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Seven out of every thousand male infants in United States is affected by Hypospadias, a birth defect. The results of an analysis which determined that no increased risk for second-or third-degree hypospadias existed among women who used loratadine, a nonsedating antihistamine commonly used for seasonal allergies, in early pregnancy.

Background: Maternal injuries during pregnancy are common and can cause adverse pregnancy outcomes. We sought to describe factors related to injury during pregnancy. Methods: We analyzed data from the National Birth Defects Prevention Study (NBDPS), a population-based, case-control study of birth defects in 10 U.S. states. We estimated the proportion of control mothers, a random sample of mothers delivering infants without major birth defects in the study regions, who reported an injury during pregnancy. We assessed associations with maternal and paternal characteristics using logistic regression to estimate adjusted odds ratios (aOR) and 95% confidence intervals (CI). Results: Between October 1997 and December 2005, 490 (7.4%) of 6609 mothers reported 527 injuries during pregnancy. Falls caused over half of reported injuries during pregnancy (51.6%), and 9.5% of reported injuries were intentionally inflicted. Mothers who reported an injury during pregnancy were more likely to be aged <18 years vs. 18-29 years (aOR 2.84, 95% CI 1.54-5.23) and less likely to be aged ≥30 years (aOR 0.67, 95% CI 0.51-0.89). They were more likely to use alcohol during pregnancy (aOR for nonbinge drinking 1.38, 95% CI 1.05-1.81), to smoke during pregnancy (aOR 1.37, 95% CI 1.02-1.85), to have epilepsy (aOR 3.31, 95% CI 1.48-7.38), and to be employed (aOR 1.44, 95% CI 1.08-1.93) than mothers who did not report an injury. Conclusions: We identified several factors associated with maternal injury during pregnancy, an important step in identifying women who may be at higher risk and in designing interventions to prevent injuries during pregnancy. [ABSTRACT FROM AUTHOR]

Objectives: Given that approximately half of all pregnancies in the United States are unplanned, the authors sought to understand the relation between pregnancy intention and health behaviors. Methods: Mothers of live-born infants without major birth defects were interviewed as part of the National Birth Defects Prevention Study. The interview assessed pregnancy intention as well as exposures to vitamins, alcohol, tobacco, illicit drugs, occupational hazards, exogenous heat (e.g., hot tubs and saunas) and caffeine. Crude odds ratios and 95% confidence intervals were calculated and stratified analyses were performed to assess interaction. Multiple logistic regression was used to calculate adjusted odds ratios. Results: Both before and after the diagnosis of pregnancy, women with unintended pregnancies were more likely to use illicit drugs, smoke, be exposed to environmental smoke, and not take folic acid or multivitamins. The degree to which women altered behaviors after they realized they were pregnant was also associated with their pregnancy intention status. For certain behaviors, maternal age or parity altered the association between pregnancy intention and changing behaviors after awareness of pregnancy. Conclusion: Pregnancy intention status is a key determinant of pregnancy-related behavior. To improve reproductive outcomes, preconceptional and prenatal programs should consider a woman's desire for pregnancy. [ABSTRACT FROM AUTHOR]

Objective: This study assessed reported use of assisted reproductive technology (ART) and other (non-ART) fertility treatments among a population-based sample and examined factors related to use. Methods: The data for this study were collected as part of the National Birth Defects Prevention Study (NBDPS), limited to women from the control group who delivered liveborn infants with no major birth defects. We described prevalence of the use of ART and clomiphene citrate (the most commonly used non-ART treatment) by demographic and lifestyle factors and examined associations among use of fertility treatments and pregnancy outcomes, timing of prenatal care initiation, and use of prenatal testing technologies. Results: Overall, 4.2% of women reported any type of maternal fertility treatment use; 1.0% reported ART use, 1.6% reported clomiphene citrate use without ART, and 1.7% reported other fertility treatments. Women who reported any fertility treatment type were more likely than women with an unassisted conception to be non-Hispanic white, >30 years of age, and more highly educated. Overall, women who reported ART use were more likely than women who reported unassisted pregnancy to have an amniocentesis; however, this association was no longer evident after adjustment for maternal age. Conclusions: Fertility treatment use and type of treatment vary by maternal characteristics. This information may be useful to inform a broad maternal and child health audience about the growing use of fertility treatments, including who is using the treatments and the choices they are making about prenatal care. [ABSTRACT FROM AUTHOR]

