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Luben T.J.,U.S. Environmental Protection Agency | Fuentes M.,North Carolina State University | Aylsworth A.S.,University of North Carolina at Chapel Hill | Herring A.H.,University of North Carolina at Chapel Hill | And 8 more authors.
Environmental Health Perspectives | Year: 2014

Background: Epidemiologic literature suggests that exposure to air pollutants is associated with fetal development. Objectives: We investigated maternal exposures to air pollutants during weeks 2-8 of pregnancy and their associations with congenital heart defects. Methods: Mothers from the National Birth Defects Prevention Study, a nine-state case-control study, were assigned 1-week and 7-week averages of daily maximum concentrations of carbon monoxide, nitrogen dioxide, ozone, and sulfur dioxide and 24-hr measurements of fine and coarse particulate matter using the closest air monitor within 50 km to their residence during early pregnancy. Depending on the pollutant, a maximum of 4,632 live-birth controls and 3,328 live-birth, fetal-death, or electively terminated cases had exposure data. Hierarchical regression models, adjusted for maternal demographics and tobacco and alcohol use, were constructed. Principal component analysis was used to assess these relationships in a multipollutant context. Results: Positive associations were observed between exposure to nitrogen dioxide and coarctation of the aorta and pulmonary valve stenosis. Exposure to fine particulate matter was positively associated with hypoplastic left heart syndrome but inversely associated with atrial septal defects. Examining individual exposure-weeks suggested associations between pollutants and defects that were not observed using the 7-week average. Associations between left ventricular outflow tract obstructions and nitrogen dioxide and between hypoplastic left heart syndrome and particulate matter were supported by findings from the multipollutant analyses, although estimates were attenuated at the highest exposure levels. Conclusions: Using daily maximum pollutant levels and exploring individual exposure-weeks revealed some positive associations between certain pollutants and defects and suggested potential windows of susceptibility during pregnancy.


Getz K.D.,Massachusetts Center for Birth Defects Research and Prevention | Anderka M.T.,Massachusetts Center for Birth Defects Research and Prevention | Werler M.M.,Boston University
Birth Defects Research Part A - Clinical and Molecular Teratology | Year: 2012

BACKGROUND: The micronutrient depletion hypothesis proposes that consecutive pregnancies spaced too closely may leave insufficient time for maternal micronutrient replenishment. Short interpregnancy intervals (IPI) have been associated with an increased risk for several adverse pregnancy outcomes, but an association with gastroschisis risk has not been previously explored. METHODS: Within a population-based, case-control study, we evaluated the association between IPI length and gastroschisis risk using multivariable logistic regression models to estimate gastroschisis odds ratios for IPI <12 months and 12 to 17 months relative to those 18 to 23 months. We further evaluated the association between IPI and gastroschisis risk stratified by maternal age, periconceptional multivitamin use, preceding pregnancy outcome, study center region, and season of conception to explore whether observed associations were compatible with the hypothesis of maternal micronutrient depletion. RESULTS: For women with IPI <12 months, the adjusted odds ratio (aOR) was 1.7 (95% confidence interval [CI]: 1.1-2.5). The magnitude of the observed effect did not differ among strata of maternal age or periconceptional multivitamin use. However, the association was more pronounced after a miscarriage or termination (aOR: 2.5; 95% CI: 1.1-5.6) and among women who resided in northern study areas (aOR: 2.8; 95% CI: 1.3-5.9). The higher risk observed with short IPI among women in northern study areas was attenuated for spring/summer conceptions. CONCLUSION: Short IPI was associated with an increased risk for gastroschisis, particularly among women whose preceding pregnancy resulted in a miscarriage or termination and among those who resided in northern study areas with winter/fall conception. © 2012 Wiley Periodicals, Inc.


Toh S.,Harvard University | Mitchell A.A.,Boston University | Anderka M.,Massachusetts Center for Birth Defects Research and Prevention | De Jong-Van Den Berg L.T.W.,University of Groningen | Hernandez-Diaz S.,Harvard University
Contraception | Year: 2011

