Mexican-American Women's Lifelong Residence in the United States Is Associated with an Increased Risk of Gastroschisis: A Population-Based Study.

OBJECTIVE: To determine whether nativity is associated with abdominal wall defects among births to Mexican-American women. STUDY DESIGN: Using a cross-sectional, population-based design, stratified and multivariable logistic regression analyses were performed on the 2014-2017 National Center for Health Statistics live-birth cohort dataset of infants of US-born (n = 1 398 719) and foreign-born (n = 1 221 411) Mexican-American women. RESULTS: The incidence of gastroschisis was greater among births to US-born compared with Mexico-born Mexican-American women: 36.7/100 000 vs 15.5/100 000, RR = 2.4 (2.0, 2.9). US-born (compared with Mexico-born) Mexican-American mothers had a greater percentage of teens and cigarette smokers, P < .0001. In both subgroups, gastroschisis rates were greatest among teens and decreased with advancing maternal age. Adjusting for maternal age, parity, education, cigarette smoking, pre-pregnancy body mass index, prenatal care usage, and infant sex), OR of gastroschisis for US-born (compared with Mexico-born) Mexican-American women was 1.7 (95% CI 1.4-2.0). The population attributable risk of maternal birth in the US for gastroschisis equaled 43%. The incidence of omphalocele did not vary by maternal nativity. CONCLUSIONS: Mexican-American women's birth in the US vs Mexico is an independent risk factor for gastroschisis but not omphalocele. Moreover, a substantial proportion of gastroschisis lesions among Mexican-American infants is attributable to factors closely related to their mother's nativity.

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.

Prevalence rates study of selected isolated non-Mendelian congenital anomalies in the Hutterite population of Alberta, 1980-2016.

A study of the prevalence rates for selected isolated non-Mendelian congenital anomalies in the Hutterite Brethren of Alberta, Canada was undertaken to further examine longitudinal data in this isolated community that was last reported in 1985 (Lowry et al., 1985), although there are numerous publications on recessive disorders (Boycott et al., 2008; Triggs-Raine et al., 2016). Cases were ascertained from the Alberta Congenital Anomaly Surveillance System for the years 1997-2016. Since our initial results showed some surprising findings in the Hutterite Brethren, such as zero cases of spina bifida, cleft lip and palate, gastroschisis, and omphalocele, and a significant excess of cases with hypospadias, we extended the study to prior years (1980-1996) for selected anomalies. For the extended study period (1980-2016), there was a significant increased prevalence of hypospadias, tetralogy of Fallot and tricuspid atresia in the Hutterite population, and although not statistically significant, zero cases of cleft lip with cleft palate, gastroschisis and omphalocele were confirmed. Further research is needed to determine the precise effects of rural environmental exposures, lifestyle factors, and genetic associations for selected multifactorial congenital anomalies.

Gastroschisis Trends and Ecologic Link to Opioid Prescription Rates - United States, 2006-2015.

Prevalence of gastroschisis, a serious birth defect of the abdominal wall resulting in some of the abdominal contents extending outside the body at birth, has been increasing worldwide (1,2). Gastroschisis requires surgical repair after birth and is associated with digestive and feeding complications during infancy, which can affect development. Recent data from 14 U.S. states indicated an increasing prevalence of gastroschisis from 1995 to 2012 (1). Young maternal age has been strongly associated with gastroschisis, but research suggests that risk factors such as smoking, genitourinary infections, and prescription opioid use also might be associated (3-5). Data from 20 population-based state surveillance programs were pooled and analyzed to assess age-specific gastroschisis prevalence during two 5-year periods, 2006-2010 and 2011-2015, and an ecologic approach was used to compare annual gastroschisis prevalence by annual opioid prescription rate categories. Gastroschisis prevalence increased only slightly (10%) from 2006-2010 to 2011-2015 (prevalence ratio = 1.1, 95% confidence interval [CI] = 1.0-1.1), with the highest prevalence among mothers aged <20 years. During 2006-2015, the prevalence of gastroschisis was 1.6 times higher in counties with high opioid prescription rates (5.1 per 10,000 live births; CI = 4.9-5.3) and 1.4 times higher where opioid prescription rates were medium (4.6 per 10,000 live births; CI = 4.4-4.8) compared with areas with low prescription rates (3.2 per 10,000 live births; CI = 3.1-3.4). Public health research is needed to understand factors contributing to the association between young maternal age and gastroschisis and assess the effect of prescription opioid use during pregnancy on this pregnancy outcome.

