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.

ABSTRACT Context Chronic stress is a risk factor for preterm birth; however, objective measures of stress in pregnancy are limited. Maternal stress biomarkers may fill this gap. Steroid hormones and neurosteroids such as allopregnanolone (ALLO) play important roles in stress physiology and pregnancy maintenance and therefore may be promising for preterm birth prediction. Objective We evaluated maternal serum ALLO, progesterone, cortisol, cortisone, pregnanolone, and epipregnanolone twice in gestation to evaluate associations with preterm birth. Methods We performed a nested case-control study using biobanked fasting serum samples from the Healthy Start prebirth cohort. We included healthy women with a singleton pregnancy and matched preterm cases with term controls (1:1; N = 27 per group). We used a new HPLC-tandem mass spectrometry assay to quantify ALLO and five related steroids. We used ANOVA, Fisher exact, χ2, t test, and linear and logistic regression as statistical tests. Results Maternal serum ALLO did not associate with preterm birth nor differ between groups. Mean cortisol levels were significantly higher in the preterm group early in pregnancy (13w0d-18w0d; P < 0.05) and higher early pregnancy cortisol associated with increased odds of preterm birth (at 13w0d; odds ratio, 1.007; 95% CI, 1.0002-1.014). Progesterone, cortisone, pregnanolone, and epipregnanolone did not associate with preterm birth. Conclusion The findings from our pilot study suggest potential utility of cortisol as a maternal serum biomarker for preterm birth risk assessment in early pregnancy. Further evaluation using larger cohorts and additional gestational timepoints for ALLO and the other analytes may be informative.

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 (similar to 10 years of age), assessed by food frequency questionnaire, with abdominal subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), and hepatic fat in adolescence (similar to 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 (beta [95% CI]: 8.5 [0.1-17.1], 25.1 [2.1-48.1], and 59.7 [16.1-103.3] mm(2) per 100 kcal/d), higher starch intake was associated with log-hepatic fat (back-transformed beta [95% CI]: 1.07 [1.01-1.15] per 100 kcal/d), and, in boys only, higher animal protein intake was associated with VAT (beta [95% CI]: 5.3 [0.3-10.3] mm(2) 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.

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/m 2 decrease ( p = 0.007) in BMI over time, after adjustment for covariates. Among girls, there was no association between BMI and aMED ( β = −0.19, p = 0.24) or DASH ( β = 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.

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]-1 beta, IL-4, IL-6, IL-10, tumor necrosis factor-alpha) 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.

Body fat distribution is a strong risk factor for metabolic dysfunction in childhood and may be a target for lifestyle interventions. Prospective studies linking childhood dietary intake and future body fat deposition are needed to develop optimal therapeutic strategies. Our objective was to examine associations of childhood nutrient intakes with hepatic fat (HF), abdominal visceral (VAT) and subcutaneous adipose tissue (SAT) in adolescence. Data were from 302 participants in the Exploring Perinatal Outcomes among Children (EPOCH) study in Colorado. Visits were completed in childhood (T1, ∼10yrs) and adolescence (T2, ∼16yrs). Diet was assessed by Block Kids Food Questionnaire at T1. HF (%) and abdominal SAT and VAT (mm2) were assessed by magnetic resonance imaging at T1 (abdominal fats only) and T2. Two types of models (energy partition and isocaloric substitution) were constructed to examine associations of nutrient intakes at T1 with HF and abdominal VAT and SAT at T2. In energy partition models adjusted for other macronutrients and confounders (sex, age, race/ethnicity, puberty), higher starch and total fat intake at T1 were associated with higher log-HF and SAT, respectively, at T2 [β (95% CI) = 0.07 (0.01,0.14) for log-HF per 100 kcal/d starch, 17.0 mm2 (4.3,29.7) for SAT per 100 kcal/d fat]. In isocaloric substitution models holding total energy intake (TEI) constant, replacing protein with starch was marginally associated with log-HF at T2 [0.12 (−0.02,0.26) per 5% TEI/d starch at the expense of protein], and replacing carbohydrates (CHO) with total fat was associated with SAT at T2 [19.3 mm2 (3.1,35.5) per 5% TEI/d fat at the expense of CHO]. There were no associations of nutrient intakes with VAT at T2. Adjusting for abdominal SAT at T1 attenuated associations between fat intake at T1 and SAT at T2 to the null [4.6 mm2 (−3.7,12.9) in energy partition models; 10.5 mm2 (−0.01,21.0) in isocaloric substitution models with CHO]. Our results suggest that higher starch intake in childhood, especially at the expense of protein, is associated with higher adolescent HF. We also found that higher fat intake in childhood, especially at the expense of CHO, was associated with higher adolescent abdominal SAT, and that this may reflect an association that was already present earlier in childhood. NIDDK; NIH/NCATS Colorado CTSA.

