Asthma Medication Use and Risk of Birth Defects: National Birth Defects Prevention Study, 1997-2011.

BACKGROUND: Evidence regarding associations between maternal asthma medication use and birth defects is mixed. OBJECTIVE: Estimate associations between asthma medciation use and 52 birth defects using National Birth Defects Prevention Study data from 1997 to 2011. METHODS: We compared self-reported maternal asthma medication use for 28,481 birth defect cases and 10,894 nonmalformed controls. We calculated adjusted odds ratios (95% CIs) to estimate the risk of birth defects associated with early pregnancy asthma medication use (the month before through the third month of pregnancy), controlling for maternal age, race/ethnicity, body mass index, smoking, folic acid-containing supplement use, and parity. We calculated risks by medication groupings: bronchodilators, anti-inflammatories, and both. RESULTS: Overall, 1304 (5%) case and 449 (4%) control women reported early pregnancy asthma medication use. We observed an association between asthma medication use and longitudinal limb deficiency (1.81; 95% CI, 1.27-2.58). Early pregnancy bronchodilator-only use was associated with cleft palate (1.50; 95% CI, 1.11-2.02), cleft lip (1.58; 95% CI, 1.12-2.23), longitudinal limb deficiency (2.35; 95% CI, 1.55-3.54), and truncus arteriosus (2.48; 95% CI, 1.13-5.42). Although early pregnancy anti-inflammatory-only use was not associated with the birth defects studied, use of both medications was associated with biliary atresia (3.60; 95% CI, 1.55-8.35) and pulmonary atresia (2.50; 95% CI, 1.09-5.78). CONCLUSIONS: Consistent with previous National Birth Defects Prevention Study analyses, asthma medication use was not associated with most birth defects examined, but we observed modest risks for bronchodilator use and several birth defects. Our findings support maintaining adequate asthma treatment during pregnancy, because early pregnancy asthma exacerbations have been associated with adverse birth outcomes, including birth defects.

Risk factors for congenital microcephaly in the pre-Zika era.

BACKGROUND: The Zika epidemic has brought increased attention to congenital microcephaly as a birth outcome. However, little is known about risks for microcephaly unrelated to Zika. METHODS: Using data from the Slone Epidemiology Center Birth Defects Study from 1993 to 2015, we identified 57 cases of microcephaly alone ("isolated") and 109 cases of microcephaly that included other major birth defects ("non-isolated"), and considered a large number of potential risk factors including demographic characteristics, illnesses, and medications used during pregnancy. Where numbers permitted, we used logistic regression models to calculate adjusted odds ratios (aORs) and 95% confidence intervals (CIs). RESULTS: Substantial differences in risk factors were observed for isolated versus non-isolated microcephaly. For isolated microcephaly, risk estimates were elevated for mothers of non-Hispanic, non-White race/ethnicity, and underweight pre-pregnancy body mass index (BMI). The risk for exposure anytime in pregnancy to acetaminophen was null; in contrast, the aOR for NSAIDs was 2.4 (95% CI: 1.3-4.2). This association was weakened (but not eliminated) after excluding those exposed to opioids or illicit drugs, and risk was not present among those reporting less frequent exposures. For non-isolated microcephaly, elevated risk estimates were found for urinary tract infection. CONCLUSIONS: Risk factors differed for isolated and non-isolated microcephaly. While some findings support previously reported associations, (e.g., smoking, alcohol, underweight BMI), we also identified risk factors not previously described, notably NSAID use for isolated microcephaly and urinary tract infection for non-isolated microcephaly; however, these results should be viewed as hypothesis generating.

An application of data mining to identify potential risk factors for anophthalmia and microphthalmia.

BACKGROUND: We examined a large number of variables to generate new hypotheses regarding a wider range of risk factors for anophthalmia/microphthalmia using data mining. METHODS: Data were from the National Birth Defects Prevention Study, a multicentre, case-control study from 10 centres in the United States. There were 134 cases of "isolated" and 87 "nonisolated" (with other major birth defects) of anophthalmia/microphthalmia and 11 052 nonmalformed controls with delivery dates October 1997-December 2011. Using random forest, a data mining procedure, we compared the two case types with controls for 201 variables. Variables considered important ranked by random forest were included in a multivariable logistic regression model to estimate odds ratios and 95% confidence intervals. RESULTS: Predictors for isolated cases included paternal race/ethnicity, maternal intake of certain nutrients and foods, and childhood health problems in relatives. Using regression, inverse associations were observed with greater maternal education and with increasing intake of folate and potatoes. Odds were slightly higher with greater paternal education, for increased intake of carbohydrates and beans, and if relatives had a childhood health problem. For nonisolated cases, predictors included paternal race/ethnicity, maternal intake of certain nutrients, and smoking in the home the month before conception. Odds were higher for Hispanic fathers and smoking in the home and NSAID use the month before conception. CONCLUSIONS: Results appear to support previously hypothesised risk factors, socio-economic status, NSAID use, and inadequate folate intake, and potentially provide new areas such as passive smoking pre-pregnancy, and paternal education and ethnicity, to explore for further understanding of anophthalmia/microphthalmia.

Vasoactive exposures during pregnancy and risk of microtia.

BACKGROUND: Little is known about the etiology of nonsyndromic microtia. This study investigated the hypothesis that microtia is caused by vascular disruption. METHODS: The study analyzed data from the population-based National Birth Defects Prevention Study (NBDPS) for deliveries between 1997 and 2005. Four hundred eleven nonsyndromic cases of microtia, with or without additional defects, were compared to 6560 nonmalformed infants with respect to maternal exposures to vasoactive medications and smoking during the periconceptional period and conditions that have previously been associated with vascular events (multiple gestation, maternal history of type 1, type 2, or gestational diabetes, and hypertension). Odds ratios (ORs) were estimated with multivariable models, controlling for the effects of race/ethnicity, education, periconceptional folic acid use, and study center. RESULTS: Risk estimates for vasoactive medications and smoking were not meaningfully increased. Maternal type 1/2 diabetes was diagnosed before or during the index pregnancy in 4% and 1% of cases, respectively, compared to 1% and 0.05% of controls; the adjusted OR for these two groups combined was 7.2 (95% confidence interval [CI], 3.9-13.1). Gestational diabetes was observed for 9% of cases and 6% of controls; the OR was moderately elevated (OR, 1.4; 95% CI, 0.9-2.0). ORs were also increased for multiple gestations (OR, 2.5; 95% CI, 1.5-4.2) and pre-existing hypertension (OR, 1.6; 95% CI, 1.0-2.5). CONCLUSIONS: Because ORs were only elevated for diabetes and not for vasoactive exposures or other potential vascular events, findings suggest that some microtia occurrences may be part of the diabetic embryopathy rather than manifestations of vascular disruption. Birth Defects Research (Part A), 2013. © 2012 Wiley Periodicals, Inc.

Classification of the myelodysplastic syndrome in a national registry of recently diagnosed patients.

BACKGROUND: It is not known to what extent the WHO classification scheme for MDS has been adopted in clinical practice. METHODS: We reviewed the medical records of 200 newly diagnosed MDS patients enrolled in our national registry during the years 2006-2008 to determine the scheme used. RESULTS: Clear WHO subtypes were recorded for 45.0% of patients, compared to 5.5% for FAB subtypes; 28.0% had MDS documented but without WHO or FAB subtype, and for 22.5%, the schema was unclear. CONCLUSION: Although many MDS patients do not have a subtype or schema documented, when they do, the WHO system is widely used.