Neighborhood Deprivation and Neural Tube Defects.

BACKGROUND: Individual measures of socioeconomic status (SES) have been associated with an increased risk of neural tube defects (NTDs); however, the association between neighborhood SES and NTD risk is unknown. Using data from the National Birth Defects Prevention Study (NBDPS) from 1997 to 2011, we investigated the association between measures of census tract SES and NTD risk. METHODS: The study population included 10,028 controls and 1829 NTD cases. We linked maternal addresses to census tract SES measures and used these measures to calculate the neighborhood deprivation index. We used generalized estimating equations to calculate adjusted odds ratios (aORs) and 95% confidence intervals (CIs) estimating the impact of quartiles of census tract deprivation on NTDs adjusting for maternal race-ethnicity, maternal education, and maternal age at delivery. RESULTS: Quartiles of higher neighborhood deprivation were associated with NTDs when compared with the least deprived quartile (Q2: aOR = 1.2; 95% CI = 1.0, 1.4; Q3: aOR = 1.3, 95% CI = 1.1, 1.5; Q4 (highest): aOR = 1.2; 95% CI = 1.0, 1.4). Results for spina bifida were similar; however, estimates for anencephaly and encephalocele were attenuated. Associations differed by maternal race-ethnicity. CONCLUSIONS: Our findings suggest that residing in a census tract with more socioeconomic deprivation is associated with an increased risk for NTDs, specifically spina bifida.

Polysubstance Use in Pregnancy: Surveillance, Interventions, and Next Steps.

Substance use during pregnancy increases risk for a wide range of adverse maternal and neonatal health outcomes. Polysubstance use is common among people who use substances during pregnancy; however, the risks of combined substance exposures during pregnancy are poorly understood. In this report, we provide an overview of the activities of the Centers for Disease Control and Prevention (CDC) and partners and identified gaps related to (1) surveillance, (2) routine screening, and (3) prevention of polysubstance use during pregnancy. Efforts by CDC and other partners to reduce polysubstance use during pregnancy can improve the health of pregnant people and their infants and children.

Substance Use Among Persons with Syphilis During Pregnancy - Arizona and Georgia, 2018-2021.

Despite universal prenatal syphilis screening recommendations and availability of effective antibiotic treatment, syphilis prevalence during pregnancy and the incidence of congenital syphilis have continued to increase in the United States (1,2). Concurrent increases in methamphetamine, injection drug, and heroin use have been described in women with syphilis (3). CDC used data on births that occurred during January 1, 2018-December 31, 2021, from two states (Arizona and Georgia) that participate in the Surveillance for Emerging Threats to Pregnant People and Infants Network (SET-NET) to describe the prevalence of substance use among pregnant persons with syphilis by congenital syphilis pregnancy outcome (defined as delivery of a stillborn or live-born infant meeting the surveillance case definition for probable or confirmed congenital syphilis). The prevalence of substance use (e.g., tobacco, alcohol, cannabis, illicit use of opioids, and other illicit, nonprescription substances) in persons with a congenital syphilis pregnancy outcome (48.1%) was nearly double that among those with a noncongenital syphilis pregnancy outcome (24.6%). Persons with a congenital syphilis pregnancy outcome were six times as likely to report illicit use of opioids and four times as likely to report using other illicit, nonprescription substances during pregnancy than were persons with a noncongenital syphilis pregnancy outcome. Approximately one half of persons who used substances during pregnancy and had a congenital syphilis pregnancy outcome had late or no prenatal care. Tailored interventions should address barriers and facilitators to accessing screening and treatment for syphilis among persons who use substances. The need for syphilis screening and treatment should be addressed at any health care encounter during pregnancy, especially among persons who use substances.

A Preparedness Model for Mother-Baby Linked Longitudinal Surveillance for Emerging Threats.

