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Background: Conflicting findings from studies evaluating associations of allergic disease with child behaviour require longitudinal studies to resolve. Objective: To estimate the magnitude of associations of atopic dermatitis (AD) in infancy, and symptoms of asthma and AD at 6.5 years, with child behaviour at 6.5 years. Methods: Secondary cohort analysis of the Promotion of Breastfeeding Intervention Trial (PROBIT). PROBIT enrolled 17 046 infants at birth and followed them up at 6.5 years (n = 13 889). Study paediatricians collected data on infantile AD at repeated follow‐up examinations during the first year of life. At 6.5 years, paediatricians performed skin prick tests and parents reported asthma and AD symptoms during the prior year. In addition, parents and teachers completed the Strength and Difficulties Questionnaire, which includes scales on hyperactivity/inattention, emotional problems, conduct problems, peer problems and prosocial behaviours. Results: Physician‐diagnosed AD in the first year of life was not associated with increased risk for behavioural problems at 6.5 years. Emotional problems at 6.5 years were more common among children with AD symptoms (OR: 2.24, 95% CI: 1.62‐3.12) and asthma symptoms (OR: 1.45; 95% CI: 1.07‐1.96) during the past year at 6.5 years and ORs for children with symptoms of more severe AD and asthma were also higher. AD in the past year was also associated with probable hyperactivity/inattention disorder at 6.5 years (OR: 2.05; 95% CI: 1.09‐3.84). Other subscales of the SDQ were not related to asthma or AD symptoms during the past year. Conclusions and clinical relevance: Children with AD symptoms were at higher risk for concomitant hyperactivity/inattention and emotional disorder, and children with asthma symptoms were at higher risk of having concomitant emotional problems. However, AD during infancy did not predict childhood behaviours. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Observational studies suggest that breastfeeding benefits later maternal child-feeding practices, which in turn may contribute to positive eating attitudes. We investigated the effect of a randomized intervention to increase duration and exclusivity of breastfeeding on pre-adolescent eating attitudes.Methods: Long-term follow-up of the Promotion of Breastfeeding Intervention Trial (PROBIT), a cluster-randomized trial in 31 maternity hospitals and affiliated polyclinics in Belarus. Sites were randomly assigned an experimental intervention to promote longer duration and exclusivity of breastfeeding in mothers who initiated breastfeeding (n = 16 sites), or a control intervention of continuing usual care (n = 15 sites); 17 046 healthy infants were enrolled in 1996-7, of whom 13 751 (80.7%) completed the Children's Eating Attitude Test (ChEAT) at 11.5 years of age. A ChEAT score ≥ 22.5 (85th percentile) was used as an indicator of problematic eating attitudes. Analysis was based on intention-to-treat, accounting for clustering within hospitals/clinics.Results: Compared with the control arm, the experimental intervention substantially increased breastfeeding exclusivity (43.3% vs 6.4% exclusively breastfed at 3 months of age) and duration of any breastfeeding throughout infancy. The proportion of children with ChEAT scores ≥ 22.5 was lower in the experimental than control arm (boys 11.4% vs 17.2%; girls 18.5% vs 23.4%) [cluster-adjusted odds ratio (OR), boys: 0.44; 95% confidence interval (CI): 0.21,0.93; girls: 0.51; 95% CI: 0.27,0.99). Results were robust to adjustment for potential confounders and using a ChEAT score ≥ 25.5 (91st percentile) as the outcome (OR: 0.53; 95% CI: 0.28,1.03).Conclusions: An intervention to improve the duration and exclusivity of breastfeeding among term infants in Belarus was associated with a reduction in problematic eating attitudes at 11.5 years of age. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

