Prenatal Exposure to Tobacco and Childhood Cognition and Behavior: Effect Modification by Maternal Folate Intake and Breastfeeding Duration.

In this exploratory analysis, we assessed whether nutrition modified the association between prenatal exposure to tobacco and childhood cognition/behavior among 366 Colorado-based mothers and their offspring (born ≥ 37 weeks with birthweights ≥ 2500 g). Interaction by folate ( 5 months, but not for shorter durations. Our findings support the need for smoking cessation campaigns throughout pregnancy and throughout the postpartum period breastfeeding to reduce neurobehavioral risks in the offspring.

Fish consumption prior to pregnancy and pregnancy outcomes in the National Birth Defects Prevention Study, 1997-2011.

OBJECTIVE: To evaluate the relationships between maternal fish consumption and pregnancy outcomes in a large, population-based sample of women in the USA. DESIGN: We collected average fish consumption prior to pregnancy using a modified version of the semi-quantitative Willett FFQ. We estimated adjusted OR (aOR) and 95 % CI for associations between different levels of fish consumption and preterm birth (<37 weeks), early preterm birth (<32 and <35 weeks) and small-for-gestational-age infants (SGA; <10th percentile). SETTING: The National Birth Defects Prevention Study (NBDPS). SUBJECTS: Control mother-infant pairs with estimated delivery dates between 1997 and 2011 (n 10 919). RESULTS: No significant associations were observed between fish consumption and preterm birth or early preterm birth (aOR = 0·7-1·0 and 0·7-0·9, respectively). The odds of having an SGA infant were elevated (aOR = 2·1; 95 % CI 1·2, 3·4) among women with daily fish consumption compared with women consuming fish less than once per month. No associations were observed between other levels of fish consumption and SGA (aOR = 0·8-1·0). CONCLUSIONS: High intake of fish was associated with twofold higher odds of having an SGA infant, while moderate fish consumption prior to pregnancy was not associated with preterm or SGA. Our study, like many other studies in this area, lacked information regarding preparation methods and the specific types of fish consumed. Future studies should incorporate information on nutrient and contaminant contents, preparation methods and biomarkers to assess these relationships.

Does Maternal Exposure to Secondhand Tobacco Smoke During Pregnancy Increase the Risk for Preterm or Small-for-Gestational Age Birth?

Introduction While associations between active smoking and various adverse birth outcomes (ABOs) have been reported in the literature, less is known about the impact of secondhand smoke (SHS) on many pregnancy outcomes. Methods We examined the relationship between maternal exposure to SHS during pregnancy and preterm (< 37 weeks gestation) and small-for-gestational age (SGA; assessed using sex-, race/ethnic-, and parity-specific growth curves) singleton births using non-smoking controls from the National Birth Defects Prevention Study (1997-2011). Multivariable logistic regression models for household, workplace/school, and combined SHS exposure-controlled for maternal education, race/ethnicity, pre-pregnancy body mass index, and high blood pressure-were used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs). Interaction was assessed for maternal folic acid supplementation, alcohol use, age at delivery, and infant sex. Results Infants of 8855 mothers were examined in the preterm birth analysis with 666 (7.5%) categorized as preterm, 574 moderately preterm (32-36 weeks), and 92 very preterm (< 32 weeks). For the SGA analysis, infants of 8684 mothers were examined with 670 (7.7%) categorized as SGA. The aORs for mothers reporting both household and workplace/school SHS were elevated for preterm (aOR 1.99; 95% CI 1.13-3.50) and moderately preterm birth (32-36 weeks) (aOR 2.17; 95% CI 1.22-3.88). No results for the SGA analysis achieved significance, nor was evidence of interaction evident. Conclusion The findings suggest an association between SHS from multiple exposure sources and preterm birth, but no evidence for association with SGA births. Continued study of SHS and ABOs is needed to best inform public health prevention programs.

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 Labor's 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.

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.

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 mother's 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.

Nitrosatable Drug Exposure during Pregnancy and Preterm and Small-for-Gestational-Age Births.

