Associations of prenatal ambient air pollution exposures with asthma in middle childhood.

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.

Association between maternal occupational exposure to cleaning chemicals during pregnancy and childhood wheeze and asthma.

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.

Characteristics of Individuals in the United States Who Used Opioids During Pregnancy.

Background: Opioid use has disproportionally impacted pregnant people and their fetuses. Previous studies describing opioid use among pregnant people are limited by geographic location, type of medical coverage, and small sample size. We described characteristics of a large, diverse group of pregnant people who were enrolled in the Environmental Influences on Child Health Outcomes (ECHO) Program, and determined which characteristics were associated with opioid use during pregnancy. Materials and Methods: Cross-sectional data obtained from 21,905 pregnancies of individuals across the United States enrolled in the ECHO between 1990 and 2021 were analyzed. Medical records, laboratory testing, and self-report were used to determine opioid-exposed pregnancies. Multiple imputation methods using fully conditional specification with a discriminant function accounted for missing characteristics data. Results: Opioid use was present in 2.8% (n = 591) of pregnancies. The majority of people who used opioids in pregnancy were non-Hispanic White (67%) and had at least some college education (69%). Those who used opioids reported high rates of alcohol use (32%) and tobacco use (39%) during the pregnancy; although data were incomplete, only 5% reported heroin use and 86% of opioid use originated from a prescription. After adjustment, non-Hispanic White race, pregnancy during the years 2010-2012, higher parity, tobacco use, and use of illegal drugs during pregnancy were each significantly associated with opioid use during pregnancy. In addition, maternal depression was associated with increased odds of opioid use during pregnancy by more than two-fold (adjusted odds ratio 2.42, 95% confidence interval: 1.95-3.01). Conclusions: In this large study of pregnancies from across the United States, we found several factors that were associated with opioid use among pregnant people. Further studies examining screening for depression and polysubstance use may be useful for targeted interventions to prevent detrimental opioid use during pregnancy, while further elucidation of the reasons for use of prescription opioids during pregnancy should be further explored.

Associations between social, biologic, and behavioral factors and biomarkers of oxidative stress during pregnancy: Findings from four ECHO cohorts.

BACKGROUND: Lower socioeconomic status (SES) and elevated psychosocial stress are known contributors to adverse pregnancy outcomes; however, biological mechanisms linking these factors to adverse pregnancy outcomes are not well-characterized. Oxidative stress may be an important, yet understudied mechanistic pathway. We used a pooled study design to examine biological, behavioral, and social factors as predictors of prenatal oxidative stress biomarkers. METHODS: Leveraging four pregnancy cohorts from the Environmental influences on Child Health Outcomes (ECHO) Program spanning multiple geographic regions across the United States (U.S.) (N = 2082), we measured biomarkers of oxidative stress in urine samples at up to three time points during pregnancy, including 8-isoprostane-prostaglandin F2α (8-isoPGF2α), its major metabolite, 2,3-dinor-5,6-dihydro-15-F2t-isoprostane, and prostaglandin F2α (PGF2α). Maternal age, pre-pregnancy body mass index, marital/partnered status, parity, and smoking status were included as biological and behavioral factors while race/ethnicity, maternal education, and stressful life events were considered social factors. We examined associations between each individual biological, behavioral, and social factor with oxidative stress biomarkers using multivariable-adjusted linear mixed models. RESULTS: Numerous biological, behavioral, and social factors were associated with elevated levels of 8-isoPGF2α, its major metabolite, and PGF2α. Pregnant people who were current smokers relative to non-smokers or had less than a high school education relative to a college degree had 11.04% (95% confidence interval [CI] = -1.97%, 25.77%) and 9.13% (95% CI = -1.02%, 20.32%) higher levels of 8-isoPGF2α, respectively. CONCLUSIONS: Oxidative stress biomarkers are elevated among pregnant people with higher socioeconomic disadvantage and may represent one pathway linking biological, behavioral, and social factors to adverse pregnancy and child health outcomes, which should be explored in future work.

Combining Urinary Biomarker Data From Studies With Different Measures of Urinary Dilution.

