Impact of Bowel Coverage and Resuscitation Protocol on Gastroschisis Mortality in Low-Income Countries: Experience and Lessons From Uganda.

BACKGROUND: Gastroschisis causes near complete mortality in low-income countries (LICs). This study seeks to understand the impact of bedside bowel reduction and silo placement, and protocolized resuscitation on gastroschisis outcomes in LICs. METHODS: We conducted a retrospective cohort study of gastroschisis patients at a tertiary referral center in Kampala, Uganda. Multiple approaches for bedside application of bowel coverage devices and delayed closure were used: sutured urine bags (2017-2018), improvised silos using wound protectors (2020-2021), and spring-loaded silos (2022). Total parental nutrition (TPN) was not available; however, with the use of improvised silos, a protocol was implemented to include protocolized resuscitation and early enteral feeding. Risk ratios (RR) for mortality were calculated in comparison to historic controls from 2014. RESULTS: 368 patients were included: 42 historic controls, 7 primary closures, 81 sutured urine bags, 133 improvised silos and 105 spring-loaded silos. No differences were found in sex (p = 0.31), days to presentation (p = 0.84), and distance traveled to the tertiary hospital (p = 0.16). Following the introduction of bowel coverage methods, the proportion of infants that survived to discharge increased from 2% to 16-29%. In comparison to historic controls, the risk of mortality significantly decreased: sutured urine bags 0.65 (95%CI: 0.52-0.80), improvised silo 0.76 (0.66-0.87), and spring-loaded silo 0.65 (0.56-0.76). CONCLUSION: Bedside application of bowel coverage and protocolization decreases the risk of death for infants with gastroschisis, even in the absence of TPN. Further efforts to expand supply of low-cost silos in LICs would significantly decrease the mortality associated with gastroschisis in this setting. TYPE OF STUDY: Treatment Study. LEVEL OF EVIDENCE: III (Retrospective Comparative Study).

Development of a low-cost congenital abdominal wall defect simulator (wall-go) for undergraduate medical education: a validation study.

BACKGROUND: Congenital Anomalies were responsible for 303,000 deaths in the neonatal period, according to the WHO, they are among the world's top 20 causes of morbidity and mortality. Expensive simulators demonstrate several diseases, but few are related to congenital anomalies. This study aims to develop, validate, and evaluate low-cost simulator models (WALL-GO) of the most common abdominal wall defects, gastroschisis, and omphalocele, to enable diagnosis through an accessible tool with study value and amenable to replication. METHODS: Market research was conducted to find materials to build low-cost models. The researchers built the model and underwent validation assessment of the selected experts who scored five or more in the adapted Fehring criteria. The experts were assessed through a 5-point Likert scale to 7 statements (S1-7). Statements were assigned values according to relevance in face and transfer validities. Concomitantly, the model was also evaluated by students from 1st to 5th year with the same instruments. Content Validity Indexes (CVIs) were considered validated between groups with concordance greater than 90%. Text feedback was also collected. Each statement was subjected to Fisher's Exact Test. RESULTS: Gastroschisis and omphalocele model costs were US $15 and US $27, respectively. In total, there were 105 simulator evaluators. 15 experts were selected. Of the 90 students, there were 16 (1st year), 22 (2nd), 16 (3rd), 22 (4th), and 14 (5th). Students and experts obtained CVI = 96.4% and 94.6%, respectively. The CVIs of each statement were not significantly different between groups (p < 0,05). CONCLUSIONS: The WALL-GO models are suitable for use and replicable at a manufacturable low cost. Mannequins with abdominal wall defects are helpful in learning to diagnose and can be applied in teaching and training health professionals in developing and low-income countries.

Optimal timing of delivery for growth restricted fetuses with gastroschisis: A decision analysis.

