Search

Oxidative stress and redox imbalance adversely affect embryonic development. We developed two oxidative balance scores (OBS) that include dietary and nondietary exposures. We hypothesized that higher scores (i.e., lower oxidative stress) would be associated with lower risk of neural tube defects, orofacial clefts, conotruncal heart defects, and limb deficiencies. We used data from the National Birth Defects Prevention Study to create a dietary OBS based on intake of 13 nutrients and an overall OBS that included the 13 nutrients and eight additional nondietary factors related to oxidative balance (e.g., smoking). We used logistic regression to examine odds ratios associated with having low or high scores (i.e., <10th or >90th percentiles). Continuous models indicated reduced odds associated with high versus low scores (i.e., comparing odds at the 90th versus 10th percentile values of the distribution) on the overall OBS for cleft lip with or without cleft palate [adjusted odds ratio (aOR) 0.72, 95% confidence interval (CI) 0.63-0.82], longitudinal limb deficiency (aOR 0.73, CI 0.54-0.99), and transverse limb deficiency (aOR 0.74, CI 0.58-0.95); increased odds for anencephaly (aOR 1.40, CI 1.07-1.84); and primarily nonsignificant associations with conotruncal heart defects. Results for the dietary OBS were similar. This study provides some evidence that oxidative stress contributes to congenital anomalies related to neural crest cell development., (© 2023 Wiley Periodicals LLC.)

Background: We conducted a meta-analysis of observational epidemiological studies to evaluate the association between periconceptional use of vitamin A and the risk of giving birth to a child with nonsyndromic orofacial clefts (NSOFCs)., Methods: We carried out a systematic literature search of Embase, PubMed, Web of Science, Google Scholar, and OpenGrey from inception to June 30, 2021. Two reviewers independently evaluated the studies that met the inclusion criteria and filled out an abstraction form for each study. Study quality was assessed using the Newcastle-Ottawa Assessment Scale (NOS). Adjusted estimates were pooled with an inverse variance weighting using a random-effects model. Heterogeneity and publication bias were assessed using the Cochran's Q test and funnel plot, respectively., Results: A total of six case-control studies with moderate risk of bias were included. The pooled OR showed a 20% reduction in the risk of NSOFCs for periconceptional use of vitamin A which was not statistically significant (OR = .80; 95% CI .54-1.17, p = .25). For nonsyndromic cleft lip with or without cleft palate (NSCL/P), the studies were homogenous, and the pooled estimate showed a 13% risk reduction, which was significant (OR = .87; 95% CI .77-.99, p = .03). For nonsyndromic cleft palate only (NSCPO), the pooled estimate showed a 33% lower likelihood, which was not statistically significant (OR = .67; 95% CI .42-1.08, p = .10)., Conclusion: Our results suggest a possible protective effect for the periconceptional use of vitamin A on the risk of NSCL/P. This finding should be investigated further in prospective studies across multiple populations., (© 2022 The Authors. Birth Defects Research published by Wiley Periodicals LLC.)

Background: The etiologies of major birth defects are still unclear and few spatial analyses have been conducted in the United States. Spatial analyses of individual-level data can help elucidate environmental and social risk factors., Methods: We used generalized additive models to analyze 52,955 cases of neural tube defects, congenital heart defects (CHDs), gastroschisis, and orofacial cleft defects, and sampled from 642,399 controls born between 1999 and 2011 in Texas. The effect of geographic location was measured using a bivariable smooth term of geocoded birth address within a logistic regression framework. We calculated and mapped odds ratios (ORs) and 95% confidence intervals (CIs) for birth defects subtypes across Texas, and adjusted for maternal characteristics, environmental indicators, and community-level covariates. We also performed time-stratified spatiotemporal analyses for more prevalent birth defects., Results: Location was significantly associated with crude odds of all birth defects except hypoplastic left heart syndrome. After adjusting for maternal characteristics, environmental indicators, and community-level factors, ORs in many geographic areas were no longer statistically significant for most defects, especially CHDs. However, areas of significant and insignificant elevated risk remained for defects in all groups in North and South Texas, with ORs for ventricular septal defects increasing over time. Low risk of birth defects was often present in the northern part of East Texas., Conclusion: Significant spatial patterns of birth defects were identified and varied depending on adjustment of different categories of covariates. Further investigation of areas with increased risks may aid in our understanding of birth defects., (© 2021 Wiley Periodicals LLC.)

