Colin D. Steer

Early life risk factors for obesity in childhood: cohort study

Abstract Objective To identify risk factors in early life (up to 3 years of age) for obesity in children in the United Kingdom. Design Prospective cohort study. Setting Avon longitudinal study of parents and children, United Kingdom. Participants 8234 children in cohort aged 7 years and a subsample of 909 children (children in focus) with data on additional early growth related risk factors for obesity. Main outcome measures Obesity at age 7 years, defined as a body mass index 3 95th centile relative to reference data for the UK population in 1990. Results Eight of 25 putative risk factors were associated with a risk of obesity in the final models: parental obesity (both parents: adjusted odds ratio, 10.44, 95% confidence interval 5.11 to 21.32), very early (by 43 months) body mass index or adiposity rebound (15.00, 5.32 to 42.30), more than eight hours spent watching television per week at age 3 years (1.55, 1.13 to 2.12), catch-up growth (2.60, 1.09 to 6.16), standard deviation score for weight at age 8 months (3.13, 1.43 to 6.85) and 18 months (2.65, 1.25 to 5.59); weight gain in first year (1.06, 1.02 to 1.10 per 100 g increase); birth weight, per 100 g (1.05, 1.03 to 1.07); and short (< 10.5 hours) sleep duration at age 3 years (1.45, 1.10 to 1.89). Conclusion Eight factors in early life are associated with an increased risk of obesity in childhood.

Selective drop-out in longitudinal studies and non-biased prediction of behaviour disorders

Background Participant drop-out occurs in all longitudinal studies, and if systematic, may lead to selection biases and erroneous conclusions being drawn from a study. Aims We investigated whether drop out in the Avon Longitudinal Study of Parents And Children (ALSPAC) was systematic or random, and if systematic, whether it had an impact on the prediction of disruptive behaviour disorders. Method Teacher reports of disruptive behaviour among currently participating, previously participating and never participating children aged 8 years in the ALSPAC longitudinal study were collected. Data on family factors were obtained in pregnancy. Simulations were conducted to explain the impact of selective drop-out on the strength of prediction. Results Drop out from the ALSPAC cohort was systematic and children who dropped out were more likely to suffer from disruptive behaviour disorder. Systematic participant drop-out according to the family variables, however, did not alter the association between family factors obtained in pregnancy and disruptive behaviour disorder at 8 years of age. Conclusions Cohort studies are prone to selective drop-out and are likely to underestimate the prevalence of psychiatric disorder. This empirical study and the simulations confirm that the validity of regression models is only marginally affected despite range restrictions after selective drop-out.

Is there an intrauterine influence on obesity? Evidence from parent–child associations in the Avon Longitudinal Study of Parents and Children (ALSPAC)

Background: It has been suggested that increasing obesity levels in young women lead to intrauterine environments that, in turn, stimulate increased obesity among their offspring, generating an intergenerational acceleration of obesity levels. If this mechanism is important, the association of maternal body mass index (BMI) with offspring BMI should be stronger than the association of paternal with offspring BMI. Objective: To compare the relative strengths of association of maternal and paternal BMI with offspring BMI at age 7.5, taking into account the possible effect of non-paternity. Methods: We compared strength of association for maternal–offspring and paternal–offspring BMI for 4654 complete parent–offspring trios in the Avon Longitudinal Study of Parents and Children (ALSPAC), using unstandardised and standardised regression analysis. We carried out a sensitivity analysis to investigate the influence of non-paternity on these associations. Results: The strength of association between parental BMI and offspring BMI at age 7.5 was similar for both parents. Taking into account correlations between maternal and paternal BMI, performing standardised rather than unstandardised regression and carrying out a sensitivity analysis for non-paternity emphasised the robustness of the general similarity of the associations. The associations between high parental BMI (top decile) and offspring BMI are also similar for both parents. Conclusion: Comparison of mother–offspring and father–offspring associations for BMI suggests that intergenerational acceleration mechanisms do not make an important contribution to levels of childhood BMI within the population. Associations at later ages and for different components of body composition now require study.

