at blocking visceral pathways that the somatic pathways. Following delivery with an epidural still in situ, if perineal repair is required, it is good practice to ensure the women remains pain free and this often requires local anaesthetic even if the epidural is topped up.

Endogenous opiates

The endogenous opiates are of particular interest in pain perceived in labour. These include β-endorphin, enkephalins and dynorphin, which are analgesic peptides. They bind to the presynaptic receptors on the neuron membrane and block pain transmission. Enkephalins comprise two short peptide chains (consisting of five amino acids) that are very unstable and have a half-life of less than a minute. Enkephalins are fragments of β-endorphin, which is more stable and also binds to opiate receptors; β-endorphin is a fragment of the pituitary hormone β-lipotrophin. β-Lipotrophin and ACTH are both derived from the same precursor.

Endogenous opiates inhibit prostaglandin synthesis. Prostaglandins are possible chemical mediators of pain. They also inhibit actions of a number of other pain transmitters. β-Endorphin levels increase throughout pregnancy, peaking at delivery, and may be further stimulated by the stress of labour. It is suggested that it is this high level of endogenous opiates that allows women to tolerate surprisingly high levels of pain during delivery; this phenomenon is known as ‘pregnancy-induced analgesia’. Acupuncture may increase enkephalin activity. Placebo responses where pain relief occurs as a result of expectation of pain relief rather than because of being given an analgesic may be due to release of endogenous opiates and genuine analgesia.

Pain relief

Pain relief in labour needs to work rapidly and effectively relieve the pain without slowing down the course of labour. It needs to be safe for the mother and fetus and not adversely affect the neonate. There is no ideal analgesic (Table 13.5); all have some side-effects but pain also can adversely affect the fetus. Maternal analgesia can alter the balance of factors promoting uterine contraction and can potentially result in increased effects of oxytocin, promoting tetanic uterine contractions, decreasing oxygen delivery and causing transient fetal bradycardia (Eberle and Norris, 1996). There are three main mechanisms of pain relief blocking the pain receptors, the propagation of the action potential or the perception of pain within the central nervous system (CNS). Mild analgesics block at the pain receptor level. The sensitivity of the pain receptors is increased by prostaglandins. Drugs which inhibit prostaglandin synthesis, such as aspirin, decrease levels of prostaglandins both at the receptor and where prostaglandins are involved in pain transmission higher in the pathway.

Table 13.5 Types of analgesics

Pain Relief






Depression of CNS

Nausea, vomiting, sedation; potentiate effect of epidural

Paracervical block


Action potentials blocked from nerves

Risk of fetal injection; could provide surgical anaesthesia


Bolus, intermittent or continuous infusion

Inhibition of neurotransmission across synapses

Maternal hypotension, motor blockade

Local anaesthetics

Local anaesthetics prevent the propagation of action potentials by blocking the sodium channels. They are particularly effective in blocking pain carried by the C fibres, possibly because unmyelinated fibres allow easier penetration. For instance, lignocaine (lidocaine) injected into the perineum is effective at blocking the pain of episiotomy.

Centrally acting opiates

Centrally acting opiates or narcotics, such as morphine and pethidine, block nerve transmission in the brain and spinal cord and decrease pain perception. There are also opiate-binding sites in the substantia gelatinosa of the dorsal horn of the spinal cord, which affect the release of neurotransmitters. Opiates increase the activity of the descending inhibitory pathways from the brain stem and act on the limbic system to elevate mood. Opiates have other physiological effects such as depressing the medullary respiratory centre, causing nausea and vomiting, sedating and affecting the heart rate.

Position in labour

Certain positions have advantages in optimizing uterine efficiency or increasing maternal comfort (Blackburn, 2007) (see Box 13.7). The lithotomy position and lying supine are probably advantageous only to those assisting at the delivery, unless medical intervention/delivery is required. Fetal monitoring and a number of procedures can usually be adapted to a variety of maternal positions. There seems to be no physiological advantage in lying supine. Fetal alignment, pelvic diameter and efficiency of contractions are not optimal. Contractions are more frequent but less intense so labour is prolonged and drug use seems to be increased. Many women appear to choose a supine position because they are presented with a bed and have no alternative option.

