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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 He...

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.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 interval12 months, residential move, aspirin use, ibuprofen use, venlafaxine use, and paroxetine use.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.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.

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.

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 (

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.

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 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.Interv

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.

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.

Study design Systematic review OBJECTIVE.: To undertake a systematic review of published literature to evaluate efficacy of bone graft substitutes on radiographic and clinical outcomes in single- or double-level anterior cervical discectomy and fusion (ACDF) for degenerative disease. Summary of background data ACDF is one of the most common spinal surgeries completed in the United States. Today bone graft substitutes including ceramic-based synthetic bone grafts, allografts, bone morphogenetic proteins (BMPs), mesenchymal stem cells, and bone marrow aspirate are widely used to enhance fusions; even though the efficacy of these substitutes is poorly defined. Critical evaluation of these products is necessary to optimize radiographic and clinical outcomes for ACDF in degenerative disease. Methods A systematic literature review of 22 published articles was conducted. All articles reported results on patients who underwent a single- or double-level ACDF performed using a bone graft substitute and reported results on radiographic fusion rates at least 6 months after surgery. Results All studies using BMP showed 100% fusion rate despite length of the study or whether additional bone graft substitutes were used. Use of only ceramic-based synthetics had the lowest fusion rate, 80.5%. Use of only mesenchymal stem cells resulted in an average fusion rate of 87.7%. When used alone, allograft resulted in an average fusion rate of 87.3%. This was significantly influenced by one outlier, Kim et al, which when removed, increased the fusion rate to 93.5%. Clinical outcomes were improved postoperatively irrespective of the graft used, although dysphagia was significantly greater in studies using BMP (P Conclusion Allograft alone has the lowest cost with similar fusion rates and clinical outcomes compared to other bone graft substitutes. Physicians should consider this when choosing to use bone graft substitutes for routine ACDFs. Level of evidence 4.

ObjectiveTo evaluate the relationships between maternal fish consumption and pregnancy outcomes in a large, population-based sample of women in the USA.DesignWe 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 (SettingThe National Birth Defects Prevention Study (NBDPS).SubjectsControl mother–infant pairs with estimated delivery dates between 1997 and 2011 (n 10 919).ResultsNo 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).ConclusionsHigh 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.

Estimate inpatient hospitalization costs for patients with microcephaly, and predict cost increases due to a potential Zika virus outbreak.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.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.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.

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

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.

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.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.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).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.

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 versus

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. Birth Defects Research (Part A) 103:243–254, 2015. © 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. Birth Defects Research (Part A) 103:144–156, 2015 © 2015 Wiley Periodicals, 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

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. Birth Defects Research (Part A) 100:852–862, 2014. © 2014 Wiley Periodicals, Inc.

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/m2 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. Birth Defects Research (Part A) 100:4–12, 2014. © 2013 Wiley Periodicals, Inc.

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. Birth Defects Research (Part A), 2012. © 2012 Wiley Periodicals, Inc.

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/m2 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. Birth Defects Research (Part A) 100:4–12, 2014. © 2013 Wiley Periodicals, Inc.

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. Birth Defects Research (Part A), 2010. © 2010 Wiley-Liss, Inc.

BACKGROUND:: Oral contraceptives (OCs) are the most commonly used reversible contraceptive method among US women. Although the majority of previous studies have reported no association between OC use during pregnancy and birth defects some studies have reported increased occurrence of neural tube defects limb reduction defects and urinary tract anomalies. METHODS:: We assessed OC use among mothers who participated in the multisite case-control National Birth Defects Prevention Study. Mothers of 9986 infants with 32 types of birth defects and 4000 infants without birth defects were included. RESULTS:: Maternal OC use during the first 3 months of pregnancy was associated with an increased odds ratio for 2 of 32 birth defects: hypoplastic left heart syndrome (adjusted odds ratio = 2.3 [95% confidence interval = 1.3-4.3) and gastroschisis (1.8 [1.3-2.7]). CONCLUSION:: Previous reports of associations between OC use and specific types of anomalies were not corroborated. Given that associations were assessed for 32 types of birth defects our findings of 2 increased associations between OC use and gastroschisis and hypoplastic left heart syndrome should be interpreted as hypotheses until they can be evaluated further. Overall our findings are consistent with the majority of previous studies that found women who use OCs during early pregnancy have no increased risk for most types of major congenital malformations.

