Healthy Start Study Research Articles

Pre- and Perinatal Correlates of Ideal Cardiovascular Health during Early Childhood: A Prospective Analysis in the Healthy Start Study

To characterize prevalence of ideal cardiovascular health (ICVH) during early childhood (4-7years of age), and to identify pre- and perinatal biological, sociodemographic, metabolic, and behavioral correlates of ICVH. Among 350 mother-child pairs in the Healthy Start Study, we defined ICVH as no exposure to second hand smoke; ≥1hour/day of moderate-to-vigorous physical activity; body mass index ≤85th percentile; systolic and diastolic blood pressure <90th percentile; cholesterol <170mg/dL, fasting glucose <100mg/dL; and healthy diet, per the American Heart Association. Pre- and perinatal characteristics were obtained from questionnaires, medical records, and in-person visits. Because of low prevalence of ICVH, we focused on prevalence of meeting ≥6 metrics in the analysis. We examined bivariate associations of each characteristic with % meeting ≥6 metrics and included those that were significant (P<.05) in a multivariable logistic regression model. ICVH prevalence at mean±SD age 4.7±0.6years was 6.9%; boys had twice the prevalence as girls (9% vs 4.4%). Most (>85%) children met criteria for second hand smoke, body mass index, blood pressure, cholesterol, and glucose, and only one-third met criteria for physical activity (31.4%) and diet (35.1%). In multivariable analyses, key correlates of ICVH were maternal weight status (ORoverweight/obese vs nonoverweight/obese=0.41 [0.23, 0.73]) and offspring sex (ORmale vs female=2.14 [1.22, 3.65]). At age 4-7years, ICVH prevalence is already low, with diet and adequate physical activity being the limiting factors. Healthy maternal weight prior to pregnancy and male sex are potential determinants of childhood ICVH. Additional work is required to explore associations of early-life ICVH with future health outcomes.

Fat Mass Accretion from Birth to 5 Years and Metabolic Homeostasis in Childhood: the Healthy Start Study.

It is unclear how fat mass accretion in early life is related to glucose-insulin homeostasis. Examine associations of fat and fat-free mass accretion from birth to early childhood with glucose-insulin homeostasis in early childhood in a multi-ethnic cohort. Observational Healthy Start study with data collection from 2010 to 2020. Air displacement plethysmography at birth and 4.8 (SD 0.7) years estimated fat mass percent (FMP, %), fat mass index (FMI, kg/m2), and fat-free mass index (FFMI, kg/m2). General population recruited from academic obstetrics clinics in Denver, Colorado, consisting of 419 mother/offspring dyads. The main outcome measures were fasting glucose, insulin, homeostasis model assessment-2 insulin resistance (HOMA2-IR), and beta-cell function (HOMA2-B) at 4.8 years. Greater fat mass accretion from birth to early childhood was associated with higher fasting glucose (ΔFMP β = 0.20 [95% CI 0.06-0.34], ΔFMI β = 0.90 [0.30-1.50]) in participants of Hispanic, Black, and Other races/ethnicities, while greater fat-free mass accretion was associated with higher fasting glucose in non-Hispanic White participants (ΔFFMI β = 0.76 [0.21-1.32]). Overall, greater fat, but not fat-free, mass accretion was also associated with higher insulin (ΔFMP β = 0.14 [0.09-0.18], ΔFMI 0.71 [0.51-0.92]), HOMA2-IR (FMP β = 0.02 [0.01-0.02], ΔFMI β = 0.09 [0.06-0.12]), and HOMA2-B (ΔFMP β = 0.92 [0.18-1.36], ΔFMI β = 4.76 [2.79-6.73]). Greater fat mass accretion in infancy and childhood is associated with shifts in fasting glucose in children of Hispanic, Black, and Other races/ethnicities at 5 years of age. Body composition beginning in early life is relevant for metabolic health, and precise assessments of adiposity in pediatric research are needed.

Prenatal Exposure to Per- and Polyfluoroalkyl Substances, Umbilical Cord Blood DNA Methylation, and Cardio-Metabolic Indicators in Newborns: The Healthy Start Study.

