Power for balanced linear mixed models with complex missing data processes.

When designing repeated measures studies, both the amount and the pattern of missing outcome data can affect power. The chance that an observation is missing may vary across measurements, and missingness may be correlated across measurements. For example, in a physiotherapy study of patients with Parkinson's disease, increasing intermittent dropout over time yielded missing measurements of physical function. In this example, we assume data are missing completely at random, since the chance that a data point was missing appears to be unrelated to either outcomes or covariates. For data missing completely at random, we propose noncentral F power approximations for the Wald test for balanced linear mixed models with Gaussian responses. The power approximations are based on moments of missing data summary statistics. The moments were derived assuming a conditional linear missingness process. The approach provides approximate power for both complete-case analyses, which include independent sampling units where all measurements are present, and observed-case analyses, which include all independent sampling units with at least one measurement. Monte Carlo simulations demonstrate the accuracy of the method in small samples. We illustrate the utility of the method by computing power for proposed replications of the Parkinson's study.

Childhood nutrient intakes are differentially associated with hepatic and abdominal fats in adolescence: The EPOCH study.

OBJECTIVE: The aim of this study was to examine whether nutrient intakes in childhood are associated with abdominal and hepatic fat depots later in adolescence. METHODS: Using data from 302 participants in the longitudinal Exploring Perinatal Outcomes among CHildren (EPOCH) study, energy partition and nutrient density models were constructed to examine associations of nutrient intakes in childhood (~10 years of age), assessed by food frequency questionnaire, with abdominal subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), and hepatic fat in adolescence (~16 years of age). RESULTS: In energy partition models (energy intake not held constant), total, monounsaturated, and polyunsaturated fat intakes in childhood were associated with higher SAT in adolescence (ß [95% CI]: 8.5 [0.1-17.1], 25.1 [2.1-48.1], and 59.7 [16.1-103.3] mm2 per 100 kcal/d), higher starch intake was associated with log-hepatic fat (back-transformed ß [95% CI]: 1.07 [1.01-1.15] per 100 kcal/d), and, in boys only, higher animal protein intake was associated with VAT (ß [95% CI]: 5.3 [0.3-10.3] mm2 per 100 kcal/d). Most associations were unchanged when adjusted for energy intake in nutrient density models. CONCLUSIONS: Childhood nutrient intakes were differentially associated with adolescent body fats; specifically, unsaturated fat intake predicted abdominal SAT, animal protein intake predicted VAT, and starch intake predicted hepatic fat. These nutrient intakes may, therefore, be targets for intervention studies aiming to modify adolescent body fat distribution.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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]). CONCLUSIONS: 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.

Disparities in Risks of Inadequate and Excessive Intake of Micronutrients during Pregnancy.

BACKGROUND: Inadequate or excessive intake of micronutrients in pregnancy has potential to negatively impact maternal/offspring health outcomes. OBJECTIVE: The aim was to compare risks of inadequate or excessive micronutrient intake in diverse females with singleton pregnancies by strata of maternal age, race/ethnicity, education, and prepregnancy BMI. METHODS: Fifteen observational cohorts in the US Environmental influences on Child Health Outcomes (ECHO) Consortium assessed participant dietary intake with 24-h dietary recalls (n = 1910) or food-frequency questionnaires (n = 7891) from 1999-2019. We compared the distributions of usual intake of 19 micronutrients from food alone (15 cohorts; n = 9801) and food plus dietary supplements (10 cohorts with supplement data; n = 7082) to estimate the proportion with usual daily intakes below their age-specific daily Estimated Average Requirement (EAR), above their Adequate Intake (AI), and above their Tolerable Upper Intake Level (UL), overall and within sociodemographic and anthropometric subgroups. RESULTS: Risk of inadequate intake from food alone ranged from 0% to 87%, depending on the micronutrient and assessment methodology. When dietary supplements were included, some women were below the EAR for vitamin D (20-38%), vitamin E (17-22%), and magnesium (39-41%); some women were above the AI for vitamin K (63-75%), choline (7%), and potassium (37-53%); and some were above the UL for folic acid (32-51%), iron (39-40%), and zinc (19-20%). Highest risks for inadequate intakes were observed among participants with age 14-18 y (6 nutrients), non-White race or Hispanic ethnicity (10 nutrients), less than a high school education (9 nutrients), or obesity (9 nutrients). CONCLUSIONS: Improved diet quality is needed for most pregnant females. Even with dietary supplement use, >20% of participants were at risk of inadequate intake of ≥1 micronutrients, especially in some population subgroups. Pregnancy may be a window of opportunity to address disparities in micronutrient intake that could contribute to intergenerational health inequalities.