Box 13.7


Over the last 20 years delivering babies in water has, increasingly, become popular and is available in many hospitals, birth centres and within the home environment (Cluett and Burns, 2009). Many women perceive waterbirth as a natural process without the need for analgesia. There have been concerns raised over the safety of waterbirth such as water inhalation and other complications such as hyponatremia, infection, haemorrhage associated with cord rupture, hypoxia and death (although these complications are rare). Research studies that show there is no significant difference in infant outcomes comparing waterbirth with conventional deliveries (Bodner et al., 2002Geissbuehler et al., 2004). These studies show that there is a reduction in episiotomies and a reduction in the use of analgesia in women who choose waterbirth. Evidence that the new born baby is no more at risk from infection following a waterbirth compared to a conventional delivery has been presented (Thoeni et al., 2004). The intensity of pain does not seem to be reduced by waterbirth but waterbirth does appear to reduce the use of conventional anaesthesia in the advanced stages of labour (Eberhard et al., 2005).

It is important that guidelines are referred and followed so that safety of both mother and baby is optimised (Geissbuehler et al., 2004). There is also some evidence to suggest that waterbirth is effective in lowering maternal blood pressure and so may be a useful intervention in mild preeclampsia. This may be a combination of relaxation and peripheral dilatation of the blood vessels due to the warming of the skin by the water. It is important to ensure the pool water temperature does not exceed 37.5 °C as prolonged immersion in hot water will eventually raise the maternal core temperature and as a consequence the fetal heart rate will be affected. The buoyancy of the water provides support and reduces the stress of weight bearing so enabling the mother move freely and change positions easily.

A lateral recumbent position reduces obstructive pressure on maternal blood vessels so venous return and cardiac output are optimal for uterine perfusion and fetal oxygenation. Uterine contractions are more intense but less frequent and have increased efficiency. In an upright position, the abdominal wall relaxes and the effect of gravity will augment the effect of the fetal head pressing on the cervix and the subsequent feedback to the myometrial activity. Both frequency and intensity of contractions are increased so uterine activity is enhanced and labour tends to be shorter. Squatting increases maternal pelvic diameter, enhances engagement and the descent of the fetal head.

During bearing down, in the second stage of labour, directed pushing with a Valsalva manoeuvre against a closed glottis increases sympathetic discharge and catecholamine release. Minimal straining with an open glottis has fewer negative effects on maternal blood pressure, maternal and fetal oxygenation levels and is associated with reduced need for episiotomy.

Key points

• Parturition in humans is poorly understood; animal studies offer limited insight into the process owing to the evolution of species-specific differences.

• Parturition is a continuous process: the defining of the various stages of labour enables clinical judgement of progress and thus intervention under the biomedical model of care.

• The fundal region of the uterus has the highest density of smooth muscle so it is responsible for the strong expelling contractions of the uterus during labour.

• Human cervical structure is complex owing to the upright stance causing an increased gravitational force as the contents of the uterus increase in mass. Structural changes within the cervix have to occur before dilatation can be achieved by uterine contractions.

• Coordinated effective contractions are facilitated by the development of gap junctions between the myometrial cells.

• The first stage of labour is measured from the onset of strong and regular effective contractions to full effacement and dilation of the cervix.

• The second stage of labour is characterized by strong expulsive contractions, aided by respiratory muscle involvement, until the fetus is delivered.

• The passage of the fetus through the pelvis is described as the mechanism of labour and is achieved through the contractions forcing the presenting part to rotate against the muscle tone, structural resistance and shape of the pelvic floor.

• The third stage of labour covers the delivery of the placenta and fetal membranes and staunching of maternal blood loss.

• Maternal blood loss immediately following separation of the placenta is limited by the myometrial fibres contracting, thus occluding the uterine vessels.