Background:Per- and polyfluoroalkyl substances (PFAS) are environmentally persistent chemicals widely detected in women of reproductive age. Prenatal PFAS exposure is associated with adverse health outcomes in children. We hypothesized that DNA methylation changes may result from prenatal PFAS exposure and may be linked to offspring cardio-metabolic phenotype.Objectives:We estimated associations of prenatal PFAS with DNA methylation in umbilical cord blood. We evaluated associations of methylation at selected sites with neonatal cardio-metabolic indicators.Methods:Among 583 mother–infant pairs in a prospective cohort, five PFAS were quantified in maternal serum (median 27 wk of gestation). Umbilical cord blood DNA methylation was evaluated using the Illumina HumanMethylation450 array. Differentially methylated positions (DMPs) were evaluated at a false discovery rate and differentially methylated regions (DMRs) were identified using comb-p (Šidák-adjusted ). We estimated associations between methylation at candidate DMPs and DMR sites and the following outcomes: newborn weight, adiposity, and cord blood glucose, insulin, lipids, and leptin.Results:Maternal serum PFAS concentrations were below the median for females in the U.S. general population. Moderate to high pairwise correlations were observed between PFAS concentrations (). Methylation at one DMP (cg18587484), annotated to the gene TJAP1, was associated with perfluorooctanoate (PFOA) at . Comb-p detected between 4 and 15 DMRs for each PFAS. Associated genes, some common across multiple PFAS, were implicated in growth (RPTOR), lipid homeostasis (PON1, PON3, CIDEB, NR1H2), inflammation and immune activity (RASL11B, RNF39), among other functions. There was suggestive evidence that two PFAS-associated loci (cg09093485, cg09637273) were associated with cord blood triglycerides and birth weight, respectively ().Discussion:DNA methylation in umbilical cord blood was associated with maternal serum PFAS concentrations during pregnancy, suggesting potential associations with offspring growth, metabolism, and immune function. Future research should explore whether DNA methylation changes mediate associations between prenatal PFAS exposures and child health outcomes. https://doi.org/10.1289/EHP6888

Sociodemographic Predictors of Adherence to National Diet and Physical Activity Guidelines at Age 5 Years: The Healthy Start Study.

To assess adherence to the 2015-2020 Dietary Guidelines for Americans and 2018 Physical Activity Guidelines, and identify sociodemographic predictors of adherence among children. Cross sectional. Colorado, United States. Children aged 5 (n = 482). Sex, race/ethnicity, maternal education, maternal employment, maternal subjective social status and household income were assessed via questionnaires. Diet was assessed via 2 interviewer-administered 24-hour dietary recalls. Physical activity was objectively-measured with accelerometry for 7 days. Adherence was defined as a Healthy Eating Index-2015 score of ≥70 and/or ≥6 hours/day of light, moderate and vigorous activity. For each predictor, logistic regression was used to estimate odds ratios for adherence to the diet guidelines only, the activity guidelines only or both guidelines. In the full sample, 29% of children were non-adherent to both guidelines, 6% adhered to the dietary guidelines only, 50% adhered to the activity guidelines only and 14% adhered to both. Girls had a 41% lower odds of adhering to the physical activity guidelines than boys (p = 0.01), after adjustment for race/ethnicity, household income and maternal education level, perceived social status and employment status. Efforts to improve the health of young children should promote adherence to the Dietary Guidelines for Americans among all children. Targeted interventions that increase physical activity among girls may help to mitigate health disparities.

Exposure to ambient air pollution during pregnancy and inflammatory markers in maternal and umbilical cord blood