Background: Evidence on the association between antibiotic use and combined oral contraceptive (COC) failure is controversial. We examined the effect of concomitant antibiotic treatment on the risk of breakthrough pregnancy among COC users. Study Designs: We performed a case-crossover study of 1330 COC failure cases among 17,721 women from the Slone Epidemiology Center Birth Defects Study (1997-2008) and among 25,941 women from the National Birth Defects Prevention Study (NBDPS, 1997-2005). Self-matched odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by comparing antibiotic use between the 4 weeks before conception ("case period") and the 4-8 weeks before conception ("control period") using conditional logistic regression. A case-time-control analysis was conducted using nonusers of COCs with unplanned pregnancies as controls. Results: For the combined data, the self-matched OR was 1.08 (95% CI: 0.63-1.84) and the case-time-control OR was 1.12 (0.63-1.98) for antibiotics overall. The results did not appreciably differ when adjusted for characteristics that might vary between the case and control period. However, among COC failure cases from the NBDPS, allowing a 1-month gap between the case and control period resulted in a self-matched OR of 1.45 (0.85-2.50) and a case-time-control OR of 1.55 (0.86-2.79) for antibiotics overall. Conclusions: We did not find an association between concomitant antibiotic use and the risk of breakthrough pregnancy among COC users. However, due to limited power and potential carryover effects, findings from this study cannot rule out an elevated risk of COC failure among antibiotic users. © 2011 Elsevier Inc. All rights reserved.


Patel S.S.,University of Iowa | Burns T.L.,University of Iowa | Botto L.D.,University of Utah | Riehle-Colarusso T.J.,Centers for Disease Control and Prevention | And 4 more authors.
American Journal of Medical Genetics, Part A | Year: 2012

Although the descriptive epidemiology of atrioventricular septal defects (AVSDs), a group of serious congenital heart defects (CHDs), has been recently reported, non-genetic risk factors have not been consistently identified. Using data (1997-2005) from the National Birth Defects Prevention Study, an ongoing multisite population-based case-control study, the association between selected non-genetic factors and non-syndromic AVSDs was examined. Data on periconceptional exposures to such factors were collected by telephone interview from 187 mothers of AVSD case infants and 6,703 mothers of unaffected infants. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were estimated from logistic regression models. Mothers who reported cigarette smoking during the periconceptional period were more likely to have infants with AVSDs compared with non-smokers, independent of maternal age, periconceptional alcohol consumption, infant gestational age, family history of CHDs, and study site (aOR 1.5, 95% CI 1.1-2.4). The association was strongest in mothers who smoked more than 25 cigarettes/day. In addition, mothers with periconceptional passive smoke exposure were more likely to have infants with AVSDs than unexposed mothers, independent of maternal age, active periconceptional smoking, infant gestational age, and family history of CHDs (aOR 1.4, 95% CI 1.0-2.0). No associations were observed between AVSDs and maternal history of a urinary tract infection or pelvic inflammatory disease, maternal use of a wide variety of medications, maternal occupational exposure, parental drug use, or maternal alcohol consumption. If the results of this preliminary study can be replicated, minimizing maternal active and passive smoke exposure may decrease the incidence of AVSDs. © 2012 Wiley Periodicals, Inc.


Lin A.E.,MassGeneral Hospital for Children | Lin A.E.,Massachusetts Center for Birth Defects Research and Prevention | Krikov S.,University of Utah | Riehle-Colarusso T.,Centers for Disease Control and Prevention | And 7 more authors.
American Journal of Medical Genetics, Part A | Year: 2014

Little is known epidemiologically about laterality defects. Using data fromthe National Birth Defects Prevention Study (NBDPS), a large multi-site case-control study of birth defects, we analyzed prevalence and selected characteristics in children born with laterality defects born from 1998 to 2007. We identified 517 nonsyndromic cases (378 heterotaxy, 73.1%; 139 situs inversus totalis [SIT], 26.9%) resulting in an estimated birth prevalence of 1.1 per 10,000 live births (95% confidence interval 1.0-1.2). Prevalence did not differ significantly across sites, over time, or by inclusion of pregnancy termination. Laterality defects were more common among preterm cases compared to term cases, and in children born to mothers who were non-white or younger than 20 years compared to white mothers or those age 25-29 years. The distribution of associated cardiac and extra-cardiac defects, excluding the expected heterotaxy anomalies, varied by type of laterality defect. Cases with heterotaxy were significantly more likely than those with SIT to have double outlet right ventricle, atrioventricular canal defects, pulmonary stenosis, non-tetralogy of Fallot pulmonary atresia with ventricular septal defect, totally and partially anomalous pulmonary venous return; also more likely to have orofacial clefts, esophageal atresia, bowel atresias, and omphalocele, though not reaching statistical significance. Relatively more common among cases with SIT were Dandy-Walker malformation, anotia/microtia, and limb deficiency. The similarity in the demographic characteristics of heterotaxy and SIT supports the hypothesis that they are part of a continuum of abnormal left-right axis patterning. These findings on laterality defects may help guide clinical care, future research, and prevention strategies. © 2014 Wiley Periodicals, Inc.