• The onset of labour is poorly understood; a fetal signal probably alters the ratio of progesterone and oestrogen and other factors, such as prostaglandin secretion and oxytocin receptor expression, are involved in the amplification of the signal.

• The evolution of bipedal locomotion and increasing cephalization have influenced parturition in humans so the presenting part has to negotiate, by rotational manoeuvres, rather than just pass through the pelvic girdle.

• The process of labour induces many changes within the fetus in preparation for extrauterine existence, which are mediated by increasing hypoxia and catecholamine production.

• Pain in labour has a complex aetiology; there are visceral and somatic components further complicated by psychological and social factors.

Application to practice

Midwives need to understand the physiological interactions and external factors that can affect human labour in order to underpin intrapartum care.

The development of observational skills allows the midwife not only to interpret how a woman may be coping with labour, but also to determine how the labour is progressing from observing behaviour and physical responses of the labouring woman. By ignoring, not noticing or misunderstanding certain physical cues, the midwife may inadvertently provide suboptimal support.

Intervention in labour must be justified and decisions surrounding this must be underpinned to maximize maternal and fetal well-being. Knowledge of the effects of intervention upon fetal and maternal physiology is essential so that the midwife can judge the effectiveness and quickly identify possible adverse outcomes of such interventions.

Annotated further reading

Abitbol, M.M., Birth and human evolution: anatomical and obstetric mechanics in primates. (1996) Greenwood Press .

This book describes the evolutionary development of the mechanisms of birth in monkeys and primates including humans.

Baston, H.; Hall, J., In: ed 1 Midwifery Essentials: LabourVol. 3 (2009) Churchill Livingstone.

This book provides a comprehensive guide but easy to follow guide to care in labour including waterbirth and caesarean section.

Blackburn, S.T., Maternal, fetal and neonatal physiology: a clinical perspective. ed 3 (2007) Saunders, Philadelphia .

An excellent in-depth description of physiological adaptation to pregnancy and consequent development of the fetus and neonate that draws from physiological research studies. The chapters are clearly organized by physiological systems and link physiological concepts to clinical applications including the assessment and management of low- and high-risk pregnancies.

Challis, J.R.; Lockwood, C.J.; Myatt, L.; et al., Inflammation and pregnancy, Reprod Sci 16 (2009) 206–215.

A brief review of the inflammatory changes in pregnancy which considers how inflammation is involved in preterm delivery.

In: (Editors: Chapman, V.; Charles, C.) The Midwife's Labour and Birth Handbook ed 2 (2008) Wiley Blackwell; Location.

This book focuses on the promotion of normality through a women centred approach to care in labour. It includes chapters on waterbirth, homebirth, breech, Caesarean section and vaginal birth after Caesarean section.

Dick-Read, G; Odent, M, Childbirth without Fear: The Principles and Practice of Natural Childbirth. ed 4 (2007) Pinter & Martin Ltd ; (Revised).

This Classic book was first published in 1942 and remains in print today. It challenges modern medical obstetric practice and essential reading for those interested in the development of modern intrapartum care.

Gary, Cunningham FG. Williams Obstetrics. ed 23 (2009) McGraw-Hill Medical .

This book, is a comprehensive book for obstetrics and is a useful reference book for midwives interested in reproductive pathophysiology.

Iams, J.D.; Romero, R.; Culhane, J.F.; et al., Primary, secondary, and tertiary interventions to reduce the morbidity and mortality of preterm birth, Lancet 371 (2008) 164–175.

A balanced discussion of the medical and therapeutic approaches to reduce the morbidity and mortality of preterm birth classified as primary (directed to all women), secondary (aimed at eliminating or reducing existing risk), or tertiary (intended to improve outcomes for preterm infants).

Liu, D., Labour Ward Manual. ed 4 (2007) Churchill Livingstone Elsevier, Edinburgh .

This book provides guidance on the clinical management of complications associated with labour.

