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Rates of neural tube defects have decreased since folic acid fortification of the food supply in the United States. The authors' objective was to evaluate the associations between neural tube defects and maternal folic acid intake among pregnancies conceived after fortification. This is a multicenter, case-control study that uses data from the National Birth Defects Prevention Study, 1998-2003. Logistic regression was used to compute crude and adjusted odds ratios between cases and controls assessing maternal periconceptional use of folic acid and intake of dietary folic acid. Among 180 anencephalic cases, 385 spina bifida cases, and 3, 963 controls, 21.1%, 25.2%, and 26.1%, respectively, reported periconceptional use of folic acid supplements. Periconceptional supplement use did not reduce the risk of having a pregnancy affected by a neural tube defect. Maternal intake of dietary folate was not significantly associated with neural tube defects. In this study conducted among pregnancies conceived after mandatory folic acid fortification, the authors found little evidence of an association between neural tube defects and maternal folic acid intake. A possible explanation is that folic acid fortification reduced the occurrence of folic acid-sensitive neural tube defects. Further investigation is warranted to possibly identify women who remain at increased risk of preventable neural tube defects. [ABSTRACT FROM AUTHOR]

The use of folic acid is a critical component in preventing birth defects. Health-care providers should take advantage of all health-care visits to counsel not only women at high risk (i.e., those with a history of having an infant with a neural tube defect [NTD]) but all women regarding the importance of folic acid use. A study conducted in Texas confirmed that white and Hispanic mothers were equally likely to recall receiving postpartum advice to use folic acid; however, Hispanic women were much less likely to use folic acid, compared with white women. This report covers data from May 2000 through November 2001. A study was conducted in Texas to determine whether women at high risk recall and follow recommendations to use folic acid. The study included 195 women at high risk and 223 control mothers who gave birth to infants without birth defects. These women participated in a telephone interview for a population-based case-control study of NTDs. Approximately 56.4% (110 of 195) of mothers who had infants affected by an NTD recalled receiving postpartum advice to use folic acid, compared with 25.6% (57 of 223) of control mothers (p < 0.01). Among nonpregnant case mothers, 54 (32.7%) of 165 reported regular use of supplements containing folic acid, and 53 (25.2%) of 210 nonpregnant control mothers reported this behavior (p = 0.11). Among case mothers, use of folic acid was significantly higher for whites (64.7%) versus Hispanics (16.5%) (p < 0.001); for women with some college education (57.1%) versus no college education (20.2%; p < 0.001); for women who were trying to get pregnant (66.7%) versus those using birth control (38.3%) or reporting using no contraceptive method (18.8%) (p = 0.001); and for women who reported receiving advice to use folic acid (40.9%) versus those who did not (22.2%; p = 0.01). Findings from this study support the need to implement NTD recurrence prevention activities in Texas. Data also identify a need for educational strategies in Texas that target Hispanic women at high risk, especially those who primarily speak Spanish. Further efforts should be made to determine why Hispanic women have low rates of folic acid use (e.g., the cost of vitamins and language and cultural barriers). On the basis of a review of research and current practice, recommendations developed by the Public Health Service include 1) women at risk for a recurrent NTD-affected pregnancy should take 0.4 mg of folic acid per day; and 2) if a woman at high risk is planning a pregnancy, she should consult her physician regarding taking the higher dose of 4.0 mg per day. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to examine the risk of birth defects in relation to diabetes mellitus and the lack of use of periconceptional vitamins or supplements that contain folic acid.Study Design: The National Birth Defects Prevention Study (1997-2004) is a multicenter, population-based case-control study of birth defects (14,721 cases and 5437 control infants). Cases were categorized into 18 types of heart defects and 26 noncardiac birth defects. We estimated odds ratios for independent and joint effects of preexisting diabetes mellitus and a lack of periconceptional use of vitamins or supplements that contain folic acid.Results: The pattern of odds ratios suggested an increased risk of defects that are associated with diabetes mellitus in the absence vs the presence of the periconceptional use of vitamins or supplements that contain folic acid.Conclusion: The lack of periconceptional use of vitamins or supplements that contain folic acid may be associated with an excess risk for birth defects due to diabetes mellitus. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To estimate the prevalence of awareness and use of evidence-based reproductive health interventions and to describe the barriers associated with the use of evidence-based interventions among health providers in north-west Cameroon. METHODS: In February 2004, a population-based descriptive study of the awareness and use of 13 evidence-based interventions targeted health workers providing reproductive health care. Their awareness and use of a composite of four vital interventions was also evaluated. These were peripartum use of antiretrovirals to prevent transmission of HIV, antenatal corticosteroid administration, magnesium sulfate prophylaxis and active management of placental delivery with uterotonics. In-depth interviews with key informants were conducted as part of a qualitative substudy to discover the barriers to the use of evidence-based interventions. FINDINGS: Overall, 91.4% (328/359) of reproductive health workers were surveyed. Their awareness of evidence-based interventions varied from 29% for the use of antenatal corticosteroids to 97% for the use of iron and folic acid supplementation during pregnancy. Their use of these interventions ranged from 10.2% for antenatal corticosteroids to 94.8% for iron and folic acid supplementation. Only 50/322 (15.5%; 95% confidence interval (CI)=11.8-20.0) of health workers were aware of all four vital interventions, and only 12/312 (3.8%; 95% CI=2.0- 6.6) reported using all of them regularly. A total of 26 key informants participated in the qualitative substudy. A deficiency in the education and training of health workers, especially a lack of continuing education, was commonly identified as the most important barrier to their awareness of evidence-based practices. A lack of awareness and a lack of supplies and materials were the main barriers to practice. CONCLUSION: The awareness and practice of important evidence-based reproductive health interventions were less than optimal. To improve maternal and perinatal outcomes both remedial programmes to enhance awareness, including continuing education for health workers, and the provision of necessary supplies are needed. [ABSTRACT FROM AUTHOR]

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., (© 2023 Wiley Periodicals LLC.)

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., (© 2022 Wiley Periodicals LLC.)