OBJECTIVE: Our objective was to determine the optimal timing of delivery of growth restricted fetuses with gastroschisis in the setting of normal umbilical artery (UA) Dopplers. METHODS: We designed a decision analytic model using TreeAge software for a hypothetical cohort of 2000 fetuses with isolated gastroschisis, fetal growth restriction (FGR), and normal UA Dopplers across 34-39 weeks of gestation. This model accounted for costs and quality adjusted life years (QALYs) for the pregnant individual and the neonate. Model outcomes included stillbirth, respiratory distress syndrome (RDS), necrotizing enterocolitis (NEC), intraventricular hemorrhage (IVH), short gut syndrome (SGS), neonatal sepsis, neonatal death, and neurodevelopmental disability (NDD). RESULTS: We found 38 weeks to be the optimal timing of delivery for minimizing overall perinatal mortality and leading to the highest total QALYs. Compared to 37 weeks, delivery at 38 weeks resulted in 367.98 more QALYs, 2.22 more cases of stillbirth, 2.41 fewer cases of RDS, 0.02 fewer cases of NEC, 1.65 fewer cases of IVH, 0.5 fewer cases of SGS, 2.04 fewer cases of sepsis, 11.8 fewer neonatal deaths and 3.37 fewer cases of NDD. However, 39 weeks were the most cost-effective strategy with a savings of $1,053,471 compared to 38 weeks. Monte Carlo analysis demonstrated that 38 weeks was the optimal gestational age for delivery 51.70% of the time, 39 weeks were optimal 47.40% of the time, and 37 weeks was optimal 0.90% of the time. CONCLUSION: Taking into consideration a range of adverse perinatal outcomes and cost effectiveness, 38-39 weeks gestation is ideal for the delivery of fetuses with gastroschisis, FGR, and normal UA Dopplers. However, there are unique details to consider for each case, and the timing of delivery should be individualized using shared multidisciplinary decision making.

Gastroschisis in Sub-Saharan Africa: a scoping review of the prevalence, management practices, and associated outcomes.

Gastroschisis is a congenital defect of the anterior abdominal wall characterized by a periumbilical abdominal wall defect with associated bowel protrusion. Limitations in the diagnosis and management of gastroschisis in Sub-Saharan African countries contribute to the high mortality rate. Few studies have been published despite its significant contribution to neonatal mortality in Sub-Saharan Africa. This review study explores the prevalence of gastroschisis, likewise the management and clinical outcomes. Full-text articles reporting the prevalence, management, and associated outcomes of gastroschisis in Sub-Saharan Africa were included. Data were extracted from databases such as PubMed, Google Scholar, and Ajol following a systematic search. The study was reported following the PRISMA-ScR guideline. A total of ten articles which included studies conducted from 1999 to 2022 fulfilled the criteria. The prevalence of gastroschisis varied widely, ranging from 0.026 to 1.75 with an overall mortality rate of 62.48%. Young maternal age is strongly associated with the incidence of gastroschisis. The study showed a slight male preponderance with a M: F ratio of 1.12:1. Staged closure with silos is the preferred method of management, it is explicitly linked to improved clinical outcomes. The prevalence rate and associated mortality of gastroschisis remain alarmingly high in most of the studies. There is a need for advanced diagnostic and management practices as well as increased awareness of gastroschisis to reduce mortality and improve survival outcomes.

Assessment of the neonatal referral and transport system for patients with gastroschisis in Kenya.