Background: Causes of most birth defects are largely unknown. Genetics, maternal factors (e.g., age, smoking) and environmental exposures have all been linked to some birth defects, including neural tube, oral cleft, limb reduction, and gastroschisis; however, the contribution of cumulative exposures across several environmental domains in association with these defects is not well understood., Methods: The Environmental Quality Index (EQI) and its domains (air, water, land, sociodemographic, built) were used to estimate county-level cumulative environmental exposures from 2006-2010 and matched to birth defects identified from Texas Birth Defects Registry and live birth records from births in years 2007-2010 (N = 1,610,709). Poisson regression models estimated prevalence ratios (PR) and 95% confidence intervals (CI) for associations between 10 birth defects and the EQI., Results: We observed some positive associations between worst environmental quality and neural tube, anencephaly, spina bifida, oral cleft, cleft palate, cleft lip with and without cleft palate, and gastroschisis [PR range: 1.12-1.55], but near null associations with limb reduction defects. Among domain specific results, we observed the strongest positive associations with the sociodemographic domain across birth defects but varied positive associations among the air and water domains, and negative or null associations with the land and built domains. Overall, few exposure-response patterns were evident., Conclusions: Our results highlight the complexities of cumulative, simultaneous environmental exposures in the prevalence rates of 10 selected birth defects. We were able to explore the impact of overall and domain specific environmental quality on birth defects and identify potential domain specific drivers of these associations., (© 2020 Wiley Periodicals LLC.)

Orofacial clefts (OFCs) are among the most common birth defects and impart a significant burden on afflicted individuals and their families. It is increasingly understood that many nonsyndromic OFCs are a consequence of extrinsic factors, genetic susceptibilities, and interactions of the two. Therefore, understanding the environmental mechanisms of OFCs is important in the prevention of future cases. This review examines the molecular mechanisms associated with environmental factors that either protect against or increase the risk of OFCs. We focus on essential metabolic pathways, environmental signaling mechanisms, detoxification pathways, behavioral risk factors, and biological hazards that may disrupt orofacial development., (© 2020 Wiley Periodicals LLC.)

Background: Arsenic is widely distributed in the environment in both inorganic and organic forms. Evidence from animal studies suggests that maternal inorganic arsenic may lead to the development of orofacial clefts (OFC)s in offspring. This evidence, together with the limited epidemiologic data available, supports the need for a comprehensive examination of major sources of arsenic exposure and OFCs in humans., Methods: Using interview data collected in the National Birth Defects Prevention Study, public and well water arsenic sampling data, and dietary arsenic estimates, we compared expert-rater assessed occupational arsenic exposure, individual-level exposure to arsenic through drinking water, and dietary arsenic exposure between mothers of OFC cases (N = 435) and unaffected controls (N = 1267). Associations for each source of exposure were estimated for cleft lip ± palate (CL/P) and cleft palate (CP) using unconditional logistic regression analyses., Results: Associations for maternal drinking water arsenic exposure and CL/P were near or below unity, whereas those for dietary arsenic exposure tended to be positive. For CP, positive associations were observed for maternal occupational arsenic and inorganic arsenic exposures, with confidence intervals that excluded the null value, whereas those for drinking water or dietary arsenic exposures tended to be near or below unity., Conclusions: Positive associations were observed for maternal occupational arsenic exposure and CP and for maternal dietary arsenic exposure and CL/P; the remainder of associations estimated tended to be near or below unity. Given the exploratory nature of our study, the results should be interpreted cautiously, and continued research using improved exposure assessment methodologies is recommended., (© 2018 Wiley Periodicals, Inc.)

Background: Limited epidemiologic research exists on the association between weather-related extreme heat events (EHEs) and orofacial clefts (OFCs). We estimated the associations between maternal exposure to EHEs in the summer season and OFCs in offspring and investigated the potential modifying effect of body mass index on these associations., Methods: We conducted a population-based case-control study among mothers who participated in the National Birth Defects Prevention Study for whom at least 1 day of their first two post-conception months occurred during summer. Cases were live-born infants, stillbirths, and induced terminations with OFCs; controls were live-born infants without major birth defects. We defined EHEs using the 95th and the 90th percentiles of the daily maximum universal apparent temperature distribution. We used unconditional logistic regression with Firth's penalized likelihood method to estimate adjusted odds ratios and 95% confidence intervals, controlling for maternal sociodemographic and anthropometric variables., Results: We observed no association between maternal exposure to EHEs and OFCs overall, although prolonged duration of EHEs may increase the risk of OFCs in some study sites located in the Southeast climate region. Analyses by subtypes of OFCs revealed no associations with EHEs. Modifying effect by BMI was not observed., Conclusions: We did not find a significantly increased risk of OFCs associated with maternal exposure to EHEs during the relevant window of embryogenesis. Future studies should account for maternal indoor and outdoor activities and for characteristics such as hydration and use of air conditioning that could modify the effect of EHEs on pregnant women., (© 2018 Wiley Periodicals, Inc.)

