Bridging Differences in Cohort Analyses of the Relationship between Secondhand Smoke Exposure during Pregnancy and Birth Weight: The Transportability Framework in the ECHO Program.

BACKGROUND: Estimates for the effects of environmental exposures on health outcomes, including secondhand smoke (SHS) exposure, often present considerable variability across studies. Knowledge of the reasons behind these differences can aid our understanding of effects in specific populations as well as inform practices of combining data from multiple studies. OBJECTIVES: This study aimed to assess the presence of effect modification by measured sociodemographic characteristics on the effect of SHS exposure during pregnancy on birth weights that may drive differences observed across cohorts. We also aimed to quantify the extent to which differences in the cohort mean effects observed across cohorts in the Environmental influences on Child Health Outcomes (ECHO) consortium are due to differing distributions of these characteristics. METHODS: We assessed the presence of effect modification and transportability of effect estimates across five ECHO cohorts in a total of 6,771 mother-offspring dyads. We assessed the presence of effect modification via gradient boosting of regression trees based on the H-statistic. We estimated individual cohort effects using linear models and targeted maximum likelihood estimation (TMLE). We then estimated transported effects from one cohort to each of the remaining cohorts using a robust nonparametric estimation approach relying on TMLE estimators and compared them to the original effect estimates for these cohorts. RESULTS: Observed effect estimates varied across the five cohorts, ranging from significantly lower birth weight associated with exposure [-167.3g; 95% confidence interval (CI): -270.4, -64.1] to higher birth weight with wide CIs, including the null (42.4g; 95% CI: -15.0, 99.8). Transported effect estimates only minimally explained differences in the point estimates for two out of the four cohort pairs. DISCUSSION: Our findings of weak to moderate evidence of effect modification and transportability indicate that unmeasured individual-level and contextual factors and sources of bias may be responsible for differences in the effect estimates observed across ECHO cohorts. https://doi.org/10.1289/EHP13961.

Prenatal Exposure to Cannabis: Effects on Childhood Obesity and Cardiometabolic Health.

PURPOSE OF REVIEW: To consolidate information on the obesogenic and cardiometabolic effects of prenatal exposure to cannabis. RECENT FINDINGS: A PubMed search strategy updated from January 1, 2014, through 14 June 2023, produced a total of 47 epidemiologic studies and 12 animal studies. Prenatal exposure to cannabis is consistently associated with small for gestational age and low birth weight. After birth, these offspring gain weight rapidly and have increased adiposity and higher glucose (fat mass percentage) in childhood. More preclinical and prospective studies are needed to deepen our understanding of whether these associations vary by sex, dose, timing, and composition of cannabis (e.g., ratio of delta-Δ9-tetrahydrocannabinol [Δ9-THC] to cannabidiol [CBD]). Addressing these gaps may help to solidify causality and identify intervention strategies. Based on the available data, clinicians and public health officials should continue to caution against cannabis use during pregnancy to limit its potential obesogenic and adverse cardiometabolic effects on the offspring.

Prenatal Exposure to Tobacco and Childhood Cognition and Behavior: Effect Modification by Maternal Folate Intake and Breastfeeding Duration.

In this exploratory analysis, we assessed whether nutrition modified the association between prenatal exposure to tobacco and childhood cognition/behavior among 366 Colorado-based mothers and their offspring (born ≥ 37 weeks with birthweights ≥ 2500 g). Interaction by folate ( 5 months, but not for shorter durations. Our findings support the need for smoking cessation campaigns throughout pregnancy and throughout the postpartum period breastfeeding to reduce neurobehavioral risks in the offspring.

Associations between Prenatal and Postnatal Exposure to Cannabis with Cognition and Behavior at Age 5 Years: The Healthy Start Study.