Background: Exposure to ambient air pollution during pregnancy has been associated with adverse pregnancy and birth outcomes. Inflammation has been proposed as a potential mechanistic link to explain this relationship. In a Colorado-based cohort, we estimated associations between air pollution exposure during pregnancy and inflammatory markers in maternal and cord blood. We also estimated associations between maternal inflammatory markers and infant birth and adiposity outcomes.Methods: Among 515 mother-infant dyads in the Healthy Start Study (2009-2014), trimester-specific and full pregnancy average concentrations of particulate matter of diameter ≤2.5 micrometers (PM2.5) and ozone (O3) were estimated using inverse-distance-weighted interpolation from stationary monitors. Inflammatory markers were measured in mid-pregnancy (median 27 weeks) maternal blood (CRP, IL-6, and TNFα) and cord blood at delivery (CRP, IL-6, IL-8, IL-10, MCP-1, and TNFα). Multivariable linear regression models estimated associations between PM2.5 and O3 exposure and inflammatory markers, and between maternal inflammatory markers and infant outcomes, including birth weight, gestational age at birth, and adiposity (percent fat mass) assessed via air displacement plethysmography.Results: Second trimester PM2.5 and first trimester O3 were positively associated with maternal IL-6 concentrations (PM2.5: 7.38% per IQR; 95%CI 1.40-13.72; O3: 8.09% per IQR, 95%CI 0.00-17.05). PM2.5 and O3 were positively associated with maternal TNFα (trimester 1: PM2.5: 10.77% per IQR; 95%CI 1.04-21.44; O3: 28.05% per IQR, 95%CI; 12.70-45.48; trimester 2: PM2.5: 9.19% per IQR; 95%CI 0.00-19.13, O3: 25.62% per IQR, 95%CI; 11.08-42.06). Ambient air pollution was not associated with inflammatory markers in cord blood. No consistent associations were found between maternal inflammatory markers and infant outcomes.Conclusions: We found evidence of a positive association between ambient air pollution exposure during pregnancy and maternal, but not cord blood, inflammatory markers. Further investigations should examine the health consequences for women of elevated inflammatory markers associated with air pollution exposure during pregnancy.

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

Background: Exposure to environmental toxicants during pregnancy, including maternal smoking and ambient air pollution, may influence early-life growth. These exposures may work synergistically, but few studies have explored this potential interaction. We sought to explore the potential interaction between fetal exposure to tobacco and O3 and PM2.5 with birth weight and neonatal adiposity, as well as BMI growth trajectories through age 3 years.Methods: We followed 526 mother-child pairs enrolled in the Healthy Start cohort, who were born full-term (≥37 weeks gestation). Maternal urinary cotinine was measured at ~27 weeks gestation. Maternal residential address at study enrollment was used to estimate average concentrations of fine particulate matter (PM2.5) and ozone (O3) by trimester and throughout pregnancy. Neonatal adiposity (fat mass percentage) was measured using air displacement plethysmography. Child weight and length/height were abstracted from medical records. Interaction was assessed by including cotinine categories (&lt;31.5 versus ≥31.5 ng/mL [indicating active smoking]), PM2.5 or O3 categories (first and second tertiles versus third tertile), and their product term in linear regression models, with birth weight and infant adiposity as separate outcomes. Mixed-effects regression models estimated the association between cotinine categories, PM2.5/O3 categories, and their product with childhood BMI.Results: Our interaction results suggest that the rate of BMI growth among offspring exposed to both maternal smoking and higher PM2.5 exposure in the third trimester (PM2.5≥8.1 μg/m3) was higher than would be expected due to the individual exposures alone (0.6 kg/m2 per year; 95% CI: 0.1, 2.3; p for interaction=0.03). We did not detect interactions between maternal smoking and O3 or PM2.5 at any other time point on birth weight, neonatal adiposity, or BMI growth trajectories.Conclusions: Although PM2.5 was well below EPA standards, exposure during the third trimester may influence early-life growth when combined with maternal smoking.

Prenatal exposure to ambient air pollution and traffic and indicators of adiposity in early childhood: The Healthy Start Study