Background: Maternal pregestational diabetes and obesity are risk factors for birth defects. Diabetes and obesity often occur together; it is unclear whether their co-occurrence compounds birth defect risk., Methods: We analyzed 1997-2011 data on 29,671 cases and 10,963 controls from the National Birth Defects Prevention Study, a multisite case-control study. Mothers self-reported height, pregestational weight, and diabetes (pregestational and gestational; analyzed separately). We created four exposure groups: no obesity or diabetes (referent), obesity only, diabetes only, and both obesity and diabetes. We estimated odds ratios (ORs) using logistic regression and the relative excess risk due to interaction (RERI)., Results: Among mothers with pregestational obesity without diabetes, modest associations (OR range: 1.1-1.5) were observed for neural tube defects, small intestinal atresia, anorectal atresia, renal agenesis/hypoplasia, omphalocele, and several congenital heart defects. Pregestational diabetes, regardless of obesity, was strongly associated with most birth defects (OR range: 2.0-75.9). Gestational diabetes and obesity had a stronger association than for obesity alone and the RERI (in parentheses) suggested additive interaction for hydrocephaly (1.2; 95% confidence interval [CI]: -0.1, 2.5), tetralogy of Fallot (0.9; 95% CI: -0.01, 1.8), atrioventricular septal defect (1.1; 95% CI: -0.1, 2.3), hypoplastic left heart syndrome (1.1; 95% CI: -0.2, 2.4), and atrial septal defect secundum or not otherwise specified (1.0; 95% CI: 0.3, 1.6; only statistically significant RERI)., Conclusions: Our results do not support a synergistic relationship between obesity and diabetes for most birth defects examined. However, there are opportunities for prevention by reducing obesity and improving glycemic control among women with pregestational diabetes before conception., (© 2021 Wiley Periodicals LLC. This article has been contributed to by US Government employees and their work is in the public domain in the USA.)

Background: Asthma is a chronic airway disorder with variable/recurring symptoms, airflow obstruction, bronchial hyperresponsiveness, and an inflammation. The expert panel report of the National Heart Lung and Blood Institute recommends asthma screening in sickle cell disease (SCD); however, specific approach is not mentioned. We hypothesize that the breathmobile case identification survey (BCIS) is a valid asthma screening tool in children with SCD. Methods: This prospective, single-center study enrolled 129 SCD patients aged 5 to 18 years from March 2016 to March 2018. All patients completed BCIS, spirometry, and fractional exhaled nitric oxide (FeNO). A single pulmonologist blinded to the BCIS results evaluated patients for asthma. Results: Asthma prevalence was 41%. Male gender (60.4%; p  = 0.041), allergic rhinitis (86.8%; p  < 0.01), hydroxyurea usage (73.6%; p  < 0.01), and family history of asthma (34%; p  < 0.01) were higher but not self-reported parental asthma history, eczema, and tobacco smoke exposure in the asthma group compared to the nonasthma group. FEV 1 ( p  = 0.003), FVC ( p  = 0.02), FEV 1 /FVC ( p  = 0.053), and FEF 25-75 % ( p  = 0.02) were lower in asthma. FeNO levels were comparable in both groups. The sensitivity, specificity, positive predictive value, and negative predictive value of the abbreviated BCIS were 67.3%, 90.8%, 83.3%, and 80.2% for asthma; and 82.1%, 90.8%, 76.7%, and 93.2% for persistent asthma, respectively. Persistent asthma patients had a trend of higher hydroxyurea use (82.8% vs. 58.3%; p  = 0.049) and tobacco smoke exposure (55.2% vs. 29.2%; p  = 0.057) compared to intermittent asthma. Conclusion: We have validated the BCIS to screen for asthma in SCD. Spirometry but not FeNO may support an asthma diagnosis.

Background: Diabetes is associated with an increased risk for many birth defects and is likely to have an increasing impact on birth defect prevalence because of the rise in diabetes in the United States in recent decades. One of the first analyses in which specific birth defects were assessed for their relationship with both pregestational and gestational diabetes used data from the initial 6 years of the National Birth Defects Prevention Study. That analysis reported strong associations for pregestational diabetes with several birth defects, but few exposures among some of the less common birth defects led to unstable estimates with wide confidence intervals. Since that analysis, the study continued to collect data for another 8 years, including information on approximately 19,000 additional cases and 6900 additional controls., Objective: Our objective was to use data from the National Birth Defects Prevention Study, the largest population-based birth defects case-control study in the United States, to provide updated and more precise estimates of the association between diabetes and birth defects, including some defects not previously assessed., Study Design: We analyzed data on deliveries from October 1997 through December 2011. Mothers of case and control infants were interviewed about their health conditions and exposures during pregnancy, including diagnosis of pregestational (type 1 or type 2) diabetes before the index pregnancy or gestational diabetes during the index pregnancy. Using logistic regression, we separately assessed the association between pregestational and gestational diabetes with specific categories of structural birth defects for which there were at least 3 exposed case infants. For birth defect categories for which there were at least 5 exposed case infants, we calculated odds ratios adjusted for maternal body mass index, age, education, race/ethnicity, and study site; for defect categories with 3 or 4 exposed cases, we calculated crude odds ratios., Results: Pregestational diabetes was reported by 0.6% of mothers of control infants (71 of 11,447) and 2.5% of mothers of case infants (775 of 31,007). Gestational diabetes during the index pregnancy was reported by 4.7% of mothers of control infants (536 of 11,447) and 5.3% of mothers of case infants (1,653 of 31,007). Pregestational diabetes was associated with strong, statistically significant odds ratios (range, 2.5-80.2) for 46 of 50 birth defects considered. The largest odds ratio was observed for sacral agenesis (adjusted odds ratio, 80.2; 95% confidence interval, 46.1-139.3). A greater than 10-fold increased risk was also observed for holoprosencephaly (adjusted odds ratio, 13.1; 95% confidence interval, 7.0-24.5), longitudinal limb deficiency (adjusted odds ratio, 10.1; 95% confidence interval, 6.2-16.5), heterotaxy (adjusted odds ratio, 12.3; 95% confidence interval, 7.3-20.5), truncus arteriosus (adjusted odds ratio, 14.9; 95% confidence interval, 7.6-29.3), atrioventricular septal defect (adjusted odds ratio, 10.5; 95% confidence interval, 6.2-17.9), and single ventricle complex (adjusted odds ratio, 14.7; 95% confidence interval, 8.9-24.3). For gestational diabetes, statistically significant odds ratios were fewer (12 of 56) and of smaller magnitude (range, 1.3- 2.1; 0.5 for gastroschisis)., Conclusion: Pregestational diabetes is associated with a markedly increased risk for many specific births defects. Because glycemic control before pregnancy is associated with a reduced risk for birth defects, ongoing quality care for persons with diabetes is an important opportunity for prevention., (Published by Elsevier Inc.)

