Sociodemographic, health behavioral, and clinical risk factors for anotia/microtia in a population-based case-control study.

OBJECTIVE: Anotia and microtia are congenital malformations of the external ear with few known risk factors. We conducted a comprehensive assessment of a wide range of potential risk factors using data from the National Birth Defects Prevention Study (NBDPS), a population-based case-control study of non-chromosomal structural birth defects in the United States. METHODS: Mothers of 699 infants with anotia or microtia (cases) and 11,797 non-malformed infants (controls) delivered between 1997 and 2011 were interviewed to obtain information about sociodemographic, health behavioral, and clinical characteristics. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were estimated with logistic regression. RESULTS: Infants with anotia/microtia were more likely to be male (aOR, 1.29; 95% CI, 1.10-1.50) and from a multifetal pregnancy (aOR, 1.68; 95% CI, 1.16-2.42). Cases were also more likely to have parents of Hispanic ethnicity (maternal aOR, 3.19; 95% CI, 2.61-3.91; paternal aOR, 2.11; 95% CI, 1.54-2.88), and parents born outside the United States (maternal aOR, 1.29; 95% CI, 1.06-1.57; paternal aOR, 1.92; 95% CI, 1.53-2.41). Maternal health conditions associated with increased odds of anotia/microtia included obesity (aOR, 1.31; 95% CI, 1.06-1.61) and pre-pregnancy diabetes (type I aOR, 9.89; 95% CI, 5.46-17.92; type II aOR, 4.70; 95% CI, 2.56-8.63). Reduced odds were observed for black mothers (aOR, 0.57; 95% CI, 0.38-0.85) and mothers reporting daily intake of folic acid-containing supplements (aOR, 0.59; 95% CI, 0.46-0.76). CONCLUSION: We identified several risk factors for anotia/microtia, some which have been previously reported (e.g., diabetes) and others which we investigate for perhaps the first time (e.g., binge drinking) that warrant further investigation. Our findings point to some potentially modifiable risk factors and provide further leads toward understanding the etiology of anotia/microtia.

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.

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.

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.

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.

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.