Congenital heart disease is the most common type of birth defect with a prevalence of approximately 1% and is the leading cause of neonatal death. Common congenital heart defects are described in Table 9-3. The etiology for the majority of these anomalies remains unknown, but there are some known etiologies for CHD, such as maternal diabetes or systemic lupus erythematosus, teratogen exposure, and certain genetic causes such as aneuploidy or 22q11 microdeletion (ie, DiGeorge syndrome). There is a long-established association between congenital heart defects and aneuploidy. The frequency of cytogenetic abnormalities with a congenital heart defect has been estimated to be 33% to 42% prenatally and 5% to 15% postnatally; the discrepancy in these rates is secondary to antenatal death occurring in fetuses with chromosomal abnormalities. The likelihood of a cardiac defect exceeds 50% for Down syndrome and is 90% for trisomies 13 and 18.
Parental diagnosis of CHD has increased secondary to advances in ultrasound resolution and fetal echocardiography. A fetal echocardiogram is recommended for any abnormality detected in the standard heart views and for any fetus at high risk for a congenital heart defect (eg, diabetic mother, exposure to a teratogen in the first trimester, previous child with CHD). Some CHDs need a higher level of surveillance during the pregnancy to watch for signs of fetal heart failure in utero. Hydrops in utero is a poor prognostic sign.
The functional consequences of cardiac anomalies are usually not evident until conversion from fetal to neonatal circulation after birth. Some common defects, such as ventriculoseptal defects and coarctation of the aorta, can be missed on prenatal ultrasounds and fetal echocardiograms.
Management depends on the specific type of cardiac defect. Parental management entails offering genetic counseling secondary to the association of a chromosomal or genetic etiology for the CHD, the option of prenatal diagnosis with amniocentesis, and appropriate pediatric cardiology and pediatric cardiac surgery consultations. Most cardiac defects can be corrected surgically, although multiple procedures are usually required. Secondary to the complex nature of these cases, delivery at a tertiary care center is recommended.
Neural tube defects are congenital structural abnormalities of the brain and spine and are the second most common form of structural congenital anomalies. The NTDs result from failure of neuropore closure during the third and fourth weeks after fertilization (fifth and sixth weeks of gestation). The main forms of NTD are anencephaly and spina bifida (Table 9-4). Spina bifida can be closed or open, and there are different types. The prevalence of NTDs is highly variable worldwide, reflecting differences in genetic and environmental predispositions. In the United States, they occur in approximately 5 per 10 000 births. The NTDs may occur as an isolated malformation, in combination with other malformations, as part of a genetic syndrome, or as a result of teratogenic exposure. The NTD risk factors include family history of NTD, poorly controlled diabetes, severe obesity, seizure medications, and poor nutritional status or low folate stores.
Prevention with preconception folate supplementation (0.4 mg/d) significantly lowers the incidence of NTDs. For women with a previously affected pregnancy, a higher dose of 4.0 mg of daily folate is recommended.
Parental screening by ultrasonography in the second trimester is recommended for all pregnant women with optimal examination between 18 and 22 weeks' gestation. Maternal serum α-fetoprotein (MSAFP) has been used as a primary prenatal screening method for NTDs since the 1980s. The MSAFP is elevated in 89% to 100% of pregnancies complicated by NTDs, and an abnormal value is defined as more than 2.5 times the normal. However, MSAFP can be elevated with multiple gestations, inaccurate dating, or in association with other fetal or placental conditions. It can also be normal in closed NTDs and thus has limited value in prenatal screening. With advances in ultrasonography, MSAFP is less important for detection of NTDs when high-quality, second-trimester fetal anomaly screen via ultrasonography can be obtained.
Parental diagnosis can be made by ultrasound with confirmation by amniocentesis for α-fetoprotein and acetylcholinesterase levels. The prenatal ultrasound shows splaying of dorsal vertebral elements and a meningeal sac. Other intracranial findings are the “lemon sign” from scalloping of the frontal bones and the “banana sign” of the compressed cerebellum. Ventriculomegaly is also common along with Arnold Chiari II abnormalities. The NTD is associated with aneuploidy in 4% of isolated cases and in 14% of cases when other anomalies are present.