Objective: Estimate inpatient hospitalization costs for patients with microcephaly, and predict cost increases due to a potential Zika virus outbreak., Methods: We identified Texas-wide inpatient hospitalization discharge records (2008-2015), for newborns and non-newborns with microcephaly. We estimated the cost of each hospitalization by applying cost-to-charge ratios on the actual hospitalization charge. For comparison, newborn visits for patients without microcephaly were also identified, and hospital costs were compared between patients with and without microcephaly. We estimated costs for microcephaly during the first year of life following a Zika outbreak (possible 1-50% increase in birth prevalence) in Texas., Results: There were 8005 microcephaly hospitalizations ($203,899,042; total cost). The median admission cost for newborns with microcephaly (N = 1393) was higher compared to those without microcephaly ($6751 vs $725, p < 0.001). Microcephaly hospitalizations of newborns had a lower median cost compared to non-newborns ($6751 vs $9754, p < 0.001). Based on these observed hospitalization costs, we estimated that a potential Zika virus outbreak in Texas could result in an additional $1-6 million per year for hospitalizations., Conclusion: Hospitalizations of patients with microcephaly are associated with high costs. An increase in microcephaly prevalence due to a Zika outbreak in Texas could have a considerable impact on health care costs., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: Assess temporal trends in congenital microcephaly., Methods: We used Texas inpatient discharge diagnoses between 2000 and 2015, restricting to newborns. Between 2000 and 2003, the maximum number of fields for recording diagnostic codes was eight, and between 2004 and 2015 it was 24. Microcephaly was classified into four subgroups based on co-occurring diagnoses: A (Known Causes), B (Other Birth Defects), C (Preterm Birth or Fetal Growth Restriction) and D (Isolated Cases)., Results: We identified 2,301 cases of microcephaly or 4.0 cases per 10,000 live births. There was an increase in the prevalence of microcephaly in 2012-2015 compared with 2000-2003, odds ratio = 1.85 (95% CI 1.64-2.10) Significant temporal increases in microcephaly were observed within each of the four microcephaly subgroups and significant temporal increases were also observed for eight other neonatal diagnoses during the same time period. When we restricted our analysis to cases with microcephaly identified using only the eight diagnostic codes available throughout the entire study period, the temporal trend for microcephaly was diminished or absent., Conclusions: It remains uncertain whether the observed increases in microcephaly and other neonatal diagnoses are real or an artifact of the change in the number of fields. However, since it is unlikely that there would be a simultaneous increase in microcephaly and eight other neonatal diagnoses, it is likely that some or all of the temporal increases in neonatal diagnoses are artifactual., (© 2019 Wiley Periodicals, Inc.)

Background: We examined the association between the maternal genotype for celiac disease-associated variants and risk of neural tube defects (NTDs)., Methods: We conducted a case-control study, using data from the National Birth Defects Prevention Study. We evaluated 667 cases (women with an offspring with NTD) and 743 controls (women with an offspring without a birth defect). We classified women as having low, intermediate, or high risk of celiac disease based on human leukocyte antigen (HLA) variants. We used logistic regression to assess the relationship between HLA celiac risk group (low, intermediate, high) and risk of NTDs. Fifteen non-HLA variants (identified from genome-wide association studies of celiac disease) were individually evaluated and modeled additively., Results: There was no association between HLA celiac risk group and NTDs (intermediate vs. low risk: aOR, 1.0; 95% CI, 0.8-1.3; high vs. low risk: aOR, 0.8; 95% CI, 0.5-1.3). Of the fifteen non-HLA variants, we observed five significant associations after accounting for multiple comparisons. Three negative associations were observed with rs10903122, rs13314993, rs13151961 (aOR range: 0.69-0.81), and two positive associations were observed with rs13003464 and rs11221332 (aOR range: 1.27-1.73)., Conclusion: If confirmed, our results suggest that the maternal variants related to celiac disease may be involved in the risk of NTDs., (© 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.)

Background: The risk of neural tube defect (NTD)-affected pregnancies is reduced with adequate folic acid intake during early pregnancy. However, NTDs have been observed among offspring of women with adequate folic acid intake. Some of these women are possibly not absorbing enough folic acid. Because lactase deficiency can lead to poor nutrient absorption, we hypothesized that lactase-deficient women will be at increased risk of having offspring with NTDs., Objective: We examined the association between maternal rs4988235 (a lactase deficiency genetic marker) and NTDs in offspring., Methods: We conducted a case-control study using data from the National Birth Defects Prevention Study, United States, 1997-2009, restricting to non-Hispanic white (NHW) and Hispanic women. Cases were women with an offspring with an NTD (n = 378 NHW, 207 Hispanic), and controls were women with an offspring without a birth defect (n = 461 NHW, 165 Hispanic). Analyses were conducted separately by race/ethnicity, using logistic regression. Women with the CC genotype were categorized as being lactase deficient. To assess potential effect modification, analyses were stratified by lactose intake, folic acid supplementation, dietary folate, and diet quality., Results: Among NHW women, the odds of being lactase deficient were greater among cases compared with controls (OR: 1.37; 95% CI: 1.02, 1.82). Among Hispanic women, the odds of being lactase deficient were significantly lower among cases compared with controls (OR: 0.50, 95% CI: 0.33, 0.77). The association differed when stratified by lactose intake in NHW women (higher odds among women who consumed ≥12 g lactose/1000 kcal) and by dietary folate in Hispanic women (opposite direction of associations). The association did not differ when stratified by folic acid supplementation or diet quality., Conclusions: Our findings suggest that maternal lactase deficiency is associated with NTDs in offspring. However, we observed opposite directions of effect by race/ethnicity that could not be definitively explained., (© 2019 American Society for Nutrition.)

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 (&lt;37 weeks), early preterm birth (&lt;32 and &lt;35 weeks) and small-for-gestational-age infants (SGA; &lt;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.

Background: Gastroschisis, a congenital defect of the abdominal wall, occurs disproportionately more in offspring of young mothers and has been increasing in prevalence over the past decades. A wide range of exposures have been reported in association with an increased gastroschisis risk, independent of mother's age; many have also been correlated with stress responses., Methods: We explored cumulative exposures to such stressor exposures among 1,261 mothers of gastroschisis cases and 10,682 mothers of controls in the National Birth Defects Prevention Study (1997-2011). We considered 16 exposures as stressors in the first trimester: fever, genitourinary infection, anti-herpetic medication use, injury, bronchodilator use, cigarette smoking, alcohol intake, illicit drug use, prescription opioid use, oral contraceptive use, interpregnancy interval < 12 months, residential move, aspirin use, ibuprofen use, venlafaxine use, and paroxetine use., Results: Mothers of cases reported more stressor exposures than controls. For 1, 2, 3, and ≥ 4 stressor exposures compared with none, the age-adjusted odds ratios (95% confidence interval) were 1.3 (1.1, 1.6), 1.7 (1.4, 2.1), 2.5 (2.0, 3.1), and 3.6 (2.9, 4.4), respectively. When we weighted cumulative stress scores according to the magnitude of stressor-specific odds ratios, similar associations were observed. Cumulative stressor exposure did not account for the strong inverse association between age and gastroschisis risk., Conclusions: These findings show that gastroschisis risk appears to increase with accumulation of widely different types of exposures, consistent with the hypothesis that stress-induced inflammation might play an etiologic role.

