As the newborn exits the birth canal, it takes its first breath, which not only expands the lungs but also triggers a series of changes in the circulatory system. At the same time, the newborn loses its nutritional connection to the mother and confronts a cold new world. Three major challenges to metabolism accompany birth: hypoxia, hypoglycemia, and hypothermia. We discuss the adaptations of the respiratory and cardiovascular systems in this subchapter, and adjustments of other organ systems in the next.
Loss of the placental circulation requires the newborn to breathe on its own
Although separation of the placenta does not occur until several minutes after birth, vasoconstriction in the umbilical arteries terminates the ability of the placenta to deliver oxygenated blood to the newborn immediately upon birth. Thus, even though the newborn may remain attached to its placenta during the first few moments of life, it is essential that the baby begin to breathe immediately. Umbilical vasoconstriction has two origins. First, the stretching of the umbilical arteries during delivery stimulates them to constrict. Second, the sudden rise in the systemic arterial in the newborn also stimulates and maintains vasoconstriction in the umbilical arteries. Birth may also be associated with an “autotransfusion” as blood in the placental circulation preferentially moves into the body of the emerging baby. Because the umbilical veins do not constrict as do the umbilical arteries, blood flows from placenta to newborn if the infant is held below the level of the placenta, and if the umbilical cord is not clamped. This autotransfusion may constitute 75 to 100 mL, which is a substantial fraction of the newborn's total blood volume of ~300 mL (90 mL/kg).
At birth, the newborn must transform its circulatory system from one that supports gas exchange in the placenta to one that supports O2 and CO2 exchange in the lungs. In addition, other circulatory adjustments must occur as the gastrointestinal tract, liver, and kidneys assume their normal roles. As the lungs become functional at birth, the pulmonary and systemic circulations shift from interconnected and parallel systems to separate entities that function in series.
Mild hypoxia and hypercapnia, as well as tactile stimuli and cold skin, trigger the first breath
The first breath is the defining event for the newborn. Not only does it inflate the lungs, but also—as discussed below—it triggers circulatory changes that convert the fetal pattern of blood flow to the adult pattern. The functional capabilities of the lungs depend on the surface area available for gas exchange, the ability of surfactant to maximize lung compliance, neural mechanisms that control breathing and the aforementioned circulatory changes.
The first breath is normally also the most difficult inspiration of a lifetime. A considerable negative pressure within the intrapleural space is necessary to overcome the effects of surface tension (stage 1 in Fig. 27-4B). The infant's first inspiratory effort requires a transpulmonary pressure (PTP)—the pressure difference between the intrapleural space and alveolar air spaces (see p. 608)—of 60 cm H2O to increase the lung volume by ~40 mL. In contrast, a typical adult only needs to change PTP by ~2.5 cm H2O during a typical tidal volume of 500 mL (see Fig. 27-5). The newborn's first ventilatory effort creates an air-water interface for the first time, opening the alveoli. Breathing becomes far easier once the alveoli are open and the type II alveolar pneumocytes deliver surfactant to the air-water interface. Thus, the second inspiration may require a PTP of only 40 cm H2O. The newborn may not achieve the adult level of relative lung compliance until 1 hour after birth. Very immature neonates, who lack adequate surfactant (see Box 57-2), may have persistent difficulty expanding the lungs.
The rapid onset of breathing immediately after delivery appears to be induced by a temporary state of hypoxia and hypercapnia. In most normal deliveries, these changes in and result from the partial occlusion of the umbilical cord. Tactile stimulation and decreased skin temperature also promote the onset of breathing. When newborns do not begin to breathe immediately, hypercapnia and hypoxia increase and provide further simulation for the infant to breathe.
The peripheral and central chemoreceptors (see pp. 709–717) are responsible for sensing the blood-gas parameters (i.e., low , high , and low pH), detecting asphyxia, and stimulating respiration. In addition, increased sympathetic tone may stimulate breathing at the time of birth by constricting vessels to the peripheral chemoreceptors (see pp. 711–712) and thereby lowering the local in the microenvironment of the glomus cells and mimicking even more severe hypoxia. Finally, independent of the initial stimuli that trigger breathing, other central nervous system mechanisms may help to sustain breathing in the newborn. However, when asphyxia is severe, the changes in blood-gas concentrations may obtund rather than stimulate breathing, so that assisted ventilation and resuscitation are required.
