Healthy Start Study Research Articles

Comparing the Diagnostic Accuracy of Measures of Maternal Diet During Pregnancy for Offspring Allergy Outcomes: The Healthy Start Study

Allergic diseases in children are increasing. Although maternal diet quality in pregnancy may be protective, it is unclear which measure of maternal diet best predicts offspring diseases. To examine the associations between multiple diet measures and allergy outcomes, and to compare the diagnostic accuracy of the measures for the prediction of allergy outcomes. Maternal diet during pregnancy was measured using a validated instrument, and scored using 5 measures: the maternal diet index (MDI), Healthy Eating Index, total diet diversity, healthy diet diversity, and unhealthy diet diversity. Unadjusted and adjusted logistic regression models assessed associations between maternal diet measures and offspring allergy outcomes up to age 4 years. The diagnostic accuracy of the diet measures was compared. There were significant associations between MDI (odds ratio [OR], 0.78; 95% CI, 0.70-0.87), Healthy Eating Index (OR, 0.98; 95% CI, 0.97-0.99), and healthy diet diversity scores (OR, 0.91; 95% CI, 0.85-0.98) during pregnancy and the primary combined outcome "any allergy excluding wheeze" in children up to age 4 years. Neither maternal total diet diversity (OR, 0.99; 95% CI, 0.95-1.03) nor unhealthy diet diversity scores (OR, 1.05; 95% CI, 0.98-1.13) were associated with the "any allergy excluding wheeze" outcome. For all outcomes studied, except for food allergy, there was a significant difference in the diagnostic accuracy between the 5 measures of maternal diet. The area under the curve for MDI was highest for every disease outcome, although not always significantly higher. Better quality and higher diversity of a woman's diet during pregnancy, measured in various ways, is associated with offspring allergy outcomes, with healthy foods associated with decreased risk, and unhealthy foods associated with a higher risk. The MDI, which appropriately weighted both healthy and unhealthy foods, best predicted childhood allergic disease.

Fetal exposure to cannabis and childhood behavior at age 5 years: The Healthy Start study

Fetal exposure to cannabis and childhood behavior at age 5 years: The Healthy Start study

Fetal exposure to cannabis, neonatal adiposity, and postnatal growth trajectories: The Healthy Start study

Objective: Cannabis use during pregnancy is associated with lower birth weight and may influence postnatal growth. We estimated associations of fetal exposure to cannabis with neonatal adiposity and body mass index (BMI) z-score trajectories through age 3 years, as well as effect modification by breastfeeding. Methods: We leveraged a subsample of 130 mother-child pairs from a Colorado-based cohort. Twelve cannabinoids/metabolites (including delta 9-tetrahydrocannabinol [THC] and cannabidiol [CBD]) were measured in maternal urine collected at ~27 weeks gestation. Fetal exposure to cannabis was dichotomized as exposed (any cannabinoid≥limit of quantification) and not exposed (cannabinoids<limit of quantification). Generalized linear models estimated the associations between fetal exposure to cannabis with birth weight and neonatal adiposity (measured by air displacement plethysmography). A mixed-effects model estimated the association between fetal cannabis exposure and BMI z-score trajectories. Interaction by breastfeeding duration was assessed by including a product term (with fetal exposure to cannabis) in a mixed-effects model. Results: Fetal exposure to cannabis was associated with lower birth weight (-206g; 95% CI: -393, -18; p=0.03) and neonatal adiposity (-2.0%; 95% CI: -3.7, -0.02; p=0.03) followed by rapid postnatal growth through 3 years (0.37 increase in BMI z-score per square root year; 95% CI: 0.01, 0.60; p=0.02). Breastfeeding modified this association (p for interaction<0.01). Among cannabis-exposed offspring who were not breastfed, BMI z-scores were 0.42 lower at 6 months (95% CI: -1.15, 0.31) but 0.54 higher at 36 months (95% CI: -0.36, 1.44). Conversely, BMI z-scores were no different by fetal cannabis exposure among offspring who were breastfed for ~5 months. Conclusions: Our data suggests that fetal exposure to cannabis alters fetal and postnatal growth, and that breastfeeding may stabilize over-compensatory growth among cannabis-exposed offspring. Although the impact of lactational exposure to cannabis requires further investigation, it remains important to caution against cannabis use during pregnancy and lactation.

Characterization of Maternal Psychosocial Stress During Pregnancy: The Healthy Start Study.

