ABSTRACT
BACKGROUND: We investigated the individual and interaction effects of maternal plasma ð- and Ï-tocopherol levels (vitamin E isomers) on child asthma and wheeze at age 8-9. METHODS: Mother-child dyads were enrolled between 2006 and 2011 into the Conditions Affecting Neurocognitive Development and Learning in Early Childhood (CANDLE) prenatal cohort. Maternal second-trimester samples were analyzed for tocopherol and lipid concentrations. We assessed child asthma/wheeze using the International Study of Asthma and Allergies in Childhood (ISAAC) and other self-reported Ent wheeze. In multivariable logistic regression analyses, we assessed associations between vitamin E isomers and child asthma/wheeze outcomes (n = 847 mother-child dyads) and tested for prespecified interaction terms. RESULTS: Median cholesterol-corrected tocopherol levels (interquartile range (IQR)) were 5.0 (4.3-5.7) and 0.8 (0.7-0.9) (umol/mmol) for ð- and Ï-tocopherol, respectively. Associations between ð-tocopherol and asthma outcome variables were inverse but not statistically significant. In contrast, for Ï-tocopherol, associations were in the positive direction, but also nonsignificant. Interactions analysis between tocopherols did not reach statistical significance for any outcome. Among children of women with a history of asthma, the likelihood of ever asthma in the child appears to be decreasing with increasing maternal ð-tocopherol levels, whereas this trend was not observed among those without a history of asthma (p-interaction = .05). CONCLUSION: We observed no associations for prenatal ð- or Ï-tocopherol concentrations with child asthma/wheeze. We detected some evidence of effect modification by maternal asthma history in associations between ð-tocopherol and child asthma.
Subject(s)
Asthma , Prenatal Exposure Delayed Effects , Respiratory Sounds , Vitamin E , Humans , Asthma/epidemiology , Asthma/blood , Female , Pregnancy , Child , Male , Vitamin E/blood , Prenatal Exposure Delayed Effects/epidemiology , Adult , gamma-Tocopherol/blood , Cohort Studies , alpha-Tocopherol/bloodABSTRACT
Pharmacoepidemiological studies commonly examine the association between drug dose and adverse health outcomes. In situations where no safe dose exists, the choice of modeling strategy can lead to identification of an apparent safe low dose range in the presence of a non-linear relationship or due to the modeling strategy forcing a linear relationship through a dose of 0. We conducted a simulation study to assess the performance of several regression approaches to model the drug dose-response curve at low doses in a setting where no safe range exists, including the use of a (1) linear dose term, (2) categorical dose term, and (3) natural cubic spline terms. Additionally, we introduce and apply an expansion of prior work related to modeling dose-response curves at low and infrequently used doses in the setting of no safe dose ("spike-at-zero" and "slab-and-spline"). Furthermore, we demonstrate and empirically assess the use of these regression strategies in a practical scenario examining the association between the dose of the initial postpartum opioid prescribed after vaginal delivery and the subsequent total dose of opioids prescribed in the entire postpartum period among a cohort of opioid-naïve women with a vaginal delivery enrolled in a State Medicaid program (2007-2014).
ABSTRACT
BACKGROUND: Exposure to phenols, endocrine-disrupting chemicals used in personal care and consumer products, is widespread. Data on infant exposures are limited despite heightened sensitivity to endocrine disruption during this developmental period. We aimed to describe distributions and predictors of urinary phenol concentrations among U.S. infants ages 6-12 weeks. METHODS: The Infant Feeding and Early Development (IFED) study is a prospective cohort study of healthy term infants enrolled during 2010-2013 in the Philadelphia region. We measured concentrations of seven phenols in 352 urine samples collected during the 6- or 8- and/or 12-week study visits from 199 infants. We used linear mixed models to estimate associations of maternal, sociodemographic, infant, and sample characteristics with natural-log transformed, creatinine-standardized phenol concentrations and present results as mean percent change from the reference level. RESULTS: Median concentrations (µg/L) were 311 for methylparaben, 10.3 for propylparaben, 3.6 for benzophenone-3, 2.1 for triclosan, 1.0 for 2,5-dichlorophenol, 0.7 for BPA, and 0.3 for 2,4-dichlorophenol. Geometric mean methylparaben concentrations were approximately 10 times higher than published estimates for U.S. children ages 3-5 and 6-11 years, while propylparaben concentrations were 3-4 times higher. Infants of Black mothers had higher concentrations of BPA (83%), methylparaben (121%), propylparaben (218%), and 2,5-dichorophenol (287%) and lower concentrations of benzophenone-3 (-77%) and triclosan (-53%) than infants of White mothers. Triclosan concentrations were higher in breastfed infants (176%) and lower in infants whose mothers had a high school education or less (-62%). Phenol concentrations were generally higher in summer samples. CONCLUSIONS: Widespread exposure to select environmental phenols among this cohort of healthy U.S. infants, including much higher paraben concentrations compared to those reported for U.S. children, supports the importance of expanding population-based biomonitoring programs to infants and toddlers. Future investigation of exposure sources is warranted to identify opportunities to minimize exposures during these sensitive periods of development.
