Oakland, CA, United States
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Ma C.,California Research Division | Carmichael S.L.,California Research Division | Shaw G.M.,Stanford University
American Journal of Medical Genetics, Part A | Year: 2010

The study objective was to examine the association of microtia with maternal intake of folic-acid-containing supplements and obesity. The study data included deliveries from 1997 to 2005 from the National Birth Defects Prevention Study. Non-syndromic cases of microtia were compared to non-malformed, population-based liveborn control infants, by estimating adjusted odds ratios (AORs) and 95% confidence intervals (CIs) from logistic regression models that included maternal race/ethnicity, education, and study site. Maternal obesity was only weakly associated with microtia. Maternal periconceptional intake of folic-acid-containing vitamin supplements reduced the risk for microtia, but only among non-obese women (OR: 0.63; 95% CI: 0.44-0.91). The reduced risk was stronger when analyses were restricted to isolated cases (OR: 0.51; 95% CI: 0.34-0.77), and it was independent of the level of maternal dietary folate intake. Adjusting for maternal race/ethnicity did not reveal alternative interpretations of this association. This analysis suggests that maternal periconceptional intake of folic-acid-containing supplements may provide protection from microtia for non-obese women. © 2010 Wiley-Liss, Inc.


Carmichael S.L.,California Research Division | Rasmussen S.A.,Centers for Disease Control and Prevention | Lammer E.J.,Childrens Hospital Oakland Research Institute | Ma C.,California Research Division | Shaw G.M.,Stanford University
Birth Defects Research Part A - Clinical and Molecular Teratology | Year: 2010

Objective: To examine the association of craniosynostosis with maternal intake of folic acid-containing supplements and dietary nutrients. Methods: The study included deliveries from 1997 to 2005 from the National Birth Defects Prevention Study. Nonsyndromic infants with craniosynostosis (n = 815) were compared to nonmalformed, population-based liveborn control infants (n = 6789), by estimating adjusted odds ratios (AORs) and 95% confidence intervals (CIs) from logistic regression models that included mother's age, parity, race-ethnicity, education, body mass index, smoking, alcohol, fertility treatments, plurality, and study center. We compared quartiles of intake and specified nutrients as continuous. Results: Intake of folic acid-containing supplements was not associated with craniosynostosis (AORs were close to 1). Analyses of dietary nutrients were restricted to mothers who took supplements during the first trimester (i.e., most women). Based on continuous specifications of nutrients, sagittal synostosis risk was significantly lower among women with higher intake of riboflavin and vitamins B 6, E, and C; metopic synostosis risk was significantly higher among women with higher intakes of choline and vitamin B 12; and coronal synostosis risk was significantly lower among women with higher intake of methionine and vitamin C. As examples, AORs for sagittal synostosis among women with intakes of vitamin B 6 and riboflavin in the highest versus lowest quartiles were 0.4 (95% CI, 0.2-0.6) and 0.5 (95% CI, 0.3-0.7), respectively. Conclusion: This analysis suggests that dietary intake of certain nutrients may be associated with craniosynostosis, and results may vary by suture type. © 2010 Wiley-Liss, Inc.


Sanchez-Lara P.A.,Childrens Hospital Los Angeles | Carmichael S.L.,California Research Division | Graham Jr. J.M.,Cedars Sinai Medical Center | Lammer E.J.,Childrens Hospital Oakland Research Institute | And 4 more authors.
American Journal of Medical Genetics, Part A | Year: 2010

Non-syndromic craniosynostosis is multifactorial, and fetal head constraint has been hypothesized as one factor thought to play a role. Data from the National Birth Defects Prevention Study (NBDPS), a large multi-site case-control study of birth defects, were used to evaluate associations between four selected factors related to fetal constraint and craniosynostosis: plurality (twins or higher), macrosomia (birth weight >4,000 g), post-term gestational age (≥42 weeks), and nulliparity (no previous live births). Case infants (n = 675) had craniosynostosis documented either by radiographic evidence or by surgical intervention. Infants with a recognized or strongly suspected single-gene conditions or chromosomal abnormalities were excluded. Control infants (n = 5,958) had no major birth defects and were randomly selected from the same population as case infants. Logistic regression was used to estimate odds ratios for the association between these four factors and craniosynostosis, while adjusting for several covariates. We found that plurality and nulliparity were associated with a twofold increased risk for metopic craniosynostosis, and macrosomia had almost twice the risk of developing coronal craniosynostosis. Contrary to our hypothesis, prematurity and low birth weight were also associated with craniosynostosis. In conclusion, these four constraint-related factors were not found to be associated with craniosynostosis when all suture types were combined, though some types of craniosynostosis were associated with individual constraint-related factors. © 2010 Wiley-Liss, Inc.


