Our study further characterizes the association of poor fetal weight gain and gastroschisis that has been reported by others [5, 6, 10–13, 32–34]. Intrauterine growth restriction of some degree often accompanies gastroschisis, even when the BW percentile is > 10th percentile . In many cases, the degree of growth restriction is marked. The adjusted mean growth deficit with gastroschisis was 317 g. This growth deficit could not be explained by maternal factors, which might be common to mothers delivering a baby with either gastroschisis or with growth restriction associated with another condition [17, 18]. Our limited prenatal ultrasound data suggested that growth restriction began early in the second trimester and worsened with increasing gestation. This is consistent with others' observations [10–13]. Taken together our data confirm that intrauterine growth restriction is a near universal finding with a gastroschisis defect.
The degree of intrauterine growth restriction was actually greater than that seen with chromosomal anomalies. The ponderal index was very slightly increased, consistent with a reduction in length that was proportional to the reduction in weight. The relatively symmetrical nature of the growth restriction probably reflects early onset . Compounding intrauterine growth deficits, GI dysfunction contributes to suboptimal nutrition after birth in the neonatal period [5, 6, 36].
Our findings imply that gastroschisis patients, because of their marked intrauterine growth restriction, are at increased risk for cardiovascular disease, adult-onset diabetes, and perhaps most importantly, intellectual disability [37, 38]. Leonard, et al., found that growth restriction increased the odds of intellectual disability by about 71% in a large Australian cohort . Most gastroschisis patients are born in the late preterm period (mean gestational age at birth = 36 weeks). Late preterm birth has also been associated with adverse cognitive and socioemotional outcomes . Gastroschisis patients warrant close monitoring for developmental and intellectual problems throughout childhood [40, 41].
Our study extends pathogenetic considerations to include the placenta. Placental histology suggested that placental dysfunction may contribute to growth restriction. Chorangiosis and severe villous edema were more common in gastroschisis patients than in controls. Chorangiosis is an increase in vascular channels in the terminal villi of the placenta. It is thought to represent fetal hypoxemia and the placenta's attempt to improve gas exchange across the terminal villi  and takes weeks to develop. It has been associated with delivery at high altitude, severe maternal anemia, and diabetes mellitus [31, 32]. Villous edema also suggested placental dysfunction. In a separate study, we found evidence that gestational hypertension is less common in the mothers of gastroschisis patients . The placenta plays a central role in the development of gestational hypertension . It is unclear how the development of gastroschisis in the fetus might be associated with decreased gestational hypertension in the mother. The placenta is often small in cases of gestational hypertension associated with fetal growth restriction . However, we did not find a significant difference in the placental weight z-score between gastroschisis patients and controls. Stoll, et al. also reported that placental size was not reduced in a smaller series of gastroschisis cases . These findings, if confirmed, suggest that the placenta may develop abnormally and lead to growth restriction in gastroschisis cases, but not in the manner seen with gestational hypertension.
The exact mechanism by which growth restriction occurs in gastroschisis cases is not known. Carroll, et al. reproted diminished cord serum protein and elevated amniotic fluid protein in the amniotic fluid compared to omphalocele patients and controls . Unfortunately, the patients and controls were not well matched with respect to gestational age, which could have affected the results. Protein loss through exudation of proteinaceous fluid from the intestine, which is often inflamed and exposed to the amniotic fluid throughout gestation, might well contribute to poor intrauterine growth, but probably would not account for chorangiosis. Chorangiosis provided indirect evidence of poor oxygen transfer from the placenta to the fetus. The presence of intestinal obstruction or dysfunction did not likely contribute to fetal growth restriction, since other GI anomalies, most of which were atresias, were not associated with decreased birth weight. It is possible that multiple mechanisms contribute to poor fetal growth in the presence of gastroschisis.
Several limitations should be considered when interpreting our study. All cases were referred and do not represent population-based data. However, the demographic findings of our patients are similar to previous reports [2–6]. Another concern might be error in physical measurements obtained by clinical personnel. BW of gastroschisis patients could have been biased upward due to bowel edema or the bandages used to protect exposed intestine. However, nurses routinely weigh and subtract the weight of bandages when recording BW. Even if present, this bias would have reduced the observed BW difference between cases and controls and cannot explain our findings. Furthermore, measurements of LT and OFC, were also low and not as likely to have been influenced by the presence of gastroschisis. We were limited in the number of prenatal ultrasounds available for study. Patients were often evaluated and received their prenatal ultrasounds at satellite clinics. Only when patients received their prenatal ultrasound at the main perinatal center were the ultrasound data available to us. The strengths of this study are the large numbers of patients examined, the multiple approaches to quantifying the growth deficit and our examination of placental findings.