INTRODUCTION: Public health responses often lack the infrastructure to capture the impact of public health emergencies on pregnant women and infants, with limited mechanisms for linking pregnant women with their infants nationally to monitor long-term effects. In 2019, the Centers for Disease Control and Prevention (CDC), in close collaboration with state, local, and territorial health departments, began a 5-year initiative to establish population-based mother-baby linked longitudinal surveillance, the Surveillance for Emerging Threats to Mothers and Babies Network (SET-NET). OBJECTIVES: The objective of this report is to describe an expanded surveillance approach that leverages and modernizes existing surveillance systems to address the impact of emerging health threats during pregnancy on pregnant women and their infants. METHODS: Mother-baby pairs are identified through prospective identification during pregnancy and/or identification of an infant with retrospective linking to maternal information. All data are obtained from existing data sources (e.g., electronic medical records, vital statistics, laboratory reports, and health department investigations and case reporting). RESULTS: Variables were selected for inclusion to address key surveillance questions proposed by CDC and health department subject matter experts. General variables include maternal demographics and health history, pregnancy and infant outcomes, maternal and infant laboratory results, and child health outcomes up to the second birthday. Exposure-specific modular variables are included for hepatitis C, syphilis, and Coronavirus Disease 2019 (COVID-19). The system is structured into four relational datasets (maternal, pregnancy outcomes and birth, infant/child follow-up, and laboratory testing). DISCUSSION: SET-NET provides a population-based mother-baby linked longitudinal surveillance approach and has already demonstrated rapid adaptation to COVID-19. This innovative approach leverages existing data sources and rapidly collects data and informs clinical guidance and practice. These data can help to reduce exposure risk and adverse outcomes among pregnant women and their infants, direct public health action, and strengthen public health systems.

Alcohol Use and Co-Use of Other Substances Among Pregnant Females Aged 12-44 Years - United States, 2015-2018.

Drinking alcohol during pregnancy can cause fetal alcohol spectrum disorders, including birth defects, behavioral disorders, and impaired cognitive development (1). Little is known about the co-use of other substances by females who drink during pregnancy. CDC used 2015-2018 data from the National Survey on Drug Use and Health (NSDUH) to estimate the overall and trimester-specific prevalence of self-reported drinking in the past 12 months, current drinking, and binge drinking, overall and by trimester, and the co-use of other substances among pregnant females aged 12-44 years. Past drinking (12 months) was reported by 64.7% of pregnant respondents. Current drinking (at least one drink in the past 30 days) was reported by 19.6% of respondents who were in their first trimester of pregnancy and 4.7% of respondents who were in their second or third trimester. Binge drinking (consuming four or more drinks on at least one occasion in the past 30 days) was reported by 10.5% of first trimester respondents and 1.4% of second or third trimester respondents. Overall, 38.2% of pregnant respondents who reported current drinking also reported current use of one or more other substances. The substances used most with alcohol were tobacco and marijuana. Self-reported drinking prevalence was substantially lower among second or third trimester respondents than among first trimester respondents. The American College of Obstetricians and Gynecologists (ACOG) recommends alcohol use and substance use disorders screening for all females seeking obstetric-gynecologic care and counseling patients that there is no known safe level of alcohol use during pregnancy (2).

Use of antihistamine medications during early pregnancy and selected birth defects: The National Birth Defects Prevention Study, 1997-2011.

BACKGROUND: It is estimated that approximately 10-15% of pregnant women report antihistamine use during pregnancy. Although antihistamines are generally considered safe during pregnancy, results from published studies are inconsistent. METHODS: Using a case-control study design we analyzed 41,148 pregnancies (30,091 cases and 11,057 controls) from the National Birth Defects Prevention Study (1997-2011). Logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals for 64 birth defect groupings in relation to early pregnancy exposure to 14 distinct antihistamines. Models were adjusted for maternal age, race, parity, education level, prenatal care, folic acid use, smoking and alcohol use, and study site. RESULTS: Approximately 13% of cases and controls were exposed to an antihistamine during early pregnancy. Analyses were restricted to those defects where more than five cases were exposed to the antihistamine of interest, generating 340 analyses which yielded 20 (5.9%) significant positive associations (adjusted ORs ranging from 1.21 to 4.34). CONCLUSIONS: Only a few of our findings were consistent with previous studies. There is a lack of strong evidence to conclude that birth defects are associated with exposure to antihistamines during early pregnancy.