SummaryThe PROmotion of Breastfeeding Intervention Trial (PROBIT) is a multicentre, cluster-randomized controlled trial conducted in the Republic of Belarus, in which the experimental intervention was the promotion of increased breastfeeding duration and exclusivity, modelled on the Baby-friendly hospital initiative. Between June 1996 and December 1997, 17 046 mother–infant pairs were recruited during their postpartum hospital stay from 31 maternity hospitals, of which 16 hospitals and their affiliated polyclinics had been randomly assigned to the arm of PROBIT investigating the promotion of breastfeeding and 15 had been assigned to the control arm, in which breastfeeding practices and policies in effect at the time of randomization was continued. Of the mother–infant pairs originally recruited for the study, 16 492 (96.7%) were followed at regular intervals until the infants were 12 months of age (PROBIT I) for the outcomes of breastfeeding duration and exclusivity; gastrointestinal and respiratory infections; and atopic eczema. Subsequently, 13 889 (81.5%) of the children from these mother–infant pairs were followed-up at age 6.5 years (PROBIT II) for anthropometry, blood pressure (BP), behaviour, dental health, cognitive function, asthma and atopy outcomes, and 13 879 (81.4%) children were followed to the age of 11.5 years (PROBIT III) for anthropometry, body composition, BP, and the measurement of fasted glucose, insulin, adiponectin, insulin-like growth factor-I, and apolipoproteins. The trial registration number for Current Controlled Trials is ISRCTN37687716 and that for ClinicalTrials.gov is NCT01561612. Proposals for collaboration are welcome, and enquires about PROBIT should be made to an executive group of the study steering committee (M.S.K., R.M.M., and E.O.). More information, including information about how to access the trial data, data collection documents, and bibliography, is available at the trial website (http://www.bristol.ac.uk/social-community-medicine/projects/probit/). [ABSTRACT FROM PUBLISHER]

Background: The duration and exclusivity of breastfeeding in infancy have been inversely associated with future cardiometabolic risk. We investigated the effects of an experimental intervention to promote increased duration of exclusive breastfeeding on cardiometabolic risk factors in childhood.Methods and Results: We followed-up children in the Promotion of Breastfeeding Intervention Trial, a cluster-randomized trial of a breastfeeding promotion intervention based on the World Health Organization/United Nations Children's Fund Baby-Friendly Hospital Initiative. In 1996 to 1997, 17 046 breastfeeding mother-infant pairs were enrolled from 31 Belarusian maternity hospitals and affiliated polyclinics (16 intervention versus 15 control sites); 13 879 (81.4%) children were followed up at 11.5 years, with 13 616 (79.9%) who had fasted and did not have diabetes mellitus. The outcomes were blood pressure; fasting insulin, adiponectin, glucose, and apolipoprotein A1; and the presence of metabolic syndrome. Analysis was by intention to treat, accounting for clustering within hospitals/clinics. The intervention substantially increased breastfeeding duration and exclusivity in comparison with the control arm (43% versus 6% and 7.9% versus 0.6% exclusively breastfed at 3 and 6 months, respectively). Cluster-adjusted mean differences at 11.5 years between experimental versus control groups were as follows: 1.0 mm Hg (95% confidence interval, -1.1 to 3.1) for systolic and 0.8 mm Hg (-0.6 to 2.3) for diastolic blood pressure; -0.1 mmol/L (-0.2 to 0.1) for glucose; 8% (-3% to 34%) for insulin; -0.3 μg/mL (-1.5 to 0.9) for adiponectin; and 0.0 g/L (-0.1 to 0.1) for apolipoprotein A1. The cluster-adjusted odds ratio for metabolic syndrome, comparing experimental versus control groups, was 1.21 (0.85 to 1.72).Conclusions: An intervention to improve breastfeeding duration and exclusivity among healthy term infants did not influence cardiometabolic risk factors in childhood.Clinical Trial Registration: Current Controlled Trials: ISRCTN37687716 (http://www.controlled-trials.com/ISRCTN37687716). URL: http://clinicaltrials.gov. Unique identifier: NCT01561612. [ABSTRACT FROM AUTHOR]

