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BackgroundGastroschisis is a birth defect where loops of bowel are protruding from the abdominal wall at birth. Previous research has suggested that gastroschisis cases can occur in clusters. The objective of this study was to identify if there were areas of elevated gastroschisis risk using data from the National Birth Defects Prevention Study (NBDPS), 1997 through 2007.MethodsWe obtained data on cases (n = 371) through population-based birth defects surveillance systems in Arkansas, California, and Utah; controls (n = 2359) were selected from the same geographic areas as cases. Mothers were interviewed on demographic information and exposures during pregnancy, including residential history. We used first trimester maternal addresses and generalized additive models to create a continuous map surface of odds ratios (OR) by smoothing over latitude and longitude. Permutation tests were used to assess whether location of maternal residence was important and identify locations with statistically significant ORs.ResultsIn Arkansas, adjusted ORs in the southwest corner were 2.0 and the global deviance was not statistically significant (p-value: 0.57). Adjusted ORs for California indicated areas of increased risk with ORs 1.3 (p-value: 0.34). In Utah, the adjusted ORs were elevated (OR: 2.4) in the south-eastern corner of the study area (p-value: 0.34).ConclusionThe results of this study, while not statistically significant, suggest there were spatial variations in gastroschisis births. We cannot rule out that these variations were due to edge effects or residual confounding.

PurposePrevious research has suggested gastroschisis, a congenital malformation, may be linked to environmental or infectious factors and cases can occur in clusters. The objective of this study was to identify geographic areas of elevated gastroschisis risk.MethodsCases of gastroschisis were identified from birth defect registries in Massachusetts and Texas. Random samples of live births were selected as controls. Generalized additive models were used to create a continuous map surface of odds ratios (ORs) by smoothing over latitude and longitude. Maternal age, race/ethnicity, education, cigarette smoking, and insurance status (MA only) were assessed for confounding. We used permutation tests to identify statistically significant areas of increased risk.ResultsAn area of increased risk was identified in North Central Massachusetts but was not significant after adjustment (P value = .07; OR = 2.0). In Texas, two statistically significant areas of increased risk were identified after adjustment (P value = .02; OR = 1.3 and 1.2). Texas had sufficient data to assess the combination of space and time, which identified an increased risk in 2003 and 2004.ConclusionsThis study suggests there were areas of elevated gastroschisis risk in Massachusetts and Texas, which cannot be explained by the risk factors we assessed. Additional exploration of underlying artifactual, environmental, infectious, or behavioral factors may further our understanding of gastroschisis.

National estimates suggest that COVID-19 vaccination coverage among pregnant persons is lower among those identifying as Hispanic or Latino (Hispanic) and non-Hispanic Black or African American. When examining COVID-19 vaccination coverage during pregnancy by race and ethnicity, however, data are typically limited to large, aggregate categories that might obscure within-group inequities. To address this, Massachusetts examined COVID-19 vaccination coverage among pregnant persons by combinations of 12 racial and 34 ethnic groupings. Among 102,275 persons with a live birth in Massachusetts during May 1, 2021–October 31, 2022, receipt of ≥1 dose of a COVID-19 vaccine before or during pregnancy was 41.6% overall and was highest among persons who identified as Asian (55.0%) and lowest among those who identified as Hispanic (26.7%). However, within all broad racial and ethnic groupings, disparities in COVID-19 vaccination coverage were identified when the data were disaggregated into more granular categories; for example, COVID-19 vaccination coverage ranged from 10.8%–61.1% among pregnant persons who identified as Hispanic. Disaggregated analyses reveal diverse experiences within broad racial and ethnic groupings. This information can be used to guide outreach to pregnant persons in communities with lower rates of COVID-19 vaccination coverage during pregnancy. [ABSTRACT FROM AUTHOR]

