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

doi:10.1016/j.jpedsurg.2008.10.109

Journal of Pediatric Surgery

Volume 44, Issue 8, August 2009, Pages 1546-1551

https://doi.org/10.1016/j.jpedsurg.2008.10.109 Get rights and content

Abstract

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.

Section snippets

Population

The population for this study included infants who were enrolled in the NBDPS with an expected date of delivery between October 1, 1997, and December 31, 2003. The NBPDS is an ongoing multisite case-control study incorporating data collected from 10 population-based state birth defects surveillance systems (Arkansas, California, Georgia, Iowa, Massachusetts, New York, New Jersey, North Carolina, Texas, and Vermont). Approximately 65% of eligible gastroschisis cases, 68% of eligible omphalocele

Results

A total of 485 cases of gastroschisis, 168 cases of omphalocele, and 4967 controls were included. Of those, 446 (92%) cases of gastroschisis and 105 (62.5%) cases of omphalocele had no other major structural birth defect. Table 1 presents demographic characteristics of cases and controls. More than 31% of women with pregnancies affected by gastroschisis were Hispanic, 8% were black, and 53% were white. Nearly 34% of mothers of infants with gastroschisis had household annual incomes of less than

Discussion

The current study investigated associations between maternal exposures and demographic factors in both gastroschisis and omphalocele within a large, population-based, case-control study, and found large differences in the demographic profiles of the 2 defects, while finding some similarities in their exposure profiles. This study increases our understanding of the epidemiological influences of gastroschisis and omphalocele by lending support to many previously reported risk factors while

Conclusion

Gastroschisis and omphalocele have an almost entirely discordant profile of demographic and exposure variables. Two strong vasoconstrictors, pseudoephedrine and cocaine, were not found to be significantly associated with gastroschisis despite previous reports of an association [2], [8], [9], [10], [12]. Neither did we find significant associations between gastroschisis and other often reported exposures including aspirin [6], [9], [10], acetaminophen [8], [10], and marijuana [5], [7], [26].

References (37)

JonesK.L.
Developmental pathogenesis of defects associated with prenatal cocaine exposure: fetal vascular disruption
Clin Perinatol
(1991)
HwangP.J. et al.
Omphalocele and gastroschisis: an 18-year review study
Genet Med
(2004)
YazbeckS. et al.
Omphalocele: a 25-year experience
J Pediatr Surg
(1986)
ReidK.P. et al.
The epidemiologic incidence of congenital gastroschisis in Western Australia
Am J Obstet Gynecol
(2003)
SalihuH.M. et al.
Parity effect on preterm birth and growth outcomes among infants with isolated omphalocele
Eur J Obstet Gynecol Reprod Biol
(2006)
CanfieldM.A. et al.
National estimates and race/ethnic-specific variation of selected birth defects in the United States, 1999-2001
Birth Defects Res A Clin Mol Teratol
(2006)
TorfsC.P. et al.
A population-based study of gastroschisis: demographic, pregnancy, and lifestyle risk factors
Teratology
(1994)
GoldbaumG. et al.
Risk factors for gastroschisis
Teratology
(1990)
HaddowJ.E. et al.
Young maternal age and smoking during pregnancy as risk factors for gastroschisis
Teratology
(1993)
LamP.K. et al.
Interaction between maternal smoking and malnutrition in infant risk of gastroschisis
Birth Defects Res A Clin Mol Teratol
(2006)

Martinez-FriasM.L. et al.

Prenatal exposure to salicylates and gastroschisis: a case-control study

Teratology

(1997)

WerlerM.M. et al.

Association of vasoconstrictive exposures with risks of gastroschisis and small intestinal atresia

Epidemiology

(2003)

WerlerM.M. et al.

First trimester maternal medication use in relation to gastroschisis

Teratology

(1992)

TorfsC.P. et al.

Maternal medications and environmental exposures as risk factors for gastroschisis

Teratology

(1996)

WerlerM.M. et al.

Maternal medication use and risks of gastroschisis and small intestinal atresia

Am J Epidemiol

(2002)

MorrisonJ.J. et al.

Recreational drugs and fetal gastroschisis: maternal hair analysis in the peri-conceptional period and during pregnancy

BJOG

(2005)

CalzolariE. et al.