PURPOSE: To assess the neonatal referral and transport system for gastroschisis patients referred to a tertiary level hospital in Kenya. METHODS: This was a prospective cross-sectional study carried out at Kenyatta National Hospital (KNH) which recruited patients with gastroschisis using consecutive sampling approach. Data were collected on pre-, intra-transit factors, time and distance covered. Assessment was done using pre and intra transit factors as per the standard transport protocols in literature. RESULTS: Twenty-nine patients presented with gastroschisis during the eight month study period. Mean age was 7.07 h. There were 16 (55.2%) males and 13 (44.8%) females. Mean birthweight was 2020 g, and a mean gestational age of 36.5 weeks. Mean duration of transit was 5 h. Mean distance from referring facility was 153.1 km. Most affected factors in the pre-transit protocol were lack of monitoring chart (0%), comment on blood investigations (0%), gastric decompression (3.4%), and prenatal obstetric scan (44.8%). For intra-transit scores, most affected were incubator use (0%), bowel monitoring (0%), functioning nasogastric tube (13.8%), and adequate bowel cover (34.5%). CONCLUSION: This study demonstrates that pre-transit and transit care of neonates with gastroschisis is inadequate in Kenya. Interventions needed, as identified by this study, to promote care of neonates with gastroschisis are advised.

Surgical neonates in a low-resource setting: Baseline nutrition and outcome assessment.

INTRODUCTION: Congenital anomalies necessitating prolonged fasting have a high mortality in low-income settings, partially due to malnutrition and electrolyte disturbances in the absence of parenteral nutrition (PN). Interventions to address these problems require an accurate baseline quantification of the morbidity and mortality of this population. This prospective study aimed to determine peri-operative morbidity, fluid and electrolyte disturbance, growth, and mortality in neonates with gastroschisis (GS), intestinal atresia (IA), and esophageal atresia (EA) in Uganda. METHODS: Standardized patient care of 45 neonates treated in Uganda from Oct 2021 to March 2022 with protocolized fluid and nutrition, vital signs, and routine laboratory measurements. Patient demographics, admission and hospital characteristics are described with mean ± SD. Characteristics of survivors and non-survivors were compared with Fischer's exact tests, logrank tests, and CoX Ph model. RESULTS: Twenty-eight (62.2%) patients had GS, 4 (8.9%) EA, and 13 (28.9%) IA. Thirty-six percent (16/44) of patients survived to discharge (26% GS, 50% EA, 54% IA) with an average length of stay of 17.3 days ( ± 2.2) (survivors) and 9 days ( ± 1.7) (non-survivors). Average weight was 2.21 kg ( ± 0.62) at presentation, with no significant weight change during the study. Abnormal serum sodium in 64%, phosphate 36.5%, and magnesium 20.8% of measurements. Mortality did not correlate with diagnosis (p = 0.47), electrolyte derangement, or weight change. CONCLUSION: Mortality of neonates born with GS, EA, and IA is high in Uganda. Malnutrition and fluid/electrolyte derangements are common and may affect mortality. This study provides a comparison group for studying interventions to improve outcomes for these populations. TYPE OF STUDY: Prospective cohort. LEVEL OF EVIDENCE: Level 3.

Impact of Social Vulnerability on Long-Term Growth Outcomes in Sutureless Versus Sutured Repair of Gastroschisis.

INTRODUCTION: The purpose of this study is to describe the long-term growth and nutrition outcomes of sutureless versus sutured gastroschisis repair. We hypothesized that weight z-score at 1 year would be affected by social determinants of health measured by the U.S. Centers for Disease Control Social Vulnerability Index (SVI). MATERIALS AND METHODS: We conducted a single-center retrospective review of patients who underwent gastroschisis repair (n = 97) from 2007 to 2018. Growth z-scores collected through 5 years of age and long-term clinical outcomes were compared based on the closure method and the type of gastroschisis (simple vs. complicated). Multiple regression analysis was performed to identify the impact of SVI themes and other covariates on weight for age z-score at 1 year. RESULTS: In total, 46 patients underwent sutureless repair and 51 underwent sutured repair with median follow-up duration of 2.5 and 1.9 years, respectively. Weight and length z-scores decreased after birth but normalized within the first year of life. Growth and long-term clinical outcomes were similar regardless of the closure method, while patients with complicated gastroschisis had higher rates of hospitalizations, small bowel obstructions, and additional abdominal surgeries. Using multiple regression, both low discharge weight and high SVI in the "minority status and language" theme were associated with lower weight for age z-scores at 1 year (p = 0.003 and p = 0.03). CONCLUSION: Sutureless and sutured gastroschisis repairs result in similar growth and long-term outcomes. Patients living in areas with greater social vulnerability may be at increased risk of poor weight gain. Patients should be followed at least through their first year to ensure appropriate growth.

