Associations of Abnormal Maternal Glucose Regulation in Pregnancy with Offspring Adiposity, Insulin Resistance, and Adipokine Markers During Childhood and Adolescence.

OBJECTIVE: To examine the associations of abnormal maternal glucose regulation in pregnancy with offspring adiposity, insulin resistance, adipokine, and inflammatory markers during childhood and adolescence. STUDY DESIGN: Project Viva is a prospective prebirth cohort (n = 2128 live births) initiated from 1999 through 2002 in Eastern Massachusetts, US. During the second trimester of pregnancy, clinicians used 2-step oral glucose challenge testing to screen for gestational diabetes mellitus. In the offspring, we measured anthropometry, insulin resistance, adipokines, lipids, and inflammatory markers in mid-childhood (n = 1107), early adolescence (n = 1027), and mid-adolescence (n = 693). We used multivariable linear regression models and generalized estimating equations adjusted for child age and sex, and for maternal age, race/ethnicity, education, parity, and smoking during pregnancy; we further adjusted for prepregnancy body mass index (BMI). RESULTS: In mid-adolescence (17.1 [0.8] years of age), offspring of mothers with gestational diabetes mellitus (n = 27) had a higher BMI z-score (ß; 95% Cl; 0.41 SD; 0.00, 0.82), sum of skinfolds (8.15 mm; 2.48, 13.82), homeostatic model assessment for insulin resistance (0.81 units; 0.13, 1.50), leptin z-score (0.40 SD; 0.01, 0.78), and leptin/adiponectin ratio z-score (0.51 SD; CI 0.09, 0.93) compared with offspring of mothers with normoglycemia (multivariable-adjusted models). The associations with BMI, homeostatic model assessment for insulin resistance, and adiponectin seemed stronger in mid-adolescence compared with earlier time points. The associations were attenuated toward the null after adjustment for maternal prepregnancy BMI. CONCLUSION: Exposure to gestational diabetes mellitus is associated with higher adiposity, insulin resistance, and altered adipokines in mid-adolescence. Our findings suggest that the peripubertal period could be a key time for the emergence of prenatally programmed metabolic abnormalities.

Growth Velocities Across Distinct Early Life Windows and Child Cognition: Insights from a Contemporary US Cohort.

OBJECTIVE: To evaluate the relative importance of overall and period-specific postnatal growth and their interaction with fetal growth on cognition in a generally well-nourished population. STUDY DESIGN: We included 1052 children from Project Viva, a prospective cohort in Boston, Massachusetts. Using linear spline mixed-effects models, we modeled length/height and body mass index (BMI) trajectories from birth to 7 years and estimated standardized overall (0-7 years) and period-specific growth velocities ie, early infancy (0-4 months), late infancy (4-15 months), toddlerhood (15-37 months), and early childhood (37-84 months). We investigated associations of growth velocities as well as their interactions with birthweight-for-gestational age on mid-childhood (mean age: 7.9 years) IQ, visual memory and learning, and visual motor ability. RESULTS: Greater overall height velocity was associated with modestly higher design memory score, (adjusted ß [95% CI] 0.19 [-0.01,0.38] P = .057])points per SD increase but lower verbal IQ (-0.88 [-1.76,0.00] P = .051). Greater early infancy height velocity was associated with higher visual motor score (1.92 [0.67,3.18]). Greater overall BMI velocity was associated with lower verbal IQ (-0.71 [-1.52,0.11] P = .090). Greater late infancy BMI velocity was associated with lower verbal IQ (-1.21 [-2.07,-0.34]), design memory score (-0.22 [-0.42,-0.03)], but higher picture memory score (0.22 [0.01,0.43]). Greater early infancy height velocity (-1.5 SD vs 1.5 SD) was associated with higher nonverbal IQ (margins [95% CI] 102.6 [98.9106.3] vs 108.2 [104.9111.6]) among small-for-gestational age infants (P-interaction = 0.04). CONCLUSIONS: Among generally well-nourished children, there might not be clear cognitive gains with faster linear growth except for those with lower birthweight-for-gestational age, revealing the potential importance of early infancy compensatory growth.