Possible etiologies of increased incidence of gastroschisis.

PURPOSE: Gastroschisis incidence has increased over the past decade nationally and in Hawaii. Pesticides have been implicated as potential causative factors for gastroschisis, and use of restricted use pesticides (RUPs) is widespread in Hawaii. This study was conducted to characterize gastroschisis cases in Hawaii and determine whether RUP application correlates with gastroschisis incidence. METHODS: Gastroschisis patients treated in Hawaii between September, 2008 and August, 2015 were mapped by zip code along with RUP use. Spatial analysis software was used to identify patients' homes located within the pesticide application zone and agricultural land use areas. RESULTS: 71 gastroschisis cases were identified. 2.8% of patients were from Kauai, 64.8% from Oahu, 16.9% from Hawaii, 14.1% from Maui, and 1.4% from Molokai. RUPs have been used on all of these islands. 78.9% of patients lived in zip codes overlapping agricultural land use areas. 85.9% of patients shared zip codes with RUP-use areas. CONCLUSION: The majority of gastroschisis patients were from RUP-use areas, supporting the idea that pesticides may contribute to the development of gastroschisis, although limited data on specific releases make it difficult to apply these findings. As more RUP-use data become available to the public, these important research questions can be investigated further.

Increasing Prevalence of Gastroschisis--14 States, 1995-2012.

Gastroschisis is a serious congenital defect in which the intestines protrude through an opening in the abdominal wall. Gastroschisis requires surgical repair soon after birth and is associated with an increased risk for medical complications and mortality during infancy. Reports from multiple surveillance systems worldwide have documented increasing prevalence of gastroschisis since the 1980s, particularly among younger mothers; however, since publication of a multistate U.S. report that included data through 2005, it is not known whether prevalence has continued to increase. Data on gastroschisis from 14 population-based state surveillance programs were pooled and analyzed to assess the average annual percent change (AAPC) in prevalence and to compare the prevalence during 2006-2012 with that during 1995-2005, stratified by maternal age and race/ethnicity. The pooled data included approximately 29% of U.S. births for the period 1995-2012. During 1995-2012, gastroschisis prevalence increased in every category of maternal age and race/ethnicity, and the AAPC ranged from 3.1% in non-Hispanic white (white) mothers aged <20 years to 7.9% in non-Hispanic black (black) mothers aged <20 years. These corresponded to overall percentage increases during 1995-2012 that ranged from 68% in white mothers aged <20 years to 263% in black mothers aged <20 years. Gastroschisis prevalence increased 30% between the two periods, from 3.6 per 10,000 births during 1995-2005 to 4.9 per 10,000 births during 2006-2012 (prevalence ratio = 1.3, 95% confidence interval [CI]: 1.3-1.4), with the largest increase among black mothers aged <20 years (prevalence ratio = 2.0, 95% CI: 1.6-2.5). Public health research is urgently needed to identify factors contributing to this increase.

Early pregnancy agricultural pesticide exposures and risk of gastroschisis among offspring in the San Joaquin Valley of California.

