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Importance: Prenatal experiences can influence fetal brain development., Objective: To examine associations of maternal prenatal body mass index (BMI) with cognition and behavior of offspring born full-term., Design, Setting, and Participants: This cohort study examined follow-up data from a breastfeeding promotion intervention at 31 hospitals and affiliated polyclinics in the Republic of Belarus. Participants included 11 276 children who were evaluated from birth (1996-1997) to adolescence (2017-2019), with maternal BMI information available in prenatal medical records., Exposures: Maternal BMI, calculated as weight in kilograms divided by height in meters squared, after 35 weeks gestation; secondary analyses examined maternal BMI at other time points and paternal BMI., Main Outcomes and Measures: Trained pediatricians assessed child cognition with the Wechsler Abbreviated Scales of Intelligence (WASI) at 6.5 years and the computerized self-administered NeuroTrax battery at 16 years, both with an approximate mean (SD) of 100 (15). Parents and teachers rated behaviors at 6.5 years using the Strengths and Difficulties Questionnaire (SDQ, range 0-40). Mixed-effects linear regression analyses corrected for clustering, adjusted for the randomized intervention group and baseline parental sociodemographic characteristics, and were considered mediation by child BMI., Results: Among 11 276 participants, 9355 women (83%) were aged 20 to 34 years, 10 128 (89.8%) were married, and 11 050 (98.0%) did not smoke during pregnancy. Each 5-unit increase in of maternal late-pregnancy BMI (mean [SD], 27.2 [3.8]) was associated with lower offspring WASI performance intelligence quotient (IQ) (-0.52 points; 95% CI, -0.87 to -0.17 points) at 6.5 years and lower scores on 5 of 7 NeuroTrax subscales and the global cognitive score at 16 years (-0.67 points; 95% CI, -1.06 to -0.29 points). Results were similar after adjustment for sociodemographic characteristics, pregnancy complications, and paternal BMI and were not mediated by child weight. Higher late pregnancy maternal BMI was also associated with more behavioral problems reported on the SDQ by teachers but not associated with parent-reported behaviors (externalizing behaviors: 0.13 points; 95% CI, 0.02 to 0.24 points; and total difficulties: 0.14 points, 95% CI, -0.02 to 0.30 points). Results were similar for maternal BMI measured in the first trimester or postpartum. In contrast, higher 6.5-year paternal BMI was associated with slightly better child cognition (WASI verbal IQ: 0.42 points; 95% CI, 0.02 to 0.82 points; NeuroTrax executive function score: 0.68 points; 95% CI, 0.24 to 1.12 points) and fewer teacher-reported behavioral problems (total difficulties: -0.29 points; 95% CI, -0.46 to -0.11 points)., Conclusions and Relevance: This cohort study supports findings from animal experiments and human observational studies in settings with higher maternal BMI and obesity rates. Higher maternal prenatal BMI may be associated with poorer offspring brain development, although residual confounding cannot be excluded.

For longitudinal studies with multivariate observations, we propose statistical methods to identify clusters of archetypal subjects by using techniques from functional data analysis and to relate longitudinal patterns to outcomes. We demonstrate how this approach can be applied to examine associations between multiple time-varying exposures and subsequent health outcomes, where the former are recorded sparsely and irregularly in time, with emphasis on the utility of multiple longitudinal observations in the framework of dimension reduction techniques. In applications to children's growth data, we investigate archetypes of infant growth patterns and identify subgroups that are related to cognitive development in childhood. Specifically, "Stunting" and "Faltering" time-dynamic patterns of head circumference, body length and weight in the first 12 months are associated with lower levels of long-term cognitive development in comparison to "Generally Large" and "Catch-up" growth. Our findings provide evidence for the statistical association between multivariate growth patterns in infancy and long-term cognitive development., Competing Interests: The authors have declared that no competing interests exist.

