Maternal intake of vitamin E and birth defects,national birth defects prevention study, 1997 to 2005

BACKGROUND In a recent study, high maternal periconceptional intake of vitamin E was found to be associated with risk of congenital heart defects (CHDs). To explore this association further, we investigated the association between total daily vitamin E intake and selected birth defects. METHODS: We analyzed data from 4525 controls and 8665 cases from the 1997 to 2005 National Birth Defects Prevention Study. We categorized estimated periconceptional energy‐adjusted total daily vitamin E intake from diet and supplements into quartiles (referent, lowest quartile). Associations between quartiles of energy‐adjusted vitamin E intake and selected birth defects were adjusted for demographic, lifestyle, and nutritional factors. RESULTS: We observed a statistically significant association with the third quartile of vitamin E intake (odds ratio [OR], 1.17; 95% confidence interval [CI], 1.01–1.35) and all CHDs combined. Among CHD sub‐types, we observed associations with left ventricular outflow tract obstruction defects, and its sub‐type, coarctation of the aorta and the third quartile of vitamin E intake. Among defects other than CHDs, we observed associations between anorectal atresia and the third quartile of vitamin E intake (OR, 1.66; 95% CI, 1.01–2.72) and hypospadias and the fourth quartile of vitamin E intake (OR, 1.42; 95% CI, 1.09–1.87). CONCLUSION: Selected quartiles of energy‐adjusted estimated total daily vitamin E intake were associated with selected birth defects. However, because these few associations did not exhibit exposure‐response patterns consistent with increasing risk associated with increasing intake of vitamin E, further studies are warranted to corroborate our findings. Birth Defects Research (Part A), 100:647–657, 2014. © 2014 Wiley Periodicals, Inc.     

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. © 2012 Wiley Periodicals, Inc.     

Maternal self-reported genital tract infections during pregnancy and the risk of selected birth defects

BACKGROUND: Genital tract infections are common during pregnancy and can result in adverse outcomes including preterm birth and neonatal infection. This hypothesis‐generating study examined whether these infections are associated with selected birth defects. METHODS: We conducted a case‐control study of 5913 children identified as controls and 12,158 cases with birth defects from the National Birth Defects Prevention Study (1997–2004). Maternal interviews provided data on genital tract infections that occurred from one month before pregnancy through the end of the first trimester. Infections were either grouped together as a single overall exposure or were considered as a subgroup that included chlamydia/gonorrhea/pelvic inflammatory disease. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression with adjustment for potential confounders. RESULTS: Genital tract infections were associated with bilateral renal agenesis/hypoplasia (OR, 2.89; 95% CI, 1.11–7.50), cleft lip with or without cleft palate (OR, 1.46; 95% CI, 1.03–2.06), and transverse limb deficiency (OR, 1.84; 95% CI, 1.04–3.26). Chlamydia/gonorrhea/pelvic inflammatory disease was associated with cleft lip only (OR, 2.81; 95% CI, 1.39–5.69). These findings were not statistically significant after adjustment for multiple comparisons. CONCLUSIONS: Caution is needed in interpreting these findings due to the possible misclassification of infection, the limited sample size that constrained consideration of the effects of treatment, and the possibility of chance associations. Although these data do not provide strong evidence for an association between genital tract infections and birth defects, additional research on the possible effects of these relatively common infections is needed. Birth Defects Research (Part A), 2010. © 2010 Wiley‐Liss, Inc.     

