Williams Manual of Pregnancy Complications, 23 ed.

CHAPTER 93. Meconium Aspiration, Cerebral Palsy, and Other Diseases of the Fetus and Newborn


Term infants can have significant respiratory complications, although much less frequently than those born preterm (see Chapter 90). Common causes in term infants include sepsis and intrauterine-acquired pneumonia, persistent pulmonary hypertension, meconium aspiration syndrome, and pulmonary hemorrhage. Septicemia, especially from group B streptococcal disease, is a relatively common cause of respiratory distress in the term infant.

Treatment is similar to that for respiratory distress from surfactant deficiency in preterm neonates previously described (see Chapter 90). Advances in neonatal care have improved the survival rate and decreased morbidity. Two important advances are the use of high-frequency oscillatory ventilation, and the use of nitric oxide as a pulmonary vasodilator for pulmonary hypertension. Compared with traditional therapy, nitric oxide significantly improves oxygenation and reduces the incidence of death or the need for extracorporeal membrane oxygenation (ECMO).

Meconium Aspiration

This is a severe pulmonary disease characterized by chemical pneumonitis and mechanical obstruction of the airways. It results from inhalation of meconium-stained amnionic fluid leading to inflammation of pulmonary tissues and hypoxia. Such inhalation can occur before labor, during labor, or at delivery. In severe cases, the pathological process progresses to persistent pulmonary hypertension and death.

In about 20 percent of pregnancies at term, amnionic fluid is contaminated by the passage of fetal meconium. In the past, this was considered a sign of “fetal distress” occurring only in response to hypoxia. It is now recognized, however, that in the majority of cases meconium passage is a manifestation of a normally maturing gastrointestinal tract, or is the result of inevitable vagal stimulation from umbilical cord compression. In a global sense, however, it continues to be a marker for adverse perinatal outcomes.

Aspiration of meconium-stained amnionic fluid before labor is a relatively common occurrence. In healthy, well-oxygenated fetuses with normal amnionic fluid volume, meconium is diluted and is readily cleared from the lungs by normal physiological mechanisms. In some infants, however, the inhaled meconium is not cleared, and meconium aspiration syndrome results. The syndrome may occur after otherwise normal labor, but it is more often encountered in post-term pregnancy or in association with fetal growth restriction. Meconium varies in concentration, and the syndrome is more likely when meconium is viscous or “thick.” Pregnancies at highest risk are those in which there is diminished amnionic fluid volume, along with cord compression or uteroplacental insufficiency that may cause meconium passage. In these cases, meconium is thick and undiluted, and the compromised fetus cannot clear it.


Early studies suggested that meconium aspiration syndrome could be prevented by oropharyngeal suctioning of the infant following delivery of the head, but before delivery of the chest. This maneuver is then followed by laryngoscopic visualization of the cords and, when meconium is visualized, additional suctioning of the trachea. Although this combined obstetric–pediatric delivery protocol is in common use, its efficacy in preventing meconium aspiration syndrome has been questioned.


Saline infused into the amnionic cavity may be beneficial when meconium straining is thick and there are recurrent variable decelerations. Amnioinfusion does not reduce moderate or severe meconium aspiration, perinatal death, or cesarean deliveries and American College of Obstetricians and Gynecologists (Amnioinfusion does not prevent meconium aspiration syndromeCommittee Opinion No. 346, 2006) does not recommend amnioinfusion to reduce meconium aspiration syndrome.


The mouth and nares should be carefully suctioned before the shoulders are delivered. A suction bulb is usually adequate. The DeLee trap can also be used, but should be connected to wall suction so that the attendant does not suction by mouth.

Infants who are depressed, or those who have passed thick, particulate meconium, are placed on the radiant warmer and residual meconium in the hypopharynx is removed by suctioning under direct visualization. The trachea is then intubated and meconium suctioned from the lower airway. The stomach is emptied to avoid the possibility of further meconium aspiration. It remains controversial whether a vigorous infant with thinly meconium-stained fluid requires such tracheal suctioning.