Neighborhood Conditions and Resources in Mid-Childhood and Dampness and Pests at Home in Adolescence.

OBJECTIVE: To examine prospectively associations of neighborhood opportunity with the presence of dampness or pests in the home environment during early adolescence. STUDY DESIGN: We geocoded residential addresses from 831 children (mean age 7.9 years, 2007-2011) in the Project Viva cohort. We linked each address with census tract-level Child Opportunity Index scores, which capture neighborhood conditions and resources influencing child heath including educational, health, environmental, and socioeconomic factors. Our primary outcome was presence of dampness or pests in the home in early adolescence (mean age 13.2 years, 2013-2016). Secondary outcomes included current asthma and lung function testing results. Mixed-effects regression models estimated longitudinal associations of Child Opportunity Index scores with outcomes, adjusting for individual and family sociodemographics. RESULTS: Children residing in neighborhoods with greater overall opportunity were less likely to live in homes with dampness or pests approximately 5 years later (aOR 0.85 per 20-unit increase in Child Opportunity Index percentile rank, 95% CI 0.73-0.998). We observed no significant associations in adjusted models of overall neighborhood opportunity with current asthma or lung function. Lower school poverty or single-parent households and greater access to healthy food or economic resource index were associated with lower odds of a home environment with dampness or pests. CONCLUSIONS: More favorable neighborhood conditions in mid-childhood were associated with lower likelihood of living in a home with dampness or pests in the early adolescence.

Antimüllerian hormone and adiposity across midlife among women in Project Viva.

OBJECTIVE: This study aimed to examine the association of antimüllerian hormone (AMH) with concurrent and prospective measures of adiposity during approximately 9 years of follow-up. METHODS: Participants were 697 parous women from the Project Viva prebirth cohort without polycystic ovarian syndrome. We measured AMH at approximately 3 years postpartum (baseline). Outcomes were weight, body mass index (BMI), and waist circumference assessed at baseline, 4, and 9 years later; % body fat was assessed by bioimpedance at the 4- and 9-year visit. We used linear mixed-effect models including all outcome time points and accounting for age across follow-up and hormonal contraception prescription. In an additional model, we further adjusted for height. RESULTS: Median AMH was 1.97 ng/mL (interquartile range, 0.83-4.36 ng/mL), 29.1% had AMH <1.0 ng/mL, and mean age at AMH measurement was 36.7 years (SD, 4.9 y; range, 20-48 y). AMH was inversely associated with average weight, BMI, and waist circumference over follow-up. In age-adjusted models, women with AMH <1.0 versus ≥1.0 ng/mL were 4.92 kg (95% CI, 2.01-7.82 kg) heavier, had a 2.51 cm (95% CI, 0.12-4.89 cm) greater waist circumference, and a 1.46 kg/m 2 (95% CI, 0.44-2.48 kg/m 2 ) greater BMI across the 9 years of follow-up. Findings were similar after covariate adjustment and when AMH was modeled continuously. AMH was also inversely associated with higher fat mass %; however, the CI crossed the null. CONCLUSION: Low AMH at baseline was associated with greater adiposity concurrently and across approximately 9 years of follow-up. Whether low AMH is a useful marker of metabolic risk across midlife requires further research.

History of infertility and pregnancy outcomes in Project Viva: a prospective study.