Background--The duration and exclusivity of breastfeeding in infancy have been inversely associated with future cardiometabolic risk. We investigated the effects of an experimental intervention to promote increased duration of exclusive breastfeeding on cardiometabolic risk factors in childhood. Methods and Results--We followed-up children in the Promotion of Breastfeeding Intervention Trial, a cluster-randomized trial of a breastfeeding promotion intervention based on the World Health Organization/United Nations Children's Fund Baby-Friendly Hospital Initiative. In 1996 to 1997, 17 046 breastfeeding mother-infant pairs were enrolled from 31 Belarusian maternity hospitals and affiliated polyclinics (16 intervention versus 15 control sites); 13 879 (81.4%) children were followed up at 11.5 years, with 13 616 (79.9%) who had fasted and did not have diabetes mellitus. The outcomes were blood pressure; fasting insulin, adiponectin, glucose, and apolipoprotein A1; and the presence of metabolic syndrome. Analysis was by intention to treat, accounting for clustering within hospitals/clinics. The intervention substantially increased breastfeeding duration and exclusivity in comparison with the control arm (43% versus 6% and 7.9% versus 0.6% exclusively breastfed at 3 and 6 months, respectively). Cluster-adjusted mean differences at 11.5 years between experimental versus control groups were as follows: 1.0 mm Hg (95% confidence interval, -1.1 to 3.1) for systolic and 0.8 mm Hg (-0.6 to 2.3) for diastolic blood pressure; -0.1 mmol/L (-0.2 to 0.1) for glucose; 8% (-3% to 34%) for insulin; -0.3 μg/mL (-1.5 to 0.9) for adiponectin; and 0.0 g/L (-0.1 to 0.1) for apolipoprotein A1. The cluster-adjusted odds ratio for metabolic syndrome, comparing experimental versus control groups, was 1.21 (0.85 to 1.72). Conclusions--An intervention to improve breastfeeding duration and exclusivity among healthy term infants did not influence cardiometabolic risk factors in childhood. Clinical Trial Registration--Current Controlled Trials: ISRCTN37687716 (http://www.controlled-trials.com/ISRCTN37687716). URL: http://clinicaltrials.gov. Unique identifier: NCT01561612. [ABSTRACT FROM AUTHOR]

Background: Adiponectin is an adipocyte-derived hormone that acts as a marker of insulin sensitivity. Bloodspot sampling by fingerstick onto filter paper may increase the feasibility of large-scale studies of the determinants of insulin sensitivity. We first describe the validation of an enzyme-linked immunoassay (ELISA) for quantifying adiponectin from dried blood spots and then demonstrate its application in a large trial (PROBIT). Methods: We quantified adiponectin from 3-mm diameter discs (≈3 µL of blood) punched from dried blood spots obtained from: i) whole blood standards (validation); and ii) PROBIT trial samples (application) in which paediatricians collected blood spots from 13,879 children aged 11.5 years from 31 sites across Belarus. We examined the distribution of bloodspot adiponectin by demographic and anthropometric factors, fasting insulin and glucose. Results: In the validation study, mean intra-assay coefficients of variation (n = 162) were 15%, 13% and 10% for ‘low’ (6.78 µg/ml), ‘medium’ (18.18 µg/ml) and 'high’ (33.13 µg/ml) internal quality control (IQC) samples, respectively; the respective inter-assay values (n = 40) were 23%, 21% and 14%. The correlation coefficient between 50 paired whole bloodspot versus plasma samples, collected simultaneously, was 0.87 (95% CI: 0.78 to 0.93). Recovery of known quantities of adiponectin (between 4.5 to 36 µg/ml) was 100.3–133%. Bloodspot adiponectin was stable for at least 30 months at −80°C. In PROBIT, we successfully quantified fasting adiponectin from dried blood spots in 13,329 of 13,879 (96%) children. Mean adiponectin (standard deviation) concentrations were 17.34 µg/ml (7.54) in boys and 18.41 µg/ml (7.92) in girls and were inversely associated with body mass index, fat mass, triceps and subscapular skin-fold thickness, waist circumference, height and fasting glucose. Conclusions: Bloodspot ELISA is suitable for measuring adiponectin in very small volumes of blood collected on filter paper and can be applied to large-scale studies. [ABSTRACT FROM AUTHOR]