BACKGROUND: Guidance is lacking for how to combine urinary biomarker data across studies that use different measures of urinary dilution, that is, creatinine or specific gravity. METHODS: Among 741 pregnant participants from four sites of The Infant Development and Environment Study (TIDES) cohort, we assessed the relation of maternal urinary di-2-ethylhexyl phthalate (DEHP) concentrations with preterm birth. We compared scenarios in which all sites measured either urinary creatinine or specific gravity, or where measure of dilution differed by site. In addition to a scenario with no dilution adjustment, we applied and compared three dilution-adjustment approaches: a standard regression-based approach for creatinine, a standard approach for specific gravity (Boeniger method), and a more recently developed approach that has been applied to both (covariate-adjusted standardization method). For each scenario and dilution-adjustment method, we estimated the association between a doubling in the molar sum of DEHP (∑DEHP) and odds of preterm birth using logistic regression. RESULTS: All dilution-adjustment approaches yielded comparable associations (odds ratio [OR]) that were larger in magnitude than when we did not perform dilution adjustment. A doubling of ∑DEHP was associated with 9% greater odds of preterm birth (OR = 1.09, 95% confidence interval [CI] = 0.91, 1.30) when applying no dilution-adjustment method, whereas dilution-adjusted point estimates were higher, and similar across all scenarios and methods: 1.13-1.20 (regression-based), 1.15-1.18 (Boeniger), and 1.14-1.21 (covariate-adjusted standardization). CONCLUSIONS: In our applied example, we demonstrate that it is possible and straightforward to combine urinary biomarker data across studies when measures of dilution differ.

Knowledge, Attitudes, and Behaviors Regarding Chemical Exposure among a Population Sample of Reproductive-Aged Women.

We examined the knowledge and attitudes of reproductive-age women toward environmental chemicals and determined how these affect consumer behaviors. At the 2018 Minnesota State Fair, a large community sample of reproductive-age women was recruited to complete a survey on environmental health attitudes and behaviors. Descriptive statistics, chi-square tests, and logistic regression models were used to characterize current attitudes about chemicals. Multivariable logistic regression models examined how sociodemographic characteristics predict knowledge, attitudes, and consumer behaviors. A total of 871 women completed the survey; 74% strongly agreed that chemicals in the environment are dangerous, and 44% of women reported having heard of phthalates, while only 29% reported always practicing at least one environmentally healthy behavior (such as consuming food and beverages from safe plastics). Older age (35-39 versus 18-24: aOR 2.3, 95% CI 1.3, 4.3; 40-44 versus 18-24; aOR 2.0, 95% CI 1.2, 3.2) and working in a healthcare profession (aOR: 1.7, 95% CI: 1.2, 2.5) were associated with strong agreement that chemicals in the environmental are dangerous. Women who strongly agreed chemicals are dangerous were more likely to practice consumer behaviors to reduce their exposure. Interventions targeting knowledge and attitudes towards environmental chemicals could be an effective strategy for reducing harmful exposures.

Urinary glyphosate concentration in pregnant women in relation to length of gestation.

Human exposure to glyphosate-based herbicides (GBH) is increasing rapidly worldwide. Most existing studies on health effects of glyphosate have focused on occupational settings and cancer outcomes and few have examined this common exposure in relation to the health of pregnant women and newborns in the general population. We investigated associations between prenatal glyphosate exposure and length of gestation in The Infant Development and the Environment Study (TIDES), a multi-center US pregnancy cohort. Glyphosate and its primary degradation product [aminomethylphosphonic acid (AMPA)] were measured in urine samples collected during the second trimester from 163 pregnant women: 69 preterm births (<37 weeks) and 94 term births, the latter randomly selected as a subset of TIDES term births. We examined the relationship between exposure and length of gestation using multivariable logistic regression models (dichotomous outcome; term versus preterm) and with weighted time-to-event Cox proportional hazards models (gestational age in days). We conducted these analyses in the overall sample and secondarily, restricted to women with spontaneous deliveries (n = 90). Glyphosate and AMPA were detected in most urine samples (>94 %). A shortened gestational length was associated with maternal glyphosate (hazard ratio (HR): 1.31, 95 % confidence interval (CI) 1.00-1.71) and AMPA (HR: 1.32, 95%CI: 1.00-1.73) only among spontaneous deliveries using adjusted Cox proportional hazards models. In binary analysis, glyphosate and AMPA were not associated with preterm birth risk (<37 weeks). Our results indicate widespread exposure to glyphosate in the general population which may impact reproductive health by shortening length of gestation. Given the increasing exposure to GBHs and the public health burden of preterm delivery, larger confirmatory studies are needed, especially in vulnerable populations such as pregnant women and newborns.