Purpose: Exposure misclassification, selection bias, and confounding are important biases in epidemiologic studies, yet only confounding is routinely addressed quantitatively. We describe how to combine two previously described methods and adjust for multiple biases using logistic regression., Methods: Weights were created from selection probabilities and predictive values for exposure classification and applied to multivariable logistic regression models in a case-control study of prepregnancy obesity (body mass index ≥30 vs. <30 kg/m 2 ) and cleft lip with or without cleft palate (CL/P) using data from the National Birth Defects Prevention Study (2523 cases, 10,605 controls)., Results: Adjusting for confounding by race/ethnicity, prepregnancy obesity, and CL/P were weakly associated (odds ratio [OR]: 1.10; 95% confidence interval: 0.98, 1.23). After weighting the data to account for exposure misclassification, missing exposure data, selection bias, and confounding, multiple bias-adjusted ORs ranged from 0.94 to 1.03 in nonprobabilistic bias analyses and median multiple bias-adjusted ORs ranged from 0.93 to 1.02 in probabilistic analyses., Conclusions: This approach, adjusting for multiple biases using a logistic regression model, suggested that the observed association between obesity and CL/P could be due to the presence of bias., (Published by Elsevier Inc.)

Background: There are limited population-based studies on microcephaly. We characterized the epidemiology of microcephaly in Texas during a 5-year period (2008-2012), prior to the Zika epidemic in the Western hemisphere (2015). The associations of suspected risk factors were compared across four clearly defined case groups., Methods: Data from the Texas Birth Defects Registry were used to calculate the prevalence of congenital microcephaly and crude and adjusted prevalence ratios using Poisson regression. Twelve maternal and infant factors were assessed across case groups, which included total (explained + unexplained), explained (e.g., syndromic), unexplained, and severe unexplained microcephaly (head circumference <3 rd percentile)., Results: The birth prevalence for total and total severe microcephaly were 14.7 and 4.8 per 10,000 livebirths, respectively. For explained and unexplained cases, significantly elevated risks were noted for mothers who were older (35+), less educated (≤12 years), diabetic (pre-pregnancy or gestational), or had a preterm delivery. Unlike explained cases, however, mothers who were non-White or smoked had an increased risk for unexplained microcephaly. Furthermore, young maternal age (<20), multiparity, and higher BMI reduced the risk for unexplained microcephaly. For severe unexplained cases, the risk profile was similar to that for all unexplained cases-with the exception of null associations noted for diabetes and birth year., Conclusions: We found that risk patterns for microcephaly varied across case groupings. Risk factors included maternal race/ethnicity, age, and smoking during pregnancy. Among severe unexplained cases, notable positive associations were seen among mothers who were non-Hispanic Black or less educated, while inverse associations were noted for obesity., (© 2017 Wiley Periodicals, Inc.)

Background: As maternal fever affects approximately 6-8% of early pregnancies, it is important to expand upon previous observations of an association between maternal fever and birth defects., Methods: We analyzed data from the National Birth Defects Prevention Study, a multistate, case-control study of major structural birth defects. Telephone interviews were completed by mothers of cases (n = 17,162) and controls (n = 10,127). Using multivariable logistic regression, we assessed the association between maternal self-report of cold or flu with fever and cold or flu without fever during early pregnancy and 30 categories of non-cardiac birth defects., Results: Maternal report of cold or flu with fever was significantly associated with 8 birth defects (anencephaly, spina bifida, encephalocele, cleft lip with or without cleft palate, colonic atresia/stenosis, bilateral renal agenesis/hypoplasia, limb reduction defects, and gastroschisis) with elevated adjusted odds ratios ranging from 1.2 to 3.7. Maternal report of cold or flu without fever was not associated with any of the birth defects studied., Conclusions: This study adds to the evidence that maternal fever during early pregnancy is associated with an increased risk for selected birth defects. Elevated associations were limited to mothers who reported a fever, suggesting that it is fever that contributes to the excess risk rather than illnesses associated with it. However, fever may also serve as a marker for more severe infections., (© 2017 Wiley Periodicals, Inc.)

Background: Thyroid disorders are common among reproductive-aged women, with hypothyroidism affecting 2 to 3% of pregnancies, and hyperthyroidism affecting an additional 0.1 to 1%. We examined associations between thyroid medications and individual birth defects using data from the National Birth Defects Prevention Study (NBDPS)., Methods: The NBDPS is a multisite, population-based, case-control study that included pregnancies with estimated delivery dates from 1997 to 2011. We analyzed self-reported thyroid medication use from mothers of 31,409 birth defect cases and 11,536 unaffected controls. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression for birth defects with five or more exposed cases, controlling for maternal age, race/ethnicity, and study center. Crude ORs and exact 95% CIs were estimated for defects with 3 to 4 exposed cases., Results: Thyroid hormone was used by 738 (2.3%) case and 237 (2.1%) control mothers, and was associated with anencephaly (OR = 1.68; 95% CI, 1.03-2.73), holoprosencephaly (OR = 2.48; 95% CI, 1.13-5.44), hydrocephaly (1.77; 95% CI, 1.07-2.95) and small intestinal atresia (OR = 1.81; 95% CI, 1.04-3.15). Anti-thyroid medication was used by 34 (0.1%) case and 10 (<0.1%) control mothers, and was associated with aortic valve stenosis (OR = 6.91; 95% CI, 1.21-27.0)., Conclusion: While new associations were identified, our findings are relatively consistent with previous NBDPS analyses. Our findings suggest thyroid medication use is not associated with most birth defects studied in the NBDPS, but may be associated with some specific birth defects. These results should not be interpreted to suggest that medications used to treat thyroid disease are teratogens, as the observed associations may reflect effects of the underlying thyroid disease. Birth Defects Research 109:1471-1481, 2017.© 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Introduction: Previous studies found that aircraft maintenance workers may be exposed to organophosphates in hydraulic fluid and engine oil. Studies have also illustrated a link between long-term low-level organophosphate pesticide exposure and depression., Methods: A questionnaire containing the Patient Health Questionnaire 8 depression screener was e-mailed to 52,080 aircraft maintenance workers (with N = 4801 complete responses) in a cross-sectional study to determine prevalence and severity of depression and descriptions of their occupational exposures., Results: There was no significant difference between reported depression prevalence and severity in similar exposure groups in which aircraft maintenance workers were exposed or may have been exposed to organophosphate esters compared to similar exposure groups in which they were not exposed. However, a dichotomous measure of the prevalence of depression was significantly associated with self-reported exposure levels from low (OR: 1.21) to moderate (OR: 1.68) to high exposure (OR: 2.70) and with each exposure route including contact (OR: 1.68), inhalation (OR: 2.52), and ingestion (OR: 2.55). A self-reported four-level measure of depression severity was also associated with a self-reported four-level measure of exposure., Discussion: Based on self-reported exposures and outcomes, an association is observed between organophosphate exposure and depression; however, we cannot assume that the associations we observed are causal because some workers may have been more likely to report exposure to organophosphate esters and also more likely to report depression. Future studies should consider using a larger sample size, better methods for characterizing crew chief exposures, and bioassays to measure dose rather than exposure. Hardos JE, Whitehead LW, Han I, Ott DK, Waller DK. Depression prevalence and exposure to organophosphate esters in aircraft maintenance workers. Aerosp Med Hum Perform. 2016; 87(8):712-717.