Importance: Evidence that longer-term and exclusive breastfeeding reduces child obesity risk is based on observational studies that are prone to confounding.Objective: To investigate effects of an intervention to promote increased duration and exclusivity of breastfeeding on child adiposity and circulating insulin-like growth factor (IGF)-I, which regulates growth.Design, Setting, and Participants: Cluster-randomized controlled trial in 31 Belarusian maternity hospitals and their affiliated clinics, randomized into 1 of 2 groups: breastfeeding promotion intervention (n = 16) or usual practices (n = 15). Participants were 17,046 breastfeeding mother-infant pairs enrolled in 1996 and 1997, of whom 13,879 (81.4%) were followed up between January 2008 and December 2010 at a median age of 11.5 years.Intervention: Breastfeeding promotion intervention modeled on the WHO/UNICEF Baby-Friendly Hospital Initiative (World Health Organization/United Nations Children's Fund).Main Outcome Measures: Body mass index (BMI), fat and fat-free mass indices (FMI and FFMI), percent body fat, waist circumference, triceps and subscapular skinfold thicknesses, overweight and obesity, and whole-blood IGF-I. Primary analysis was based on modified intention-to-treat (without imputation), accounting for clustering within hospitals and clinics.Results: The experimental intervention substantially increased breastfeeding duration and exclusivity when compared with the control (43% vs 6% exclusively breastfed at 3 months and 7.9% vs 0.6% at 6 months). Cluster-adjusted mean differences in outcomes at 11.5 years of age between experimental vs control groups were: 0.19 (95% CI, -0.09 to 0.46) for BMI; 0.12 (-0.03 to 0.28) for FMI; 0.04 (-0.11 to 0.18) for FFMI; 0.47% (-0.11% to 1.05%) for percent body fat; 0.30 cm (-1.41 to 2.01) for waist circumference; -0.07 mm (-1.71 to 1.57) for triceps and -0.02 mm (-0.79 to 0.75) for subscapular skinfold thicknesses; and -0.02 standard deviations (-0.12 to 0.08) for IGF-I. The cluster-adjusted odds ratio for overweight/obesity (BMI ≥ 85th vs <85th percentile) was 1.18 (95% CI, 1.01 to 1.39) and for obesity (BMI ≥ 95th vs <85th percentile) was 1.17 (95% CI, 0.97 to 1.41).Conclusions: AND RELEVANCE Among healthy term infants in Belarus, an intervention that succeeded in improving the duration and exclusivity of breastfeeding did not prevent overweight or obesity, nor did it affect IGF-I levels at age 11.5 years. Breastfeeding has many advantages but population strategies to increase the duration and exclusivity of breastfeeding are unlikely to curb the obesity epidemic.Trial Registration: isrctn.org: ISRCTN37687716; and clinicaltrials.gov: NCT01561612. [ABSTRACT FROM AUTHOR]

The article focuses on a randomized-controlled trial which aims to investigate effects of an intervention to promote increased duration and exclusivity of breastfeeding on child adiposity and circulating insulin-like growth factor (IGF)-I in Belarus. It mentions that the participants of this study included 17,046 breastfeeding mothers enrolled in 1996 and 1997, of whom 13,879 were followed up between January 2008 and December 2010 at a median age of 11.5 years. The main outcome measures included body mass index, percent body fat and waist circumference. The results indicated that breastfeeding has many advantages but population strategies to increase the duration and exclusivity of breastfeeding are unlikely to curb the obesity epidemic.

Background: In large-scale epidemiology, bloodspot sampling by fingerstick onto filter paper has many advantages, including ease and low costs of collection, processing and transport. We describe the development of an enzyme-linked immunoassay (ELISA) for quantifying insulin from dried blood spots and demonstrate its application in a large trial. Methods: We adapted an existing commercial kit (Mercodia Human Insulin ELISA, 10-1113-01) to quantify insulin from two 3-mm diameter discs (≈6 µL of blood) punched from whole blood standards and from trial samples. Paediatricians collected dried blood spots in a follow-up of 13,879 fasted children aged 11.5 years (interquartile range 11.3-11.8 years) from 31 trial sites across Belarus. We quantified bloodspot insulin levels and examined their distribution by demography and anthropometry. Results: Mean intra-assay (n = 157) coefficients of variation were 15% and 6% for 'low' (6.7 mU/L) and 'high' (23.1 mU/L) values, respectively; the respective inter-assay values (n = 33) were 23% and 11%. The intraclass correlation coefficient between 50 paired whole bloodspot versus serum samples, collected simultaneously, was 0.90 (95% confidence interval 0.85 to 0.95). Bloodspot insulin was stable for at least 31 months at -80°C, for one week at +30°C and following four freeze-thaw cycles. Paediatricians collected a median of 8 blood spots from 13,487 (97%) children. The geometric mean insulin (log standard deviation) concentrations amongst 12,812 children were 3.0 mU/L (1.1) in boys and 4.0 mU/L (1.0) in girls and were positively associated with pubertal stage, measures of central and peripheral adiposity, height and fasting glucose. Conclusions: Our simple and convenient bloodspot assay is suitable for the measurement of insulin in very small volumes of blood collected on filter paper cards and can be applied to large-scale epidemiology studies of the early-life determinants of circulating insulin. [ABSTRACT FROM AUTHOR]