Background: Prenatal exposure to ambient air pollution and traffic have been associated with lower birth weight, but relationships with weight and body composition in childhood are unclear. The aim of this study was to examine associations of prenatal exposure to ambient air pollution and traffic with indicators of adiposity in early childhood. Methods: We included 738 participants of the Colorado-based Healthy Start Study whose height, weight, waist circumference and/or fat mass (via air displacement plethysmography, n=652) were measured at age 4-6 years. We estimated residential exposure to ambient concentrations of particulate matter with a diameter of &lt;2.5µm (PM2.5) and ozone (O3) averaged by trimester and throughout pregnancy via inverse distance-weighted interpolation of stationary monitoring data. We assessed the distance to the nearest major roadway and traffic density in multiple buffers surrounding the participants’ homes. Associations of prenatal exposure to air pollution and traffic with overweight (yes/no), waist circumference and fat mass index (fat mass/height2) were assessed by logistic and linear regression, adjusting for potential confounders. Results: Third trimester average 8-hour maximum O3 was associated with a higher odds of being overweight (adjusted odds ratio 1.71 [95%CI 1.12, 2.62] per IQR increase) and higher fat mass index (adjusted difference 0.27kg/m2 [95%CI 0.09, 0.44kg/m2] per IQR increase) at age 4-6 years. We found associations of third trimester PM2.5 with a lower fat mass index (adjusted difference -0.19kg/m2 [95%CI -0.32, -0.07kg/m2] per IQR increase), while first trimester O3 was associated with a lower odds of being overweight and lower fat mass index. Residential proximity to a highway was associated with a higher odds of being overweight and a non-significant higher waist circumference and fat mass index. Conclusion: Higher ambient concentrations of O3 during the third trimester of pregnancy and residential proximity to a highway during pregnancy may contribute to overweight in early childhood.

Familial associations in hair cortisol concentration: A cross-sectional analysis based on the Healthy Start study

A few studies have shown a direct association between maternal and child hair cortisol concentrations (HCC), but the potential correlations within paternal–child and maternal–paternal dyads are not clear from the current evidence. Thus, we aimed to thoroughly examine associations between family members HCC. We conducted a cross-sectional study based on 159 children and their parents (159 mothers and 159 fathers) participating in the Danish Healthy Start Study. Information was available on HCC from both children, mothers and fathers, as well as on several sociodemographic factors. First, Pearson’s correlation coefficients were applied to assess crude correlations between family members’ HCC. Secondly, analysis of covariance, adjusted for covariates, was applied to estimate child mean HCC in quartiles of maternal and paternal HCC, and mean paternal HCC in quartiles of maternal HCC. Our results showed direct associations between HCC of all family members. We found statistically robust correlations between maternal and child HCC (r = 0.33; P < 0.001), paternal and child HCC (r = 0.37; P < 0.001) and between maternal and paternal HCC (r = 0.31; P < 0.001). Similar results were found when adjusting for covariates in analyses of covariance. Our data provides evidence of associations between family members' HCC. However, we were unable to determine the extent to which these associations were due to shared genetics, assortative mating or environmental factors.

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

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. 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. Forty-nine children (48%) were exposed to maternal overweight or obesity in utero (mean age=5years, 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). These novel results suggest altered brain function among children exposed to maternal overweight and obesity in utero.

1245-P: Maternal HbA1c Is Related to Childhood Fat Mass and Only Partially Mediated by Neonatal Fat Mass

Maternal diabetes during pregnancy impacts offspring body composition and has been associated with greater offspring adiposity across the life course. However, the extent to which the relationship between maternal glycemia and offspring adiposity during later life is independent of neonatal adiposity is unclear. In a prospective study of 544 mother-child pairs in the Healthy Start Study, we estimated the total effect of maternal HbA1c on childhood fat mass (FM) %, and the direct effect independent of neonatal FM %. We measured maternal fasting HbA1c at a gestational age of 20-34 weeks, and offspring FM % using air displacement plethysmography at birth and during childhood (age 4-7 y). We used multivariable linear regression with HbA1c tertiles (T1 [reference], T2, T3) as the exposure, neonatal FM % as the mediator, and childhood FM % as the outcome. A counterfactual-based approach was used to estimate total and direct effects, while also accounting for exposure-mediator interaction. Covariates were maternal race, education, gestational weight gain and smoking, and offspring sex and age. The medians (interquartile ranges) of the HbA1c tertiles were T1: 4.80 (3.70, 4.90), T2: 5.05 (5.00, 5.10), and T3: 5.30 (5.20, 6.30). The estimated total effect on child FM % was 1.27 (95% CI: 0.00, 2.54) units higher for T2 vs. T1, and 1.53 (0.23, 2.82) units higher for T3 vs. T1 (P-trend=0.02). After adjusting for pre-pregnancy BMI, the total effect was 1.18 (-0.09, 2.44) and 1.31 (0.00, 2.62) units higher for T2 vs. T1 and T3 vs. T1, respectively (P-trend=0.04). The direct effect after accounting for neonatal FM % was slightly attenuated (T2 vs. T1: 1.14 [-0.11, 2.39], T3 vs. T1: 1.20 [-0.11, 2.51]; P-trend=0.07). Excluding women with gestational diabetes mellitus (n=27) did not substantially impact the results. Our data suggest that maternal glycemia during pregnancy, even within normal levels, may influence childhood adiposity through pathways that are in part mediated by programming of neonatal adiposity. Disclosure E.C. Francis: None. B. Ringham: None. D.H. Glueck: None. W. Perng: None. D. Dabelea: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (5R01DK076648-10)