BACKGROUND: Prenatal exposure to cannabis may influence childhood cognition and behavior, but the epidemiologic evidence is mixed. Even less is known about the potential impact of secondhand exposure to cannabis during early childhood. OBJECTIVE: This study sought to assess whether prenatal and/or postnatal exposure to cannabis was associated with childhood cognition and behavior. STUDY DESIGN: This sub-study included a convenience sample of 81 mother-child pairs from a Colorado-based cohort. Seven common cannabinoids (including delta 9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD)) and their metabolites were measured in maternal urine collected mid-gestation and child urine collected at age 5 years. Prenatal and postnatal exposure to cannabis was dichotomized as exposed (detection of any cannabinoid) and not exposed. Generalized linear models examined the associations between prenatal or postnatal exposure to cannabis with the NIH Toolbox and Child Behavior Checklist T-scores at age 5 years. RESULTS: In this study, 7% (n = 6) of the children had prenatal exposure to cannabis and 12% (n = 10) had postnatal exposure to cannabis, with two children experiencing this exposure at both time points. The most common cannabinoid detected in pregnancy was Δ9-THC, whereas the most common cannabinoid detected in childhood was CBD. Postnatal exposure to cannabis was associated with more aggressive behavior (ß: 3.2; 95% CI: 0.5, 5.9), attention deficit/hyperactivity problems (ß: 8.0; 95% CI: 2.2, 13.7), and oppositional/defiant behaviors (ß: 3.2; 95% CI: 0.2, 6.3), as well as less cognitive flexibility (ß: -15.6; 95% CI: -30.0, -1.2) and weaker receptive language (ß: -9.7; 95% CI: -19.2, -0.3). By contrast, prenatal exposure to cannabis was associated with fewer internalizing behaviors (mean difference: -10.2; 95% CI: -20.3, -0.2) and fewer somatic complaints (mean difference: -5.2, 95% CI: -9.8, -0.6). CONCLUSIONS: Our study suggests that postnatal exposure to cannabis is associated with more behavioral and cognitive problems among 5-year-old children, independent of prenatal and postnatal exposure to tobacco. The potential risks of cannabis use (including smoking and vaping) during pregnancy and around young children should be more widely communicated to parents.

Maternal Diet Quality During Pregnancy and Offspring Hepatic Fat in Early Childhood: The Healthy Start Study.

BACKGROUND: Overnutrition in utero may increase offspring risk of nonalcoholic fatty liver disease (NAFLD), but the specific contribution of maternal diet quality during pregnancy to this association remains understudied in humans. OBJECTIVES: This study aimed to examine the associations of maternal diet quality during pregnancy with offspring hepatic fat in early childhood (median: 5 y old, range: 4-8 y old). METHODS: Data were from 278 mother-child pairs in the longitudinal, Colorado-based Healthy Start Study. Multiple 24-h recalls were collected from mothers during pregnancy on a monthly basis (median: 3 recalls, range: 1-8 recalls starting after enrollment), and used to estimate maternal usual nutrient intakes and dietary pattern scores [Healthy Eating Index-2010 (HEI-2010), Dietary Inflammatory Index (DII), and Relative Mediterranean Diet Score (rMED)]. Offspring hepatic fat was measured in early childhood by MRI. Associations of maternal dietary predictors during pregnancy with offspring log-transformed hepatic fat were assessed using linear regression models adjusted for offspring demographics, maternal/perinatal confounders, and maternal total energy intake. RESULTS: Higher maternal fiber intake and rMED scores during pregnancy were associated with lower offspring hepatic fat in early childhood in fully adjusted models [Back-transformed ß (95% CI): 0.82 (0.72, 0.94) per 5 g/1000 kcal fiber; 0.93 (0.88, 0.99) per 1 SD for rMED]. In contrast, higher maternal total sugar and added sugar intakes, and DII scores were associated with higher offspring hepatic fat [Back-transformed ß (95% CI): 1.18 (1.05, 1.32) per 5% kcal/d added sugar; 1.08 (0.99, 1.18) per 1 SD for DII]. Analyses of dietary pattern subcomponents also revealed that lower maternal intakes of green vegetables and legumes and higher intake of "empty calories" were associated with higher offspring hepatic fat in early childhood. CONCLUSIONS: Poorer maternal diet quality during pregnancy was associated with greater offspring susceptibility to hepatic fat in early childhood. Our findings provide insights into potential perinatal targets for the primordial prevention of pediatric NAFLD.

Using non-parametric Bayes shrinkage to assess relationships between multiple environmental and social stressors and neonatal size and body composition in the Healthy Start cohort.