Subject(s)
Environmental Exposure , Phenols , Humans , Infant , Female , Phenols/urine , Male , Environmental Exposure/analysis , Prospective Studies , Environmental Pollutants/urine , Endocrine Disruptors/urine , Endocrine Disruptors/analysis , AdultABSTRACT
BACKGROUND AND AIM: Studies suggest prenatal exposure to polycyclic aromatic hydrocarbons (PAHs) may influence wheezing or asthma in preschool-aged children. However, the impact of prenatal PAH exposure on asthma and wheeze in middle childhood remain unclear. We investigated these associations in socio-demographically diverse participants from the ECHO PATHWAYS multi-cohort consortium. METHODS: We included 1,081 birth parent-child dyads across five U.S. cities. Maternal urinary mono-hydroxylated PAH metabolite concentrations (OH-PAH) were measured during mid-pregnancy. Asthma at age 8-9 years and wheezing trajectory across childhood were characterized by caregiver reported asthma diagnosis and asthma/wheeze symptoms. We used logistic and multinomial regression to estimate odds ratios of asthma and childhood wheezing trajectories associated with five individual OH-PAHs, adjusting for urine specific gravity, various maternal and child characteristics, study site, prenatal and postnatal smoke exposure, and birth year and season in single metabolite and mutually adjusted models. We used multiplicative interaction terms to evaluate effect modification by child sex and explored OH-PAH mixture effects through Weighted Quantile Sum regression. RESULTS: The prevalence of asthma in the study population was 10%. We found limited evidence of adverse associations between pregnancy OH-PAH concentrations and asthma or wheezing trajectories. We observed adverse associations between 1/9-hydroxyphenanthrene and asthma and persistent wheeze among girls, and evidence of inverse associations with asthma for 1-hydroxynathpthalene, which was stronger among boys, though tests for effect modification by child sex were not statistically significant. CONCLUSIONS: In a large, multi-site cohort, we did not find strong evidence of an association between prenatal exposure to PAHs and child asthma at age 8-9 years, though some adverse associations were observed among girls.
Subject(s)
Asthma , Phenanthrenes , Polycyclic Aromatic Hydrocarbons , Prenatal Exposure Delayed Effects , Child , Pregnancy , Male , Female , Child, Preschool , Humans , Longitudinal Studies , Polycyclic Aromatic Hydrocarbons/adverse effects , Prenatal Exposure Delayed Effects/chemically induced , Prenatal Exposure Delayed Effects/epidemiology , Respiratory Sounds , Asthma/chemically induced , Asthma/epidemiologyABSTRACT
We examined associations between prenatal fine particulate matter (PM2.5), nitrogen dioxide (NO2), and ozone (O3) exposures and child respiratory outcomes through age 8-9 years in 1279 ECHO-PATHWAYS Consortium mother-child dyads. We averaged spatiotemporally modeled air pollutant exposures during four fetal lung development phases: pseudoglandular (5-16 weeks), canalicular (16-24 weeks), saccular (24-36 weeks), and alveolar (36+ weeks). We estimated adjusted relative risks (RR) for current asthma at age 8-9 and asthma with recent exacerbation or atopic disease, and odds ratios (OR) for wheezing trajectories using modified Poisson and multinomial logistic regression, respectively. Effect modification by child sex, maternal asthma, and prenatal environmental tobacco smoke was explored. Across all outcomes, 95% confidence intervals (CI) included the null for all estimates of associations between prenatal air pollution exposures and respiratory outcomes. Pseudoglandular PM2.5 exposure modestly increased risk of current asthma (RRadj = 1.15, 95% CI: 0.88-1.51); canalicular PM2.5 exposure modestly increased risk of asthma with recent exacerbation (RRadj = 1.26, 95% CI: 0.86-1.86) and persistent wheezing (ORadj = 1.28, 95% CI: 0.86-1.89). Similar findings were observed for O3, but not NO2, and associations were strengthened among mothers without asthma. While not statistically distinguishable from the null, trends in effect estimates suggest some adverse associations of early pregnancy air pollution exposures with child respiratory conditions, warranting confirmation in larger samples.