Using Supervised Learning Methods to Develop a List of Prescription Medications of Greatest Concern during Pregnancy.

INTRODUCTION: Women and healthcare providers lack adequate information on medication safety during pregnancy. While resources describing fetal risk are available, information is provided in multiple locations, often with subjective assessments of available data. We developed a list of medications of greatest concern during pregnancy to help healthcare providers counsel reproductive-aged and pregnant women. METHODS: Prescription drug labels submitted to the U.S. Food and Drug Administration with information in the Teratogen Information System (TERIS) and/or Drugs in Pregnancy and Lactation by Briggs & Freeman were included (N = 1,186 medications; 766 from three data sources, 420 from two). We used two supervised learning methods ('support vector machine' and 'sentiment analysis') to create prediction models based on narrative descriptions of fetal risk. Two models were created per data source. Our final list included medications categorized as 'high' risk in at least four of six models (if three data sources) or three of four models (if two data sources). RESULTS: We classified 80 prescription medications as being of greatest concern during pregnancy; over half were antineoplastic agents (n = 24), angiotensin converting enzyme inhibitors (n = 10), angiotensin II receptor antagonists (n = 8), and anticonvulsants (n = 7). DISCUSSION: This evidence-based list could be a useful tool for healthcare providers counseling reproductive-aged and pregnant women about medication use during pregnancy. However, providers and patients may find it helpful to weigh the risks and benefits of any pharmacologic treatment for both pregnant women and the fetus when managing medical conditions before and during pregnancy.

Maternal occupational exposure to polycyclic aromatic hydrocarbons and the risk of isolated congenital heart defects among offspring.

BACKGROUND: Although there is evidence in experimental model systems that exposure to polycyclic aromatic hydrocarbons (PAHs) is linked with congenital heart defects (CHDs), few studies have examined the association in humans. We conducted a case-control study to examine the association between maternal exposure to PAHs and CHDs in offspring using data from the National Birth Defects Prevention Study (NBDPS) (1997-2011). METHODS: We obtained detailed information on maternal occupation during the month before to three months after conception. Expert raters, masked to case-control status, assessed job descriptions to assign categorical levels of exposure. Categories were quantitatively mapped to estimate cumulative exposure to PAHs, incorporating exposure intensity, frequency, work duration, and work hours. Quartiles were generated for cumulative maternal exposure to PAHs. Crude and adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were estimated using unconditional logistic regression for quartiles of PAH exposure and six CHD groupings (e.g. conotruncal) and specific subtypes (e.g. tetralogy of Fallot [ToF]). Final models were adjusted for maternal age, race/ethnicity, education, smoking, anticonvulsant use, folic acid supplementation, and study center. RESULTS: There were 4,775 case and 7,734 control infants eligible for the study. The prevalence of occupational exposure to PAHs was 10.2% among both case and control mothers. In adjusted analysis, compared to mothers with no occupational PAH exposure, those in the highest quartile of exposure were more likely to have offspring in the conotruncal heart defects group (OR 1.41; 95% CI 1.00-2.00), and with ToF (OR 1.83; 95% CI 1.21-2.78). CONCLUSIONS: Women in the highest quartile of estimated cumulative occupational PAH exposure during early pregnancy were more likely to have offspring with conotruncal heart defects, specifically ToF, compared to women with no occupational PAH exposure. Other comparisons between PAHs and other CHDs subgroups did not show any statistically precise associations.

