- Email: [email protected]
SCREENING FOR FETAL ABDOMINAL WALL DEFECTS
UTILIZING SONOGRAPHY IN A GENERAL OBSTETRIC PRACTICE
0889-8545/98 $8.00
+ .OO
SCREENING FOR FETAL ABDOMINAL WALL DEFECTS Rick W. Martin, MD
Fetal abdominal wall abnormalities are a common group of birth defects with a reported incidence of nearly 3.5 cases per 10,000 live births2 Because of an increase in morbidity, mortality, and chromosomal aneuploidy associated with abdominal wall defects, all ultrasound examinations performed during the second and third trimesters of pregnancy should include a screen for their presence. In addition, some patients in whom fetal abdominal wall defects are diagnosed are referred for obstetric complications of increased fundal height or an abnormal maternal serum biochemical screen. Antenatal diagnosis followed by a careful survey for other fetal anomalies results in optimal antenatal management and planned delivery at a facility capable of providing necessary neonatal support. This article describes how the ultrasound screen for fetal abdominal wall defects is performed, with a focus on the two most commonly encountered abdominal wall defects, gastroschisis and omphalocele. EPIDEMIOLOGY
Gastroschisis occurs at a frequency of 0.94 cases per 10,000 live births, whereas omphalocele occurs nearly three times as often with a reported incidence of 2.52 cases per 10,000 live births.2 Roeper and associates'* have noted a more than 10-fold increase in the incidence of gastroschisis in California from 0.06 cases per 10,000 live births in 1968
From the Department of Obstetrics and Gynecology, University of Mississippi Medical Center, Jackson, Mississippi
OBSTETRICS AND GYNECOLOGY CLINICS OF NORTH AMERICA VOLUME 25 * NUMBER 3 * SEETEMBER 1998
517
518
MARTIN
to 0.89 cases per 10,000 live births in 1977. Other investigators have also noted a significant rise in the incidence of gastroschisis in other geographic areas of the world.22Furthermore, a recent investigation has reported the observation that gastroschisis occurs more commonly in young patients.2 In fact, that study demonstrated women less than 20 years of age were 11times more likely to have a child with gastroschisis. Gastroschisis is considered a disruptive lesion of the abdominal wall. The abdominal wall develops normally in these fetuses but later, owing to a vascular injury, a full-thickness abdominal wall defect occurs with subsequent herniation of small and occasionally large bowel. A leading theory to explain both the recent increase in gastroschisis as well as its association with younger-age mothers involves vasoactive substances. Women of younger age and in greater overall numbers use vasoactive agents during pregnancy. Nicotine and other substances in cigarette smoke are vasoactive; studies report a relative risk of 2.1 for smoking mothers to deliver a child with gastroschisis.IOPseudoephedrine and phenylpropanolamine, two common vasoactive agents present in many over-the-counter preparations, have been found by Torfs and colleagues25to increase the risk of gastroschisis. Not surprisingly, the potent vasoactive effect of cocaine has been shown to be related to an increase in the incidence of gastroschisis.12 Despite the evidence to support the theory that gastroschisis is the result of a teratogen, gastroschisis has a recurrence risk of 3% to 5%. This would suggest a multifactorial mode of inheritance. Cases have been reported of a familial pattern of inheritance among siblings.24 Unlike the data for gastroschisis, there does not seem to be an increase in the incidence of omphalocele. Because an omphalocele is associated with other fetal anomalies, its incidence is higher in series that include cases of fetal demise. In contrast to gastroschisis, the incidence of omphalocele is related to an increase in maternal age. This is partially explained by the association of chromosomal abnormalities with omphalocele that occurs in approximately 30%of cases. In addition, abnormalities of the cardiovascular, skeletal, gastrointestinal, genitourinary tract, and central nervous system are seen in 50% of fetuses with an omphalocele and reinforce the need for a thorough targeted ultrasound examination in all cases. Only through such a careful categorizing of fetal defects can one appropriately appraise families of reasonable neonatal expectations in addition to aiding families in the difficult decision of possible pregnancy termination. EMBRYOLOGY
During the sixth week of embryonic development, rapid growth of the bowel causes the intestinal loops to enter the extraembryonic coelom. During the next few weeks, further elongation of the intestinal loops occurs along with a 270-degree rotation. The herniated loops of intestines usually return to the abdominal cavity by the end of the third month.