Background: SARS‐CoV‐2 infection during pregnancy has been linked to preterm birth, but this association is not well understood. Objectives: To examine the association between SARS‐CoV‐2 infection and spontaneous and provider‐initiated preterm birth (PTB), and how timing of infection, and race/ethnicity as a marker of structural inequality, may modify this association. Methods: We conducted a retrospective cohort study among pregnant people who delivered singleton, liveborn infants (22–44 weeks gestation) from 1 March 2020 to 31 March 2021 (n = 68,288). We used Cox proportional hazards models to compare the hazard of PTB between pregnant people with and without laboratory‐confirmed SARS‐CoV‐2 infection during pregnancy. We evaluated this association according to the trimester of infection, timing from infection to birth, and timing of PTB. We also examined the joint associations of SARS‐CoV‐2 infection and race/ethnicity with PTB using the relative excess risk due to interaction (RERI). Results: Positive SARS‐CoV‐2 tests were identified for 2195 pregnant people (3.2%). The prevalence of PTB was 7.2% (3.8% spontaneous, 3.6% provider‐initiated). SARS‐CoV‐2 infection during pregnancy was associated with an increased risk of PTB overall (adjusted hazard ratio [HR] 1.53, 95% confidence interval [CI] 1.34, 1.74), and provider‐initiated PTB (HR 1.79, 95% CI 1.50, 2.12) but not spontaneous PTB (HR 1.09, 95% CI 0.89, 1.36). Second trimester infections were associated with an increased risk of provider‐initiated PTB, and third trimester infections were associated with an increased risk of both PTB subtypes. A joint inverse association between White non‐Hispanic race/ethnicity and SARS‐CoV‐2 infection and spontaneous PTB (HR 0.56, 95% CI 0.34, 0.94; RERI −0.6, 95% CI −1.0, −0.2) was also observed. Conclusions: SARS‐CoV‐2 infections were primarily associated with an increased risk for provider‐initiated PTB in this study. These findings highlight the importance of promoting infection‐prevention strategies among pregnant people. [ABSTRACT FROM AUTHOR]

Objectives: Pregnant people infected with SARS-CoV-2, the virus that causes COVID-19, are at increased risk for severe illness and death compared with nonpregnant people. However, population-based information comparing characteristics of people with and without laboratory-confirmed SARS-CoV-2 infection during pregnancy is limited. We compared the characteristics of people with and without SARS-CoV-2 infection during pregnancy in Massachusetts. Methods: We compared maternal demographic characteristics, pre-pregnancy conditions, and pregnancy complications of people with and without SARS-CoV-2 infection during pregnancy with completed pregnancies resulting in a live birth in Massachusetts during March 1, 2020–March 31, 2021. We tested for significant differences in the distribution of characteristics of pregnant people by SARS-CoV-2 infection status overall and stratified by race and ethnicity. We used modified Poisson regression analyses to examine the association between race and ethnicity and SARS-CoV-2 infection during pregnancy. Results: Of 69 960 completed pregnancies identified during the study period, 3119 (4.5%) had laboratory-confirmed SARS-CoV-2 infection during pregnancy. Risk for SARS-CoV-2 infection was higher among Hispanic (adjusted risk ratio [aRR] = 2.3; 95% CI, 2.1-2.6) and non-Hispanic Black (aRR = 1.9; 95% CI, 1.7-2.1) pregnant people compared with non-Hispanic White pregnant people. Conclusions: This study demonstrates the disproportionate impact of SARS-CoV-2 infection on Hispanic and non-Hispanic Black pregnant people in Massachusetts, which may widen existent inequities in maternal morbidity and mortality. Future research is needed to elucidate the structural factors leading to these inequities. [ABSTRACT FROM AUTHOR]

Background: Many previous studies have identified risk factors for stillbirth, but few examine stillbirth among pregnancies affected with birth defects. Because many hypothesized etiologies of stillbirth work through vascular pathologies of the placenta, we examined maternal use of vasoactive medications in relation to stillbirth among pregnancies affected with birth defects. Methods: Data were analyzed from the National Birth Defects Prevention Study (1997–2011). We examined use of nonsteroidal anti‐inflammatory drugs (NSAIDs), decongestants, short‐ or long‐acting beta‐agonists (SABA/LABA), and antihypertensive medications in relation to pregnancies affected by birth defects ending in stillbirth compared to live birth. Associations were measured with odds ratios (ORs) for early pregnancy use and hazard ratios (HRs) for time‐varying late pregnancy use. Results: Among all birth defects (n = 12,394), the risk of stillbirth was associated with use of antihypertensive medications in early (odds ratio [OR]: 1.8; 95% confidence interval [CI]: 1.0, 3.1) and late pregnancy (HR: 2.0; 95% CI: 1.1, 3.6). Other vasoactive medications were not associated with increased risk of stillbirth. Of 27 specific defect groups, increased risks were observed for only one medication/defect pair: early decongestant use was more common among mothers of stillbirth versus live birth cases with spina bifida (OR: 2.4; 95% CI: 0.9, 6.5). Conclusion: This exploratory analysis of vasoactive medication use suggests that use of NSAIDs, decongestants, and SABA/LABA is not associated with increased risk of stillbirth among pregnancies affected with birth defects. Our finding of increased risks associated with antihypertensive medication use raises questions of confounding by indication, which we were not able to fully address. [ABSTRACT FROM AUTHOR]

