Gastroschisis

Duhamel (1963) suggested a discrete teratogenic insult to the somatopleural mesenchyme resulting in an isolated defect in differentiation. Another theory is that the physiologic hernia of the cord ruptures in utero, before closure of the umbilical ring (Shaw, 1975 and Glick et al. 1985). Others have suggested that in-utero regression of the right umbilical vein leaves a weakness on right side of the abdominal cord insertion, or that there is a disruption of the right omphalomesenteric artery again leading to a weakness predisposing to what we clinically recognize as gastroschisis (Hoyme et al., 1983 and Torfs et al., 1990).

At birth, in patients with gastroschisis, the bowel may have an abnormal appearance which is referred to as an intestinal “peel”. The peel is a layer of fibrin and collagen on the serosal surface of the bowel, which likely is caused by the combination of inflammatory reaction to constituents in the amniotic fluid and constriction of the bowel as it herniates through the abdominal wall defect. In addition, the bowel in fetuses with gastroschisis is often foreshortened (Amoury et al., 1977; Klein et al., 1983; Tibboel et al., 1986 a, b; Amoury et al., 1988; Langer et al., 1990, Moore, 1992).

Most cases of gastroschisis are detected prenatally. Ultrasound will often detect an abdominal wall defect at the time of the “dating” ultrasound, which is usually done around 20 weeks of gestation. Occasionally the abdominal wall defect is seen before 20 weeks gestation, if an ultrasound is obtained late in the first trimester. In the second trimester, maternal serum alpha-fetoprotein (MSAFP) screening will be elevated in most mothers pregnant with a fetus with gastroschisis, but the test is not specific for gastroschisis. MSAFP is also elevated in twin pregnancies as well as in fetuses with neural tube defects, omphalocele, and in autosomal chromosomal anomalies.

The incidence of gastroschisis is 4.7 per 10,000 live births (Mowrer 2022). The number of babies born with gastroschisis has increased over the last 2 decades, but the incidence has abruptly decreased during the pandemic. The reason for the increase is not known. Epidemiologic data have shown that young maternal age is associated with an increased risk of gastroschisis.

Goldbaum et al (1990) studied infants with gastroschisis in the state of Washington and found a 4-fold increased risk in mothers less than 20 years of age. Cigarette smoking has been associated with gastroschisis (Haddow et al., 1993). Medications and recreational drugs that can cause vascular constriction have been linked to an increased risk of gastroschisis (Van Allen, 1981; Colorado et al., 1997; Plessinger, 1998)

It is difficult to diagnose gastroschisis in the first trimester because of the normal herniation of the intestine into the umbilical cord (Cyr et al., 1986). The intestine reduces back into the abdominal cavity by 11 weeks gestation; therefore, it is difficult to differentiate between a physiologic and a pathologic sonographic finding. The earliest reported diagnosis of gastroschisis is 13 weeks 3 days gestation (Guzman, 1990).

Ultrasound findings typically demonstrate a full-thickness abdominal wall defect, almost always, to the right of the umbilical cord. There is a bowel floating freely in the amniotic fluid without a limiting membrane, which is seen in the omphalocele. In omphalocele, the bowel is contained within the omphalocele sac, which is comprised of the parietal peritoneum and the amnion with a layer of hyaluronic acid in between. Omphalocele can be confused with gastroschisis if the omphalocele sac ruptures, which is a relatively rare event.

The prenatal detection rate for gastroschisis is over 80% (Barisic et al., 2001). Gastroschisis and omphalocele were shown to be accurately distinguished in 79.3% of cases on initial diagnosis and in 84.5% of cases after referral for further evaluation (Walkinshaw et al., 1992).

A ruptured hernia of the umbilical cord can present late as gastroschisis. In these cases, the gastroschisis may develop later in pregnancy and may not be present on ultrasound early in pregnancy (Knott and Colley, 1987).

The differential diagnosis of gastroschisis should include omphalocele, ruptured omphalocele, hernia of the cord, and limb-body wall complex. Omphalocele and gastroschisis are differentiated by the presence of a sac in omphalocele with cord insertion on the sac. In gastroschisis, the umbilical cord inserts into the abdominal wall with the abdominal wall defect immediately to the right of its insertion. In gastroschisis, there is no sac and the intestine floats freely in the amniotic cavity. In addition, the abdominal wall defect is small, usually less than 4 cm in diameter, even at term.