SCREENING FOR FETAL ABDOMINAL WALL DEFECTS
519
The proximal jejunum is the first to enter the abdominal cavity and comes to lie on the left side. The remainder of the bowel fills in to the fetal right as it enters the abdomen.I5 An omphalocele occurs when there is a failure of the intestinal loops to return to the abdominal cavity. At birth, the herniated loops of intestine, with the possible accompanying large bowel and liver, are covered with amnion, parietal peritoneum, and a thin connective tissue matrix. One theory regarding the development of an omphalocele involves incomplete fetal enfolding7 If a defect occurs in the cephalic portion of the ventral surface of the embryo, there is extrusion of upper midline structures along with the abdominal contents. This severe birth defect is the pentalogy of Cantrell anomaly and consists of an omphalocele with associated defects of the sternum, diaphragm, and pericardium with a resultant ectopic cordis. A failure of just the lateral folds along the ventral surface of the embryo produces the classic omphalocele. Failure of enfolding of the lateral and inferior ventral surface of the embryo results in cloaca1 and bladder extrophy deformities. Another competing theory for the development of an omphalocele is that proposed by DeVries6and involves the persistence of the body stalk in the region normally occupied by the somatopleure.6 In gastroschisis, the umbilicus is normally developed and correctly positioned. Because of a disruption of the right omphalomesenteric artery, a full-thickness abdominal wall defect develops with extrusion of normally positioned abdominal contents.” As a result, the common ultrasound findings of gastroschisis include extruded abdominal contents into the amniotic space to the right side of the fetus with the umbilical cord present and at its normal insertion site. ANTENATAL DIAGNOSIS
Because the intestines are normally extra-abdominal in early embryogenesis, one must be careful in making the diagnosis of an abdominal wall defect prior to 12 weeks’ gestation.*I Cyr and associates4 recorded longitudinally with ultrasound the process of bowel migration in 10 fetuses. Their research supports the recommendation that the diagnosis of an abdominal wall defect be delayed until 14 weeks’ gestation. Although the bowel consistently returns to the abdominal cavity by 11 weeks, the 14-week recommendation allows for possible errors in gestational dating. Utilizing the superior resolution of transvaginal sonography, Timor-Tritsch and co-workersZ3demonstrated that the bowel had returned to the abdominal cavity by 12 weeks’ gestation. Gastroschisis is the result of a full-thickness abdominal wall defect that generally occurs to the right of a normally inserted umbilical cord. A small amount of normal skin is present between the abdominal defect and the umbilicus. Extrusion of small bowel consistently occurs with gastroschisis and, on occasion, is associated with extrusion of large bowel. The liver, however, rarely if ever protrudes through the defect; if
520
MARTIN
it is seen, one can usually exclude the diagnosis of gastroschisis. Doppler color flow mapping is helpful to demonstrate the normal umbilical cord insertion in gastroschisis. In cases complicated by oligohydramnios, bowel anterior to the abdominal wall can be difficult to visualize. In such cases, transabdominal amnioinfusion may be necessary to confirm sonographically the diagnosis of gastroschisis. In an omphalocele, the bowel is also external to the abdominal wall but is covered with a membrane. Not uncommonly, abdominal ascites is present. Because of the embryonic defect of the body stalk in the formation of the omphalocele, a normal umbilical cord insertion is not visualized. The size of the abdominal wall defect varies but can be large enough to allow the liver to be displaced into the sac. Most abdominal wall defects can be detected with ultrasound. A recent investigation by Fisher and associatess found that 98% of cases of gastroschisis and 95% of cases of omphalocele were accurately diagnosed with ultrasound. Advances in maternal biochemical screening for open neural tube defects have aided in the antenatal diagnosis of fetal abdominal wall defects. Both gastroschisis and omphalocele are associated with elevations of maternal serum alpha-fetoprotein (MSAFP). The median value for MSAFP is 9.42 multiples of the median (MOM) in gastroschisis and 4.18 MOM in omphalocele.20The MSAFP level in gastroschisis is often markedly elevated. In the investigation by Saller and co11eagues,2° all cases of gastroschisis and 70% of cases of omphalocele were associated with a significant elevation of AFP. The other biochemical markers of human chorionic gonadotropin (hCG) and unconjugated estriol (uEJ are not significantly altered in cases of abdominal wall defects and therefore are not helpful in identifying women at risk for a fetus with such an abnormality. Amniotic fluid levels of AFP are elevated in 40% of patients with fetuses with abdominal wall defects, and some of these cases also have a positive assay for acetyl cholinesterase.16 Currently, maternal biochemical screening combined with ultrasound seems to be the most appropriate method to screen for fetal abdominal wall defects and should diagnose the vast majority of cases. ROUTINE ULTRASOUND SCREENING
Regardless of the reason for the performance of an ultrasound examination, a routine screen for fetal abdominal wall defects should be obtained. As discussed elsewhere in this text, screens for central nervous system, cardiac, genitourinary tract, and skeletal abnormalities should also be incorporated into the routine ultrasound examination. The crucial step in screening for fetal abdominal wall defects is a careful imaging of the umbilical cord insertion site. The preferred image is the transverse view (Fig. 1).With this view, one can diagnose most omphaloceles by noting tissue protruding into the base of the umbilical cord. In cases of gastroschisis, this same view allows one to visualize herniated loops of
SCREENING FOR FETAL ABDOMINAL WALL DEFECTS
521
Figure 1. A normal fetus with a transverse scan at the level of the umbilicus. The umbilical cord insertion site (arrow) is easily seen.
bowel in the amniotic cavity to the right of the umbilical cord insertion site. Careful scanning in fetuses with gastroschisis usually reveals that the umbilical cord insertion site is normal. Because of fetal position, the preferred transverse view at the umbilical cord insertion site cannot always be obtained. In these situations, one should try to obtain the longitudinal view (Fig. 2), which must also include the umbilical cord
Figure 2. A normal fetus with a midplane longitudinal scan. The umbilical cord insertion site (arrow) is also easily seen in this view.
522
MARTIN
insertion site. Although an omphalocele can usually be diagnosed with this view, the defect of gastroschisis may not be identified because it lies to the fetal right of the displayed view.