Objective:To capture multidimensional maternal psychosocial stress using responses from the Edinburgh Postnatal Depression Scale (EPDS) and Cohen's Perceived Stress Scale (PSS) administered during pregnancy, and to identify sociodemographic, biological, and health behavioral correlates of the stress domains.Methods:Using data from 1,079 pregnant women, we implemented principal component analysis on EPDS and PSS responses and retained factors based on the Scree plot and Eigenvalues >1. We then used linear regression to identify perinatal correlates of each domain.Results:We identified three stress domains: “Feeling Overwhelmed,” “Anhedonia,” and “Lack of Control,” which accounted for 10.6% of variance in questionnaire responses. In multivariable analyses, household income ≤$70,000 (β = 0.21 confidence interval [95% CI: 0.05–0.39]), primiparity (0.36 [0.02–0.71]), inadequate (0.21 [0.04–0.39]) or excessive gestational weight gain (0.27 [0.11–0.42]), and Healthy Eating Index (HEI) score ≤57 (0.14 [0.00–0.28]) were associated with Feeling Overwhelmed. Older age (0.02 [0.00–0.03] per 1-year), Hispanic ethnicity (0.19 [0.00–0.38]), and HEI score ≤57 (0.15 [0.02–0.28]) were associated with Anhedonia. Non-Hispanic Black race/ethnicity (0.37 [0.10–0.63]), not having graduated from college (0.16 [−0.02 to 0.35]), having a partner born outside the United States (0.17 [−0.02 to 0.37]), household size of ≥5 persons (0.21 [−0.02 to 0.37]), receiving public assistance (0.18 [−0.02 to 0.37]), and prenatal smoking (0.32 [0.05–0.59]) were associated with Lack of Control.Conclusions:Three domains of maternal psychosocial stress during pregnancy (Feeling Overwhelmed, Anhedonia, and Lack of Control) were differentially related to sociodemographic, biological, and health behavioral characteristics that may be targets for interventions to ameliorate stress in pregnant women.Clinical Trial Registry: The Healthy Start study is registered as an observational study at clinicaltrials.gov (NCT #002273297).

Infant Mesenchymal Stem Cell Insulin Action Is Associated With Maternal Plasma Free Fatty Acids, Independent of Obesity Status: The Healthy Start Study.

Preclinical rodent and nonhuman primate models investigating maternal obesity have highlighted the importance of the intrauterine environment in the development of insulin resistance in offspring; however, it remains unclear if these findings can be translated to humans. To investigate possible intrauterine effects in humans, we isolated mesenchymal stem cells (MSCs) from the umbilical cord tissue of infants born to mothers of normal weight or mothers with obesity. Insulin-stimulated glycogen storage was determined in MSCs undergoing myogenesis in vitro. There was no difference in insulin action based on maternal obesity. However, maternal free fatty acid (FFA) concentration, cord leptin, and intracellular triglyceride content were positively correlated with insulin action. Furthermore, MSCs from offspring born to mothers with elevated FFAs displayed elevated activation of the mTOR signaling pathway. Taken together, these data suggest that infants born to mothers with elevated lipid availability have greater insulin action in MSCs, which may indicate upregulation of growth and lipid storage pathways during periods of maternal overnutrition.

Ambient air pollution during pregnancy and DNA methylation in umbilical cord blood, with potential mediation of associations with infant adiposity: The Healthy Start study

BackgroundPrenatal exposure to ambient air pollution has been associated with adverse offspring health outcomes. Childhood health effects of prenatal exposures may be mediated through changes to DNA methylation detectable at birth. MethodsAmong 429 non-smoking women in a cohort study of mother-infant pairs in Colorado, USA, we estimated associations between prenatal exposure to ambient fine particulate matter (PM2.5) and ozone (O3), and epigenome-wide DNA methylation of umbilical cord blood cells at delivery (2010–2014). We calculated average PM2.5 and O3 in each trimester of pregnancy and the full pregnancy using inverse-distance-weighted interpolation. We fit linear regression models adjusted for potential confounders and cell proportions to estimate associations between air pollutants and methylation at each of 432,943 CpGs. Differentially methylated regions (DMRs) were identified using comb-p. Previously in this cohort, we reported positive associations between 3rd trimester O3 exposure and infant adiposity at 5 months of age. Here, we quantified the potential for mediation of that association by changes in DNA methylation in cord blood. ResultsWe identified several DMRs for each pollutant and period of pregnancy. The greatest number of significant DMRs were associated with third trimester PM2.5 (21 DMRs). No single CpGs were associated with air pollutants at a false discovery rate <0.05. We found that up to 8% of the effect of 3rd trimester O3 on 5-month adiposity may be mediated by locus-specific methylation changes, but mediation estimates were not statistically significant. ConclusionsDifferentially methylated regions in cord blood were identified in association with maternal exposure to PM2.5 and O3. Genes annotated to the significant sites played roles in cardiometabolic disease, immune function and inflammation, and neurologic disorders. We found limited evidence of mediation by DNA methylation of associations between third trimester O3 exposure and 5-month infant adiposity.