BACKGROUND: Nitrosatable drugs react with nitrite in the stomach to form N-nitroso compounds, observed in animal models to result in adverse pregnancy outcomes, such as birth defects and reduced fetal weight. Previous studies examining prenatal exposure to medications classified as nitrosatable have reported an increased risk of preterm births (PTBs) and small-for-gestational-age (SGA) infants. METHODS: Using data from mothers (controls) of babies without major birth defects from the National Birth Defects Prevention Study, prenatal nitrosatable drug usage by trimester and month of gestation was examined in relation to PTBs and SGA infants. RESULTS: Positive associations were observed with nitrosatable drug use and PTBs, with the strongest relationship with second trimester exposure (adjusted hazard ratio [aHR] 1.37, [95% confidence interval (CI) 1.10, 1.70]). Of the nitrosatable functional groups, secondary amines were the most notable, with a higher association among women with second (aHR 1.37, [95% CI 1.05, 1.79]) and third (aHR 1.34, [95% CI 1.02, 1.76]) trimester exposure compared with women with no prenatal nitrosatable drug use. Among SGA infants, a borderline association was noted with amide exposure during the third trimester (adjusted odds ratio 1.43 [95% confidence interval [CI] 1.00, 2.05]). CONCLUSIONS: Prenatal exposure to nitrosatable drugs during the second and third trimester of pregnancy, particularly secondary amines, might increase the risk of PTBs. However, prenatal exposure to nitrosatable drugs was not associated with SGA infants, with the exception of amide drugs.

Sociodemographic and hispanic acculturation factors and isolated anotia/microtia.

BACKGROUND: It has been observed in several studies that infants with anotia/microtia are more common among Hispanics compared with other racial/ethnic groups. We examined the association between selected Hispanic ethnicity and acculturation factors and anotia/microtia in the National Birth Defects Prevention Study. METHODS: We examined data from mothers of 351 infants with isolated anotia/microtia and 8435 unaffected infants from the National Birth Defects Prevention Study with an expected delivery date from 1997 to 2007. Sociodemographic, maternal, and acculturation factors (e.g., age, maternal education, household income, body mass index, gestational diabetes, folic acid, smoking, alcohol intake, study center, parental birthplace, and years lived in the United States, maternal language) were assessed as overall risk factors and also as risk factors among subgroups of Hispanics (United States- and foreign-born) versus non-Hispanic whites. RESULTS: Compared with non-Hispanic whites, both United States- and foreign-born Hispanic mothers demonstrated substantially higher odds of delivering infants with anotia/microtia across nearly all strata of sociodemographic and other maternal factors (adjusted odds ratios range: 2.1-11.9). The odds of anotia/microtia was particularly elevated among Hispanic mothers who emigrated from Mexico after age five (adjusted odds ratios = 4.88; 95% confidence interval = 2.93-8.11) or who conducted the interview in Spanish (adjusted odds ratios = 4.97; 95% confidence interval = 3.00-8.24). CONCLUSION: We observed that certain sociodemographic and acculturation factors are associated with higher risks of anotia/microtia among offspring of Hispanic mothers.

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 caffeine consumption and small for gestational age births: results from a population-based case-control study.

Caffeine is consumed in various forms during pregnancy, has increased half-life during pregnancy and crosses the placental barrier. Small for gestational age (SGA) is an important perinatal outcome and has been associated with long term complications. We examined the association between maternal caffeine intake and SGA using National Birth Defects Prevention Study data. Non-malformed live born infants with an estimated date of delivery from 1997-2007 (n = 7,943) were included in this analysis. Maternal caffeine exposure was examined as total caffeine intake and individual caffeinated beverage type (coffee, tea, and soda); sex-, race/ethnic-, and parity-specific growth curves were constructed to estimate SGA births. Crude and adjusted odds ratios (aORs) and 95% confidence intervals were estimated using unconditional logistic regression. Interaction with caffeine exposures was assessed for maternal smoking, vasoconstrictor medication use, and folic acid. Six hundred forty-eight infants (8.2%) were found to be SGA in this analysis. Increasing aORs were observed for increasing intakes of total caffeine and for each caffeinated beverage with aORs (adjusting for maternal education, high blood pressure, and smoking) ranging from 1.3 to 2.1 for the highest intake categories (300+ mg/day total caffeine and 3+ servings/day for each beverage type). Little indication of additive interaction by maternal smoking, vasoconstrictor medication use, or folic acid intake was observed. We observed an increase in SGA births for mothers with higher caffeine intake, particularly for those consuming 300+ mg of caffeine per day. Increased aORs were also observed for tea intake but were more attenuated for coffee and soda intake.

Newborn screening analytes and structural birth defects among 27,000 newborns.

BACKGROUND: Emerging evidence suggests newborn screening analytes may yield insights into the etiologies of birth defects, yet no effort has evaluated associations between a range of newborn screening analytes and birth defects. METHODS: This population-based study pooled statewide data on birth defects, birth certificates, and newborn screening analytes from Texas occurring between January 1, 2007 and December 31, 2009. Associations between a panel of thirty-six newborn screening analytes, collected by the statewide Texas Newborn Screening Program, and the presence of a birth defect, defined as at least one of 39 birth defects diagnoses recorded by the Texas Birth Defects Registry, were assessed using regression analysis. FINDINGS: Of the 27,643 births identified, 20,205 had at least one of the 39 birth defects of interest (cases) as identified by the Texas Birth Defects Registry, while 7,438 did not have a birth defect (controls). Among 1,404 analyte-birth defect associations evaluated, 377 were significant in replication analysis. Analytes most consistently associated with birth defects included the phenylalanine/tyrosine ratio (N = 29 birth defects), tyrosine (N = 28 birth defects), and thyroxine (N = 25 birth defects). Birth defects most frequently associated with a range of analytes included gastroschisis (N = 29 analytes), several cardiovascular defects (N = 26 analytes), and spina bifida (N = 23 analytes). CONCLUSIONS: Several significant and novel associations were observed between newborn screening analytes and birth defects. While some findings could be consequences of the defects themselves or to the care provided to infants with these defects, these findings could help to elucidate mechanisms underlying the etiology of some birth defects.