Low Cost Gastroschisis Silo for Sub-Saharan Africa: Testing in a Porcine Model.

BACKGROUND: Gastroschisis mortality in sub-Saharan Africa (SSA) remains high at 59-100%. Silo inaccessibility contributes to this disparity. Standard of care (SOC) silos cost $240, while median monthly incomes in SSA are < $200. Our multidisciplinary American and Ugandan team designed and bench-tested a low-cost (LC) silo that costs < $2 and is constructed from locally available materials. Here we describe in vivo LC silo testing. METHODS: A piglet gastroschisis model was achieved by eviscerating intestines through a midline incision. Eight piglets were randomized to LC or SOC silos. Bowel was placed into the LC or SOC silo, maintained for 1-h, and reduced. Procedure times for placement, intestinal reduction, and silo removal were recorded. Tissue injury of the abdominal wall and intestine was assessed. Bacterial and fungal growth on silos was also compared. RESULTS: There were no gross injuries to abdominal wall or intestine in either group or difference in minor bleeding. Times for silo application, bowel reduction, and silo removal between groups were not statistically or clinically different, indicating similar ease of use. Microbiologic analysis revealed growth on all samples, but density was below the standard peritoneal inoculum of 105 CFU/g for both silos. There was no significant difference in bacterial or fungal growth between LC and SOC silos. CONCLUSION: LC silos designed for manufacturing and clinical use in SSA demonstrated similar ease of use, absence of tissue injury, and acceptable microbiology profile, similar to SOC silos. The findings will allow our team to proceed with a pilot study in Uganda.

Gastroschisis for the Gastroenterologist: Updates on Epidemiology, Management, and Outcomes.

Gastroschisis is a common congenital abdominal wall defect, likely influenced by environmental factors in utero, with increasing prevalence in the United States. Early detection of gastroschisis in utero has become the standard with improved prenatal care and screening. There are multiple surgical management techniques, though sutureless closure is being used more frequently. Postoperative feeding difficulty is common and requires vigilance for complications, such as necrotizing enterocolitis. Infants with simple gastroschisis are expected to have eventual catch-up growth and normal development, while those with complex gastroschisis have higher morbidity and mortality. Management requires collaboration amongst several perinatal disciplines, including obstetrics, maternal fetal medicine, neonatology, pediatric surgery, and pediatric gastroenterology for optimal care and long-term outcomes.

Prevalence, management, and outcome of cryptorchidism associated with gastroschisis: A systematic review and meta-analysis.

PURPOSE: Cryptorchidism associated with gastroschisis has been poorly investigated. We aimed to assess the prevalence of this association, and to address the management and outcome of cryptorchidism in this context. MATERIALS AND METHODS: In this systematic review, we searched electronic databases (PubMed, Web of Science, and Google Scholar), without language restrictions from inception to March 31, 2021, for studies on cryptorchidism and gastroschisis co-occurrence. Random effects meta-analysis was used to calculate pooled prevalence estimates of cryptorchidism in gastroschisis and spontaneous testicular descent in this population. RESULTS: Twenty-five studies were included for the systematic review. All were retrospective case reports or series for a total of 175 patients. Pooled prevalence estimate for cryptorchidism in gastroschisis was 19% (95% CI 13-26). Complete data sets for management and outcome analysis were available in 94 patients, involving 120 undescended testes [63 (52.5%) nonpalpable, 34 (28.3%) prolapsed outside the abdominal wall defect, and 23 (19.2%) palpable]. Fifty-five descended spontaneously, with a pooled prevalence estimate of 50% (95% CI 31-69). Twelve testes/remnants were primarily removed or absent, while 49 testes underwent orchiopexy (success rate, 63%). Excluding 4 testes still awaiting orchiopexy, 30 of the remaining 116 (25.8%) testes had a dismal outcome, including testicular loss (19), hypoplasia (8) or recurrent cryptorchidism (3). CONCLUSION: Cryptorchidism in gastroschisis appears to occur more frequently than in the normal population. The overall mediocre testicular outcome seems to reflect the most unfavorable presentation of cryptorchidism in gastroschisis, which is represented by originally intrabdominal or prolapsed testis in the majority of cases. LEVEL OF EVIDENCE: IV.