To evaluate the representativeness of controls in an ongoing, population-based, case-control study of birth defects in 10 centers across the United States, researchers compared 1997-2003 birth certificate data linked to selected controls (n = 6,681) and control participants (n = 4,395) with those from their base populations (n = 2,468,697). Researchers analyzed differences in population characteristics (e.g., percentage of births at > or =2,500 g) for each group. Compared with their base populations, control participants did not differ in distributions of maternal or paternal age, previous livebirths, maternal smoking, or diabetes, but they did differ in other maternal (i.e., race/ethnicity, education, entry into prenatal care) and infant (i.e., birth weight, gestational age, and plurality) characteristics. Differences in distributions of maternal, but not infant, characteristics were associated with participation by selected controls. Absolute differences in infant characteristics for the base population versus control participants were < or =1.3 percentage points. Differences in infant characteristics were greater at centers that selected controls from hospitals compared with centers that selected controls from electronic birth certificates. These findings suggest that control participants in the National Birth Defects Prevention Study generally are representative of their base populations. Hospital-based control selection may slightly underascertain infants affected by certain adverse birth outcomes. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Craniosynostosis, a malformation caused by premature closure of 1 or more cranial sutures, is a rare birth defect usually of unknown cause; however, it is often associated with advanced maternal age. Because fertility treatments are also associated with increased maternal age, this study investigated the possible association between fertility treatments and craniosynostosis. METHODS: Data from the Birth Defect Risk Factor Surveillance study were used, which included infants who were delivered from 1993 through 1997 in California, Georgia, and Iowa. Cases were defined as infants who had nonfamilial, nonsyndromic craniosynostosis and were ascertained through existing birth defect surveillance systems. Controls, infants without birth defects, were selected from the same regions and time period. RESULTS: Mothers of 99 case infants and 777 control infants from the 3 study locations participated in this study by completing a telephone interview. Unadjusted analyses showed associations with craniosynostosis for mothers who had used clomiphene citrate (odds ratio[OR]: 3.8; 95% confidence interval [CI]: 1.1-12.3), artificial insemination (OR: 4.2; 95% CI: 0.8-9.4), or assisted reproductive techniques (OR: 4.2; 95% CI: 0.5-27.3). CONCLUSIONS: This is the first study that has found associations between fertility treatments and craniosynostosis. However, the numbers are small; therefore, the results should be viewed with caution. [ABSTRACT FROM AUTHOR]

Focuses on the evaluation of an association between loratadine and hypospadias in the U.S. Characterization of hypospadias as a birth defect; Study on the prevalence of hypospadias with respect to the intake of the antihistamine during pregnancy; Usefulness of the results of the study for women and health care providers.

Many examples of the use of real-world data in the area of pharmacoepidemiology include "big data," such as insurance claims, medical records, or hospital discharge databases. However, "big" is not always better, particularly when studying outcomes with narrow windows of etiologic relevance. Birth defects are such an outcome, for which specificity of exposure timing is critical. Studies with primary data collection can be designed to query details about the timing of medication use, as well as type, dose, frequency, duration, and indication, that can better characterize the "real world." Because birth defects are rare, etiologic studies are typically case‑control in design, like the National Birth Defects Prevention Study, Birth Defects Study to Evaluate Pregnancy Exposures, and Slone Birth Defects Study. Recall bias can be a concern, but the ability to collect detailed information about both prescription and over-the-counter medication use and other exposures such as diet, family history, and sociodemographic factors is a distinct advantage over claims and medical record data sources. Case‑control studies with primary data collection are essential to advancing the pharmacoepidemiology of birth defects. This article is part of a Special Collection on Pharmacoepidemiology., (Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2024.)