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.

Sunspot activity and birth defects among Texas births (1999-2016).

BACKGROUND: Building on findings that linked higher levels of sunspot (SS) activity with a range of health and adverse birth outcomes, we sought to understand how SS activity over a 17-year time period may be correlated with the occurrence of birth defects. METHODS: Data from the Texas Birth Defects Registry, vital events from the Texas Center for Health Statistics, and mean monthly numbers of sunspots from the National Oceanic and Atmospheric Administration were utilized. Poisson regression was used to calculate crude/adjusted prevalence ratios (cPRs/aPRs) and 95% confidence intervals for three quartiles (Q) of increasing SS activity (compared to a referent of low activity) and 44 birth defects (31 non-cardiac; 13 cardiac) with estimated dates of conception from 1998 to 2016. RESULTS: We found moderately protective aPRs (range: 0.60-0.89) in a little over half of the case groups examined in our quartiles of higher SS activity (19 non-cardiac; 6 cardiac), after adjusting for maternal age, race/ethnicity, and education. Particularly protective aPRs in the highest SS quartiles (Q3-4) were noted for: anophthalmia, cataract, gastroschisis, trisomy 18, ventricular septal defects, atrial septal defects, and pulmonary valve atresia or stenosis. Conversely, modestly elevated aPRs were noted for two defect groups (agenesis, aplasia, and hypoplasia of the lung and microcephaly [Q2-3]). Following an additional adjustment of year of conception, results remained similar although many of the estimates were attenuated. CONCLUSION: The seemingly protective associations between increasing SS activity may be an artifact of increasing spontaneous abortions that occur following conception during these periods of heightened SS activity.

Associations between Prenatal and Postnatal Exposure to Cannabis with Cognition and Behavior at Age 5 Years: The Healthy Start Study.

BACKGROUND: Prenatal exposure to cannabis may influence childhood cognition and behavior, but the epidemiologic evidence is mixed. Even less is known about the potential impact of secondhand exposure to cannabis during early childhood. OBJECTIVE: This study sought to assess whether prenatal and/or postnatal exposure to cannabis was associated with childhood cognition and behavior. STUDY DESIGN: This sub-study included a convenience sample of 81 mother-child pairs from a Colorado-based cohort. Seven common cannabinoids (including delta 9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD)) and their metabolites were measured in maternal urine collected mid-gestation and child urine collected at age 5 years. Prenatal and postnatal exposure to cannabis was dichotomized as exposed (detection of any cannabinoid) and not exposed. Generalized linear models examined the associations between prenatal or postnatal exposure to cannabis with the NIH Toolbox and Child Behavior Checklist T-scores at age 5 years. RESULTS: In this study, 7% (n = 6) of the children had prenatal exposure to cannabis and 12% (n = 10) had postnatal exposure to cannabis, with two children experiencing this exposure at both time points. The most common cannabinoid detected in pregnancy was Δ9-THC, whereas the most common cannabinoid detected in childhood was CBD. Postnatal exposure to cannabis was associated with more aggressive behavior (ß: 3.2; 95% CI: 0.5, 5.9), attention deficit/hyperactivity problems (ß: 8.0; 95% CI: 2.2, 13.7), and oppositional/defiant behaviors (ß: 3.2; 95% CI: 0.2, 6.3), as well as less cognitive flexibility (ß: -15.6; 95% CI: -30.0, -1.2) and weaker receptive language (ß: -9.7; 95% CI: -19.2, -0.3). By contrast, prenatal exposure to cannabis was associated with fewer internalizing behaviors (mean difference: -10.2; 95% CI: -20.3, -0.2) and fewer somatic complaints (mean difference: -5.2, 95% CI: -9.8, -0.6). CONCLUSIONS: Our study suggests that postnatal exposure to cannabis is associated with more behavioral and cognitive problems among 5-year-old children, independent of prenatal and postnatal exposure to tobacco. The potential risks of cannabis use (including smoking and vaping) during pregnancy and around young children should be more widely communicated to parents.

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 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.

Prenatal exposure to tobacco and adverse birth outcomes: effect modification by folate intake during pregnancy.