BACKGROUND: Infertility has been associated with the risk of adverse pregnancy outcomes. It is not clear whether infertility and underlying causes of infertility or the use of medically assisted reproduction (MAR) therapies are responsible for the observed associations. In this study, we aimed to evaluate the association of history of infertility with pregnancy outcomes and identify whether the associations, if present, differed by subgroups defined by the use of MAR. METHODS: Prospective study of 2201 pregnant women from the Boston-area Project Viva cohort. The exposure was history of infertility based on self-reported time to pregnancy ≥12 mo (or ≥ 6 mo if ≥35 y) or use of MAR; a diagnosis of infertility or claims for infertility treatments from medical records. The outcomes included: gestational glucose tolerance (gestational diabetes, impaired glucose tolerance, isolated hyperglycemia vs. normoglycemia), hypertensive disorders (gestational hypertension/preeclampsia vs. normotension), gestational weight gain (inadequate/excessive vs. adequate), systolic (SBP) and diastolic blood pressure, birthweight-for-gestational age z-score (tertile 2 and 3 vs. 1), preterm birth (<37 vs. ≥37 weeks at delivery), and birth outcome (pregnancy loss vs. live birth). We performed linear and logistic/multinomial regression analyses adjusted for age, race/ethnicity, age at menarche, pre-pregnancy BMI, and prenatal smoking. RESULTS: Mean (SD) age was 32.0 (5.0) years, and 18.8% of women had history of infertility, 32.6% of whom used MAR. SBP across pregnancy was 0.72 mmHg higher in women with vs. without infertility (95% CI 0.02, 1.42). The associations were stronger among women who used MAR (ß 1.32 mmHg, 95% CI 0.21, 2.44), especially among those who used gonadotropins or gonadotropin-releasing hormone [GnRH] agonists (ß 1.91 mmHg, 95% CI 0.48, 3.35). Other outcomes were not associated with history of infertility. CONCLUSIONS: A history of infertility was associated with higher SBP during pregnancy, with stronger associations among those who used gonadotropins or GnRH agonists. Future studies are needed to confirm these findings and determine their clinical implications.

Menstrual cycle length and adverse pregnancy outcomes among women in Project Viva.

BACKGROUND: Retrospective studies suggest that menstrual cycle length may be a risk marker of adverse pregnancy outcomes, but this evidence is susceptible to recall bias. OBJECTIVE: To evaluate the prospective association between menstrual cycle length and the risk of adverse pregnancy outcomes. METHODS: Secondary analysis of 2046 women enrolled in Project Viva at ~10 weeks of gestation and followed through delivery. The exposure was menstrual cycle length. The outcomes included gestational glucose tolerance (gestational diabetes/impaired glucose tolerance [GDM/IGT] and isolated hyperglycaemia), hypertensive disorders of pregnancy (gestational hypertension/preeclampsia), gestational weight gain, birthweight-for-gestational age z-scores (BWZ) categorised in tertiles, preterm birth and birth outcome (live birth and pregnancy loss). We used modified Poisson and multinomial logistic regression adjusted for age, race/ethnicity, parity, age at menarche and pre-pregnancy body mass index. RESULTS: Mean (SD) age at enrolment was 32.1 (4.9) years. Most women (74.3%) had a cycle length of 26-34 days (reference group), 16.2% reported short cycles (≤25 days), and 9.5% reported long/irregular cycles (≥35 days/too irregular to estimate). Compared with the reference group, women with short cycles had lower odds of GDM/IGT (odds ratio [OR] 0.50, 95% confidence interval [CI] 0.28, 0.89), whereas women with long/irregular cycles had higher odds (OR 1.72, 95% CI 1.04, 2.83). Additionally, women with short cycles had higher odds of having a newborn in the lowest tertile of BWZ (OR 1.45, 95% CI 1.06, 1.98). There was a U-shaped relation between cycle length and preterm birth with both short (relative risk [RR] 1.49, 95% CI 0.98, 2.27) and long/irregular (RR 2.04, 95% CI 1.30, 3.20) cycles, associated with a higher risk. CONCLUSIONS: Variation in menstrual cycle length may be a risk marker of GDM/IGT, lower birth size and preterm birth and flag women who may benefit from targeted monitoring and care before and during pregnancy.

Impact of paternal education on epigenetic ageing in adolescence and mid-adulthood: a multi-cohort study in the USA and Mexico.

BACKGROUND: Both parental and neighbourhood socio-economic status (SES) are linked to poorer health independently of personal SES measures, but the biological mechanisms are unclear. Our objective was to examine these influences via epigenetic age acceleration (EAA)-the discrepancy between chronological and epigenetic ages. METHODS: We examined three USA-based [Coronary Artery Risk Disease in Adults (CARDIA) study, Fragile Families and Child Wellbeing Study (FFCWS) and Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS)] and one Mexico-based (Project Viva) cohort. DNA methylation was measured using Illumina arrays, personal/parental SES by questionnaire and neighbourhood disadvantage from geocoded address. In CARDIA, we examined the most strongly associated personal, parental and neighbourhood SES measures with EAA (Hannum's method) at study years 15 and 20 separately and combined using a generalized estimating equation (GEE) and compared with other EAA measures (Horvath's EAA, PhenoAge and GrimAge calculators, and DunedinPoAm). RESULTS: EAA was associated with paternal education in CARDIA [GEEs: ßsome college = -1.01 years (-1.91, -0.11) and ß

Weight Trajectories After Delivery are Associated with Adiposity and Cardiometabolic Markers at 3 Years Postpartum Among Women in Project Viva.