Omphalocele and gastroschisis: a collaborative study of five Italian congenital malformation registries

Teratology

(1993)

CalzolariE. et al.

Omphalocele and gastroschisis in Europe: a survey of 3 million births 1980-1990. EUROCAT Working Group

Am J Med Genet

(1995)

Cited by (79)

The association between prenatal cannabis use and congenital birth defects in offspring: A cumulative meta-analysis
2024, Neurotoxicology and Teratology
To examine the association between prenatal cannabis use and structural birth defects in exposed offspring.
In line with the preregistered protocol (PROSPERO: CRD42022368623), we systematically searched PubMed/Medline, CINHAL, EMBASE, Web of Science, ProQuest, Psych-Info, and Google Scholar for published articles until 25 January 2024. The methodological quality of the included studies was appraised by the Newcastle-Ottawa Quality Assessment Scale (NOS). A meta-analysis was carried out to report the pooled effect estimates from the included studies. We further performed subgroup, leave-one-out sensitivity, and meta-regression analyses, which increased the robustness of our findings.
In this cumulative meta-analysis, thirty-six observational studies, consisting of 18 case-control and 18 cohort studies, with 230, 816 cases of birth defects and 18,049,013 controls (healthy babies) were included in the final analysis. We found that offspring exposed to maternal prenatal cannabis are at greater risks of a wide range of structural birth defects: cardiovascular/heart [OR = 2.35: 95 % CI 1.63 – 3.39], gastrointestinal [OR = 2.42: 95 % CI 1.61 – 3.64], central nervous system [OR = 2.87: 95 % CI 1.51 – 5.46], genitourinary [OR = 2.39: 95 % CI 1.11 – 5.17], and any (unclassified) birth defects [OR = 1.25: 95 % CI 1.12 – 1.41].
The findings from the current study suggest that maternal prenatal cannabis exposure is associated with a higher risk of different forms of structural birth defects in offspring. The findings underscore the significance of implementing preventive strategies, including enhanced preconception counselling, to address cannabis use during pregnancy and mitigate the risk of birth defects in offspring.
Associations between maternal periconceptional alcohol consumption and risk of omphalocele among offspring, National Birth Defects Prevention Study, 1997–2011
2024, Preventive Medicine
Previous studies of alcohol consumption during pregnancy and omphalocele have produced mixed results. We updated an earlier analysis of National Birth Defects Prevention Study (NBDPS) data, adding six years of participants, to examine associations between maternal alcohol consumption and omphalocele.
NBDPS was a multi-site, population-based case-control study in the United States. Cases were identified from birth defect surveillance programs in 10 states; controls were liveborn infants without a birth defect randomly selected from the same catchment areas. Mothers self-reported alcohol consumption during the periconceptional period (one month before through the third gestational month) via telephone interview. Our study included mothers of 410 omphalocele cases and 11,219 controls with estimated dates of delivery (EDDs) during 1997–2011. We used logistic regression to estimate adjusted odds ratios (AORs) and 95% confidence intervals (CIs) for periconceptional alcohol consumption and omphalocele. We performed a probabilistic bias analysis to evaluate the impact of alcohol exposure misclassification on our results.
Overall, 44% of case and 38% of control mothers reported periconceptional alcohol consumption; 22% and 17%, respectively, reported binge drinking. Any maternal periconceptional alcohol consumption was associated with modestly increased odds of omphalocele (AOR 1.35, 95% CI 1.09, 1.68), as was binge drinking (AOR 1.47, 95% CI 1.08, 2.01). Our bias analysis yielded estimates further from the null.
We observed modest associations between maternal periconceptional alcohol consumption and omphalocele. Based on our bias analysis, studies of alcohol and birth defects not accounting for exposure misclassification may underestimate associations.
Childhood Educational Outcomes of Children Born with Gastroschisis
2022, Journal of Pediatrics
Citation Excerpt :
The clinical characteristics of patients with gastroschisis have been previously described in the literature.30 Consistent with previous reports, many of these patients were SGA, moderately preterm, and born to Caucasian young primiparous mothers.30,31 The reported risk of rehospitalization in patients with gastroschisis varies in the literature.32
To compare third grade literacy and mathematics test proficiency among children born with gastroschisis vs unaffected controls and identify predictors of academic proficiency among these children.
Infants born with gastroschisis (2000-2005) were identified from the Arkansas Reproductive Health Monitoring System. For each case, 2 controls were selected at random from birth certificates and matched for hospital and month of birth, sex, and race/ethnicity. Data on rehospitalization within the first 6 years and payer data were abstracted from the Arkansas Hospital Inpatient Discharge database. Surviving cases and controls were linked to the Arkansas Department of Education database containing achievement test scores. The primary outcome was proficiency, defined as performance at or above grade level, on third grade achievement tests. Cases and controls who did not attend public schools could not be linked to education records. Multivariable logistic regression models evaluated the association between study characteristics and academic proficiency.
The final study cohort included 47 cases and 63 controls. There was no statistically significant difference in the rate of literacy (68% vs 81%; P = .65) or mathematics proficiency (89% vs 87%; P = .15) between cases and controls. On multivariable analysis, a complex gastroschisis (defined as atresia, volvulus, necrosis, or perforation of the bowel) was associated with lower proficiency in literacy (aOR, 0.1; 95% CI, 0.02-0.58; P = .01). No neonatal or maternal characteristics predictive of lower proficiency in mathematics were identified.
