Erin M. Bell

Residential mobility during pregnancy and the potential for ambient air pollution exposure misclassification.

Studies of environmental exposures and adverse birth outcomes often rely on maternal address at birth obtained from the birth certificate to classify exposure. Although the gestational age of interest is often early pregnancy, maternal addresses are not available for women who move during pregnancy when using maternal addresses abstracted from birth certificates. The aim of this study was to explore the extent of ambient air pollutant exposure misclassification due to maternal residential mobility during pregnancy among the subgroup of a New York birth cohort. The authors obtained the maternal addresses at birth from the New York Birth Certificate, and the maternal addresses by gestational age from the National Birth Defect Prevention Study for New York participants for the study period 1997-2002. Among the 1324 mothers, 172 (13.0%) moved once during pregnancy and 46 (3.5%) moved at least twice. When accounting for multiple addresses among some individuals, of the 218 mothers who moved, 38 (2.9%) moved in the 3rd to 8th weeks after conception (critical period, not exclusive from the 1st trimester), 80 (6.0%) moved in the 1st trimester, 112 (8.5%) in the 2nd trimester, and 51 (3.9%) in the 3rd trimester. Air monitoring data from the New York Department of Environmental Conservation were used as surrogates to compute the ambient ozone and PM(10) exposures for mothers with complete residential data. This study estimates exposure using maternal address at birth obtained from birth certificates, compared to exposure estimates when using maternal addresses by gestational age obtained from maternal interview, the gold standard. Average exposures during pregnancy were similar when using interview based versus birth certificate addresses (0.035 vs. 0.035 ppm for ozone, and 20.11 vs. 20.09 microg/m(3) for PM(10), respectively). Kappa statistics and percent agreement were calculated to measure the degree of agreement for dichotomous exposure measurements (=median) and weighted kappa for quartile exposure measurements by gestational age. All the statistics indicated a high agreement between the two measurements. For mothers who moved, the majority maintained their address in the same exposure region. Given the low mobility during pregnancy and the short distance moved, the exposure assignment did not change substantially when using the more accurate interview based addresses in this study. However, the level of observed agreement may decrease for studies that require smaller geographic zones for exposure assignments or with more mobile study populations.

Maternal periconceptional exposure to cigarette smoking and alcohol and esophageal atresia +/- tracheo-esophageal fistula.

BACKGROUNDnEsophageal atresia (EA) is a moderately frequent birth defect that often occurs with tracheo-esophageal fistula (TEF). Etiologic studies for EA+/-TEF have produced inconsistent results.nnnMETHODSnThis study used data from the National Birth Defects Prevention Study (NBDPS) to examine the association between maternal periconceptional exposure to cigarette smoking and alcohol and EA+/-TEF. Cases of EA+/-TEF and unaffected controls with an estimated date of delivery from October 1997 through December 2003 were identified, and telephone interview reports for smoking and alcohol exposure were obtained from birth mothers of 334 cases and 4,967 controls. Odds ratios (OR)s and 95% confidence intervals (CI)s, adjusted for several covariates, were calculated to assess associations.nnnRESULTSnORs were near unity for all EA+/-TEF cases combined and any periconceptional exposure to cigarette smoking (OR = 1.1; CI = 0.8,1.6) or alcohol (OR = 1.2; CI = 0.8,1.8). For cigarette smoking, some elevated ORs were found but varied by type of smoking exposure. No consistent patterns were identified for number of cigarettes smoked per day. For alcohol, ORs were weak to moderately elevated with increasing number of drinks consumed and for binge drinkers compared to non-binge drinkers. ORs were further elevated among mothers who reported active+passive exposure to cigarette smoking and alcohol (OR = 2.5; CI = 1.1,5.6). For both exposures, ORs were higher for cases with additional major defects compared to isolated cases.nnnCONCLUSIONSnThese results, based on one of the largest published samples of EA+/-TEF cases, suggest a role for these exposures in the etiology of EA+/-TEF, although further study is needed to replicate the observed associations.