ASSOCIATED ANOMALIES Whenever one fetal anomaly is identified, it is prudent to conduct a careful search for other abnormalities. Associated chromosomal abnormalities are unusual in gastroschisis; however, other anomalies are seen in approximately 13% of cases? Most are associated gastrointestinal abnormalities, which occur in 20% to 40% of cases of gastroschisis, and include intestinal malrotation, atresia, volvulus, a type of ileal deformity known as “Christmas tree” atresia, and infar~ti0n.I~ Associated cardiovascular and genitourinary tract abnormalities are infrequently seen in gastroschisis. Extraintestinal abnormalities are seen in 70% of cases of omphalocele. Cardiovascular malformations are the most common associated abnormalities, but skeletal, other gastrointestinal, genitourinary tract, and central nervous system anomalies also occur. Associated chromosomal aneuploidy is typically seen in more than one-third of cases of omphalocele. Of note is the observation that fetal aneuploidy is more commonly seen in association with a small ~mphalocele.~ Fetal echocardiography and genetic amniocentesis for fetal karyotype are recommended procedures to categorize fully cases of omphalocele. Two well-documented syndromes are associated with omphalocele. The pentalogy of Cantrell deformity consists of an omphalocele and a sternal defect in conjunction with a diaphragmatic and pericardial defect resulting in an ectopic cordis. This rare abnormality carries a grave prognosis for the fetus, with no cases of recurrence recorded in the obstetric literature.9 The Beckwith-Wiedemann syndrome is associated with an omphalocele in addition to macroglossia and macrosomia. Whenever an omphalocele is visualized, an attempt should be made to image the fetal tongue. If the fetal tongue extends past an imaginary line between the maxilla and mandible, the diagnosis of macroglossia can be made. Because the Beckwith-Wiedemann syndrome is not associated with chromosomal abnormalities, such a finding would preclude the need for a genetic amniocentesis and fetal karyotype. Although some cases of Beckwith-Wiedemann syndrome are transmitted in an autosomal dominant fashion, most cases are sporadic with a female-tomale predominance of 6 to 4.27
ANTENATAL MANAGEMENT Once an omphalocele or gastroschisis is identified, a careful search should be undertaken to identify any associated anomalies. Thorough
SCREENING FOR FETAL ABDOMINAL WALL DEFECTS
523
counseling should be provided with an emphasis on nondirective techniques. Additional information regarding corrective surgery and a realistic hospital course for the neonate is best provided by neonatal colleagues. At the author’s institution, all patients are offered genetic amniocentesis for a fetal karyotype. Although chromosomal abnormalities are uncommonly associated with gastroschisis, such patients have been encountered at the antenatal diagnostic unit. Fetal echocardiography should be an integral part of the evaluation of all cases of omphalocele. Pregnancy termination options should be discussed with the family contingent upon the gestational age of the fetus and local legal limits for such procedures. For families that elect pregnancy continuation, serial sonography is recommended to detect any alteration in fetal growth as well as other sonographic evidence of fetal compromise. Numerous parameters to predict fetal and neonatal outcome have been evaluated in cases of gastroschisis. As a result of prolonged exposure to amniotic fluid with possible torsion, echogenic bowel thickening of 3 mm may be related to an increase in the time needed to establish oral feedings. Although some researchers have suggested that concomitant bowel dilation portends a poorer neonatal pr0gnosis,1~a more recent investigation suggests that bowel dilation of 17 mm or more does not predict severe intestinal damage and poor neonatal outcome.’ The current consensus is that bowel dilation alone is not sufficient sonographic evidence to predict preventable bowel injury and mandate early delivery. Gastroschisis is associated with intrauterine fetal growth restriction. In a series reported on by Tan and associates,22significant growth impairment below the fifth percentile occurred in 31.9% of fetuses with gastroschisis. An additional perinatal hazard is preterm delivery, which occurs in one-third of cases. Accompanying hydramnios with resultant uterine distention is presumed to be the etiologic factor responsible for the increase incidence of preterm delivery. Surprisingly, oligohydramnios is also associated with gastroschisis. These alterations of amniotic fluid volume, along with a quoted perinatal mortality rate of 65 per 1000 live births, justify an attitude of increased fetal Such increased surveillance should consist of serial sonography with antenatal fetal heart rate testing with a nonstress test or biophysical profile. Because of the observation by Crawford and associates3of an excessive fetal wastage of 12.5% that primarily occurs in the late third trimester of pregnancy, most clinicians initiate intense fetal surveillance by 30 to 32 weeks’ gestation. Patients should be educated regarding the early signs and symptoms of preterm labor and have periodic cervical examinations. As is true for gastroschisis, omphaloceles are associated with an increased incidence of fetal growth restriction and preterm delivery. Neonatal morbidity and mortality in fetuses with omphalocele are largely reflective of associated abnormalities and chromosomal anomalies.
524
MARTIN
INTRAPARTUM MANAGEMENT
The optimal mode of delivery for fetuses with antenatally diagnosed abdominal wall defects has been the subject of intense controversy. Retrospective data are available but are most likely flawed by confounding variables such as the site of delivery in cases in which the diagnosis was not made prior to birth. Randomized clinical trials necessary to answer these clinical questions scientifically have not been performed. Sakala and colleagues14reported on a limited series in which infants with gastroschisis did significantly better than historic controls when delivery was by elective cesarean section. The total number of days to enteral feedings was decreased in the cesarean group, which also had a decreased incidence of neonatal sepsis, small bowel obstruction, and short bowel syndrome; however, the failure to control for a multitude of factors, such as associated anomalies and gestational age at delivery, leads one to question the conclusions of the study. An increase in meconium staining of the amniotic fluid has been well-described in gastroschisis and occurs in more than 70% of Therefore, regardless of whether one delivers a fetus with gastroschisis by cesarean section or vaginally, the obstetric health care provider must be prepared to provide prompt, deep nasopharyngeal suction to the infant to lower the incidence and severity of meconium aspiration syndrome. Attending pediatricians should be notified of the association of meconium staining of the amniotic fluid with gastroschisis. NEONATAL MANAGEMENT
After the delivery of an infant with gastroschisis, the exposed bowel should be covered with a sterile plastic bag. In addition, a nasogastric tube should be quickly placed to prevent gaseous distention of the bowel with an increased risk of bowel ischemia and possible infar~ti0n.l~ Some clinicians recommend extending the abdominal wall defect to lessen the likelihood of bowel ischemia. The overall survival rate for live-born infants with abdominal wall defects has recently improved and is reported to be 79% for omphalocele and 97% for gastroschisis. Some of the advancements reflect the improved ability of providers to categorize abdominal wall defects coupled with the election of families to proceed with pregnancy termination for those cases associated with severe anomalies.s SUMMARY
Failure of the lateral ventral folds to close by the third month of embryonic life results in an omphalocele. Although the abdominal wall defect is easily closed, the survival rate for infants with an omphalocele remains only 79%, largely the result of coexistent anomalies and chromo-
SCREENING FOR FETAL ABDOMINAL WALL DEFECTS
525
soma1 abnormalities. Gastroschisis is a deformation caused by disruption of the right omphalomesenteric artery and a resultant full-thickness defect in the abdominal wall. As a result, small bowel and, on occasion, even large bowel herniate into the amniotic space. Despite evidence of increased bowel irritability manifested by echogenic bowel wall thickening in fetuses with gastroschisis, the survival rate of more than 95% is largely the result of the lack of other severe anomalies associated with this defect. In addition, recent evidence suggests that the improvement in survival rate is also the result of improved perinatal care. The ability of perinatal specialists to categorize the defect along with associated anomalies and improved counseling regarding neonatal outcome have measurably increased the ability of families to assess the reproductive consequences and make informed decisions. This article outlines methods to identify patients at risk for having a fetus with an abdominal wall defect along with sonographic techniques to diagnose the majority of cases. Prompt consultation with individuals skilled in evaluating such defects ensures that appropriate perinatal care is provided.