The neonate's ability to control blood-gas parameters depends on the sensitivity of the lung's mechanical (i.e., stretch) reflexes, sensitivity of the central and peripheral chemoreceptors, gestational and postnatal age, ability of the respiratory muscles to resist fatigue, and effects of the sleep state. Variability in tidal volume (see p. 601) and timing of breathing as well as episodes of decreased arterial (<90%) are common in healthy infants and are even more pronounced in premature infants. However, the variability decreases over the first few weeks, so that by ~1 month after normal term gestation (i.e., 44 weeks postconceptional age), periods with desaturation are rare, with no discernible differences between preterm and full-term infants.
Sleeping newborns, especially premature newborns, tend to have increased respiratory variability from breath to breath. For example, they exhibit periodic breathing, which consists of breaths with intermittent respiratory pauses (generally of a few to several seconds' duration) and varying tidal volumes. Periodic breathing and increased respiratory variability occur more frequently during rapid eye movement sleep than during quiet sleep, a state characterized by regular breathing, but the mechanisms underlying periodic breathing in the newborn remain unclear. N57-6
Apnea in the Newborn
Contributed by Gabriel Haddad
Apnea of prematurity or apnea in a full-term infant is defined in two ways:
1. Statistically: Based on the distribution of respiratory pauses in a population of infants. Using this definition, respiratory pauses >20 seconds in premature infants and >30 seconds in full-term infants during the first several months of life are too long to be normal and hence are termed apneas.
2. Physiologically: Based on the physiological consequences of respiratory pauses. For example, if a respiratory pause induces deleterious cardiovascular effects (e.g., bradycardia or cyanosis), that respiratory pause may also be termed apnea even if the duration of the apnea is <20 or 30 seconds as stated above. Hence, this latter definition is based on functional consequences and is therefore more clinically relevant.
At birth, removal of the placenta increases systemic vascular resistance, whereas lung expansion decreases pulmonary vascular resistance
As noted on pages 1157–1158, the fetal circulation has four unique pathways for blood flow absent in the adult: the placental circulation, ductus venosus, foramen ovale, and ductus arteriosus. In this and the next three sections, we discuss the closure of each of these four pathways.
At birth, blood flow to the placenta ceases when the umbilical vessels are ligated, and the shunts progressively disappear over the ensuing hours to days. In addition, the pulmonary circulation, which received only ~7% of the CCO in the fetus, now accepts the entire cardiac output.
Removal of the Placental Circulation
The placental circulation, which receives ~50% of the CCO (see Fig. 57-3A), represents a major parallel path in the systemic circulation and accounts for the low vascular resistance of the fetal systemic circulation. When the placental circulation disappears at birth, the total peripheral resistance doubles. Because blood flow through the descending aorta is essentially unchanged, aortic and left ventricular systolic pressure must increase.
Increase in Pulmonary Blood Flow
During fetal life, hypoxic vasoconstriction (see p. 687) markedly limits pulmonary blood flow and thereby diverts right ventricular flow through the ductus arteriosus. At birth, pulmonary vascular resistance abruptly decreases >5-fold with breathing (Fig. 57-4), owing to lung expansion, an increase in alveolar , a decrease in alveolar —each of which has discernible independent effects—and perhaps the release of PGI2 (or prostacyclin). As a result, blood flow through the pulmonary vasculature increases by ~4-fold at birth, whereas pulmonary arterial and right ventricular pressure fall abruptly. These pressures continue to decline over the ensuing few months because of a regression of the pulmonary arterial musculature, growth of new pulmonary vessels, and, to some extent, the decline in blood viscosity as hematocrit falls.
FIGURE 57-4 Effect of birth on pulmonary vascular resistance, blood flow, and mean arterial pressure. In the fetus, pulmonary vascular resistance is high, pulmonary blood flow is low, and mean pulmonary arterial pressure is high. At birth, each of these three situations rapidly reverses. The primary event is the fall in resistance, which occurs because (1) the pulmonary blood vessels are no longer being crushed; (2) breathing causes an increased , which in turn causes vasodilation; and (3) local prostaglandins cause vasodilation. The reason that pressure falls after birth is that the fall in pulmonary vascular resistance is greater than the rise in blood flow. (Data from Rudolph AM: Congenital Diseases of the Heart: Clinical-Physiological Considerations. Armonk NY, Futura, 2001.)