242 Characterization of Maternal Stress During Pregnancy

OBJECTIVES/GOALS: 1. To characterize domains of maternal psychosocial stress from the Edinburgh Postnatal Depression Scale (EPDS) and Cohens Perceived Stress Scale (PSS) administered during pregnancy using principal components analysis (PCA). 2. To identify sociodemographic, perinatal, and lifestyle correlates of maternal psychosocial stress domains. METHODS/STUDY POPULATION: Using data from 1,079 pregnant women in the Healthy Start Study who completed both the EPDS and PSS in early pregnancy, we ran PCA and retained factors representative of uncorrelated domains of maternal psychosocial stress based on the Scree plot and Eigenvalues &gt;1. We then used linear regression to identify sociodemographic, perinatal, and lifestyle correlates of each maternal stress domain, followed by multivariable models that mutually adjusted for all characteristics that were statistically significant at alpha = 0.10. RESULTS/ANTICIPATED RESULTS: We identified three domains of maternal psychosocial stress based on PCA results: Feeling Overwhelmed (Domain 1), Anhedonia (Domain 2), and Lack of Control (Domain 3). In unadjusted analyses, lower household income and poor diet quality were associated with higher scores for all three domains. In adjusted analyses, lower household income, being multiparous, inadequate or excessive GWG, and poor diet quality were associated with Feeling Overwhelmed. Older age, Hispanic ethnicity, and poor diet quality were associated with Anhedonia. Non-Hispanic, Black race/ethnicity, lower educational attainment, having a partner born outside the US, larger household size, receiving public assistance, and smoking during pregnancy were associated with Lack of Control. DISCUSSION/SIGNIFICANCE: We identify three unique domains of maternal psychosocial stress that are differentially related to sociodemographic, perinatal, and lifestyle characteristics. Correlates of stress domains shed light on upstream determinants and biological and psychosocial mechanisms through which experiences of stress manifest.

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

ObjectiveTo assess the impact of fetal exposure to cannabis on adiposity and glucose-insulin traits in early life.Research Design and MethodsWe 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]).ResultsApproximately 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.ConclusionsWe 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.

Exposure to maternal fuels during pregnancy and offspring hepatic fat in early childhood: The healthy start study.

Intrauterine overnutrition has been associated with paediatric nonalcoholic fatty liver disease (NAFLD), but the exact mechanisms involved remain unclear. To examine whether maternal fuels and metabolic markers during pregnancy are associated with offspring hepatic fat in childhood. This analysis included 286 mother-child pairs from the Healthy Start Study, a longitudinal pre-birth cohort in Colorado. Fasting blood draws were collected in early pregnancy (~17 weeks) and mid-pregnancy (~27 weeks). Offspring hepatic fat was assessed by magnetic resonance imaging (MRI) at ~5 years. In early pregnancy, maternal triglycerides (TGs) and free fatty acids (FFAs) were positively associated with offspring hepatic fat [Back-transformed β (95% CI): 1.15 (1.05, 1.27) per 1 standard deviation (SD) TGs; 1.14 (1.05, 1.23) per 1 SD FFAs]. Maternal total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were also associated with offspring hepatic fat, but only among boys [1.22 (1.08, 1.37) per 1 SD TC; 1.21 (1.07, 1.37) per 1 SD LDL-C]. In mid-pregnancy, only maternal TGs remained associated with offspring hepatic fat. Adjusting for potential confounders or mediators did not affect associations. Maternal lipid concentrations, especially in early pregnancy, are associated with higher offspring hepatic fat, and may, therefore, be targeted in future interventions among pregnant women.

Prenatal exposure to ambient air pollution and traffic and indicators of adiposity in early childhood: the Healthy Start study.