Prenatal Stress as a Modifier of Associations between Phthalate Exposure and Reproductive Development: results from a Multicentre Pregnancy Cohort Study.

BACKGROUND: Prenatal phthalate exposure is associated with altered male reproductive tract development, and in particular, shorter anogenital distance (AGD). AGD, a sexually dimorphic index of prenatal androgen exposure, may also be altered by prenatal stress. How these exposures interact to impact AGD is unknown. Here, we examine the extent to which associations between prenatal phthalate exposure and infant AGD are modified by prenatal exposure to stressful life events (SLEs). METHODS: Phthalate metabolites [including those of diethylhexyl phthalate (DEHP) and their molar sum (ΣDEHP)] were measured in first trimester urine from 738 pregnant women participating in The Infant Development and the Environment Study (TIDES). Women completed questionnaires on SLEs, and permitted infant AGD measurements at birth. Subjects were classified as 'lower' and 'higher' stress (0 first trimester SLEs vs. 1+).We estimated relationships between phthalate concentrations and AGD (by infant sex and stress group) using adjusted multiple regression interaction models. RESULTS: In the lower stress group, first trimester ΣDEHP was inversely associated with two measures of male AGD: anoscrotal distance (AGD-AS; ß = -1.78; 95% CI -2.97, -0.59) and anopenile distance (AGD-AP; ß = -1.61; 95% CI -3.01, -0.22). By contrast, associations in the higher stress group were mostly positive and non-significant in male infants. No associations were observed in girls. CONCLUSIONS: Associations between prenatal phthalate exposure and altered genital development were only apparent in sons of mothers who reported no SLEs during pregnancy. Prenatal stress and phthalates may interact to shape fetal development in ways that have not been previously explored.

Frequency, impact, and predictors of persistent pain after root canal treatment: a national dental PBRN study.

Root canal treatment (RCT) is commonly performed surgery and persistent pain is known to occur, but little is known about how these patients are affected by this pain. Although biopsychosocial mechanisms are thought to be associated with the development of such pain, similar to persistent pain after surgery in other body sites, little is known about the baseline predictors for persistent pain. We assessed the frequency of persistent pain 6 months after RCT, measured the impact this pain had on patients, and determined predictive factors for persistent tooth pain in a multicenter prospective cohort study conducted within the National Dental Practice-Based Research Network. Of 708 patients enrolled, 651 (91.9%) provided follow-up data, with 65 (10.0%) meeting criteria for pain 6 months after RCT. On average, these patients reported their pain as mild to moderate in intensity, present for approximately 10 days in the preceding month, and minimally interfered with daily activities. After adjusting for the type of dental practitioner and patient age, gender, and household income, pain duration over the week before RCT significantly increased the risk of developing persistent pain (odds ratio = 1.19 per 1 day increase in pain duration, 95% confidence interval: 1.07-1.33), whereas optimism about the procedure reduced the risk (odds ratio = 0.39, 95% confidence interval: 0.22-0.67). Our data suggest that persistent pain 6 months after RCT is fairly common, but generally does not have a large impact on those experiencing it. Furthermore, patient age and gender did not predict persistent pain, whereas preoperative pain duration and the patient's expectation did.

The Impact of Gender Differences in Attitudes and Beliefs Concerning HBV Vaccination and Screening in the Lao Community.