Trisomies 21, 18, and 13 are the three most common trisomies among infants who survive to 20 weeks gestation or more. Overall information about birth prevalence, natural history, and mortality for all three trisomies is well defined, but information about ethnic-specific rates is limited. Only a few studies have examined mortality rates of trisomies 18 and 13 because so few cases are liveborn and most have very short life spans. This study assessed ethnic-specific population-based survival probabilities among infants for each trisomy. All cases of trisomies 21, 18, and 13 born in Texas between 1999 and 2003 were obtained from the Texas Birth Defects Registry and included 2,260 cases of trisomy 21, 398 cases of trisomy 18, and 213 cases of trisomy 13. Date and cause of death were obtained from the Texas vital statistics records and the National Death Index. Overall, birth prevalence rates (per 10,000 adjusted live births) for the three trisomies were 11.74 (95% CI: 11.25-12.25), 1.34 (95% CI: 1.18-1.52), 0.92 (95% CI: 0.79-1.07), respectively, and are consistent with previously reported rates. There were no differences in survival rates by ethnicity and the median survival for each trisomy was consistent with previous reports. The results of this study provide comprehensive population-based information for survival of infants with trisomies 21, 18, and 13.

Background Women may become pregnant while using contraceptives. Commonly used contraceptives containing spermicides may or may not be associated with an increased occurrence of structural birth defects. Study Design Utilizing data from the National Birth Defects Prevention Study, we assessed maternal reports of spermicide and male condom use 1 to 3 months following conception among case ( n =11,050) and control ( n =4723) mothers. We assessed the association between spermicide use and 27 types of birth defects and that between condom use and 32 types of birth defects. Results Maternal spermicide use during the first 3 months following conception was associated with a significant increase in the occurrence of only 1 of 27 birth defects, perimembranous ventricular septal defects (adjusted odds ratio=2.40, 95% confidence interval=1.25���4.62). There was no significant association between maternal use of male condoms during the first 3 months following conception and any of 32 types of birth defects. Conclusions The increased occurrence of perimembranous ventricular septal defects among spermicide users may be real or may be a chance finding. Overall, the findings are consistent with those of most previous studies that observed no increased risk for birth defects among spermicide users.

BACKGROUND: Literature on the risk of birth defects among foreign- versus U.S.–born Hispanics is limited or inconsistent. We examined the association between country of birth, immigration patterns, and birth defects among Hispanic mothers. METHODS: We used data from the National Birth Defects Prevention Study and calculated odds ratios (ORs) and 95% confidence intervals and assessed the relationship between mothers' country of birth, years lived in the United States, and birth defects among 575 foreign-born compared to 539 U.S.–born Hispanic mothers. RESULTS: Hispanic mothers born in Mexico/Central America were more likely to deliver babies with spina bifida (OR = 1.53) than their U.S.–born counterparts. Also, mothers born in Mexico/Central America or who were recent United States immigrants (≤5 years) were less likely to deliver babies with all atrial septal defects combined, all septal defects combined, or atrial septal defect, secundum type. However, Hispanic foreign-born mothers who lived in the United States for >5 years were more likely to deliver babies with all neural tube defects combined (OR = 1.42), spina bifida (OR = 1.89), and longitudinal limb defects (OR = 2.34). Foreign-born mothers, regardless of their number of years lived in the United States, were more likely to deliver babies with anotia or microtia. CONCLUSIONS: Depending on the type of birth defect, foreign-born Hispanic mothers might be at higher or lower risk of delivering babies with the defects. The differences might reflect variations in predisposition, cultural norms, behavioral characteristics, and/or ascertainment of the birth defects. Birth Defects Research (Part A), 2009. © 2009 Wiley-Liss, Inc.