References 1. Alsulyman OM, Monteiro H, Ouzounian JG, et al: Clinical significance of prenatal ultrasonographic intestinal dilatation in fetuses with gastroschisis. Am J Obstet Gynecol 175982, 1996 2. Calzolari E, Bianchi F, Dolk H, et a1 Omphalocele and gastroschisis in Europe: A survey of 3 million births, 1980-1990. Am J Med Genet 58:187,1995 3. Crawford RA, Ryan G, Wright VM,et al: The importance of serial biophysical assessment of fetal wellbeing in gastroschisis. Br J Obstet Gynaecol 99599, 1992 4. Cyr DR, Mack LA, Schoenecker SA, et a 1 Bowel migration in the normal fetus: US detection. Radiology 161:119, 1986 5. De Veciana M, Major CA, Porto M Prediction of an abnormal karyotype in fetuses with omphalocele. Prenat Diagn 14:487, 1994 6. DeVries PA: The pathogenesis of gastroschisis and omphalocele. J Pediatr Surg 15245, 1980 7. Duhammel B: Embryology of exomphalos and allied malformations. Arch Dis Child 38142, 1963 8. Fisher R, Attah A, Partington A, et a1 Impact of antenatal diagnosis on incidence and prognosis in abdominal wall defects. J Pediatr Surg 31:538, 1996 9. Ghidini A, Sirtoni M, Romero R, et al: Prenatal diagnosis of pentalogy of Cantrell. J Ultrasound Med 7567,1988 10. Haddow JE, Palomaki GE, Holman MS: Young maternal age and smoking during pregnancy as risk factors for gastroschisis. Teratology 47225, 1993 11. Hoyme HE, Higginbottom MC, Jones K L The vascular pathogenesis of gastroschisis: Intrauterine interruption of the omphalomesenteric artery. J Pediatr 98:228, 1981 12. Hume RF, Gingras JL, Martin LS, et al: Ultrasound diagnosis of fetal anomalies associated with in utero cocaine exposure: Further support for cocaine-induced vascular disruption teratogenesis. Fetal Diagn Ther 9:239, 1994 13. Karamanoukian HL, OToole SJ, Glick PL Antenatal diagnosis and perinatal care of anterior abdominal wall defects. Fetal Mat Med Rev 7:109, 1995 14. Langer JC, Khanna J, Caco C, et a 1 Prenatal diagnosis of gastroschisis: Development of objective sonographic criteria for predicting outcome. Obstet Gynecol 81:53, 1993 15. Langman J: Medical embryology. In Digestive Tube and Its Derivatives. Baltimore, Williams and Wilkins, 1972
526
MARTIN
16. Loft AGR, Hogdall E, Larsen So, et a1 A comparison of amniotic fluid alpha-fetoprotein and acetylcholinesterase in the prenatal diagnosis of open neural tube defects and anterior abdominal wall defects. Prenat Diagn 1393, 1993 17. Paidas MJ, Crombleholme TM, Robertson FM: Prenatal diagnosis and management of the fetus with an abdominal wall defect. Semin Perinatol 18196, 1994 18. Roeper PJ, Harris J, Lee G, et al: Secular rates and correlates for gastroschisis in California (1968-1977). Teratology 35203, 1987 19. Sakala El', Erhard LN, White JJ: Elective cesarean section improves outcomes of neonates with gastroschisis. Am J Obstet Gynecol 169:1050, 1993 20. Saller DN, Canick JA, Palomaki GE, et al: Second-trimester maternal serum alphafetoprotein, unconjugated estriol, and hCG levels in pregnancies with ventral wall defects. Obstet Gynecol 84:852, 1994 21. Schmidt W, Yarkoni S, Crelin ES, et al: Sonographic visualization of physiologic anterior abdominal wall hernia in the first trimester. Obstet Gynecol 69:911, 1987 22. Tan KH, Kilby MD, Whittle MJ, et a1 Congenital anterior abdominal wall defects in England and Wales 1987-1993: Retrospective analysis of OPCS data. BMJ 313:903, 1996 23. Timor-Tritsch IE, Warren WB, Peisner DB, et al: First-trimester midgut herniation: A high-frequency transvaginal sonographic study. Am J Obstet Gynecol 161:831, 1989 24. Torfs CP, Curry CJ: Familial cases of gastroschisis in a population-based registry. Am J Med Genet 45465, 1993 25. Torfs CP, Katz EA, Bateson TF, et al: Maternal medications and environmental exposures as risk factors for gastroschisis. Teratology 54:84, 1996 26. Usta IM, Mercer BM, Sibai BM: Risk factors for meconium aspiration syndrome. Obstet Gynecol86230, 1995 27. Wieacker P, Wilhelm LH, Greiner P, et al: Prenatal diagnosis of Wiedemann-Beckwith syndrome. J Perinat Med 17351, 1989 Address reprint requests to Rick W. Martin, MD Department of Obstetrics and Gynecology University of Mississippi Medical Center 2500 North State Street Jackson, Mississippi 392164505
0889-8545/98 $8.00
+ .OO
SCREENING FOR FETAL ABDOMINAL WALL DEFECTS Rick W. Martin, MD