Among children born with gastroschisis, the presence of a complex gastroschisis was associated with lower proficiency on third grade literacy achievement tests.
Gastroschisis annual incidence, mortality, and trends in extreme Southern Brazil
2022, Jornal de Pediatria
To analyze gastroschisis annual incidence, mortality rates, and trends in the Brazilian state of Rio Grande do Sul from the year 2000 to the year 2017.
Population-based study with the analysis of the temporal trend of gastroschisis annual incidence and mortality rates. Data were obtained from the Live Birth Information System and the Mortality Information System, with the analysis performed by polynomial regression modeling.
There were 2,612,532 live births, 705 hospitalizations, and 233 deaths due to gastroschisis. The annual incidence of gastroschisis was 2.69 per 10,000 live births. The annual incidence rate increased by 85% in the total period (p = 0.003), and mortality was 33% in the 2000-2017 period. Maternal age < 25 years was a risk factor for gastroschisis (p < 0.001). Children were more likely to be born weighing < 2,500 g (p < 0.001) and with a gestational age < 37 weeks (p < 0.001). The annual incidence trend was to increase, and the mortality trend was to decrease.
Similar to what has been described in several regions/countries, there was a trend showing an 85% increase in the annual incidence of gastroschisis (p = 0.003) and the mortality was 33% with a trend of decreasing (p = 0.002).
Extended spectrum penicillins reduce the risk of omphalocele: A population-based case-control study
2021, Journal of Pediatric Surgery
Citation Excerpt :
There is also limited evidence, that maternal smoking is a risk factor for omphalocele. According to previous reports, elevated risk has been associated with heavy smoking [19], and second-hand smoke exposure [20]. Paradoxically, Feldkamp et al. found no risk to be associated with active smoking, and no dose-response relationship was observed [20].
Omphalocele is a major congenital anomaly associated with significant morbidity and mortality. Regardless, the influence of maternal use of prescription drugs on the risk of omphalocele has only been addressed in a handful of studies. The aim of this study was to assess the influence of maternal risk factors and prescription drugs in early pregnancy on the risk of omphalocele.
We performed a nationwide register-based case-control study in Finland. The analysis is based on the Finnish Register of Congenital Malformations and Drugs and Pregnancy databases, both upheld by the Finnish Institute for Health and Welfare. All omphalocele cases were identified between Jan 1, 2004, and Dec 31, 2014. Five age-matched controls from the same geographical region were randomly selected for each case. The main outcome measures were maternal risk factors for omphalocele. Our analysis compared the maternal characteristics and the use of prescription drugs during the first trimester of pregnancy between case and control mothers.
Mothers of 359 omphalocele cases were compared with 1738 randomly selected age and area-matched mothers of healthy infants between 1 January 2014 and 31 December 2014. Both maternal obesity (BMI ≥30) and diabetes increased the risk for omphalocele, and their co-occurrence accumulated this risk (aOR 5.06, 95% Cl 1.19–21.4). Similarly, history of multiple miscarriages was an independent risk factor (2.51, 1.16–5.43). The oral use of extended spectrum penicillins during the first trimester of pregnancy had a significant, protective influence (0.17, 0.04–0.71). These analyses were adjusted for sex, parity, and risk factors reported above. No significant changes in risk were observed with any other medication used during the first trimester.
In conclusion, these findings may suggest that extended spectrum penicillins in the first trimester reduces the risk of omphalocle formation. Additionally, consistent with earlier studies, previous repeated miscarriages, maternal obesity, and diabetes were significant risk factors for omphalocele.
Gastro-intestinal function and quality of life are favorable in adolescent and adult gastroschisis patients
2020, Early Human Development
Studies on long-term sequelae of gastroschisis are scarce. The limited data suggest increased abdominal complaints in young children. To provide proper counseling for both parents and patients, more information on long-term outcome is needed. This study aims to evaluate long-term outcome regarding GI function, gastroesophageal reflux (GER), health-related quality of life (HRQoL) and cosmetic satisfaction.
An observational longitudinal cohort study was performed. All patients (N = 43) born between 1982 and 2008 with gastroschisis that were admitted to the University Medical Centre Utrecht, Wilhelmina Children's Hospital were invited to fill in a survey. Data of included patients were compared to validated Dutch reference standards.
Fourteen patients responded to the survey. The median follow-up was 18 years. Abdominal pain on weekly basis was present in two patients (14%) and feeding difficulties were present in one patient. Presence of a complication during gastroschisis treatment led to more GI symptoms (80% versus 22%). One patient experienced moderate complaints of regurgitation or dyspepsia. Although the overall HRQoL was lower in teenage gastroschisis patients as compared to healthy controls (73/100 versus 83/100, respectively), we found no relevant difference in overall HRQoL in the other age groups. Seven patients (50%) were satisfied with the cosmetic result of the scar.
GI function and HRQoL in gastroschisis patients seem similar to healthy controls at adolescent and adult age. Complications during gastroschisis treatment led to an increase of abdominal complaints later in life. The surgical technique had no significant effect on the cosmetic results.

