Adrienne T. Hoyt

Is maternal parity an independent risk factor for birth defects

BACKGROUND Although associations between maternal parity and birth defects have been observed previously, few studies have focused on the possibility that parity is an independent risk factor for birth defects. We investigated the relation between levels of parity and a range of birth defects, adjusting each defect group for the same covariates. METHODS We included infants who had an estimated delivery date between 1997 and 2007 and participated in the National Birth Defects Prevention Study, a multisite case-control study. Cases included infants or fetuses belonging to 38 phenotypes of birth defects (n = 17,908), and controls included infants who were unaffected by a major birth defect (n = 7173). Odds ratios (ORs) were adjusted for 12 covariates using logistic regression. RESULTS Compared with primiparous mothers, nulliparous mothers were more likely to have infants with amniotic band sequence, hydrocephaly, esophageal atresia, hypospadias, limb reduction deficiencies, diaphragmatic hernia, omphalocele, gastroschisis, tetralogy of Fallot, and septal cardiac defects, with significant ORs (1.2 to 2.3). Compared with primiparous mothers, multiparous mothers had a significantly increased risk of omphalocele, with an OR of 1.5, but had significantly decreased risk of hypospadias and limb reduction deficiencies, with ORs of 0.77 and 0.77. CONCLUSIONS Nulliparity was associated with an increased risk of specific phenotypes of birth defects. Most of the phenotypes associated with nulliparity in this study were consistent with those identified by previous studies. Research into biologic or environmental factors that are associated with nulliparity may be helpful in explaining some or all of these associations.

Maternal thyroid disease, thyroid medication use, and selected birth defects in the National Birth Defects Prevention Study.

BACKGROUND Although thyroid disorders are present in approximately 3% of pregnant women, little is known about the association between maternal thyroid disease and birth defects. METHODS We assessed the association between maternal thyroid disease, thyroid medication use, and 38 types of birth defects among 14,067 cases and 5875 controls in the National Birth Defects Prevention Study, a multisite, population-based, case-control study. Infants in this study were born between October 1997 and December 2004. Information on exposures including maternal diseases and use of medications was collected by telephone interview. RESULTS We found statistically significant associations between maternal thyroid disease and left ventricular outflow tract obstruction heart defects (1.5; 95% CI, 1.0-2.3), hydrocephaly (2.9; 95% CI, 1.6-5.2), hypospadias (1.6; 95% CI, 1.0-2.5), and isolated anorectal atresia (2.4; 95% CI, 1.2-4.6). Estimates for the association between periconceptional use of thyroxine and specific types of birth defects were similar to estimates for any thyroid disease. Given that antithyroid medication use was rare, we could not adequately assess risks for their use for most case groups. CONCLUSIONS Our results are consistent with the positive associations between maternal thyroid disease or thyroid medication use and both hydrocephaly and hypospadias observed in some previous studies. New associations with left ventricular outflow tract obstruction heart defects and anorectal atresia may be chance findings.

Maternal caffeine intake and risk of selected birth defects in the National Birth Defects Prevention Study.

BACKGROUND Caffeine intake is common during pregnancy, yet few epidemiologic studies have examined the association between maternal caffeine consumption and birth defects. Using data from the National Birth Defects Prevention Study (NBDPS), we examined the association between maternal caffeine consumption and anotia/microtia, esophageal atresia, small intestinal atresia, craniosynostosis, diaphragmatic hernia, omphalocele, and gastroschisis. METHODS The NBDPS is a multi-site population-based case-control study. The present analysis included 3,346 case infants and 6,642 control infants born from October 1997 through December 2005. Maternal telephone interview reports of demographic characteristics and conditions and exposures before and during pregnancy were collected. Odds ratios and 95% confidence intervals, adjusted for relevant covariates, were calculated to estimate the associations between maternal dietary caffeine intake (coffee, tea, soda, and chocolate) and maternal use of caffeine-containing medications and each defect. RESULTS We observed small, statistically significant elevations in adjusted odds ratios ranging from 1.3 to 1.8 for total maternal dietary caffeine intake or specific types of caffeinated beverages and anotia/microtia, esophageal atresia, small intestinal atresia, and craniosynostosis; however, dose-response patterns were absent. Periconceptional use of caffeine-containing medications was infrequent and estimates were imprecise. CONCLUSIONS We did not find convincing evidence of an association between maternal caffeine intake and the birth defects included in this study. The increasing popularity of caffeine-containing energy drinks and other caffeinated products may result in higher caffeine intake among women of childbearing age. Future studies should consider more detailed evaluation of such products.

