Co-occurring non-omphalocele and non-gastroschisis anomalies among cases with congenital omphalocele and gastroschisis.

The pathogenesis of omphalocele and gastroschisis is not obvious. Their etiology is disputed. The prevalence and the types of anomalies co-occurring with omphalocele and gastroschisis are variable in the different series published. The aim of this study was to estimate the frequency and the types of co-occurring anomalies in cases with gastroschisis and omphalocele. This study was performed in a well-described population of 387,067 consecutive births between 1979 and 2007. Hundred-one cases with omphalocele were registered (2.61 per 10,000), 75 (74.3%) had co-occurring anomalies comprising chromosomal anomalies (28 cases, 27.7%, including 18 trisomy 18), non-chromosomal syndromes (16 cases, 15.8%, including 3 cases with Beckwith-Wiedemann syndrome, 2 cases with the OEIS sequence, and one case with the Pentalogy of Cantrell complex), and 31 cases, 30.7% with MCA (multiple congenital anomalies). The most common MCA were musculoskeletal (23.5%), urogenital (20.4%), cardiovascular (15.1%), and central nervous (9.1%). Seventy-one cases of gastroschisis were ascertained (1.83 per 10,000). However, the prevalence increased during the study period. The frequency was highest in the mothers 15-19 years old. Sixteen out of the 71 cases with gastroschisis, (22.5%) had co-occurring anomalies including 11 cases of MCA and 5 cases with syndromes. To conclude, the frequency and the types of anomalies co-occurring with omphalocele and gastroschisis are peculiar. Therefore, cases with gastroschisis and omphalocele need to be screened for co-occurring anomalies.

Investigation of a connection between abdominal wall defects and severity of the herniation in fetuses with gastroschisis and omphalocele.

Analyze the biometric parameters and the size (area) of abdominal wall defect (AWD) in fetuses with gastroschisis and omphaloceles and correlate them with the herniated internal organs. We studied 22 fetuses (11 with AWDs and 11 without anomalies). In all fetuses we evaluated the xiphopubic distance (XPD) and iliac crest distance (ICD). In fetuses with AWDs we dissected the abdominal wall and measured the width and length of the defect for calculating its area and studying the correlation between the size of the defect with the organs that were herniated. For statistical analysis, the Anova and Tukey post-test were used (p < 0.05). The XPD in the control group had mean of 4.2 mm (2.3-5.9; SD ± 1.11), while in the AWDs it was 4.2 mm (2.9-5.5; SD ± 0.98) (p = 0.4366). The ICD had mean values of 2.5 mm (1.6-3.4; SD ± 0.58) in the control group, and 2.3 mm (1.2-3.0; SD ± 0.56) in AWDs fetuses (p = 0.6963). The number of herniate organs do not have significant correlation with the area of the defect (r2 = 0.2504, p = 0.5068). There is no correlation between the size (area) of abdominal wall defects and the number of the internal organs that herniated. Therefore, the hole size is not a predictor of the severity of the gastroschisis or omphalocele.

Antibiotic Utilization and Infection Among Infants with Abdominal Wall Defects.

BACKGROUND: Neonates with abdominal wall defects are at an increased infection risk because of the defect itself and prolonged neonatal intensive care unit (NICU) stays. Antibiotic prophylaxis until closure of the defect is common. However, infection risk and antibiotic use have not been well quantified in these infants. METHODS: A retrospective cohort study of infants with abdominal wall defects (gastroschisis and omphalocele) admitted to a single-center NICU from 2007 to 2018. Demographic and clinical information, including microbiologic studies, antibiotic dosing and surgical care, were collected. Antibiotic use was quantified using days of therapy (DOT) per 1000 patient-days. Sepsis was defined as culture of a pathogen from a normally sterile site. RESULTS: Seventy-four infants were included; 64 (86%) with gastroschisis and 10 (14%) with omphalocele. Median day of closure was 8 days [interquartile range (IQR) 6-10, range 0-31]. All infants received ≥1 course of antibiotics; median antibiotic DOT/infant was 24.5 (IQR 18-36) for an average of 416.5 DOT per 1000 patient-days. Most antibiotic use was preclosure prophylaxis (44%) and treatment of small intestinal bowel overgrowth (24%). Suspected and proven infection accounted for 26% of all antibiotic use. Skin and soft tissue infection (13/74, 18%) and late-onset sepsis (11/74, 15%) were the most common infections; 2 infants had sepsis while on antibiotic prophylaxis. All infants survived to discharge. CONCLUSIONS: Most antibiotic use among infants with abdominal wall defects was prophylactic. Infection on prophylaxis was rare, but 35% of infants had infection after prophylaxis. Improved stewardship strategies are needed for these high-risk infants.