The role of feeding advancement strategy on length of stay and hospital costs in newborns with gastroschisis.

BACKGROUND: Infants with gastroschisis require prolonged hospitalization for surgical repair and gradual advancement of feeds. The present study explores the effect of a change in a protocolized enteral feeding regimen with length of hospital stay (LOS) and total costs in newborns with gastroschisis. METHODS: A retrospective review was performed in neonates with uncomplicated gastroschisis at a free-standing pediatric institution from 2012 to 2020. The effect of two different enteral feed advancement protocols on clinical outcomes and hospital costs was analyzed. RESULTS: Seventy-four patients were identified, of which 50 (68%) underwent 10 ml/kg/day feeding advancements, and 24 (32%) underwent 20 ml/kg/day feeding advancements. Compared to neonates who underwent 10 ml/kg/day enteral advancements, neonates receiving 20 ml/kg/day advancements reached goal feeds faster (14 vs 20 days, p<0.001), were younger at goal feeds (26 vs 34 days, p = 0.001), required fewer days of parenteral nutrition (22 vs 29 days, p = 0.001), and had shorter LOS (30 vs 36 days, p = 0.001). On multivariable analysis, total costs decreased by 9.77% in the 20 ml/kg/day advancement cohort (p = 0.071). CONCLUSION: In neonates with uncomplicated gastroschisis who underwent primary repair, a nutritional protocol that incorporated 20 ml/kg/day feeding advancements was safe and resulted in faster attainment of goal feeds and shorter LOS. LEVEL OF EVIDENCE: II/III.

Individualized growth assessment in pregnancies complicated by fetal gastroschisis.

OBJECTIVE: Prenatal ultrasound (US) has been shown to overestimate the incidence of suspected fetal growth restriction (FGR) in gastroschisis cases. This is largely because of altered sonographic abdominal circumference (AC) measurements when comparing gastroschisis cases with population nomograms. Individualized Growth Assessment (IGA) evaluates fetal growth using serial US measurements that allow consideration of the growth potential for a given case. Our goal was to assess the utility of IGA for distinguishing normal and pathological fetal growth in gastroschisis cases. STUDY DESIGN: Pregnancies with prenatally diagnosed fetal gastroschisis were managed and delivered at a single academic medical center. US fetal biometry including head circumference (HC), abdominal circumference (AC), and femur diaphysis length (FDL), and neonatal measurements including birthweight and HC were collected and analyzed for 32 consecutive fetal gastroschisis cases with at least two 2nd and two 3rd trimester measurements. Second trimester growth velocities were compared to a group of 118 non-anomalous fetuses with normal neonatal growth outcomes. Gastroschisis cases were classified into groups based on fetal growth pathology score (FGPS9) patterns. Agreement between IGA (FGPS9) and serial conventional estimated fetal weight (EFW) measurements for determining growth pathology was evaluated. Neonatal size outcomes were compared between conventional birthweight classifications for determining small for gestational age (SGA) and IGA Growth Potential Realization Index (GPRI) for weight and head circumference measurements. RESULTS: Fetal growth pathology score (FGPS9) measurements identified three in-utero growth patterns: no growth pathology, growth restriction and recovery, and progressive growth restriction. In the no growth pathology group (n = 19), there was 84% agreement between IGA and conventional methods in determining pathological growth in both the 3rd trimester and at birth. In the growth restriction and recovery group (n = 7), there was 71% agreement both in the 3rd trimester and at birth between IGA and conventional methods. In the progressive growth restriction group (n = 5), there was 100% agreement in the 3rd trimester and 60% agreement at birth between IGA and conventional methods. CONCLUSION: We present the first study using IGA to evaluate normal and pathological fetal growth in prenatally diagnosed gastroschisis cases. IGA was able to delineate two 3rd trimester growth pathology patterns - one with persistent growth restriction and another with in-utero growth recovery. Further validation of these initial findings with larger cohorts is warranted.