Prenatal exposure to ambient air pollution and traffic have been related to a lower birth weight and may be associated with greater adiposity in childhood. We aimed to examine associations of maternal exposure to ambient air pollution and traffic during pregnancy with indicators of adiposity in early childhood. We included 738 participants of the Colorado-based Healthy Start study whose height, weight, waist circumference and/or fat mass were measured at age 4-6 years. We estimated residential exposure to ambient concentrations of fine particulate matter (PM2.5) and ozone (O3) averaged by trimester and throughout pregnancy via inverse distance-weighted interpolation of central site 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, waist circumference, percent fat mass and fat mass index (FMI) were assessed by logistic and linear regression. Associations of exposure to PM2.5 and O3 at the residential address during pregnancy with percent fat mass and FMI at age 4-6 years were inconsistent across trimesters. For example, second trimester PM2.5 was associated with a higher percent fat mass (adjusted difference 0.70% [95% CI 0.05, 1.35%] per interquartile range (IQR; 1.3 µg/m3) increase), while third trimester PM2.5 was associated with a lower percent fat mass (adjusted difference -1.17% [95% CI -1.84, -0.50%] per IQR (1.3 µg/m3) increase). Residential proximity to a highway during pregnancy was associated with higher odds of being overweight at age 4-6 years. We observed no associations of prenatal exposure to PM2.5 and O3 with overweight and waist circumference. We found limited evidence of associations of prenatal exposure to ambient PM2.5 and O3 with indicators of adiposity at age 4-6 years. Suggestive relationships between residential proximity to a highway during pregnancy and greater adiposity merit further investigation.

Advanced glycation end product intake during pregnancy and offspring allergy outcomes: A Prospective cohort study

Associations have been shown between concurrent assessment of dietary intake of advanced glycation end products (AGEs) and childhood allergic outcomes. We examined the association between maternal AGEs intake and development of offspring asthma, wheeze, atopic dermatitis, allergic rhinitis and food allergies, and sought to determine whether the intake of AGEs was associated with cord sera cytokines/chemokines. Pregnant women ≥16years were recruited in the Healthy Start study, a prospective pre-birth cohort from Colorado (N=1410). The analysis included 962 dyads with adequate diet (≥2 recalls) and allergy outcome details. AGEs intake was estimated for each mother by matching intakes reported using 24-h dietary recalls during pregnancy to a reference database of commonly consumed foods' AGEs values. Child diagnoses of asthma and allergies up to 8years were obtained from electronic medical records. Cord sera cytokines and chemokines were analysed in a subset (N=462) of children. The median [IQR] AGEs intake for the overall sample was 11,919kU/day [8293, 16,573]. Unadjusted analysis showed a positive association between maternal AGEs intake in pregnancy and rhinitis up to 8years of age (HR=1.03; 95% CI: 1.01, 1.06), but the association was attenuated and no longer significant in adjusted models (HR=1.01; 95% CI: 0.98, 1.04). Both adjusted and unadjusted models showed no associations between AGEs intake in pregnancy and any of the other outcomes (p>.05). There were no significant associations between any cytokine or chemokine measured and AGEs intake or any of the outcomes studied (p>.05). The study showed that maternal AGEs intake was not associated with offspring asthma and allergy outcomes. AGEs exposure during pregnancy may not have the same impact on child development as postnatal exposure.

Prenatal exposure to per- and polyfluoroalkyl substances and child adiposity at age 5 years: a multipollutant analysis