Intraoperative Findings Associated to Inpatient Mortality From Patients With Gastroschisis in Western Mexico.

BACKGROUND: Intraoperative findings during gastroschisis surgery are the main predictor associated with increased mortality. The aim of our study was to determine the type of surgical findings associated with inpatient mortality in a cohort of patients with gastroschisis from a university hospital in Western Mexico. MATERIALS AND METHODS: Infants with surgically repaired gastroschisis during the period 2011-2017 at the Dr. Juan I. Menchaca Civil Hospital of Guadalajara (Guadalajara, Mexico) were studied. Data regarding demographics, perinatal history, and intraoperative findings were collected and compared according to whether they were nonsurvivors (cases) or survivors (controls) at hospital discharge. Data were analyzed using logistic regression, determining its adjusted odds ratio (aOR) and its respective 95% confidence intervals (95% CIs). The proper adjustment of the model was verified using the Hosmer and Lemeshow test. RESULTS: Ninety-four patients with gastroschisis were studied, of which 13 were nonsurvivors (13.8%), and 81 (86.2%) were survivors at hospital discharge. In the group of survivors, primary surgical closure was performed more frequently (P = 0.018), whereas staged reduction with a silo predominated in the group of nonsurvivors (P = 0.018), and an increased frequency of complex gastroschisis (0.0001). After logistic regression analysis, intraoperative findings associated with nonsurvival were severe bowel matting (aOR: 7.3; 95% CI: 1.2-44), and prolapse of the small intestine and large intestine, plus any other organ (aOR: 15.9; 95% CI: 1.1-219.6). CONCLUSIONS: Mortality in our cohort was high (13.8%) and was significantly associated with severe bowel matting, and the prolapse of the small and large intestines, plus any other organ.

Change in prepregnancy body mass index and gastroschisis.

PURPOSE: Maternal body mass index (BMI) is inversely associated with gastroschisis, but a causal relationship has not been established. As data demonstrating that a change in exposure status is related to a change in the frequency of the outcome can add to the evidence for causality, we conducted a case-control study of change in maternal BMI, assessed using interpregnancy change in BMI (IPC-BMI), and gastroschisis. METHODS: Data for 258 gastroschisis cases and 2561 controls were obtained from the Texas Birth Defects Registry and vital records (2006-2012). Logistic regression was used to estimate the adjusted association between IPC-BMI and gastroschisis. RESULTS: The continuous IPC-BMI variable was inversely associated with gastroschisis (adjusted odds ratio [aOR] = 0.90, 95% confidence interval [CI]: 0.86, 0.95). When assessed as a six-level categorical variable, with weight stable women as the referent, the odds of gastroschisis were higher following a BMI decrease of greater than 1 unit (aOR = 1.37, 95% CI: 0.91, 2.06) and lower after a BMI increase of ≥3 units (aOR = 0.62, 95% CI: 0.42, 0.94). CONCLUSIONS: Our findings suggest that maternal change in BMI is associated with gastroschisis and, thus, add to the epidemiological evidence that can be used to inform our understanding of the relationship between BMI and gastroschisis.

Gastroschisis Is Associated With Placental Delayed Villous Maturation.