Background: The use of chlorine to treat drinking water produces disinfection by-products (DBPs), which have been associated with congenital heart defects (CHDs) in some studies., Methods: Using National Birth Defects Prevention Study data, we linked geocoded residential addresses to public water supply measurement data for DBPs. Self-reported water consumption and filtration methods were used to estimate maternal ingestion of DBPs. We estimated adjusted odds ratios and 95% confidence intervals using logistic regression controlling for maternal age, education, body mass index (BMI), race/ethnicity, and study site to examine associations between CHDs and both household DBP level and estimated ingestion of DBPs., Results: Household DBP exposure was assessed for 2717 participants (1495 cases and 1222 controls). We observed a broad range of positive, null, and negative estimates across eight specific CHDs and two summary exposures (trihalomethanes and haloacetic acids) plus nine individual DBP species. Examining ingestion exposure among 2488 participants (1347 cases, 1141 controls) produced similarly inconsistent results., Conclusions: Assessing both household DBP level and estimated ingestion of DBPs, we did not find strong evidence of an association between CHDs and DBPs. Despite a large study population, DBP measurements were available for less than half of participant addresses, limiting study power., (© 2024 Wiley Periodicals LLC.)

Background: Primary congenital glaucoma (PCG) affects approximately 1 in 10,000 live born infants in the United States (U.S.). PCG has a autosomal recessive inheritance pattern, and variable expressivity and reduced penetrance have been reported. Likely causal variants in the most commonly mutated gene, CYP1B1, are less prevalent in the U.S., suggesting that alternative genes may contribute to the condition. This study utilized exome sequencing to investigate the genetic architecture of PCG in the U.S. and to identify novel genes and variants., Methods: We studied 37 family trios where infants had PCG and were part of the National Birth Defects Prevention Study (births 1997-2011), a U.S. multicenter study of birth defects. Samples underwent exome sequencing and sequence reads were aligned to the human reference sample (NCBI build 37/hg19). Variant filtration was conducted under de novo and Mendelian inheritance models using GEMINI., Results: Among candidate variants, CYP1B1 was most represented (five trios, 13.5%). Twelve probands (32%) had potentially pathogenic variants in other genes not previously linked to PCG but important in eye development and/or to underlie Mendelian conditions with potential phenotypic overlap (e.g., CRYBB2, RXRA, GLI2)., Conclusion: Variation in the genes identified in this population-based study may help to further explain the genetics of PCG., (© 2024 Wiley Periodicals LLC.)

Zolpidem is a non-benzodiazepine agent indicated for treatment of insomnia. While zolpidem crosses the placenta, little is known about its safety in pregnancy. We assessed associations between self-reported zolpidem use 1 month before pregnancy through to the end of the third month ("early pregnancy") and specific birth defects using data from two multi-site case-control studies: National Birth Defects Prevention Study and Slone Epidemiology Center Birth Defects Study. Analysis included 39,711 birth defect cases and 23,035 controls without a birth defect. For defects with ≥ 5 exposed cases, we used logistic regression with Firth's penalised likelihood to estimate adjusted odds ratios and 95% confidence intervals, considering age at delivery, race/ethnicity, education, body mass index, parity, early-pregnancy antipsychotic, anxiolytic, antidepressant use, early-pregnancy opioid use, early-pregnancy smoking, and study as potential covariates. For defects with three-four exposed cases, we estimated crude odds ratios and 95% confidence intervals. Additionally, we explored differences in odds ratios using propensity score-adjustment and conducted a probabilistic bias analysis of exposure misclassification. Overall, 84 (0.2%) cases and 46 (0.2%) controls reported early-pregnancy zolpidem use. Seven defects had sufficient sample size to calculate adjusted odds ratios, which ranged from 0.76 for cleft lip to 2.18 for gastroschisis. Four defects had odds ratios > 1.8. All confidence intervals included the null. Zolpidem use was rare. We could not calculate adjusted odds ratios for most defects and estimates are imprecise. Results do not support a large increase in risk, but smaller increases in risk for certain defects cannot be ruled out., (© 2023 European Sleep Research Society.)