Anencephaly and spina bifida among Hispanics: Maternal,sociodemographic, and acculturation factors in the National Birth Defects Prevention Study

BACKGROUND : We used data from the multisite National Birth Defects Prevention Study for expected delivery dates from October 1997 through 2003, to determine whether the increased risk in anencephaly and spina bifida (neural tube defects (NTDs)) in Hispanics was explained by selected sociodemographic, acculturation, and other maternal characteristics. METHODS : For each type of defect, we examined the association with selected maternal characteristics stratified by race/ethnicity and the association with Hispanic parents' acculturation level, relative to non‐Hispanic whites. We used logistic regression and calculated crude odds ratios (ORs) and their 95% confidence intervals (CIs). RESULTS : Hispanic mothers who reported the highest level of income were 80% less likely to deliver babies with spina bifida. In addition, highly educated Hispanic and white mothers had 76 and 35% lower risk, respectively. Other factors showing differing effects for spina bifida in Hispanics included maternal age, parity, and gestational diabetes. For spina bifida there was no significant elevated risk for U.S.–born Hispanics, relative to whites, but for anencephaly, corresponding ORs ranged from 1.9 to 2.3. The highest risk for spina bifida was observed for recent Hispanic immigrant parents from Mexico or Central America residing in the United States <5 years (OR = 3.28, 95% CI = 1.46–7.37). CONCLUSIONS : Less acculturated Hispanic parents seemed to be at highest risk of NTDs. For anencephaly, U.S.–born and English‐speaking Hispanic parents were also at increased risk. Finally, from an etiologic standpoint, spina bifida and anencephaly appeared to be etiologically heterogeneous from these analyses. Birth Defects Research (Part A), 2009. © 2009 Wiley‐Liss, Inc.     

Maternal obesity and morbid obesity: The risk for birth defects in the offspring

BACKGROUND : The objective of this study was to assess, in a large data set from Swedish Medical Health Registries, whether maternal obesity and maternal morbid obesity were associated with an increased risk for various structural birth defects. METHODS : The study population consisted of 1,049,582 infants born in Sweden from January 1, 1995, through December 31, 2007, with known maternal weight and height data. Women were grouped in six categories of body mass index (BMI) according to World Health Organization classification. Infants with congenital birth defects were identified from three sources: the Swedish Medical Birth Registry, the Register of Birth Defects, and the National Patient Register. Maternal age, parity, smoking, and year of birth were thought to be potential confounders and were included as covariates in the adjusted odds ratio analyses. RESULTS : Ten percent of the study population was obese. Morbid obesity (BMI ≥ 40) occurred in 0.7%. The prevalence of congenital malformations was 4.7%, and the prevalence of relatively severe malformations was 3.2%. Maternal prepregnancy morbid obesity was associated with neural tube defects OR 4.08 (95% CI 1.87–7.75), cardiac defects OR 1.49 (95% CI 1.24–1.80), and orofacial clefts OR 1.90 (95% CI 1.27–2.86). Maternal obesity (BMI ≥ 30) significantly increased the risk of hydrocephaly, anal atresia, hypospadias, cystic kidney, pes equinovarus, omphalocele, and diaphragmatic hernia. CONCLUSION : The risk for a morbidly obese pregnant woman to have an infant with a congenital birth defect is small, but for society the association is important in the light of the ongoing obesity epidemic. Birth Defects Research (Part A), 2010. © 2009 Wiley‐Liss, Inc.     

Maternal asthma,asthma medication use,and the risk of congenital heart defects

BACKGROUND: Asthma is a common problem that complicates pregnancy. Several drugs are considered acceptable for use during pregnancy, although none have been classified as safe. Few studies have assessed the health impact of maternal asthma/medication use on the fetus. METHODS: A population‐based case‐control study was conducted in New York State to determine if cardiac congenital malformations in offspring were associated with maternal use of asthma medication and/or maternal asthma. Cases were cardiac anomalies in the New York State Congenital Malformations Registry. Controls were live births without any major birth defects randomly selected from birth certificates and frequency matched by year of birth. Data were collected through a 30 min telephone interview. Exposure was maternal asthma/medication use, maternal asthma/no medication use, no asthma/medication use, and no asthma/no medication use (reference). RESULTS: A total of 502 (59.4%) cases and 1,066 (53.8%) controls participated. A positive association was seen between any heart defect and women with asthma who used medication (OR 2.38; 95% CI: 1.18, 4.82). No significant associations were observed between heart defects and either women with asthma who did not use medication or women without asthma who used asthma medications. When considering types of medication used, offspring of women with asthma who used bronchodilators had an increased risk of any heart defect (OR 2.20; 95%CI: 1.05, 4.61). CONCLUSIONS: These results suggest that both maternal asthma status (controlled vs. uncontrolled; severe vs. mild) and asthma medication use, particularly bronchodilators, may play a role in cardiac malformations in offspring. Birth Defects Research (Part A), 2009. © 2008 Wiley‐Liss, Inc.     