Gastroschisis is a congenital abnormality characterized by visceral herniation through an abdominal wall defect. While the cause of gastroschisis is unknown, it has been linked to risk factors including young maternal age, smoking, and alcohol use during pregnancy. To date, the only established placental correlate is amniocyte vacuolization. Based on our clinical experience, we hypothesized that delayed villous maturation (DVM) is also associated with gastroschisis. We conducted a retrospective slide review of 23 placentas of neonates with gastroschisis. Additionally, we selected 2 control groups of placentas: 1 with a previous diagnosis of DVM and 1 with normal villous morphology. All placentas were randomized and reviewed by 2 perinatal pathologists, who were blinded to the group; DVM and amniocyte vacuolization were assessed. Gastroschisis was associated with increased placental DVM in 65.2% of cases (vs 13.6% of controls; P = .0007) and increased amniocyte vacuolization in 52.2% of cases (vs 9.1% of controls; P = .003) compared to the control group. Based on the normal and DVM groups, kappa agreement between current slide review and initial pathology diagnosis was 0.419, indicating moderate agreement. Our study shows that gastroschisis is associated with placental DVM. This association may be due to (1) a common upstream factor contributing to both gastroschisis and DVM or (2) DVM may be a consequence of the altered placental and amniotic environment in the context of gastroschisis.

Fetal intra-abdominal bowel dilation in prediction of complex gastroschisis.

OBJECTIVE: To investigate intra-abdominal bowel dilation (IABD) in the prediction of complex gastroschisis. METHODS: This was a retrospective study of 174 singleton pregnancies with isolated fetal gastroschisis, resulting in live birth and with available ultrasound images from visits at both 20-22 and 30-32 weeks' gestation. IABD was measured as the greatest transverse diameter of the most dilated intra-abdominal bowel segment, by an operator blinded to postnatal outcome. The distribution of IABD measurements in those with complex and those with simple gastroschisis was determined and the best cut-off value to predict complex gastroschisis was selected using receiver-operating characteristics (ROC) curves. The area under the ROC curve (AUC), detection rate (DR), false-positive rate (FPR), positive predictive value (PPV) and negative predictive value (NPV) were determined. RESULTS: The study population included 39 (22.4%) cases of complex and 135 (77.6%) cases of simple gastroschisis. In the prediction of complex gastroschisis, the AUC at 20-22 weeks' gestation was 0.742 (95% CI, 0.628-0.856) and the respective value for 30-32 weeks was 0.820 (95% CI, 0.729-0.910). At the IABD cut-off of 7 mm at 20-22 weeks, DR, FPR, PPV and NPV for complex gastroschisis were 61.5%, 6.7%, 72.7% and 89.4%, respectively, and at IABD cut-off of 14 mm at 30-32 weeks, the respective values were 64.9%, 5.9%, 75.0% and 90.7%. CONCLUSION: Measurement of IABD at 20-22 or at 30-32 weeks' gestation is useful in the prediction of complex gastroschisis. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

An evolutionary and developmental biology approach to gastroschisis.

Recent advances have now made it possible to speak of gastroschisis narrowly in morphogenetic terms invoking the Rittler-Beaudoin (R-B) model. This proceeds from the appreciation of gastroschisis as a congenital intestinal herniation (without cover or liver) within the primordial umbilical ring, mostly to the right side of a normally formed umbilical cord. Presently, it is unresolved whether this visceral prolapse represents failure of ring closure before return of the physiological hernia into the abdomen or rupture of the delicate amniotic/peritoneal membrane at the ring's edge to the right of the cord. Animal observations and experiments will be required to address this question effectively. If gastroschisis is, in fact, a primary malformation with the primordial umbilical ring as the developmental field involved, then homology implies potential gastroschisis in all amniotes with corresponding nourishment from yolk sac (aka omphalomesenteric) vessels going into the embryo and excretory products out via the ancient umbilical connection. It also implies homology of corresponding morphogenetic signal transduction cascades. We review the history of gastroschisis, its presumed pathogenesis, and the developmental biology of the amniotic umbilical ring from this perspective. Therefore, based on the animal and human evidence to date, we propose that gastroschisis is a primary midline malformation that involves the umbilical canal from amniotic to peritoneal space and its primordial umbilical ring, either through nonclosure or rupture of the membrane covering the area, mostly to the right, between the cord and the edge of the ring.

The intestinal fatty acid-binding protein as a marker for intestinal damage in gastroschisis.