Potential risk factors for Ebstein anomaly, National Birth Defects Prevention Study, 1997-2011.

BACKGROUND: Ebstein anomaly is a rare congenital heart defect (CHD) that, when severe, requires corrective surgery or other catheter-based intervention in the first year of life. Due to its rarity, risk factors for Ebstein anomaly remain largely unknown. Using national data, we examined 18 potential risk factors for Ebstein anomaly. METHODS: Using 1997-2011 data from the National Birth Defects Prevention Study, a population-based case-control study, we calculated crude and adjusted odds ratios and 95% confidence intervals for paternal age, maternal socio-demographics, reproductive history, and modifiable risk factors, and infant characteristics reported by mothers of 135 Ebstein anomaly cases and 11,829 controls. RESULTS: Mothers of Ebstein anomaly cases had 4.1 (95% confidence interval: 1.8, 9.5) times the odds of reporting a family history of CHD compared with mothers of controls. Ebstein anomaly was associated with maternal second-hand cigarette smoke exposure at home (odds ratio = 2.2 [95% confidence interval: 1.1, 4.4]), but not maternal cigarette smoking (odds ratio = 1.3 [95% confidence interval: 0.8, 2.1]). Odds were elevated, but the 95% confidence interval included 1.0, for maternal marijuana use (odds ratio = 1.8 [95% confidence interval: 0.9, 3.8]) and paternal age ≥40 years at delivery (odds ratio = 1.9 [95% confidence interval: 1.0, 3.5]). CONCLUSIONS: Maternal exposure to second-hand cigarette smoke at home and a family history of CHD were associated with elevated odds of Ebstein anomaly. Genetic analyses could clarify the potential heritability of Ebstein anomaly.

Factors associated with employment status before and during pregnancy: Implications for studies of pregnancy outcomes.

BACKGROUND: Potential confounding or effect modification by employment status is frequently overlooked in pregnancy outcome studies. METHODS: To characterize how employed and non-employed women differ, we compared demographics, behaviors, and reproductive histories by maternal employment status for 8,343 mothers of control (non-malformed) infants in the National Birth Defects Prevention Study (1997-2007) and developed a multivariable model for employment status anytime during pregnancy and the 3 months before conception. RESULTS: Sixteen factors were independently associated with employment before or during pregnancy, including: maternal age, pre-pregnancy body mass index, pregnancy intention, periconceptional/first trimester smoking and alcohol consumption, and household income. CONCLUSIONS: Employment status was significantly associated with many common risk factors for adverse pregnancy outcomes. Pregnancy outcome studies should consider adjustment or stratification by employment status. In studies of occupational exposures, these differences may cause uncontrollable confounding if non-employed women are treated as unexposed instead of excluded from analysis. Am. J. Ind. Med. 60:329-341, 2017. © 2017 Wiley Periodicals, Inc.

Maternal exposure to ozone and PM2.5 and the prevalence of orofacial clefts in four U.S. states.

BACKGROUND: While there is some evidence that maternal exposure to ambient air pollution is associated with orofacial clefts in offspring, the epidemiologic studies have been largely equivocal. We evaluated whether maternal exposure to elevated county-level ambient fine particulate matter with aerodynamic diameter ≤2.5µm (PM2.5) and ozone during early gestation was associated with a higher prevalence of orofacial clefts. METHODS: Birth data consisting of 4.7 million births from 2001 to 2007 were obtained from National Birth Defects Prevention Network for four states - Arizona, Florida, New York (excluding New York City), and Texas. The air pollution exposure assessment for gestational weeks 5-10 was based on county-level average concentrations of PM2.5 and ozone data generated using a Bayesian fusion model available through CDC's Environmental Public Health Tracking Network. Two outcomes were analyzed separately: cleft lip with or without cleft palate, cleft palate alone. In logistic regression analyses, we adjusted for factors that were suspected confounders or modifiers of the association between the prevalence of orofacial clefts and air pollution, i.e., infant sex, race-ethnicity, maternal education, smoking status during pregnancy, whether this was mother's first baby, maternal age. RESULTS: Each 10µg/m3 increase in PM2.5 concentration was significantly associated with cleft palate alone (OR =1.43, 95% CI: 1.11-1.86). There was no significant association between PM2.5 concentration and cleft lip with or without cleft palate. No associations were observed between ozone exposure and the two outcomes of orofacial clefts. CONCLUSIONS: Our study suggests that PM2.5 significantly increased the risk of cleft palate alone, but did not change the incidence of cleft lip with or without palate. Ozone levels did not correlate with incidence of orofacial clefts.