The etiology of cerebral palsy has been debated since 1862 when a London physician, William Little, described 47 children with spastic rigidity and implied that birth asphyxia caused this clinical picture. Sigmund Freud questioned this scenario over 100 years ago because abnormal birth processes frequently produced no such effects. It is now recognized that cerebral palsy is caused by a combination of genetic, physiological, environmental, and obstetrical factors. Although cerebral palsy is a complex multifactorial disease, the presumed birth asphyxia etiology for cerebral palsy has endured and has influenced the opinions and practices of countless obstetricians and pediatricians. This myth likely is one of the major reasons that at least one in three infants in the United States is currently born by cesarean delivery. Unfortunately, despite the substantive increase in cesarean delivery over 6 years, there has not been any significant decline in the rate of cerebral palsy. Some obstetricians, pediatricians, and neurologists—and most if not all plaintiff attorneys—still erroneously attribute many cases of cerebral palsy to “birth asphyxia.”

The term cerebral palsy refers to a group of disorders that are characterized by chronic movement or posture abnormalities that are cerebral in origin arise early in life and are nonprogressive.

Cerebral palsy may be categorized by the type of neurological dysfunction (spastic, dyskinetic, or ataxic) and by the number of limbs involved (quadriplegia, diplegia, hemiplegia, or monoplegia).

The major types of cerebral palsy are (1) spastic quadriplegia—which has an increased association with mental retardation and seizure disorders, (2) diplegia—which is common in preterm or low-birth-weight infants, (3) hemiplegia, (4) choreoathetoid types, and (5) mixed varieties. Significant mental retardation, defined as an intelligence quotient (IQ) less than 50, is associated with 25 percent of cerebral palsy cases.

Incidence and Epidemiological Correlates

The incidence of cerebral palsy is approximately 1 to 2 per 1000 live births. Importantly, the incidence has remained essentially unchanged since the 1950s, and it may actually have increased in some countries. As perhaps expected, cerebral palsy has increased coincidentally with an increase in survival of low-birth-weight infants. Advances in the care of very preterm infants have improved their survival, but not without significant handicaps such as cerebral palsy. Important antecedents and most commonly associated risk factors of cerebral palsy are (1) genetic abnormalities such as maternal mental retardation, microcephaly, and congenital malformations; (2) birth weight less than 2000 g; (3) gestational age less than 32 weeks; and (4) infection (Table 93-1).

TABLE 93-1. Prenatal and Perinatal Risk Factors in Children with Cerebral Palsy



Intrapartum Events

Obstetricians and the legal system naturally want to know whether cerebral palsy is related to the mismanagement of labor, which could be prevented or avoided. This usually is not the case as fully 70 to 90 percent of cases are due to factors other than intrapartum asphyxia. The role of continuous electronic fetal monitoring in predicting or allowing prevention of cerebral palsy has been studied. Data from a variety of sources indicate that such monitoring neither predicts nor reduces the risk of cerebral palsy. Moreover, no specific heart rate pattern has been identified that predicts cerebral palsy (see Chapter 13).

Neonatal Encephalopathy

Neonatal encephalopathy is used to describe a defined syndrome of disturbed neurological function in the earliest days of life in the term infant. It consists of difficulty in initiating and maintaining respiration, depressed tone and reflexes, subnormal level of consciousness, and frequently seizures. There are many different etiologies of encephalopathy which may or may not result in cerebral palsy (ACOG, AAP 2003). One etiology is hypoxic insult which can occur both during labor and/or earlier in the pregnancy depending on the cause.

American College of Obstetricians and Gynecologists (Inappropriate use of the terms fetal distress and birth asphyxia. Committee Opinion No. 197, February 1998, Committee Opinion No. 303, October2004) defines birth asphyxia by (1) profound metabolic or mixed acidemia (pH less than 7.00) determined on an umbilical cord arterial blood sample; (2) persistent Apgar score of 0 to 3 for longer than 5 minutes; and (3) evidence of neonatal neurological sequelae such as seizures, coma, or hypotonia, or dysfunction of one or more of the following systems: cardiovascular, gastrointestinal, hematological, pulmonary, or renal. Mild encephalopathy is generally defined as hyperalertness, irritability, jitteriness, and hypertonia and hypotonia. Moderate encephalopathy includes lethargy, severe hypertonia, and occasional seizures. Severe encephalopathy is defined by coma, multiple seizures, and recurrent apnea. Severe encephalopathy is an important predictor of cerebral palsy and future cognitive defects.