BACKGROUND/PURPOSE: We analyzed the capacity of urinary Intestinal fatty acid-binding protein (I-FABP) to quantify the degree of mucosal injury in neonates with gastroschisis (GS) and to predict the speed of their clinical recovery after surgery. METHODS: In this prospective study, we collected urine during the first 48h after surgery from neonates operated between 2012 and 2015 for GS. Neonates with surgery that did not include gut mucosa served as controls for simple GS and neonates with surgery for intestinal atresia served as control for complex GS patients. The I-FABP levels were analyzed by ELISA. RESULTS: Urinary I-FABP after the surgery is significantly higher in GS newborns than in control group; I-FABP in complex GS is higher than in simple GS. I-FABP can predict subsequent operation for ileus in patients with complex GS. Both ways of abdominal wall closure (i.e. primary closure and stepwise reconstruction) led to similar levels of I-FABP. None of the static I-FABP values was useful for the outcome prediction. The steep decrease in I-FABP after the surgery is associated with faster recovery, but it cannot predict early start of minimal enteral feeding, full enteral feeding or length of hospitalization. CONCLUSION: Urinary I-FABP reflects the mucosal damage in gastroschisis but it has only a limited predictive value for patients' outcome.

Maternal administration of cannabidiol promotes an anti-inflammatory effect on the intestinal wall in a gastroschisis rat model.

Gastroschisis (GS) is an abdominal wall defect that results in histological and morphological changes leading to intestinal motility perturbation and impaired absorption of nutrients. Due to its anti-inflammatory, antioxidant, and neuroprotective effects, cannabidiol (CBD) has been used as a therapeutic agent in many diseases. Our aim was to test the effect of maternal CBD in the intestine of an experimental model of GS. Pregnant rats were treated over 3 days with CBD (30 mg/kg) after the surgical induction of GS (day 18.5 of gestation) and compared to controls. Fetuses were divided into 4 groups: 1) control (C); 2) C+CBD (CCBD); 3) gastroschisis (G), and 4) G+CBD (GCBD). On day 21.5 of gestation, the fetuses were harvested and evaluated for: a) body weight (BW), intestinal weight (IW), and IW/BW ratio; b) histometric analysis of the intestinal wall; c) immunohistochemically analysis of inflammation (iNOS) and nitrite/nitrate level. BW: GCBD was lower than CCBD (P<0.005), IW and IW/BW ratio: GCBD was smaller than G (P<0.005), GCBD presented lower thickness in all parameters compared to G (P<0.005), iNOS and nitrite/nitrate were lower concentration in GCBD than to G (P<0.005). Maternal use of CBD had a beneficial effect on the intestinal loops of GS with decreased nitrite/nitrate and iNOS expression.

Maternal administration of cannabidiol promotes an anti-inflammatory effect on the intestinal wall in a gastroschisis rat model

Gastroschisis (GS) is an abdominal wall defect that results in histological and morphological changes leading to intestinal motility perturbation and impaired absorption of nutrients. Due to its anti-inflammatory, antioxidant, and neuroprotective effects, cannabidiol (CBD) has been used as a therapeutic agent in many diseases. Our aim was to test the effect of maternal CBD in the intestine of an experimental model of GS. Pregnant rats were treated over 3 days with CBD (30 mg/kg) after the surgical induction of GS (day 18.5 of gestation) and compared to controls. Fetuses were divided into 4 groups: 1) control (C); 2) C+CBD (CCBD); 3) gastroschisis (G), and 4) G+CBD (GCBD). On day 21.5 of gestation, the fetuses were harvested and evaluated for: a) body weight (BW), intestinal weight (IW), and IW/BW ratio; b) histometric analysis of the intestinal wall; c) immunohistochemically analysis of inflammation (iNOS) and nitrite/nitrate level. BW: GCBD was lower than CCBD (P<0.005), IW and IW/BW ratio: GCBD was smaller than G (P<0.005), GCBD presented lower thickness in all parameters compared to G (P<0.005), iNOS and nitrite/nitrate were lower concentration in GCBD than to G (P<0.005). Maternal use of CBD had a beneficial effect on the intestinal loops of GS with decreased nitrite/nitrate and iNOS expression.