Subject(s)
Air Pollutants , Air Pollution , Asthma , Child , Pregnancy , Female , Humans , Respiratory Sounds , Air Pollution/adverse effects , Air Pollution/analysis , Air Pollutants/analysis , Asthma/epidemiology , Asthma/chemically induced , Particulate Matter/analysis , Nitrogen Dioxide , Environmental Exposure/adverse effectsABSTRACT
Importance: Opioid exposure during pregnancy has been associated with preterm birth, but prior studies have not differentiated between spontaneous and indicated preterm birth or fully investigated these associations as functions of opioid dose. Objective: To determine whether prescription opioid use during pregnancy is associated with spontaneous preterm birth and whether the association is dose-dependent. Design, Setting, and Participants: This case-control study examined a retrospective cohort of pregnant patients enrolled in Tennessee Medicaid. Enrollment files were linked to health care encounters, hospital discharge information, birth certificate data, and prescription fills. Eligible participants were pregnant people ages 15 to 44 years without opioid use disorder who experienced birth of a single fetus at 24 weeks gestation or greater between 2007 and 2019 with linked birth certificate data. Cases of spontaneous preterm birth were matched with up to 10 controls based on pregnancy start date, race, ethnicity, age at delivery within 2 years, and history of prior preterm birth. Cases and matched controls were continuously enrolled in TennCare for at least 90 days prior to the index date (case delivery date). Exposure: Total opioid MME filled during the 60 days prior to the index date. Main Outcomes and Measures: The primary outcome was spontaneous preterm birth determined by a validated algorithm using birth certificate data. Conditional logistic regression was used to estimate the association between spontaneous preterm birth and total opioid morphine milligram equivalents (MME) dispensed, adjusting for parity, prepregnancy body mass index, education level, tobacco use, hepatitis infections, and pain indications. Results: A total of 25â¯391 cases (median [IQR] age, 23 [20-28] years; 127 Asian [0.5%], 9820 Black [38.7%], 664 Hispanic [2.6%]; 14â¯748 non-Hispanic White [58.1%]) with spontaneous preterm birth were identified and matched with 225â¯696 controls (median [IQR] age, 23 [20-27] years; 229 Asian [0.1%], 89â¯819 Black [39.8%], 3590 Hispanic [1.6%]; 132â¯002 non-Hispanic White [58.5%]) (251â¯087 patients total), with 18â¯702 patients (7.4%) filling an opioid prescription in the 60 days prior to the index date. Each doubling of nonzero opioid MME was associated with a 4% increase in the odds of spontaneous preterm birth compared with no opioid exposure (adjusted odds ratio, 1.04; 95% CI, 1.01-1.08). Conclusions and Relevance: In this case-control study, a positive association was found between total prescription opioid dose dispensed and the odds of spontaneous preterm birth. These findings support guidance to minimize opioid exposure during pregnancy and prescribe the lowest dose necessary.
Subject(s)
Endrin/analogs & derivatives , Opioid-Related Disorders , Premature Birth , Infant, Newborn , United States , Female , Pregnancy , Humans , Young Adult , Adult , Analgesics, Opioid/adverse effects , Premature Birth/epidemiology , Case-Control Studies , Retrospective Studies , Opioid-Related Disorders/epidemiologyABSTRACT
BACKGROUND: Ozone (O3) exposure interrupts normal lung development in animal models. Epidemiologic evidence further suggests impairment with higher long-term O3 exposure across early and middle childhood, although study findings to date are mixed and few have investigated vulnerable subgroups. METHODS: Participants from the CANDLE study, a pregnancy cohort in Shelby County, TN, in the ECHO-PATHWAYS Consortium, were included if children were born at gestational age >32 weeks, completed a spirometry exam at age 8-9, and had a valid residential history from birth to age 8. We estimated lifetime average ambient O3 exposure based on each child's residential history from birth to age 8, using a validated fine-resolution spatiotemporal model. Spirometry was performed at the age 8-9 year study visit to assess Forced Expiratory Volume in the first second (FEV1) and Forced Vital Capacity (FVC) as primary outcomes; z-scores were calculated using sex-and-age-specific reference equations. Linear regression with robust variance estimators was used to examine associations between O3 exposure and continuous lung function z-scores, adjusted for child, sociodemographic, and home environmental factors. Potential susceptible subgroups were explored using a product term in the regression model to assess effect modification by child sex, history of bronchiolitis in infancy, and allergic sensitization. RESULTS: In our sample (n = 648), O3 exposure averaged from birth to age 8 was modest (mean 26.6 [SD 1.1] ppb). No adverse associations between long-term postnatal O3 exposure were observed with either FEV1 (ß = 0.12, 95% CI: -0.04, 0.29) or FVC (ß = 0.03, 95% CI: -0.13, 0.19). No effect modification by child sex, history of bronchiolitis in infancy, or allergic sensitization was detected for associations with 8-year average O3. CONCLUSIONS: In this sample with low O3 concentrations, we did not observe adverse associations between O3 exposures averaged from birth to age 8 and lung function in middle childhood.