Unconjugated or free bilirubin is readily transferred across the placenta from fetal to maternal circulation—and vice versa, if the maternal plasma level of unconjugated bilirubin is high. Bilirubin glucuronide from the fetus is water soluble and normally excreted into the bile by the liver and into the urine by the kidney when the plasma level is elevated. Conversely, fetal unconjugated bilirubin is not excreted in the urine or to any extent in the bile and may lead to serious disease in the infant.


The great concern over unconjugated hyperbilirubinemia in the fetus–newborn, especially the preterm neonate, is its association with kernicterus. Yellow staining of the basal ganglia and hippocampus by bilirubin is indicative of profound degeneration in these regions. Surviving infants show spasticity, muscular incoordination, and varying degrees of mental retardation. There is a positive correlation between kernicterus and unconjugated bilirubin levels higher than 18 to 20 mg/dL, although kernicterus may develop at much lower concentrations, especially in very preterm infants.

Breast Milk Jaundice

Jaundice in breastfed infants has been attributed to the maternal excretion of pregnane-3α, 20β-diol into breast milk. This steroid blocks bilirubin conjugation by inhibiting glucuronyl transferase activity. Bovine and human milk appear to block the reabsorption of free bilirubin, whereas the milk of mothers with jaundiced offspring does not, and may even enhance its reabsorption. With breast milk jaundice, the serum bilirubin level rises from about the fourth day after birth to a maximum by 15 days. If breast feeding is continued, the high levels persist for another 10 to 14 days and slowly decline over the next several weeks. No cases of kernicterus have been reported as a result of this phenomenon.

Physiological Jaundice

By far the most common form of unconjugated nonhemolytic jaundice is so-called physiological jaundice. In the mature infant, the serum bilirubin increases for 3 to 4 days to achieve serum levels up to 10 mg/dL or so and then falls rapidly. In preterm infants, the rise is more prolonged and may be more intense.


Phototherapy is now widely used to treat hyperbilirubinemia. By some unknown mechanism, light seems to promote hepatic excretion of unconjugated bilirubin. In most instances, its use leads to oxidation of bilirubin, resulting in a lower bili-rubin level. As much surface area as possible should be exposed, and the infant should be turned every 2 hours with close temperature monitoring to prevent dehydration. The fluorescent bulbs must be of the appropriate wavelength, and the eyelids should be closed and completely shielded from light. Serum bilirubin should be monitored for at least 24 hours after discontinuance of phototherapy. Rarely, exchange transfusion is required.


Hydrops is defined by the presence of excess fluid in two or more body areas, such as the thorax, abdomen, or skin, and it is usually associated with hydramnios and placental thickening. Because ultrasound examination has become routine, fetal hydrops is identified frequently and the etiology is often discovered. A variety of pathogenic mechanisms (Table 93-2) can lead to fetal hydrops. The outcome for hydrops caused by any of these mechanisms is poor especially if diagnosed prior to 24 weeks.

TABLE 93-2. Some Causes of Hydrops Fetalis





Ultrasound evaluation may provide a diagnosis. Depending on circumstances, maternal blood analysis might include hemoglobin electrophoresis, Kleihauer–Betke smear, indirect Coombs, and serological tests for syphilis, toxoplasmosis, cytomegalovirus, rubella, and parvovirus B19. Cordocentesis may be considered for karyotyping, hemoglobin concentration and electrophoresis, liver transaminases, and serological testing for IgM-specific antibodies to infectious agents.


Some cardiac arrhythmias can be treated pharmacologically, severe anemia due to fetal–maternal hemorrhage or parvovirus infection can be treated with blood transfusions, and hydrops of one fetus in twin-to-twin transfusion syndrome (see Chapter 41) may resolve with therapeutic amniocentesis. Because most lesions associated with these syndromes ultimately prove fatal for the fetus or newborn, however, treatment is often not possible. In general, when hydrops persists, and cardiac abnormalities and aneuploidy have been ruled out, and the fetus is mature enough that survival is likely, then delivery should be accomplished. Very preterm fetuses usually are managed expectantly.