Clinicoplacental correlates of amniocyte vacuolization in association with gastroschisis.

INTRODUCTION/OBJECTIVES: Gastroschisis has been associated with a characteristic type of amniocyte vacuolization. In this study, we determined the frequency and clinicoplacental correlates of this apparently unique alteration of the amniotic epithelium. METHODS: We performed a retrospective clinicopathologic analysis of 74 consecutive cases of isolated gastroschisis. Placental membrane sections were reviewed for presence and extent of amniocyte vacuolization, and immunostained for adipophilin, a lipid droplet-associated protein. Controls included placentas from pregnancies complicated by omphalocele, meconium exposure or chorioamnionitis. RESULTS: A distinct type of diffuse, fine and homogeneous amniocyte vacuolization was present in 15/74 (20%), absent in 41/74 (55%), and equivocal in 18/74 (24%) gastroschisis cases. Similar amniocyte vacuolization was seen in only 1/30 meconium-stained controls, and in none of the other non-gastroschisis controls. Adipophilin immunostaining enhanced the visualization of the cytoplasmic vacuoles and confirmed their lipid nature. Compared to gastroschisis cases without such vacuolization, cases with typical, extensive amniocyte vacuolization had a tendency to lower birth weight percentile (26% versus 40%; P < 0.08), a significantly lower fetal:placental weight ratio (4.72 versus 5.51; P < 0.01), and a significantly higher frequency of associated meconium exposure (14/15 versus 15/41, P < 0.001) and/or chorioamnionitis (8/15 versus 6/41; P < 0.01). The length of hospital stay was equivalent for infants with or without amniocyte vacuolization. CONCLUSION: Diffuse, fine and homogeneous lipid droplet accumulation in amniocytes is highly characteristic of gastroschisis, but only seen in about 20% of cases. The functional implications of excessive lipid accumulation, and the exact mechanisms underlying the strong association between amniocyte lipid accumulation and chorioamnionitis/meconium exposure in a subset of gastroschisis cases remain undetermined.

Association between a Maternal History of Miscarriages and Birth Defects.

BACKGROUND: Some studies, mainly in the older literature, observed a significant association between miscarriages and birth defects (BDs) occurring in the same sibship. However, few studies examined the BD/miscarriage relationship in depth. In addition nothing has been added to the underlying mechanisms possibly linking both events. The purpose of this work was to identify specific BDs associated with maternal miscarriages. In particular, it examined whether the risk depended on the number of losses, and to suggest the existence of specific factors for each BD/miscarriage association observed. METHODS: The study relied on the Latin American Collaborative Study on Congenital Malformations (ECLAMC) database registries including 26,906 live and stillborn infants with one of 19 selected isolated BDs and 93,853 normal controls. Infants born to primigravid mothers were excluded from the present study. Demographic and reproductive variables were compared between control mothers With and Without previous miscarriages. The number, frequency, and distribution of miscarriages were observed for each BD and controls. A conditional logistic regression was applied to evaluate the miscarriage risk for each BD. RESULTS: Control mothers with previous miscarriages were older, had had more pregnancies, and were less educated. Three risk patterns of miscarriages were observed: a very high risk of miscarriages associated with gastroschisis, omphalocele, and talipes; only one miscarriage associated with spina bifida, and two or more miscarriages associated with hypospadias. CONCLUSION: These three patterns suggest that different factors underly each BD/miscarriage association: infertility for hypospadias, vascular disruption for gastroschisis and talipes, while for spina bifida, the much debated trophoblastic cell residue theory could not be discarded. Birth Defects Research 109:254-261, 2017. © 2017 Wiley Periodicals, Inc.

Intrauterine Fetal Death With Vanishing Gastroschisis and Post Mortem Examination Findings.

We present a severe case of vanishing gastroschisis resulting in intrauterine death with post mortem examination findings. Gastroschisis is defined as a full thickness paraumbilical abdominal wall defect associated with evisceration of fetal intestine. It is almost always right-sided. Vanishing gastroschisis is an extremely rare form of gastroschisis that results in short bowel syndrome due to exteriorized bowel disconnected from the lumen of the rest of the bowel proximally as well as distally in association with partial or complete closure of the abdominal wall. This case is only the second published case of vanishing gastroschisis resulting in intrauterine fetal death including post mortem examination findings. It highlights the importance of being aware of this rare form of gastroschisis and provides insights regarding pathogenesis, ultrasound surveillance, and antenatal counseling.