Association between antibiotic use among pregnant women with urinary tract infections in the first trimester and birth defects, National Birth Defects Prevention Study 1997 to 2011.

BACKGROUND: Previous studies noted associations between birth defects and some antibiotics (e.g., nitrofurantoin, sulfonamides) but not others (e.g., penicillins). It is unclear if previous findings were due to antibiotic use, infections, or chance. To control for potential confounding by indication, we examined associations between antibiotic use and birth defects, among women reporting urinary tract infections (UTIs). METHODS: The National Birth Defects Prevention Study is a multi-site, population-based case-control study. Case infants/fetuses have any of over 30 major birth defects and controls are live-born infants without major birth defects. We analyzed pregnancies from 1997 to 2011 to estimate the association between maternally reported periconceptional (month before conception through the third month of pregnancy) use of nitrofurantoin, trimethoprim-sulfamethoxazole, or cephalosporins and specific birth defects, among women with periconceptional UTIs. Women with periconceptional UTIs who reported penicillin use served as the comparator. RESULTS: Periconceptional UTIs were reported by 7.8% (2029/26,068) of case and 6.7% (686/10,198) of control mothers. Most (68.2% of case, 66.6% of control mothers) also reported antibiotic use. Among 608 case and 231 control mothers reporting at least one periconceptional UTI and certain antibiotic use, compared with penicillin, nitrofurantoin use was associated with oral clefts in the offspring (adjusted odds ratio, 1.97 [95% confidence interval, 1.10-3.53]), trimethoprim-sulfamethoxazole use with esophageal atresia (5.31 [1.39-20.24]) and diaphragmatic hernia (5.09 [1.20-21.69]), and cephalosporin use with anorectal atresia/stenosis (5.01 [1.34-18.76]). CONCLUSION: Periconceptional exposure to some antibiotics might increase the risk for certain birth defects. However, because individual birth defects are rare, absolute risks should drive treatment decisions.Birth Defects Research (Part A) 106:940-949, 2016.© 2016 Wiley Periodicals, Inc.

Limitations, depressive symptoms, and quality of life among a population-based sample of young adults with congenital heart defects.

BACKGROUND: Little population-based data exist on limitations and health-related quality of life (HRQoL) in adults with congenital heart defects (CHD). METHODS: We used 2004 to 2012 Medical Expenditure Panel Survey data to identify a population-based sample of young adults ages 18 to 40 years reporting health symptoms or healthcare encounters in the previous year. Comparing adults reporting CHD to others, we examined the prevalence of cognitive, physical, and activity limitations, depressive symptoms, and physical and mental HRQoL. We used chi square tests to examine differences in demographic characteristics, logistic regression to generate adjusted prevalence ratios (aPR), and linear regression to examine HRQoL. Multivariable associations were adjusted for sex, age, race/ethnicity, and smoking status. All analyses were conducted in SUDAAN using weights to account for clustering within sampling units and nonresponse. RESULTS: Fifty-nine adults reported CHD (weighted prevalence = 0.1%; representing 700,000 U.S. adults from 2004 to 2012 or, on average, 80,000 per year) and 54,011 did not. No demographic characteristics differed significantly by CHD status except health insurance; 31.5% of adults with CHD, compared with 11.0% without, reported public insurance (p = 0.01). Compared with their counterparts, adults reporting CHD had a higher prevalence of cognitive (aPR = 2.7, 95% confidence interval (CI): 1.0, 7.2), physical (aPR = 4.0, 95% CI: 1.9, 8.2), and activity limitations (aPR = 4.8, 95% CI: 2.6, 9.1), and poorer physical HRQoL (p = 0.004). No differences were observed in depressive symptoms and mental HRQoL by CHD status. CONCLUSION: Physical health and cognitive abilities of adults with CHD were compromised compared with adults without CHD. Birth Defects Research (Part A) 106:580-586, 2016. © 2016 Wiley Periodicals, Inc.