Background: : Weight loss products are frequently used by reproductive-aged women and these products may be taken (inadvertently or intentionally) during pregnancy. This study assessed the association between periconceptional use of weight loss products and major structural birth defects. Methods: : Mothers of infants with birth defects (case infants) and a random sample of livebirths (control infants) born during the period 1998-2003 in 10 states participated in the National Birth Defects Prevention Study. Adjusted ORs (aORs) for the association between self-reported use of weight loss products and 23 categories of birth defects were calculated. Results: : Mothers of control infants (2.4%) and 2.6% of mothers of case infants reported periconceptional use of weight loss products; 1.2% of mothers of control infants and 1.3% of mothers of case infants reported using an ephedra-containing product. Use of any weight loss product was associated with anencephaly (aOR 2.6; 95% CI: 1.3-5.3), dextro-transposition of the great arteries (aOR 2.1; 95% CI: 1.1-4.3), and aortic stenosis (aOR 3.4; 95% CI: 1.5-7.9). Use of products containing ephedra showed an increased aOR with anencephaly (aOR 2.8; 95% CI: 1.0-7.3), while other weight loss products were associated with dextro-transposition of the great arteries (aOR 1.8; 95% CI: 1.2-2.7), and aortic stenosis (aOR 2.1; 95% CI: 1.3-3.5). Conclusions: : These results suggest an association between periconceptional use of weight loss products and certain birth defects but the possible mechanism is not clear. This is the first finding of such an association and, because we examined a large number of exposure-outcome associations in a hypothesis-generating analysis, these results might have been due to chance.

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.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.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.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.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.

Several large-scale cohort studies suggest that obese mothers are at increased risk of having infants with neural tube defects and, possibly, other central nervous system (CNS) birth defects. Because obesity and diabetes share similar metabolic abnormalities, a study was planned to determine whether gestational diabetes influences the association between maternal obesity and CNS birth defects. In this population-based case–control study, covering the years 1997 to mid-2000, structured telephone interviews were conducted with mothers of offspring having anencephaly (n = 120), spina bifida (n = 184), holoprosencephaly (n = 49), or isolated hydrocephaly (n = 124). Control women whose infants were neurologically normal were randomly chosen from the same hospitals. Approximately 60% of both cases and control subjects responded. Maternal obesity was defined as a body mass index of 30 kg/m2 or higher. Pregestational diabetes, both type 1 and type 2, correlated closely with holoprosencephaly (adjusted odds ratio [OR], 47; 95% confidence interval [CI], 9.5–230), and isolated hydrocephaly (OR, 12; 95% CI, 2.9–47). There was no increase in the risk of anencephaly or spina bifida. Gestational diabetes increased only the risk of holoprosencephaly (OR, 2.9; 95% CI, 1.0–8.4). Mothers of infants with anencephaly were less likely than control mothers to have gestational diabetes. Obese mothers were likelier than control subjects to have infants with any of the 4 CNS birth defects. Underweight women were less likely to have an infant with spina bifida. The association between maternal obesity and an increased risk of neural tube defects and isolated hydrocephaly held for all ethnic groups. Associations between maternal obesity and anencephaly (OR, 2.3; 95% CI, 1.2–4.3), spina bifida (OR, 2.8; 95% CI, 1.7–4.5), and isolated hydrocephaly (OR, 2.7; 95% CI, 1.5–5.0) persisted after adjusting for maternal age, ethnicity, education, smoking, alcohol use, and periconceptional vitamin use. For both spina bifida and holoprosencephaly, the joint effects of maternal obesity and gestational diabetes appeared to be interactive. These findings suggest that gestational diabetes and maternal obesity may increase the risk of CNS birth defects through common mechanisms, and they strongly support the need for ways of preventing these conditions.