Maternal bronchodilator use and the risk of orofacial clefts.

BACKGROUNDnFew epidemiological studies have explored the relationship between orofacial clefts and bronchodilators. We assessed whether mothers who used bronchodilators during early pregnancy were at an increased risk of delivering infants with orofacial clefts.nnnMETHODSnWe used National Birth Defects Prevention Study case-control data from mothers of 2711 infants with orofacial clefts and 6482 mothers of live born infants without birth defects, delivered during 1997 through 2005. Information on medication use from 3 months before pregnancy through delivery was collected using a standardized interview. Logistic regression was used to estimate adjusted odds ratios (aOR) and 95% confidence intervals (CIs) for maternal bronchodilator use during the periconceptional period (1 month before pregnancy through the third month of pregnancy) while controlling for other covariates.nnnRESULTSnWe observed an association between maternal bronchodilator use during the periconceptional period and cleft lip only (CLO) (aOR = 1.77, 95% CI: 1.08-2.88). The risk of cleft palate only (CPO) (aOR = 1.53, 95% CI: 0.99-2.37) was elevated but was not statistically significant. No association was observed for maternal bronchodilator use and the risk of cleft lip with cleft palate (aOR = 0.78, 95% CI: 0.46-1.31). The most commonly used bronchodilator was albuterol (88.7%). Maternal albuterol use was associated with CLO (aOR = 1.79, 95% CI: 1.07-2.99) and CPO (aOR = 1.65, 95% CI: 1.06-2.58).nnnCONCLUSIONSnWe observed a statistically significant association between maternal bronchodilator use during the periconceptional period and the risk of CLO after controlling for other risk factors. It is unclear whether the increased odds ratios observed in this study are due to the bronchodilators, the severity of asthma, or both, or to chance alone. Further studies to disentangle the role of asthma or asthma medications would help clarify these findings.

Assisted reproductive technologies and children's neurodevelopmental outcomes

Initial reports suggested that children conceived with assisted reproductive technologies (ART) may be at increased risk for a spectrum of developmental disabilities. Evolving evidence suggests that some of the early risks may have been overstated when not taking plurality of birth or gestational age at delivery into consideration, as both are independent risk factors for neurodevelopmental disabilities arising from alterations in structure and function or limitations in activities. Continued research is needed to overcome lingering data gaps in light of the equivocal literature for many neurodevelopmental disabilities relative to ART, increasing utilization of services, and changes in the clinical management of infecund couples such as the adoption of natural cycles or in vitro maturation treatment options. Population-based cohorts with longitudinal assessment of the multifaceted nature of neurodevelopment across critical and sensitive windows is paramount for the development of empirically based guidance for clinical and population health.

A pilot study of seafood consumption and exposure to mercury, lead, cadmium and arsenic among infertile couples undergoing in vitro fertilization (IVF)

This cross-sectional pilot study was conducted to assess environmental exposures to toxic elements through seafood consumption, among infertile couples undergoing in vitro fertilization (IVF). Twenty-five women and 15 men completed a questionnaire, and provided biologic specimens for quantification of Hg, Pb, Cd, and As using ICP-MS. Consumption of mollusks and shellfish are associated with increased blood Hg. Other seafood consumption predicts blood Pb, and urine Cd and As. Though limited by small numbers and the cross-sectional design, these results suggest that consumption of specific seafood items increases exposure to toxic elements in couples undergoing IVF.

Maternal self-reported genital tract infections during pregnancy and the risk of selected birth defects.