Maternal occupational exposure to polycyclic aromatic hydrocarbons and small for gestational age offspring.

OBJECTIVES: While some of the highest maternal exposures to polycyclic aromatic hydrocarbons (PAHs) occur in the workplace, there is only one previous study of occupational PAH exposure and adverse pregnancy outcomes. We sought to extend this literature using interview data combined with detailed exposure assessment. METHODS: Data for 1997-2002 were analysed from mothers of infants without major birth defects in the National Birth Defects Prevention Study, a large population-based case-control study in the USA. Maternal telephone interviews yielded information on jobs held in the month before conception through delivery. From 6252 eligible control mothers, 2803 completed the interview, had a job, met other selection criteria, and were included in the analysis. Two industrial hygienists independently assessed occupational exposure to PAHs from the interview and reviewed results with a third to reach consensus. Small for gestational age (SGA) was the only adverse pregnancy outcome with enough exposed cases to yield meaningful results. Logistic regression estimated crude and adjusted ORs. RESULTS: Of the 2803 mothers, 221 (7.9%) had infants who were SGA. Occupational PAH exposure was found for 17 (7.7%) of the mothers with SGA offspring and 102 (4.0%) of the remaining mothers. Almost half the jobs with exposure were related to food preparation and serving. After adjustment for maternal age, there was a significant association of occupational exposure with SGA (OR=2.2, 95% CI 1.3 to 3.8). CONCLUSIONS: Maternal occupational exposure to PAHs was found to be associated with increased risk of SGA offspring.

Maternal exposure to criteria air pollutants and congenital heart defects in offspring: results from the national birth defects prevention study.

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.

Late detection of critical congenital heart disease among US infants: estimation of the potential impact of proposed universal screening using pulse oximetry.

IMPORTANCE: Critical congenital heart disease (CCHD) was added to the Recommended Uniform Screening Panel for Newborns in the United States in 2011. Many states have recently adopted or are considering requirements for universal CCHD screening through pulse oximetry in birth hospitals. Limited previous research is directly applicable to the question of how many US infants with CCHD might be identified through screening. OBJECTIVES: To estimate the proportion of US infants with late detection of CCHD (>3 days after birth) based on existing clinical practice and to investigate factors associated with late detection. DESIGN, SETTING, AND PARTICIPANTS: Descriptive and multivariable analysis. Data were obtained from a multisite population-based study of birth defects in the United States, the National Birth Defects Prevention Study (NBDPS). We included all live-born infants with estimated dates of delivery from January 1, 1998, through December 31, 2007, and nonsyndromic, clinically verified CCHD conditions potentially detectable through screening via pulse oximetry. MAIN OUTCOMES AND MEASURES: The main outcome measure was the proportion of infants with late detection of CCHD through echocardiography or at autopsy under the assumption that universal screening at birth hospitals might reduce the number of such late diagnoses. Secondary outcome measures included prevalence ratios for associations between selected demographic and clinical factors and late detection of CCHD. RESULTS: Of 3746 live-born infants with nonsyndromic CCHD, late detection occurred in 1106 (29.5% [95% CI, 28.1%-31.0%]), including 6 (0.2%) (0.1%-0.4%) first receiving a diagnosis at autopsy more than 3 days after birth. Late detection varied by CCHD type from 9 of 120 infants (7.5% [95% CI, 3.5%-13.8%]) with pulmonary atresia to 497 of 801 (62.0% [58.7%-65.4%]) with coarctation of the aorta. In multivariable analysis, late detection varied significantly by CCHD type and study site, and infants with extracardiac defects were significantly less likely to have late detection of CCHD (adjusted prevalence ratio, 0.58 [95% CI, 0.49-0.69]). CONCLUSIONS AND RELEVANCE: We estimate that 29.5% of live-born infants with nonsyndromic CCHD in the NBDPS received a diagnosis more than 3 days after birth and therefore might have benefited from routine CCHD screening at birth hospitals. The number of infants in whom CCHD was detected through screening likely varies by several factors, including CCHD type. Additional population-based studies of screening in practice are needed.