Idiopathic talipes equinovarus (ITEV) is the most common form of clubfoot with a birth prevalence of 1 per 1,000 births. Serial casting and surgical correction impose a substantial financial burden on families and the health care system. While the etiology of ITEV is considered to be complex, the causes remain elusive. Genetic, maternal, and environmental factors have been suggested to play an etiologic role. This study was undertaken to determine the prevalence of ITEV and define maternal and environmental factors associated with ITEV in Texas from 1996 to 1999. Data on 682 cases of nonsyndromic ITEV were compared with all births (n = 923,543) in Texas during the same period. The overall prevalence and prevalence odds ratios (PORs) were calculated for gender, year of birth, public health region (PHR), race, maternal age, education, folic acid fortification, and parity. The overall prevalence of ITEV was 0.74/1,000 or 1/1,354 live births. Adjusted PORs were similar among blacks and US and foreign-born Hispanics (POR = 0.92, 95% CI = 0.69-1.21; POR = 0.99, 95% CI = 0.79-1.25; and POR = 0.94, 95% CI = 0.74-1.19), respectively, compared to whites. College education and higher parity were significantly associated with a lower risk of giving birth to offspring with ITEV. Babies born after folic acid fortification of grains had a very small decrease in ITEV that may be due to chance.

BACKGROUND Neural tube defects (NTDs) affect approximately 4000 US pregnancies annually. Folic acid supplementation taken before conception protects against the occurrence of NTDs. Adequate levels of vitamin B12 also appear to play a significant role. Gastrointestinal disturbances, such as those caused by diarrhea, might negatively affect the availability of these vitamins, thereby increasing the risk of these birth defects. METHODS To determine whether periconceptional diarrhea increases the risk of NTD-affected pregnancies, a population-based case-control study was conducted in the 14 Texas–Mexico border counties. Information on diarrhea and other risk factors was ascertained by in-person interview. Study subjects were Mexican-American women who resided and delivered in any border county during 1995–2000. Case women, identified through active surveillance, had liveborn or stillborn infants or fetuses diagnosed with anencephalus, spina bifida, or encephalocele. Control women were randomly selected from women delivering normal live births in study area health facilities. RESULTS One or more episodes of periconceptional diarrhea were associated with increased risk of NTD-affected pregnancies compared to no episodes of diarrhea (OR = 3.7, 95% CI = 1.8–7.6). This association was independent of fever, obesity, maternal age, maternal birthplace, income, prior unproductive pregnancy, and dietary plus multivitamin folate intake, known risk factors for NTDs. CONCLUSIONS Confirmation of this new risk factor might have public health implications due to the feasibility of modifying exposure. Birth Defects Research (Part A) 67:504–508, 2003. © 2003 Wiley-Liss, Inc.

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.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.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.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.

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.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.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.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.

Background Approximately 85% of primary congenital hypothyroidism (CH) is sporadic and due to malformations of the thyroid gland. Past studies have reported an increased birth weight among infants with CH. We have attempted to replicate and expand these observations, examining the association between different birth weight categories and CH stratified by infant's sex. We have also examined the prevalence of CH by mother's age and infant's ethnicity, gender, and year of birth. Methods A cross-sectional study was conducted on 5,049,185 infants screened by the statewide California Newborn Screening Program between 1990 and 1998, an estimated 98.6% of all newborns in the state. Dried blood spots from a heel stick were assayed for thyroxine (T4), and presumptive positives had follow-up assays of thyroid-stimulating hormone (TSH) to determine definite positives. Results A total of 1,806 cases of CH were identified. The following findings are unlikely to be due to chance. Compared with infants with birth weights of 3,000–3,499 g, infants weighing

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 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.