Risk Factors for Inpatient Mortality in Patients Born with Gastroschisis in the United States.

OBJECTIVE: This study aimed to characterize risk factors for inpatient mortality in patients born with gastroschisis in a contemporary cohort. STUDY DESIGN: This was a retrospective cohort study of infants born with gastroschisis using the Kids' Inpatient Database 2016. Simple descriptive statistics were used to characterize the patients by demographics, and illness severity was estimated using the All-Patient Refined Diagnosis-Related Groups classification. Variables associated with an increased risk of mortality on univariate analysis were incorporated into a multivariable logistic regression model to generate adjusted odds ratios (aORs) for mortality. RESULTS: An estimated 1,990 patient with gastroschisis were born in 2016, with a 3.7% mortality rate during the initial hospitalization. Multivariable logistic regression demonstrated the following variables to be associated with an increased risk of inpatient mortality: black or Asian race compared with white (aOR: 2.6, 95% confidence interval [CI]: 1.1-6.1, p = 0.03 and aOR: 4.1, 95% CI: 1.3-13.3, p = 0.02, respectively), whereas private health insurance compared with government (aOR: 0.2; 95% CI: 0.2-0.8; p = 0.007) and exurban domicile compared with urban (aOR: 0.5; 95% CI: 0.2-0.9; p = 0.04) appeared to be associated with a decreased risk of inpatient mortality. CONCLUSION: Inpatient mortality for neonates with gastroschisis is relatively low. Even after correcting for illness severity, race, health insurance status, and domicile appear to play a role in mortality disparities. Opportunities may exist to further decrease mortality in at-risk populations.

Multidisciplinary Development of a Low-Cost Gastroschisis Silo for Use in Sub-Saharan Africa.

BACKGROUND: Gastroschisis silos are often unavailable in sub-Saharan Africa (SSA), contributing to high mortality. We describe a collaboration between engineers and surgeons in the United States and Uganda to develop a silo from locally available materials. METHODS: Design criteria included the following: < $5 cost, 5 ± 0.25 cm opening diameter, deformability of the opening construct, ≥ 500 mL volume, ≥ 30 N tensile strength, no statistical difference in the leakage rate between the low-cost silo and preformed silo, ease of manufacturing, and reusability. Pugh scoring matrices were used to assess designs. Materials considered included the following: urine collection bags, intravenous bags, or zipper storage bags for the silo and female condom rings or O-rings for the silo opening construct. Silos were assembled with clothing irons and sewn with thread. Colleagues in Uganda, Malawi, Tanzania, and Kenya investigated material cost and availability. RESULTS: Urine collection bags and female condom rings were chosen as the most accessible materials. Silos were estimated to cost < $1 in SSA. Silos yielded a diameter of 5.01 ± 0.11 cm and a volume of 675 ± 7 mL. The iron + sewn seal, sewn seal, and ironed seal on the silos yielded tensile strengths of 31.1 ± 5.3 N, 30.1 ± 2.9 N, and 14.7 ± 2.4 N, respectively, compared with the seal of the current standard-of-care silo of 41.8 ± 6.1 N. The low-cost silos had comparable leakage rates along the opening and along the seal with the spring-loaded preformed silo. The silos were easily constructed by biomedical engineering students within 15 min. All silos were able to be sterilized by submersion. CONCLUSIONS: A low-cost gastroschisis silo was constructed from materials locally available in SSA. Further in vivo and clinical studies are needed to determine if mortality can be improved with this design.

