Alissa R. Van Zutphen

Excessive Heat and Respiratory Hospitalizations in New York State: Estimating Current and Future Public Health Burden Related to Climate Change

Background: Although many climate-sensitive environmental exposures are related to mortality and morbidity, there is a paucity of estimates of the public health burden attributable to climate change. Objective: We estimated the excess current and future public health impacts related to respiratory hospitalizations attributable to extreme heat in summer in New York State (NYS) overall, its geographic regions, and across different demographic strata. Methods: On the basis of threshold temperature and percent risk changes identified from our study in NYS, we estimated recent and future attributable risks related to extreme heat due to climate change using the global climate model with various climate scenarios. We estimated effects of extreme high apparent temperature in summer on respiratory admissions, days hospitalized, direct hospitalization costs, and lost productivity from days hospitalized after adjusting for inflation. Results: The estimated respiratory disease burden attributable to extreme heat at baseline (1991–2004) in NYS was 100 hospital admissions, US

A Population-Based Case–Control Study of Extreme Summer Temperature and Birth Defects

644,069 in direct hospitalization costs, and 616 days of hospitalization per year. Projections for 2080–2099 based on three different climate scenarios ranged from 206–607 excess hospital admissions, US

Maternal Hypertension, Medication Use, and Hypospadias in the National Birth Defects Prevention Study

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Maternal Butalbital Use and Selected Defects in the National Birth Defects Prevention Study

76 million in hospitalization costs, and 1,299–3,744 days of hospitalization per year. Estimated impacts varied by geographic region and population demographics. Conclusions: We estimated that excess respiratory admissions in NYS due to excessive heat would be 2 to 6 times higher in 2080–2099 than in 1991–2004. When combined with other heat-associated diseases and mortality, the potential public health burden associated with global warming could be substantial.

Extreme winter temperature and birth defects: A population-based case-control study

Background: Although hyperthermia is a recognized animal teratogen and maternal fever has been associated with birth defects in humans, data on the relationship between high environmental temperatures and birth defects are limited. Objective: To determine whether pregnancies are potentially vulnerable to the weather extremes anticipated with climate change, we evaluated the relationship between extreme summer temperature and the occurrence of birth defects. Methods: We performed a population-based case–control study by linking the New York State Congenital Malformations Registry to birth certificates for the years 1992–2006. We selected nonmalformed infants from a 10% random sample of live births as controls. We assigned meteorologic data based on maternal residence at birth, summarized universal apparent temperature (UAT; degrees Fahrenheit) across the critical period of embryogenesis, and estimated adjusted odds ratios (aOR) and 95% confidence intervals (CI) with multivariable logistic regression, controlling for confounders available on the birth certificate. Results: Among 6,422 cases and 59,328 controls that shared at least 1 week of the critical period in summer, a 5-degree increase in mean daily minimum UAT was significantly associated with congenital cataracts (aOR = 1.51; 95% CI: 1.14, 1.99). Congenital cataracts were significantly associated with all ambient temperature indicators as well: heat wave, number of heat waves, and number of days above the 90th percentile. Inconsistent associations with a subset of temperature indicators were observed for renal agenesis/hypoplasia (positive) and anophthalmia/microphthalmia and gastroschisis (negative). Conclusions: We found positive and consistent associations between multiple heat indicators during the relevant developmental window and congenital cataracts which should be confirmed with other data sources.

Maternal Antihypertensive Medication Use and Congenital Heart DefectsNovelty and Significance: Updated Results From the National Birth Defects Prevention Study

OBJECTIVE: To investigate whether antihypertensive classes and specific medications in early pregnancy increase the risk of severe hypospadias and to assess prior associations detected for late-treated and untreated hypertension in the National Birth Defects Prevention Study. METHODS: Using telephone interviews from mothers of 2,131 children with severe hypospadias and 5,129 nonmalformed male control children for 1997–2009 births in a population-based case–control study, we estimated adjusted odds ratios (ORs) and 95% confidence intervals (CIs) with multivariable logistic regression. We adjusted P values to account for multiple testing. RESULTS: Forty-eight (2.3%) case and 70 (1.4%) control mothers reported early pregnancy antihypertensive treatment, 45 (2.1%) case and 31 (0.6%) control mothers reported late treatment, and 315 (14.8%) case and 394 (7.7%) control mothers reported untreated hypertension. Selective &bgr;-blockers, centrally acting agents, renin–angiotensin system-acting agents, diuretics, and specific medications, methyldopa and atenolol, were not associated with hypospadias. Nonselective &bgr;-blockers (adjusted OR 3.22, 95% CI 1.47–7.05) were associated with hypospadias; however, P values adjusted for multiple testing were not statistically significant. We confirmed prior findings for associations between hypospadias and untreated hypertension (adjusted OR 2.09, 95% CI 1.76–2.48) and late initiation of treatment (adjusted OR 3.98, 95% CI 2.41–6.55). The increased risks would translate to severe hypospadias prevalences of 11.5, 17.7, and 21.9 per 10,000 births for women with untreated hypertension, nonselective &bgr;-blocker use, and late initiation of treatment, respectively. CONCLUSION: Our study suggests a relationship between hypospadias and the severity of hypertension. LEVEL OF EVIDENCE: II

Thyroid Medication Use and Birth Defects in the National Birth Defects Prevention Study

Butalbital is a barbiturate contained in combination products with caffeine and an analgesic prescribed for the treatment of migraine and tension‐type headaches. Controversy exists as to whether butalbital should continue to be prescribed in the United States because of the potential for abuse, overuse headache, and withdrawal syndromes. Butalbital crosses the placenta but there is limited information about potential teratogenicity.