Liver cancer incidence is increasing among Asian Americans. Laotians in the US have greater risk of liver cancer death compared to other Asian American groups. However, ethnicity is not the only disparity; Laotian men are at increased risk of liver cancer compared to Laotian women. Use of hepatitis B virus (HBV) vaccination and screening is low among Laotians. The impact of gender differences in attitudes and beliefs concerning HBV vaccination and screening is unknown. This secondary analysis of a cross-sectional community-based participatory research study. Although men were more likely to believe that infection with HBV is preventable, and treatable, causes liver cancer, and that healthy persons should be vaccinated, of those who thought people should get vaccinated, women were four times more likely to receive vaccine than men (adj. OR 4.0, CI 1.2-19). Understanding and addressing gender differences may increase HBV screening and vaccination uptake, thus reducing disparities within the Laotian community.

Effect of maternal cystic fibrosis genotype on diabetes in pregnancy.

OBJECTIVE: To evaluate the association between the cystic fibrosis (CF) genotype and the rate of diabetes complicating pregnancy. METHODS: We conducted a retrospective cohort analysis of all pregnant patients with CF from 1972-2011 at a single institution. Patients who were homozygous for the ΔF508 mutation were compared with patients who were heterozygous for the ΔF508 mutation. Primary outcomes measured were incidence of CF-related diabetes and gestational diabetes mellitus (GDM) stratified by CF genotype. Secondary outcomes measured included pancreatic insufficiency, preterm premature rupture of membranes, preterm delivery, mode of delivery, gestational age at delivery, and maternal mortality. RESULTS: We identified 54 pregnancies among 36 women who met inclusion criteria. Of these pregnancies, 28 (51.9%) were carried by women who were homozygous for the ΔF508 mutation. Homozygous women had a significantly greater incidence of pancreatic insufficiency (89.3% compared with 61.5%, P=.03) and diabetes complicating pregnancy (60.7% compared with 23.1%, P<.01) compared with heterozygous women. In addition, there was some evidence of an increased incidence of GDM specifically among homozygous women (35.7% compared with 15.4%, P=.12). Regarding neonatal outcome, there was a lower mean birthweight (2,881 g compared with 3,203 g, P=.04) among the women who were homozygous for the ΔF508 mutation. There was no statistical difference in preterm deliveries, mode of delivery, gestational age at delivery, rate of preterm premature rupture of membranes, or incidence of maternal mortality between the two groups. CONCLUSION: Women with CF who are homozygous for the ΔF508 mutation have an increased risk of having a pregnancy complicated by diabetes.

Co-morbid pain conditions and feelings of invalidation and isolation among women with vulvodynia.

Many women with vulvodynia also suffer from other chronic co-morbid pain conditions. Alone, these pain conditions are associated with feeling invalidated by others and feeling socially isolated. It is unclear, however, how the presence of additional pain co-morbidities are associated with the psychosocial wellbeing of women with vulvodynia. We used data from a survey administered by the National Vulvodynia Association. Women reported clinician-diagnosed vulvodynia, presence of co-morbid pain, and how often they felt that they felt no one believed their pain existed (invalidated) and isolated. Analyses determined prevalence of feeling invalidated or isolated, and the difference in prevalence when co-morbidities existed. Forty-five percent of these 1847 women with vulvodynia reported having at least one of the following five chronic pain conditions, chronic fatigue syndrome, endometriosis, fibromyalgia, interstitial cystitis, or irritable bowel syndrome. Adjusted baseline prevalence among all women of feeling invalidated was 9% and of feeling isolated was 14%. Having a co-morbid condition with vulvodynia, as well as having an increasing number of co-morbid conditions with vulvodynia, was significantly associated with the presence of feeling both invalidated and isolated. Chronic fatigue syndrome was the co-morbidity most strongly associated with feelings invalidation and isolation. One or more co-morbid pain conditions in addition to vulvodynia were significantly associated with psychosocial wellbeing. However, the temporality of the association could not be elucidated and therefore we cannot conclude that these pain conditions cause poor psychosocial wellbeing. Despite this, future studies should explore the utility of promoting validation of women's pain conditions and reducing social isolation for women with chronic pain.