Subject(s)
Air Pollutants , Bronchiolitis , Ozone , Female , Pregnancy , Humans , Child , Infant , Air Pollutants/analysis , Lung , Vital Capacity , Ozone/toxicity , Ozone/analysis , Forced Expiratory Volume , Environmental ExposureABSTRACT
BACKGROUND: Studies have linked prenatal maternal psychosocial stress to childhood wheeze/asthma but have rarely investigated factors that may mitigate risks. OBJECTIVE: To investigate associations between prenatal stress and childhood wheeze/asthma, evaluating factors that may modify stress effects. METHODS: Participants included 2056 mother-child dyads from Environmental influences on Child Health Outcomes (ECHO)-PATHWAYS, a consortium of 3 prospective pregnancy cohorts (the Conditions Affecting Neurocognitive Development and Learning in Early Childhood study, The Infant Development and Environment Study, and a subset of the Global Alliance to Prevent Prematurity and Stillbirth study) from 6 cities. Maternal stressful life events experienced during pregnancy (PSLEs) were reported using the Pregnancy Risk Assessment Monitoring System Stressful Life Events questionnaire. Parents reported child wheeze/asthma outcomes at age 4 to 6 years using standardized questionnaires. We defined outcomes as ever asthma, current wheeze, current asthma, and strict asthma. We used modified Poisson regression with robust standard errors (SEs) to estimate risk ratios (RRs) and 95% CI per 1-unit increase in PSLE, adjusting for confounders. We evaluated effect modification by child sex, maternal history of asthma, maternal childhood traumatic life events, neighborhood-level resources, and breastfeeding. RESULTS: Overall, we observed significantly elevated risk for current wheeze with increasing PSLE (RR, 1.09 [95% CI, 1.03-1.14]), but not for other outcomes. We observed significant effect modification by child sex for strict asthma (P interaction = .03), in which risks were elevated in boys (RR, 1.10 [95% CI, 1.02-1.19]) but not in girls. For all other outcomes, risks were significantly elevated in boys and not in girls, although there was no statistically significant evidence of effect modification. We observed no evidence of effect modification by other factors (P interactions > .05). CONCLUSION: Risk of adverse childhood respiratory outcomes is higher with increasing maternal PSLEs, particularly in boys.
Subject(s)
Asthma , Prenatal Exposure Delayed Effects , Respiratory Sounds , Stress, Psychological , Humans , Female , Pregnancy , Asthma/epidemiology , Asthma/psychology , Prenatal Exposure Delayed Effects/epidemiology , Male , Child, Preschool , Child , Stress, Psychological/epidemiology , Adult , Surveys and Questionnaires , Prospective Studies , Risk FactorsABSTRACT
Background: Asthma is a leading cause of childhood morbidity in the U.S. and a significant public health concern. The prenatal period is a critical window during which environmental influences, including maternal occupational exposures, can shape child respiratory health. Cleaning chemicals are commonly encountered in occupational settings, yet few studies have examined the potential link between prenatal occupational exposures to cleaning chemicals and risk of childhood wheeze and asthma. Methods: We evaluated the potential influence of maternal occupational exposure to cleaning chemicals during pregnancy on pediatric asthma and wheeze at child age 4-6 years in 453 mother-child pairs from two longitudinal pregnancy cohorts, TIDES and GAPPS, part of the ECHO prenatal and early childhood pathways to health (ECHO-PATHWAYS) consortium. Maternal occupational exposure to cleaning chemicals was defined based on reported occupation and frequency of occupational use of chemicals during pregnancy. Child current wheeze and asthma outcomes were defined by parental responses to a widely-used, standardized respiratory outcomes questionnaire administered at child age 4-6 years. Multivariable Poisson regression with robust standard errors was used to estimate relative risk (RR) of asthma in models adjusted for confounding. Effect modification by child sex was assessed using product interaction terms. Results: Overall, 116 mothers (25.6%) reported occupational exposure to cleaning chemicals during pregnancy, 11.7% of children had current wheeze, and 10.2% had current asthma. We did not identify associations between prenatal exposure to cleaning chemicals and current wheeze [RRadjusted 1.03, 95% confidence interval (CI): 0.56, 1.90] or current asthma (RRadjusted 0.89, CI: 0.46, 1.74) in the overall sample. Analyses of effect modification suggested an adverse association among females for current wheeze (RR 1.82, CI: 0.76, 4.37), compared to males (RR 0.68, CI: 0.29, 1.58), though the interaction p-value was >0.05. Conclusion: We did not observe evidence of associations between maternal prenatal occupational exposure to cleaning chemicals and childhood wheeze or asthma in the multi-site ECHO-PATHWAYS consortium. We leveraged longitudinal U.S. pregnancy cohorts with rich data characterization to expand on limited and mixed literature. Ongoing research is needed to more precisely characterize maternal occupational chemical exposures and impacts on child health in larger studies.
ABSTRACT
BACKGROUND: Research on health effects and potential harms of electronic cigarette (EC) use during pregnancy is limited. We sought to determine the risks of pregnancy EC use on pregnancy-related adverse birth outcomes and assess whether quitting ECs reduces the risks. METHODS: Women with singleton live births who participated in the US Pregnancy Risk Assessment Monitoring System (PRAMS) survey study 2016-2020 were classified into four mutually exclusive groups, by their use of ECs and combustible cigarettes (CCs) during pregnancy: non-use, EC only use, CC only use, and dual use. We determined the risk of preterm birth, low birth weight, and small-for-gestational-age (SGA) by comparing cigarette users to non-users with a modified Poisson regression model adjusting for covariates. In a subset of women who all used ECs prior to pregnancy, we determined whether quitting EC use reduces the risk of preterm birth, low birth weight, and SGA by comparing to those who continued its use. All analyses were weighted to account for the PRAMS survey design and non-response rate. RESULTS: Of the 190,707 women (weighted N = 10,202,413) included, 92.1% reported cigarette non-use, 0.5% EC only use, 6.7% CC only use, and 0.7% dual use during pregnancy. Compared with non-use, EC only use was associated with a significantly increased risk of preterm birth (adjusted risk ratio [aRR]: 1.29, 95% confidence interval [CI]: 1.00, 1.65) and low birth weight (aRR: 1.38, 95%CI: 1.09, 1.75), but not SGA (aRR: 1.04, 95%CI: 0.76, 1.44). Among 7,877 (weighted N = 422,533) women EC users, quitting use was associated with a significantly reduced risk of low birth weight (aRR: 0.76, 95%CI: 0.62, 0.94) and SGA (aRR: 0.77, 95%CI: 0.62, 0.94) compared to those who continued to use ECs during pregnancy. CONCLUSIONS: Pregnancy EC use, by itself or dual use with CC, is associated with preterm birth and low birth weight. Quitting use reduces that risk. ECs should not be considered as a safe alternative nor a viable gestational smoking cessation strategy.
