article July/August 2004 䡠 Vol. 6 䡠 No.

Omphalocele and gastroschisis: An 18-year review

study
Pei-Jen Hwang, MD, and Boris G. Kousseff, MD
Purpose: Using data from a single University Genetics Division practice, the authors sought to determine if
gastroschisis is increasing in occurrence compared to omphalocele. Associated abnormalities were also exam-
ined. In addition, prenatal exposure to teratogens and other parameters were compared. Methods: All fetal and
infant cases of omphalocele and gastroschisis seen in the University of South Florida Division of Genetics between
January 2, 1982 and December 31, 1999 were retrieved through the database and analyzed through chart review.
Results: There were 127 cases of omphalocele and 121 cases of gastroschisis. Ninety-three of the 127 probands
with omphalocele had karyotype determinations and 20% were abnormal; for gastroschisis, 37 had cytogenetic
studies and none had chromosomal anomalies. Seventy-six percent of the probands with omphalocele had
associated abnormalities; twenty-three percent of the probands with gastroschisis, none of which were syndromic,
had associated anomalies. The prematurity rate for omphalocele was 42% and mortality was 22%; for gastros-
chisis, the figures were 57% and 9%, respectively. There were no significant differences in teratogen exposure
between the two groups. Familial cases of both defects occurred in ⬍ 4%, and the prevalence of dizygous twinning
was increased in both groups. Mean maternal age was 21.8 years for the gastroschisis group, 27.2 years for the
omphalocele group. Conclusions: In this study, the number of cases of omphalocele and gastroschisis were
similar, compared to the expected 3:2 ratio, suggesting an increase in the occurrence of gastroschisis. Cases with
omphalocele had more syndromic and nonsyndromic anomalies, more chromosomal anomalies, a higher mortality
rate, and older mothers. Genet Med 2004:6(4):232–236.
Key Words: gastroschisis, omphalocele, abnormalities, teratogens

Gastroschisis and omphalocele are abdominal wall defects graphic features and outcomes of patients with these two
that were first described as early as the 16th century.1 However, conditions.
it was not until recently that these two conditions were catego-
rized as separate entities. In 1953, Moore and Stokes2 defined
MATERIALS AND METHODS
the two separate conditions, and in 1963, Duhamel3 empha-
sized their distinct pathogenesis and clinical presentations. It is A historical analysis of all probands with omphalocele and
currently taught that omphalocele is a more common condi- gastroschisis evaluated in the Genetics Division at the Univer-
tion than gastroschisis, occurring in 1 per 4000 live births com- sity of South Florida College of Medicine between January 2,
pared to 1 per 6000 for gastroschisis.4 Gastroschisis tends to be 1982 and December 31, 1999 was performed. All cases were
an isolated anomaly, whereas omphaloceles are frequently as- seen through the prenatal genetic clinics or as pediatric con-
sociated with chromosome abnormalities and other birth de- sultations, and were part of the 36,665 families evaluated by
fects.5 Thus, the long-term prognosis for infants with gastros- USF Genetics during the period. USF Genetics receives all ge-
chisis is considerably better than that for infants with netic consultations requested by pediatricians and obstetri-
omphalocele, in whom a 50% to 60% survival rate and fre- cians within the Tampa Bay area counties. Probands were re-
quently chronic medical problems are seen.5 trieved through the USF Genetics database and a chart analysis
Using the records of a single University Division of Genetics was performed on each proband. There were 127 probands
over a period of 18 years, the occurrence of omphalocele and with omphalocele (74 prenatal, 53 pediatric) and 121 with gas-
gastroschisis were compared, and associated abnormalities troschisis (92 prenatal, 29 pediatric).
and karyotypes were contrasted in addition to maternal demo- For each record, karyotype, associated anomalies, prematu-
rity, 1-year mortality rate, environmental exposures during
pregnancy, maternal diabetes, familial recurrence, and mater-
From the Division of Genetics, Department of Pediatrics, University of South Florida College nal age were analyzed. Additional analyzed factors were incor-
of Medicine, Tampa, Florida.
rect or missed prenatal diagnosis, twinning, and race. In order
Boris G. Kousseff, One Davis Blvd, Suite 604, Tampa, FL 33606.
to compare the two groups, P-values were calculated through
DOI: 10.1097/01.GIM.0000133919.68912.A3 the chi-square test. Polyhydramnios, oligohydramnios, patent