Closure of the ductus venosus within the first days of life forces portal blood to perfuse the liver
Although blood flow through the umbilical vein ceases soon after birth, the majority of the portal blood continues to flow through the ductus venosus. Thus, immediately after birth, portal flow through the liver remains low. However, within a few days after term birth (longer after preterm birth), constriction of the vascular smooth muscle within the ductus venosus causes functional closure of this shunt pathway. As a result, pressure in the portal vein increases markedly, thereby diverting blood into the liver. The mechanisms underlying the contraction of the muscular walls of the ductus venosus remain unknown.
Closure of the foramen ovale occurs as left atrial pressure begins to exceed right atrial pressure
After birth, the decrease in the pulmonary vascular resistance permits increased blood flow through the lungs, which increases venous return to the left atrium and elevates left atrial pressure. At the same time, the increase in pulmonary blood flow, the closing of the ductus arteriosus, and the increase in systemic resistance (due to removal of the placenta) conspire to decrease blood flow down the descending aorta and thus the venous return to the right atrium. As a result, right atrial pressure falls. The net effect of the rise in left atrial pressure and the fall in right atrial pressure is a reversal of the pressure gradient across the atrial septum that pushes a flap of tissue—which previously protruded into the left atrium—back against the septum, functionally closing the foramen ovale (Fig. 57-5A). Closing the foramen usually prevents flow of blood from the left to the right atrium of the newborn.
FIGURE 57-5 Changes in the circulation at and around birth. A, The closure of the foramen ovale and ductus arteriosus establish separate right and left circulatory systems. As the pressure in the left atrium rises above the pressure in the right atrium—due to the large decrease in pulmonary vascular resistance—the flap of the foramen ovale pushes against the septum, preventing blood flow from the left to the right atrium. Eventually this flap seals shut. As aortic pressure exceeds the pressure of the pulmonary artery, blood flow through the ductus arteriosus reverses. Well-oxygenated aortic blood now flows through the ductus arteriosus. This high causes vasoconstriction, which functionally closes the ductus arteriosus within a few hours. Falling prostaglandin levels also contribute to the rapid closure. Eventually, the lumen of the ductus becomes anatomically obliterated. B, The elimination of the fetal shunts and the oxygenation of blood in the lungs lead to major increases in the O2 saturation and in the circulation.
The separation between the atria often becomes permanent as additional tissue grows over the foramen ovale in a few months. However, in some infants, the two flaps of atrial septal tissue that overlie the foramen N57-5 do not completely adhere, so that a potential remnant pathway is left between the two atria. About 15% to 25% of adults still have a patent foramen ovale that can permit blood to flow from the right to the left atrium if right atrial pressure exceeds left atrial pressure. Such a right-to-left shunt can occur pathologically in pulmonary hypertension or physiologically following heavy weightlifting. The shunt can also create a path by which a thrombus that develops in the systemic venous circulation can bypass the lungs and travel right to left into the systemic arterial circulation—a well-recognized mechanism for stroke in susceptible adults.
Closure of the ductus arteriosus completes the separation between the pulmonary and systemic circulations
Immediately after birth, the ductus arteriosus remains open but blood flow, which follows the path of least resistance, now begins to shunt (left to right) from the descending aorta to the pulmonary circulation because of the two events that change the relationship between pulmonary and systemic vascular resistance: (1) increased systemic resistance because of the removal of the placenta, and (2) decreased pulmonary resistance because of the expansion of the lungs.
Within a few hours after term birth, the ductus arteriosus closes functionally because its muscular wall constricts (see Fig. 57-5A). Usually, all blood flow through the ductus arteriosus ceases within 1 week after birth. Within a month or so, the lumen becomes obliterated anatomically because of thrombosis (i.e., blood clot within the lumen), intimal thickening, and loss of smooth-muscle cells.