BACKGROUND: Prevalence of gastroschisis has inexplicably been increasing over the past few decades. Our intent was to explore whether early gestational exposures to pesticides were associated with risk of gastroschisis. METHODS: We used population-based data, accompanied by detailed information from maternal interviews as well as information on residential proximity to a large number of commercial pesticide applications during early pregnancy. The study population derived from the San Joaquin Valley of California (). Cases were 156 infants/fetuses with gastroschisis and controls were 785 infants without birth defects. RESULTS: Among 22 chemical pesticide groups analyzed, none had an elevated odds ratio with an associated confidence interval that excluded 1.0, although exposure to the triazine group showed borderline significance. Among 36 specific pesticide chemicals analyzed, only exposure to petroleum distillates was associated with an elevated risk, odds ratio = 2.5 (1.1-5.6). In general, a substantially different inference was not derived when analyses were stratified by maternal age or when risk estimation included adjustment for race/ethnicity, body mass index, folic acid supplement use, and smoking. CONCLUSION: Our study rigorously adds to the scant literature on this topic. Our a priori expectation was that we would observe certain pesticide compounds to be particularly associated with young age owing to the disproportionate risk observed for young women to have offspring with gastroschisis. We did not observe an exposure profile unique to young women.

Ethnic variation of gastroschisis and omphalocele in the United States of America.

OBJECTIVE: Gastroschisis and omphalocele are the most common fetal abdominal wall defects (AWDs). Ethnic factors have been implicated in the incidence data from some states in the United States. Our aim was to examine ethnic variation in the prevalence of gastroschisis and omphalocele in the US live birth population between 2006 and 2010. METHODS: AWDs were identified through gastroschisis and omphalocele checkboxes from publicly available US Natality data (2006 to 2010). Ethnicity was evaluated by individual category using National Center for Health Statistics (NCHS) definitions. Adjusted multinomial logistic regression (SPSS v.19) was used to generate odds ratios (OR) in order to quantify the disparities. RESULTS: In the US, 7867 live births were identified with AWD. All ethnic groups showed a significantly higher OR when compared with women of East/South Asian descent, which experienced the lowest prevalence. Women of indigenous ethnicity had the highest individual OR while their adjusted OR remained greater than 4.0. CONCLUSIONS: Women of indigenous origin from North America and the Pacific had the highest rates of AWD. Within this group, women of Hawaiian descent had the highest point estimate of AWD when compared with other ethnic groups, though not significant.

Maternal reporting of prenatal ultrasounds among women in the National Birth Defects Prevention Study.

BACKGROUND: Increased availability and usage of ultrasound screening have led to improved identification of fetal structural abnormalities prenatally. Few population-based studies have been published on prenatal detection for structural birth defects in the United States. The aim of this study is to determine the frequency of maternal reporting of abnormal prenatal ultrasounds for selected birth defects and to investigate associated maternal characteristics. METHODS: Participants included 4013 mothers enrolled in the National Birth Defects Prevention Study who carried a fetus with at least one of 14 structural birth defects between 1997 and 2004. Frequencies of abnormal prenatal ultrasounds were based on maternal report and computed for isolated and multiple defects. Associations between maternal characteristics and abnormal prenatal ultrasounds were assessed using logistic regression. RESULTS: Overall, 46% of participants reported an abnormal ultrasound. Infants with omphalocele, anencephaly, gastroschisis, and renal agenesis were more likely to have abnormal prenatal ultrasounds than those with cleft and limb abnormalities. Hispanic women were less likely to report abnormal prenatal ultrasounds of birth defects than Caucasians, as were women who had a body mass index ≥ 30 kg/m(2) compared with those with a normal body mass index. CONCLUSION: Of the 14 selected birth defects in this study, less than half were reported by mothers of affected infants to have had an abnormal ultrasound during pregnancy. The frequency of reporting abnormal prenatal ultrasounds varies by type of defect, maternal race/ethnicity, and maternal body mass index status.

Prevalence and trends of selected congenital malformations in New York State, 1983 to 2007.