López Bernal, A., The regulation of uterine relaxation, Semin Cell Dev Biol 18 (2007) 340–347.

A review of the mechanisms controlling myometrial contraction which describes how uterine quiescence changes during pregnancy and tocolytic therapy in preterm labour.

National Collaborating Centre for Women's and Children's Health, Intrapartum care – care of healthy women and their babies during childbirth. (2007) National Institute of Clinical Excellence ; (Clinical guideline 55).

This guideline presents clinical based labour care from an evidenced based care perspective.

Quigley, E.M., Impact of pregnancy and parturition on the anal sphincters and pelvic floor, Best Pract Res Clin Gastroenterol 21 (2007) 879–891.

A thorough discussion of the underlying pathophysiology of anal sphincter and pelvic floor damage in childbirth which can lead to incontinence and defaecation difficulties.

Reuwer, P., Proactive Support of Labor: The Challenge of Normal Childbirth. ed 1 (2009) Cambridge University Press, Cambridge .

Written by obstetricians, this book challenges current obstetric practice within the United States of America by focusing on the promotion of normality.

Walsh, D., Evidence-based Care for Normal Labour and Birth. A Guide for Midwives. ed 1 (2007) Routledge, London ; (Paperback).

This is essential reading for practitioners wanting to extend their knowledge and skills in intrapartum care outside current medical models of care.

In: (Editors: Walsh, D.; Downe, S.) Intrapartum Care, Essential Midwifery Practice ed 1 (2010) Wiley-Blackwell.

This book describes how intrapartum care has evolved and developed in relation with the development of midwifery practice. It has chapters that explore issues such as psychology, sexuality, spirituality, feminism and complimentary therapies in relation to intrapartum care.


Aitken, M.A.; Rice, G.E.; Brennecke, S.P., Gestational tissue phospholipase A2 messenger RNA content and the onset of spontaneous labour in the human, Reprod Fertil Dev 2 (1990) 575–580.

Apostolakis, E.M.; Rice, K.E.; Longo, L.D.; et al., Time of day of birth and absence of endocrine and uterine contractile activity rhythms in sheep, Am J Physiol 264 (1993) E534–E540.

Bani, D., Relaxin: a pleiotropic hormone, Gen Pharmacol 28 (1997) 13–22.

Barret, J.F.R.; Savage, J.; Phillips, K.; et al., Randomised trial of amniotomy in labour versus the intention to leave membranes intact until the second stage, Br J Obstet Gynaecol 99 (1992) 5.

Beck, S.; Wojdyla, D.; Say, L.; et al., The worldwide incidence of preterm birth: a systematic review of maternal mortality and morbidity, Bull World Health Organ 88 (2010) 31–38.

Bennett, V.R.; Brown, L.K., In: Myles' textbook for midwives ed 13 (1999) Churchill Livingstone, Edinburgh, pp. 393–396; 431, 451, 468, 473, 509, 993.

Berkman, N.D.; Thorp Jr., J.M.; Lohr, K.N.; et al., Tocolytic treatment for the management of preterm labor: a review of the evidence, Am J Obstet Gynecol 188 (2003) 1648–1659.

Bernal, A.L.; Europe-Finner, G.N.; Phaneuf, S.; et al., Preterm labour: a pharmacological challenge, Trends Pharmacol Sci 16 (1995) 129–133.

Blackburn, S.T., Maternal, fetal, and neonatal physiology: a clinical perspective. ed 3 (2007) Saunders, Philadelphia .

Blumenfeld, Y.J.; Lyell, D.J., Prematurity prevention: the role of acute tocolysis, Curr Opin Obstet Gynecol 21 (2009) 136–141.

Bodner, K.; Bodner-Adler, B.; Wierrani, F.; et al., Effects of water birth on maternal and neonatal outcomes, Wien Klin Wochenschr 114 (10–11) (2002) 391–395.