Maternal occupational exposure to polycyclic aromatic hydrocarbons and risk of neural tube defect‐affected pregnancies

BACKGROUND This study evaluated whether there is an association between maternal occupational exposure to polycyclic aromatic hydrocarbons (PAHs) and neural tube defects (NTDs) in offspring. This is the first such study of which the authors are aware. METHODS Data were analyzed from 1997 to 2002 deliveries in the National Birth Defects Prevention Study, a large population-based case-control study in the United States. Maternal interviews yielded information on jobs held in the month before through 3 months after conception. Three industrial hygienists blinded to case or control status assessed occupational exposure to PAHs. Crude and adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were estimated using unconditional logistic regression. RESULTS Of the 520 mothers of children with NTDs, 5.0% were classified as exposed to occupational PAHs, as were 3.5% of the 2989 mothers of controls. The crude OR for PAH exposure was 1.43 (95% CI, 0.92-2.22) for any NTD and 1.71 (95% CI, 1.03-2.83) for spina bifida. Adjusted ORs were smaller in magnitude and not significant. Among women who were normal weight or underweight, the crude OR for spina bifida was 3.13 (95% CI, 1.63-6.03) and adjusted OR was 2.59 (95% CI, 1.32-5.07). Based on estimated cumulative exposure, a statistically significant dose-response trend was observed for spina bifida; however, it was attenuated and no longer significant after adjustment. CONCLUSION Maternal occupational exposure to PAHs may be associated with increased risk of spina bifida in offspring among women who are normal weight or underweight. Other comparisons between PAHs and NTDs were consistent with no association.

Associations between maternal periconceptional exposure to secondhand tobacco smoke and major birth defects