BACKGROUND: Major birth defects result in high infant mortality and morbidity. It is important to evaluate the burden of birth defects and trends for future intervention and public health improvement. Using the New York State (NYS) Congenital Malformations Registry data, we examined the prevalence and trends of birth defects among children in NYS during 25 years of surveillance. METHODS: Children who had any of the 21 selected birth defects and were born to NYS residents between 1983 and 2007 were selected. The prevalence of each defect was characterized by demographic and birth factors, and the prevalence ratio was calculated. Live births of NYS residents for the same birth year period were used as the denominators for calculating the prevalence. The prevalence trends of birth defects were analyzed by maternal age and race/ethnicity. RESULTS: Compared with non-Hispanic whites, we detected 33%, 21%, and 37% higher prevalence of encephalocele, lower limb deficiencies and omphalocele among non-Hispanic blacks, respectively, and 22% higher prevalence of gastroschisis among Hispanics. Increasing trends of gastroschisis and Down syndrome among non-Hispanic blacks and decreasing trends of spina bifida and limb deficiencies were observed in NYS. CONCLUSION: The findings from this study suggest the existence of racial disparities among children with selected birth defects in NYS. The increasing trends of gastroschisis and Down syndrome observed in NYS are consistent with nationwide trends.

Rising prevalence of gastroschisis in Washington State.

The aim of this study was to assess gastroschisis prevalence in Washington (WA) State in relation to putative risk factors. Gastroschisis prevalence was calculated from the WA State birth cohort during 1987-2006 using an administrative database with birth certificate data linked with hospital discharge records and the ICD-9 procedure code 54.71, which specifies gastroschisis repair. Poisson regression analysis was used to evaluate time trends while adjusting for risk factors. Birth year was included as a linear term. Maternal age, smoking, race, residence in urban versus rural area, geographic region (eastern versus western Washington), paternal age, and infant gender were included as categorical factors. Prevalence ratios were adjusted for birth year and all of the preceding factors. Two hundred and eighty-two infants with gastroschisis were identified. In the adjusted analysis, the prevalence ratio for gastroschisis was 1.1 per year (95% CI 1.08-1.13), indicating an average 10% increase per birth year. Teen mothers were at a higher risk compared to mothers≥25 yr old (adjusted rate ratio [aRR] 8.02; 95% CI 5.30-12.13), as were teen fathers (aRR 2.35; 95% CI 1.48-3.74) compared to fathers≥25 years old. Maternal smoking was associated with a higher risk compared to those who were nonsmokers (aRR 1.58; 95% CI 1.19-2.09). Black mothers had a lower risk compared with white mothers. There was no association with geographic classification of mother's residence. Gastroschisis prevalence has increased in WA, particularly in teen mothers and in smokers. This is not explained by a rise in teenage pregnancies or maternal smoking. Further investigation of factors specific to teenage lifestyle is warranted.

Demographic and environmental risk factors for gastroschisis and omphalocele in the National Birth Defects Prevention Study.

BACKGROUND: Primary prevention efforts for both gastroschisis and omphalocele are limited by the lack of known risk factors. Our objective was to investigate associations between potential maternal risk factors and gastroschisis and omphalocele within a large population-based sample of participants enrolled in the National Birth Defects Prevention Study (NBDPS). METHODS: Demographic, health-related, and environmental exposure data from the NBDPS were collected from women with expected delivery dates between October 1997 and December 2003. Data were collected on 485 cases of gastroschisis, 168 cases of omphalocele, and 4967 controls. RESULTS: Women who had offspring with gastroschisis were younger (adjusted odds ratio [AOR], 0.84; 95% confidence interval [CI], 0.81-0.86) and less likely to be black (AOR, 0.54; 95% CI, 0.34-0.85) than controls. They also were more likely to have smoked (AOR, 1.51; 95% CI, 1.12-2.03), taken ibuprofen (AOR, 1.61; 95% CI, 1.23-2.10), and consumed alcohol (AOR, 1.38; 95% CI, 1.06-1.79) than controls. Women who had offspring with omphaloceles were more likely to have consumed alcohol (AOR, 1.53; 95% CI, 1.04-2.25) and be heavy smokers (AOR, 4.26; 95% CI, 1.58-11.52) than controls. CONCLUSIONS: Our results suggest a moderately increased risk of gastroschisis among women who used tobacco, alcohol, and ibuprofen during early pregnancy. A modestly elevated risk was observed for omphaloceles among women who used alcohol during the first trimester and among women who were heavy smokers.