Bowen, J.M.; Chamley, L.; Keelan, J.A.; et al., Cytokines of the placenta and extra-placental membranes: roles and regulation during human pregnancy and parturition, Placenta 23 (4) (2002) 257–273.

Boyle, J.T., Motility of the upper gastrointestinal tract in the fetus and neonate, In: (Editors: Polin, R.A.; Fox, WW,) Fetal and neonatal physiologyVol. 2 (1992) Saunders, Philadelphia, pp. 1028–1032.

Carp, H.; Jayaram, A.; Stoll, M., Ultrasound examination of the stomach contents of parturients, Anesth Analg 74 (1992) 683–687.

Challis, J.R.G.; Matthews, S.G.; Gibb, W.; et al., Endocrine and paracrine regulation of birth at term and preterm, Endocr Rev 21 (2000) 514–550.

Clifton, V.L.; Read, M.A.; Leitch, I.M.; et al., Corticotropin-releasing hormone-induced vasodilatation in the human fetal placental circulation, J Clin Endocrinol Metab 79 (2) (1994) 666–669.

Cluett, E.R.; Burns, E., Immersion in water in labour and birth, Cochrane Database Syst Rev (2009); CD000111, 2009.

De Ziegler, D.; Bulletti, C.; Fanchin, R.; et al., Contractility of the nonpregnant uterus: the follicular phase, Ann N Y Acad Sci 943 (2001) 172–184.

Duff, P., Premature rupture of the membranes in term patients, Semin Perinatol 20 (1996) 401–408.

Eberhard, J; Stein, S.; Geissbuehler, V.; et al., Experience of pain and analgesia with water and land births, J Psychosom Obstet Gynecol 26 (2) (2005) 127–133.

Eberle, R.L.; Norris, M.C., Labor analgesia: a risk-benefit analysis, Drug Saf 14 (1996) 239–251.

Field, D.J.; Dorling, J.S.; Manktelow, B.N.; et al., Survival of extremely premature babies in a geographically defined population: prospective cohort study of 1994–9 compared with 2000–5, BMJ 336 (2008) 1221–1223.

Fuchs, A.R.; Fuchs, F.; Husslein, P.; et al., Oxytocin receptors in the human uterus during pregnancy and parturition, Am J Obstet Gynecol 150 (1984) 734–741.

Fuchs, A.R.; Romero, R.; Keefe, D.; et al., Oxytocin secretion and human parturition: pulse frequency and duration increase during spontaneous labour in women, Am J Obstet Gynecol 165 (1991) 1515–1522.

Garfield, R.E.; Blennerhassett, M.G.; Miller, S.M., Control of myometrial contractility: role and regulation of gap junctions, Oxf Rev Reprod Biol 10 (1988) 436–490.

Gee, H.; Olah, K.S., Failure to progress in labour, Prog Obstet Gynaecol 10 (1993) 159–181.

Geissbuehler, V.; Stein, S.; Eberhard, J.; et al., Waterbirths compared with landbirths: an observational study of nine years, J Perinat Med 32 (4) (2004) 308–314.

Germain, A.M.; Valenzuela, G.J.; Ivankovic, M.; et al., Relationship of circadian rhythms of uterine activity with term and preterm delivery, Am J Obstet Gynecol 168 (1993) 1271–1277.

Gluckman, P.D.; Sizonenko, S.V.; Bassett, N.S., The transition from fetus to neonate: an endocrine perspective, Acta Paediatr Suppl 88 (428) (1999) 7–11.

Goldenberg, R.L.; Culhane, J.F.; Iams, J.D.; et al., Epidemiology and causes of preterm birth, Lancet 371 (2008) 75–84.

Goldman, S.; Shalev, E., Progesterone receptor profile in the decidua and fetal membrane, Front Biosci 12 (2007) 634–648.

Goodwin, T.M., A role for estriol in human labor, term and preterm, Am J Obstet Gynecol 180 (1 Pt 3) (1999) S208–S213.

Grummer, R.; Winterhager, E., Regulation of gap junction connexins in the endometrium during early pregnancy, Cell Tissue Res 293 (2) (1998) 189–194.