BACKGROUND While associations between secondhand smoke and a few birth defects (namely, oral clefts and neural tube defects) have been noted in the scientific literature, to our knowledge, there is no single or comprehensive source of population-based information on its associations with a range of birth defects among nonsmoking mothers. OBJECTIVE We utilized data from the National Birth Defects Prevention Study, a large population-based multisite case-control study, to examine associations between maternal reports of periconceptional exposure to secondhand smoke in the household or workplace/school and major birth defects. STUDY DESIGN The multisite National Birth Defects Prevention Study is the largest case-control study of birth defects to date in the United States. We selected cases from birth defect groups having >100 total cases, as well as all nonmalformed controls (10,200), from delivery years 1997 through 2009; 44 birth defects were examined. After excluding cases and controls from multiple births and whose mothers reported active smoking or pregestational diabetes, we analyzed data on periconceptional secondhand smoke exposure-encompassing the period 1 month prior to conception through the first trimester. For the birth defect craniosynostosis, we additionally examined the effect of exposure in the second and third trimesters as well due to the potential sensitivity to teratogens for this defect throughout pregnancy. Covariates included in all final models of birth defects with ≥5 exposed mothers were study site, previous live births, time between estimated date of delivery and interview date, maternal age at estimated date of delivery, race/ethnicity, education, body mass index, nativity, household income divided by number of people supported by this income, periconceptional alcohol consumption, and folic acid supplementation. For each birth defect examined, we used logistic regression analyses to estimate both crude and adjusted odds ratios and 95% confidence intervals for both isolated and total case groups for various sources of exposure (household only; workplace/school only; household and workplace/school; household or workplace/school). RESULTS The prevalence of secondhand smoke exposure only across all sources ranged from 12.9-27.8% for cases and 14.5-15.8% for controls. The adjusted odds ratios for any vs no secondhand smoke exposure in the household or workplace/school and isolated birth defects were significantly elevated for neural tube defects (anencephaly: adjusted odds ratio, 1.66; 95% confidence interval, 1.22-2.25; and spina bifida: adjusted odds ratio, 1.49; 95% confidence interval, 1.20-1.86); orofacial clefts (cleft lip without cleft palate: adjusted odds ratio, 1.41; 95% confidence interval, 1.10-1.81; cleft lip with or without cleft palate: adjusted odds ratio, 1.24; 95% confidence interval, 1.05-1.46; cleft palate alone: adjusted odds ratio, 1.31; 95% confidence interval, 1.06-1.63); bilateral renal agenesis (adjusted odds ratio, 1.99; 95% confidence interval, 1.05-3.75); amniotic band syndrome-limb body wall complex (adjusted odds ratio, 1.66; 95% confidence interval, 1.10-2.51); and atrial septal defects, secundum (adjusted odds ratio, 1.37; 95% confidence interval, 1.09-1.72). There were no significant inverse associations observed. CONCLUSION Additional studies replicating the findings are needed to better understand the moderate positive associations observed between periconceptional secondhand smoke and several birth defects in this analysis. Increased odds ratios resulting from chance (eg, multiple comparisons) or recall bias cannot be ruled out.

Maternal occupational exposure to polycyclic aromatic hydrocarbons and risk of oral cleft-affected pregnancies.

Objective To evaluate whether there is an association between maternal occupational exposure to polycyclic aromatic hydrocarbons and oral clefts in offspring. This is the first human study of polycyclic aromatic hydrocarbons and clefts of which the authors are aware. Design Case-control study. Setting, Participants Data for 1997 to 2002 from the National Birth Defects Prevention Study, a large population-based case-control study in the United States, were analyzed. Maternal telephone interviews yielded information on jobs held in the month before through 3 months after conception. Two industrial hygienists independently assessed occupational exposure to polycyclic aromatic hydrocarbons; all jobs rated as exposed or with rating difficulty were reviewed with a third industrial hygienist to reach consensus on all exposure parameters. Logistic regression estimated crude and adjusted odds ratios with 95% confidence intervals for cleft lip with or without cleft palate and cleft palate alone. Results There were 2989 controls (3.5% exposed), 805 cases of cleft lip with or without cleft palate (5.8% exposed), and 439 cases of cleft palate alone (4.6% exposed). The odds of maternal occupational exposure to polycyclic aromatic hydrocarbons (any versus none) during pregnancy was increased for cleft lip with or without cleft palate cases as compared with controls (odds ratio, 1.69; 95% confidence interval, 1.18 to 2.40); the odds ratio was 1.47 (95% confidence interval 1.02 to 2.12) when adjusted for maternal education. There was a statistically significant adjusted exposure-response relationship for cleft lip with or without cleft palate (Ptrend = .02). Odd ratios for cleft palate alone were not statistically significant. Conclusions Maternal occupational exposure to polycyclic aromatic hydrocarbons was associated with increased risk of cleft lip with or without cleft palate in offspring.

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.

