Studies have reported an increased stillbirth rate after 37 weeks of gestation in fetuses with gastroschisis, which has prompted many perinatal centers to implement a program of increased fetal surveillance in later pregnancy.6,7,31 Animal and human studies also have described inflammatory changes in the bowel of fetuses with gastroschisis, suggesting that such changes are attributable to prolonged bowel exposure to amniotic fluid, especially in later pregnancy.22,23 Elective delivery by induction thus has been proposed to minimize this harmful exposure of the bowel to amniotic fluid; however, this management remains controversial.1,5 Our data suggest that a policy of elective induction of labor at 37 weeks of gestation is reasonable because, in our experience, it reduced the risk of neonatal sepsis, bowel damage, and neonatal death. In addition, elective delivery decreased the median time to oral feeding, length of time on TPN, and duration of hospital stay, although significance was not reached. These improved neonatal outcomes were not at the expense of increased obstetric intervention because the rate of cesarean was similar between the two treatment groups. Similar to other findings,32–34 cesarean delivery was not found to be associated with better neonatal survival of newborns with gastroschisis.
Those who oppose early elective delivery usually argue that this strategy can result in increased prematurity-related complications, such as respiratory distress syndrome. We observed no significant difference for this complication between the two groups, perhaps because induction was not electively performed before 37 weeks of gestation. Similar results were observed in the HYPITAT study, in which adverse neonatal outcomes were similar in women induced at 37 weeks of gestation and those managed expectantly for mild preeclampsia.35 In the DIGITAT study, there were no differences in adverse obstetric or neonatal outcomes after induction of labor compared with expectant monitoring in women with suspected intrauterine growth restriction at term.29 An increased risk of stillbirth has been reported in fetuses with gastroschisis,6,7,30,36 which supports the rationale for elective (relatively) preterm delivery. Unlike previous reports,29 we did not observe a single intrauterine fetal death among 261 cases of gastroschisis, although this may be related to our policy of increased surveillance of fetal well-being in the majority of pregnancies in this study.
There are conflicting recommendations in the literature concerning timing of delivery in pregnancies with gastroschisis. Part of this may be attributable to the variability in the definition of “early delivery” in different studies, ranging from 33 weeks to 38 weeks of gestation. Moreover, many studies mixed vaginal, elective, and emergency cesarean deliveries in the same report. We have identified 19 other studies that examined the timing of delivery for Gastroschisis. Seven showed some benefit to induction of labor (possibly explained by limiting the period of bowel exposure to amniotic fluid),9,13–15,19,37 whereas 12 failed to show any advantage associated with early delivery8,10,11,16–18,20,25–28 (Table 4). To our knowledge, only one randomized controlled trial18 (RCT) and one prospective study19 have investigated the effect of timing of delivery on neonatal outcome. All other reports were retrospective and observational, and only one of which27 included more than 100 patients. Two studies, including the RCT, did not support a policy of early delivery, although there was a trend toward a shorter neonatal hospital stay and a shorter length of time on TPN.17,18 Of note, the RCT18 included seven emergency cesarean deliveries for fetal distress in the elective preterm group, thus minimizing any benefit of early delivery. Emergency cesarean delivery is usually indicated in the case of fetal distress and, arguably, these cases should be excluded when assessing different management strategies for otherwise uncomplicated gastroschisis.14 Of the 12 studies that failed to show any significant benefit to early delivery, eight also failed to show any significant benefit to expectant management.8,10,11,17,18,25,26,38
The study design and groups evaluated differed between reports that showed a benefit to elective delivery and those that did not. Eleven of 12 studies8,10,11,16,17,20,25–28,38 that failed to support elective delivery compared only the effect of gestational age and not the effect of a specific intervention (eg, scheduled delivery) on neonatal outcome. In those studies, preterm deliveries were a result of spontaneous labor (eg, attributable to polyhydramnios), abnormal ultrasound findings, or nonreassuring fetal heart rate monitoring. It is possible that these fetuses may have been somewhat compromised, with higher complication rates, and thus may have had worse neonatal outcomes than a comparative group of fetuses delivered at term.
The U-shape of the curve plotting neonatal death against gestational age at birth (Fig. 2) shows that an optimal compromise exists between mortality and prematurity. Figure 2 also shows that preterm neonates born before 34 weeks of gestation are at high risk for neonatal death. If these newborns are compared with term newborns, as was performed in several studies,8,10,11,16,26–28,38 this would favor term delivery, because the power of global prematurity is higher than its benefit on the fetal intestine.
Several limitations of our study must be acknowledged. First, lack of randomization is a study limitation. Second, these are retrospective data, collected over a lengthy time period. The groups have been stratified by time, given our change in policy to favor elective delivery at 37 weeks of gestation in 1994. Incremental improvements in pediatric surgical and medical care over this long study period may explain some of the differences observed between expectant management and induction at 37 weeks of gestation. As noted, however, there were no differences in neonatal outcome in patients who labored and delivered spontaneously before 37 weeks of gestation before and after 1994. Moreover, time to oral feeds, length of time on TPN, and hospital stay were all increased after 1994 compared with before 1994, when all 261 gastroschisis cases were considered.
Despite the retrospective design of our study and thus possible information bias, our population of 261 fetuses with gastroschisis is one of the largest reported series studying the effect of timing of delivery (Table 4). Moreover, our study was conducted in a single tertiary care perinatal center, thus minimizing the effect of multiple prenatal and postnatal management policies. According to our results (Table 2), RCTs comparing induction of labor at 37 weeks of gestation with expectant management (with a power of 0.90) would require 3,561 patients in each arm to demonstrate significance for a reduction in neonatal death from 4% to 2.6%, or 160 patients in each arm to demonstrate significance for a reduction in composite neonatal outcome (neonatal death and bowel damage) from 21.1% to 7.8%. Given the substantial research costs of mounting such a study, together with the implied additional health care costs of nonintervention at 37 weeks of gestation, we believe it is unlikely that this level of evidence will ever be attained.
In conclusion, our study supports elective delivery at 37 weeks of gestation for fetuses with uncomplicated gastroschisis. In addition to improving neonatal outcomes, this policy also is likely to be cost-effective because it reduces antenatal costs and shortens the duration of neonatal hospital stay.39,40 A multicenter, prospective, randomized study with stringent recruitment criteria would be needed to reach a definitive conclusion.
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