BACKGROUND AND AIM: Prenatal exposure to per- and polyfluoroalkyl substances (PFAS) is linked to lower birthweight and adiposity at birth. In some but not all previous studies, prenatal PFAS predict greater childhood BMI. However, few have directly measured child adiposity. We hypothesized that prenatal PFAS would be positively associated with child adiposity, evaluated using a precise method. METHODS: Pregnant women enrolled in the Healthy Start study (2009-2014). Blood samples were collected at a median of 27 weeks of gestation. Eleven PFAS were quantified in maternal serum; five were detected in 75% of participants and analyzed here. Child body composition at age 5 years was assessed using air displacement plethysmography. Adiposity was calculated as fat mass/total body mass x 100%. Three statistical approaches estimated associations between prenatal PFAS and child adiposity: single pollutant linear regression models; multipollutant linear regression model; and Bayesian Kernel Machine Regression (BKMR). Multipollutant models included five PFAS and a common covariate set. RESULTS:Among 340 participants, median child adiposity was 20.2% [interquartile range: 8.6%]. Pairwise Spearman correlations between PFAS were moderate to high (range: 0.32-0.78). In single pollutant models, each ln-unit increase in perfluorooctanoate (PFOA) was associated with 1.3% (95% CI 0.2, 2.5) greater child adiposity; no other PFAS was associated with adiposity. In the multipollutant model, PFOA was more strongly associated with adiposity than in the single pollutant model and there was an inverse association between perfluorodecanoate (PFDA) and adiposity; all variance inflation factors were 5. BKMR confirmed PFOA as the only PFAS with a posterior inclusion probability 0.3, but also showed a weak inverse association with PFDA. No pairwise interactions between exposures or strong non-linear trends were detected. CONCLUSIONS:Prenatal exposure to PFOA was positively associated with child adiposity at age 5. Multipollutant linear regression and BKMR produced similar results in this relatively simple scenario. KEYWORDS: PFAS, Obesity and metabolic disorders, Mixtures analysis, Children’s Environmental Health

Ambient air pollution exposure during pregnancy and cardio-metabolic markers in cord blood: The Healthy Start study

BACKGROUND AND AIM: Prenatal air pollution exposure has been associated with adverse cardiometabolic outcomes in childhood. It is unknown whether evidence of metabolic disruption associated with air pollution may be identified at birth. We estimated associations between maternal residential exposure to air pollution during pregnancy and metabolic and lipid biomarkers in cord blood collected at delivery. METHODS: This study included 812 mother-infant pairs enrolled in the prospective, Colorado-based Healthy Start study (2009-2014). Using inverse-distance-weighted interpolation of data obtained from stationary monitors, we estimated daily particulate matter ≤2.5 micrometers (PM2.5) and ozone (O3) concentrations at participant residences. Daily estimates were averaged by trimester, full pregnancy, and the 7- and 30- days prior to delivery. Outcomes were cord blood concentrations of glucose, insulin, leptin, total and high-density lipoprotein cholesterol, free fatty acids, and triglycerides. Glucose-insulin ratio was calculated as an indirect measure of insulin sensitivity. We used multiple linear regression to estimate associations between PM2.5 and O3 and cord blood metabolic and lipid biomarkers. Covariates included maternal, infant, and meteorological characteristics. RESULTS:Higher O3 exposure, during both recent and longer-term exposure periods during pregnancy, was consistently associated with higher insulin and lower glucose-insulin ratio in cord blood. For example, an interquartile range increase in full pregnancy O3 (6.3 ppb) was associated with a 0.12 log-µIU/ml (95% confidence interval: 0.03, 0.21) increase in cord blood insulin, after adjusting for covariates. There was limited evidence supporting positive associations between PM2.5 and leptin and O3 and total cholesterol. There were inverse associations between PM2.5 and triglycerides, during certain periods of pregnancy. CONCLUSIONS:Prenatal air pollution exposure was associated with cardiometabolic biomarkers in cord blood, most notably for O3 and insulin. Future studies should examine whether these changes persist into childhood and their implications on offspring health. KEYWORDS: prenatal exposure, air pollution, lipids, metabolism, neonate

Green space, neighborhood walkability and cardiometabolic health in early pregnancy: The Healthy Start study

BACKGROUND AND AIM: Green space and neighborhood walkability have been associated with cardiometabolic health, but relationships with cardiometabolic markers during pregnancy are unclear. We estimated associations of residential green space and neighborhood walkability with cardiometabolic health in early pregnancy. METHODS: We included 1208 pregnant women enrolled in the Colorado-based Healthy Start study (2009-2014). During a study visit in early pregnancy (median 17 weeks of gestation), we measured systolic and diastolic blood pressure and collected fasting blood samples. We measured serum glucose and insulin and calculated the Homeostatic Model for Assessment of Insulin Resistance (HOMA-IR). We used the average Normalized Difference Vegetation Index (NDVI) in circular buffers of 250m, 500m and 1000m surrounding the participants’ homes to estimate exposure to green space. The walkability of the Census block group of the maternal residence was assessed by the National Walkability Index of 2010. Associations of green space and neighborhood walkability with cardiometabolic markers in early pregnancy were assessed by linear regression, adjusting for covariates. RESULTS:A higher average NDVI in all buffer sizes was associated with a lower diastolic blood pressure and (non-significantly) lower systolic blood pressure in early pregnancy. For example, women in the highest tertile of green space in a buffer of 500m (NDVI ≥0.21) had a 1.21mmHg [95%CI -2.23, -0.20] lower diastolic blood pressure than women in the lowest tertile. Additionally, pregnant women who lived in the most walkable neighborhoods had a 3.41mmHg [95%CI -5.31, -1.51] lower systolic and 2.18mmHg [95%CI -3.73, -0.63] lower diastolic blood pressure than women residing in the least walkable neighborhoods. We found no associations of green space or neighborhood walkability with glucose, insulin or HOMA-IR. CONCLUSIONS:In this racially and ethnically diverse population, higher exposure to residential green space and higher neighborhood walkability were associated with lower systolic and diastolic blood pressure in early pregnancy. KEYWORDS: Green space, Walkability, Female, Obesity and metabolic disorders