1328-P: Infant Mesenchymal Stem Cell Insulin Sensitivity Is Associated with Maternal Plasma-Free Fatty Acids, Independent of Obesity Status: The Healthy Start Study

Introduction: Maternal obesity is associated with greater neonatal adiposity and increased offspring risk for type 2 diabetes (T2D) later in life. We have previously reported that mesenchymal stem cells (MSCs) isolated from umbilical cord tissue maintain similar metabolic phenotype to the infant, particularly when differentiated to adipocytes or myocytes. A well-established driver in the pathogenesis of T2D is skeletal muscle insulin resistance. Therefore, we hypothesized that MSCs from infants born to mothers with obesity would display insulin resistance when differentiated to myocytes. Objectives: The objective was to determine the effect of maternal obesity on offspring MSC insulin sensitivity (Si). Methods: MSCs were isolated from umbilical cord tissue from offspring born to either normal weight (BMI 21.1 ± 0.9, n = 9) or obese (BMI 32.9 ± 2.1, n = 10) mothers enrolled in the Healthy Start pre-birth cohort study in Colorado. Following differentiation into skeletal muscle myocytes, MSCs were serum starved and incubated with 14C-glucose, in the presence or absence of insulin. The rate of insulin-mediated 14C-glucose incorporation into glycogen, was used as an index of offspring Si. Results: Offspring Si did not correlate with maternal BMI (r = 0.26), nor was BMI different between groups when median-stratified by offspring Si. However, maternal free fatty acid levels positively correlated with offspring Si (r = 0.63, p &amp;lt; 0.05) and were significantly elevated in the high Si group (low Si vs. high Si; 332.1 ± 30.9 vs. 483.3 ± 48.7 uEq/L, p &amp;lt; 0.05). Conclusions: Offspring Si was not related to the BMI of the mother. Moreover, offspring Si was higher in cells from infants born to mothers with higher free fatty acids during pregnancy. Considering the role of insulin in somatic growth pathways, this phenomenon may serve to increase available nutrient storage capacity during early development. Disclosure A.B. Chaves: None. J.A. Johnson: None. D. Zheng: None. D. Dabelea: None. J.A. Houmard: None. K.E. Boyle: None. Funding American Heart Association (14PRE18230008); Nutrition Obesity Research Center (P30DK048520); National Institutes of Health (R01DK076648); Colorado National Center for Advancing Translational Sciences (UL1TR001082)

Associations between the activity of placental nutrient-sensing pathways and neonatal and postnatal metabolic health: the ECHO Healthy Start cohort.