BACKGROUND: Both environmental and social factors have been linked to birth weight and adiposity at birth, but few studies consider the effects of exposure mixtures. Our objective was to identify which components of a mixture of neighborhood-level environmental and social exposures were driving associations with birth weight and adiposity at birth in the Healthy Start cohort. METHODS: Exposures were assessed at the census tract level and included air pollution, built environment characteristics, and socioeconomic status. Prenatal exposures were assigned based on address at enrollment. Birth weight was measured at delivery and adiposity was measured using air displacement plethysmography within three days. We used non-parametric Bayes shrinkage (NPB) to identify exposures that were associated with our outcomes of interest. NPB models were compared to single-predictor linear regression. We also included generalized additive models (GAM) to assess nonlinear relationships. All regression models were adjusted for individual-level covariates, including maternal age, pre-pregnancy BMI, and smoking. RESULTS: Results from NPB models showed most exposures were negatively associated with birth weight, though credible intervals were wide and generally contained zero. However, the NPB model identified an interaction between ozone and temperature on birth weight, and the GAM suggested potential non-linear relationships. For associations between ozone or temperature with birth weight, we observed effect modification by maternal race/ethnicity, where effects were stronger for mothers who identified as a race or ethnicity other than non-Hispanic White. No associations with adiposity at birth were observed. CONCLUSIONS: NPB identified prenatal exposures to ozone and temperature as predictors of birth weight, and mothers who identify as a race or ethnicity other than non-Hispanic White might be disproportionately impacted. However, NPB models may have limited applicability when non-linear effects are present. Future work should consider a two-stage approach where NPB is used to reduce dimensionality and alternative approaches examine non-linear effects.

Early-life exposure to tobacco and childhood adiposity: Identifying windows of susceptibility.

BACKGROUND: Early-life exposure to tobacco is associated with obesity, but the most susceptible developmental periods are unknown. OBJECTIVE: To explore windows of susceptibility in a cohort of 568 mother-child pairs. METHODS: We measured seven measures of tobacco exposure (five self-reported and two biomarkers) spanning from pre-conception to age 5 years. Mothers self-reported active smoking (pre-conception, 17 weeks, and delivery) and household smokers (5 and 18 months postnatally). Cotinine was measured in maternal urine (27 weeks) and child urine (5 years). Adiposity (fat mass percentage) was measured at birth and 5 years via air displacement plethysmography. Using a multiple informant approach, we tested whether adiposity (5 years) and changes in adiposity (from birth to 5 years) differed by the seven measures of tobacco exposure. RESULTS: The associations may depend on timing. For example, only pre-conception (ß = 3.1%; 95% CI: 1.0-5.1) and late gestation (ß = 4.0%; 95% CI: 0.4-7.6) exposures influenced adiposity accretion from birth to 5 years (p for interaction = 0.01). Early infancy exposure was also associated with 1.7% higher adiposity at 5 years (95% CI: 0.1-3.2). Mid-pregnancy and early childhood exposures did not influence adiposity. CONCLUSIONS: Pre-conception, late gestation, and early infancy exposures to tobacco may have the greatest impact on childhood adiposity.

Prenatal exposure to tobacco and adverse birth outcomes: effect modification by folate intake during pregnancy.

BACKGROUND: Fetal exposure to tobacco increases the risk for many adverse birth outcomes, but whether diet mitigates these risks has yet to be explored. Here, we examined whether maternal folate intake (from foods and supplements) during pregnancy modified the association between prenatal exposure to tobacco and with preterm delivery, small-for-gestational age (SGA) births, or neonatal adiposity. METHODS: Mother-child pairs (n = 701) from Healthy Start were included in this analysis. Urinary cotinine was measured at ~ 27 weeks gestation. Diet was assessed using repeated 24-h dietary recalls. Neonatal adiposity (fat mass percentage) was measured via air displacement plethysmography. Interaction was assessed by including a product term between cotinine (< / ≥ limit of detection [LOD]) and folate (< / ≥ 25th percentile [1077 µg/day]) in separate logistic or linear regression models, adjusting for maternal age, race, ethnicity, education, pre-pregnancy body mass index, and infant sex. RESULTS: Approximately 26% of women had detectable levels of cotinine. Folate intake was significantly lower among women with cotinine ≥ LOD as compared to those with cotinine < LOD (1293 µg/day vs. 1418 µg/day; p = 0.01). Folate modified the association between fetal exposure to tobacco with neonatal adiposity (p for interaction = 0.07) and SGA (p for interaction = 0.07). Among those with lower folate intake, fetal exposure to tobacco was associated with lower neonatal adiposity (mean difference: -2.09%; 95% CI: -3.44, -0.74) and increased SGA risk (OR: 4.99; 95% CI: 1.55, 16.14). Conversely, among those with higher folate intake, there was no difference in neonatal adiposity (mean difference: -0.17%; 95% CI: -1.13, 0.79) or SGA risk (OR: 1.15; 95% CI: 0.57, 2.31). CONCLUSIONS: Increased folate intake during pregnancy (from foods and/or supplements) may mitigate the risk of fetal growth restriction among those who are unable to quit smoking or cannot avoid secondhand smoke during pregnancy.