Background Research suggests short interpregnancy intervals increase risks for adverse perinatal outcomes, including some birth defects. A hypothesized cause is nutritional depletion, including folic acid (FA). Objectives We evaluated associations between short interpregnancy intervals, alone and in combination with FA intake, and the occurrence of select malformations. Methods Data were from the National Birth Defects Prevention Study (US case–control, 1997–2011). Participants included multiparous women whose prior pregnancy resulted in live birth. Cases included 8 noncardiac and 6 cardiac defect groups (n  = 3219); controls were nonmalformed live-borns (n  = 2508). We categorized interpregnancy interval (<6, 6–11, 12–17, and 18–23 mo) and periconceptional FA intake [no FA supplement use and dietary folate equivalents (DFE) <400 µg/d, no FA supplement use and DFE ≥400 µg/d, or any FA supplement use]. We controlled for age, race/ethnicity, income, pregnancy intention, and study center. ORs <0.8 or >1.2 were considered to represent potentially meaningful associations. Results ORs for <6 compared with 18–23 mo were >1.2 for 4/8 noncardiac and 3/6 cardiac malformations. Among participants with any FA supplement use, ORs comparing <6 with 6–23 mo were <1.2 for most defects. Conversely, most ORs were >1.2 for <6 mo + no FA supplement use and DFE <400 µg/d compared with 6–23 mo + any FA supplement use. Magnitude and precision varied by defect. Conclusions Short interpregnancy intervals were associated with a trend of higher risks for several defects, notably in the absence of FA supplement use. To our knowledge, our study is the first to provide preliminary empirical support that these etiologies may be related to shorter interpregnancy intervals and possible nutritional deficiencies. Because FA intake is highly correlated with other nutrients, and because our estimates were generally imprecise, more research with larger sample sizes is needed to better understand the role of FA compared with other nutrients in each defect-specific etiology. [ABSTRACT FROM AUTHOR]

Recent public health emergencies have highlighted the unique vulnerabilities of pregnant women and infants to emerging health threats and the critical role of public health surveillance. Surveillance systems can collect critical data to measure the impact of a disease or disaster and can be used to inform clinical guidance and prevention strategies. These systems can also be tailored to collect data on vulnerable populations, such as pregnant women and their infants. Novel surveillance systems to assess risks and outcomes of pregnant women and infants have been established during public health emergencies but typically cease data collection once the public health response has ended, limiting our ability to collect data to understand longer-term outcomes. State-based birth defects surveillance systems are not available in all states, and no national surveillance system linking pregnancy exposure data to longitudinal outcomes for infants and children exists. In this report, we describe ongoing surveillance efforts to monitor congenital syphilis, Zika virus infection during pregnancy, and neonatal abstinence syndrome. We describe the need and rationale for an ongoing integrated surveillance system to monitor pregnant women and their infants and to detect emerging threats. We also discuss how data collected through this type of system can better position federal, state, and local health departments to more rapidly and comprehensively respond to the next public health emergency. [ABSTRACT FROM AUTHOR]

Background Clubfoot is associated with maternal cigarette smoking in several studies, but it is not clear if this association is confined to women who smoke throughout the at-risk period. Maternal alcohol and coffee drinking have not been well studied in relation to clubfoot. Methods The present study used data from a population-based case-control study of clubfoot conducted in Massachusetts, New York, and North Carolina from 2007 to 2011. Mothers of 646 isolated clubfoot cases and 2037 controls were interviewed about pregnancy events and exposures, including the timing and frequency of cigarette smoking, alcohol intake, and coffee drinking. Results More mothers of cases than controls reported smoking during early pregnancy (28.9% vs. 19.1%). Of women who smoked when they became pregnant, those who quit in the month after a first missed period had a 40% increase in clubfoot risk and those who continued to smoke during the next 3 months had more than a doubling in risk, after controlling for demographic factors, parity, obesity, and specific medication exposures. Adjusted odds ratios for women who drank >3 servings of alcohol or coffee per day throughout early pregnancy were 2.38 and 1.77, respectively, but the numbers of exposed women were small and odds ratios were unstable. Conclusions Clubfoot risk appears to be increased for offspring of women who smoke cigarettes, particularly those who continue smoking after pregnancy is recognisable, regardless of amount. For alcohol and coffee drinkers, suggested increased risks were only observed in higher levels of intake. [ABSTRACT FROM AUTHOR]