BACKGROUND: Postpartum weight trajectories and its implications on later cardiometabolic health are not entirely understood. OBJECTIVES: Our objectives were: 1) to characterize maternal weight trajectories from 1 to 24 mo postpartum, 2) to determine the association of prepregnancy BMI, gestational weight gain (GWG), and pregnancy behaviors with the trajectories, and 3) to evaluate the association of weight trajectories with BMI, waist circumference (WC), lipid profile, glucose, insulin resistance, blood pressure, and inflammatory markers at 3 y postpartum. METHODS: We studied 1359 mothers from the prospective cohort Project Viva. Using weights at 1, 6, 12, and 24 mo postpartum, we characterized weight trajectories using a latent class growth model. For objectives 2 and 3, we used multinomial logistic regression and multiple linear regression models, respectively. RESULTS: Around 85% of women fell into a trajectory of sustained weight loss (1-12 mo) + maintenance (12-24 mo) (reference), 5.7% followed a trajectory characterized by fast weight loss + slight gain, and 9.7% fell into a trajectory of little weight loss + slight gain. Prepregnancy overweight and obesity increased the odds of falling into the fast weight loss + slight gain trajectory, compared with the reference. Prepregnancy overweight [OR 1.57 (95% CI: 1.01, 2.46)] and a higher total GWG rate [3.69 (2.90, 4.68)] increased the odds of falling into the little weight loss + slight gain trajectory, whereas a higher Prudent dietary pattern score was protective [0.73 (0.54, 0.98)]. Women in this trajectory had higher BMI, WC, weight gain from prepregnancy, low-density lipoprotein cholesterol, and inflammatory markers at 3 y postpartum. CONCLUSIONS: Women following a trajectory of little weight loss + slight gain during the first 2 y postpartum had an adverse cardiometabolic profile 3 y after delivery. Targeting diet and GWG during pregnancy and facilitating postpartum weight loss could improve women's long-term health.

Associations of acetaminophen use during pregnancy and the first year of life with neurodevelopment in early childhood.

BACKGROUND: Over-the-counter analgesic use during pregnancy, particularly acetaminophen, may be associated with negative developmental outcomes in children. OBJECTIVE: Estimate associations of prenatal and early-life exposure to acetaminophen in early childhood with cognitive, motor, and language skills in two birth cohorts. METHODS: The American Project Viva cohort (1217 mother-child pairs enrolled 1999-2002) assessed cognition at approximately 3 years using the Peabody Picture Vocabulary Test and the Wide Range Achievement of Visual Motor Abilities (WRAVMA). The Brazilian 2015 Pelotas Birth Cohort (3818 mother-child pairs) assessed cognition at 2 years using the INTERGROWTH-21st Neurodevelopment Assessment. We used linear regression to estimate associations of acetaminophen use during pregnancy (Project Viva and Pelotas) and infancy (Project Viva) with children's cognitive scores adjusted for maternal age, pre-pregnancy body mass index, education, parity, race/ethnicity, smoking and alcohol use during pregnancy, depression during pregnancy, antibiotic and ibuprofen use during pregnancy, household income, and child's sex. RESULTS: In Project Viva, exposure to acetaminophen in both the 1st and 2nd trimester of pregnancy was associated with lower WRAVMA drawing scores (ß -1.51, 95% CI -2.92, -0.10). However, in Pelotas, exposure to acetaminophen in both the 1st and 2nd trimester of pregnancy was not associated with INTER-NDA motor scores (ß 0.02; 95% CI -0.05, 0.09) and was associated with higher INTER-NDA total scores (ß 0.08, 95% CI 0.01, 0.16). Other comparisons did not show evidence for any associations. CONCLUSIONS: Inconsistencies and lack of specificity of the findings did not clarify the research question considering that we still have a large variability and uncertainty to define the risk or safety in the use of acetaminophen related to cognition in early childhood. More studies using better exposure assessment and better confounding variables are needed to clarify these associations.