In contrast, the abdominal wall defect in omphalocele is quite large often with herniated liver and stomach, which is typically not the case with gastroschisis. A ruptured omphalocele may be mistaken for gastroschisis, however, if the abdominal wall defect is sufficiently large that it allows the liver to herniate through the abdominal wall defect, the diagnosis is more likely to be omphalocele and not gastroschisis. A ruptured hernia of the cord will present later in pregnancy and may be impossible to differentiate from gastroschisis unless a prior ultrasound shows a hernia of the cord without an abdominal wall defect.

Limb body wall complex is characterized by very severe limb defects and anterior wall defects, these can be of the head, chest, or abdomen, and are usually not in the midline. These fetuses also have spinal abnormalities, which together are rarely mistaken for gastroschisis.

Chromosomal anomalies are rare in gastroschisis (Mayer et al., 1980; Mann and Ferguson-Smith, 1984; Sermer et al., 1987; Romero et al., 1988; Lewinsky et al., 1990; Sipes et al., 1990). Only in cases where sonographic abnormalities in addition to gastrointestinal abnormalities are seen, is chromosomal evaluation recommended.

In a study of 24 international birth defects registries including over 3300 cases of gastroschisis, 10% were found to have associated major unrelated defects, with 2% part of a recognized syndromes and cardiac abnormalities detected in 2-3% (Mastroiacovo 2007). A report from the Texas Birth Defects Registry found up to a third of cases of gastroschisis had associated anomalies (Benjamin 2014). However, in a prospectively collected database of 4700 infants with gastroschisis discharged from 348 neonatal intensive care units in North America found associated anomalies in only 8% of cases and cardiac defects in 1% (Corey 2014).

Postnatally, gastroschisis is classified into one of two categories: simple and complex. In patients with complex gastroschisis, there may be a concomitant atresia, perforation, volvulus, stenosis, and necrosis. Between 10 and 25% of cases of gastroschisis will be complex. The focus of prenatal diagnosis has been on trying to distinguish simple from complex gastroschisis in order to better understand the prenatal natural history of gastroschisis that might influence the rate of intrauterine fetal demise, fetal distress, and prematurity.

Additionally, understanding which fetuses are at risk of having complex gastroschisis will allow us to better guide prenatal management. Simple gastroschisis has a survival of over 98% and low morbidity rates (Bradnoch et al 2011, Gamba et al 2014), but complex gastroschisis is associated with survival rates of 70 to 80% with prolonged hospital stay and higher long-term morbidity rates with feeding difficulties and need for parenteral nutrition (Bradnoch et al 2011, Cowan et al 2012).

In utero bowel dilatation is one of the most commonly noted abnormalities on fetal ultrasound. Its significance for the outcome has not been established. A large study from Canada including 100 patients diagnosed prenatally with gastroschisis did not find that prenatal bowel dilatation over 18 mm was associated with a worse outcome (Skarsgaard et al., 2007). Piper and Jaksic (2006) reviewed the experience at Boston Children’s Hospital and found no difference in length of stay, time on TPN, mortality, or time in the NICU for babies who had bowel dilatation over 6 mm prenatally.

Bowel dilatation and bowel thickening may indicate bowel damage, but the existing data does not provide evidence for changing the delivery time or mode if these features are present on ultrasound. A more recent meta-analysis of 2023 fetuses with gastroschisis found a positive association between intra-abdominal bowel dilation, polyhydramnios, and bowel atresia. In addition, prenatal gastric dilation was found to be associated with an increased risk of neonatal death (D’Antonio et al 2018).

Intrauterine growth retardation (IUGR) is common and may affect as many as 77% of babies (Carpenter et al., 1984; Molenaar and Tibboel, 1993). A study by Royner and Richards (1977) found a large difference between predicted IUGR (43%) and actual IUGR at birth (23%). The weight of the fetus is often underestimated because the abdominal circumference is taken into account. In babies with gastroschisis, the abdominal circumference is small because most of the bowel is outside the abdomen.

