Adrienne T. Hoyt

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.

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.

Background There are often questions about the impact of exposures on a range of birth defects, but there are few rigorous approaches for evaluating these associations. Using maternal smoking as an example we applied a phenome‐wide association study (PheWAS) approach to evaluate the impact of this exposure on a comprehensive range of birth defects. Methods Cases were obtained from the Texas Birth Defects Registry for the period 1999–2015. A total of 127 birth defects were examined. Maternal smoking at any time during the pregnancy was ascertained from the vital record. Data were randomly divided into discovery (60%) and replication (40%) partitions. Poisson regression models were run in the discovery partition, using a Bonferroni threshold of p < 3.9×10⁻⁴. Birth defects passing that threshold in adjusted models were evaluated in the replication partition using p < 0.05 to determine statistical significance. Results Four birth defects were positively and significantly associated with maternal smoking in both partitions: cleft palate, anomalies of the pulmonary artery, other specified anomalies of the mouth and pharynx, and congenital hypertrophic pyloric stenosis. Obstructive defects of the renal pelvis and ureter showed consistent negative associations. All five defects exhibited significant dose–response relationships. Conclusions We demonstrated that a statistically rigorous approach can be applied to birth defects registry data to examine the association between specified exposures and a range of birth defects. While we confirmed previously reported associations, others were not validated, likely due to misclassification in exposure based on vital records.

Background There are noted birth defects prevalence differences between race/ethnicity groups. For instance, non‐Hispanic (NH) Black mothers are more likely to have an infant with encephalocele, although less likely to have an infant with anotia/microtia compared to NH Whites. When stratifying by nativity and years lived within the United States, additional variations become apparent. Methods Data from the National Birth Defects Prevention Study were used to calculate descriptive statistics and estimate crude/adjusted odds ratios (aORs) and 95% confidence intervals (95%CIs) among NH Blacks with one of 30 major defects and non‐malformed controls. Total case/controls were as follows: U.S.‐ (2,773/1101); Foreign‐ (343/151); African‐born (161/64). Study participants were also examined by number of years lived in the U.S. (≤5 vs. 6+ years). Results Compared to U.S.‐born, foreign‐born NH Black controls tended to be older, had more years of education, and were more likely to have a higher household income. They also had fewer previous livebirths and were less likely to be obese. In the adjusted analyses, two defect groups were significantly attenuated: limb deficiencies, aORs/95%CIs = (0.44 [0.20–0.97]) and septal defects (0.69 [0.48–0.99]). After stratifying by years lived in the United States, the risk for hydrocephaly (2.43 [1.03–5.74]) became apparent among those having lived 6+ years in the United States. When restricting to African‐born mothers, none of the findings were statistically significant. Conclusions Foreign‐born NH Blacks were at a reduced risk for a few selected defects. Results were consistent after restricting to African‐born mothers and did not change considerably when stratifying by years lived in the United States.

Background: Neural tube defects (NTD)s are common birth defects with a multifactorial etiology. Findings from human studies examining environmental (non‐inherited) exposures tend to be inconclusive. In particular, although animal studies of alcohol exposure and NTDs support its teratogenic potential, human studies are equivocal. Using data from the National Birth Defects Prevention Study (NBDPS), associations between maternal periconceptional (1 month before through 1 month after conception) alcohol consumption and NTDs in offspring were examined.Methods: NTD cases and unaffected live born singleton controls with expected dates of delivery from October 1997–December 2011 were enrolled in the NBDPS. Interview reports of alcohol consumption (quantity, frequency, variability, type) from 1,922 case and 11,251 control mothers were analyzed. Crude and adjusted odds ratios (aOR)s and 95% confidence intervals (CI)s for alcohol consumption and all NTDs combined and selected subtypes (spina bifida, anencephaly, encephalocele) were estimated using unconditional logistic regression analysis.Results: Among mothers in the NBDPS, 28% of NTD case and 35% of control mothers reported any periconceptional alcohol consumption. For each measure of alcohol consumption, inverse associations were observed for all NTDs combined (aORs = 0.6–1.0). Results for NTD subtypes tended to be similar, but CIs for spina bifida and encephalocele were more likely to include the null.Conclusions: These findings suggest a lack of positive associations between maternal periconceptional alcohol consumption and NTDs. Future studies should continue to evaluate the association between maternal alcohol consumption and NTDs in offspring accounting for methodological limitations such as potential misclassification from self‐reported alcohol consumption.