Background: Evidence on the long-term effect of breastfeeding on neurocognitive development is based almost exclusively on observational studies. In the 16-year follow-up study of a large, cluster-randomized trial of a breastfeeding promotion intervention, we evaluated the long-term persistence of the neurocognitive benefits of the breastfeeding promotion intervention previously observed at early school age., Methods and Findings: A total of 13,557 participants (79.5% of the 17,046 randomized) of the Promotion of Breastfeeding Intervention Trial (PROBIT) were followed up at age 16 from September 2012 to July 2015. At the follow-up, neurocognitive function was assessed in 7 verbal and nonverbal cognitive domains using a computerized, self-administered test battery among 13,427 participants. Using an intention-to-treat (ITT) analysis as our prespecified primary analysis, we estimated cluster- and baseline characteristic-adjusted mean differences between the intervention (prolonged and exclusive breastfeeding promotion modelled on the Baby-Friendly Hospital Initiative) and control (usual care) groups in 7 cognitive domains and a global cognitive score. In our prespecified secondary analysis, we estimated mean differences by instrumental variable (IV) analysis to account for noncompliance with the randomly assigned intervention and estimate causal effects of breastfeeding. The 16-year follow-up rates were similar in the intervention (79.7%) and control groups (79.3%), and baseline characteristics were comparable between the two. In the cluster-adjusted ITT analyses, children in the intervention group did not show statistically significant differences in the scores from children in the control group. Prespecified additional adjustment for baseline characteristics improved statistical precision and resulted in slightly higher scores among children in the intervention for verbal function (1.4 [95% CI 0.3-2.5]) and memory (1.2 [95% CI 0.01-2.4]). IV analysis showed that children who were exclusively breastfed for ≥3 (versus <3) months had a 3.5-point (95% CI 0.9-6.1) higher verbal function, but no differences were observed in other domains. While our computerized, self-administered cognitive testing reduced the cluster-level variability in the scores, it may have increased individual-level measurement errors in adolescents., Conclusions: We observed no benefit of a breastfeeding promotion intervention on overall neurocognitive function. The only beneficial effect was on verbal function at age 16. The higher verbal ability is consistent with results observed at early school age; however, the effect size was substantially smaller in adolescence., Probit Trial Registration: ClinicalTrials.gov NCT01561612.

Objectives: Few studies have prospectively investigated associations of child cognitive ability and behavioural difficulties with later eating attitudes. We investigated associations of intelligence quotient (IQ), academic performance and behavioural difficulties at 6.5 years with eating attitudes five years later., Methods: We conducted an observational cohort study nested within the Promotion of Breastfeeding Intervention Trial, Belarus. Of 17,046 infants enrolled at birth, 13,751 (80.7%) completed the Children's Eating Attitude Test (ChEAT) at 11.5 years, most with information on IQ (n = 12,667), academic performance (n = 9,954) and behavioural difficulties (n = 11,098) at 6.5 years. The main outcome was a ChEAT score ≥ 85th percentile, indicative of problematic eating attitudes., Results: Boys with higher IQ at 6.5 years reported fewer problematic eating attitudes, as assessed by ChEAT scores ≥ 85th percentile, at 11.5 years (OR per SD increase in full-scale IQ = 0.87; 0.79, 0.94). No such association was observed in girls (1.01; 0.93, 1.10) (p for sex-interaction = 0.016). In both boys and girls, teacher-assessed academic performance in non-verbal subjects was inversely associated with high ChEAT scores five years later (OR per unit increase in mathematics ability = 0.88; 0.82, 0.94; and OR per unit increase in ability for other non-verbal subjects = 0.86; 0.79, 0.94). Behavioural difficulties were positively associated with high ChEAT scores five years later (OR per SD increase in teacher-assessed rating = 1.13; 1.07, 1.19)., Conclusion: Lower IQ, worse non-verbal academic performance and behavioural problems at early school age are positively associated with risk of problematic eating attitudes in early adolescence.