Hartman R.J.,Centers for Disease Control and Prevention | Hartman R.J.,Oak Ridge Institute for Science and Education | Riehle-Colarusso T.,Centers for Disease Control and Prevention | Lin A.,Massachusetts Center for Birth Defects Research and Prevention | And 8 more authors.
American Journal of Medical Genetics, Part A | Year: 2011

Nonsyndromic atrioventricular septal defects (AVSDs) are serious congenital heart defects for which information on prevalence and descriptive characteristics based on large, geographically, and ethnically diverse populations has been limited. To describe the birth prevalence and phenotype of nonsyndromic AVSDs, we used data from the National Birth Defects Prevention Study (NBDPS), a multisite, population-based case-control study aimed at identifying genetic and environmental risk factors for birth defects. For this analysis, infants born during the period 1997-2005 and meeting the NBDPS case definition for AVSDs were included. Infants with an AVSD associated with recognized or strongly suspected chromosomal abnormalities or single-gene disorders (syndromic case infants) were excluded. We identified 302 infants with a nonsyndromic AVSD for a birth prevalence of 0.83/10,000 livebirths. Over 20% of infants with an AVSD had an additional major birth defect, with gastrointestinal, renal or urinary, and central nervous system defects being the most common. A lower prevalence of AVSDs was seen among infants born to Hispanic mothers compared with those born to non-Hispanic White mothers [prevalence ratio=0.63 (95% confidence interval: 0.46-0.86)]. Understanding the prevalence of nonsyndromic AVSDs, demographic factors associated with their occurrence, and associated defects could help guide clinical care, as well as contribute to a better understanding of pathogenesis. © 2011 Wiley-Liss, Inc.


Dawson A.L.,National Center on Birth Defects and Developmental Disabilities | Tinker S.C.,National Center on Birth Defects and Developmental Disabilities | Jamieson D.J.,National Center for Chronic Disease Prevention and Health Promotion | Hobbs C.A.,University of Arkansas for Medical Sciences | And 6 more authors.
Journal of Epidemiology and Community Health | Year: 2016

Background Twinning has been associated with many types of birth defects, although previous studies have had inconsistent findings. Many studies lack information about potential confounders, particularly use of fertility treatment. Our objective was to assess the association between twinning and birth defects in the National Birth Defects Prevention Study (NBDPS). Methods We used data from the NBDPS, a population-based, case-control study of major birth defects in the USA, to evaluate associations between twinning and birth defects. The study population included mothers of twin and singleton controls (live-born infants without major birth defects), and cases (fetuses or infants with a major birth defect) born October 1997-December 2007. Adjusted ORs and 95% CIs were estimated using multivariable logistic regression stratified by use of fertility treatment. Twin sex-pairing data and a simulation approach were used to estimate the zygosity of twins. Results In the unassisted conception stratum, we observed significant positive associations between twinning and 29 of 45 defect groups. The largest effect estimates were observed for multiple ventricular septal defects and cloacal exstrophy. Among mothers reporting any use of fertility treatments, we observed a significant association with twinning for 5 of 25 defect groups, with the largest effect estimates for hypoplastic left heart syndrome and omphalocele. OR estimates in the estimated monozygotic stratum were generally further from the null than in the dizygotic stratum. Conclusions Compared with singletons, a wide range of birth defects are significantly more common among twins. Birth defect risk in twins may be differential by use of fertility treatment. © 2016 by the BMJ Publishing Group Ltd.


PubMed | University of Arkansas for Medical Sciences, Massachusetts Center for Birth Defects Research and Prevention, Office of Infectious Diseases, National Center for Chronic Disease Prevention and Health Promotion and 3 more.
Type: Journal Article | Journal: Journal of epidemiology and community health | Year: 2016