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.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.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.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.

Neural tube defects (NTDs) are among the most common, most costly, and most deadly of all human congenital anomalies whose etiologies remain largely unknown (1, 2). NTDs include a range of malformations (e.g., spina bifida, anencephaly), which further complicates the identification of risk factors. Two well-established risk factors for NTDs are maternal pregestational diabetes and prepregnancy obesity (3–12). Although mechanisms underlying these risks remain unclear, there is evidence that infants born to obese mothers and infants born to diabetic mothers may share some common underlying pathogenic exposures, including alteration of glucose homeostasis and hyperglycemia (13–18). Glucose is monitored and regulated by the pancreas and is an essential fuel for oxidative metabolism. During early organogenesis, there is high demand for glucose, since the embryo is dependent on uninterrupted anaerobic glycolysis before the chorioallantoic placenta is developed. Evidence suggests that the early embryo does not have pancreatic function until the development of β cells, which occurs after the seventh week of gestation (19). Thus, at the time of neural tube closure (approximately the fourth week of gestation), mothers with poorly regulated glucose levels are likely to have an altered in utero environment, which cannot be managed by the developing embryo, leading to abnormal organogenesis (20–22). Several genes related to glucose homeostasis have been previously identified in human and animal studies. Furthermore, genes related to glucose homeostasis have been associated with type 2 diabetes and obesity risk in genome-wide association studies (23, 24). A few studies have investigated some of these genes in relation to NTD risk, with positive findings (25, 26); however, these analyses have been limited to a small number of single nucleotide polymorphisms (SNPs) or have not assessed the role of maternal genetic effects. Therefore, our objective in this study was to investigate the roles of several maternal and offspring genes related to glucose homeostasis in the risk of NTDs.

Our purpose was to determine whether obese women and underweight women have an increased risk of birth defects in their offspring.A geographically based case-control study of women living in California and Illinois was performed. There were 499 mothers of offspring with neural tube defects, 337 mothers of offspring with other major birth defects, and 534 mothers of offspring without birth defects who participated.Compared with women of normal weight, women who were extremely obese before pregnancy (body mass indexor = 31 kg/m2) showed a significantly increased risk of having an infant with a neural tube defect (odds ratio 1.8, 95% confidence interval 1.1 to 3.0), especially spina bifida (odds ratio 2.6, 95% confidence interval 1.5 to 4.5), after adjustments for age, race, education, and family income. Obese women also had significantly increased risks (p0.05) of having an infant with other defects of the central nervous system, great vessel defects, ventral wall defects, or other intestinal defects.Our data suggest that offspring of obese women (but not underweight women) are at an increased risk of neural tube defects and several other malformations. If these findings are confirmed, further research will be necessary before it can be concluded that weight reduction before pregnancy will lower the risk of birth defects among obese women. Until then, obese women can address their risk of birth defects with the same measures that are recommended for all women, such as adequate daily intake of folic acid and alpha-fetoprotein screening to identify malformed fetuses.

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.

Beginning in 1977, numerous studies have reported an association between high levels of maternal serum alpha-fetoprotein, measured in early pregnancy, and low birthweight and perinatal death. It has been suggested, however, that these findings may be explained by bias. We reviewed 21 studies and found that they were unanimous in reporting this association and that the association cannot be explained by any of the proposed biases. Comparing women whose alpha-fetoprotein levels were 2.5 times the median or more with all other women, the highest relative risk of fetal death was 21.0, with a 95% confidence interval of 8.4-52.2, and the lowest relative risk of fetal death was 4.4, with a 95% confidence interval of 2.8-7.0. For low birthweight (< 2,500 grams), the highest relative risk was 6.4 (95% confidence interval = 3.1-13.1) and the lowest relative risk was 1.9 (95% confidence interval = 1.5-2.5).

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. Birth Defects Research (Part A), 2011. © 2011 Wiley-Liss, Inc.