Background: Despite numerous population-based randomized intervention trials, the impact of such interventions on socioeconomic inequalities has rarely been examined. We used data from a large cluster-randomized trial to assess the impact of a breastfeeding promotion intervention on socioeconomic inequalities in breastfeeding (exclusivity and duration) and in child cognitive ability at early school age., Methods: The Promotion of Breastfeeding Intervention Trial (PROBIT) randomized 31 Belarusian maternity hospitals and their affiliated polyclinics either to receive a breastfeeding promotion intervention modelled on the WHO/UNICEF Baby-Friendly Hospital Initiative or to continue the standard practices in effect at the time of randomization. We estimated and compared inequalities in discontinuation of exclusive breastfeeding before 3 months and of any breastfeeding before 12 months and in child verbal IQ at age 6.5 years, across maternal education strata between the two intervention arms., Findings: Socioeconomic inequalities in discontinuing exclusive breastfeeding before 3 months were negligible in the control group. However, graded inequalities by maternal education emerged in the intervention group {relative risk [RR] = 1.12 [95% confidence interval (CI): 1.04, 1.20] for partial university and RR = 1.20 [95% CI: 1.11, 1.31] for secondary education or less vs complete university; risk difference [RD] = 0.06 [95% CI: 0.03, 0.09] and 0.10 [95% CI: 0.06, 0.14], respectively}. For discontinuing any breastfeeding before 12 months, small socioeconomic gradients in the control group were widened in the intervention group (RR = 1.04 and 1.16, respectively, for mothers with secondary education or less). Despite these differential effects on breastfeeding, however, we observed a small, nonsignificant reduction in socioeconomic inequalities in child verbal IQ at age 6.5 years., Conclusions: A population-based intervention to promote breastfeeding slightly widened socioeconomic inequalities in breastfeeding but not those in child cognitive ability., (© The Author 2014; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Background: Most studies of the associations between pre-natal or post-natal growth and cognitive ability have been based on children with pathologically slow growth measured between two time points only, rather than children with normal growth trajectories estimated from multiple measures of growth., Methods: We investigated the associations of pre-natal and post-natal trajectories in both weight and length/height through the first 5 years of life with cognitive ability and mental health at 6.5 years of age among healthy children. Our study is based on 11 899 children who were born healthy at ≥37 completed weeks with birth weight ≥2500 g and had up to 13 measures of weight and length/height from birth to age 5 years and cognitive ability and behaviour measured at 6.5 years. Using a linear spline random-effects model with 2 knots at 3 and 12 months, we estimated growth trajectories for each child from birth to age 5 years in weight and length/height in four periods: gestational age-specific birth weight and length (pre-natal 'growth'), early infancy (0-3 months), late infancy (3-12 months) and early childhood (1-5 years). We used generalized estimating equations to estimate mean differences in IQ and mental health according to pre-natal and post-natal growth trajectory. IQ was measured using the Wechsler Abbreviated Scales of Intelligence, and mental health was assessed using the Strengths and Difficulties Questionnaire., Results: A 1 standard deviation (SD) in birth weight was positively associated with cognitive ability (0.82 IQ points, 95% CI: 0.54-1.10) after adjusting for confounders. For post-natal weight gain trajectories, a 1 SD faster weight gain was associated with an increase of 0.77 (95% CI: 0.42-1.11) IQ points for early infancy, 0.30 (95% CI: 0.02-0.58) points for late infancy, and 0.40 (95% CI: 0.04-0.76) for early childhood after adjusting for confounders and for earlier growth. For length/height trajectories, the magnitudes of increase in cognitive ability were similar to each other (~0.6 points) across the four periods. Pre-natal and infancy growth, but not early childhood growth, were associated with reduced externalising behaviours., Conclusions: Although the effect sizes are small and residual confounding cannot be excluded, our results suggest that among healthy children, faster growth from the pre-natal period through age 5 years is positively associated with cognitive ability, whereas faster growth in the pre-natal period and infancy is positively associated with mental health at early school age.