View all citing articles on Scopus

^☆: This work was supported by funds from the Centers for Disease Control and Prevention (CDC), grant no. 3U50DD613236. The contents are solely the responsibility of the authors and do not necessarily represent the official views of the CDC.

^☆☆: This study was approved by the Institutional Review Board of the University of Arkansas for Medical Sciences (Little Rock, Ark), protocol no. 04812.

View full text

Original articleDemographic and environmental risk factors for gastroschisis and omphalocele in the National Birth Defects Prevention Study☆,☆☆

Abstract

Background

Methods

Results

Conclusions

Section snippets

Population

Results

Discussion

Conclusion

Clin Perinatol

Genet Med

J Pediatr Surg

Am J Obstet Gynecol

Eur J Obstet Gynecol Reprod Biol

National estimates and race/ethnic-specific variation of selected birth defects in the United States, 1999-2001

Birth Defects Res A Clin Mol Teratol

A population-based study of gastroschisis: demographic, pregnancy, and lifestyle risk factors

Teratology

Risk factors for gastroschisis

Teratology

Young maternal age and smoking during pregnancy as risk factors for gastroschisis

Teratology

Interaction between maternal smoking and malnutrition in infant risk of gastroschisis

Birth Defects Res A Clin Mol Teratol

Prenatal exposure to salicylates and gastroschisis: a case-control study

Teratology

Association of vasoconstrictive exposures with risks of gastroschisis and small intestinal atresia

Epidemiology

First trimester maternal medication use in relation to gastroschisis

Teratology

Maternal medications and environmental exposures as risk factors for gastroschisis

Teratology

Maternal medication use and risks of gastroschisis and small intestinal atresia

Am J Epidemiol

Recreational drugs and fetal gastroschisis: maternal hair analysis in the peri-conceptional period and during pregnancy

BJOG

Omphalocele and gastroschisis: a collaborative study of five Italian congenital malformation registries

Teratology

Omphalocele and gastroschisis in Europe: a survey of 3 million births 1980-1990. EUROCAT Working Group

Am J Med Genet

Original article
Demographic and environmental risk factors for gastroschisis and omphalocele in the National Birth Defects Prevention Study☆,☆☆