Management of NTDs entails delivery at a tertiary care center where neonatology and neurosurgery are available. Delivery at term is preferred. The mode of delivery is determined on an individual basis, however; there have been no improved outcomes with cesarean delivery for these fetuses. In terms of when to repair this defect, the Management of Myelomeningocele Study (MOMS) trial compared prenatal versus postnatal closure and found that the children who had prenatal surgery had some improved outcomes but with an increased risk of preterm delivery and uterine dehiscence at delivery.
Hydrocephalus is a pathologic dilatation of the brain's ventricular system due to an increase in intracranial cerebrospinal fluid volume with resultant increased pressure. The majority of cases are secondary to an obstruction at some level in the brain's ventricular system. In the fetus, this appears as ventriculomegaly, defined as dilation of the fetal cerebral ventricles and mild lateral ventriculomegaly (1.0-1.2 cm) and is a relatively common finding on second trimester ultrasound. Ventriculomegaly can be a normal variation or it can be secondary to various causes, some of which may result in or be associated with neurologic, motor, and/or cognitive impairment. Causes include structural abnormalities such as brain dysgenesis or atrophy, inability to resorb cerebrospinal fluid, fetal aneuploidy, genetic disorders such as X-linked hydrocephalus (L1CAM gene), genetic syndromes, or infections such as cytomegalovirus or toxoplasmosis. A less common cause of ventriculomegaly is cerebral hemorrhage. If this diagnosis is being considered, a workup for neonatal alloimmune thrombocytopenia should be offered (see chapter 20). In most cases of ventriculomegaly, the workup is negative and deemed idiopathic.
Parental diagnosis of ventriculomegaly is made when enlarged ventricles are found on second-trimester ultrasound. The fetal biparietal diameter may or may not be increased with the finding of enlarged ventricles. The method for appropriately assessing ventricular size is by measuring the atrial diameter of the lateral ventricle with the fetal head in axial plane and at the level of the frontal horns and cavum septum pellucidum. If the mean diameter is greater than 10 mm, this indicates the presence of ventriculomegaly. After ventriculomegaly is detected, comprehensive sonographic examination for additional anomalies is important for diagnostic workup and appropriate patient counseling.
Management of the pregnancy with enlarged ventricles includes a determination of the cause and follow-up ultrasounds to assess progression, stability, or resolution. Diagnostic studies may include amniocentesis for karyotype, DNA analysis for L1CAM mutations, viral studies, and fetal magnetic resonance imaging. A multidisciplinary team that includes perinatologists, genetic counselors, pediatric neurosurgeons, and neonatologists should be involved in the care of this pregnancy. Pregnancy termination may be considered in some cases. Fetuses with ventriculomegaly should be delivered at a tertiary care center where a pediatric neurosurgery team is available. The timing and mode of delivery should be based on standard obstetric indications. Because most cases have a normal head circumference, a vaginal delivery is reasonable. Significant head enlargement may preclude vaginal delivery and may be an indication for cesarean delivery and/or early delivery.
Prognosis for ventriculomegaly depends on etiology, severity of ventriculomegaly, and the presence of associated abnormalities. The degree of ventricular dilation is not independently predictive of poor long-term outcome.
Congenital diaphragmatic hernia (CDH) is a failure of the diaphragm to fuse properly during embryologic development, resulting in abdominal contents occupying the thoracic cavity. This creates a mass effect that can lead to underdevelopment of the lungs (pulmonary hypoplasia), potentially resulting in persistent pulmonary hypertension, with significant morbidity and mortality in the newborn. The CDH affects approximately 1 in 2500 newborns. Diaphragmatic hernias are most often unilateral, posterolateral, and left sided.
Parental diagnosis of CDH is accomplished in 60% to 90% of cases by ultrasonography or fetal magnetic resonance imaging. On ultrasound, abdominal contents (stomach, bowel, and/or liver) are seen in the thoracic cavity. Other signs seen on ultrasound are mediastinal shift, polyhydramnios, and abnormal cardiac axis. Associated structural anomalies are found in 40% of cases, and the most common anomalies are congenital heart defect, renal anomalies, central nervous system anomalies, and gastrointestinal anomalies. A detailed ultrasound and a fetal echocardiogram should be performed to assess for additional anomalies. Amniocentesis should be offered for karyotype and chromosomal microarray to evaluate for a chromosomal abnormality or genetic syndrome.
Management of the pregnancy may include expectant management with prenatal referral to a tertiary center with expertise in caring for infants with CDH, termination of pregnancy, or fetal intervention. A multidisciplinary team that involves MFM, neonatology, pediatric surgery, and genetic counselors can help the patient and her family determine a treatment plan. Delivery should be performed at tertiary center where pediatric extracorporeal membrane oxygenation is available.