Hampson, V.; Lui, D.; Billett, E.; et al., Amniotic membrane collagen content and type distribution in women with preterm premature rupture of the membranes in pregnancy, Br J Obstet Gynaecol 104 (1997) 1087–1091.

Hertelendy, F.; Zakar, T., Prostaglandins and the myometrium and cervix, Prostaglandins Leukot Essent Fatty Acids 70 (2) (2004) 207–222.

Hillhouse, E.W.; Grammatopoulos, D.K., Role of stress peptides during human pregnancy and labour, Reproduction 124 (3) (2002) 323–329.

Honnebier, M.B.O.M.; Nathanielsz, P.W., Primate parturition and the role of the maternal circadian system. European Journal of Obstetrics, Gynecol Reprod Biol 55 (1994) 193–203.

Honnebier, W.J.; Jobsis, A.C.; Swaab, D.F., The effect of hypophysial hormones and human chorionic gonadotrophin (HCG) on the anencephalic fetal adrenal cortex and on parturition in the human, J Obstet Gynaecol Br Commonw81 (6) (1974) 423–438.

Houlihan, C.M.; Knuppel, R.A., Meconium-stained amniotic fluid: current controversies, J Reprod Med 39 (11) (1994) 888–898.

Husslein, P., Pregnancy and plasma oxytocin levels, J Perinat Med 13 (1985) 314–315.

Jenkin, G.; Young, I.R., Mechanisms responsible for parturition; the use of experimental models, Anim Reprod Sci 82–83 (2004) 567–581.

Karalis, K.; Goodwin, G.; Majzoub, J.A., Cortisol blockade of progesterone: a possible mechanism involved in the initiation of labour, Nat Med 2 (1996) 556–560.

Karteris, E.; Grammatopoulos, D.; Dai, Y.; et al., The human placenta and fetal membranes express the corticotropin-releasing hormone receptor 1alpha (CRH-1alpha) and the CRH-C variant receptor, J Clin Endocrinol Metab 83 (4) (1998) 1376–1379.

Katz, V.; Bowes, W.A., Meconium aspiration syndrome: reflections on a murky subject, Am J Obstet Gynecol 166 (1 Pt 1) (1992) 171–183.

Lawn, J.E.; Lee, A.C.; Kinney, M.; et al., Two million intrapartum-related stillbirths and neonatal deaths: where, why, and what can be done? Int J Gynaecol Obstet 107 (Suppl. 1) (2009) S5–S18; S19.

Leppert, P.C., Anatomy and physiology of cervical ripening, Clin Obstet Gynaecol 38 (2) (1995) 267–279.

López Bernal, A., Mechanisms of labour: biochemical aspects, Br J Obstet Gynaecol 110 (Suppl. 20) (2003) 39–45.

MacLaughlin, S.M.; McMillen, I.C., Impact of periconceptional undernutrition on the development of the hypothalamo-pituitary-adrenal axis: does the timing of parturition start at conception? Curr Drug Targets 8 (2007) 880–887.

Melzack, R.; Wall, P.D., Pain mechanisms: a new theory, Science 150 (699) (1965) 971–979.

Mesiano, S., Myometrial progesterone responsiveness and the control of human parturition, J Soc Gynecol Investig 11 (4) (2004) 193–202.

Miller, F.D.; Chibbar, R.; Mitchell, B.F., Synthesis of oxytocin in amnion, chorion and decidua: a potential paracrine role for oxytocin in the onset of human parturition, Regul Pept 45 (1993) 247.

Mitchell, B.F.; Taggart, M.J., Are animal models relevant to key aspects of human parturition? Am J Physiol Regul Integr Comp Physiol 297 (2009) R525–R545.

Mitchell, B.F.; Wong, S., Changes in 17 beta,20 alpha-hydroxysteroid dehydrogenase activity supporting an increase in the estrogen/progesterone ratio of human fetal membranes at parturition, Am J Obstet Gynecol 168 (1993) 1377–1385.