Our hypothesis was that the activity of placental nutrient-sensing pathways is associated with adiposity and metabolic health in childhood. Using placental villus samples from healthy mothers from the Healthy Start Study, we measured the abundance and phosphorylation of key intermediates in the mTOR, insulin, AMPK, and ER stress signaling pathways. Using multivariate multiple regression models, we tested the association between placental proteins and offspring adiposity (%fat mass) at birth (n = 109), 4-6 months (n = 104), and 4-6 years old (n = 64), adjusted for offspring sex and age. Placental mTORC1 phosphorylation was positively associated with adiposity at birth (R2 = 0.13, P = 0.009) and 4-6 years (R2 = 0.15, P = 0.046). The mTORC2 target PKCα was positively associated with systolic blood pressure at 4-6 years (β = 2.90, P = 0.005). AMPK phosphorylation was positively associated with adiposity at birth (β = 2.32, P = 0.023), but the ratio of phosphorylated to total AMPK was negatively associated with skinfold thickness (β = -2.37, P = 0.022) and body weight (β = -2.92, P = 0.005) at 4-6 years. This is the first report of associations between key placental protein activity measures and longitudinal child outcomes at various life stages. Our data indicate that AMPK and mTOR signaling are linked to cardiometabolic measures at birth and 4-6 years, providing novel insight into potential mechanisms underpinning how metabolic signaling in the placenta is associated with future risk of cardiovascular disease.

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

BackgroundPrenatal 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. ObjectiveTo estimate associations between prenatal ambient air pollution and traffic exposure, and infant weight and adiposity in a Colorado-based prospective cohort study. MethodsParticipants 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. ResultsParticipants 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. ConclusionsWe 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.

Child behaviour and subsequent changes in body weight, composition and shape.

ObjectiveStudies have found an association between child behavioural problems and overweight, but the existing evidence for this relationship is inconsistent, and results from longitudinal studies are sparse. Thus, we examined the association between behavioural problems and subsequent changes in body mass index (BMI) and anthropometry over a follow-up period of 1.3 years among children aged 2–6 years.DesignThe study was based on a total of 345 children from The Healthy Start Study; all children were healthy weight but predisposed to develop overweight. The Danish version of the Strengths and Difficulties Questionnaire (SDQ), classified as SDQ Total Difficulties (SDQ-TD) and SDQ Prosocial Behaviour (SDQ-PSB), was used to assess child behaviour. Linear regression analyses were used to examine associations between SDQ scores and subsequent change in BMI z-score, body fat percentage, waist circumference and waist-hip ratio, while taking possible confounding factors into account.ResultsWe found an association between SDQ-PSB and subsequent change in BMI z-score (β: 0.040 [95% CI: 0.010; 0.071, p = 0.009]). However, there was no evidence of an association between SDQ-PSB and measures of body composition or body shape.ConclusionsAmong 2 to 6 years old children predisposed to overweight, the association between SDQ-scores and weight gain is either absent or marginal. The SDQ-PSB score may be associated with subsequent increases in BMI z-score, but this association does not seem driven by an increased relative fat accumulation.

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

To explore the associations between prenatal exposure to tobacco and neurocognitive development, in the absence of prematurity or low birth weight. We followed mother-child pairs within Healthy Start through 6years of age. Children were born at ≥37weeks of gestation with a birth weight of ≥2500g. 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 27weeks 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. 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. 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.

Fetal exposure to tobacco smoke and offspring early-life neurodevelopment in the Healthy Start study

TPS 731: Neurological effects in children, Exhibition Hall, Ground floor, August 26, 2019, 3:00 PM - 4:30 PM Background: Fetal exposure to tobacco is linked to impaired cognitive ability in the offspring. It is not clear whether these associations persist in the absence of other known risk factors, such as pre-term delivery and low birth weight. We aimed to explore the associations between fetal exposure to tobacco with cognitive function, independent of pre-term delivery or low birth weight. Methods: We followed 246 mother-child pairs enrolled in the Healthy Start cohort through age 4.5 years, who were born full-term (≥37 weeks gestation) and with a birth weight>2,500-g. Maternal urinary cotinine was measured at 27 weeks gestation. At age 4.5 year, parents completed the Third Edition Ages and Stages Questionnaire (ASQ-3) and children completed the National Institutes of Health (NIH) Toolbox Cognition Battery. The five domains of the ASQ-3 were dichotomized as fail/monitor and pass. Logistic regression models examined the association between cotinine categories (below limit of detection (LOD) or ≥LOD) and the five ASQ-3 domains as separate outcomes. Linear regression models examined the association between cotinine categories and fully-adjusted T-scores for inhibitory control (Flanker test), cognitive flexibility (Dimensional Change Card Sort test), and receptive language (Picture Vocabulary test). Our models adjusted for sex, race/ethnicity, maternal age, maternal education, and maternal psychiatric diagnosis. Results: Approximately 65 of the 246 children were exposed to some level of tobacco during pregnancy. Compared to non-exposed offspring, those prenatally exposure to tobacco were more likely to have a fail/monitor score for fine motor skills (adjusted odds ratio: 3.9, 95% CI: 1.6, 9.9) and to exhibit decreased inhibitory control (adjusted beta coefficient: -3.5, 95% CI: -6.5, -0.4). Conclusions: Any exposure to tobacco in utero may have long-lasting effects on cognitive ability, independent of other known risk factors. Increased developmental screening may be warranted for children prenatally exposed to tobacco.