Subject(s)
Electronic Nicotine Delivery Systems , Premature Birth , Vaping , Pregnancy , Infant, Newborn , Humans , Female , Premature Birth/epidemiology , Premature Birth/etiology , Vaping/adverse effects , Cross-Sectional Studies , Risk Assessment , Arrhythmias, Cardiac/complications , Fetal Growth RetardationABSTRACT
Background and aim: Studies suggest prenatal exposure to polycyclic aromatic hydrocarbons (PAHs) may influence wheezing or asthma in preschool-aged children. However, the impact of prenatal PAH exposure on asthma and wheeze in middle childhood remain unclear. We investigated these associations in diverse participants from the ECHO PATHWAYS multi-cohort consortium. Methods: We included 1,081 birth parent-child dyads across five U.S. cities. Maternal urinary mono-hydroxylated PAH metabolite concentrations (OH-PAH) were measured during mid-pregnancy. Asthma at age 8-9 years and wheezing trajectory across childhood were characterized by caregiver reported asthma diagnosis and asthma/wheeze symptoms. We used logistic and multinomial regression to estimate odds ratios of asthma and childhood wheezing trajectories associated with five individual OH-PAHs, adjusting for urine specific gravity, various maternal and child characteristics, study site, prenatal and postnatal smoke exposure, and birth year and season in single metabolite and mutually adjusted models. We used multiplicative interaction terms to evaluate effect modification by child sex and explored OH-PAH mixture effects through Weighted Quantile Sum regression. Results: The prevalence of asthma in the study population was 10%. We found limited evidence of adverse associations between pregnancy OH-PAH concentrations and asthma or wheezing trajectories. We observed adverse associations between 1/9-hydroxyphenanthrene and asthma and persistent wheeze among girls, and evidence of inverse associations with asthma for 1-hydroxynathpthalene, which was stronger among boys, though tests for effect modification by child sex were not statistically. Conclusions: In a large, multi-site cohort, we did not find strong evidence of an association between prenatal exposure to PAHs and child asthma at age 8-9 years, though some adverse associations were observed among girls.
ABSTRACT
Importance: The risk of serious long-term outcomes for infants born to individuals with opioid use disorder (OUD) is not fully characterized, nor is it well understood whether risks are modified by infant diagnosis of neonatal opioid withdrawal syndrome (NOWS). Objective: To characterize the risk of postneonatal infant mortality among infants with a NOWS diagnosis or born to individuals with OUD. Design, Setting, and Participants: The study team conducted a retrospective cohort study of 390â¯075 infants born from 2007 through 2018 to mothers who were enrolled in Tennessee Medicaid from 183 days prior to delivery through 28 days post partum (baseline). Maternal and infant baseline characteristics were measured using administrative claims and birth certificates, and infants were followed up from day 29 post partum through day 365 or death. Deaths were identified using linked death certificates through 2019. These data were analyzed from February 10, 2022, through March 3, 2023. Exposure: Infant exposures included birth to an individual with OUD or postnatal diagnosis of NOWS. The study team defined a pregnant individual's OUD status (maternal OUD) as having OUD diagnosis or a maintenance medication prescription fill during baseline; this study defined NOWS as having NOWS diagnosis up to day 28. Groups were categorized by exposures as maternal OUD with NOWS (OUD positive/NOWS positive), maternal OUD without NOWS (OUD positive/NOWS negative), no documented maternal OUD with NOWS (OUD negative/NOWS positive), and no documented maternal OUD or NOWS (OUD negative/NOWS negative, unexposed). Main Outcome and Measures: The outcome was postneonatal infant death, confirmed by death certificates. Cox proportional hazards models were used, adjusting for baseline maternal and infant characteristics, to estimate adjusted hazard ratios (aHRs) and 95% CIs for the association between maternal OUD or NOWS diagnosis with postneonatal death. Results: Pregnant individuals in the cohort had a mean (SD) age of 24.5 (5.2) years; 51% of infants were male. The study team observed 1317 postneonatal infant deaths and incidence rates of 3.47 (OUD negative/NOWS negative, 375â¯718), 8.41 (OUD positive/NOWS positive, 4922); 8.95 (OUD positive/NOWS negative, 7196), and 9.25 (OUD negative/NOWS positive, 2239) per 1000 person-years. After adjustment, the risk of postneonatal death was elevated for all groups, relative to the unexposed: OUD positive/NOWS positive (aHR, 1.54; 95% CI, 1.07-2.21), OUD positive/NOWS negative (aHR, 1.62; 95% CI, 1.21-2.17), and OUD negative/NOWS positive (aHR, 1.64; 95% CI, 1.02-2.65). Conclusions and Relevance: Infants born to individuals with OUD or with a NOWS diagnosis had an increased risk of postneonatal infant mortality. Future work is necessary to create and evaluate supportive interventions for individuals with OUD during and after pregnancy to reduce adverse outcomes.