Twinning has been associated with many types of birth defects, although previous studies have had inconsistent findings. Many studies lack information about potential confounders, particularly use of fertility treatment. Our objective was to assess the association between twinning and birth defects in the National Birth Defects Prevention Study (NBDPS).We used data from the NBDPS, a population-based, case-control study of major birth defects in the USA, to evaluate associations between twinning and birth defects. The study population included mothers of twin and singleton controls (live-born infants without major birth defects), and cases (fetuses or infants with a major birth defect) born October 1997-December 2007. Adjusted ORs and 95% CIs were estimated using multivariable logistic regression stratified by use of fertility treatment. Twin sex-pairing data and a simulation approach were used to estimate the zygosity of twins.In the unassisted conception stratum, we observed significant positive associations between twinning and 29 of 45 defect groups. The largest effect estimates were observed for multiple ventricular septal defects and cloacal exstrophy. Among mothers reporting any use of fertility treatments, we observed a significant association with twinning for 5 of 25 defect groups, with the largest effect estimates for hypoplastic left heart syndrome and omphalocele. OR estimates in the estimated monozygotic stratum were generally further from the null than in the dizygotic stratum.Compared with singletons, a wide range of birth defects are significantly more common among twins. Birth defect risk in twins may be differential by use of fertility treatment.


Anderka M.,Massachusetts Center for Birth Defects Research and Prevention | Romitti P.A.,Massachusetts Center for Birth Defects Research and Prevention | Sun L.,Massachusetts Center for Birth Defects Research and Prevention | Druschel C.,Massachusetts Center for Birth Defects Research and Prevention | And 2 more authors.
Acta obstetricia et gynecologica Scandinavica | Year: 2010

OBJECTIVES: To describe maternal exposure to tobacco in the three months before conception and throughout pregnancy, examine risk factors associated with tobacco exposure in pregnancy and smoking cessation, assess use of pharmacotherapy for smoking cessation and evaluate birth outcomes by smoking status. DESIGN: A cohort of women from a multi-site United States study were asked retrospectively about their exposure to tobacco. POPULATION: The study population was comprised of 4,667 mothers of non-malformed control infants who participated in the National Birth Defects Prevention Study from 1997 to 2003. METHODS: Using computer-assisted telephone interview responses from this population-based sample, we assessed patterns of maternal smoking and exposure to environmental tobacco smoke (ETS) as well as use of pharmacotherapy for quitting smoking during pregnancy. RESULTS: Overall, 961 (20.6%) mothers reported any smoking and 1,401 (30.0%) reported any exposure to ETS at home or work during the three months before conception through pregnancy. Of the 961 smokers, 512 (53.3%) reportedly quit smoking before or during pregnancy, including 379 (74% of quitters) in the first trimester, and 420 (43.7%) continued to smoke throughout the pregnancy. Only 2.1% of smokers reportedly used pharmacotherapy to quit smoking anytime from three months before conception through pregnancy. Low birthweight and preterm delivery rates were lowest among offspring of non-smokers and highest in offspring of those who continued to smoke throughout pregnancy. CONCLUSIONS: About one-half of mothers who reported preconceptional smoking quit before or during pregnancy. Use of pharmacotherapy to quit smoking during pregnancy was not common.


PubMed | Massachusetts Center for Birth Defects Research and Prevention
Type: Journal Article | Journal: Birth defects research. Part A, Clinical and molecular teratology | Year: 2012

The micronutrient depletion hypothesis proposes that consecutive pregnancies spaced too closely may leave insufficient time for maternal micronutrient replenishment. Short interpregnancy intervals (IPI) have been associated with an increased risk for several adverse pregnancy outcomes, but an association with gastroschisis risk has not been previously explored.Within a population-based, case-control study, we evaluated the association between IPI length and gastroschisis risk using multivariable logistic regression models to estimate gastroschisis odds ratios for IPI <12 months and 12 to 17 months relative to those 18 to 23 months. We further evaluated the association between IPI and gastroschisis risk stratified by maternal age, periconceptional multivitamin use, preceding pregnancy outcome, study center region, and season of conception to explore whether observed associations were compatible with the hypothesis of maternal micronutrient depletion.For women with IPI <12 months, the adjusted odds ratio (aOR) was 1.7 (95% confidence interval [CI]: 1.1-2.5). The magnitude of the observed effect did not differ among strata of maternal age or periconceptional multivitamin use. However, the association was more pronounced after a miscarriage or termination (aOR: 2.5; 95% CI: 1.1-5.6) and among women who resided in northern study areas (aOR: 2.8; 95% CI: 1.3-5.9). The higher risk observed with short IPI among women in northern study areas was attenuated for spring/summer conceptions.Short IPI was associated with an increased risk for gastroschisis, particularly among women whose preceding pregnancy resulted in a miscarriage or termination and among those who resided in northern study areas with winter/fall conception.

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