Genitourinary infections (GUIs) have been associated with increased risk of gastroschisis in 2 studies. Using data collected in the Slone Epidemiology Center Birth Defects Study, we examined the association between GUI and gastroschisis. From 1998 to 2010, mothers of 249 gastroschisis cases and 7,104 controls were interviewed within 6 months of delivery about pregnancy events, including vaginal infections, genital herpes, urinary tract infections (UTIs), and other sexually transmitted diseases (STDs). Women were considered exposed if they reported at least 1 instance of a GUI in the first trimester. Logistic regression models were used to calculate odds ratios and 95% confidence intervals. Women who reported having any GUI had an adjusted odds ratio of 1.8 (95% confidence interval (CI): 1.3, 2.4). The highest risk was seen among women who reported a UTI only (adjusted odds ratio = 2.3, 95% CI: 1.5, 3.5), while the odds ratio for an STD only was slightly elevated (adjusted odds ratio = 1.2, 95% CI: 1.0, 1.5). Among women under 25 years of age, the odds ratio for UTI only was 2.6 (95% CI: 1.7, 4.0), and among older women it was 1.8 (95% CI: 0.6, 5.9). When we considered the joint association of UTIs and young maternal age, a synergistic effect was observed. The results of this study add further evidence that UTIs may increase the risk of gastroschisis. [ABSTRACT FROM PUBLISHER]

Clubfoot, a common major structural malformation, develops early in gestation. Epidemiologic studies have identified higher risks among boys, first-born children, and babies with a family history of clubfoot, but studies of risks associated with maternal exposures are lacking. We conducted the first large-scale, population-based, case-control study of clubfoot with detailed information on maternal medication use in pregnancy. Study subjects were ascertained from birth defect registries in Massachusetts, New York, and North Carolina during 2007-2011. Cases were 646 mothers of children with clubfoot without other major structural malformations (i.e., isolated clubfoot); controls were mothers of 2,037 children born without major malformations. Mothers were interviewed within 12 months of delivery about medication use, including product, timing, and frequency. Odds ratios were estimated for exposure to 27 medications in pregnancy months 2-4 after adjustment for study site, infant sex, first-born status, body mass index (weight (kg)/height (m)²), and smoking. Odds ratios were less than 1.20 for 14 of the medications; of the remainder, most odds ratios were only slightly elevated (range, 1.21-1.66), with wide confidence intervals. The use of antiviral drugs was more common in clubfoot cases than in controls (odds ratio = 4.22, 95% confidence interval: 1.52, 11.73). Most of these results are new findings and require confirmation in other studies. [ABSTRACT FROM AUTHOR]

Clubfoot is a common structural malformation, occurring in approximately 1/1,000 live births. Previous studies of sociodemographic and pregnancy-related risk factors have been inconsistent, with the exception of the strong male preponderance and association with primiparity. Hypotheses for clubfoot pathogenesis include fetal constraint, Mendelian-inheritance, and vascular disruption, but its etiology remains elusive. We conducted a population-based case-control study of clubfoot in North Carolina, Massachusetts, and New York from 2007 to 2011. Mothers of 677 clubfoot cases and 2,037 non-malformed controls were interviewed within 1 year of delivery about socio-demographic and reproductive factors. Cases and controls were compared for child's sex, maternal age, education, cohabitation status, race/ethnicity, state, gravidity, parity, body mass index (BMI), and these pregnancy-related conditions: oligohydramnios, breech delivery, bicornuate uterus, plural birth, early amniocentesis (<16 weeks), chorionic villous sampling (CVS), and plural gestation with fetal loss. Odds ratios (ORs) and 95% confidence intervals (CIs) were adjusted for state. Cases were more likely to be male (OR: 2.7; 2.2-3.3) and born to primiparous mothers (1.4; 1.2-1.7) and mothers with BMI ≥30 kg/m2 (1.4; 1.1-1.8). These associations were greatest in isolated and bilateral cases. ORs for the pregnancy-related conditions ranged from 1.3 (breech delivery) to 5.6 (early amniocentesis). Positive associations with high BMI were confined to cases with a marker of fetal constraint (oligohydramnios, breech delivery, bicornuate uterus, plural birth), inheritance (family history in 1st degree relative), or vascular disruption (early amniocentesis, CVS, plural gestation with fetal loss). Pathogenetic factors associated with obesity may be in the causal pathway for clubfoot. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Both maternal diabetes and obesity have been associated with an increased risk of neural tube defects (NTD), possibly due to a sustained state of hyperglycemia and/or hyperinsulinemia. Data were collected in the Boston University Slone Birth Defects Study (a case-control study) from 1988 to 1998. The authors examined whether high dietary glycemic index (DGI) and high dietary glycemic load (DGL) increased the risk of NTDs in nondiabetic women. Mothers of NTD cases and nonmalformed controls were interviewed in person within 6 months after delivery about diet and other exposures. Odds ratios and 95% confidence intervals were estimated from logistic regression for high DGI (≥60) and high DGL (≥205), with cutpoints determined by cubic spline. Of 698 case mothers, 25% had high DGI and 4% had high DGL. Of 696 control mothers, 15% had high DGI and 2% had high DGL. After adjustment for sociodemographic factors and other dietary factors, the odds ratio for high DGI was 1.5 (95% confidence interval: 1.1, 2.0); for high DGL, it was 1.8 (95% confidence interval: 0.8, 4.0). Diets with proportionally high DGI or DGL may put the developing fetus at risk of an NTD, adding further evidence that hyperglycemia lies within the pathogenic pathway. [ABSTRACT FROM PUBLISHER]