232 Genetics IN Medicine

 Epidemiology of gastroschisis and omphalocele

foramen ovale, and complications of prematurity were not Table 1

considered as associated abnormalities. Cryptorchidism and Breakdown of 248 patients with gastroschisis or omphalocele in the Tampa
Bay area from 1982 to 2000
PDAs were included as additional abnormalities if the baby
was term. Prematurity was defined as a delivery before 37 Omphalocele (N ⫽ 127)
weeks gestation. Miscarriage (spontaneous termination) was a Prenatal cases (N ⫽ 74)
pregnancy ending spontaneously at ⬍ 20 weeks gestation. The Livebirths 29
study included probands with gastroschisis and omphalocele
Elective termination 12
(syndromic, nonsyndromic, and isolated) and excluded prune
belly syndrome, limb-body wall complex, and umbilical Spontaneous termination 10
hernias. Delivered elsewhere 23
Gastroschisis and omphalocele were confirmed, along with Stillbirths 0
associated anomalies, through physical examination by one of
Pediatric cases (N ⫽ 52)
the authors (B.G.K.) in the pediatric cases. For prenatal cases,
defects were described through targeted level II sonograms, Gastroschisis (N ⫽ 121)
which have a ⬍ 5% false-positive rate; autopsy/pathological Prenatal cases (N ⫽ 92)
data provided additional information for pregnancies ending Livebirths 50
in stillbirth, miscarriage, or elective termination; physical ex-
Elective termination 5
amination (B.G.K.) confirmed the diagnosis in newborns if the
pediatrician or obstetrician requested a genetics consultation. Spontaneous termination 2
Gastroschisis was defined as an anterior abdominal wall defect Delivered elsewhere 33
adjacent to the umbilicus with no sac or membrane. Ompha- Stillbirths 2
locele was defined as a midline anterior abdominal wall defect
Pediatric cases (N ⫽ 29)
covered by the peritoneum and amniotic membrane. Cases
that provided an inadequate or ambiguous description of the
defect were excluded from the study. Cause of death was de-
termined from the official cause of death listed on the autopsy cases that had chromosome studies, 19 had an abnormal
report and its description of the hospital course and autopsy karyotype (20%) (Table 2). In contrast, none of the 37 karyo-
findings to support the listed cause of death. Environmental typed probands with gastroschisis had abnormal results (P ⫽
exposures were determined through an interview with one of 0.007).
the authors (B.G.K.) at the time of birth for pediatric cases and Ninety-three of 127 omphalocele cases had additional birth
at the time of referral after the abnormal ultrasound in prenatal defects (73%) (Table 3). Thirty-two of the 50 syndromic
cases. Information about the general Tampa Bay population omphalocele were liveborn. The most common associated ab-
was obtained for comparison from the Department of Vital normality in the nonsyndromic was cardiac defects (24%).
Statistics and Health Education. Cases of cardiac defects included 16 probands with ventricular
The study was approved by the Institutional Review Board. septal defect (VSD), 4 with atrial septal defect (ASD), 4 with
tetralogy of Fallot, 2 with PDA, 2 with dextrocardia, 1 with
RESULTS ASD and VSD, and 1 with coarctation of the aorta, ASD, and
VSD. Cases of umbilical cord malformation included 7 pro-
There were 127 cases of omphalocele (74 prenatal, 53 pedi- bands with a single umbilical artery, 2 with short cords, and 1
atric; Table 1). Of the 74 prenatally detected cases, 29 were with an enlarged cord.
liveborn and then referred to the USF Genetics Division, and
23 delivered elsewhere and outcome was unknown. Twelve
pregnancies were electively terminated. Ten pregnancies
Table 2
ended in miscarriage; of those, five fetuses showed intrauterine Abnormal results in 93 karyotyped omphalocele probands
growth retardation and other abnormalities, three had trisomy
Total abnormal n %
18, one had trisomy 21, and one had an isolated omphalocele.
During this same period, there were 121 cases of gastroschi- Trisomy 18 19 20%
sis (92 prenatal, 29 pediatric; Table 1). Of the two stillborn Trisomy 21 11 12%
cases, one stillborn fetus had multiple anomalies, including Trisomy 13 2 2%
hydrops, microtia, transposition of the great vessels, horseshoe
Monosomy X 1 1%
kidney, 2-vessel cord, and bilateral syndactyly of fingers; the
fetus was delivered intact. Chromosomal abnormality was sus- 46,XX,del(18)(p11)/46,XX,i(18q) 1 1%
pected, but a karyotype was not performed. The other stillbirth 46,XY,inv(16)(p11.1q11.2) 1 1%
had an isolated gastroschisis. 46,XX,inv(2)(p11q12)mat 1 1%
Probands with omphaloceles had a higher incidence of
46,XY,inv(3)(p13q11) 1 1%
chromosome anomalies and other abnormalities. Of the 93