Parental Obesity and Offspring Pubertal Development: Project Viva.

OBJECTIVE: To investigate the association of preconception parental obesity (body mass index [BMI] ≥30 kg/m2) with offspring pubertal development. STUDY DESIGN: Among 1377 children from a prospective prebirth cohort in Boston, we examined markers of puberty (age at peak height velocity [PHV], age at menarche, self-reported pubertal development score), and adrenarche (pictograph Tanner pubic hair staging). We used multivariable regression models to examine associations of maternal and paternal obesity with offspring pubertal indices, and applied marginal structural models to estimate the controlled direct effect not mediated by offspring prepubertal BMI. RESULTS: The prevalence of paternal obesity alone, maternal obesity alone, and biparental obesity were 10.5%, 10.1%, and 5%, respectively. After adjusting for demographic and socioeconomic factors, parental heights and maternal age at menarche, maternal obesity alone (vs neither parent with obesity) was associated with earlier age at PHV (ß -0.30 years; 95% CI -0.57, -0.03) and higher early adolescent pubertal score (0.29 units; 0.10, 0.48) in boys, but not with pubertal or adrenarchal outcomes in girls. Paternal obesity alone was not associated with any outcomes in either boys or girls. Biparental obesity was associated with earlier age at PHV in boys and earlier menarche in girls. Using marginal structural models with stabilized inverse probability weighting, maternal obesity alone had significant controlled direct effects on age at PHV (-0.31 years; -0.62, 0.00) and on pubertal score (0.22 units; 0.00, 0.44) in boys, independent of prepubertal BMI. CONCLUSION: Maternal, but not paternal, obesity is associated with earlier pubertal development in boys, and such association is independent of prepubertal BMI.

Pre-, Perinatal, and Parental Predictors of Body Mass Index Trajectory Milestones.

OBJECTIVE: To assess associations of pre-, perinatal, and parental factors with age and magnitude at body mass index (BMI) peak and rebound. STUDY DESIGN: Among 1681 children with BMI data from birth to mid-childhood in Project Viva, we fitted individual BMI trajectories using mixed-effect models with natural cubic spline functions and estimated age and magnitude at peak in infancy and rebound in early childhood. We used stepwise multivariable regression to identify predictors of peak and rebound in the 1354 (63.6%) children with estimable trajectory milestones. RESULTS: The mean (SD) of age at BMI peak was 8.4 (2.7) months and at rebound was 59.8 (19.6) months, and the mean (SD) of magnitude at peak was 18.0 (1.4) kg/m2 and at rebound was 15.9 (1.2) kg/m2. Girls had a later age at peak, earlier age at rebound, and lower magnitudes at peak and rebound than boys. Maternal isolated hyperglycemia (vs normoglycemia: ß 0.7 months [95% CI 0.2-1.2]) and pre-eclampsia (vs normal blood pressure: 1.6 months [0.8-2.4]) were associated with a later peak, and impaired glucose tolerance (vs normoglycemia: -0.5 kg/m2 [-0.9, -0.1]) was associated with a lower magnitude at peak. Greater maternal first-trimester weight gain, smoking during pregnancy, no breastfeeding, parental obesity, and no university education were associated with greater BMI at rebound. CONCLUSIONS: We have identified modifiable prenatal and parental predictors of BMI peak in infancy and rebound in childhood. Early-life interventions that address these factors may be effective in changing BMI peak and rebound and potentially preventing later obesity.

Associations of Early to Mid-Childhood Adiposity with Elevated Mid-Childhood Alanine Aminotransferase Levels in the Project Viva Cohort.