Evidence of localized clustering of gastroschisis births in North Carolina, 1999-2004.

Examining the geographic distribution of birth defects can be useful in exploratory etiologic research. Identification of clusters of certain defects may uncover possible environmental or socio-economic risk factors and assist with the generation of hypotheses about underlying causes of these conditions. In North Carolina, the prevalence of gastroschisis, a serious abdominal wall defect, has increased over the past decade and anecdotal evidence from clinicians suggests the possibility of clustering of this condition. This study uses a spatial scan statistic to identify the location and extent of clusters of gastroschisis births in North Carolina between 1999 and 2004. Data on cases of gastroschisis were obtained from the North Carolina Birth Defect Monitoring Program (NCBDMP) and control births were chosen from all resident live births without birth defects contained in the North Carolina composite linked birth files. The clusters were controlled for five major risk factors (maternal age, race, parity, Medicaid status, maternal smoking) to ensure that the clusters were not artifacts of unequal population distribution. Results indicate a localized cluster of gastroschisis in the rural southern Piedmont of North Carolina which persists even after controlling for all major risk factors. Adjusting for these risk factors shifted the location of the cluster substantially, demonstrating the importance of adjusting for underlying population distribution. Since clusters persisted after adjusting for individual-level risk factors, environmental contaminants may explain the excess of gastroschisis cases. This study is among the first to assess spatial clustering of gastroschisis using GIS methods. This study also demonstrates the importance of controlling for covariates in spatial analysis and illustrates the usefulness of the spatial scan statistic in exploratory etiologic research.

Selected gene polymorphisms and their interaction with maternal smoking, as risk factors for gastroschisis.

BACKGROUND: Gastroschisis is a severe birth defect in which the infant is born with a portion of the intestines extruding through a small tear in the abdominal wall, usually to the right of the umbilical cord. Its etiology is unknown, but the prevailing hypothesis is that it results from a vascular accident at the time of involution of the right umbilical vein or of the development of the superior mesenteric artery. METHODS: In a case-control study of 57 cases of gastroschisis and 506 controls, we tested DNA for polymorphisms of 32 genes representing enzymes involved in angiogenesis, blood vessel integrity, inflammation, wound repair, and dermal or epidermal strength. RESULTS: In logistic regression, controlling for maternal ethnicity, and using the homozygote wild-type as referent, the following gene polymorphisms were associated with an increased risk for a gastroschisis for heterozygotes: ICAM1 gly241arg (odds ratio [OR], 1.9; 95% confidence interval [CI], 1.1 -3.4); NOS3 glu298asp (OR, 1.9; 95% CI, 1.1-3.4); NPPA 2238T > C (OR, 1.9; 95% CI, 1.0-3.4); and ADD1 gly460trp (OR, 1.5; 95% CI, 0.8-2.8). Additionally, for the NPPA and ADD1 single-nucleotide polymorphisms (SNPs), the homozygote variants had a significantly higher risk than the heterozygotes (OR, 7.5; 95% CI, 1.7-33.5 and OR, 4.9; 95% CI, 1.9-12.9, respectively). Three SNPs showed a strong interaction with maternal smoking. The risk for smokers with 1 or 2 variant alleles compared to nonsmokers with the wild-type allele were: NOS3 (OR, 5.2; 95% CI, 2.4-11.4); ICAM1 (OR, 5.2; 95% CI, 2.1-12.7); and NPPA (OR, 6.4; 95% CI, 2.8-14.6). CONCLUSIONS: These results support the hypothesis of a vascular compromise as part of a multifactorial etiology of gastroschisis involving both genes and environmental factors.

Omphalocele and gastroschisis: Black-White disparity in infant survival.