BACKGROUNDnGenital tract infections are common during pregnancy and can result in adverse outcomes including preterm birth and neonatal infection. This hypothesis-generating study examined whether these infections are associated with selected birth defects.nnnMETHODSnWe conducted a case-control study of 5913 children identified as controls and 12,158 cases with birth defects from the National Birth Defects Prevention Study (1997-2004). Maternal interviews provided data on genital tract infections that occurred from one month before pregnancy through the end of the first trimester. Infections were either grouped together as a single overall exposure or were considered as a subgroup that included chlamydia/gonorrhea/pelvic inflammatory disease. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression with adjustment for potential confounders.nnnRESULTSnGenital tract infections were associated with bilateral renal agenesis/hypoplasia (OR, 2.89; 95% CI, 1.11-7.50), cleft lip with or without cleft palate (OR, 1.46; 95% CI, 1.03-2.06), and transverse limb deficiency (OR, 1.84; 95% CI, 1.04-3.26). Chlamydia/gonorrhea/pelvic inflammatory disease was associated with cleft lip only (OR, 2.81; 95% CI, 1.39-5.69). These findings were not statistically significant after adjustment for multiple comparisons.nnnCONCLUSIONSnCaution is needed in interpreting these findings due to the possible misclassification of infection, the limited sample size that constrained consideration of the effects of treatment, and the possibility of chance associations. Although these data do not provide strong evidence for an association between genital tract infections and birth defects, additional research on the possible effects of these relatively common infections is needed.

Maternal periconceptional occupational pesticide exposure and neural tube defects

BACKGROUNDnAdverse associations between maternal pesticide exposure and neural tube defects (NTDs) have been suggested but not consistently observed. This study used data from the multisite National Birth Defects Prevention Study to examine associations between maternal periconceptional (1 month preconception through 2 months postconception) occupational pesticide exposure and NTDs.nnnMETHODSnMothers of 502 NTD cases and 2950 unaffected live-born control infants with estimated delivery dates from 1997 through 2002 were included. Duration, categorical intensity scores, and categorical frequency scores for pesticide classes (e.g., insecticides) were assigned using a modified, literature-based job-exposure matrix and maternal-reported occupational histories. Adjusted odds ratios (aORs) and 95% confidence intervals were estimated based on fitted multivariable logistic regression models that described associations between maternal periconceptional occupational pesticide exposure and NTDs. The aORs were estimated for pesticide exposure (any [yes/no] and cumulative exposure [intensity × frequency × duration] to any pesticide class, each pesticide class, or combination of pesticide classes) and all NTD cases combined and NTD subtypes.nnnRESULTSnPositive, but marginally significant or nonsignificant, aORs were observed for exposure to insecticidesu2009+u2009herbicides for all NTD cases combined and for spina bifida alone. Similarly, positive aORs were observed for any exposure and cumulative exposure to insecticides + herbicides + fungicides and anencephaly alone and encephalocele alone. All other aORs were near unity.nnnCONCLUSIONnPesticide exposure associations varied by NTD subtype and pesticide class. Several aORs were increased, but not significantly. Future work should continue to examine associations between pesticide classes and NTD subtypes using a detailed occupational pesticide exposure assessment and examine pesticide exposures outside the workplace.

Does maternal environmental tobacco smoke interact with social-demographics and environmental factors on congenital heart defects?

Congenital heart defects (CHDs) are a major cause of death in infancy and childhood. Major risk factors for most CHDs, particularly those resulting from the combination of environmental exposures with social determinants and behaviors, are still unknown. This study evaluated the main effect of maternal environmental tobacco smoke (ETS), and its interaction with social-demographics and environmental factors on CHDs in China. A population-based, matched case-control study of 9452 live-born infants and stillborn fetuses was conducted using the Guangdong Registry of Congenital Heart Disease data (2004-2014). The CHDs were evaluated by obstetrician, pediatrician, or cardiologist, and confirmed by cardia tomography/catheterization. Controls were randomly chosen from singleton newborns without any malformation, born in the same hospital as the cases and 1:1 matched by infant sex, time of conception, and parental residence (same city and town to ensure sufficient geographical distribution for analyses). Face-to-face interviews were conducted to collect information on demographics, behavior patterns, maternal disease/medication, and environmental exposures. Conditional logistic regression was used to estimate odds ratios and 95% confidence intervals of ETS exposure on CHDs while controlling for all risk factors. Interactive effects were evaluated using a multivariate delta method for maternal demographics, behavior, and environmental exposures on the ETS-CHD relationship. Mothers exposed to ETS during the first trimester of pregnancy were more likely to have infants with CHD than mothers who did not (aORxa0=xa01.44, 95% CI 1.25-1.66). We also observed a significant dose-response relationship when mothers were exposed to ETS and an increasing number of risk factors and CHDs. There were greater than additive interactions for maternal ETS and migrant status, low household income and paternal alcohol consumption on CHDs. Maternal low education also modified the ETS-CHD association on the multiplicative scale. These findings may help to identify high-risk populations for CHD, providing an opportunity for targeted preventive interventions.