Fetal Exposure to Cannabis and Childhood Metabolic Outcomes: The Healthy Start Study.

OBJECTIVE: To assess the impact of fetal exposure to cannabis on adiposity and glucose-insulin traits in early life. RESEARCH DESIGN AND METHODS: We leveraged a subsample of 103 mother-child pairs from Healthy Start, an ethnically diverse Colorado-based cohort. Twelve cannabinoids/metabolites of cannabis (including Δ9-tetrahydrocannabinol and cannabidiol) were measured in maternal urine collected at ~27 weeks' gestation. Fetal exposure to cannabis was dichotomized as exposed (any cannabinoid > limit of detection [LOD]) and not exposed (all cannabinoids < LOD). Fat mass and fat-free mass were measured via air displacement plethysmography at follow-up (mean age: 4.7 years). Glucose and insulin were obtained after an overnight fast. Generalized linear models estimated the associations between fetal exposure to cannabis with adiposity measures (fat mass [kg], fat-free mass [kg], adiposity [fat mass percentage], body mass index [BMI], and BMI z-scores) and metabolic measures (glucose [mg/dL], insulin [uIU/mL], and homeostatic model assessment of insulin resistance [HOMA-IR]). RESULTS: Approximately 15% of the women had detectable levels of any cannabinoid, indicating fetal exposure to cannabis. Exposed offspring had higher fat mass (1.0 kg; 95% CI, 0.3-1.7), fat-free mass (1.2 kg; 95% CI, 0.4-2.0), adiposity (2.6%; 95% CI, 0.1-5.2), and fasting glucose (5.6 mg/dL; 95% CI, 0.8-10.3) compared with nonexposed offspring. No associations were found with fasting insulin (in the fully adjusted model), HOMA-IR, BMI, or BMI z-scores. CONCLUSIONS: We provide novel evidence to suggest an association between fetal exposure to cannabis with increased adiposity and fasting glucose in childhood, a finding that should be validated in other cohorts.

Joint effects of ambient air pollution and maternal smoking on neonatal adiposity and childhood BMI trajectories in the Healthy Start study.

Coexposure to air pollution and tobacco smoke may influence early-life growth, but few studies have investigated their joint effects. We examined the interaction between fetal exposure to maternal smoking and ozone (O3) or fine particulate matter (PM2.5) on birth weight, neonatal adiposity, and body mass index (BMI) trajectories through age 3 years. METHODS: Participants were 526 mother-child pairs, born ≥37 weeks. Cotinine was measured at ~27 weeks gestation. Whole pregnancy and trimester-specific O3 and PM2.5 were estimated via. inverse-distance weighted interpolation from stationary monitors. Neonatal adiposity (fat mass percentage) was measured via. air displacement plethysmography. Child weight and length/height were abstracted from medical records. Interaction was assessed by introducing cotinine (<31.5 vs. ≥31.5 ng/mL [indicating active smoking]), O3/PM2.5 (low [tertiles 1-2] vs. high [tertile 3]), and their product term in linear regression models for birth weight and neonatal adiposity and mixed-effects models for BMI trajectories. RESULTS: The rate of BMI growth among offspring jointly exposed to maternal smoking and high PM2.5 (between 8.1 and 12.7 µg/m3) in the third trimester was more rapid than would be expected due to the individual exposures alone (0.8 kg/m2 per square root year; 95% CI = 0.1, 1.5; P for interaction = 0.03). We did not detect interactions between maternal smoking and O3 or PM2.5 at any other time on birth weight, neonatal adiposity, or BMI trajectories. CONCLUSIONS: Although PM2.5 was generally below the EPA annual air quality standards of 12.0 µg/m3, exposure during the third trimester may influence BMI trajectories when combined with maternal smoking.