Maternal asthma medication use during pregnancy and risk of congenital heart defects

BACKGROUND/OBJECTIVE We examined the relationship between extreme winter temperatures and birth defects to determine whether pregnant women might be vulnerable to the weather extremes expected with climate change. METHODS In this population-based, case-control study, we linked the New York State Congenital Malformations Registry to birth certificates (1992-2006). Cases were defined as live births with birth defects, and controls were selected from a 10% random sample of live births. We assigned meteorological data based on maternal birth residence and summarized universal apparent temperature across gestational weeks 3-8 (embryogenesis). We defined an extreme cold day as a day with mean temperature below the 10th percentile of the regional winter temperature distribution and a cold spell as 3 consecutive extreme cold days. We averaged temperature for each week of the first trimester to identify susceptible periods. We estimated adjusted odds ratios (ORs) and 95% confidence intervals (CIs) with multivariable logistic regression for 30 birth defects groups. RESULTS Among 13,044 cases and 59,884 controls with at least 1 week of embryogenesis in winter, coarctation of the aorta was associated with a 1°C decrease in mean universal apparent temperature (OR 1.06, 95% CI 1.02-1.11), cold spell (OR 1.61, 95% CI 1.11-2.34), and number of extreme cold days. We observed reduced odds of hypoplastic left heart syndrome and dislocated hip for some cold indicators. CONCLUSIONS Most birth defects were not associated with cold indicators; however, we found positive associations between cold indicators and coarctation of the aorta in the biologically-relevant developmental window which warrants replication.

Maternal Autoimmune Disease and Birth Defects in the National Birth Defects Prevention Study

Previous NBDPS (National Birth Defects Prevention Study) findings from 1997 to 2003 suggested that maternal antihypertensive use was associated with congenital heart defects (CHDs). We re-examined associations between specific antihypertensive medication classes and specific CHDs with additional NBDPS data from 2004 to 2011. After excluding mothers missing hypertension information or who reported pregestational diabetes mellitus, a multiple birth, or antihypertensive use but no hypertension, we compared self-reported maternal exposure data on 10 625 CHD cases and 11 137 nonmalformed controls. We calculated adjusted odds ratios [95% confidence intervals] to estimate the risk of specific CHDs associated with antihypertensive use during the month before conception through the third month of pregnancy, controlling for maternal age, race/ethnicity, body mass index, first trimester cigarette smoking, and NBDPS site. Overall, 164 (1.5%) case mothers and 102 (0.9%) control mothers reported early pregnancy antihypertensive use for their hypertension. We observed increased risk of 4 CHD phenotypes, regardless of antihypertensive medication class reported: coarctation of the aorta (2.50 [1.52–4.11]), pulmonary valve stenosis (2.19 [1.44–3.34]), perimembranous ventricular septal defect (1.90 [1.09–3.31]), and secundum atrial septal defect (1.94 [1.36–2.79]). The associations for these phenotypes were statistically significant for mothers who reported &bgr;-blocker use or renin–angiotensin system blocker use; estimates for other antihypertensive medication classes were generally based on fewer exposed cases and were less stable but remained elevated. Our results support and expand on earlier NBDPS findings that antihypertensive medication use may be associated with increased risk of specific CHDs, although we cannot completely rule out confounding by underlying disease characteristics.Previous NBDPS (National Birth Defects Prevention Study) findings from 1997 to 2003 suggested that maternal antihypertensive use was associated with congenital heart defects (CHDs). We re-examined associations between specific antihypertensive medication classes and specific CHDs with additional NBDPS data from 2004 to 2011. After excluding mothers missing hypertension information or who reported pregestational diabetes mellitus, a multiple birth, or antihypertensive use but no hypertension, we compared self-reported maternal exposure data on 10 625 CHD cases and 11 137 nonmalformed controls. We calculated adjusted odds ratios [95% confidence intervals] to estimate the risk of specific CHDs associated with antihypertensive use during the month before conception through the third month of pregnancy, controlling for maternal age, race/ethnicity, body mass index, first trimester cigarette smoking, and NBDPS site. Overall, 164 (1.5%) case mothers and 102 (0.9%) control mothers reported early pregnancy antihypertensive use for their hypertension. We observed increased risk of 4 CHD phenotypes, regardless of antihypertensive medication class reported: coarctation of the aorta (2.50 [1.52–4.11]), pulmonary valve stenosis (2.19 [1.44–3.34]), perimembranous ventricular septal defect (1.90 [1.09–3.31]), and secundum atrial septal defect (1.94 [1.36–2.79]). The associations for these phenotypes were statistically significant for mothers who reported β-blocker use or renin–angiotensin system blocker use; estimates for other antihypertensive medication classes were generally based on fewer exposed cases and were less stable but remained elevated. Our results support and expand on earlier NBDPS findings that antihypertensive medication use may be associated with increased risk of specific CHDs, although we cannot completely rule out confounding by underlying disease characteristics. # Novelty and Significance {#article-title-25}

Maternal Hypertension, Antihypertensive Medication Use, and Small for Gestational Age Births in the National Birth Defects Prevention Study, 1997–2011

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.