Adherence to index-based dietary patterns in childhood and BMI trajectory during the transition to adolescence: the EPOCH study.

BACKGROUND: In the United States, one in five adolescents are obese. Index-based dietary patterns are measures of the overall diet that have the potential to serve as valuable obesity risk stratification tools. However, little is known about the association between adherence to index-based dietary patterns in childhood and BMI during the transition from childhood to adolescence. OBJECTIVE: To prospectively examine the relationship between adherence to three index-based dietary patterns in childhood and BMI trajectory during the transition to adolescence. METHODS: The study included 581 children enrolled in a Colorado prospective cohort study conducted between 2006 and 2015. Dietary intake was assessed with the Block Kids Food Frequency Questionnaire at age 10 years. Scores were calculated for the Healthy Eating Index-2010 (HEI-2010), the alternate Mediterranean (aMED) diet, and the Dietary Approaches to Stop Hypertension (DASH) diet. Weight and height were assessed via anthropometry at two research visits (ages 10 and 16 years), with interim clinical measurements extracted from Kaiser Permanente medical records. Separate mixed models were used to assess the association between each diet index score and BMI over a 6-year period. Models were stratified by sex and adjusted for age, race/ethnicity, income, and exposure to gestational diabetes. RESULTS: Median (IQR) number of BMI assessments was 14 (10-18). Among girls, for every ten-unit increase in HEI-2010 score, there was an average 0.64 kg/m2 decrease (p = 0.007) in BMI over time, after adjustment for covariates. Among girls, there was no association between BMI and aMED (ß = -0.19, p = 0.24) or DASH (ß = 0.28, p = 0.38). Among boys, there was no statistically significant association between BMI and HEI-2010 (0.06, p = 0.83), aMED (0.07, p = 0.70), or DASH (0.42, p = 0.06). CONCLUSIONS: Efforts to prevent adolescent obesity could benefit from considering the degree of adherence to federal dietary guidance, as assessed by the HEI, in the period preceding adolescence, especially among girls.

A power approximation for the Kenward and Roger Wald test in the linear mixed model.

We derive a noncentral [Formula: see text] power approximation for the Kenward and Roger test. We use a method of moments approach to form an approximate distribution for the Kenward and Roger scaled Wald statistic, under the alternative. The result depends on the approximate moments of the unscaled Wald statistic. Via Monte Carlo simulation, we demonstrate that the new power approximation is accurate for cluster randomized trials and longitudinal study designs. The method retains accuracy for small sample sizes, even in the presence of missing data. We illustrate the method with a power calculation for an unbalanced group-randomized trial in oral cancer prevention.

Associations of Nutrient Intake Changes During Childhood with Adolescent Hepatic Fat: The Exploring Perinatal Outcomes Among CHildren Study.

OBJECTIVE: To examine associations of dietary changes from childhood to adolescence with adolescent hepatic fat and whether the PNPLA3 rs738409 risk allele, a strong genetic risk factor for hepatic fat, modifies associations. STUDY DESIGN: Data were from 358 participants in the Exploring Perinatal Outcomes among CHildren (EPOCH) study, a longitudinal cohort in Colorado. Diet was assessed by food frequency questionnaire in childhood (approximately 10 years of age) and adolescence (approximately 16 years of age) and converted to nutrient densities. Hepatic fat was assessed in adolescence by magnetic resonance imaging. Linear regression was used to test associations of dietary changes from childhood to adolescence with adolescent hepatic fat. RESULTS: Increases in fiber, vegetable protein, and polyunsaturated fat intake from childhood to adolescence were associated with lower adolescent hepatic fat, and increases in animal protein were associated with higher hepatic fat (ß per 5-unit increase on log-hepatic fat: -0.12 [95% CI, -0.21 to -0.02] for ▵fiber; -0.26 [95% CI, -0.45 to -0.07] for ▵vegetable protein; -0.18 [95% CI, -0.35 to -0.02] for ▵polyunsaturated fat; 0.13 [95% CI, 0.04-0.22] for ▵animal protein). There was evidence of effect modification by PNPLA3 variant, whereby inverse associations of ▵fiber and ▵vegetable protein and positive associations of ▵saturated fat with adolescent hepatic fat were stronger in risk allele carriers. Most conclusions were similar after adjusting for obesity in adolescence, but associations of ▵saturated fat with hepatic fat were attenuated toward the null. CONCLUSIONS: Our results suggest that nutrient intake changes between childhood and adolescence, particularly decreases in fiber and vegetable protein and increases in saturated fat intake, interact with the PNPLA3 variant to predict higher hepatic fat in adolescence, and may be targets for reducing hepatic fat in high-risk youth.