July/August 2004 䡠 Vol. 6 䡠 No. 4 233

Hwang and Kousseff

Table 3 among the pediatric cases. Information was not available as to

Associated abnormalities in 93 probands with omphalocele and 29 probands whether the neural tube defects were surgically corrected. The
with gastroschisis
single case of cleft lip and palate was a pregnancy electively
n % terminated at 19 weeks and the information was gathered
Omphalocele through the pathologist’s autopsy report.
Total 93 73 Among the 82 liveborn infants with omphalocele, the pre-
maturity rate was 34/82 (42%); for the 79 liveborn infants with
Syndromic 50 39
gastroschisis, the prematurity rate was 45/79 (57%) (P ⫽ 0.18).
Chromosomal 19 20 The mortality rate within the first year of life for the ompha-
Beckwith-Wiedemann 15 12 locele group was 18/82 (22%). The causes of death were not
Pentalogy of Cantrell 11 9 directly related to the omphalocele (9 respiratory distress, 4
congenital heart defects, 3 neural tube defects, 2 postoperative
OEIS 5 4
complications). One infant had a ruptured omphalocele but
Nonsyndromica 43 34 died of respiratory distress related to prematurity. In the gas-
Cardiac 30 24 troschisis group, the infant mortality rate was 7/79 (9%) (P ⬍
Cranial 14 11 0.05). The causes of death in the infants with gastroschisis were
4 cases of congenital heart defects, 2 cases of postoperative
Urogenital 13 10
complications, and 1 case of respiratory distress secondary to
Limb 13 10 prematurity.
Umbilical 10 8 Four cases of gastroschisis were undiagnosed prenatally; of
Vertebral 6 5 those, one case was undiagnosed due to lack of prenatal care.
One omphalocele case was undiagnosed prenatally due to lack
Bladder/cloacal exstrophy 5 4
of prenatal care. Five cases of omphalocele were misdiagnosed
Neural tube 4 3 on fetal sonogram as gastroschisis. Conversely, there were two
Imperforate anus 3 2 cases of gastroschisis misdiagnosed as omphalocele on fetal
Diaphragmatic hernia 3 2 sonogram.
Sixty-six of the 127 mothers of omphalocele probands
Cleft lip/palate 2 2
(52%) reported taking medication during the gestation,
Meckel diverticulum 2 2 whereas 60 of 121 probands with gastroschisis (50%) were ex-
Polydactyly 1 1 posed to medications during gestation (Table 4).
Gastroschisis In the omphalocele group, drug abuse was reported in 6 of
the 127 mothers (5%); there were 2 cases of cocaine use, 1
Total 29 23
cocaine and heroin, 1 THC and marijuana, 1 amphetamines,
Syndromic 0 0 and 1 unspecified. In the gastroschisis group, 5 of 121 mothers
Nonsyndromic b
34 28 (4%) took street drugs during pregnancy (P ⫽ 1.0); there were
Cardiac 14 12 2 cases of cocaine and marijuana use, 1 marijuana, and 2
unspecified.
Urogenital 9 7
In the omphalocele group, 30 mothers smoked during preg-
Limb 3 2 nancy compared to 29 in the gastroschisis group (24% each) (P
Vertebral 2 2 ⫽ 0.88). Twenty-two (17%) mothers with omphalocele pro-
Neural tube 2 2 bands drank alcohol during pregnancy, compared to 17 (14%)
in the gastroschisis group (P ⫽ 0.70). However, none of the
Umbilical 2 2
mothers met the criteria for chronic alcoholism and none of
Cleft lip and palate 1 1 their offspring showed evidence of fetal alcohol syndrome.
Value for Total, P ⬍ 0.001. Prenatal x-ray exposure was 8/127 (6%) for omphalocele, and
a
b
Cryptorchidism occurred in 9/38 liveborn males (24%). 4/121 (3%) for gastroschisis (P ⫽ 0.30). There were 3 cases of
Crytoorchidism occurred in 6/35 liveborn males (17%).
gestational diabetes in the each group (3%), reflecting the in-
cidence of the general Tampa Bay area population.
There were two familial cases of omphalocele (1.6%); the
In contrast, 29 of the 121 gastroschisis probands had addi- relationships were mother and full sister, respectively. Three
tional anomalies (23%) (P ⬍ 0.001; Table 3). Cases of cardiac probands with gastroschisis had a family history of the defect
defects included 8 probands with VSD, 2 with ASD, 2 with (2.4%). The relationships to the probands were dizygotic twin
tetralogy of Fallot, 1 with PDA, and 1 with transposition of the sister, full sibling, and first cousin once removed, respectively.
great vessels and VSD. Cases of umbilical cord malformation Nine of the omphalocele probands were twins (7.1%),
included 2 probands with a single umbilical artery. The two whereas the incidence of twins is 1.1% in the general Tampa
cases of neural tube defects were spina bifida aperta; both were Bay area population (P ⫽ 0.001). There were 8 dizygotic pairs