Clinician reviewers in birth defects surveillance programs: survey of the National Birth Defects Prevention Network

BACKGROUND: Some birth defects surveillance programs utilize a clinician reviewer ("Clinician") to assist the multidisciplinary staff in the process of case review, coding and classification. The untested assumption is that expertise in the evaluation of individuals with birth defects and genetic syndromes in clinical practice, usually clinical genetics, is useful in reviewing medical records. METHODS: We conducted an exploratory survey of the 50 functioning birth defects surveillance programs that participated in the National Birth Defects Prevention Network in 2004. The survey was mailed electronically to program coordinators and included 10 questions with check-off option replies. Open-ended comments were also solicited. RESULTS: Responses were received from 31 of 50 (62%) programs, 21 (68%) which used a Clinician. In addition to the 9 centers that identified themselves as participants in the National Birth Defects Prevention Study (NBDPS), there were 12 non-NBDPS programs using a Clinician, 2 of whom were not clinical geneticists (1 nurse genetic counselor and 1 primary pediatrician). A total of 86% (18/21) of Clinicians were employed part-time or as consultants; 1 was full-time, and 2 were volunteers. In addition to the core activities of classifying defects and reviewing cases to determine if a syndrome was present, over one-half of the Clinicians participated in education of birth defects surveillance programs staff, research, and program development. Most (86%; 18/21) Clinicians had been trained informally for their roles. Only 1 had received a formal performance review. CONCLUSIONS: Aside from the 9 centers in the NBDPS in which the position of Clinician is funded by the Centers for Disease Control and Prevention (CDC), about one-half of the remaining respondent birth defects surveillance programs used a Clinician. Future research is needed to determine why a birth defects surveillance program hires or refrains from using a Clinician, and whether a Clinician accomplishes the desired goals. This survey reveals a lack of formal training for the Clinicians in their roles in the surveillance programs, and a lack of quality monitors, which might be addressed in the future.     

Association between reported venlafaxine use in early pregnancy and birth defects,national birth defects prevention study, 1997–2007

BACKGROUND

Few epidemiologic studies have investigated the use of venlafaxine (Effexor XR capsules, Product Monograph, Wyeth, Montreal, Canada), an antidepressant used to treat major depression and anxiety disorders in adults, during pregnancy. Our objective was to determine whether use of venlafaxine during pregnancy is associated with specific birth defects.

METHODS

We used data from the National Birth Defects Prevention Study (NBDPS), a population‐based, case‐control study in the United States. Our analysis included mothers with pregnancies affected by one of 30 selected birth defects (cases) and babies without birth defects (controls) with estimated dates of delivery between 1997 and 2007. Exposure was any reported use of venlafaxine from 1 month preconception through the third month of pregnancy. We calculated adjusted odds ratios (aORs) and 95% Fisher Exact confidence intervals (CIs) for 24 birth defect groups for which at least 400 case mothers were interviewed. Our adjusted analyses controlled for maternal age and race/ethnicity.

RESULTS

Among the 27,045 NBDPS participants who met inclusion criteria, 0.17% (14/8002) of control mothers and 0.40% (77/19,043) of case mothers reported any use of venlafaxine from 1 month preconception through the third month of pregnancy. Statistically significant associations were found for anencephaly, atrial septal defect (ASD) secundum, or ASD not otherwise specified, coarctation of the aorta, cleft palate, and gastroschisis.

CONCLUSIONS

Our data suggest associations between periconceptional use of venlafaxine and some birth defects. However, sample sizes were small, CIs were wide, and additional studies are needed to confirm these results. Birth Defects Research (Part A), 2013. © 2012 Wiley Periodicals, Inc.