A few studies (Crawford et al.,1992; Burge and Ade-Ajayi, 1997) have reported an up to 10% rate of stillbirth in the third trimester in babies with gastroschisis. This is now thought to be an overestimate of the rate of intrauterine fetal demise in gastroschisis. The cause of death is thought to be mid-gut volvulus or cord compression. More recently, the CAPSNET data from Canada reported a fetal loss rate of only 1.4% among 700 cases of gastroschisis (www.CAPSNET.org).

Premature birth is common in pregnancies with gastroschisis. At least one-third of babies are born prematurely, and possibly the most important reason for premature labor is polyhydramnios (Mayer et al., 1980; Kirk and Wah, 1983; Carpenter et al., 1984; Caplan and McGregor, 1989; Molenaar and Tibboel, 1993). Also, oligohydramnios is seen in gastroschisis (Bair et al., 1986; Crawford et al., 1992). Mercer et al. (1988) reported amniotic fluid staining in 73% of their series of 22 babies with gastroschisis. The significance of this is unclear, but it may indicate fetal distress.

There are several considerations in the management of pregnancies with gastroschisis including imaging guidelines, methods of monitoring, and timing of delivery. A recent national survey of maternal-fetal specialists suggests that the common management strategy includes close surveillance in conjunction with weekly nonstress tests, biophysical profile, and amniotic fluid levels starting at 32 weeks gestation (Amin R, et al 2019).

Additional ultrasound findings that are assessed include the development of in-utero growth restriction, polyhydramnios, oligohydramnios, gastric distention, and intra-abdominal bowel dilation that can be indicative of higher postnatal complications. For example, intra-abdominal bowel dilation, gastric distention, and polyhydramnios have been shown to be associated with a higher incidence of neonatal death (D’Antonio, et al 2015).

Gastroschisis is not an indication for cesarean section (C-section) as outcomes are similar for babies delivered via vaginal birth (Boutros et al., 2009). In the absence of routine maternal and fetal indications for C-sections, vaginal delivery has been demonstrated to be safe and is recommended for patients with gastroschisis. In patients with gastroschisis, the risk of fetal demise is greater, suggesting that proceeding with an elective early delivery may mitigate this risk (Sparks TN, et al. 2017). However, several studies have explored this and studies have demonstrated that delivery at less than 35 weeks gestation is associated with worse outcomes (Shamshirsaz AA, et al 2020; Overcash RT, et al; Landisch RM, et al 2017).

The optimal timing of delivery is something that is debated and is presently under investigation in a multicenter, prospective, randomized control trial (Gastroschisis Outcome of Delivery Study, ClinicalTrials.gov Identifier: NCT02774746). Patients are randomized to delivery at either 35 weeks or 38 weeks gestation, and in this study outcomes being evaluated include rates of stillbirth, neonatal death, and overall morbidity. If fetal growth, amniotic fluid volume, and antenatal testing are normal, the risk of intrauterine fetal demise is minimal, and delivery prior to 37 weeks is generally not recommended. It is important to note, however, that fetuses that meet these criteria are in the minority.

In general, at the Fetal Care Center at Connecticut Children’s, we schedule patients for induction of labor at 37 weeks if they haven’t already delivered.

There are currently no fetal treatment options that will improve outcomes in gastroschisis. Amnioexchange has been proposed as a possible fetal treatment for gastroschisis. The rationale is that there are two mechanisms that cause bowel damage: constriction of the abdominal wall defect with resultant hypo-perfusion of the bowel and various irritants in the amniotic fluid (Langer et al., 1989, 1990). In France, Luton et al. (2003) performed a trial of amnio exchange, but there was no significant improvement in outcomes with this intervention.

After the delivery of the patient with gastroschisis, the major concerns are fluid loss and hypothermia due to the exposed viscera. Therefore, immediately after delivery, the newborn with gastroschisis is placed in a plastic “bowel” bag. This is done to reduce evaporative fluid and heat losses and to help keep the baby warm. The baby should be placed on the right side and the bowel should be supported to prevent kinking of the mesenteric vessels at the abdominal wall defect.

An orogastric or nasogastric tube is placed into the stomach for gastric decompression. Intravenous (IV) access is important and necessary immediately after birth for the administration of crystalloid intravenous fluids and antibiotics. Newborn babies with gastroschisis have large ongoing fluid losses and will often need in excess of 10-30 ml/kg in IV fluid boluses.

Soon after birth, the pediatric surgeon will assess the bowel for any abnormalities and decide on the next steps in the surgical treatment.