ABSTRACT Background Objective Methods Results Conclusions Empirically evaluating the potential impact of recall bias on observed associations of prenatal medication exposure is crucial.We sought to assess the effects of exposure misclassification on previous studies of the use of nonsteroidal anti‐inflammatory drugs (NSAIDs) in early pregnancy and increased risk of amniotic band syndrome (ABS).Using data from the National Birth Defects Prevention Study (NBDPS) on births from 1997 to 2011, we included 189 mothers of infants with ABS and 11,829 mothers of infants without congenital anomalies. We identified external studies of medication use during pregnancy to obtain validity parameters for a probabilistic bias analysis to adjust for exposure misclassification. Due to uncertainty about the transportability of these parameters, we conducted multidimensional bias analyses to explore combinations of values on the results.When we assumed higher specificity in cases or higher sensitivity in controls, misclassification‐adjusted estimates suggested confounding‐adjusted estimates were attenuated. However, in a few instances, when we assumed greater sensitivity in the cases than the controls (and Sp ≥ 0.9), the misclassification‐adjusted estimates suggested upward bias in the confounding‐adjusted estimates.Results from our bias analysis highlighted that the magnitude of bias depended on the mechanism and the extent of misclassification. However, the parameters available from the validation studies were not directly applicable to our study. In the absence of reliable validation studies, considering mechanisms of bias and simulation studies to outline combinations of plausible scenarios to better inform conclusions on the effects of these medications on pregnancy outcomes remains important. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to investigate the relationship between spina bifida and 2 established risk factors (pregestational diabetes mellitus and obesity) in both the presence and absence of the recommended daily folic acid intake in the periconceptional period. Study Design: Cases of spina bifida (n = 1154) and control subjects (n = 9439) from the Slone Epidemiology Center Birth Defects Study (1976-2011) were included. Information on preexisting diabetes mellitus (collected 1976-2011) and obesity (collected 1993-2011), defined as a body mass index of ≥30 kg/m2, was collected through interviews that were conducted within 6 months of delivery. Periconceptional folic acid intake was calculated with both dietary and supplement information. Mothers were classified as consuming more or less than 400 μg/day of folic acid; food folate was included at a 30% discount for its lower bioavailability. Logistic regression models that were adjusted for maternal age, race, education, and study site were used to calculate adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for the joint effects of low folic acid intake coupled with diabetes mellitus or obesity. Results: Case mothers were more likely to have diabetes mellitus or be obese (0.7% and 19.0%, respectively) than control mothers (0.4% and 10.8%, respectively). The joint effect of diabetes mellitus and lower folic acid intake on spina bifida was larger (aOR, 3.95; 95% CI, 1.56–10.00) than that of diabetes mellitus and higher folic acid intake (aOR, 1.31; 95% CI, 0.17–10.30). Folic acid intake made little difference on the association between obesity and spina bifida. Conclusion: Our findings suggest that folic acid further attenuates, although does not eliminate, the risk of spina bifida that is associated with diabetes mellitus than the risk with obesity. [ABSTRACT FROM AUTHOR]