Fetal abdominal wall abnormalities are a common group of birth defects with a reported incidence of nearly 3.5 cases per 10,000 live births2 Because of an increase in morbidity, mortality, and chromosomal aneuploidy associated with abdominal wall defects, all ultrasound examinations performed during the second and third trimesters of pregnancy should include a screen for their presence. In addition, some patients in whom fetal abdominal wall defects are diagnosed are referred for obstetric complications of increased fundal height or an abnormal maternal serum biochemical screen. Antenatal diagnosis followed by a careful survey for other fetal anomalies results in optimal antenatal management and planned delivery at a facility capable of providing necessary neonatal support. This article describes how the ultrasound screen for fetal abdominal wall defects is performed, with a focus on the two most commonly encountered abdominal wall defects, gastroschisis and omphalocele. EPIDEMIOLOGY
Gastroschisis occurs at a frequency of 0.94 cases per 10,000 live births, whereas omphalocele occurs nearly three times as often with a reported incidence of 2.52 cases per 10,000 live births.2 Roeper and associates'* have noted a more than 10-fold increase in the incidence of gastroschisis in California from 0.06 cases per 10,000 live births in 1968
From the Department of Obstetrics and Gynecology, University of Mississippi Medical Center, Jackson, Mississippi
OBSTETRICS AND GYNECOLOGY CLINICS OF NORTH AMERICA VOLUME 25 * NUMBER 3 * SEETEMBER 1998
517
518
MARTIN
to 0.89 cases per 10,000 live births in 1977. Other investigators have also noted a significant rise in the incidence of gastroschisis in other geographic areas of the world.22Furthermore, a recent investigation has reported the observation that gastroschisis occurs more commonly in young patients.2 In fact, that study demonstrated women less than 20 years of age were 11times more likely to have a child with gastroschisis. Gastroschisis is considered a disruptive lesion of the abdominal wall. The abdominal wall develops normally in these fetuses but later, owing to a vascular injury, a full-thickness abdominal wall defect occurs with subsequent herniation of small and occasionally large bowel. A leading theory to explain both the recent increase in gastroschisis as well as its association with younger-age mothers involves vasoactive substances. Women of younger age and in greater overall numbers use vasoactive agents during pregnancy. Nicotine and other substances in cigarette smoke are vasoactive; studies report a relative risk of 2.1 for smoking mothers to deliver a child with gastroschisis.IOPseudoephedrine and phenylpropanolamine, two common vasoactive agents present in many over-the-counter preparations, have been found by Torfs and colleagues25to increase the risk of gastroschisis. Not surprisingly, the potent vasoactive effect of cocaine has been shown to be related to an increase in the incidence of gastroschisis.12 Despite the evidence to support the theory that gastroschisis is the result of a teratogen, gastroschisis has a recurrence risk of 3% to 5%. This would suggest a multifactorial mode of inheritance. Cases have been reported of a familial pattern of inheritance among siblings.24 Unlike the data for gastroschisis, there does not seem to be an increase in the incidence of omphalocele. Because an omphalocele is associated with other fetal anomalies, its incidence is higher in series that include cases of fetal demise. In contrast to gastroschisis, the incidence of omphalocele is related to an increase in maternal age. This is partially explained by the association of chromosomal abnormalities with omphalocele that occurs in approximately 30%of cases. In addition, abnormalities of the cardiovascular, skeletal, gastrointestinal, genitourinary tract, and central nervous system are seen in 50% of fetuses with an omphalocele and reinforce the need for a thorough targeted ultrasound examination in all cases. Only through such a careful categorizing of fetal defects can one appropriately appraise families of reasonable neonatal expectations in addition to aiding families in the difficult decision of possible pregnancy termination. EMBRYOLOGY
During the sixth week of embryonic development, rapid growth of the bowel causes the intestinal loops to enter the extraembryonic coelom. During the next few weeks, further elongation of the intestinal loops occurs along with a 270-degree rotation. The herniated loops of intestines usually return to the abdominal cavity by the end of the third month.