There are two primary methods to closing the abdominal wall defect in gastroschisis. The surgeon’s preference, degree of viscero-abdominal disproportion, the appearance of the bowel, and how the newborn is doing clinically are some of the factors that will guide the surgical treatment. Additionally, depending on patient characteristics, the abdominal defect may be closed immediately or delayed and either the sutured or sutureless closure may be employed. It is important to note that studies have not demonstrated any differences in outcomes in patients who have undergone sutureless closure versus silo placement and closure within 5 days (Hawkins, RB et al 2020). Therefore, several factors are taken into consideration to guide the optimal closure strategy for each patient with gastroschisis.

1. Sutureless Closure

Primary closure can be achieved in a significant percentage of patients with gastroschisis. It is important that the baby is doing well and is not significantly premature and that the bowel is not very dilated and there is minimal viscero-abdominal disproportion to be able to close the defect primarily.

This can be accomplished at the bedside, without intubation, general anesthesia and with minimal sedation (Bianchi et al 1998) using the umbilical cord as a flap in a suture-less closure after reduction of herniated bowel (Sandler et al 2004). This technique also requires a clinically well neonate and that the bowel is not very dilated, the difference is that the bowel is reduced and the defect covered with the umbilical stump and a Duoderm dressing.

The sutureless closure avoids an operation around the time of birth, but it may increase the risk for an umbilical hernia which will require surgical closure later in life. Studies have also found decreased use of general anesthesia, antibiotics, time on the ventilator, and surgical site infections in patients who underwent sutureless closure (Fraser JD, et al 2020).

2. Silo Placement

If reduction of the bowel with primary flap closure is not possible without causing respiratory compromise due to pressure on the diaphragm, then placement of a preformed silo can be performed at the bedside. This will allow for the bowel to be elevated, which facilitates the resolution of bowel wall edema and allows the reduction of the loops into the abdominal cavity over time.

This reduction can be encouraged by manual reduction of the loops of bowel tying umbilical tape around the silo to prevent re-herniation. This reduction can be repeated daily or twice daily as needed until all the bowel is reduced. The abdominal wall defect can then be either closed operatively (i.e., with sutures) or an umbilical cord flap can be used (i.e., delayed suturess closure).

The most common approach and the safest approach for babies who are in distress, significantly premature, those who have dilated bowel, or in patients with complex gastroschisis is to place the bowel in a preformed silo bag and then sequentially reduce it. When all of the bowel has been reduced into the abdominal cavity, the fascia is closed with sutures or a sutureless closure can be used.

In patients with complex gastroschisis who are known to have an associated bowel atresia, the primary goal in gastroschisis is the closure of the abdominal wall defect. Any attempt at resection of the bowel atresia at the time of delivery should be avoided as the bowel wall is edematous and inflamed and resection and primary anastomosis will result in anastomotic leak and sepsis. Once the bowel has been reduced into the abdomen the inflammatory peel begins to regress, and definitive surgery is considered where the atresia can be safely addressed and a primary anastomosis safely performed.

Lastly, either a peripherally inserted central venous catheter (PICC) is placed in the NICU prior to surgery or a tunneled central venous catheter (Broviac) is placed by the surgeon. The central line is critical for the newborn with gastroschisis, as it allows for the administration of IV nutrition and medications.

Postnatally, the most common problem affecting babies with gastroschisis is intestinal dysmotility and inability to absorb nutrients. In the first few weeks of life, all babies with gastroschisis will require total parenteral nutrition (TPN) as they slowly adjust to enteral feeds. During this time a nasogastric (or orogastric) tube will drain the secretions from the stomach until the baby has bowel function.

The mean time to first enteral feed was 16 days in a Canadian study (Boutros et al., 2009) and the median time to full enteral feeds in babies with simple gastroschisis was 24 days (Bradnock et al., 2011). In patients with complex gastroschisis, the time to full enteral feeds was 81 days in a cohort study from England and Ireland (Bradnock et al., 2011). More contemporary studies where there has been an attempt to standardize feeding protocols have demonstrated that early closure of the gastroschisis defect is associated with earlier feed initiation and decreased time to when patients reach enteral autonomy (first feed on average was initiated in 17 days and enteral autonomy was reached in 25 days) (Harris J, et al 2015).