Prognosis has significantly improved in recent years due to advances in techniques of ventilation and extracorporeal membrane oxygenation. Overall, survival now exceeds 80%.
Congenital pulmonary airway malformations (CPAM) are rare developmental lung malformations characterized by an abnormal airway pattern and/or abnormal lung parenchyma that may lead to considerable morbidity and mortality. A CPAM is characterized by a malformation of pulmonary tissue that is cystic or hamartomatous with overgrowth of terminal bronchioles and reduction in the number of alveoli. Lesions can be macrocystic or microcystic. Two conditions included in this group of disorders are congenital cystic adenomatoid malformation (CCAM) and bronchopulmonary sequestration (BPS). These two abnormalities can exist in isolation or as a hybrid of the two lesions. The distinguishing feature is that CCAM typically has a pulmonary blood supply, whereas BPS has blood supply from anomalous systemic vessels.
Parental diagnosis is possible for both lesions. In CCAM, prenatal ultrasound shows a lung mass that may be cystic or solid with its vascular supply from the pulmonary artery. A BPS is distinguished from a CCAM by the identification of a systemic (often aortic) feeding vessel on color Doppler sonography. It is often challenging to differentiate between the two in utero and lesions are often hybrid. Additional ultrasound findings with CPAM are pleural effusion, mediastinal shift, hydrops, and polyhydramnios.
Management entails a detailed ultrasound examination and fetal echocardiogram to ensure there are no other anomalies. The incidence of associated chromosomal abnormalities is low; however, amniocentesis for fetal karyotype or microarray is offered, as chromosomal anomalies have been described. These fetuses should be delivered at tertiary care centers, and prenatal consultation with MFM, pediatric surgery, and neonatology is recommended. Pregnancies are serially monitored by an MFM specialist with ultrasound to watch for signs of progression or regression or an associated fetal complication such as hydrops. In the postnatal period, if these lesions persist, surgical excision is usually recommended.
Prognosis is generally favorable for fetuses with CPAM in the absence of fetal hydrops, which is a predictor of poor outcome. The risk of hydrops is highest in fetuses with large lesions that may have mass effect on the vena cava and/or heart. Cases with hydrops and macrocystic lesions should be referred for possible drainage, whereas some evidence suggests those with microcystic lesions respond to maternal administration of betamethasone. In the absence of hydrops, the long-term outcome of infants with CPAM following resection is excellent.
Gastroschisis and omphalocele are the two most common fetal abdominal wall defects that are detected in utero. Gastroschisis is an isolated abdominal wall defect where the herniated abdominal contents have no covering membrane. Omphalocele is a defect in the abdominal wall in which a membrane of peritoneum covers the herniated abdominal contents (Table 9-5).
Parental screening: Both defects are associated with an elevated MSAFP.
Parental diagnosis is usually made by ultrasound. Gastroschisis is not associated with an increased risk for aneuploidy. Omphalocele has a high incidence of associated malformations and chromosomal abnormalities. Amniocentesis for fetal karyotype and genetic testing should be offered in the case of omphalocele. Additionally, there is an increased incidence of congenital heart defects in cases of omphalocele, and fetal echocardiography is recommended.
Management in pregnancy entails serial ultrasound assessments to follow the amount and type of abdominal contents that are herniated. A multidisciplinary team should be involved including MFM, genetic counseling, neonatology, and pediatric surgery. Delivery at a tertiary care center enables optimal care of the newborn. The mode of delivery can be vaginal in most cases, if standard obstetrical indications are met.
Prognosis of infants with abdominal wall defects depends on whether there is the presence of other anomalies or an underlying chromosomal anomaly.
Congenital renal anomalies can be diagnosed in the prenatal period and include renal agenesis, multicystic dysplastic kidney disease (MCKD), infantile polycystic kidney disease, and hydronephrosis secondary to ureteropelvic junction (UPJ) obstruction and outlet obstruction.