Examining Associations Between Dietary Inflammatory Index in Pregnancy, Pro-inflammatory Cytokine and Chemokine Levels at Birth, and Offspring Asthma and/or Wheeze by Age 4 Years.

BACKGROUND: Few studies have demonstrated associations between maternal dietary inflammatory index (DII) during pregnancy and offspring asthma and/or wheeze. OBJECTIVE: The study aimed to assess associations between maternal DII during pregnancy and 1) offspring cord sera pro-inflammatory cytokines (interleukin [IL]-1ß, IL-4, IL-6, IL-10, tumor necrosis factor-α) and chemokines (IL-8, monocyte chemoattractant protein-1) at birth and 2) offspring asthma and/or wheeze at age 4 years. DESIGN: The Healthy Start study is a prospective prebirth longitudinal study that recruited pregnant women in Denver, Colorado and tracked their offspring. PARTICIPANTS AND SETTING: This study used data from 1228 mother-child dyads enrolled in the Healthy Start study. Pregnant women were recruited in Denver, Colorado, between 2009 and 2014, and offspring tracked until age 4 years. MAIN OUTCOME MEASURES: Cord sera cytokines and chemokines were analyzed with multiplex panel immunoassays. Offspring diagnosis of asthma and/or wheeze by age 4 years was extracted from electronic medical records. STATISTICAL ANALYSES PERFORMED: Unadjusted and adjusted linear and logistic regression models were used to assess associations. Covariates included factors such as nulliparity, race/ethnicity, gestational smoking, and maternal history of asthma. RESULTS: Unadjusted analysis showed that increasing maternal DII scores were associated with increased odds of child asthma and/or wheeze by 4 years (odds ratio = 1.17; 95% CI: 1.07-1.27), but the association was attenuated and no longer statistically significant in the adjusted model (odds ratio = 1.15; 95% CI: 0.99-1.33). There were no significant associations between DII scores and cord sera cytokine or chemokine levels. CONCLUSIONS: The study showed that the inflammatory profile of the maternal diet was not associated with cytokines and chemokine levels at birth. The results suggested that a more inflammatory maternal diet was associated with increased odds of offspring asthma and/or wheeze by age 4 years, which could be considered of clinical relevance but the finding was not statistically significant at the .05 level.

Neonatal Adiposity and Childhood Obesity.

OBJECTIVES: To explore the longitudinal association of neonatal adiposity (fat mass percentage) with BMI trajectories and childhood overweight and obesity from ages 2 to 6 years. METHODS: We studied 979 children from the Healthy Start cohort. Air displacement plethysmography was used to estimate fat mass percentage. Child weight and recumbent length or standing height were abstracted from medical records. Overweight and obesity were defined as BMI levels ≥85th percentile for age and sex. Mixed-effects models were used to examine the association between neonatal fat mass percentage and BMI trajectories from age 2 to 6 years. We tested for effect modification by sex, race and/or ethnicity, and breastfeeding duration. We estimated the proportion of children classified as overweight or obese at specific levels of neonatal fat mass percentage (mean ± SD). RESULTS: The mean neonatal adiposity level was 9.1% ± 4.0%. Child BMI levels differed by neonatal adiposity. Each SD increase in neonatal adiposity resulted in a 0.12 higher overall BMI level between ages 2 to 6 years (95% confidence interval: 0.03 to 0.20; P < .01), and this association was not modified by offspring sex, race and/or ethnicity, or breastfeeding duration. Increasing neonatal adiposity was associated with an increasing proportion of childhood overweight and obesity by age 5 years (P = .02). CONCLUSIONS: We provide novel evidence that higher neonatal adiposity is significantly associated with higher overall BMI levels and an increased likelihood of overweight or obesity from ages 2 to 6 years. Because various prenatal exposures may specifically influence offspring fat accretion, neonatal adiposity may be a useful surrogate end point for prenatal interventions aimed at reducing future childhood overweight and obesity.

In Utero Exposure to Maternal Overweight or Obesity is Associated with Altered Offspring Brain Function in Middle Childhood.