Objective To assess the potential impact of missing data on body mass index (BMI) on the association between prepregnancy obesity and specific birth defects. Methods Data from the National Birth Defects Prevention Study (NBDPS) were analyzed. We assessed the factors associated with missing BMI data among mothers of infants without birth defects. Four analytic methods were then used to assess the impact of missing BMI data on the association between maternal prepregnancy obesity and three birth defects; spina bifida, gastroschisis, and cleft lip with/without cleft palate. The analytic methods were: (1) complete case analysis; (2) assignment of missing values to either obese or normal BMI; (3) multiple imputation; and (4) probabilistic sensitivity analysis. Logistic regression was used to estimate crude and adjusted odds ratios (aOR) and 95 % confidence intervals (CI). Results Of NBDPS control mothers 4.6 % were missing BMI data, and most of the missing values were attributable to missing height (~90 %). Missing BMI data was associated with birth outside of the US (aOR 8.6; 95 % CI 5.5, 13.4), interview in Spanish (aOR 2.4; 95 % CI 1.8, 3.2), Hispanic ethnicity (aOR 2.0; 95 % CI 1.2, 3.4), and <12 years education (aOR 2.3; 95 % CI 1.7, 3.1). Overall the results of the multiple imputation and probabilistic sensitivity analysis were similar to the complete case analysis. Conclusions Although in some scenarios missing BMI data can bias the magnitude of association, it does not appear likely to have impacted conclusions from a traditional complete case analysis of these data.

Background: An increasing number of radiologic exams are performed in the United States, but very few studies have examined the effects of maternal exposure to radiologic exams during the periconceptional period and birth defects., Objectives: To assess the association between maternal exposure to radiologic exams during the periconceptional period and 19 categories of birth defects using a large population-based study of birth defects., Methods: We studied 27,809 case mothers and 10,200 control mothers who participated in the National Birth Defects Prevention Study and delivered between 1997 and 2009. Maternal exposure to radiologic exams that delivered ionizing radiation to the urinary tract, lumbar spine, abdomen, or pelvis were identified based on the mother's report of type of radiologic exams, organ or body part scanned and the month during which the exam occurred, Results: Overall, 0.9% of mothers reported exposure to one of these types of radiographic exams during the periconceptional period. We observed significant associations between maternal exposure during the first trimester and isolated Dandy-Walker malformation (odds ratio = 7.7; 95% confidence interval, 1.8-33) and isolated d-transposition of the great arteries (odds ratio = 3.8; 95% confidence interval, 1.4-10.3). However, the result for isolated Dandy-Walker malformation was based on only two exposed cases., Conclusion: These results should be interpreted cautiously because multiple statistical tests were conducted and measurements of exposure were based on maternal report. However, our results may be useful for generating hypotheses for future studies. Birth Defects Research (Part A) 106:563-572, 2016. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Objective: To investigate ICU utilization and hospital outcomes of oncological patients admitted to a comprehensive cancer center., Design: Observational cohort study., Setting: The University of Texas MD Anderson Cancer Center., Patients: Consecutive adults with cancer discharged over a 20-year period., Interventions: None., Measurements and Main Results: The Cochran-Armitage test for trend was used to evaluate ICU utilization and hospital mortality rates by primary service over time. A negative binomial log linear regression model was fitted to the data to investigate length of stay over time. Among 387,306 adult hospitalized patients, the ICU utilization rate was 12.9%. The overall hospital mortality rate was 3.6%: 16.2% among patients with an ICU stay and 1.8% among non-ICU patients. Among those admitted to the ICU, the mean (SD) admission Sequential Organ Failure Assessment score was 6.1 (3.8) for all ICU patients: 7.3 (4.4) for medical ICU patients and 4.9 (2.8) for surgical ICU patients. Hematologic disorders were associated with the highest hospital mortality rate in ICU patients (42.8%); metastatic disease had the highest mortality rate in non-ICU patients (4.2%); sepsis, pneumonia, and other infections had the highest mortality rate for all inpatients (8.5%)., Conclusions: This study provides a longitudinal view of ICU utilization rates, hospital and ICU length of stay, and severity-adjusted mortality rates. Although the data arise from a single institution, it encompasses a large number of hospital admissions over two decades and can serve as a point of comparison for future oncological studies at similar institutions. More studies of this nature are needed to determine whether consolidation of cancer care into specialized large-volume facilities may improve outcomes, while simultaneously sustaining appropriate resource utilization and reducing unnecessary healthcare costs.

Few studies have examined associations between polycyclic aromatic hydrocarbons (PAHs) and birth outcomes, and no studies have been conducted in El Paso County Texas, along the United States-Mexico border. Infants born from 2005-2007 to Hispanic mothers with a birth weight less than the 10th percentile for gestational age and sex were classified as small for gestational age (SGA). PAH exposures were estimated for the entire period of gestation and for each trimester of pregnancy using ambient air monitoring data from 2004-2007. Logistic regression was used to estimate odds ratios for the association between PAH levels and SGA infants. There was marked seasonal variation in the carcinogenic PAHs. Established risk factors for SGA were observed to be associated with SGA births in this population. No associations were detected between PAH levels and SGA births. These findings provide no evidence of an association between PAHs and SGA infants.