Examining the Prevalence Rates of Preexisting Maternal Medical Conditions and Pregnancy Complications by Source: Evidence to Inform Maternal and Child Research

Objectives We sought to examine whether there are systematic differences in ascertainment of preexisting maternal medical conditions and pregnancy complications from three common data sources used in epidemiologic research. Methods Diabetes mellitus, chronic hypertension, gestational diabetes mellitus (GDM), gestational hypertensive disorders (GHD), placental abruption and premature rupture of membranes (PROM) among 4821 pregnancies were identified via birth certificates, maternal self-report at approximately 4xa0months postpartum and by discharge codes from the Statewide Planning and Research Cooperative System (SPARCS), a mandatory New York State hospital reporting system. The kappa statistic (k) was estimated to ascertain beyond chance agreement of outcomes between birth certificates with either maternal self-report or SPARCS. Results GHD was under-ascertained on birth certificates (5.7u2009%) and more frequently indicated by maternal report (11u2009%) and discharge data (8.2u2009%). PROM was indicated more on birth certificates (7.4u2009%) than maternal report (4.5u2009%) or discharge data (5.7u2009%). Confirmation across data sources for some outcomes varied by maternal age, race/ethnicity, prenatal care utilization, preterm delivery, parity, mode of delivery, infant sex, use of infertility treatment and for multiple births. Agreement between maternal report and discharge data with birth certificates was generally poor (kappau2009<u20090.4) to moderate (0.4u2009≤u2009kappau2009<u20090.75) but was excellent between discharge data and birth certificates for GDM among women who underwent infertility treatment (kappau2009=u20090.79, 95u2009% CI 0.74, 0.85). Conclusions for Practice Prevalence and agreement of conditions varied across sources. Condition-specific variations in reporting should be considered when designing studies that investigate associations between preexisting maternal medical and pregnancy-related conditions with health outcomes over the life-course.

Associations between follicular fluid high density lipoprotein particle components and embryo quality among in vitro fertilization patients

PurposeFollicular redox balance is likely to be important for embryo quality during in vitro fertilization (IVF), and the anti-oxidative high desity lipoprotein (HDL) particle is the sole lipoprotein measured in follicular fluid (FF). Therefore, we investigated FF HDL particle components as predictors of embryo quality during IVF.MethodsTwo research follicles collected from each participant were individually tracked, and 103 women having at least one developed embryo were included in the analysis. Concentrations of 15 non-cholesterol HDL particle components and 26 HDL-cholesterol (HDL-C) particle size subfractions were determined. Embryo quality was assessed for embryo cell number, embryo fragmentation, and embryo symmetry. Multivariable Poisson regression with a sandwich variance estimator was used to evaluate associations between HDL particle components and embryo quality, adjusted for covariates.ResultsHigher γ-tocopherol concentration was associated with less embryo fragmentation (relative risk [RR]u2009=u20094.43; 95xa0% confidence interval [CI] 1.78, 11.06), and higher apolipoprotein A-1 concentration was associated with full embryo symmetry (RRu2009=u20093.92; 95xa0% CI 1.56, 9.90). Higher concentrations of HDL-C subfractions in the large and medium particle size ranges were associated with poorer embryo quality.ConclusionsFF HDL lipophilic micronutrients and protein components, as well as HDL-C particle size, may be important predictors of embryo quality during IVF.