OBJECTIVE: The impact of in utero exposure to maternal overweight and obesity on offspring metabolic health is well documented. Neurodevelopmental outcomes among these children are, however, less well studied. To address this gap, the current study investigated brain function among 4- to 6-year-old children exposed to maternal overweight or obesity during gestation compared with that of children born to mothers with healthy BMI in pregnancy. METHODS: Resting-state functional magnetic resonance imaging was used to study neuronal activity and connectivity during a passive viewing task (movie) among 101 typically developing children enrolled in the Healthy Start study, a longitudinal prebirth cohort in Colorado. RESULTS: Forty-nine children (48%) were exposed to maternal overweight or obesity in utero (mean age = 5 years, SD = 0.9). Children born to mothers with overweight or obesity demonstrated hyperactivity in the left posterior cingulate cortex and hypoactivity in the dorsal anterior cingulate and the supplementary motor area (P < 0.05 for all). Children born to mothers with overweight or obesity also showed ubiquitously weaker brain connectivity (P < 0.05 for all). CONCLUSIONS: These novel results suggest altered brain function among children exposed to maternal overweight and obesity in utero.

Prenatal exposure to traffic and ambient air pollution and infant weight and adiposity: The Healthy Start study.

BACKGROUND: Prenatal exposures to ambient air pollution and traffic have been associated with adverse birth outcomes, and may also lead to an increased risk of obesity. Obesity risk may be reflected in changes in body composition in infancy. OBJECTIVE: To estimate associations between prenatal ambient air pollution and traffic exposure, and infant weight and adiposity in a Colorado-based prospective cohort study. METHODS: Participants were 1125 mother-infant pairs with term births. Birth weight was recorded from medical records and body composition measures (fat mass, fat-free mass, and adiposity [percent fat mass]) were evaluated via air displacement plethysmography at birth (n = 951) and at ~5 months (n = 574). Maternal residential address was used to calculate distance to nearest roadway, traffic density, and ambient concentrations of fine particulate matter (PM2.5) and ozone (O3) via inverse-distance weighted interpolation of stationary monitoring data, averaged by trimester and throughout pregnancy. Adjusted linear regression models estimated associations between exposures and infant weight and body composition. RESULTS: Participants were urban residents and diverse in race/ethnicity and socioeconomic status. Average ambient air pollutant concentrations were generally low; the median, interquartile range (IQR), and range of third trimester concentrations were 7.3 µg/m3 (IQR: 1.3, range: 3.3-12.7) for PM2.5 and 46.3 ppb (IQR: 18.4, range: 21.7-63.2) for 8-h maximum O3. Overall there were few associations between traffic and air pollution exposures and infant outcomes. Third trimester O3 was associated with greater adiposity at follow-up (2.2% per IQR, 95% CI 0.1, 4.3), and with greater rates of change in fat mass (1.8 g/day, 95% CI 0.5, 3.2) and adiposity (2.1%/100 days, 95% CI 0.4, 3.7) from birth to follow-up. CONCLUSIONS: We found limited evidence of an association between prenatal traffic and ambient air pollution exposure and infant body composition. Suggestive associations between prenatal ozone exposure and early postnatal changes in body composition merit further investigation.

Prenatal Exposure to Tobacco and Offspring Neurocognitive Development in the Healthy Start Study.

OBJECTIVE: To explore the associations between prenatal exposure to tobacco and neurocognitive development, in the absence of prematurity or low birth weight. STUDY DESIGN: We followed mother-child pairs within Healthy Start through 6 years of age. Children were born at ≥37 weeks of gestation with a birth weight of ≥2500 g. Parents completed the Third Edition Ages and Stages Questionnaire (n = 246) and children completed a subset of the National Institutes of Health Toolbox Cognition Battery (n = 200). The Ages and Stages Questionnaire domains were dichotomized as fail/monitor and pass. Maternal urinary cotinine was measured at approximately 27 weeks of gestation. Separate logistic regression models estimated associations between prenatal exposure to tobacco (cotinine below vs above the limit of detection) and the Ages and Stages Questionnaire domains. Separate linear regression models estimated associations between prenatal exposure to tobacco and fully corrected T-scores for inhibitory control, cognitive flexibility, and receptive language, as assessed by the National Institutes of Health Toolbox. A priori covariates included sex, maternal age, maternal education, daily caloric intake during pregnancy, race/ethnicity, household income, maternal psychiatric disorders, and, in secondary models, postnatal exposure to tobacco. RESULTS: Compared with unexposed offspring, exposed offspring were more likely to receive a fail/monitor score for fine motor skills (OR, 3.9; 95% CI, 1.5-10.3) and decreased inhibitory control (B: -3.0; 95% CI, -6.1 to -0.7). After adjusting for postnatal exposure, only the association with fine motor skills persisted. CONCLUSIONS: Prenatal and postnatal exposures to tobacco may influence neurocognitive development, in the absence of preterm delivery or low birth weight. Increased developmental screening may be warranted for exposed children.