Mulder, E.J.H.; Boersma, M.; Meeuse, M.; et al., Patterns of breathing movements in the near-term fetus: relationship to behavioural states, Early Hum Dev 36 (1994) 127–135.

Nakamura, K.; Sheps, S.; Arck, P.C., Stress and reproductive failure: past notions, present insights and future directions, J Assist Reprod Genet 25 (2008) 47–62.

NCCWCH, Intrapartum care – care of healthy women and their babies during childbirth. (2007) National Institute of Clinical Excellence ; (Clinical guideline 55).

Neulen, J.; Breckwoldt, M., Placental progesterone, prostaglandins and mechanisms leading to initiation of parturition in the human, Exp Clin Endocrinol 102 (3) (1994) 195–202.

Nijhuis, J.G., Fetal behavior, Neurobiol Aging 24 (Suppl. 1) (2003) S41–S46.

Odent, M., New reasons and new ways to study birth physiology, Int J Gynecol Obstet 75 (2001) S39–S45.

Olah, K.S., Changes in cervical electromyographic activity and their correlation with cervical response to myometrial activity during labour, Eur J Obstet Gynecol Reprod Biol 3 (1994) 157–159.

Olah, K.S.; Gee, H.; Brown, J.S., Cervical contractions: the response of the cervix to oxytocic stimulation in the latent phase of labour, Br J Obstet Gynaecol 100 (1993) 635–640.

Olson, D.M.; Zaragoza, D.B.; Shallow, M.C.; et al., Myometrial activation and preterm labour: evidence supporting a role for the prostaglandin F receptor: a review, Placenta 24 (Suppl. A) (2003) S47–S54.

Petersen, L.K.; Oxlund, H.; Uldberg, N.; et al., In vitro analysis of muscular contractile ability and passive biomechanical properties of uterine cervical samples from non-pregnant women, Obstet Gynaecol 77(1991) 772–776.

Petraglia, F.; Benedetto, C.; Florio, P.; et al., Effect of corticotropin-releasing factor-binding protein on prostaglandin release from cultured maternal decidua and on contractile activity of human myometrium in-vitro, J Clin Endocrinol Metab 80 (1995) 3073–3076.

Romero, R.; Chaiworapongsa, T.; Espinoza, J., Micronutrients and intrauterine infection, preterm birth and the fetal inflammatory response syndrome, J Nutr 133 (5 Suppl. 2) (2003) 1668S–1673S.

Rosenberg, K.; Trevathan, W., Birth, obstetrics and human evolution, Br J Obstet Gynaecol 109 (11) (2002) 1199–1206.

Rowe, T.F., Acute gastric aspiration: prevention and treatment, Semin Perinatol 21 (1997) 313–319.

Saigal, S.; Doyle, L.W., An overview of mortality and sequelae of preterm birth from infancy to adulthood, Lancet 371 (2008) 261–269.

Scheepers, H.C.; de Jong, P.A.; Essed, G.G.; et al., Fetal and maternal energy metabolism during labor in relation to the available caloric sustrate, J Perinat Med 29 (6) (2001) 457–464.

Scutton, M.; Lowy, C.; O'Sullivan, G., Eating in labour: an assessment of the risks and benefits, Int J Obstet Anesth 5 (1996) 214–215.

Shynlova, O.; Tsui, P.; Jaffer, S.; et al., Integration of endocrine and mechanical signals in the regulation of myometrial functions during pregnancy and labour, Eur J Obstet Gynecol Reprod Biol 144 (Suppl. 1) (2009) S2–110.

Slattery, M.M.; Brennan, C.; O'Leary, M.J.; et al., Human chorionic gonadotrophin inhibition of pregnant human myometrial contractility, Br J Obstet Gynaecol 108 (7) (2001) 704–708.

Smith, R., Parturition, N Engl J Med 356 (2007) 271–283.