OBJECTIVES: To examine the longitudinal relationship of early to mid-childhood adiposity measures with mid-childhood alanine aminotransferase (ALT) levels. STUDY DESIGN: We studied 635 children in the Project Viva cohort. Research staff measured weight, height, skinfolds thicknesses, and waist and hip circumferences at early (median 3.2 years) and mid-childhood (median 7.7 years) visits. At mid-childhood, we collected blood for ALT analysis. We used established sex-specific ALT cut-offs to define elevated ALT. In multivariable linear and logistic regression models, we assessed the association of adiposity measures from early to mid-childhood with mid-childhood ALT level, adjusting for confounders. RESULTS: Children were 48% female, 59% white, 21% black, 6% Hispanic/Latino, and 3% Asian. At early childhood, 29% had overweight/obesity and mean waist circumference was 51.5 (SD 3.8) cm. At mid-childhood, mean ALT was 20.3 (SD 7.3) units/L, and 23% had an elevated ALT. In multivariable-adjusted regression models, each additional 10-cm greater waist circumference at early childhood was associated with 1.99 (95% CI 1.19-3.33) greater odds of elevated ALT at mid-childhood. Greater increases from early to mid-childhood in body mass index z score, sum of subscapular and triceps skinfold thicknesses, waist circumference, and hip circumference were associated with greater ALT at mid-childhood. CONCLUSIONS: In this prospective cohort, greater waist circumference at early childhood and greater increases in adiposity measures from early to mid-childhood were associated with greater ALT levels at mid-childhood.

Racial/Ethnic and Socio-Contextual Correlates of Chronic Sleep Curtailment in Childhood.

STUDY OBJECTIVES: To examine the association between race/ethnicity and sleep curtailment from infancy to mid-childhood, and to determine the extent to which socioeconomic and contextual factors both explain racial/ethnic differences and are independently associated with sleep curtailment. METHODS: We studied 1,288 children longitudinally in Project Viva, a pre-birth cohort study, from 6 months to 7 years of age. The main exposure was the child's race/ethnicity. The main outcome was a sleep curtailment score from 6 months to 7 years. The score ranged from 0-13, where 0 indicated maximal sleep curtailment and 13 indicated never having curtailed sleep. RESULTS: The mean (standard deviation) sleep curtailment score was 10.2 (2.7) points. In adjusted models (ß [95% CI]), black (-1.92, [-2.39, -1.45] points), Hispanic (-1.58, [-2.43, -0.72] points), and Asian (-1.71, [-2.55, -0.86] points) children had lower sleep scores than white children. Adjustment for sociodemographic covariates attenuated racial/ethnic differences in sleep scores for black (by 24%) and Hispanic children (by 32%) but strengthened the differences for Asian children by 14%. Further adjustment for environmental and behavioral variables did not substantially change these differences. Independently, low maternal education, living in households with incomes < $70,000, viewing more TV, and having a TV in the child's bedroom were associated with lower sleep scores. CONCLUSIONS: Chronic sleep curtailment from infancy to mid-childhood was more prevalent among black, Hispanic, and Asian children. These differences were partially but not entirely explained by socio-contextual variables. Independently, children from lower socioeconomic status and those with greater exposures to TV also had greater sleep curtailment.

Birth Size, Early Life Weight Gain, and Midchildhood Cardiometabolic Health.

OBJECTIVE: To examine associations of birth size and weight gain during 4 early-life age intervals with midchildhood adiposity and metabolic profile and to evaluate for an interaction between birth size and early-life weight gain. STUDY DESIGN: Using data from 963 participants of Project Viva, a US prebirth cohort, we used multivariable linear regression to examine relations of birth size (tertiles of birthweight-for-gestational-age z-score) and weight gain (body mass index z-score [BMIZ] change) during 4 age intervals (birth-6 months, 6 months-1 year, 1-2 years, 2-3 years) with body composition and metabolic biomarkers during midchildhood (6.6-10.7 years). RESULTS: After accounting for confounders and previous growth, greater BMIZ change during all 4 age intervals corresponded with higher midchildhood adiposity, with larger effect sizes for later (1-2 years and 2-3 years) vs earlier (birth-6 months and 6 months-1 year) time frames. We observed effect modification by birth size for the birth-6 months and 6 months-1 year intervals. Greater birth-6 months BMIZ change was associated with higher overall adiposity (0.40 [95% CI 0.29, 0.51] kg dual x-ray absorptiometry total fat mass per z-score) among children in the highest birth size tertile. Similar associations were observed for central adiposity. Each increment in 6 months-1 year BMIZ change corresponded with 0.55 (0.05, 1.05) units higher homeostatic model assessment of insulin resistance and 2.68 (0.96, 4.40) ng/mL higher leptin among the smallest infants. CONCLUSIONS: BMIZ gain after 1 year is associated with greater midchildhood adiposity regardless of birth size, whereas the long-term influence of weight gain during the first postnatal year may depend on size at birth. Future studies are warranted to validate findings and examine relations with conventional birth size cut-offs.