Subject(s)
Neonatal Abstinence Syndrome , Opioid-Related Disorders , Infant , Infant, Newborn , Pregnancy , Female , Male , Humans , Young Adult , Adult , Retrospective Studies , Infant Mortality , Opioid-Related Disorders/epidemiology , Mothers , Neonatal Abstinence Syndrome/epidemiology , Neonatal Abstinence Syndrome/drug therapy , Analgesics, Opioid/adverse effectsABSTRACT
BACKGROUND: Infants experiencing bronchiolitis are at increased risk for asthma, but few studies have identified modifiable risk factors. We assessed whether early life air pollution influenced child asthma and wheeze at age 4-6 years among children with a history of bronchiolitis in the first postnatal year. METHODS: Children with caregiver-reported physician-diagnosed bronchiolitis were drawn from ECHO-PATHWAYS, a pooled longitudinal cohort from six US cities. We estimated their air pollution exposure from age 1 to 3 years from validated spatiotemporal models of fine particulate matter (PM 2.5 ), nitrogen dioxide (NO 2 ), and ozone (O 3 ). Caregivers reported children's current wheeze and asthma at age 4-6 years. We used modified Poisson regression to estimate relative risks (RR) and 95% confidence intervals (CI), adjusting for child, maternal, and home environmental factors. We assessed effect modification by child sex and maternal history of asthma with interaction models. RESULTS: A total of 224 children had caregiver-reported bronchiolitis. Median (interquartile range) 2-year pollutant concentrations were 9.3 (7.8-9.9) µg/m 3 PM 2.5 , 8.5 (6.4-9.9) ppb NO 2 , and 26.6 (25.6-27.7) ppb O 3 . RRs (CI) for current wheeze per 2-ppb higher O 3 were 1.3 (1.0-1.7) and 1.4 (1.1-1.8) for asthma. NO 2 was inversely associated with wheeze and asthma whereas associations with PM 2.5 were null. We observed interactions between NO 2 and PM 2.5 and maternal history of asthma, with lower risks observed among children with a maternal history of asthma. CONCLUSION: Our results are consistent with the hypothesis that exposure to modest postnatal O 3 concentrations increases the risk of asthma and wheeze among the vulnerable subpopulation of infants experiencing bronchiolitis.
Subject(s)
Air Pollutants , Air Pollution , Asthma , Bronchiolitis , Child , Child, Preschool , Humans , Infant , Air Pollutants/analysis , Air Pollution/adverse effects , Air Pollution/analysis , Asthma/epidemiology , Bronchiolitis/epidemiology , Bronchiolitis/chemically induced , Bronchiolitis/complications , Environmental Exposure/adverse effects , Ozone/adverse effects , Ozone/analysis , Particulate Matter/adverse effects , Particulate Matter/analysisABSTRACT
OBJECTIVE: Our study examines the association between social vulnerability index (SVI) and pharmacotherapy initiation for gestational diabetes mellitus (GDM). METHODS: We studied a retrospective cohort of pregnant patients with GDM, enrolled in Tennessee Medicaid, who gave birth between 2007 and 2019. Enrollment files were linked to birth and death certificates, state hospitalization registries, and pharmacy claims. SVI, measured at the community level and determined by residential census tract, ranged from 0 to 100 (low to high vulnerability). Multivariable logistic regression assessed the association between SVI and the odds of initiating the most common pharmacotherapies for GDM-insulin, glyburide, or metformin-and adjusted for relevant covariates. SVI was modeled with restricted cubic splines to account for nonlinear associations, using the median Tennessee SVI as a reference. Secondary analysis assessed associations with the SVI subthemes. RESULTS: Among 33,291 patients with GDM, 21.7% (7,209) initiated pharmacotherapy during pregnancy. Patients from areas with higher SVI were more likely to be non-Hispanic Black with higher body mass index, whereas those with lower SVI were more likely to be nulliparous. Multivariable modeling demonstrated a complex nonlinear association between SVI and GDM pharmacotherapy initiation, relative to the reference. Higher SVI was associated with elevated odds of GDM pharmacotherapy initiation (e.g., odds ratio 1.11 [95% confidence interval 1.02-1.22] for SVI 80) and low to medium SVI had variable nonsignificant associations with GDM pharmacotherapy initiation, relative to the reference (lower odds of initiation for values 25-50, higher odds of initiation for values < 25). Secondary analysis demonstrated a nonlinear association between subtheme 3 and the odds of GDM pharmacotherapy initiation. CONCLUSION: Social vulnerability is associated with initiation of pharmacotherapy for GDM, highlighting the possible role of social determinants of health in achieving glycemic control.