US assessment of estrogen-responsive organ growth among healthy term infants: piloting methods for assessing estrogenic activity.

BACKGROUND: A mother's circulating estrogen increases over the third trimester, producing physiological effects on her newborn that wane postnatally. Estrogenization might be prolonged in newborns exposed to exogenous estrogens, such as isoflavones in soy formula. OBJECTIVE: We evaluated ultrasonography for monitoring growth of multiple estrogen-responsive organs in healthy infants and developed organ-growth trajectories. MATERIALS AND METHODS: We studied 38 boys (61 visits) from birth to age 6 months and 41 girls (96 visits) from birth to age 1 year using a partly cross-sectional, partly longitudinal design. We measured uterus and ovaries in girls, testes and prostate in boys, and kidneys, breasts, thymus, and thyroid in all children. We imaged all organs from the body surface in one session of < 1 h. RESULTS: Uterine volume decreased from birth (P < 0.0001), whereas ovarian volume increased sharply until age 2 months and then decreased (P < 0.001). Testicular volume increased with age (P < 0.0001), but prostatic volume showed minimal age trend. Breast bud diameter showed no age trend in girls but declined from birth in boys (P = 0.03). CONCLUSION: US examination of multiple estrogen-responsive organs in infants in a single session is feasible and yields volume estimates useful for assessing potential endocrine disruptor effects on organ growth.

Men's body mass index and infertility.

BACKGROUND: In men, excess weight may be linked with altered testosterone, estradiol levels, poor semen quality and infertility. We investigated whether higher BMI among men is associated with infertility and if so, to what extent that effect might be mediated by altered sexual function. METHODS: A retrospective cohort study of pregnancies from 1999 through 2005 based within the Norwegian Mother and Child Cohort Study (MoBa). Questionnaires assessed mother's and father's height and weight and time to pregnancy. Our sample comprises 26 303 planned pregnancies. Couples were considered infertile if they took >or=12 months to achieve pregnancy or received infertility treatment. RESULTS: After adjusting for the woman's BMI, coital frequency and the ages and smoking habits of both partners, the odds ratio for infertility was 1.20 for overweight men [BMI 25-29.9; 95% confidence interval (CI) = 1.04-1.38] and 1.36 for obese men (BMI 30-34.9; 95% CI = 1.13-1.63) relative to men with low-normal BMI (20.0-22.4). When BMI was divided into eight categories, there was a trend of increased infertility with increased male BMI. The effect of men's BMI was nearly identical when coital frequency was not included indicating that the effect is not mediated by sexual dysfunction in heavier men. CONCLUSIONS: This study adds further support that men with excess body weight are at increased risk of infertility. Values may be underestimated because the most severe cases, couples who do not conceive, are not included in this birth cohort. Research is needed to see if weight loss improves fertility for these men.

Can men provide accurate confounder data about their partners for Time-to-Pregnancy studies?

PURPOSE: In studies of time to pregnancy (TTP), women's health-related behaviors may confound other determinants of TTP. In many occupation-based TTP studies, all information is collected through the male partner. There are no data on the validity of the man's report of his partner's fertility-related behavior. METHODS: We studied 202 men and their partners from the most recent pregnancy. Validity of men's reporting on their partner's use of oral contraceptives (OCs) as the last birth control method and her smoking around the beginning of TTP and agreement of coital frequency were assessed. RESULTS: The index pregnancy was an average of 6 years before interview. Overall percentage of agreement was 81% for OCs as the last contraceptive method (kappa agreement = 0.44). Ninety-five percent of men accurately reported whether their partner smoked (kappa agreement = 0.83). Among couples agreeing on smoking status, 90% agreed on the categorical cigarette number (weighted kappa = 0.60). Reporting accuracy was not influenced by men's characteristics. Median coital frequency was eight times per month, with a weighted kappa = 0.34 after categorization. CONCLUSIONS: Our data generally justify the use of men's reports of potential confounders in TTP studies when women's reports are not available.