SCREENING FOR FETAL ABDOMINAL WALL DEFECTS
519
The proximal jejunum is the first to enter the abdominal cavity and comes to lie on the left side. The remainder of the bowel fills in to the fetal right as it enters the abdomen.I5 An omphalocele occurs when there is a failure of the intestinal loops to return to the abdominal cavity. At birth, the herniated loops of intestine, with the possible accompanying large bowel and liver, are covered with amnion, parietal peritoneum, and a thin connective tissue matrix. One theory regarding the development of an omphalocele involves incomplete fetal enfolding7 If a defect occurs in the cephalic portion of the ventral surface of the embryo, there is extrusion of upper midline structures along with the abdominal contents. This severe birth defect is the pentalogy of Cantrell anomaly and consists of an omphalocele with associated defects of the sternum, diaphragm, and pericardium with a resultant ectopic cordis. A failure of just the lateral folds along the ventral surface of the embryo produces the classic omphalocele. Failure of enfolding of the lateral and inferior ventral surface of the embryo results in cloaca1 and bladder extrophy deformities. Another competing theory for the development of an omphalocele is that proposed by DeVries6and involves the persistence of the body stalk in the region normally occupied by the somatopleure.6 In gastroschisis, the umbilicus is normally developed and correctly positioned. Because of a disruption of the right omphalomesenteric artery, a full-thickness abdominal wall defect develops with extrusion of normally positioned abdominal contents.” As a result, the common ultrasound findings of gastroschisis include extruded abdominal contents into the amniotic space to the right side of the fetus with the umbilical cord present and at its normal insertion site. ANTENATAL DIAGNOSIS
Because the intestines are normally extra-abdominal in early embryogenesis, one must be careful in making the diagnosis of an abdominal wall defect prior to 12 weeks’ gestation.*I Cyr and associates4 recorded longitudinally with ultrasound the process of bowel migration in 10 fetuses. Their research supports the recommendation that the diagnosis of an abdominal wall defect be delayed until 14 weeks’ gestation. Although the bowel consistently returns to the abdominal cavity by 11 weeks, the 14-week recommendation allows for possible errors in gestational dating. Utilizing the superior resolution of transvaginal sonography, Timor-Tritsch and co-workersZ3demonstrated that the bowel had returned to the abdominal cavity by 12 weeks’ gestation. Gastroschisis is the result of a full-thickness abdominal wall defect that generally occurs to the right of a normally inserted umbilical cord. A small amount of normal skin is present between the abdominal defect and the umbilicus. Extrusion of small bowel consistently occurs with gastroschisis and, on occasion, is associated with extrusion of large bowel. The liver, however, rarely if ever protrudes through the defect; if
520
MARTIN
it is seen, one can usually exclude the diagnosis of gastroschisis. Doppler color flow mapping is helpful to demonstrate the normal umbilical cord insertion in gastroschisis. In cases complicated by oligohydramnios, bowel anterior to the abdominal wall can be difficult to visualize. In such cases, transabdominal amnioinfusion may be necessary to confirm sonographically the diagnosis of gastroschisis. In an omphalocele, the bowel is also external to the abdominal wall but is covered with a membrane. Not uncommonly, abdominal ascites is present. Because of the embryonic defect of the body stalk in the formation of the omphalocele, a normal umbilical cord insertion is not visualized. The size of the abdominal wall defect varies but can be large enough to allow the liver to be displaced into the sac. Most abdominal wall defects can be detected with ultrasound. A recent investigation by Fisher and associatess found that 98% of cases of gastroschisis and 95% of cases of omphalocele were accurately diagnosed with ultrasound. Advances in maternal biochemical screening for open neural tube defects have aided in the antenatal diagnosis of fetal abdominal wall defects. Both gastroschisis and omphalocele are associated with elevations of maternal serum alpha-fetoprotein (MSAFP). The median value for MSAFP is 9.42 multiples of the median (MOM) in gastroschisis and 4.18 MOM in omphalocele.20The MSAFP level in gastroschisis is often markedly elevated. In the investigation by Saller and co11eagues,2° all cases of gastroschisis and 70% of cases of omphalocele were associated with a significant elevation of AFP. The other biochemical markers of human chorionic gonadotropin (hCG) and unconjugated estriol (uEJ are not significantly altered in cases of abdominal wall defects and therefore are not helpful in identifying women at risk for a fetus with such an abnormality. Amniotic fluid levels of AFP are elevated in 40% of patients with fetuses with abdominal wall defects, and some of these cases also have a positive assay for acetyl cholinesterase.16 Currently, maternal biochemical screening combined with ultrasound seems to be the most appropriate method to screen for fetal abdominal wall defects and should diagnose the vast majority of cases. ROUTINE ULTRASOUND SCREENING
Regardless of the reason for the performance of an ultrasound examination, a routine screen for fetal abdominal wall defects should be obtained. As discussed elsewhere in this text, screens for central nervous system, cardiac, genitourinary tract, and skeletal abnormalities should also be incorporated into the routine ultrasound examination. The crucial step in screening for fetal abdominal wall defects is a careful imaging of the umbilical cord insertion site. The preferred image is the transverse view (Fig. 1).With this view, one can diagnose most omphaloceles by noting tissue protruding into the base of the umbilical cord. In cases of gastroschisis, this same view allows one to visualize herniated loops of
SCREENING FOR FETAL ABDOMINAL WALL DEFECTS
521
Figure 1. A normal fetus with a transverse scan at the level of the umbilicus. The umbilical cord insertion site (arrow) is easily seen.
bowel in the amniotic cavity to the right of the umbilical cord insertion site. Careful scanning in fetuses with gastroschisis usually reveals that the umbilical cord insertion site is normal. Because of fetal position, the preferred transverse view at the umbilical cord insertion site cannot always be obtained. In these situations, one should try to obtain the longitudinal view (Fig. 2), which must also include the umbilical cord
Figure 2. A normal fetus with a midplane longitudinal scan. The umbilical cord insertion site (arrow) is also easily seen in this view.
522
MARTIN
insertion site. Although an omphalocele can usually be diagnosed with this view, the defect of gastroschisis may not be identified because it lies to the fetal right of the displayed view.