Objective: To investigate first‐year survival of infants born with spina bifida, and examine the association of maternal prepregnancy body mass index (BMI) with infant mortality.Methods: This is a retrospective cohort study of 1,533 liveborn infants with nonsyndromic spina bifida with estimated dates of delivery from 1998 to 2011 whose mothers were eligible for the National Birth Defects Prevention Study (NBDPS). NBDPS data were linked to death records to conduct survival analyses. Kaplan–Meier survival functions estimated mortality risk over the first year of life. Cox proportional hazards models estimated hazard ratios (HRs) for maternal prepregnancy BMI categorized as underweight (<18.5), normal (18.5–24.9), overweight (25–29.9), and obese (≥30).Results: Infant mortality risk among infants with spina bifida was (4.4% [3.52, 5.60%]). Infants with multiple co‐occurring defects, very preterm delivery, multiple gestation, high‐level spina bifida lesions, or non‐Hispanic Black mothers had an elevated risk of infant mortality. Maternal prepregnancy underweight and obesity were associated with higher infant mortality (15.7% [7.20, 32.30%] and 5.82% [3.60, 9.35%], respectively). Adjusted HR estimates showed underweight and obese mothers had greater hazard of infant mortality compared to normal weight mothers (HR: 4.5 [1.08, 16.72] and 2.6 [1.36, 8.02], respectively).Conclusion: The overall risk of infant mortality for infants born with spina bifida was lower than most previously reported estimates. Infants born with spina bifida to mothers who were underweight or obese prepregnancy were at higher risk of infant mortality. This study provides additional evidence of the importance of healthy maternal weight prior to pregnancy.

Background: There is considerable variability in the prevalence of birth defects among racial/ethnic groups. This study estimated birth defect prevalence among the less studied non‐Hispanic (NH) Asian/Pacific Islander (PI) and American Indian/Alaska Native (AI/AN) populations in Texas relative to NH Whites.Methods: Data were obtained from the Texas Birth Defect Registry from 1999 to 2015 for deliveries to Texas‐resident women who were NH White, NH Asian/PI, or AI/AN. This covers a live birth population of 2.6 million. Prevalence ratios and 95% confidence intervals (95% CIs) were calculated for NH Asian/PIs and AI/ANs (relative to NH Whites) for 44 birth defects using Poisson regression adjusting for maternal age.Results: After adjustment there were 33 statistically significant prevalence ratios (aPRs). Among NH Asian/PIs, 23 defects had a lower aPR (0.38–0.86) and three defects had a higher aPR (1.19–2.50). AI/ANs had one defect with a significantly lower aPR (0.64) and six with a higher aPR (1.36–4.63).Conclusions: Non‐Hispanic Asian/PIs generally have a lower prevalence ratio for many birth defects while AI/ANs have a higher prevalence ratio compared to NH Whites. These findings update the limited literature on this topic and warrant additional research to identify the true associations across a range of birth defects among these understudied racial/ethnic groups.

Background: Acculturation has been examined with respect to various pregnancy adverse outcomes, including birth defects. Given the mixed and limited findings on the association between nativity and birth defects, we sought to further explore parental nativity and years lived in the U.S. across a range of defects.Methods: Data from the National Birth Defects Prevention Study were used for this analysis. Infants with one of 46 major isolated birth defects (30 noncardiac/16 cardiac conditions) and infants without birth defects (controls) born during 1997–2011 were included. We examined parental nativity (foreign‐born mothers, fathers, and both parents combined compared to a referent of both U.S.‐born parents) and the number of years lived in the U.S. (≤5/6+ years). Descriptive statistics and logistic regression analyses were performed to estimate crude/adjusted odds ratios and 95% confidence intervals.Results: Compared to U.S.‐born mothers, foreign‐born mothers tended to be older (25+ years), of Hispanic or Other race/ethnicity and were less likely to have reported drinking, smoking, illicit drug use, or having taken folic acid. In the adjusted analysis, seven findings among both parents reporting a foreign‐birth were significant, including an increased association with spina bifida, anotia/microtia, and diaphragmatic hernia (aORs range: 1.3–1.7), and a reduced association with craniosynostosis and gastroschisis (aORs = 0.7). A generally protective effect was observed among foreign‐born subjects living in the U.S. ≤5 years.Conclusions: We found that nativity was associated with some selected isolated defects, although the direction of effect varied by phenotype and by a number of years residing in the U.S.

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: This is the first study to utilize the index of concentration at the extremes (ICE) to examine risk factors for spina bifida in Texas. The ICE is a useful measure for providing the degree to which residents in a certain area are concentrated into groups at the extremes of disadvantage and privilege. We introduce two novel ICE measures (language and nativity), and three existing ICE measures (race/ethnicity, income, and education), which we applied specifically to Texas residents.Methods: We used multivariable mixed‐model Poisson regression analyses to estimate spina bifida birth prevalence and prevalence ratios among singleton live births in Texas, 1999–2014, for each of our ICE measures. Maternal census tract at delivery was included in the models as a random effect. Analyses were stratified by maternal race/ethnicity (Hispanics and non‐Hispanic whites). Live births served as denominators for each category.Results: Among non‐Hispanic white women, those in the most disadvantaged versus the advantaged census tract quintile had adjusted relative risk between 1.6 and 8.5 for having a baby affected by spina bifida. However, Hispanic women in the most disadvantaged versus advantaged census tract quintile for four ICE measures had a 33% to 87% lower risk of having an affected pregnancy.Conclusions: Findings suggest spina bifida risk is associated with neighborhood disadvantage or advantage, and that relationship seems to vary by race‐ethnicity. The varied associations between ICE measures and spina bifida by race/ethnicity highlights the importance of using targeted interventions in the prevention of spina bifida.