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.

Maternal blood glucose level and offspring glucose-insulin homeostasis: what is the role of offspring adiposity?

AIMS/HYPOTHESIS: The aim of this work was to investigate the association of maternal HbA1c during mid-pregnancy with biomarkers of glucose-insulin homeostasis during early childhood (4-7 years of age) and to assess whether and how offspring adiposity at birth and at age 4-7 years mediates this relationship among 345 mother-child pairs in the Healthy Start Study. METHODS: The exposure was maternal HbA1c (mmol/mol) measured at 20-34 gestational weeks and categorised into tertiles. The outcomes were offspring fasting glucose, 1/insulin, HOMA2-IR, and HOMA2-B at age 4-7 years. The mediators were per cent fat mass (%FM) at birth, %FM at age 4-7 years, and the sum of the two as a metric of cumulative adiposity. Mediation analyses were conducted via a counterfactual-based approach. All models accounted for maternal race/ethnicity, offspring age and sex. RESULTS: There was a significant total effect of maternal HbA1c on offspring glucose and 1/insulin. Specifically, we observed a positive trend across tertiles of HbA1c and offspring glucose (p trend <0.001), and an inverse trend across tertiles of HbA1c and offspring 1/insulin (p trend = 0.04). For instance, compared with offspring of women in the lowest tertile of HbA1c, those whose mothers were in the second and third tertiles had 0.04 mmol/l (95% CI -0.05, 0.13) and 0.17 mmol/l (95% CI 0.08, 0.26) higher fasting glucose concentrations at age 4-7 years, respectively. Adjustment for pre-pregnancy BMI did not appreciably change the results. We found no evidence of mediation by offspring adiposity at any life stage. CONCLUSIONS/INTERPRETATION: Offspring of women with higher HbA1c during pregnancy had higher fasting glucose and lower insulin sensitivity by early childhood. These relationships were largely unaffected by the child's own adiposity. Graphical abstract.

A Prudent dietary pattern is inversely associated with liver fat content among multi-ethnic youth.

OBJECTIVES: To identify dietary patterns associated with hepatic fat fraction (HFF), a measure of liver fat content and risk factor for non-alcoholic fatty liver disease, in a prospective study of 397 multi-ethnic youth. METHODS: We obtained information on habitual dietary intake via the Block Kids Food Frequency Questionnaire at age 6 to 15 years ('T1') and 12 to 19 years ('T2'), and measured HFF using magnetic resonance imaging at T2. We derived dietary patterns via principal components analysis and examined associations with ln-transformed HFF using linear regression models that accounted for maternal education, gestational diabetes exposure and smoking habits; and child pubertal status, BMI and physical activity. RESULTS: At T1, none of the dietary patterns identified were associated with HFF measured at T2. At T2, a Prudent dietary pattern characterized by high fruit and vegetable intake was inversely associated with HFF (-0.08 [95% CI: -0.16, -0.00]). Similarly, increased adherence to the Prudent pattern across T1 and T2 corresponded with lower ln-HFF (-0.11 [-0.18, -0.04] units). On the other hand, adherence to a Western pattern comprising fried foods and refined carbohydrates at T2 correlated with higher HFF among non-Hispanic White participants (0.16 [0.06, 0.26]). These findings persisted after accounting for child BMI. CONCLUSIONS: Even in healthy youth, a diet high in fruits and vegetables is associated with lower HFF, whereas a diet high in fried foods and refined carbohydrates is related to higher HFF. Dietary changes may serve as an early preventive measure to mitigate liver fat accrual.