The relatively rapid functional closure of the ductus arteriosus after birth is primarily the result of an increased of the arterial blood (caused by breathing) that perfuses this vessel, a decrease in circulating PGE2 (caused by placenta removal and increased pulmonary PGE2 uptake), and a decrease in PGE2 receptors in the ductus wall. As the of blood flowing through the ductus arteriosus rises from 18 to 22 mm Hg in utero to ~60 mm Hg a few hours after birth, the smooth muscle in the wall of the ductus arteriosus contracts, which reduces or eliminates flow through the ductus. This contraction also constricts the vasa vasorum of the ductus, contributing to smooth-muscle apoptosis in the vessel wall. It is quite common, however, for the ductus arteriosus to remain patent in preterm infants, especially those who are most premature, and occasionally in the full-term infant. A patent ductus arteriosus allows a left-to-right shunt of blood from the aorta to the pulmonary artery because the aorta has a higher pressure. In the premature infant, reduced O2 sensitivity and less smooth muscle contribute to prolonged patency. If the shunt is large, it has significant hemodynamic consequences because of the excess flow to the lungs and reduced flow to systemic organs. In such cases, administration of a cyclooxygenase (COX) inhibitor (see Box 3-3) such as indomethacin (which decreases levels of the vasodilator PGE2; see p. 1158) or surgical ligation can close the ductus. In some newborns with congenital cardiac defects that block or severely decrease pulmonary blood flow, the ductus arteriosus may be the only route for getting blood to the lungs for gas exchange (Box 57-4).
Congenital Cardiac Disease
Cardiac malformations are the most common significant congenital defects (~7 in 1000 live births). Many of the most severe defects still permit normal growth in utero but become life threatening when the infant is born. Despite progress in elucidating the genetic basis for these malformations, treatment of infants still relies on early diagnosis and medical and surgical management. Application of the findings of basic laboratory studies has contributed to dramatic reversal of prognosis for malformations that were nearly universally fatal 50 years ago. Of those severe cardiac defects, some produce complete or nearly complete obstruction of blood flow from the right ventricle to the lungs (e.g., pulmonic valve atresia or severe pulmonary valve stenosis) and some cause obstruction of blood flow from the left ventricle to the systemic tissues (e.g., aortic valve atresia, severe aortic valve stenosis, or severe narrowing of the aortic arch).
The infants with obstruction to pulmonary blood flow experience extreme hypoxemia unless the ductus arteriosus remains sufficiently patent to permit blood from the aorta to flow to the lungs and exchange oxygen. For those infants, infusion of PGE2 (to dilate the ductus) has become a life-saving therapy that permits adequate blood flow to the lungs and maintenance of a stable circulation for days until the valve is opened or bypassed in a surgical procedure. Indeed, the first major cardiac surgery in an infant was performed on a “blue baby” to create a connection (shunt) from the subclavian artery to the pulmonary artery—the Blalock-Taussig shunt—in 1944.
Infants with obstruction to systemic blood flow frequently present in circulatory shock with severe metabolic acidosis. When the ductus arteriosus is patent, blood flow can travel from the pulmonary artery to the aorta and perfuse the upper body (with retrograde flow) and the lower body. However, when the ductus narrows or closes as it usually does soon after birth, the situation becomes life threatening. Again, infusion of PGE2 can nearly instantly improve systemic perfusion and ameliorate the shock-like state unless there has already been sustained damage to organs from inadequate circulation. Surgical management of some lesions—such as coarctation (narrowing) of the aorta—can result in a normal or near-normal life.
Other lesions—such as hypoplastic left heart syndrome, which includes aortic and mitral valve atresia and only a single right ventricle that is functional—present a much more complex surgical problem that require either a staged-management approach or even heart transplantation.
The closure of the ductus arteriosus completes the separation of the right and left circulations initiated with closure of the foramen ovale. Whereas the ventricles functioned in parallel in the fetus, now they function in series in the neonate. As a result, the O2 saturation of the newborn's Hb is similar to that of the adult's (see Fig. 57-5B). Although intrapulmonary shunting and mismatch cause the arterial in the infant to be lower than that in the adult, the leftward shift of the O2 saturation curve of HbF (see p. 654) allows the newborn to achieve the same O2 saturation as an adult. In the neonate, the sum of the ventricular outputs of the two ventricles (i.e., twice the cardiac output) is larger than the CCO in the fetus, a result primarily of a marked rise in the output of the left ventricle, which doubles its stroke volume. Compared with the adult, the newborn has a markedly lower systemic vascular resistance and thus can achieve a relatively high blood flow with a relatively low perfusion pressure (see Box 57-4).