BACKGROUND: Racial/ethnic variations in the occurrence of abdominal wall defects have been previously noted but it remains poorly understood whether race/ethnicity is a determinant of survival among affected infants. METHODS: Study was conducted on cases of gastroschisis and omphalocele recorded for the years 1983-1999 at the New York Congenital Malformation Registry. Adjusted and unadjusted hazard ratios were generated from a Proportional Hazards Regression model to compare survival among affected Blacks, Hispanics and Whites. The major end point of analysis was differences in all cause mortality among infants with abdominal wall birth defects across different racial/ethnic groups. RESULTS: Among the three racial/ethnic groups, 1481 infants were diagnosed with either omphalocele (978 or 66%) or gastroschisis (503 or 34%). Overall infant mortality rate (IMR) was 182 per 1000, with 74% of the deaths occurring within the first 28 days of life. Omphalocele infants had significantly higher infant mortality (IMR = 215 per 1000) than infants with gastroschisis (IMR = 118 per 1000)[p < 0.0001]. Overall, Black infants with abdominal wall defects had lower mortality indices than Whites and Hispanics. However, when considered as separate disease entities, Black infants were twice as likely to survive as compared to Whites if they had omphalocele [Adjusted Hazard Ratio (AHR) = 0.52; 95% Confidence Interval (CI) = 0.37-0.74], and twice as likely to die as Whites if they had gastroschisis instead (AHR = 2.23; 95% CI = 1.16-4.28). For both defect subtypes, Hispanics have risks for infant mortality comparable to Whites. CONCLUSIONS: The natural history of omphalocele and gastroschisis co-varies with race. Black infants with gastroschisis have worse survival outcomes while those with omphalocele have better chances of survival than their White or Hispanic counterparts.

Rising birth prevalence of gastroschisis.

OBJECTIVE: Gastroschisis is a congenital anomaly that has been reported to be increasing in frequency. The objective of this study was to determine the birth prevalence of gastroschisis using two large databases. STUDY DESIGN: We reviewed data from a statewide database and a national database from a neonatal health care provider, abstracting cases of gastroschisis. RESULTS: In North Carolina, the birth prevalence of gastroschisis increased from 1.96 per 10,000 births in 1997 to 4.49 per 10,000 births in 2000 (p=0.0007). The overall increase was almost entirely because of the increase in infants born to mothers less than 20 years old. Among infants receiving care from the national neonatal provider, the prevalence of gastroschisis increased from 2.9 per 1000 patients in 1997 to five per 1000 patients in 2001 (p=0.044). CONCLUSION: The birth prevalence of gastroschisis is increasing in North Carolina, and this trend may be occurring nationally. The rapid change in the birth prevalence in the subset of population most at risk for gastroschisis implicates environmental or pharmacologic teratogens rather than changing population characteristics as a causal factor in the development of gastroschisis.

Omphalocele and gastroschisis in the State of New York, 1992-1999.

BACKGROUND: Variations in the temporal distribution and risk factors for omphalocele and gastroschisis have been suggested although results have not been conclusive. This study examines the trend and risk factors for both conditions among live births in New York State. METHODS: Analysis of surveillance data from the New York Congenital Malformation Registry for the years 1992-1999. RESULTS: Five hundred and ninety-five (595) infants with either omphalocele (287) or gastroschisis (308) were identified. It appeared that the prevalence of gastroschisis was rising from 1992-1999, while prevalence of omphalocele was decreasing. Cases of gastroschisis were clustered among younger mothers while the maternal age distribution among omphalocele infants was U-shaped. As compared to Whites, Black infants were more likely to present with omphalocele (OR = 1.73; 95% confidence interval = 1.28-2.33) and Hispanic infants with gastroschisis (OR = 1.50; 95% CI = 1.12-2.00). For both anomalies, residents of rural New York were significantly at higher risk than those living in urban New York. Twenty-three chromosomal aberrations were detected, all among omphalocele babies. Infant survival was substantially greater among gastroschisis (92%) as compared to omphalocele newborn (81%)[p < 0.0001]. CONCLUSIONS: Prevalence of gastroschisis has been on the rise while that of omphalocele has been declining in New York State. Geographical and racial/ethnic variations were observed, further confirming the notion of different etiologies for the two congenital anomalies.