Is vacuolization in amniocytes really pathognomonic for fetal gastroschisis?

Cytoplasmic vacuolization in amniocytes reportedly is specific to gastroschisis, but documentation is anecdotal. To test this point, we compared 47 placentas from documented cases of gastroschisis to 48 placentas from patients without gastroschisis. We found amniocyte vacuolization is highly sensitive (0.94), but not nearly as specific (0.44) for gastroschisis even after accounting for extent or prominence of vacuoles (specificities <0.73). The lack of specificity results from similar, if not identical, cytoplasmic vacuolization seen in term placentas. If one limits comparison to cases delivered before 37 weeks' gestation, then amniocyte vacuolization is highly sensitive (0.95) and specific (0.82) for gastroschisis.

What prenatal ultrasound features are predictable of complex or vanishing gastroschisis? A retrospective study.

OBJECTIVE: To evaluate prenatal ultrasound parameters as prognostic factors for complex and vanishing gastroschisis. METHODS: Retrospective multicentre study of 200 gastroschisis over 13 years (2000-2013). Collection of prenatal ultrasound evaluation on maternal and fetal growth parameters, intra- and extra-abdominal bowel and stomach dilation, abdominal wall defect diameter and changes in bowel appearance. Correlation of these factors with the presence of mechanical intestinal complications at birth, named 'complex gastroschisis'. RESULTS: Fifty-two patients (26%) had complex gastroschisis (CG), including ten vanishing gastroschisis. The presence of intra-abdominal bowel dilation at the second (T2) or third (T3) trimester ultrasound was predictive for CG, with odds ratios at 6.69 (95%CI 2.41-18.55) and 4.72 (95%CI 2.16-10.28), respectively, with a cut-off value at the last examination of >19 mm. A small abdominal wall defect diameter was also predictive for CG, with cut-off values of <9.2 mm at T2 and <12.5 mm at T3. Vanishing gastroschisis recorded earlier intra-abdominal bowel dilation diagnosis, associated with a small wall defect and no extra-abdominal dilation. CONCLUSION: Intra-abdominal bowel dilation and a small abdominal wall defect diameter accurately predict CG and could be a first sign of vanishing gastroschisis when they occur early. © 2016 John Wiley & Sons, Ltd.

Transamniotic stem cell therapy (TRASCET) in a leporine model of gastroschisis.

BACKGROUND/PURPOSE: Transamniotic stem cell therapy (TRASCET) with amniotic fluid mesenchymal stem cells (afMSCs) has been shown to mitigate bowel damage in a rodent model of gastroschisis. As a prerequisite to clinical translation, we sought to study TRASCET in a larger animal model. METHODS: New Zealand rabbit fetuses (n=64) with surgically created gastroschisis were divided into three groups. One group (untreated) had no further manipulations. Two groups received volume-matched intraamniotic injections of either saline or a suspension of afMSCs. Nonmanipulated fetuses served as controls. Histomorphologic measurements of intestinal damage, along with biochemical profiling of inflammation markers, were performed at term. Statistical comparisons were by Fisher's exact test, ANOVA and the Wald test (P<0.05). RESULTS: Overall survival was 62.5%. Segmental and total intestinal wall thicknesses were significantly decreased in the afMSC group compared with the untreated and saline groups (all P<0.001), with no significant differences between untreated and saline groups (P=0.24 to 1.00, depending on layer). Muscularis and serosal layers were significantly thicker in the afMSC group than in normal controls (P=0.045 and P<0.001, respectively). CONCLUSIONS: Concentrated intraamniotic injection of afMSC lessens, yet does not prevent, intestinal damage in a leporine model of gastroschisis. TRASCET may become a valuable strategy in the management of gastroschisis. LEVEL OF EVIDENCE: N/A - animal/experimental studies.