Prenatal exposure to per- and polyfluoroalkyl substances and infant growth and adiposity: the Healthy Start Study

BackgroundPrenatal exposures to certain per- and polyfluoroalkyl substances (PFAS) have been linked to lower weight and adiposity at birth but greater weight and adiposity in childhood. We hypothesized that faster growth in early infancy may be associated with maternal PFAS concentrations. MethodsAmong 415 mother-infant pairs in a longitudinal cohort study, we estimated associations between maternal pregnancy serum concentrations of six PFAS and offspring weight and adiposity at ~5 months of age, and growth in early infancy. Linear and logistic regression models were adjusted for potential confounders including maternal pre-pregnancy body mass index. Effect modification by infant sex was evaluated. We evaluated potential confounding by correlated exposures via multipollutant linear regression and elastic net penalized regression. ResultsAssociations between maternal PFAS concentrations and infant weight and adiposity differed by offspring sex. In male infants, maternal perfluorooctanoate and perfluorononanoate were positively associated with adiposity, with percent fat mass increases of 1.5–1.7% per ln-ng/mL increase in PFAS (median adiposity at ~5 months: 24.6%). Maternal perfluorooctane sulfonate (PFOS) and perfluorohexane sulfonate (PFHxS) were associated with lower weight-for-age z-score among female infants only (−0.26 SD per ln-ng/mL PFOS, 95% CI −0.43, −0.10; −0.17 SD per ln-ng/mL PFHxS, 95% CI −0.33, −0.01). In analyses pooled by sex, 2-(N-methyl-perfluorooctane sulfonamido) acetate above vs. below the limit of detection was associated with greater odds of rapid growth in weight-for-age (odds ratio [OR] 2.2, 95% CI 1.1, 4.3) and weight-for-length (OR 3.3, 95% CI 1.8, 6.2). Multipollutant models generally confirmed the results and strengthened some associations. DiscussionWe observed sex- and chemical-specific associations between maternal serum PFAS concentrations and infant weight and adiposity. Multipollutant models suggested confounding by correlated PFAS with opposing effects. Although maternal PFAS concentrations are inversely associated with infant weight and adiposity at birth, rapid gain may occur in infancy, particularly in fat mass.

Childhood Metabolic Biomarkers Are Associated with Performance on Cognitive Tasks in Young Children

To evaluate the hypothesis that metabolic measures (fasting glucose, insulin, and Homeostatic Model of Assessment for Insulin Resistance [HOMA-IR] levels) are inversely associated with performance on cognitive tasks using data from young (4- to 6-year-old), typically developing, healthy children. Data were obtained from children participating in the Healthy Start study, a pre-birth cohort in Colorado. HOMA-IR, glucose, and insulin values were centered and scaled using the study sample means and SD. Thus, they are reported in number of SD units from the mean. Fully corrected T scores for inhibitory control (Flanker task), cognitive flexibility (Dimensional Change Card Sort test), and receptive language (Picture Vocabulary test) were obtained via the National Institutes of Health Toolbox cognition battery. Children included in this analysis (n=137) were 4.6years old, on average. Per 1-SD unit, fasting glucose (B = -2.0, 95% CI -3.5, -0.5), insulin (B = -1.7, 95% CI -3.0, -0.4), and HOMA-IR values (B = -1.8, 95% CI -3.1, -0.5) were eachsignificantly and inversely associated with inhibitory control (P<.05 for all, respectively). Fasting glucose levels were also inversely associated with cognitive flexibility (B = -2.0, 95% CI -3.7, -0.2, P = .03). Our data suggest that metabolic health may impact fluid cognitive function in healthy, young children.