Background: Gastroschisis has increased worldwide over several decades; however, there are significant gaps in understanding risk factors for development of the defect, particularly those that might be modifiable. Despite advances in survival, little is known about longer-term outcomes for affected individuals., Methods: On April 27- and 28, 2023, the National Center on Birth Defects and Developmental Disabilities at the Centers for Disease Control and Prevention (CDC) and March of Dimes sponsored a meeting entitled "Public Health Priorities for Gastroschisis". The meeting goals were to review current knowledge on gastroschisis, discuss research gaps, and identify future priorities for public health surveillance, research, and action related to gastroschisis. Meeting participants encompassed a broad range of expertise and experience, including public health, clinical care of individuals with gastroschisis, affected individuals and families, and representatives from professional organizations and federal agencies., Results: Several goals were identified for future public health surveillance and research, including focused theory-driven research on risk factors and increased study of longer-term effects of gastroschisis through improved surveillance. Certain public health actions were identified, that which could improve the care of affected individuals, including increased education of providers and enhanced resources for patients and families., Conclusions: These efforts may lead to an improved understanding of pathogenesis, risk factors, and outcomes and to improved care throughout the lifespan., (© 2024 Wiley Periodicals LLC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Background: The relationship between maternal physical activity (PA)/sitting and birth defects is largely unexplored. We examined whether pre-pregnancy PA/sitting were associated with having a pregnancy affected by a birth defect., Methods: We used data from two United States population-based case-control studies: 2008-2011 deliveries from the National Birth Defects Prevention Study (NBDPS; 9 states) and 2014-2018 deliveries from the Birth Defects Study To Evaluate Pregnancy exposureS (BD-STEPS; 7 states). Cases with one of 12 non-cardiac birth defects (n = 3798) were identified through population-based registries. Controls (n = 2682) were live-born infants without major birth defects randomly sampled using vital/hospital records. Mothers self-reported pre-pregnancy PA/sitting. Unconditional logistic regression models estimated associations between PA/sitting categories and the 12 birth defects., Results: Mothers engaging in pre-pregnancy PA was associated with a reduced odds of five (spina bifida, cleft palate, anorectal atresia, hypospadias, transverse limb deficiency) and a higher odds of two (anencephaly, gastroschisis) birth defects. Mothers spending less time sitting in pre-pregnancy was associated with a reduced odds of two (anorectal atresia, hypospadias) and a higher odds of one (cleft lip with or without cleft palate) birth defect., Conclusions: Reasonable next steps include replication of these findings, improved exposure assessment, and elucidation of biologic mechanisms., Impact: Using data from two population-based case-control studies, we found that mothers engaging in different types of physical activity in the 3 months before pregnancy had an infant with a reduced odds of five and a higher odds of two birth defects. Mothers spending less time sitting in the 3 months before pregnancy had an infant with a reduced odds of two and a higher odds of one birth defect. Clarification and confirmation from additional studies are needed using more precise exposure measures, distinguishing occupational from leisure-time physical activity, and elucidation of mechanisms supporting these associations., (© 2023. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Background: Gastroschisis prevalence more than doubled between 1995 and 2012. While there are individual-level risk factors (e.g., young maternal age, low body mass index), the impact of environmental exposures is not well understood., Methods: We used the U.S. Environmental Protection Agency's Environmental Quality Index (EQI) as a county-level estimate of cumulative environmental exposures for five domains (air, water, land, sociodemographic, and built) and overall from 2006 to 2010. Adjusted odds ratios (aOR) and 95% confidence interval (CI) were estimated from logistic regression models between EQI tertiles (better environmental quality (reference); mid; poorer) and gastroschisis in the National Birth Defects Prevention Study from births delivered between 2006 and 2011. Our analysis included 594 cases with gastroschisis and 4105 infants without a birth defect (controls)., Results: Overall EQI was modestly associated with gastroschisis (aOR [95% CI]: 1.29 [0.98, 1.71]) for maternal residence in counties with poorer environmental quality, compared to the reference (better environmental quality). Within domain-specific indices, only the sociodemographic domain (aOR: 1.51 [0.99, 2.29]) was modestly associated with gastroschisis, when comparing poorer to better environmental quality., Conclusions: Future work could elucidate pathway(s) by which components of the sociodemographic domain or possibly related psychosocial factors like chronic stress potentially contribute to risk of gastroschisis., (© 2023 Wiley Periodicals LLC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)