Feasibility and impact of Creciendo Sanos, a clinic-based pilot intervention to prevent obesity among preschool children in Mexico City.

BACKGROUND: Mexico has the highest adult overweight and obesity prevalence in the Americas; 23.8% of children <5 years old are at risk for overweight and 9.7% are already overweight or obese. Creciendo Sanos was a pilot intervention to prevent obesity among preschoolers in Instituto Mexicano del Seguro Social (IMSS) clinics. METHODS: We randomized 4 IMSS primary care clinics to either 6 weekly educational sessions promoting healthful nutrition and physical activity or usual care. We recruited 306 parent-child pairs: 168 intervention, 138 usual care. Children were 2-5 years old with WHO body mass index (BMI) z-score 0-3. We measured children's height and weight and parents reported children's diet and physical activity at baseline and 3 and 6-month follow-up. We analyzed behavioral and BMI outcomes with generalized mixed models incorporating multiple imputation for missing values. RESULTS: 93 (55%) intervention and 96 (70%) usual care families completed 3 and 6-month follow-up. At 3 months, intervention v. usual care children increased vegetables by 6.3 servings/week (95% CI, 1.8, 10.8). In stratified analyses, intervention participants with high program adherence (5-6 sessions) decreased snacks and screen time and increased vegetables v. usual care. No further effects on behavioral outcomes or BMI were observed. Transportation time and expenses were barriers to adherence. 90% of parents who completed the post-intervention survey were satisfied with the program. CONCLUSIONS: Although satisfaction was high among participants, barriers to participation and retention included transportation cost and time. In intention to treat analyses, we found intervention effects on vegetable intake, but not other behaviors or BMI. TRIAL REGISTRATION: ClinicalTrials.gov NCT01539070.Comisión Nacional de Investigación Científica del IMSS: 2009-785-120.

Second trimester estimated fetal weight and fetal weight gain predict childhood obesity.

OBJECTIVE: To determine the extent to which fetal weight during mid-pregnancy and fetal weight gain from mid-pregnancy to birth predict adiposity and blood pressure (BP) at age 3 years. STUDY DESIGN: Among 438 children in the Project Viva cohort, we estimated fetal weight at 16-20 (median 18) weeks' gestation using ultrasound biometry measures. We analyzed fetal weight gain as change in quartile of weight from the second trimester until birth, and we measured height, weight, subscapular and triceps skinfold thicknesses, and BP at age 3. RESULTS: Mean (SD) estimated weight at 16-20 weeks was 234 (30) g and birth weight was 3518 (420) g. In adjusted models, weight estimated during the second trimester and at birth were associated with higher body mass index (BMI) z-scores at age 3 years (0.32 unit [95% CI, 0.04-0.60 unit] and 0.53 unit [95% CI, 0.24-0.81 unit] for the highest vs lowest quartile of weight). Infants with more rapid fetal weight gain and those who remained large from mid-pregnancy to birth had higher BMI z-scores (0.85 unit [95% CI, 0.30-1.39 unit] and 0.63 unit [95% CI, 0.17-1.09 unit], respectively) at age 3 than did infants who remained small during fetal life. We did not find associations between our main predictors and sum or ratio of subscapular and triceps skinfold thicknesses or systolic BP. CONCLUSION: More rapid fetal weight gain and persistently high fetal weight during the second half of gestation predicted higher BMI z-score at age 3 years. The rate of fetal weight gain throughout pregnancy may be important for future risk of adiposity in childhood.