Variation in hospital costs for gastroschisis closure techniques.

BACKGROUND: In newborns with gastroschisis, both primary repair and delayed fascial closure with initial silo placement are considered safe with similar outcomes although cost differences have not been explored. METHODS: A retrospective review was performed of newborns admitted with gastroschisis at a single center from 2011 to 2016. Demographic, clinical, and cost data during the initial hospitalization were collected. Differences between procedure costs and clinical endpoints were analyzed using multivariable linear regression adjusting for prematurity, complicated gastroschisis, and performance of additional operations. RESULTS: 80 patients with gastroschisis met inclusion criteria. Rates of primary fascial, primary umbilical cord closure, and delayed closure were 14%, 65%, and 21%, respectively. Delayed closure was associated with an increase in total hospital costs by 57% compared to primary repair (p < 0.001). In addition, delayed closure was associated with increased total and NICU LOS (p < 0.05), parenteral nutrition duration (p = 0.02), ventilator days (p < 0.001), time to goal enteral feeds (p = 0.01), and all cost sub-categories except ward room costs (p < 0.01). CONCLUSION: Delayed fascial closure was associated with significantly greater hospital costs during the index admission.

Major abdominal wall defects in the low- and middle-income setting: current status and priorities.

Major congenital abdominal wall defects (gastroschisis and omphalocele) may account for up to 21% of emergency neonatal interventions in low- and middle-income countries. In many low- and middle-income countries, the reported mortality of these malformations is 30-100%, while in high-income countries, mortality in infants with major abdominal wall reaches less than 5%. This review highlights the challenges faced in the management of newborns with major congenital abdominal wall defects in the resource-limited setting. Current high-income country best practice is assessed and opportunities for appropriate priority setting and collaborations to improve outcomes are discussed.

Lifestyle and sociodemographic risk factors for gastroschisis: a systematic review and meta-analysis.

BACKGROUND: Gastroschisis is strongly associated with young maternal age. This association suggests the need for further investigations on non-genetic risk factors. Identifying these risk factors is a public health priority in order to develop prevention strategies aimed at reducing the prevalence and health consequences in offspring. OBJECTIVE: To systematically assess and quantitatively synthesise the available epidemiological studies to evaluate the association between non-genetic risk factors and gastroschisis. METHODS: Literature from PubMed, EMBASE and Scopus was searched for the period 1990-2018. Epidemiological studies reporting risk estimates between lifestyle and sociodemographic risk factors and gastroschisis were included. Two pairs of reviewers independently extracted information on study characteristics following Preferred Reporting Items for Systematic Reviews and Meta-Analyses and MOOSE (Meta-analysis Of Oservational Studies in Epidemiology) guidelines. Relative risk (RR) estimates were calculated across the studies and meta-analysis was performed using random-effects model. RESULTS: We identified 58 studies. Meta-analyses were conducted on 29 studies. Maternal smoking (RR 1.56, 95% CI 1.40 to 1.74), illicit drug use (RR 2.14, 95% CI 1.48 to 3.07) and alcohol consumption (RR 1.40, 95% CI 1.13 to 1.70) were associated with an increased risk of gastroschisis. A decreased risk among black mothers compared with non-Hispanic white mothers (RR 0.49, 95% CI 0.38 to 0.63) was found. For Hispanic mothers no association was observed. CONCLUSIONS: Exposure to smoking, illicit drugs and alcohol during pregnancy is associated with an increased risk of gastroschisis. A significantly decreased risk for black mothers was observed. Further epidemiological studies to assess the potential role of other environmental factors are strongly recommended. PROSPERO REGISTRATION NUMBER: CRD42018104284.