BACKGROUND: Fetal exposure to tobacco increases the risk for many adverse birth outcomes, but whether diet mitigates these risks has yet to be explored. Here, we examined whether maternal folate intake (from foods and supplements) during pregnancy modified the association between prenatal exposure to tobacco and with preterm delivery, small-for-gestational age (SGA) births, or neonatal adiposity. METHODS: Mother-child pairs (n = 701) from Healthy Start were included in this analysis. Urinary cotinine was measured at ~ 27 weeks gestation. Diet was assessed using repeated 24-h dietary recalls. Neonatal adiposity (fat mass percentage) was measured via air displacement plethysmography. Interaction was assessed by including a product term between cotinine (< / ≥ limit of detection [LOD]) and folate (< / ≥ 25th percentile [1077 µg/day]) in separate logistic or linear regression models, adjusting for maternal age, race, ethnicity, education, pre-pregnancy body mass index, and infant sex. RESULTS: Approximately 26% of women had detectable levels of cotinine. Folate intake was significantly lower among women with cotinine ≥ LOD as compared to those with cotinine < LOD (1293 µg/day vs. 1418 µg/day; p = 0.01). Folate modified the association between fetal exposure to tobacco with neonatal adiposity (p for interaction = 0.07) and SGA (p for interaction = 0.07). Among those with lower folate intake, fetal exposure to tobacco was associated with lower neonatal adiposity (mean difference: -2.09%; 95% CI: -3.44, -0.74) and increased SGA risk (OR: 4.99; 95% CI: 1.55, 16.14). Conversely, among those with higher folate intake, there was no difference in neonatal adiposity (mean difference: -0.17%; 95% CI: -1.13, 0.79) or SGA risk (OR: 1.15; 95% CI: 0.57, 2.31). CONCLUSIONS: Increased folate intake during pregnancy (from foods and/or supplements) may mitigate the risk of fetal growth restriction among those who are unable to quit smoking or cannot avoid secondhand smoke during pregnancy.

Associations between maternal reports of periconceptional fever from miscellaneous causes and structural birth defects.

BACKGROUND: Associations between birth defects and fevers attributed to colds, influenza, and urinary tract infections (UTIs) have been observed in previous studies. Our aim was to study associations between birth defects and fevers attributed to other causes. METHODS: We analyzed data from 34,862 participants in the National Birth Defects Prevention Study, a multistate case-control study of major structural birth defects. Using multivariable logistic regression, we assessed the association between maternal report of fever during early pregnancy due to causes other than colds, influenza, or UTI and 36 categories of birth defects. RESULTS: Maternal reports of fever due to other causes were associated with significantly elevated odds ratios ranging from 1.93 to 10.60 for 8 of 36 birth defects, primarily involving the spine, limbs, and heart (spina bifida, intestinal atresia, intercalary limb deficiency, transverse limb deficiency, congenital heart defect with heterotaxy, tetralogy of Fallot, pulmonary atresia and atrial septal defect, not otherwise specified). CONCLUSION: Our data suggests fever itself or other physiologic changes associated with many infections are associated with some birth defects. Women who are pregnant or planning to become pregnant may want to consider speaking with their healthcare provider about the best ways to avoid infections that may cause fever and for guidance on how to treat fevers during pregnancy.

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.

Leveraging a phenome-wide approach to identify novel exposure-birth defect associations: A proof of concept using maternal smoking and a spectrum of birth defects.

BACKGROUND: There are often questions about the impact of exposures on a range of birth defects, but there are few rigorous approaches for evaluating these associations. Using maternal smoking as an example we applied a phenome-wide association study (PheWAS) approach to evaluate the impact of this exposure on a comprehensive range of birth defects. METHODS: Cases were obtained from the Texas Birth Defects Registry for the period 1999-2015. A total of 127 birth defects were examined. Maternal smoking at any time during the pregnancy was ascertained from the vital record. Data were randomly divided into discovery (60%) and replication (40%) partitions. Poisson regression models were run in the discovery partition, using a Bonferroni threshold of p < 3.9×10-4 . Birth defects passing that threshold in adjusted models were evaluated in the replication partition using p < 0.05 to determine statistical significance. RESULTS: Four birth defects were positively and significantly associated with maternal smoking in both partitions: cleft palate, anomalies of the pulmonary artery, other specified anomalies of the mouth and pharynx, and congenital hypertrophic pyloric stenosis. Obstructive defects of the renal pelvis and ureter showed consistent negative associations. All five defects exhibited significant dose-response relationships. CONCLUSIONS: We demonstrated that a statistically rigorous approach can be applied to birth defects registry data to examine the association between specified exposures and a range of birth defects. While we confirmed previously reported associations, others were not validated, likely due to misclassification in exposure based on vital records.