Gestational glucose tolerance and cord blood leptin levels predict slower weight gain in early infancy.

OBJECTIVE: To determine the extent to which known prenatal and perinatal predictors of childhood obesity also predict weight gain in early infancy. STUDY DESIGN: We studied 690 infants participating in the prospective cohort Project Viva. We measured length and weight at birth and at 6 months. Using multivariable linear regression, we examined relationships of selected maternal and infant factors with change in weight-for-length z-score (WFL-z) from 0 to 6 months. RESULTS: Mean (standard deviation) change in WFL-z from 0 to 6 months was 0.23 (1.11), which translates to 4500 grams gained from birth to 6 months of life in an infant with average birth weight and length. After adjustment for confounding variables and birth weight-for-gestational age z-score (-0.28 [95% confidence interval, -0.37, -0.19] per unit), cord blood leptin (-0.40 [95%confidence interval, -0.61, -0.19] per 10 ng/mL), and gestational diabetes -0.50 [95%confidence interval, -0.88, -0.11] versus normal glucose tolerance)were each associated with slower gain in WFL-z from 0 to 6 months. CONCLUSIONS: Higher neonatal leptin and gestational diabetes predicted slower weight gain in the first 6 months of life. The hormonal milieu of the intrauterine environment may determine growth patterns in early infancy and thus later obesity.

Size at birth, infant growth, and blood pressure at three years of age.

OBJECTIVES: Our aim was to determine the extent to which infant growth-in weight-for-length-from birth to 6 months is associated with systolic blood pressure (SBP) at 3 years and to determine whether this association varies with birth size. STUDY DESIGN: In 530 children from the prospective cohort Project Viva, we measured birth length and 6-month weight and length with research standard instruments and SBP at age 3 years with a Dinamap automated recorder. We derived weight-for-length z-scores (WFL-z) and analyzed data with mixed effects regression models. RESULTS: The mean (SD) WFL-z was 0.47 (0.75) at birth and 0.70 (0.96) at 6 months. Mean (SD) SBP at 3 years was 91.7 (9.4) mm Hg. After adjusting for confounding variables and birth WFL-z, child SBP was 1.0 mm Hg (95% CI 0.2, 1.8) higher for each z-score increment in 6-month WFL-z. The SBP of children in the lowest birth WFL-z quartile and the highest 6-month WFL-z quartile was 5.5 mm Hg (95% CI 2.6, 8.4) higher than that of children in the highest birth and lowest 6-month WFL-z quartiles. CONCLUSIONS: More rapid increase in weight-for-length, a measure of adiposity, in the first 6 months of life is associated with higher early childhood SBP, particularly in children who are thin at birth.

Maternal age and other predictors of newborn blood pressure.

OBJECTIVE: To investigate perinatal predictors of newborn blood pressure. STUDY DESIGN: Among 1059 mothers and their newborn infants participating in Project Viva, a US cohort study of pregnant women and their offspring, we obtained five systolic blood pressure readings on a single occasion in the first few days of life. Using multivariate linear regression models, we examined the extent to which maternal age and other pre- and perinatal factors predicted newborn blood pressure level. RESULTS: Mean (SD) maternal age was 32.0 (5.2) years, and mean (SD) newborn systolic blood pressure was 72.6 (9.0) mm Hg. A multivariate model showed that for each 5-year increase in maternal age, newborn systolic blood pressure was 0.8 mm Hg higher (95% CI, 0.2, 1.4). In addition to maternal age, independent predictors of newborn blood pressure included maternal third trimester blood pressure (0.9 mm Hg [95% CI, 0.2, 1.6] for each increment in maternal blood pressure); infant age at which we measured blood pressure (2.4 mm Hg [95% CI 1.7, 3.0] for each additional day of life); and birth weight (2.9 mm Hg [95% CI, 1.6, 4.2] per kg). CONCLUSIONS: Higher maternal age, maternal blood pressure, and birth weight were associated with higher newborn systolic blood pressure. Whereas blood pressure later in childhood predicts adult hypertension and its consequences, newborn blood pressure may represent different phenomena, such as pre- and perinatal influences on cardiac structure and function.