234 Genetics IN Medicine

 Epidemiology of gastroschisis and omphalocele

Table 4
Medication use during pregnancy in mothers of 127 probands with
omphalocele and 121 probands with gastroschisis
Omphalocele, 66 cases (52%)
Prenatal vitamins 30
a
OTC analgesic 21
Antibiotic 16
OTCa cold medication 10
Corticosteroids 3
Iron 3
Synthroid 3
Fig. 1. Characteristics of study participants as compared to general Tampa Bay area
Anticonvulsant 3 population.

Antidepressant 3
Birth control pills 2 DISCUSSION
Insulin 1
This study was initiated because an increase in the number of
Gastroschisis, 60 cases (50%) gastroschisis cases was observed by the Genetics Division at USF.
Prenatal vitamins 30 In this study, the ratio of omphalocele to gastroschisis was 127 to
a
OTC analgesic 15 121 or 1:1, compared to the expected ratio of 3:2. If only the live-
born were included, the ratio remains 1:1, with 82 cases of ompha-
Antibiotic 22
locele and 79 cases of gastroschisis. Other studies around the
OTCa cold medication 7 world have found increases in gastroschisis prevalence, along with
Corticosteroids 5 a decrease in omphalocele.4,6 –9 Rankin et al.7 reported an increase
Iron 4 in the incidence of gastroschisis without a corresponding change
in omphalocele. Theories to account for these incidence changes
Insulin 1
have included an environmental agent, inaccurate classification,
P ⫽ 0.86. limited family histories, and a higher familial recurrence risk.10 No
a
Over-the-counter.
cases of gastroschisis were recorded in British Columbia before
1969 because the condition was unknown and previous cases were
diagnosed as omphalocele.11
and 1 pair of monozygotic girls. All 9 pairs were discordant for There were no reported cases of omphalocele stillbirths, al-
the defect. In the monozygotic pair, twin A had the omphalo- though the figure in the literature is 11% to 12% (P ⬍ 0.001).9
cele as an isolated anomaly, whereas twin B had defects (exstro- However, excluding elective terminations and pregnancies of
phy of the bladder, imperforate anus, and spinal abnormali- unknown outcome, the spontaneous termination or miscar-
ties) that complemented her sister’s omphalocele in the OEIS riage rate was 25% (10/39). Perhaps differences in criteria for
complex. Twin B died at age 9 hours due to respiratory arrest. stillbirth versus miscarriage contribute to the discrepancy, or
There were three dizygotic twin pregnancies in the gastros- maybe there was a bias in reporting.
chisis group (2.5%), with 1 pair concordant for the defect. A The percentage of associated anomalies was 73% for
fourth pregnancy ended in miscarriage and a resorbed twin omphaloceles versus 23% for gastroschisis. In addition, the
proportion of cases with chromosomal abnormalities was also
was suspected. The DZ twin prevalence was higher compared
higher in the omphalocele group (20%) compared to the gas-
to the incidence in the general Tampa Bay area population (P
troschisis group (0%). Similar findings have been reported in
⫽ 0.98). No consanguinity was reported in either group.
previous studies,5,7,9 with cardiac defects as the most common
Mean maternal age was 21.8 years for gastroschisis and 27.2
associated anomaly with both omphalocele and gastroschisis.5
years for omphalocele. Maternal age distribution for all cases of The prematurity rate in the two groups was higher than the