Background: Maternal exposure to drinking water disinfection byproducts (DBP)s may contribute to orofacial cleft (OFC) development, but studies are sparse and beset with limitations., Methods: Population-based, maternal interview reports of drinking water filtration and consumption for 680 OFC cases (535 isolated) and 1826 controls were linked with DBP concentration data using maternal residential addresses and public water system monitoring data. Maternal individual-level exposures to trihalomethanes (THM)s and haloacetic acids (HAA)s (µg/L of water consumed) were estimated from reported consumption at home, work, and school. Compared to no exposure, associations with multisource maternal exposure <1/2 or ≥1/2 the Maximum Contaminant Levels (MCL)s for total THMs (TTHM)s and HAAs (HAA5) or Maximum Contaminant Level Goals (MCLG)s for individual THMs and HAAs (if non-zero) were estimated for all OFCs and isolated OFCs, cleft palate (CP), and cleft lip ± cleft palate (CL/P) using logistic regression analyses., Results: Compared to controls, associations were near or below unity for maternal TTHM, HAA5, and individual THM exposures with all OFCs and isolated OFCs, CP, and CL/P. Associations also were near or below unity for individual HAAs with statistically significant, inverse associations observed with each OFC outcome group except CL/P., Conclusions: This study examined associations for maternal reports of drinking water filtration and consumption and maternal DBP exposure from drinking water with OFCs in offspring. Associations observed were near or below unity and mostly nonsignificant. Continued, improved research using maternal individual-level exposure data will be useful in better characterizing these associations., (© 2018 Wiley Periodicals, Inc.)

Background: Oral clefts are among the most common congenital anomalies. Most studies on risk factors of oral clefts have been carried out in developed countries. We investigated the associations between maternal exposures in the first trimester and oral clefts in South Vietnam., Methods: We conducted a hospital-based case-control study during October 2014-November 2015. Cases included 170 patients with nonsyndromic cleft lip with or without cleft palate and those with cleft palate only. Controls were 170 children without oral clefts, matched to each case by age and gender. Mothers were interviewed using structured questionnaire. We performed conditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs)., Results: Passive smoking was associated with increased risk of oral clefts in univariate analysis, but not in multivariable analysis (adjusted OR [aOR] = 1.68; 95% CI, 0.53-5.37). No association was observed between liver intake and oral clefts. Compared with nondrinkers, mothers who reported consumption of caffeine-containing beverages were more likely to have an infant with oral cleft (aOR = 5.89; 95% CI, 1.08-32.00). Periconceptional use of folic acid and multivitamins supplementation was associated with reduced risk of oral clefts (aOR = 0.01; 95% CI, 0.00-0.09 and aOR = 0.03; 95% CI, 0.01-0.13, respectively)., Conclusions: The results suggest no associations of maternal passive smoking or liver intake with oral clefts. Periconceptional use of folic acid or multivitamins may protect against oral clefts. Further studies are warranted to examine the roles of caffeine consumption in pregnant mothers on occurrence of oral clefts in offspring., (© 2018 Wiley Periodicals, Inc.)

Background: Orofacial clefts (OFC) are linked with several genetic and environmental factors. The aim of this study was to explore the association of potential risk factors with OFCs in India., Methods: This was a hospital-based, matched case-control (1:4 ratio; matching done for parity) study conducted in Hyderabad, Bengaluru, and Delhi-National Capital Region. Cases (nonsyndromic clefts) were recruited from treatment centers, while controls (live births) were recruited from maternity centers. Information on exposures was collected during personal interviews. Exposures of interest included folic acid supplementation during the peri-conceptional period, consanguineous marriage, exposure to drugs, infections during pregnancy, family history of OFC, and dietary factors., Results: A total of 785 participants were included in the study: 157 cases and 628 controls. A family history of cleft lip/palate (adjusted odds ratio [AOR], 15.48; 95% confidence interval [CI], 4.36-54.96; p value = 0.001), exclusive vegetarianism (AOR, 4.47; 95% CI, 1.83-10.98; p value = 0.001), and delayed first conception (AOR, 2.55, 95% CI, 1.25-5.21, p = 0.01) were found to be strongly associated with higher risk of OFCs. Supplementation with folic acid during first 3 months of pregnancy was not found to be protective against OFCs (AOR, 1.24; 95% CI, 0.59-2.58; p value = 0.56)., Conclusion: Our study confirmed the importance of family history as a risk factor for OFC. Our study did not show an association with folic acid supplementation but was underpowered to detect small effects. Our finding of higher risk among vegetarians requires replication. Birth Defects Research 109:1284-1291, 2017. © 2017 The Authors. Birth Defects Research Published by Wiley Periodicals, Inc., (© 2017 The Authors. Birth Defects Research Published by Wiley Periodicals, Inc.)