Background: Clostridium difficile-associated diarrhea (CDAD) is increasingly diagnosed in children in community settings. This study aims to assess recent antibiotic use and other risk factors in children with community-associated (CA-) CDAD compared with children with other diarrheal illnesses in a tertiary care setting., Methods: Children with CA-CDAD evaluated at Texas Children's Hospital (Houston, TX) from January 1, 2012 to June 30, 2013 were identified. Two control subjects with community-associated diarrhea who tested negative for C. difficile were matched to case subjects. Data on demographics, medication exposure and outpatient healthcare encounters were collected from medical records. Multivariate logistic regression was performed to identify predictors of pediatric CA-CDAD., Results: Of 69 CA-CDAD cases, most (62.3%) had an underlying chronic medical condition and 40.6% had antibiotic exposure within 30 days of illness. However, no traditional risk factor for CDAD was identified in 23.2% and 15.9% of CA-CDAD cases within 30 and 90 days of illness onset, respectively. Outpatient healthcare encounters within 30 days were more common among CA-CDAD cases than control subjects (66.7% vs. 48.6%; P = 0.01). In the final multivariate model, CA-CDAD was associated with cephalosporin use within 30 days [odds ratio: 3.32; 95% confidence interval: 1.10-10.01] and the presence of a gastrointestinal feeding device (odds ratio: 2.59; 95% confidence interval: 1.07-6.30)., Conclusions: Recent use of cephalosporins and the presence of gastrointestinal feeding devices are important risk factors for community- associated CDAD in children. Reduction in the use of outpatient antibiotics may decrease the burden of CA-CDAD in children.

Background: The majority of hospital deaths in the United States occur after ICU admission. The characteristics associated with the place of death within the hospital are not known for patients with cancer., Objective: The study objective was to identify patient characteristics associated with place of death among hospitalized patients with cancer who were at the end of life., Methods: A retrospective cohort study design was implemented. Subjects were consecutive patients hospitalized between 2003 and 2007 at a large comprehensive cancer center in the United States. Multinomial logistic regression analysis was used to identify patient characteristics associated with place of death (ICU, hospital following ICU, hospital without ICU) among hospital decedents., Results: Among 105,157 hospital discharges, 3860 (3.7%) died in the hospital: 42% in the ICU, 14% in the hospital following an ICU stay, and 44% in the hospital without ICU services. Individuals with the following characteristics had an increased risk of dying in the ICU: nonlocal residence, newly diagnosed hematologic or nonmetastatic solid tumor malignancies, elective admission, surgical or pediatric services. A palliative care consultation on admission was associated with dying in the hospital without ICU services., Conclusions: Understanding existing patterns of care at the end of life will help guide decisions about resource allocation and palliative care programs. Patients who seek care at dedicated cancer centers may elect more aggressive care; thus the generalizability of this study is limited. Although dying in a hospital may be unavoidable for patients who have uncontrolled symptoms that cannot be managed at home, palliative care consultations with patients and their families in advance regarding end-of-life preferences may prevent unwanted admission to the ICU.

Background: Ionizing radiation (IR) is known to be carcinogenic and mutagenic, but little is known about the association between maternal occupational exposure to IR and birth defects., Methods: We studied 38,009 mothers who participated in the National Birth Defects Prevention Study and delivered between 1997 and 2009. We assessed odds ratios [ORs] for the association between maternal occupations with potential exposure to IR and 39 birth defects., Results: We observed significant odds ratios (ORs) for isolated hydrocephaly (adjusted OR [AOR], 2.1; 95% confidence interval [CI], 1.1-4.2), isolated anotia/microtia (AOR, 2.0; 95% CI, 1.0-4.0), isolated colonic atresia (crude OR, 7.5; 95% CI, 2.5-22.3), isolated omphalocele (AOR, 2.3; 95% CI, 1.1-4.6) and isolated anencephaly (crude OR, 0.23; 95% CI, 0.06-0.94). We also observed a nonsignificant OR for birth defects in aggregate (AOR, 2.0; 95% CI, 0.9-4.6) among mothers with potential occupational exposure to fluoroscopy., Conclusion: We assessed 39 birth defects, observing that maternal occupations with potential exposure to IR were associated with a significantly increased risk for 4 birth defects and a significantly protected risk for 1 birth defect. These results should be interpreted cautiously because our measurement of exposure is qualitative, some of these associations may be due to occupational exposures that are correlated with IR and some may be due to chance. However, these findings serve as the first evaluation of these relationships in a large study and may be useful for generating hypotheses for future studies., (© 2015 Wiley Periodicals, Inc.)

Background: Previous studies observed that first birth is associated with an increased risk of some categories of birth defects. However, multiple statistical tests were conducted and it was unclear which of these associations would be replicated in a larger study. We used a large database to assess the association between maternal parity and 65 birth defects including birth defects that have not been previously studied., Methods: Using data from the Texas Birth Defects Registry for years 1999-2009, the risk of a birth defect occurring in a first, third, or fourth or higher birth was compared to the risk of a birth defect occurring in a second birth., Results: Women having their first birth had significantly increased odds of having an infant with 24 of 65 categories of birth defects when compared to women having their second birth. We also observed associations between first birth and an increased risk of five birth defects not previously reported (small penis, preaxial polydactyly, anomalies of the thoracic vertebrae, anomalies of the lumbar vertebrae, and sacroccygeal anomalies). Women having their third or fourth or higher birth had significantly increased odds of giving birth to infants with five of 65 birth defects when compared to second births., Conclusions: Our observations regarding the categories of birth defects that were associated with first births were highly consistent with observations from two previous studies. Research into biological, behavioral, and environmental factors that may increase the risk of specific birth defects among first births is needed to further explore these associations., (© 2015 Wiley Periodicals, Inc.)

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., (© 2014 Wiley Periodicals, Inc.)

Background: Most studies and national programs aggregate the different types of surgical site infections (SSIs) potentially masking and misattributing risk. Determining that risk factors for superficial, deep, and organ space SSIs are unique is essential to improve SSI rates., Methods: This cohort study utilized data of 59,365 patients who underwent colon resection at hospitals participating in the American College of Surgeons National Surgical Quality Improvement Program from 2007 to 2009. Four independent, multivariable, predictive models were developed to assess the unique associations between risk factors and each SSI group: Superficial, deep, organ space, and an aggregate of all 3 types of SSIs., Results: Overall, 13% of colon cases developed SSIs: Superficial (8%), deep (1.4%), and organ space (3.8%). Each model was different. Morbidly obese patients were more likely to develop SSIs than normal weight patients across all models; however, risk factors common to all models (eg, body mass index [BMI], duration of operation, wound class, laparoscopic approach) had very different levels of risk. Unique risks for superficial SSIs include diabetes, chronic obstructive pulmonary disease, and dyspnea. Deep SSIs had the greatest magnitude of association with BMI and the greatest incidence of wound disruption (19.8%). Organ space SSIs were often owing to anastomotic leaks and were uniquely associated with disseminated cancer, preoperative dialysis, preoperative radiation treatment, and a bleeding disorder, suggesting a physically frail or compromised patient may put the anastomosis at risk., Conclusion: Risk factors for superficial, deep, and organ space SSI differ. More effective prevention strategies may be developed by reporting and examining each type of SSI separately., (Copyright © 2014 Elsevier Inc. All rights reserved.)