A Correction to this paper has been published:

We derive a noncentral F 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.

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.

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 (beta per 5-unit increase on log-hepatic fat: -0.12 [95% CI, -0.21 to -0.02] for Delta fiber; - 0.26 [95% CI, -0.45 to -0.07] for Delta vegetable protein; -0.18 [95% CI, -0.35 to -0.02] for Delta polyunsaturated fat; 0.13 [95% CI, 0.04-0.22] for Delta animal protein). There was evidence of effect modification by PNPLA3 variant, whereby inverse associations of Delta fiber and Delta vegetable protein and positive associations of Delta 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 Delta 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.

SummaryObjectivesTo 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.MethodsWe 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.ResultsAt 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.ConclusionsEven 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 Correction to this paper has been published: https://doi.org/10.1007/s00125-021-05432-4

Fatty liver is increasingly common in adolescents with obesity. Diet patterns often shift from childhood to adolescence and may contribute to hepatic fat (HF), but no studies have empirically tested this. We examined whether nutrient intake changes from childhood to adolescence are associated with adolescent HF and if a genetic risk factor for HF (PNPLA3 rs738409) modifies associations using data from 358 participants in the EPOCH Cohort in Colorado. Diet was assessed by food frequency questionnaire at ~10 yrs (T1) and ~16 yrs (T2). HF was assessed by magnetic resonance imaging at T2. Linear regression was used to examine associations of energy-adjusted nutrient intake changes (T2-T1) with HF at T2. Decreases in fiber, vegetable protein (VP), and polyunsaturated fat, and increases in animal protein were associated with HF at T2 (Table). Evidence of effect modification by PNPLA3 was observed for associations of certain nutrients with HF (p-interaction<0.05), whereby inverse associations of fiber and VP and positive associations of saturated fat (SFA) with HF were stronger with the risk allele (Table). Adjusting for body mass index z-score at T2 did not alter conclusions, but associations of SFA with HF were attenuated. Our results suggest that dietary changes from childhood to adolescence interact with genetics to influence HF, and may be targeted for reducing HF in high-risk youth.View largeDownload slideView largeDownload slide DisclosureC. C. Cohen: None. D. Dabelea: None. W. Perng: None. K. A. Sauder: None. B. Ringham: None. A. Bellatorre: None. A. Scherzinger: None. M. Stanislawski: None. L. Lange: None. K. Shankar: None. FundingNational Institute of Diabetes and Digestive and Kidney Diseases (R01DK068001, T32DK07658)

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.

Both inadequate and excessive intake of micronutrients in pregnancy have the potential to negatively impact child health outcomes. We examined micronutrient intake in a large, diverse sample of women with singleton pregnancies across the United States, including intake by maternal age, race/ethnicity, education, and pre-pregnancy body mass index (BMI). Fifteen observational cohorts in the Environmental influences on Child Health Outcomes (ECHO) consortium assessed prenatal food intake and dietary supplement use with 24-hour dietary recalls (5 cohorts; 1859 women) or food frequency questionnaires (10 cohorts; 8064 women) from 1999–2019. We compared mean daily intake of 19 micronutrients to the age-specific estimated average requirement (EAR), adequate intake (AI), and tolerable upper intake level (UL) for pregnancy, overall and within sociodemographic and anthropometric subgroups. For recall data, we used a measurement error method to estimate distributions of usual intake, proportion below the EAR/AI, and above the UL. For FFQ data, we calculated the proportion below the EAR/AI and above the UL. Risk of inadequate intake from foods alone ranged from 0–93%, depending on the micronutrient or assessment method. With dietary supplements, more than 1 in 5 women remained at risk for inadequate intake of choline, magnesium, and vitamins D, E, and K; or excessive intake of folic acid, iron, and zinc. Higher risks for inadequate intakes were observed among women with obesity (magnesium, vitamin K), who were <18 years (magnesium, vitamin K), Hispanic (vitamin E), non-Hispanic Black (vitamin K), non-Hispanic White (choline) or less educated (magnesium, vitamin E) when compared to counterparts. Improved diet quality is needed for most pregnant women. Even with a high prevalence of dietary supplement use, at least 1 in 5 pregnant women 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. National Institutes of Health, Environmental Protection Agency, Autism Speaks.

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. 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. 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. 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.

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)

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 = 0.00014). 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 similar to 1-4 months of age may account for findings and may have lifelong implications for sex differences in body composition.