Data linkage between the national birth defects prevention study and the occupational information network (O*NET) to assess workplace physical activity, sedentary behaviors, and emotional stressors during pregnancy

BACKGROUND Knowledge of the prevalence of work-related physical activities, sedentary behaviors, and emotional stressors among pregnant women is limited, and the extent to which these exposures vary by maternal characteristics remains unclear. METHODS Data on mothers of 6,817 infants without major birth defects, with estimated delivery during 1997 through 2009 who worked during pregnancy were obtained from the National Birth Defects Prevention Study. Information on multiple domains of occupational exposures was gathered by linking mothers primary job to the Occupational Information Network Version 9.0. RESULTS The most frequent estimated physical activity associated with jobs during pregnancy was standing. Of 6,337 mothers, 31.0% reported jobs associated with standing for ≥75% of their time. There was significant variability in estimated occupational exposures by maternal age, race/ethnicity, and educational level. CONCLUSIONS Our findings augment existing literature on occupational physical activities, sedentary behaviors, emotional stressors, and occupational health disparities during pregnancy.

Role of maternal occupational physical activity and psychosocial stressors on adverse birth outcomes

Objectives We examined the association of an array of estimated maternal occupational physical activities and psychosocial stressors during pregnancy with odds for preterm birth (PTB) and small-for-gestational age (SGA). Methods Data for infants born without major birth defects delivered from 1997 to 2009 whose mothers reported working at least 1 month during pregnancy were obtained from the National Birth Defects Prevention Study. We linked occupational codes to the US Department of Labors Occupational Information Network, which provides estimates of exposure for multiple domains of physical activity and psychosocial stressors by occupational categories. We conducted factor analysis using principal components extraction with 17 occupational activities and calculated factor scores. ORs for PTB and SGA across quartiles of factor scores in each trimester were computed using logistic regression. Results Factor analysis grouped occupational domains into 4 groups based on factor loadings. These groups were ‘occupational physical activity’, ‘interpersonal stressor’, ‘automated work’ and ‘job responsibility’. High levels of ‘occupational physical activity’ were significantly associated with SGA (adjusted OR (AOR) for highest quartile compared with lowest quartile of factor score: 1.36; 95% CIs 1.02 to 1.82; p for trend=0.001) and were also positively associated with PTB (AOR: 1.24; 95% CI 0.93 to 1.64; p for trend=0.01). No clear results were observed across domains of psychosocial stressors. Conclusions Our findings expand understanding of associations between occupational physical activity and psychosocial stressors and PTB and SGA and suggest that additional research is needed to further examine these relationships.

Periconceptional Risk Factors for Birth Defects among Younger and Older Teen Mothers.

STUDY OBJECTIVES We sought to determine whether selected periconceptional health behaviors that influence risk for birth defects differ between older and younger adolescents and whether pregnancy intention predicts more positive preconception health behaviors among teens. DESIGN AND PARTICIPANTS We analyzed interview responses from 954 adolescent control group participants from the National Birth Defects Prevention Study who delivered live infants during 1997-2007. MAIN OUTCOME MEASURES Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were calculated for factors of interest by age categories (13-15, 16-17, and 18 years, relative to 19 years). To construct a composite periconceptional behavior index, we summed the following healthy behaviors: nonsmoker, nondrinker, folic acid supplementation, and eating 5 or more servings of fruits and vegetables per day. RESULTS Analyses indicated that women in the youngest group (13-15 years of age) were more likely to be Hispanic (aOR 2.83, 95% CI 1.40-5.70) and less likely to engage in some unhealthy pregnancy-related behaviors compared with 19-year-olds, such as smoking (aOR 0.45, 95% CI 0.20-0.99) and being overweight or obese (aOR 0.32, 95% CI 0.16-0.61). However, they were also less likely to have taken periconceptional folic acid (aOR 0.44, 95% CI 0.21-0.90). About one-third of teen mothers indicated that their pregnancies had been intended. Among 18- and 19-year-olds, this predicted a higher mean value for the composite periconceptional behavior index (2.30 versus 1.94, P ≤ .01). CONCLUSIONS Teen mothers are not a homogeneous group. Each age subgroup presents varied demographic and behavioral factors that put them at varying levels of risk for birth defects. Furthermore, caregivers should not assume that teens do not plan pregnancies or that they need not be informed of the importance of periconceptional health.