Subject(s)
Diabetes, Gestational , Pregnancy , Female , Humans , Diabetes, Gestational/drug therapy , Retrospective Studies , Social Vulnerability , Medicaid , Glyburide/therapeutic useABSTRACT
BACKGROUND: The pathogenesis of bronchopulmonary dysplasia (BPD) is multifactorial, and there are limited data about prenatal exposures and risk of BPD. STUDY DESIGN: Our study performed parallel analyses using a logistic regression model in a cohort of 4527 infants with data from a curated registry and using a phenome wide association study (PheWAS) based on ICD9/10-based phecodes. We examined 20 prenatal exposures from a neonatal intensive care unit (NICU) curated registry database related to pregnancy and maternal health as well as 94 maternal diagnosis phecodes with a PheWAS analysis. RESULT: In both the curated registry and PheWAS analyses, polyhydramnios was associated with an increased risk of BPD (OR 5.70, 95% CI 2.78-11.44, p = 1.37 × 10-6). CONCLUSION: Our data suggest that polyhydramnios may be a clinical indicator of premature infants at increased risk for bronchopulmonary dysplasia. Combining curated registry data with PheWAS analysis creates a valuable tool to generate hypotheses. IMPACT: Polyhydramnios was significantly associated with bronchopulmonary dysplasia in both a curated registry and by ICD coding analysis with a phenome wide association study (PheWAS). Preterm polyhydramnios may be a clinical indicator of infants at increased risk for developing bronchopulmonary dysplasia after preterm birth. Combining curated registry with PheWAS analysis creates a valuable tool to generate hypotheses about perinatal risk factors and morbidities associated with preterm birth.
Subject(s)
Bronchopulmonary Dysplasia , Polyhydramnios , Premature Birth , Infant , Pregnancy , Female , Infant, Newborn , Humans , Bronchopulmonary Dysplasia/etiology , Polyhydramnios/diagnostic imaging , Gestational Age , Risk Factors , Retrospective StudiesABSTRACT
BACKGROUND: Prenatal exposure to polycyclic aromatic hydrocarbons (PAH) may increase risk of pediatric asthma, but existing human studies are limited. OBJECTIVES: We estimated associations between gestational PAHs and pediatric asthma in a diverse US sample and evaluated effect modification by child sex, maternal asthma, and prenatal vitamin D status. METHODS: We pooled two prospective pregnancy cohorts in the ECHO PATHWAYS Consortium, CANDLE and TIDES, for an analytic sample of Nâ¯=â¯1296 mother-child dyads. Mono-hydroxylated PAH metabolites (OH-PAHs) were measured in mid-pregnancy urine. Mothers completed the International Study on Allergies and Asthma in Childhood survey at child age 4-6â¯years. Poisson regression with robust standard errors was used to estimate relative risk of current wheeze, current asthma, ever asthma, and strict asthma associated with each metabolite, adjusted for potential confounders. We used interaction models to assess effect modification. We explored associations between OH-PAH mixtures and outcomes using logistic weighted quantile sum regression augmented by a permutation test to control Type 1 errors. RESULTS: The sociodemographically diverse sample spanned five cities. Mean (SD) child age at assessment was 4.4 (0.4) years. While there was little evidence that either individual OH-PAHs or mixtures were associated with outcomes, we observed effect modification by child sex for most pairs of OH-PAHs and outcomes, with adverse associations specific to females. For example, a 2-fold increase in 2-hydroxy-phenanthrene was associated with current asthma in females but not males (RRfemaleâ¯=â¯1.29 [95â¯% CI: 1.09, 1.52], RRmaleâ¯=â¯0.95 [95â¯% CI: 0.79, 1.13]; pinteractionâ¯=â¯0.004). There was no consistent evidence of modification by vitamin D status or maternal asthma. DISCUSSION: This analysis, the largest cohort study of gestational PAH exposure and childhood asthma to date, suggests adverse associations for females only. These preliminary findings are consistent with hypothesized endocrine disruption properties of PAHs, which may lead to sexually dimorphic effects.
Subject(s)
Maternal Exposure , Polycyclic Aromatic Hydrocarbons , Female , Humans , Pregnancy , Child, Preschool , Child , Maternal Exposure/adverse effects , Polycyclic Aromatic Hydrocarbons/adverse effects , Cohort Studies , Prospective Studies , Vitamin DABSTRACT
OBJECTIVE: High maternal folic acid exposure has been studied as a risk factor for child asthma with inconclusive results. Folic acid supplementation that begins before pregnancy may propagate high exposures during pregnancy, particularly in regions with fortified food supplies. We investigated whether folic acid supplementation initiated periconceptionally is associated with childhood asthma in a US cohort. MATERIALS AND METHODS: We re-contacted mother-child dyads previously enrolled in a prospective pregnancy cohort and included children age 4 to 8 years at follow-up (n = 540). Using first trimester interviews, we assessed whether initial folic acid-containing supplement (FACS) use occurred near/before estimated conception ("periconceptional") or after (during the "first trimester"). Follow-up questionnaires were used to determine if a child ever had an asthma diagnosis ("ever asthma") or asthma diagnosis with prevalent symptoms or medication use ("current asthma"). We examined associations between FACS initiation and asthma outcomes using logistic regression, excluding preterm births and adjusting for child age, sex, maternal race, maternal education, and parental asthma. RESULTS: Approximately half of women initiated FACS use periconceptionally (49%). Nine percent of children had "ever asthma" and 6% had "current asthma." Periconceptional initiation was associated with elevated odds of ever asthma [adjusted odds ratio (95% Confidence Interval): 1.65 (0.87, 3.14)] and current asthma [1.87 (0.88, 4.01)], relative to first trimester initiation. CONCLUSION: We observed positive, but imprecisely estimated associations between periconceptional FACS initiation and child asthma. Folic acid prevents birth defects and is recommended. However, larger studies of folic acid dosing and timing, with consideration for childhood asthma, are needed.