Carmichael S.L.,California Research Division | Herring A.H.,University of North Carolina at Chapel Hill | Sjodin A.,Centers for Disease Control and Prevention | Jones R.,Centers for Disease Control and Prevention | And 4 more authors.
Chemosphere | Year: 2010

Background: Environmental contaminants that disrupt endocrine function may contribute to hypospadias etiology. Objective: To compare levels of selected halogenated organic pollutants in women delivering infants with and without hypospadias. Methods: This study examined levels of nine polybrominated flame retardants (PBDEs), 30 polychlorinated biphenyls (PCBs) and nine persistent pesticides in mid-pregnancy serum samples from 20 women who delivered infants with hypospadias and 28 women who delivered unaffected infants, in California. Analytes were measured using isotope dilution high-resolution mass spectrometry. Values below individual limits of detection (LOD) for each analyte were imputed based on a truncated multivariate normal distribution. Levels of 17 analytes for which at least 50% of cases and controls had values above the LOD were compared using t-tests and by generating odds ratios from logistic regression analyses. Results: Means were greater for cases than controls for 11 of the 17 reported analytes (4 of 5 PBDEs, 7 of 9 PCBs, and 0 of 3 other persistent pesticides), but none of the differences were statistically significant. Eleven of the 17 odds ratios exceeded one (the same analytes that had greater means), but none of the confidence intervals excluded one. After adjustment for sample processing time and foreign-born Hispanic race-ethnicity, only four of the odds ratios exceeded one. Conclusions: Levels of the PBDEs and PCBs were not statistically significantly different, but the sample size was small. The current study adds to a relatively limited knowledge base regarding the potential association of specific contaminants with hypospadias or other birth defects. © 2010 Elsevier Ltd.


Carmichael S.L.,California Research Division | Yang W.,California Research Division | Shaw G.M.,Stanford University
Birth Defects Research Part A - Clinical and Molecular Teratology | Year: 2010

BACKGROUND: This study investigated the association of neural tube defects (NTDs) with maternal periconceptional intake of folic acid-containing supplements and dietary nutrients, including folate, among deliveries that occurred after folic acid fortification in selected California counties. METHODS: The population-based case-control study included fetuses and live born infants with spina bifida (189) or anencephaly (141) and 625 nonmalformed, live born controls delivered from 1999 to 2003. Mothers reported supplement use during telephone interviews, which included a 107-item food frequency questionnaire. For dietary nutrients, intakes <25th, 25th to <75th (reference), and ≥75th percentile were compared, based on control distributions. RESULTS: After adjustment for potential confounders, any versus no supplement intake resulted in ORs of 0.8 (95% CI, 0.5-1.3) for anencephaly and 0.8 (95% CI, 0.6-1.2) for spina bifida. After stratification by maternal intake of vitamin supplements, most factors in the glycemic pathway were not associated with either NTD, with the exception of low levels of fructose and glucose that were significantly associated with anencephaly. Some nutrients that contribute to one-carbon metabolism showed lowered risks (folate, riboflavin, vitamins B6 and B12); others did not (choline, methionine, zinc). Antioxidant nutrients tended to be associated with lowered risks (vitamins C, E, A, β-carotene, lutein). CONCLUSIONS: Mothers' intake of vitamin supplements was modestly if at all associated with a lowered risk of NTDs. Dietary intake of several nutrients contributing to one-carbon metabolism and oxidative stress were associated with reduced NTD risk. © 2010 Wiley-Liss, Inc.


Carmichael S.L.,California Research Division
Birth defects research. Part A, Clinical and molecular teratology | Year: 2010

Obesity is associated with increased risk of many adverse health conditions. During pregnancy, obesity presents particularly important challenges for both mother and baby. Over the last 20 years, studies have emerged indicating an association between prepregnancy weight and risks of birth defects. However, few studies have examined the mechanisms through which this association occurs. Understanding the underlying mechanisms may provide clues to public health strategies for the prevention of birth defects associated with maternal obesity. This article briefly reviews existing literature on the association between maternal obesity and birth defects, discusses potential underlying mechanisms, and suggests research needed to improve our understanding of this important association. © 2010 Wiley-Liss, Inc.


PubMed | California Research Division
Type: Journal Article | Journal: Birth defects research. Part A, Clinical and molecular teratology | Year: 2010

This study investigated the association of neural tube defects (NTDs) with maternal periconceptional intake of folic acid-containing supplements and dietary nutrients, including folate, among deliveries that occurred after folic acid fortification in selected California counties.The population-based case-control study included fetuses and live born infants with spina bifida (189) or anencephaly (141) and 625 nonmalformed, live born controls delivered from 1999 to 2003. Mothers reported supplement use during telephone interviews, which included a 107-item food frequency questionnaire. For dietary nutrients, intakes <25th, 25th to <75th (reference), and > or =75th percentile were compared, based on control distributions.After adjustment for potential confounders, any versus no supplement intake resulted in ORs of 0.8 (95% CI, 0.5-1.3) for anencephaly and 0.8 (95% CI, 0.6-1.2) for spina bifida. After stratification by maternal intake of vitamin supplements, most factors in the glycemic pathway were not associated with either NTD, with the exception of low levels of fructose and glucose that were significantly associated with anencephaly. Some nutrients that contribute to one-carbon metabolism showed lowered risks (folate, riboflavin, vitamins B(6) and B(12)); others did not (choline, methionine, zinc). Antioxidant nutrients tended to be associated with lowered risks (vitamins C, E, A, beta-carotene, lutein).Mothers intake of vitamin supplements was modestly if at all associated with a lowered risk of NTDs. Dietary intake of several nutrients contributing to one-carbon metabolism and oxidative stress were associated with reduced NTD risk.

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