gastroschisis and omphalocele, in comparison to the general 15% rate in the general Tampa Bay area population, although
Tampa Bay area population, is shown in Fig. 1. Racial compo- the difference between the two groups is not significant. Re-
sition was similar to that of the Tampa Bay area population ports of prematurity rates in gastroschisis have been histori-
(Caucasian 75%, African American 13%, Hispanics 10%, Ori- cally higher, ranging from 40% to 67%,6 compared to the 10%
ental 2%). For the omphalocele group, 93/127 (73%) were to 23% rate for omphalocele.5 Perhaps differences in prematu-
Caucasian, 20/127 (16%) African American, 11/127 (9%) His- rity criteria may account for the higher prematurity rate in this
panic, and 4/127 (3%) Asian. In the gastroschisis group, 93/121 omphalocele group compared to previous studies.
(77%) were Caucasian, 14/121 (12%) African American, and The 1-year mortality rate for the omphalocele group was
13/121 (11%) Hispanic. significantly higher than the gastroschisis group. The 4 cases of

July/August 2004 䡠 Vol. 6 䡠 No. 4 235

Hwang and Kousseff

congenital heart defects in the gastroschisis group were 2 pro- derrepresented in this study. In addition, chart review studies
bands with tetralogy of Fallot, 1 with VSD, and 1 with trans- are also vulnerable to interpretive bias in obtaining data, but
position of the great vessels with VSD; none of the children had this bias was limited through physical examination of liveborn
additional gastrointestinal defects. children by the same physicians, and reviewing official sono-
Cocaine and ephedrine have long been suspects as teratogens gram and autopsy reports.
for gastroschisis. These chemicals are vasoconstrictors, potentially The 248 patients with gastroschisis and omphalocele evalu-
causing occlusion of fetal abdominal wall arteries, with the defect ated through the USF genetics clinics (pediatric and prenatal)
resulting from inadequate blood supply.12 In this series, only two corroborated the reported observation in other medical facili-
mothers admitted use of cocaine during pregnancy. Cold medi- ties/specialties that since the 1960s, gastroschisis is increasing
cations were taken frequently and the majority of mothers did not in prevalence relative to omphalocele,4,6 –9 and may be more
remember which ones they used. Many of the over-the-counter common than isolated omphaloceles in liveborns. Although
cold medications contain ephedrine. However, similar findings there is no clear reason for the change in numbers, this statistic
were noted in the omphalocele group. Thus, ephedrine-contain- should be reflected in the textbooks that still present ompha-
ing drugs and cocaine did not appear to play a role in the abdom- locele as more common.
inal wall defects.
The recurrence risk for nonsyndromic abdominal wall de- ACKNOWLEDGMENT
fects has been postulated to be low (⬍ 1%),10,13,14 but Torfs and
This study was funded in part by a Children Medical Service
Curry10 found a 3.5% recurrence risk for gastroschisis by ex-
grant from Florida Health and Rehabilitative Services.
tending the pedigree to second cousins. They suggested that
incomplete family histories result in underreported familial
cases10 and that counseling of families with a case of gastros- References
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236 Genetics IN Medicine