ASSOCIATED ANOMALIES Whenever one fetal anomaly is identified, it is prudent to conduct a careful search for other abnormalities. Associated chromosomal abnormalities are unusual in gastroschisis; however, other anomalies are seen in approximately 13% of cases? Most are associated gastrointestinal abnormalities, which occur in 20% to 40% of cases of gastroschisis, and include intestinal malrotation, atresia, volvulus, a type of ileal deformity known as “Christmas tree” atresia, and infar~ti0n.I~ Associated cardiovascular and genitourinary tract abnormalities are infrequently seen in gastroschisis. Extraintestinal abnormalities are seen in 70% of cases of omphalocele. Cardiovascular malformations are the most common associated abnormalities, but skeletal, other gastrointestinal, genitourinary tract, and central nervous system anomalies also occur. Associated chromosomal aneuploidy is typically seen in more than one-third of cases of omphalocele. Of note is the observation that fetal aneuploidy is more commonly seen in association with a small ~mphalocele.~ Fetal echocardiography and genetic amniocentesis for fetal karyotype are recommended procedures to categorize fully cases of omphalocele. Two well-documented syndromes are associated with omphalocele. The pentalogy of Cantrell deformity consists of an omphalocele and a sternal defect in conjunction with a diaphragmatic and pericardial defect resulting in an ectopic cordis. This rare abnormality carries a grave prognosis for the fetus, with no cases of recurrence recorded in the obstetric literature.9 The Beckwith-Wiedemann syndrome is associated with an omphalocele in addition to macroglossia and macrosomia. Whenever an omphalocele is visualized, an attempt should be made to image the fetal tongue. If the fetal tongue extends past an imaginary line between the maxilla and mandible, the diagnosis of macroglossia can be made. Because the Beckwith-Wiedemann syndrome is not associated with chromosomal abnormalities, such a finding would preclude the need for a genetic amniocentesis and fetal karyotype. Although some cases of Beckwith-Wiedemann syndrome are transmitted in an autosomal dominant fashion, most cases are sporadic with a female-tomale predominance of 6 to 4.27
ANTENATAL MANAGEMENT Once an omphalocele or gastroschisis is identified, a careful search should be undertaken to identify any associated anomalies. Thorough
SCREENING FOR FETAL ABDOMINAL WALL DEFECTS
523
counseling should be provided with an emphasis on nondirective techniques. Additional information regarding corrective surgery and a realistic hospital course for the neonate is best provided by neonatal colleagues. At the author’s institution, all patients are offered genetic amniocentesis for a fetal karyotype. Although chromosomal abnormalities are uncommonly associated with gastroschisis, such patients have been encountered at the antenatal diagnostic unit. Fetal echocardiography should be an integral part of the evaluation of all cases of omphalocele. Pregnancy termination options should be discussed with the family contingent upon the gestational age of the fetus and local legal limits for such procedures. For families that elect pregnancy continuation, serial sonography is recommended to detect any alteration in fetal growth as well as other sonographic evidence of fetal compromise. Numerous parameters to predict fetal and neonatal outcome have been evaluated in cases of gastroschisis. As a result of prolonged exposure to amniotic fluid with possible torsion, echogenic bowel thickening of 3 mm may be related to an increase in the time needed to establish oral feedings. Although some researchers have suggested that concomitant bowel dilation portends a poorer neonatal pr0gnosis,1~a more recent investigation suggests that bowel dilation of 17 mm or more does not predict severe intestinal damage and poor neonatal outcome.’ The current consensus is that bowel dilation alone is not sufficient sonographic evidence to predict preventable bowel injury and mandate early delivery. Gastroschisis is associated with intrauterine fetal growth restriction. In a series reported on by Tan and associates,22significant growth impairment below the fifth percentile occurred in 31.9% of fetuses with gastroschisis. An additional perinatal hazard is preterm delivery, which occurs in one-third of cases. Accompanying hydramnios with resultant uterine distention is presumed to be the etiologic factor responsible for the increase incidence of preterm delivery. Surprisingly, oligohydramnios is also associated with gastroschisis. These alterations of amniotic fluid volume, along with a quoted perinatal mortality rate of 65 per 1000 live births, justify an attitude of increased fetal Such increased surveillance should consist of serial sonography with antenatal fetal heart rate testing with a nonstress test or biophysical profile. Because of the observation by Crawford and associates3of an excessive fetal wastage of 12.5% that primarily occurs in the late third trimester of pregnancy, most clinicians initiate intense fetal surveillance by 30 to 32 weeks’ gestation. Patients should be educated regarding the early signs and symptoms of preterm labor and have periodic cervical examinations. As is true for gastroschisis, omphaloceles are associated with an increased incidence of fetal growth restriction and preterm delivery. Neonatal morbidity and mortality in fetuses with omphalocele are largely reflective of associated abnormalities and chromosomal anomalies.
524
MARTIN
INTRAPARTUM MANAGEMENT
The optimal mode of delivery for fetuses with antenatally diagnosed abdominal wall defects has been the subject of intense controversy. Retrospective data are available but are most likely flawed by confounding variables such as the site of delivery in cases in which the diagnosis was not made prior to birth. Randomized clinical trials necessary to answer these clinical questions scientifically have not been performed. Sakala and colleagues14reported on a limited series in which infants with gastroschisis did significantly better than historic controls when delivery was by elective cesarean section. The total number of days to enteral feedings was decreased in the cesarean group, which also had a decreased incidence of neonatal sepsis, small bowel obstruction, and short bowel syndrome; however, the failure to control for a multitude of factors, such as associated anomalies and gestational age at delivery, leads one to question the conclusions of the study. An increase in meconium staining of the amniotic fluid has been well-described in gastroschisis and occurs in more than 70% of Therefore, regardless of whether one delivers a fetus with gastroschisis by cesarean section or vaginally, the obstetric health care provider must be prepared to provide prompt, deep nasopharyngeal suction to the infant to lower the incidence and severity of meconium aspiration syndrome. Attending pediatricians should be notified of the association of meconium staining of the amniotic fluid with gastroschisis. NEONATAL MANAGEMENT
After the delivery of an infant with gastroschisis, the exposed bowel should be covered with a sterile plastic bag. In addition, a nasogastric tube should be quickly placed to prevent gaseous distention of the bowel with an increased risk of bowel ischemia and possible infar~ti0n.l~ Some clinicians recommend extending the abdominal wall defect to lessen the likelihood of bowel ischemia. The overall survival rate for live-born infants with abdominal wall defects has recently improved and is reported to be 79% for omphalocele and 97% for gastroschisis. Some of the advancements reflect the improved ability of providers to categorize abdominal wall defects coupled with the election of families to proceed with pregnancy termination for those cases associated with severe anomalies.s SUMMARY
Failure of the lateral ventral folds to close by the third month of embryonic life results in an omphalocele. Although the abdominal wall defect is easily closed, the survival rate for infants with an omphalocele remains only 79%, largely the result of coexistent anomalies and chromo-
SCREENING FOR FETAL ABDOMINAL WALL DEFECTS
525
soma1 abnormalities. Gastroschisis is a deformation caused by disruption of the right omphalomesenteric artery and a resultant full-thickness defect in the abdominal wall. As a result, small bowel and, on occasion, even large bowel herniate into the amniotic space. Despite evidence of increased bowel irritability manifested by echogenic bowel wall thickening in fetuses with gastroschisis, the survival rate of more than 95% is largely the result of the lack of other severe anomalies associated with this defect. In addition, recent evidence suggests that the improvement in survival rate is also the result of improved perinatal care. The ability of perinatal specialists to categorize the defect along with associated anomalies and improved counseling regarding neonatal outcome have measurably increased the ability of families to assess the reproductive consequences and make informed decisions. This article outlines methods to identify patients at risk for having a fetus with an abdominal wall defect along with sonographic techniques to diagnose the majority of cases. Prompt consultation with individuals skilled in evaluating such defects ensures that appropriate perinatal care is provided.