Maternal occupational exposure to polycyclic aromatic hydrocarbons and congenital heart defects among offspring in the national birth defects prevention study.

BACKGROUND: There is evidence in experimental model systems that exposure to polycyclic aromatic hydrocarbons (PAHs) results in congenital heart defects (CHDs); however, to our knowledge, this relationship has not been examined in humans. Therefore, we conducted a case-control study assessing the association between estimated maternal occupational exposure to PAHs and CHDs in offspring. METHODS: Data on CHD cases and control infants were obtained from the National Birth Defects Prevention Study for the period of 1997 to 2002. Exposure to PAHs was assigned by industrial hygienist consensus, based on self-reported maternal occupational histories from 1 month before conception through the third month of pregnancy. Logistic regression was used to evaluate the association between maternal occupational PAH exposure and specific CHD phenotypic subtypes among offspring. RESULTS: The prevalence of occupational PAH exposure was 4.0% in CHD case mothers (76/1907) and 3.6% in control mothers (104/2853). After adjusting for maternal age, race or ethnicity, education, smoking, folic acid supplementation, and study center, exposure was not associated with conotruncal defects (adjusted odds ratio [AOR], 0.98; 95% confidence interval [CI], 0.58-1.67), septal defects (AOR, 1.28; 95% CI, 0.86-1.90), or with any isolated CHD subtype. CONCLUSIONS: Our findings do not support an association between potential maternal occupational exposure to PAHs and various CHDs in a large, population-based study. For CHD phenotypic subtypes in which modest nonsignificant associations were observed, future investigations could be improved by studying populations with a higher prevalence of PAH exposure and by incorporating information on maternal and fetal genotypes related to PAH metabolism. Birth Defects Research (Part A), 2012.

Association between maternal occupational exposure to organic solvents and congenital heart defects, National Birth Defects Prevention Study, 1997-2002.

OBJECTIVE: To examine the relation between congenital heart defects (CHDs) in offspring and estimated maternal occupational exposure to chlorinated solvents, aromatic solvents and Stoddard solvent during the period from 1 month before conception through the first trimester. METHODS: The study population included mothers of infants with simple isolated CHDs and mothers of control infants who delivered from 1997 through 2002 and participated in the National Birth Defects Prevention Study. Two methods to assess occupational solvent exposure were employed: an expert consensus-based approach and a literature-based approach. Multiple logistic regression was used to calculate adjusted ORs and 95% CIs for the association between solvent classes and CHDs. RESULTS: 2951 control mothers and 2047 CHD case mothers were included. Using the consensus-based approach, associations were observed for exposure to any solvent and any chlorinated solvent with perimembranous ventricular septal defects (OR 1.6, 95% CI 1.0 to 2.6 and OR 1.7, 95% CI 1.0 to 2.8, respectively). Using the literature-based approach, associations were observed for: any solvent exposure with aortic stenosis (OR 2.1, 95% CI 1.1 to 4.1) and Stoddard solvent exposure with d-transposition of the great arteries (OR 2.0, 95% CI 1.0 to 4.2), right ventricular outflow tract obstruction defects (OR 1.9, 95% CI 1.1 to 3.3) and pulmonary valve stenosis (OR 2.1, 95% CI 1.1 to 3.8). CONCLUSIONS: The authors found evidence of associations between occupational exposure to solvents and several types of CHDs. These results should be interpreted in light of the potential for misclassification of exposure.