Recognition of fetal cardiac rhythm disturbances has become more common because of extensive use of real-time ultrasound. Whereas most of these arrhythmias are transient and benign, some tachyarrhythmias, if sustained, can result in congestive heart failure, nonimmune hydrops, and fetal death. Sustained bradycardia, although less often associated with hydrops, may signify underlying cardiac pathology that includes structural lesions or autoimmune myocarditis. Benign arrhythmias (isolated extrasystoles) were by far the most common arrhythmias encountered (see Table 93-3).

TABLE 93-3. Types of Arrhythmias in 198 Fetuses from Pregnancies Referred to Yale University


The prognosis for the fetus with persistent bradycardia is less promising. Bradycardia typically results from a major structural abnormality of the atrialventricular septum, or from heart block. Half of the mothers of children with congenital heart block have antibodies to fetal myocardial tissue. Anti-SS-A (anti-Ro) antibody is one of the most common and appears to bind to the conduction tissue. Unfortunately, tissue inflammation provoked by these antibodies leads to permanent damage, and survivors frequently require a pacemaker at birth.


This is a disorder of the newborn characterized by spontaneous internal or external bleeding accompanied by hypoprothrombinemia and very low levels of other vitamin K–dependent coagulation factors (V, VII, IX, and X). Bleeding may begin any time after birth but is typically delayed for a day or two. The infant may be mature and healthy in appearance, although there is a greater incidence in preterm infants. Causes other than vitamin K deficiency include hemophilia, congenital syphilis, sepsis, thrombocytopenia purpura, erythroblastosis, and intracranial hemorrhage.

Hypoprothrombinemia appears to be the consequence of poor placental transport of vitamin K1 to the fetus. Plasma vitamin K1 levels are somewhat lower in pregnant women than in nonpregnant adults, and it is not clear to what extent vitamin K crosses the placenta. The main cause of hemorrhagic disease of the newborn from vitamin K deficiency appears to be a dietary deficiency of vitamin K as the consequence of ingesting solely breast milk, which contains only very small amounts of the vitamin. Vitamin K–dependent clotting factors may also be reduced in infants of mothers taking anticonvulsant drugs (see Chapter 8).

Hemorrhagic disease of the newborn can be avoided by the intramuscular injection of 1 mg of vitamin K1 (phytonadione) at delivery. For treatment of active bleeding, it is injected intravenously.


Immune Thrombocytopenia

Rarely, antiplatelet IgG is transferred from the mother to cause thrombocytopenia in the fetus–neonate. The most severe cases are usually due to alloimmune thrombocytopenia but can also be found in association with maternal autoimmune disease, especially immune thrombocytopenia (ITP). Maternal thrombocytopenia therapy consists of corticosteroids, which increase maternal platelet levels; however, such treatment generally does not affect fetal thrombocytopenia (see Chapter 70).

Alloimmune (Isoimmune) Thrombocytopenia

Alloimmune thrombocytopenia (ATP) differs from immunological thrombocytopenia in several important ways. Because it is caused by maternal isoimmunization to fetal platelet antigens in a manner similar to D-antigen isoimmunization (see Chapter 91), the maternal platelet count is always normal. Thus, alloimmunization is not suspected until after the birth of an affected child. Another important difference is that the fetal thrombocytopenia associated with ATP is frequently severe leading to fetal intracranial hemorrhage (see Chapter 90). The incidence of ATP is reported to be from 1 in 1000 to 1 in 10,000 live births.

The diagnosis can often be made on clinical grounds in the mother who has a normal platelet count with no evidence of any immunological disorder, and an infant who has thrombocytopenia without evidence of other disease. Fetal thrombocytopenia recurs in 70 to 90 percent of subsequent pregnancies. Importantly, management in future pregnancies includes diagnosis of fetal thrombocytopenia by cordocentesis followed by maternally administered intravenous immunoglobulin in massive doses.


Several conditions predispose to neonatal polycythemia and resultant blood hyperviscosity. These include chronic hypoxia in utero and placental transfusion from a twin. As the hematocrit rises above 65, blood viscosity markedly increases. Signs and symptoms include plethora, cyanosis, and neurological aberrations.

For further reading in Williams Obstetrics, 23rd ed.,

see Chapter 29, “Disease and Injuries of the Fetus and Newborn.”