Additionally, feeding advancement strategies are also actively being investigated in order to safely shorten the time to when patients reach enteral autonomy (Utria AF, et al 2022).

Rates of patients with complex gastroschisis are variable. Bradnock et al. (2011) identified 11% with atresia, necrosis or bowel perforation in their cohort study and Emil et al. (2011) identified 23% with complex gastroschisis in a smaller cohort. Boutros et al., found that 22% of the patients in the Canadian study required multiple operations, likely related to complex gastroschisis. This group of patients with gastroschisis has a significantly longer NICU stay, ranging from 84 days (Bradnock et al., 2011) to 104 days (Emil et al., 2011), and will more likely develop short bowel syndrome and be at risk for TPN-induced liver failure. These studies highlight that there is a subset of patients with gastroschisis who are at risk of higher complication rates, need for reoperation, and have a longer length of stay.

Intestinal failure may result from gastroschisis. It can either be secondary to short bowel syndrome as a result of loss of bowel length, or it can be a result of severe dysmotility and chronic intestinal pseudo-obstruction. Both conditions will require long-term TPN dependency, which can result in liver failure, and sepsis and may require bowel and liver transplantation. Fortunately, it is rare that patients born with gastroschisis end up needing bowel and liver transplantation.

Pneumatosis intestinalis is seen in up to 10% of infants with gastroschisis. Pneumatosis is a sign of necrotizing enterocolitis (NEC) in newborn babies, but in gastroschisis medical NEC is more common than surgical NEC which requires laparotomy to address perforation or medically refractory systemic illness. Medical NEC is managed with bowel rest and IV antibiotics for 7-10 days until pneumatosis resolves.

Cryptorchidism is common in baby boys with gastroschisis, about a third of baby boys with gastroschisis will have cryptorchidism at birth and a third of these babies will need to undergo orchidopexy (Hill and Durham, 2011). Hernias, both inguinal and incisional are common in infants with gastroschisis which may not present for several months after discharge from the NICU.

Infants born with gastroschisis are often small typically < 5% of body weight at delivery and their small size tends to persist through the end of the first year of life. Linear growth failure is common in patients with gastroschisis and requires ongoing monitoring after discharge from the hospital (Strobel KM, et al 2021). Most children will begin catching up in somatic growth after their first year of life.

The duration of hospitalization is directly related to the degree of gastrointestinal compromise or presence of gastrointestinal atresia. Approximately 10% of patients with gastroschisis will have hypoperistalsis syndrome. These infants remain dependent on parenteral nutrition for an indefinite period, sometimes permanently.

The average hospital stay following the primary closure of gastroschisis is usually on the order of 7 to 14 days. Often feeding difficulties after repair of gastroschisis will delay discharge because of the need for gavage feedings. Although primary closure may be achieved and infants are weaned from mechanical ventilatory support, they often remain quite tachypneic, which impairs their ability to suckle. Once further abdominal wall relaxation and accommodation have had time to occur, there is less tension and pressure on the diaphragm and the respiratory rate decreases. Once a respiratory rate of less than 60 breaths per minute is achieved, infants can suckle effectively and be weaned from supplemental gavage feeding.

Hospitalization for infants with gastroschisis requiring staged closure is much longer, related to the need for gradual reduction, greater visceroperitoneal disproportion, and a second procedure to achieve fascial closure. The hospitalization in these infants may be prolonged by several weeks.

Inguinal hernias will develop in most infants with gastroschisis because of increased intraabdominal pressure. Occasionally, incisional hernias seen as bulging from attenuated fascia at the closure site will require remedial surgery months or years later. There are no long-term sequelae from gastroschisis if there is no associated hypoperistalsis syndrome.

Gastroschisis has been generally considered a sporadic event, with a multifactorial cause, but there have been reports of familial recurrence (Hershey et al. 1989; Lowry and Baird 1982; Salinar et al. 1979). Torfs et al. (1991) described a 4.3% sibling recurrence rate in a population-based study. A 4.3% recurrence risk implies a mixture of genetic predisposition with environmental factors. In one study, Torfs and Curry (1993) found only 6 published reports of familial occurrence of gastroschisis.

Therefore, a single-gene defect is unlikely for this condition. Families should receive genetic counseling regarding recurrence risk and they should be offered MSAFP testing and prenatal sonography in future pregnancies.

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