Cord Blood Vitamin D Levels and Early Childhood Blood Pressure: The Healthy Start Study.

BackgroundVitamin D deficiency is associated with cardiovascular events among adults, but it is unclear whether early‐life vitamin D deficiency influences cardiovascular risk factors in children.Methods and ResultsWe measured total and bioavailable 25‐dihydroxyvitamin D (25OHD) in cord blood and in blood from 4‐ to 6‐year‐old children, and we assessed cardiovascular risk factors (blood pressure, arterial stiffness, body size, and adiposity) at 4 to 6 years. We tested for racial/ethnic differences in total and bioavailable 25OHD (n=715) and modeled the adjusted association between cord blood 25OHD and childhood cardiovascular risk factors (n=171). We observed racial/ethnic differences in total and bioavailable 25OHD levels in both cord and child blood samples (all P<0.05). Each 25‐nmol/L increase in cord blood total 25OHD was associated with a 2.5–mm Hg (SE 0.8) decrease in systolic blood pressure (P=0.002) and a 1.7–mm Hg (SE 0.6) decrease in diastolic blood pressure (P=0.01), independent of childhood 25OHD levels, race/ethnicity, and other covariates. There was no association between cord blood total 25OHD and any other cardiovascular risk factors. Cord blood levels of bioavailable and free 25OHD were not associated with any cardiovascular risk factor in childhood.ConclusionsIn this diverse prebirth cohort, we observed lower systolic and diastolic blood pressure among children with higher total 25OHD levels at birth. Our findings suggest that intrauterine exposure to vitamin D may contribute to early‐life programming of offspring blood pressure. Intervention studies are needed to determine whether increasing fetal vitamin D exposure can reduce the risk of elevated blood pressure in childhood.

Parental support in promoting children\u2019s health behaviours and preventing overweight and obesity \u2013 a long-term follow-up of the cluster-randomised healthy school start study II trial

BackgroundEffects of obesity prevention interventions in early childhood are only meaningful if they are sustained over time, but long-term follow-up studies are rare. The school-based cluster-randomised Healthy School Start (HSS) trial aimed at child health promotion and obesity prevention through parental support was carried out in 31 pre-school classes (378 families) in disadvantaged areas in Sweden during 2012–2013. Post-intervention results showed intervention effects on intake of unhealthy foods and drinks, and lower BMI-sds in children with obesity at baseline. This study aimed to evaluate the long-term effectiveness 4 years post-intervention.MethodsData were collected from 215 children in March–June 2017. Child dietary intake, screen time, and physical activity were measured through parental-proxy questionnaires. Child height and weight were measured by the research group. Group effects were examined using Poisson, linear, logistic, and quantile regression for data on different levels. Analyses were done by intention to treat, per protocol, and sensitivity analyses using multiple imputation.ResultsNo between-group effects on dietary intake, screen time, physical activity, or BMI-sds were found for the entire group at the four-year follow-up. In girls, a significant subgroup-effect was found favouring intervention compared to controls with a lower intake of unhealthy foods, but this was not sustained in the sensitivity analysis. In boys, a significant sub-group effect was found where the boys in the intervention group beyond the 95th percentile had significantly higher BMI-sds compared to boys in the control group. This effect was sustained in the sensitivity analysis. Analyses per protocol showed significant intervention effects regarding a lower intake of unhealthy foods and drinks in the children with a high intervention dose compared to controls.ConclusionsFour years after the intervention, only sub-group effects were found, and it is unlikely that the HSS intervention had clinically meaningful effects on the children. These results suggest that school-based prevention programmes need to be extended for greater long-term effectiveness by e.g. integration into school routine practice. In addition, results showed that children with a high intervention dose had better long-term outcomes compared to controls, which emphasises the need for further work to increase family engagement in interventions.Trial registration ISRCTN, ISRCTN39690370, retrospectively registered March 1, 2013, http://www.isrctn.com/ISRCTN39690370.