Diet, Secondhand Smoke, and Glycated Hemoglobin (HbA1c) Levels among Singapore Chinese Adults.

The combination of poor diet and exposure to secondhand smoke may increase hemoglobin A1c (HbA1c) levels, but few studies have explored this interaction. We explored an interaction among 574 never-smoking adults from the Singapore Chinese Health Study. At baseline (age 59 ± 8 years), intakes of omega-3 polyunsaturated fatty acids, vitamin C, vitamin E and fiber were estimated using a modified food frequency questionnaire. At follow-up (age 64 ± 9 years), HbA1c and cotinine were measured. A product term between cotinine (above or below the median value) and each nutrient (high or low intake) was included in separate linear regression models with HbA1c as the outcome. HbA1c among those with high cotinine and low omega-3 polyunsaturated fatty acids intakes were higher than would be expected due to the individual effects alone (p-for-interaction = 0.05). Among those with lower intakes of omega-3 polyunsaturated fatty acids, high cotinine levels were associated with 0.54% higher HbA1c levels (95% confidence interval [CI]: 0.02, 1.06). Conversely, among those with higher intakes of omega-3 polyunsaturated fatty acids, HbA1c differ not differ by exposure (-0.09%; 95% CI: -0.45, 0.30). No evidence of interaction was observed for other nutrients. Diets high in omega-3 polyunsaturated fatty acids may ameliorate secondhand smoke-induced increases in HbA1c.

Persistent effects of in utero overnutrition on offspring adiposity: the Exploring Perinatal Outcomes among Children (EPOCH) study.

AIMS/HYPOTHESIS: We previously showed that intrauterine exposure to gestational diabetes mellitus (GDM) increases selected markers of adiposity in pre-pubertal adolescents. In the present study, we examined these associations in adolescence, and explored whether they are strengthened as the participants transition through puberty. METHODS: Data from 597 individuals (505 unexposed, 92 exposed) participating in the longitudinal Exploring Perinatal Outcomes among Children (EPOCH) study in Colorado were collected at two research visits when the participants were, on average, 10.4 and 16.7 years old. Adiposity measures included BMI, waist/height ratio, and visceral and subcutaneous adipose tissue (as determined by MRI). Separate general linear mixed models were used to assess the longitudinal relationships between exposure to maternal GDM and each adiposity outcome. We tested whether the effect changed over time by including an interaction term between exposure and age in our models, and whether the associations were explained by postnatal behaviours. RESULTS: Compared with unexposed participants, those exposed to maternal GDM had higher BMI (ß = 1.28; 95% CI 0.35, 2.21; p < 0.007), waist/height ratio (ß = 0.03; 95% CI 0.01, 0.04; p = 0.0004), visceral adipose tissue (ß = 4.81; 95% CI 1.08, 8.54; p = 0.01) and subcutaneous adipose tissue (ß = 35.15; 95% CI 12.43, 57.87; p < 0.003). The magnitude of these differences did not change over time and the associations did not appear to be explained by postnatal behaviours. CONCLUSIONS/INTERPRETATION: Our data provide further evidence that intrauterine exposure to maternal GDM is associated with increased offspring adiposity, an effect that appears early in life and tracks throughout adolescence. Efforts to prevent childhood obesity following intrauterine exposure to maternal GDM should target the prenatal or early life periods.

Fetal exposure to maternal active and secondhand smoking with offspring early-life growth in the Healthy Start study.