It remains unclear when the fetus is most susceptible to the effects of particulate air pollution. We conducted a population-based study in a large urban area to evaluate associations between preterm birth (PTB) and fetal growth and exposures to fine particles (PM(2.5)) during narrow periods of gestation. We identified 177,816 births during 2005-2007 among mothers who resided in Harris County, Texas at the time of delivery. We created three mutually exclusive categories of mildly (33-36 completed weeks of gestation), moderately (29-32 weeks of gestation), and severely (20-28 weeks of gestation) PTB, and among full term infants, we identified those who were born small for their gestational age. Using routine air monitoring data, we generated county-level daily time series of estimated ambient air levels of PM2.5 and then computed exposure metrics during every 4 weeks of a mother's pregnancy. We evaluated associations in each 4-week period using multiple logistic regression. A 10 μg/m(3) increase in PM(2.5) exposure in the first 4 weeks of pregnancy significantly increased the odds of mildly, moderately and severely PTB by 16, 71 and 73 %, respectively. Associations were stronger when infants with birth defects were excluded. Our findings indicate an association between PM(2.5) and PTB, with stronger associations for moderately and severely PTB infants. Efforts should continue to implement stricter air quality standards and improve ambient air quality.

Background: Increased availability and usage of ultrasound screening have led to improved identification of fetal structural abnormalities prenatally. Few population-based studies have been published on prenatal detection for structural birth defects in the United States. The aim of this study is to determine the frequency of maternal reporting of abnormal prenatal ultrasounds for selected birth defects and to investigate associated maternal characteristics., Methods: Participants included 4013 mothers enrolled in the National Birth Defects Prevention Study who carried a fetus with at least one of 14 structural birth defects between 1997 and 2004. Frequencies of abnormal prenatal ultrasounds were based on maternal report and computed for isolated and multiple defects. Associations between maternal characteristics and abnormal prenatal ultrasounds were assessed using logistic regression., Results: Overall, 46% of participants reported an abnormal ultrasound. Infants with omphalocele, anencephaly, gastroschisis, and renal agenesis were more likely to have abnormal prenatal ultrasounds than those with cleft and limb abnormalities. Hispanic women were less likely to report abnormal prenatal ultrasounds of birth defects than Caucasians, as were women who had a body mass index ≥ 30 kg/m(2) compared with those with a normal body mass index., Conclusion: Of the 14 selected birth defects in this study, less than half were reported by mothers of affected infants to have had an abnormal ultrasound during pregnancy. The frequency of reporting abnormal prenatal ultrasounds varies by type of defect, maternal race/ethnicity, and maternal body mass index status., (Copyright © 2013 Wiley Periodicals, Inc.)

Background: Nearly all women shower or take baths during early pregnancy; however, bathing habits (i.e., shower and bath length and frequency) may be related to the risk of maternal hyperthermia and exposure to water disinfection byproducts, both of which are suspected to increase risk for multiple types of birth defects. Thus, we assessed the relationships between bathing habits during pregnancy and the risk for several nonsyndromic birth defects in offspring., Methods: Data for cases with one of 13 types of birth defects and controls from the National Birth Defects Prevention Study delivered during 2000-2007 were evaluated. Logistic regression analyses were conducted separately for each type of birth defect., Results: There were few associations between shower frequency or bath frequency or length and risk for birth defects in offspring. The risk for gastroschisis in offspring was increased among women who reported showers lasting ≥15 compared to <15 minutes (adjusted odds ratio: 1.43, 95% confidence interval: 1.18-1.72). In addition, we observed modest increases in the risk for spina bifida, cleft lip with or without cleft palate, and limb reduction defects in offspring of women who showered ≥15 compared to <15 minutes. The results of comparisons among more specific categories of shower length (i.e., <15 minutes versus 15-19, 20-29, and ≥ 30 minutes) were similar., Conclusions: Our findings suggest that shower length may be associated with gastroschisis, but the modest associations with other birth defects were not supported by analyses of bath length or bath or shower frequency. Given that showering for ≥15 minutes during pregnancy is very common, further evaluation of the relationship between maternal showering habits and birth defects in offspring is worthwhile.

Few studies have evaluated genetic susceptibility related to diabetes and obesity as a risk factor for neural tube defects (NTDs). The authors investigated 23 single nucleotide polymorphisms among 9 genes (ADRB3, ENPP1, FTO, LEP, PPARG, PPARGC1A, SLC2A2, TCF7L2, and UCP2) associated with type 2 diabetes or obesity. Samples were obtained from 737 NTD case-parent triads included in the National Birth Defects Prevention Study during 1999-2007. Log-linear models were used to evaluate maternal and offspring genetic effects. After application of the false discovery rate, there were 5 significant maternal genetic effects. The less common alleles at the 4 FTO single nucleotide polymorphisms showed a reduction of NTD risk (for rs1421085, relative risk (RR) = 0.73 (95% confidence interval (CI): 0.62, 0.87); for rs8050136, RR = 0.79 (95% CI: 0.67, 0.93); for rs9939609, RR = 0.79 (95% CI: 0.67, 0.94); and for rs17187449, RR = 0.80 (95% CI: 0.68, 0.95)). Additionally, maternal LEP rs2071045 (RR = 1.31, 95% CI: 1.08, 1.60) and offspring UCP2 rs660339 (RR = 1.32, 95% CI: 1.06, 1.64) were associated with NTD risk. Furthermore, the maternal genotype for TCF7L2 rs3814573 suggested an increased NTD risk among obese women. These findings indicate that maternal genetic variants associated with glucose homeostasis may modify the risk of having an NTD-affected pregnancy.

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., (Copyright © 2012 Wiley Periodicals, Inc.)

Background: We examined differences in selected pregnancy-related risk factors, including maternal sociodemographic characteristics, health-related conditions, and periconceptional behavioral factors, among foreign-born versus U.S.-born control mothers across race/ethnic groups., Methods: We used data from the National Birth Defects Prevention Study, and calculated odds ratios (ORs) and 95% confidence intervals (CIs) of the risk factors, for foreign-born Hispanic, non-Hispanic white, non-Hispanic black, and Asian/Pacific Islander (API) mothers, compared to their U.S.-born counterparts., Results: Across all race/ethnic groups, foreign-born mothers were older and had lower odds of obesity compared to their U.S.-born counterparts. With the exception of foreign-born black mothers, foreign-born mothers from other race/ethnic groups had significantly lower odds of binge drinking during the periconceptional period. Compared to U.S.-born, foreign-born Hispanic mothers had twice the odds of gestational diabetes (OR = 2.23; 95% CI = 1.36-3.66). Certain health behaviors were less prevalent in foreign-born black mothers (e.g., folic acid use; OR = 0.54; 95% CI = 0.31-0.96) and foreign-born API mothers (e.g., cigarette smoking; OR = 0.10; 95% CI = 0.02-0.48)., Conclusions: Significant differences in pregnancy related risk factors during the periconceptional period and throughout pregnancy were observed between maternal nativity groups and across race/ethnicity. Prevention efforts for both prepregnancy and after conception should be designed and delivered according to maternal nativity for each racial/ethnic group., (Copyright © 2011 Wiley-Liss, Inc.)