A prospective study of associations between in utero exposure to gestational diabetes mellitus and metabolomic profiles during late childhood and adolescence.

AIMS/HYPOTHESIS: This study aimed to: (1) identify metabolite patterns during late childhood that differ with respect to exposure to maternal gestational diabetes mellitus (GDM); (2) examine the persistence of GDM/metabolite associations 5 years later, during adolescence; and (3) investigate the associations of metabolite patterns with adiposity and metabolic biomarkers from childhood through adolescence. METHODS: This study included 592 mother-child pairs with information on GDM exposure (n = 92 exposed), untargeted metabolomics data at age 6-14 years (T1) and at 12-19 years (T2), and information on adiposity and metabolic risk biomarkers at T1 and T2. We first consolidated 767 metabolites at T1 into factors (metabolite patterns) via principal component analysis (PCA) and used multivariable regression to identify factors that differed by GDM exposure, at α = 0.05. We then examined associations of GDM with individual metabolites within factors of interest at T1 and T2, and investigated associations of GDM-related factors at T1 with adiposity and metabolic risk throughout T1 and T2 using mixed-effects linear regression models. RESULTS: Of the six factors retained from PCA, GDM exposure was associated with greater odds of being in quartile (Q)4 (vs Q1-3) of 'Factor 4' at T1 after accounting for age, sex, race/ethnicity, maternal smoking habits during pregnancy, Tanner stage, physical activity and total energy intake, at α = 0.05 (OR 1.78 [95% CI 1.04, 3.04]; p = 0.04). This metabolite pattern comprised phosphatidylcholines, diacylglycerols and phosphatidylethanolamines. GDM was consistently associated with elevations in a subset of individual compounds within this pattern at T1 and T2. While this metabolite pattern was not related to the health outcomes in boys, it corresponded with greater adiposity and a worse metabolic profile among girls throughout the follow-up period. Each 1-unit increment in Factor 4 corresponded with 0.17 (0.08, 0.25) units higher BMI z score, 8.83 (5.07, 12.59) pmol/l higher fasting insulin, 0.28 (0.13, 0.43) units higher HOMA-IR, and 4.73 (2.15, 7.31) nmol/l higher leptin. CONCLUSIONS/INTERPRETATION: Exposure to maternal GDM was nominally associated with a metabolite pattern characterised by elevated serum phospholipids in late childhood and adolescence at α = 0.05. This metabolite pattern was associated with greater adiposity and metabolic risk among female offspring throughout the late childhood-to-adolescence transition. Future studies are warranted to confirm our findings.

Combined environmental and social exposures during pregnancy and associations with neonatal size and body composition: the Healthy Start study.

BACKGROUND: Prenatal environmental and social exposures have been associated with decreased birth weight. However, the effects of combined exposures in these domains are not fully understood. Here we assessed multi-domain exposures for participants in the Healthy Start study (Denver, CO) and tested associations with neonatal size and body composition. METHODS: In separate linear regression models, we tested associations between neonatal outcomes and three indices for exposures. Two indices were developed to describe exposures to environmental hazards (ENV) and social determinants of health (SOC). A third index combined exposures in both domains (CE = ENV/10 × SOC/10). Index scores were assigned to mothers based on address at enrollment. Birth weight and length were measured at delivery, and weight-for-length z-scores were calculated using a reference distribution. Percent fat mass was obtained by air displacement plethysmography. RESULTS: Complete data were available for 897 (64%) participants. Median (range) ENV, SOC, and CE values were 31.9 (7.1-63.2), 36.0 (2.8-75.0), and 10.9 (0.4-45.7), respectively. After adjusting for potential confounders, 10-point increases in SOC and CE were associated with 27.7 g (95%CI: 12.4 - 42.9 g) and 56.3 g (19.4 - 93.2 g) decreases in birth weight, respectively. SOC and CE were also associated with decreases in % fat mass. CONCLUSIONS: Combined exposures during pregnancy were associated with lower birth weight and % fat mass. Evidence of a potential synergistic effect between ENV and SOC suggests a need to more fully consider neighborhood exposures when assessing neonatal outcomes.