BACKGROUND: Previous studies have modeled the association between fetal exposure to tobacco smoke and body mass index (BMI) growth trajectories, but not the timing of catch-up growth. Research on fetal exposure to maternal secondhand smoking is limited. OBJECTIVES: To explore the associations between fetal exposure to maternal active and secondhand smoking with body composition at birth and BMI growth trajectories through age 3 years. METHODS: We followed 630 mother-child pairs enrolled in the Healthy Start cohort through age 3 years. Maternal urinary cotinine was measured at ~ 27 weeks gestation. Neonatal body composition was measured using air displacement plethysmography. Child weight and length/height were abstracted from medical records. Linear regression models examined the association between cotinine categories (no exposure, secondhand smoke, active smoking) with weight, fat mass, fat-free mass, and percent fat mass at birth. A mixed-effects regression model estimated the association between cotinine categories and BMI. RESULTS: Compared to unexposed offspring, birth weight was significantly lower among offspring born to active smokers (-343-g; 95% CI: -473, -213), but not among offspring of women exposed to secondhand smoke (-47-g; 95% CI: -130, 36). There was no significant difference in the rate of BMI growth over time between offspring of active and secondhand smokers (p = 0.58). Therefore, our final model included a single growth rate parameter for the combined exposure groups of active and secondhand smokers. The rate of BMI growth for the combined exposed group was significantly more rapid (0.27 kg/m2 per year; 95% CI: 0.05, 0.69; p < 0.01) than the unexposed. CONCLUSIONS: Offspring prenatally exposed to maternal active or secondhand smoking experience rapid and similar BMI growth in the first three years of life. Given the long-term consequences of rapid weight gain in early childhood, it is important to encourage pregnant women to quit smoking and limit their exposure to secondhand smoke.

The Fort Collins commuter study: Variability in personal exposure to air pollutants by microenvironment.

This study investigated the role of microenvironment on personal exposures to black carbon (BC), fine particulate mass (PM2.5 ), carbon monoxide (CO), and particle number concentration (PNC) among adult residents of Fort Collins, Colorado, USA. Forty-four participants carried a backpack containing personal monitoring instruments for eight nonconsecutive 24-hour periods. Exposures were apportioned into five microenvironments: Home, Work, Transit, Eateries, and Other. Personal exposures exhibited wide heterogeneity that was dominated by within-person variability (both day-to-day and between microenvironment variability). Linear mixed-effects models were used to compare mean personal exposures in each microenvironment, while accounting for possible within-person correlation. Mean personal exposures during Transit and at Eateries tended to be higher than exposures at Home, where participants spent the majority of their time. Compared to Home, mean exposures to BC in Transit were, on average, 129% [95% confidence interval: 101% 162%] higher and exposures to PNC were 180% [101% 289%] higher in Eateries.

Proinflammatory Diets during Pregnancy and Neonatal Adiposity in the Healthy Start Study.

OBJECTIVE: To evaluate the association between dietary inflammatory index (DII) scores during pregnancy and neonatal adiposity. STUDY DESIGN: The analysis included 1078 mother-neonate pairs in Healthy Start, a prospective prebirth cohort. Diet was assessed using repeated 24-hour dietary recalls. DII scores were obtained by summing nutrient intakes, which were standardized to global means and multiplied by inflammatory effect scores. Air displacement plethysmography measured fat mass and fat-free mass within 72 hours of birth. Linear and logistic models evaluated the associations of DII scores with birth weight, fat mass, fat-free mass, and percent fat mass, and with categorical outcomes of small- and large-for-gestational age. We tested for interactions with prepregnancy BMI and gestational weight gain. RESULTS: The interaction between prepregnancy BMI and DII was statistically significant for birth weight, neonatal fat mass, and neonatal percent fat mass. Among neonates born to obese women, each 1-unit increase in DII was associated with increased birth weight (53 g; 95% CI, 20, 87), fat mass (20 g; 95% CI, 7-33), and percent fat mass (0.5%; 95% CI, 0.2-0.8). No interaction was detected for small- and large-for-gestational age. Each 1-unit increase in DII score was associated a 40% increase in odds of a large-for-gestational age neonate (1.4; 95% CI, 1.0-2.0; P = .04), but not a small-for-gestational age neonate (1.0; 95% CI, 0.8-1.2; P = .80). There was no evidence of an interaction with gestational weight gain. CONCLUSIONS: Our findings support the hypothesis that an increased inflammatory milieu during pregnancy may be a risk factor for neonatal adiposity. TRIAL REGISTRATION: Clinicaltrials.gov: NCT02273297.