Renal agenesis can be unilateral or bilateral. Unilateral renal agenesis has a normal prognosis, and there is usually compensatory hypertrophy of the contralateral side. A portion of patients with unilateral renal agenesis have contralateral vesicoureteral reflux. Bilateral renal agenesis is rarely diagnosed prior to 18 weeks' gestation because the fetal kidneys do not contribute to the majority of amniotic fluid until after this gestation. On the prenatal ultrasound, the fetal kidneys and bladder are not visualized. This condition causes severe oligohydramnios or anhydramnios and is lethal secondary to severe pulmonary hypoplasia. Case reports have suggested the possibility of survival with serial amnioinfusions to preserve the fetal lungs. Surviving infants would still require dialysis and renal transplant. Current trials are in process to evaluate this fetal intervention.
Multicystic dysplastic kidney disease is a severe renal abnormality characterized by increased renal size and numerous large noncommunicating cysts alternating with areas of increased echogenicity on ultrasound. Because of the size of the kidney and the numerous cysts, this is usually detected by prenatal ultrasound. The MCKD is usually unilateral. In almost half of cases, the contralateral kidney has other malformations, the severity of which determines the overall prognosis. There is also an association with other nongenitourinary anomalies and some genetic syndromes. Amniocentesis should be offered during a prenatal consultation. With unilateral MCKD, prenatal pediatric urology consultation is recommended. Bilateral multicystic dysplasia is associated with severe oligohydramnios and is fatal secondary to pulmonary hypoplasia.
Polycystic kidney disease encompasses two inherited disorders with diffuse involvement of both kidneys. Autosomal recessive polycystic kidney disease is a single-gene disorder inherited in an autosomal recessive fashion. From the perspective of prenatal diagnosis and neonatal presentation, the recessive polycystic kidney disease is much more common. This disease is characterized by bilateral, enlarged, echogenic kidneys. Oligohydramnios can be present. The main cause of perinatal morbidity and mortality is pulmonary hypoplasia. Aggressive neonatal management has led to 1-year survival rates of 82% to 85% in autosomal recessive polycystic kidney disease. If infants survive the first month of life, they are predicted to live for many years. Autosomal dominant polycystic kidney disease rarely presents in the prenatal period; this disease usually has clinical findings in the third or fourth decade of life. Sonogram reveals enlarged kidneys with multiple cysts. Individuals with this form of polycystic kidney disease also have liver cysts, pancreatic cysts, and intracranial aneurysms. Renal ultrasound is recommended in both parents to evaluate for autosomal dominant polycystic kidney disease.
Urinary tract dilation is diagnosed when the fetal renal pelvis is >0.4 cm at the time of an anatomy ultrasound. A follow-up ultrasound to evaluate for resolution or progression is recommended at 32 weeks' gestation. The most common etiology of pathologic fetal urinary tract dilation is ureteropelvic junction obstruction, which prevents urinary flow from the renal pelvis to the ureter. Most cases are unilateral; bilateral cases have a worse prognosis. Pregnancy management is generally unchanged in unilateral cases, but with bilateral UPJ obstruction, a fetal intervention of urinary shunting may be necessary. There is an overall increased incidence of chromosomal abnormalities with obstructive uropathy, thus amniocentesis for prenatal karyotype should be offered. A consultation with a pediatric urologist should be offered to the patient as well. With isolated UPJ obstruction, the prognosis is usually favorable.
Bladder outlet obstructions have the potential to affect the entire urinary and pulmonary system. In males, the most common cause of bladder outlet obstruction is posterior urethral valves. In females, the most common cause is urethral atresia. The characteristic prenatal finding on ultrasound is a dilated bladder (megacystis) and bilateral hydroureteronephrosis. With posterior urethral valves, the bladder wall is thickened, and the urethra may have a characteristic keyhole appearance. There is an association with chromosomal abnormalities, thus amniocentesis and fetal karyotype should be offered in cases of bladder outlet obstruction. In utero interventions may be helpful in some cases, but there is often severe irreversible renal impairment. Pediatric urology consultation should be offered prenatally. Prognosis is determined by evaluation of amniotic fluid volume. The degree of oligohydramnios determines the extent of pulmonary hypoplasia, which is the most important determinant of prognosis for the fetus.
Musculoskeletal disorders can be diagnosed prenatally. The most common skeletal dysplasia disorders that are diagnosed prenatally are achondroplasia, thanatophoric dysplasia, and osteogenesis imperfecta (Table 9-6). Ultrasound findings include shortened limbs, three to four standard deviations below the mean for gestational age as well as abnormalities in the skull, spine, and thorax. Options for further management of the pregnancy may depend on these ultrasound findings because type II osteogenesis imperfecta and thanatophoric dysplasia are lethal.