Maternal diet quality during pregnancy is associated with biomarkers of metabolic risk among male offspring.

Limited data exist on the association between maternal diet quality during pregnancy and metabolic traits in offspring during early childhood, which is a sensitive period for risk of obesity-related disorders later in life. We aimed to examine the association of maternal diet quality, as indicated by the Healthy Eating Index-2010 (HEI), in pregnancy with offspring metabolic biomarkers and body composition at age 4-7years. We used data from 761 mother-offspring pairs from the Healthy Start study to examine sex-specific associations of HEI >57 vs ≤57 with offspring fasting glucose, leptin, cholesterol, HDL, LDL, percentage fat mass, BMI z score and log-transformed insulin, 1/insulin, HOMA-IR, adiponectin, triacylglycerols, triacylglycerols:HDL, fat mass, and sum of skinfolds. Multivariable linear regression models accounted for maternal race/ethnicity, age, education, smoking habits during pregnancy and physical activity, and child's age. During pregnancy, mean (SD) HEI score was 55.0 (13.3), and 43.0% had an HEI score >57. Among boys, there was an inverse association of maternal HEI with offspring glucose, insulin, HOMA-IR and adiponectin. For instance, maternal HEI >57 was associated with lower fasting glucose (-0.11; 95% CI -0.20, -0.02mmol/l), and lower concentrations of: insulin by 15.3% (95% CI -24.6, -5.0), HOMA-IR by 16.3% (95% CI -25.7, -5.6) and adiponectin by 9.3% (95% CI -16.1, -2.0). Among girls, there was an inverse association of maternal HEI with insulin and a positive association with LDL. However, following covariate adjustment, all estimates among girls were attenuated to the null. Greater compliance with the USA Dietary Guidelines via the HEI may improve the maternal-fetal milieu and decrease susceptibility for poor metabolic health among offspring, particularly boys. Future studies are warranted to confirm these associations and determine the underlying mechanisms.

Hepatic Fat in Early Childhood Is Independently Associated With Estimated Insulin Resistance: The Healthy Start Study.

Fatty liver disease is a common metabolic abnormality in adolescents with obesity but remains understudied in early childhood. To describe hepatic fat deposition in prepubertal children and examine cross-sectional associations with metabolic markers and body composition. Data were from 286 children ages 4 to 8 years old in the Healthy Start Study, a longitudinal prebirth cohort in Colorado (USA). Assessments included magnetic resonance imaging to quantify hepatic and abdominal fats, fasting blood draws to measure metabolic markers, and air displacement plethysmography to measure body composition (fat mass and fat-free mass). The median (interquartile range) for hepatic fat was 1.65% (1.24%, 2.11%). Log-transformed hepatic fat was higher in Hispanic [mean (95% CI): 0.63 (0.52, 0.74)] vs non-Hispanic white children [0.46 (0.38, 0.53), P = 0.01] and children with overweight/obesity [0.64 (0.49, 0.79)] vs normal-weight [0.47 (0.40, 0.53), P = 0.02]. Higher log-hepatic fat was associated with higher insulin [β (95% CI): 1.47 (0.61, 2.33) uIU/mL, P = 0.001] and estimated insulin resistance (homeostatic model assessment) [0.40 (0.20, 0.60), P < 0.001] in the full sample and glucose [5.53 (2.84, 8.21) mg/dL, P < 0.001] and triglycerides [10.92 (2.92,18.91) mg/dL, P = 0.008] in boys, in linear regression models adjusted for sociodemographics, maternal/perinatal confounders, and percentage body fat. Log-hepatic fat was also associated with abdominal subcutaneous adipose tissue [SAT; 7.37 (1.12,13.60) mm2, P = 0.02] in unadjusted models, but this was attenuated and insignificant after adjusting for confounders. While hepatic fat was low in children 4 to 8 years old, it was independently associated with estimated insulin resistance and exhibited sex-specific associations with glucose and triglycerides, suggesting hepatic fat may be an early indicator of metabolic dysfunction in youth.