Maternal smoking and congenital heart defects in the Baltimore-Washington Infant Study.

OBJECTIVE: We investigated associations between maternal cigarette smoking during the first trimester and the risk of congenital heart defects (CHDs) among the infants. METHODS: The Baltimore-Washington Infant Study was the first population-based case-control study of CHDs conducted in the United States. Case and control infants were enrolled during the period 1981-1989. We excluded mothers with overt pregestational diabetes and case mothers whose infants had noncardiac anomalies (with the exception of atrioventricular septal defects with Down syndrome) from the analysis, which resulted in 2525 case and 3435 control infants. Self-reported first-trimester maternal cigarette consumption was ascertained via an in-person interview after delivery. Associations for 26 different groups of CHDs with maternal cigarette consumption were estimated by using logistic regression models. Odds ratios (ORs) corresponded to a 20-cigarette-per-day increase in consumption. RESULTS: We observed statistically significant positive associations between self-reported first-trimester maternal cigarette consumption and the risk of secundum-type atrial septal defects (OR: 1.36 [95% confidence interval (CI): 1.04-1.78]), right ventricular outflow tract defects (OR: 1.32 [95% CI: 1.06-1.65]), pulmonary valve stenosis (OR: 1.35 [95% CI: 1.05-1.74]), truncus arteriosus (OR: 1.90 [95% CI: 1.04-3.45]), and levo-transposition of the great arteries (OR: 1.79 [95% CI: 1.04-3.10]). A suggestive association was observed for atrioventricular septal defects among infants without Down syndrome (OR: 1.50 [95% CI: 0.99-2.29]). CONCLUSIONS: These findings add to the existing body of evidence that implicates first-trimester maternal cigarette smoking as a modest risk factor for select CHD phenotypes.

Including prenatal diagnoses in birth defects monitoring: Experience of the Metropolitan Atlanta Congenital Defects Program.

BACKGROUND: Advances in prenatal diagnosis have led to changes in the management of pregnancies affected with birth defects. These changes pose unique challenges for birth defects monitoring programs which use hospital-based sources. METHODS: In 1994, Metropolitan Atlanta Congenital Defects Program (MACDP) abstractors began to visit area perinatologists' offices to identify pregnancies diagnosed prenatally with fetal defects. These pregnancies were then linked with existing MACDP cases and the hospital deliveries abstracted. Those without a hospital delivery were included as having unknown outcomes. Prenatally diagnosed defects were classified as definite or possible based on the certainty of the prenatal description. For 1995-2004, we calculated minimum and maximum adjusted defect prevalences by adding definite prenatal defects, and definite plus possible prenatal defects, to the hospital-based cases. RESULTS: We identified 1009 pregnancies with a prenatally diagnosed defect not ascertained from MACDP hospital sources. Including these increased the total defect prevalence from 28 per 1000 live births to a minimum of 29.94 (6.9% increase) and maximum of 30.14 (7.7% increase) per 1000. The minimum increase was greater than 50% for conjoined twins, triploidy, craniorachischisis, cystic hygroma, Klinefelter syndrome, anencephaly, Turner syndrome, and trisomies 13, 18 and 21 among mothers >or=35. CONCLUSIONS: These data reflect the variety of congenital abnormalities that can be detected prenatally and the importance of including prenatal diagnoses in birth defects monitoring data. Birth defects monitoring programs should assess individually the extent to which prenatal diagnosis can affect the accuracy and completeness of their data. Birth Defects Research (Part A), 2009. Published 2008 Wiley-Liss, Inc.