Subject(s)
Asthma , Folic Acid , Pregnancy , Infant, Newborn , Female , Humans , Child , Child, Preschool , Follow-Up Studies , Prospective Studies , Folic Acid/therapeutic use , Dietary Supplements , Asthma/epidemiologyABSTRACT
BACKGROUND: Childhood wheeze, asthma, and allergic rhinitis are common and likely have prenatal origins. Oxidative stress is associated with respiratory disease, but the association of oxidative stress during the prenatal period with development of respiratory and atopic disease in childhood, particularly beyond the infancy period, is unknown. This study aims to investigate associations between prenatal oxidative stress, measured by maternal urinary F2-isoprostanes, and child respiratory outcomes, including effect modification by maternal race. METHODS: We prospectively studied Black (n = 717) and White (n = 363) mother-child dyads. We measured F2-isoprostanes in 2nd-trimester urine (ng/mg-creatinine). At approximately age 4, we obtained parent report of provider-diagnosed asthma (ever), current wheeze, current asthma (diagnosis, symptoms and/or medication), and current allergic rhinitis (current defined as previous 12 months). We used multivariable logistic regression to estimate adjusted odds ratios (aOR) and 95% confidence intervals (95%CI) per interquartile range (IQR) increase in F2-isoprostane concentration, controlling for confounders. We examined modification by maternal race using interaction terms. RESULTS: The prevalence of provider-diagnosed asthma and current wheeze, asthma and allergic rhinitis was 14%, 19%, 15%, and 24%, respectively. Median (IQR) F2-isoprostane levels were 2.1 (1.6, 2.9) ng/mg-creatinine. Associations between prenatal F2-isoprostanes and provider-diagnosed asthma, current wheeze, and current asthma were modified by maternal race. Results were strongest for current wheeze (aOR [95%CI]: 1.55 [1.16, 2.06] for White; 0.98 [0.78, 1.22] for Black; p-interaction = 0.01). We observed no association between F2-isoprostanes and allergic rhinitis. CONCLUSION: Prenatal urinary F2-isoprostanes may be a marker associated with childhood wheeze/asthma in certain populations. Research is needed to understand underlying mechanisms and racial differences.
Subject(s)
Asthma , Rhinitis, Allergic , Asthma/diagnosis , Asthma/epidemiology , Child, Preschool , Creatinine , F2-Isoprostanes , Female , Humans , Isoprostanes , Pregnancy , Respiratory Sounds , Rhinitis, Allergic/diagnosis , Rhinitis, Allergic/epidemiologyABSTRACT
BACKGROUND: Postnatal exposures, including breastfeeding, may influence asthma development. OBJECTIVE: To investigate the association between breastfeeding duration and child asthma. METHODS: We studied 2021 mother-child dyads in the ECHO PATHWAYS consortium of prospective pregnancy cohorts (GAPPS, CANDLE, TIDES). Women reported the duration of any and exclusive breastfeeding and child asthma outcomes during follow-up at child age 4 to 6 years. Outcomes included current wheeze (previous 12 months), ever asthma, current asthma (having ≥2 of current wheeze, ever asthma, medication use in past 12-24 months), and strict current asthma (ever asthma with either or both current wheeze and medication use in past 12-24 months). We used multivariable logistic regression to assess associations (odds ratios and 95% confidence intervals) between breastfeeding and asthma outcomes adjusting for potential confounders. We assessed effect modification by mode of delivery, infant sex, and maternal asthma. RESULTS: Among women, 33%, 13%, 9%, and 45% reported 0 to less than 2, 2 to 4, 5 to 6, and more than 6 months of any breastfeeding, respectively. The duration of any breastfeeding had a protective linear trend with ever asthma but no other outcomes. There was a duration-dependent protective association of exclusive breastfeeding and child asthma outcomes (eg, current asthma adjusted odds ratio [95% confidence interval], 0.64 [0.41-1.02], 0.61 [0.38-0.98], and 0.52 (0.31-0.87) for 2to 4 months, 5 to 6 months, and more than 6 months, respectively, compared with <2 months). For exclusive breastfeeding, protective associations were stronger in dyads with children born by vaginal vs cesarean delivery although interactions did not reach statistical significance (Pinteractions 0.12-0.40). CONCLUSION: Longer duration of exclusive breastfeeding had a protective association with child asthma.