The maternal diet index in pregnancy is associated with offspring allergic diseases: the Healthy Start study.

A systematic review showed limited associations between pregnancy diet and offspring allergy. We developed a maternal diet index during pregnancy that was associated with offspring allergy outcomes. Data came from Healthy Start, a Colorado pre-birth cohort of mother/offspring dyads. Food propensity questionnaires were completed during pregnancy. Offspring allergic rhinitis, atopic dermatitis, asthma, wheeze, and food allergy diagnosis up to age four were verified from electronic medical records. Data were randomized into test and replication sets. The index included the weighted combination of variables that best predicted a combined outcome of any allergy in the test set. Index utility was verified in the replication set. Separate adjusted and unadjusted logistic models estimated associations between the index and each offspring allergy diagnosis in the full sample. The index included weighted measures of intake of vegetables, yogurt, fried potatoes, rice/grains, red meats, pure fruit juice, and cold cereals. Vegetables and yogurt were associated with the prevention of any allergy, while other components were associated with increased disease. In adjusted models, a one-unit increase in the index was significantly associated with reduced odds of offspring allergic rhinitis (odds ratio (CI) 0.82 [0.72-0.94]), atopic dermatitis (0.77 [0.69-0.86]), asthma (0.84 [0.74-0.96]), and wheeze (0.80 [0.71-0.90]), but not food allergy (0.84 [0.66-1.08]). This is the first study that has shown associations between an index of maternal dietary intake during pregnancy and multiple offspring allergic diseases. The results give hope for prevention of allergic diseases in utero.

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

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. 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. 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.

Exposure to ambient air pollution during pregnancy and inflammatory biomarkers in maternal and umbilical cord blood: The Healthy Start study

BackgroundAir pollution exposure during pregnancy has been associated with adverse pregnancy and birth outcomes. Inflammation has been proposed as a potential link. We estimated associations between air pollution exposure during pregnancy and inflammatory biomarkers in maternal and cord blood. We evaluated whether maternal inflammation was associated with infant outcomes. MethodsAmong 515 mother-infant dyads in the Healthy Start study (2009–2014), trimester-long, 7- and 30-day average concentrations of particulate matter ≤2.5 μm (PM2.5) and ozone (O3) during pregnancy were estimated, using inverse-distance-weighted interpolation. Inflammatory biomarkers were measured in maternal blood in mid-pregnancy (C-reactive protein [CRP], Interleukin [IL]-6, and tumor necrosis factor-α [TNFα]) and in cord blood at delivery (CRP, IL-6, IL-8, IL-10, monocyte chemoattractant protein-1 [MCP-1], and TNFα). We used linear regression to estimate associations between pollutants and inflammatory biomarkers and maternal inflammatory biomarkers and infant weight and body composition. ResultsThere were positive associations between PM2.5 during certain exposure periods and maternal IL-6 and TNFα. There were negative associations between recent O3 and maternal CRP, IL-6, and TNFα and positive associations between trimester-long O3 exposure and maternal inflammatory biomarkers, though some 95% confidence intervals included the null. Patterns were inconsistent for associations between PM2.5 and O3 and cord blood inflammatory biomarkers. No consistent associations between maternal inflammatory biomarkers and infant outcomes were identified. ConclusionsAir pollution exposure during pregnancy may impact maternal inflammation. Further investigations should examine the health consequences for women and infants of elevated inflammatory biomarkers associated with air pollution exposure during pregnancy.

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

BackgroundFew studies have demonstrated associations between maternal dietary inflammatory index (DII) during pregnancy and offspring asthma and/or wheeze. ObjectiveThe study aimed to assess associations between maternal DII during pregnancy and 1) offspring cord sera pro-inflammatory cytokines (interleukin [IL]-1β, 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. DesignThe Healthy Start study is a prospective prebirth longitudinal study that recruited pregnant women in Denver, Colorado and tracked their offspring. Participants and settingThis 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 measuresCord 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 performedUnadjusted 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. ResultsUnadjusted 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. ConclusionsThe 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.