References 1. Alsulyman OM, Monteiro H, Ouzounian JG, et al: Clinical significance of prenatal ultrasonographic intestinal dilatation in fetuses with gastroschisis. Am J Obstet Gynecol 175982, 1996 2. Calzolari E, Bianchi F, Dolk H, et a1 Omphalocele and gastroschisis in Europe: A survey of 3 million births, 1980-1990. Am J Med Genet 58:187,1995 3. Crawford RA, Ryan G, Wright VM,et al: The importance of serial biophysical assessment of fetal wellbeing in gastroschisis. Br J Obstet Gynaecol 99599, 1992 4. Cyr DR, Mack LA, Schoenecker SA, et a 1 Bowel migration in the normal fetus: US detection. Radiology 161:119, 1986 5. De Veciana M, Major CA, Porto M Prediction of an abnormal karyotype in fetuses with omphalocele. Prenat Diagn 14:487, 1994 6. DeVries PA: The pathogenesis of gastroschisis and omphalocele. J Pediatr Surg 15245, 1980 7. Duhammel B: Embryology of exomphalos and allied malformations. Arch Dis Child 38142, 1963 8. Fisher R, Attah A, Partington A, et a1 Impact of antenatal diagnosis on incidence and prognosis in abdominal wall defects. J Pediatr Surg 31:538, 1996 9. Ghidini A, Sirtoni M, Romero R, et al: Prenatal diagnosis of pentalogy of Cantrell. J Ultrasound Med 7567,1988 10. Haddow JE, Palomaki GE, Holman MS: Young maternal age and smoking during pregnancy as risk factors for gastroschisis. Teratology 47225, 1993 11. Hoyme HE, Higginbottom MC, Jones K L The vascular pathogenesis of gastroschisis: Intrauterine interruption of the omphalomesenteric artery. J Pediatr 98:228, 1981 12. Hume RF, Gingras JL, Martin LS, et al: Ultrasound diagnosis of fetal anomalies associated with in utero cocaine exposure: Further support for cocaine-induced vascular disruption teratogenesis. Fetal Diagn Ther 9:239, 1994 13. Karamanoukian HL, OToole SJ, Glick PL Antenatal diagnosis and perinatal care of anterior abdominal wall defects. Fetal Mat Med Rev 7:109, 1995 14. Langer JC, Khanna J, Caco C, et a 1 Prenatal diagnosis of gastroschisis: Development of objective sonographic criteria for predicting outcome. Obstet Gynecol 81:53, 1993 15. Langman J: Medical embryology. In Digestive Tube and Its Derivatives. Baltimore, Williams and Wilkins, 1972
526
MARTIN
16. Loft AGR, Hogdall E, Larsen So, et a1 A comparison of amniotic fluid alpha-fetoprotein and acetylcholinesterase in the prenatal diagnosis of open neural tube defects and anterior abdominal wall defects. Prenat Diagn 1393, 1993 17. Paidas MJ, Crombleholme TM, Robertson FM: Prenatal diagnosis and management of the fetus with an abdominal wall defect. Semin Perinatol 18196, 1994 18. Roeper PJ, Harris J, Lee G, et al: Secular rates and correlates for gastroschisis in California (1968-1977). Teratology 35203, 1987 19. Sakala El', Erhard LN, White JJ: Elective cesarean section improves outcomes of neonates with gastroschisis. Am J Obstet Gynecol 169:1050, 1993 20. Saller DN, Canick JA, Palomaki GE, et al: Second-trimester maternal serum alphafetoprotein, unconjugated estriol, and hCG levels in pregnancies with ventral wall defects. Obstet Gynecol 84:852, 1994 21. Schmidt W, Yarkoni S, Crelin ES, et al: Sonographic visualization of physiologic anterior abdominal wall hernia in the first trimester. Obstet Gynecol 69:911, 1987 22. Tan KH, Kilby MD, Whittle MJ, et a1 Congenital anterior abdominal wall defects in England and Wales 1987-1993: Retrospective analysis of OPCS data. BMJ 313:903, 1996 23. Timor-Tritsch IE, Warren WB, Peisner DB, et al: First-trimester midgut herniation: A high-frequency transvaginal sonographic study. Am J Obstet Gynecol 161:831, 1989 24. Torfs CP, Curry CJ: Familial cases of gastroschisis in a population-based registry. Am J Med Genet 45465, 1993 25. Torfs CP, Katz EA, Bateson TF, et al: Maternal medications and environmental exposures as risk factors for gastroschisis. Teratology 54:84, 1996 26. Usta IM, Mercer BM, Sibai BM: Risk factors for meconium aspiration syndrome. Obstet Gynecol86230, 1995 27. Wieacker P, Wilhelm LH, Greiner P, et al: Prenatal diagnosis of Wiedemann-Beckwith syndrome. J Perinat Med 17351, 1989 Address reprint requests to Rick W. Martin, MD Department of Obstetrics and Gynecology University of Mississippi Medical Center 2500 North State Street Jackson, Mississippi 392164505