Sex differences in infant body composition emerge in the first 5 months of life.

Background Sex differences in body composition are appreciated throughout the lifespan with probable contributions from sex steroids: testosterone and estrogen. The purpose of this longitudinal observational study was to determine if sex differences in body composition emerge during the first months of life in healthy infants, corresponding to the age at which male infants produce endogenous testosterone. Methods Linear growth and body composition parameters using air displacement plethysmography were obtained from 602 healthy infants after birth and again at 5 months of age. Rate of change in body composition parameters were compared between sexes. Results Sex differences in length, total mass, fat free mass (FFM), and percent fat mass (%FM) were present both at birth and at 5 months (p < 0.001 for all), with males having greater total mass and FFM but lower %FM. Gain in %FM over the first 5 months was significantly lower in males (p = 0.0004). This difference was secondary to a gain of 17 g/week more in FFM in males compared to females. Conclusions Sex differences in body composition emerge in the first months of life, with lower adiposity accumulation in males. Endogenous testosterone production in males ~1-4 months of age may account for findings and may have lifelong implications for sex differences in body composition.

Improving the diagnostic accuracy of a stratified screening strategy by identifying the optimal risk cutoff.

BACKGROUND: The American Cancer Society (ACS) suggests using a stratified strategy for breast cancer screening. The strategy includes assessing risk of breast cancer, screening women at high risk with both MRI and mammography, and screening women at low risk with mammography alone. The ACS chose their cutoff for high risk using expert consensus. METHODS: We propose instead an analytic approach that maximizes the diagnostic accuracy (AUC/ROC) of a risk-based stratified screening strategy in a population. The inputs are the joint distribution of screening test scores, and the odds of disease, for the given risk score. Using the approach for breast cancer screening, we estimated the optimal risk cutoff for two different risk models: the Breast Cancer Screening Consortium (BCSC) model and a hypothetical model with much better discriminatory accuracy. Data on mammography and MRI test score distributions were drawn from the Magnetic Resonance Imaging Screening Study Group. RESULTS: A risk model with an excellent discriminatory accuracy (c-statistic [Formula: see text]) yielded a reasonable cutoff where only about 20% of women had dual screening. However, the BCSC risk model (c-statistic [Formula: see text]) lacked the discriminatory accuracy to differentiate between women who needed dual screening, and women who needed only mammography. CONCLUSION: Our research provides a general approach to optimize the diagnostic accuracy of a stratified screening strategy in a population, and to assess whether risk models are sufficiently accurate to guide stratified screening. For breast cancer, most risk models lack enough discriminatory accuracy to make stratified screening a reasonable recommendation.

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.

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

OBJECTIVE: 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. STUDY DESIGN: 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. RESULTS: Children included in this analysis (n = 137) were 4.6 years 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 each significantly 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). CONCLUSIONS: 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.

Background Vitamin 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 Results We 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. Conclusions In 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.

Infant Feeding Practices In a Diverse Group of Women: The Healthy Start Study.

BACKGROUND: To describe infant feeding practices among a diverse group of mother-offspring pairs and identify factors associated with adherence to the American Academy of Pediatrics (AAP) recommendations. METHODS: Data were analyzed from 835 mother-offspring dyads in The Healthy Start Study, an ongoing longitudinal prebirth cohort in Denver, Colorado. Maternal report of infant feeding practices was obtained at 4 to 6 months and 18 to 24 months postnatally. Practices were classified according to the following AAP recommendations: exclusive breastfeeding for first 6 months, continued breastfeeding through 12 months, and introduction of solid foods around 6 months of age. Participants who met all 3 recommendations were categorized as "adherent." All others were categorized as "not adherent." RESULTS: About 77% of dyads did not adhere fully to the AAP recommendations. Women who worked ⩾35 hours/week or had a higher prepregnancy body mass index were more likely to be nonadherent. Women who were older, college educated, or had offspring with greater weight for gestational age at birth were less likely to be nonadherent. CONCLUSIONS: Most of the women in a large contemporary cohort are not adhering to AAP infant feeding recommendations. Our results highlight the specific subgroups of women who may need additional support to optimize infant feeding practices.

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.