The authors investigated variations in cognitive ability by gestational age among 13,824 children at age 6.5 years who were born at term with normal weight, using data from a prospective cohort recruited in 1996-1997 in Belarus. The mean differences in the Wechsler Abbreviated Scales of Intelligence were examined by gestational age in completed weeks and by fetal growth after controlling for maternal and family characteristics. Compared with the score for those born at 39-41 weeks, the full-scale intelligence quotient (IQ) score was 1.7 points (95% confidence interval (CI): -2.7, -0.7) lower in children born at 37 weeks and 0.4 points (95% CI: -1.1, 0.02) lower at 38 weeks after controlling for confounders. There was also a graded relation in postterm children: a 0.5-points (95% CI: -2.6, 1.6) lower score at 42 weeks and 6.0 points (95% CI: -15.1, 3.1) lower at 43 weeks. Compared with children born large for gestational age (>90th percentile), children born small for gestational age (<10th percentile) had the lowest IQ, followed by those at the 10th-50th percentile and those at the >50th-90th percentile. These findings suggest that, even among healthy children born at term, cognitive ability at age 6.5 years is lower in those born at 37 or 38 weeks and those with suboptimal fetal growth.

Objectives: The purpose of this work was to examine whether the positive association between birth weight and childhood cognitive ability is seen within siblings from the same family, as well as between nonsiblings, and to determine whether these associations vary with age., Methods: We compared the association of birth weight with cognitive ability measured at ages 5 to 6, 7 to 9, and 11 to 12 years among a total of 5402 children from different families with that among 2236 to 3083 sibships from the National Longitudinal Study of Youth 1979-Children., Results: In the whole cohort, there were positive associations between birth weight and cognitive ability at all ages, with the association increasing with age from a 0.81-point increase at ages 5 to 6 years to 1.30 and 1.44 points at ages 7 to 9 and 11 to 12 years, respectively, per 1 SD of gestational age- and gender-adjusted birth weight z score. With adjustment for covariates, there was marked attenuation of these associations. Mean differences were 0.28 points in children aged 5 to 6 years, 0.67 points in those aged 7 to 9 years, and 0.52 points in those aged 11 to 12 years after adjusting for child's gender, race or ethnicity, year of birth, and age at test; maternal age, height, parity, education, smoking during pregnancy, and cognitive ability; and household income. Our family-based analyses that separated within- and between-family effects found that the between-family associations were much stronger than the within-family associations. However, adjustment for potential confounders attenuated the between-family associations, and there was no evidence for a difference in association comparing the between- and within-family associations., Conclusions: In these data, the positive association between birth weight and childhood cognitive ability at ages 5 to 12 years is explained largely by family characteristics rather than a specific intrauterine effect.

Background: Most studies of associations between child growth and cognitive ability were based on size at one or two ages and a single measure of cognition. We aimed to characterize different aspects of early growth and their associations with cognitive outcomes in childhood through adolescence.Methods: In a sample of 12 368 Belarusian children born at term, we examined associations of length/height and weight trajectories over the first 6.5 years of life with cognitive ability at 6.5 and 16 years and its change over time. We estimated growth trajectories using two random-effects models-the SuperImposition by Translation and Rotation to model overall patterns of growth and the Jenss-Bayley to distinguish growth in infancy from post infancy. Cognitive ability was measured using the Wechsler Abbreviated Scales of Intelligence at 6.5 years and the computerized NeuroTrax test at 16 years.Results: Higher length/height between birth and 6.5 years was associated with higher cognitive scores at 6.5 and 16 years {2.7 points [95% confidence interval (CI): 2.1, 3.2] and 2.5 points [95% CI: 1.9, 3.0], respectively, per standard deviation [SD] increase}. A 1-SD delay in the childhood height-growth spurt was negatively associated with cognitive scores [-2.4 (95% CI: -3.0, -1.8) at age 6.5; -2.2 (95% CI: -2.7, -1.6) at 16 years]. Birth size and post-infancy growth velocity were positively associated with cognitive scores at both ages. Height trajectories were not associated with the change in cognitive score. Similar results were observed for weight trajectories.Conclusions: Among term infants, the overall size, timing of the childhood growth spurt, size at birth and post-infancy growth velocity were all associated with cognitive ability at early-school age and adolescence. [ABSTRACT FROM AUTHOR]