Background: Previous studies have reported positive associations between maternal exposure to air pollutants and several adverse birth outcomes. However, there have been no studies assessing the association between environmental levels of hazardous air pollutants, such as benzene, and neural tube defects (NTDs), a common and serious group of congenital malformations., Objective: Our goal was to conduct a case-control study assessing the association between ambient air levels of benzene, toluene, ethylbenzene, and xylene (BTEX) and the prevalence of NTDs among offspring., Methods: The Texas Birth Defects Registry provided data on NTD cases (spina bifida and anencephaly) delivered between 1999 and 2004. The control group was a random sample of unaffected live births, frequency matched to cases on year of birth. Census tract-level estimates of annual BTEX levels were obtained from the U.S. Environmental Protection Agency 1999 Assessment System for Population Exposure Nationwide. Restricted cubic splines were used in mixed-effects logistic regression models to determine associations between each pollutant and NTD phenotype., Results: Mothers living in census tracts with the highest benzene levels were more likely to have offspring with spina bifida than were women living in census tracts with the lowest levels (odds ratio = 2.30; 95% confidence interval, 1.22-4.33). No significant associations were observed between anencephaly and benzene or between any of the NTD phenotypes and toluene, ethylbenzene, or xylene., Conclusion: In the first study to assess the relationship between environmental levels of BTEX and NTDs, we found an association between benzene and spina bifida. Our results contribute to the growing body of evidence regarding air pollutant exposure and adverse birth outcomes.

Background: In birth defect epidemiology, phenotypic subgroups are often combined into a composite phenotype in an effort to increase statistical power. Although the validity of using composite phenotypes has been questioned, formal evaluations of the underlying assumption of effect homogeneity across component phenotypes have not been conducted., Methods: Polytomous logistic regression was used to assess effect heterogeneity of several generally accepted neural tube defect (NTD) risk factors across the component phenotypes of anencephaly and spina bifida. Data for these analyses were obtained from the National Birth Defects Prevention Study., Results: The use of a composite phenotype has the potential to mask associations specific to a component phenotype and in some cases the effect of a variable may be misattributed to the composite phenotype. For example, an association between infant sex and anencephaly (adjusted odds ratio [AOR], 1.5; 95% CI, 1.1-1.9) was masked when data from all NTDs were analyzed (AOR, 1.1; 95% CI, 0.9-1.3), whereas an association with maternal body mass index that was specific to spina bifida (AOR, 1.9; 95% CI, 1.6-2.4) was attributed to all NTDs (AOR, 1.6; 95% CI, 1.4-2.0). Furthermore, conclusions regarding effect heterogeneity based on ad hoc comparisons, rather than some formal assessment, may be vulnerable to considerable subjectivity, as was the case for the association of maternal Hispanic ethnicity with spina bifida (AOR, 1.4; 95% CI, 1.2-1.8) and anencephaly (AOR, 2.0; 95% CI, 1.5-2.8)., Conclusions: Polytomous logistic regression provides a useful tool for evaluating putative risk factors for which there is no a priori basis for assuming effect homogeneity across component phenotypes.

In studies of reproductive outcomes, maternal residence at delivery is often the only information available to characterise environmental exposures during pregnancy. The goal of this investigation was to describe residential mobility during pregnancy and to assess the extent to which change of residence may result in exposure misclassification when exposure is based on the address at delivery. Maternal residential mobility was compared between neural tube defect cases and unaffected controls from Texas participants in the National Birth Defects Prevention Study (NBDPS). Maternal residential information was obtained from the NBDPS interview. Data from the U.S. EPA National Air Toxics Assessment [Assessment System for Population Exposure Nationwide (ASPEN)], modelled at the census tract level, were used to estimate benzene exposure based on address at conception and address at delivery. Quartiles of exposure were assigned based on these estimates and the quartile assignments based on address at conception and address at delivery were compared using traditional methods (kappa statistics) and a novel application of mixed-effects ordinal logistic regression. Overall, 30% of case mothers and 24% of control mothers moved during pregnancy. Differences in maternal residential mobility were not significant between cases and controls, other than case mothers who moved did so earlier during pregnancy than control mothers (P = 0.01). There was good agreement between quartiles of estimated benzene exposure at both addresses (kappa = 0.78, P < 0.0001). Based on the mixed-effects regression model, address at delivery was not significantly different from using address at conception when assigning quartile of benzene exposure based on estimates from ASPEN (odds ratio 1.03, 95% confidence interval 0.85, 1.25). Our results indicate that, in this Texas population, maternal residential movement is generally within short distances, is typically not different between cases and controls, and does not significantly influence benzene exposure assessment.

An increased risk of birth defects after hyperthermic exposures has been confirmed in animal studies, but population studies have yielded inconsistent results. Oral clefts are a common birth defect and have been associated with these exposures in some of these studies. In this study, data from the National Birth Defects Prevention Study was used to evaluate the association of maternal report of febrile illness in early pregnancy and the risk of oral clefts. All oral cleft cases born between 1997 and 2004 were compared with nonmalformed controls born in the same geographical region during the same time period. Mothers reporting febrile illness during pregnancy were stratified by fever grade and antipyretic use. Logistic regression models were used to generate crude and adjusted odds ratios for exposure to fever and association with each oral cleft phenotype. The dataset included 5821 controls, 1567 cases of cleft lip with or without cleft palate (CL+/-P) and 835 cases of cleft palate only. A modestly increased risk was observed for isolated CL+/-P (odds ratio, 1.28; 95% confidence interval, 1.01-1.63). Stratification by fever grade (body temperature <101.5 degrees or > or =101.5 degrees F) did not yield significant differences in risk. Risk estimates were higher among women who reported a fever, but did not take antipyretics to control their fever, particularly for nonisolated compared with isolated oral clefts. This finding suggests that adequate control of fever may diminish the deleterious effects of fever in cases of oral cleft., (Copyright 2010 Wiley-Liss, Inc.)