Smith, R.; Nicholson, R.C., Corticotrophin releasing hormone and the timing of birth, Front Biosci 12 (2007) 912–918.

Smith, R.; Van Helden, D.; Hirst, J.; et al., Pathological interactions with the timing of birth and uterine activation, Aust N Z J Obstet Gynaecol 47 (2007) 430–437.

Steer, P.J.; Johnson, M.R., The genital system, In: (Editors: Chamberlain, G.; Broughton Pipkin, F.) Clinical physiology in obstetrics ed 3 (1998) Blackwell, Oxford, pp. 308–355.

Stephens, B.E.; Vohr, B.R., Neurodevelopmental outcome of the premature infant, Pediatr Clin North Am 56 (2009) 631–646.

Stewart, D.B., The pelvis as a passageway I. Evolution and adaptations, Br J Obstet Gynaecol 91 (1984) 611–617.

Stjernholm, Y.; Sahlin, L.; Akerberg, S.; et al., Cervical ripening in humans: potential roles of estrogen, progesterone and insulin-like growth factor-I, Am J Obstet Gynecol 174 (1996) 1065–1071.

Sullivan, J.M.; Ramanathan, K.B., Management of medical problems in pregnancy: severe cardiac disease, N Engl J Med 313 (1985) 304–309.

Sweet, B.; Tiran, D., In: Mayes' midwifery ed 12 (1996) Baillière Tindall, London, pp. 31–224; 225, 340, 358, 993.

Symonds, E.M.; Symonds, I.M., In: Essential obstetrics and gynaecology ed 3 (1997) Churchill Livingstone, Edinburgh, p. 134.

Terzidou, V., Preterm labour. Biochemical and endocrinological preparation for parturition, Best Pract Res Clin Obstet Gynaecol 21 (2007) 729–756.

Thoeni, A.; Zech, N.; Moroder, L.; et al., Water birth and the risk of infection. Experience after 1500 water births, Pol J Gyn Invest 7 (1/4) (2004) 21–26.

Thong, K.J.; Baird, D.T., Induction of abortion with mifepristone and misoprostol in early pregnancy, Br J Obstet Gynaecol 99 (1992) 1004–1007.

Thorburn, G.D., The placenta, PGE2 and parturition, Early Hum Dev 29 (1992) 63–73.

Uldbjerg, N.; Malstrom, A., The role of proteoglycans in cervical dilatation, Semin Perinatol 15 (1991) 127–132.

Warnes, K.E.; Morris, M.J.; Symonds, M.E.; et al., Effects of increasing gestation, cortisol and maternal undernutrition on hypothalamic neuropeptide Y expression in the sheep fetus, J Neuroendocrinol 10(1998) 51–57.

Weiss, A.; Goldman, S.; Shalev, E., The matrix metalloproteinases MMPS in the decidua and fetal membranes, Front Biosci 12 (2007) 649–659.

Wilmsatt, J.; Myers, D.A.; Myers, T.R.; et al., Prostaglandin synthase activity of fetal sheep cotyledons at 122 days of gestation and term-expression of prostaglandin synthetic capacity in fetal cotyledonary tissue near labor is location-dependent, Biol Reprod 52 (1995) 737–744.

Wolfe, C.D.A.; Petruckevitch, A.; Quartero, R.; et al., The rate of rise of corticotropin releasing-factor and endogenous digoxin-like immunoreactivity in normal and abnormal pregnancy, Br J Obstet Gynaecol97 (1990) 832–837.

Wray, S., Uterine contraction and physiological mechanisms of modulation, Am J Physiol 264 (1993) C1–C18.

Wray, S.; Jones, K.; Kupittayanant, S.; et al., Calcium signaling and uterine contractility, J Soc Gynecol Investig 10 (5) (2003) 252–264.

Yuan, W.; López Bernal, A., Cyclic AMP signalling pathways in the regulation of uterine relaxation, BMC Pregnancy Childbirth 7 (Suppl. 1) (2007) S10.