Genetic variants of the fatty acid desaturase gene cluster predict amounts of red blood cell docosahexaenoic and other polyunsaturated fatty acids in pregnant women: findings from the Avon Longitudinal Study of Parents and Children

BACKGROUND Blood and tissue long-chain polyunsaturated fatty acid (LC-PUFA) amounts, which have been associated with early development and lifelong health, depend on dietary intake and endogenous conversion of precursor fatty acids (FAs) by the enzymes Δ⁵-desaturase and Δ⁶-desaturase. Polymorphisms in the desaturase encoding genes FADS1 and FADS2 have been associated with several n-6 (omega-6) and n-3 (omega-3) FAs and especially with arachidonic acid (AA) amounts. Associations with docosahexaenoic acid (DHA), which is considered particularly important for brain and retina development, are hardly existent. OBJECTIVE We explored the relation between FADS gene cluster polymorphisms and red blood cell (RBC) FA amounts in > 4000 pregnant women participating in the Avon Longitudinal Study of Parents and Children. DESIGN Linear regression analysis of 17 single nucleotide polymorphisms (SNPs) in the FADS gene cluster was conducted with RBC phospholipid FAs from 6711 samples from 4457 women obtained throughout pregnancy (mean ± SD gestational age: 26.8 ± 8.2 wk). RESULTS Independent of dietary effects, the minor alleles were consistently positively associated with precursor FAs and negatively associated with LC-PUFAs and product:substrate ratios of the n-6 (AA:linoleic acid ratio) and n-3 (eicosapentaenoic acid:α-linolenic acid ratio) pathways. In contrast to previous studies, we also showed significant inverse associations with DHA. Similar but weaker associations were shown for the FADS3 SNP rs174455. CONCLUSIONS FADS genotypes influence DHA amounts in maternal RBC phospholipids and might affect the childs DHA supply during pregnancy. It is highly likely that a gene product of FADS3 has a desaturating activity.

Feeding Symptoms, Dietary Patterns, and Growth in Young Children With Autism Spectrum Disorders

OBJECTIVE: To investigate the feeding, diet and growth of young children with autism spectrum disorders (ASD). METHOD: Data on feeding and food frequency were collected by questionnaires completed at 6, 15, 24, 38 and 54 months by participants in the Avon Longitudinal Study of Parents and Children. A food variety score was created, and the content of the diet was calculated at 38 m. The feeding and dietary patterns of 79 children with ASD were compared with 12 901 controls. RESULTS: The median ages of ASD children were 28 months at referral and 45 months at diagnosis. ASD infants showed late introduction of solids after 6 months (p = .004) and were described as “slow feeders” at 6 months (p = .04). From 15–54 months ASD children were consistently reported to be “difficult to feed” (p < .001) and “very choosy” (p < .001). From 15 months, the ASD group had a less varied diet than controls, were more likely to have different meals from their mother from 24 months, and by 54 months 8% of ASD children were taking a special diet for “allergy.” ASD children consumed less vegetables, salad and fresh fruit, but also less sweets and fizzy drinks. At 38 months intakes of energy, total fat, carbohydrate and protein were similar, but the ASD group consumed less vitamins C (p = .02) and D (p = .003). There were no differences in weight, height or BMI at 18 months and 7 years, or in hemoglobin concentrations at 7 years. CONCLUSIONS: ASD children showed feeding symptoms from infancy and had a less varied diet from 15 months, but energy intake and growth were not impaired.

Habitual Levels of physical activity influence bone mass in 11-year-old children from the United Kingdom: findings from a large population-based cohort

We examined the influence of habitual levels of physical activity on bone mass in childhood by studying the relationship between accelerometer recordings and DXA parameters in 4457 11‐year‐old children. Physical activity was positively related to both BMD and bone size in fully adjusted models. However, further exploration revealed that this effect on bone size was modified by fat mass.

Social communication competence and functional adaptation in a general population of children: preliminary evidence for sex-by-verbal IQ differential risk.

OBJECTIVE The proportion of schoolchildren with mild social communicative deficits far exceeds the number diagnosed with an autistic spectrum disorder (ASD). We aimed to ascertain both the population distribution of such deficits and their association with functional adaptation and cognitive ability in middle childhood. METHOD The parent-report Social and Communication Disorders Checklist was administered to participants (n = 8,094) in the Avon Longitudinal Study of Parents and Children. We correlated impairment severity with independent clinical diagnoses of ASD, cognitive abilities, and teacher-rated maladaptive behavior. RESULTS Social and Communication Disorders Checklist scores were continuously distributed in the general population; boys had mean scores 30% higher than girls. Social communicative deficits were associated with functional impairment at school, especially in domains of hyperactivity and conduct disorders. A sex-by-verbal IQ interaction effect occurred: verbal IQ was protective against social communication impairments across the range of abilities in female subjects only. In male subjects, this protective effect did not exist for those with above-average verbal IQ. CONCLUSIONS Social communicative deficits are of prognostic significance, in terms of behavioral adjustment at school, for boys and girls. Their high general population prevalence emphasizes the importance of measuring such traits among clinically referred children who do not meet diagnostic ASD criteria. Above-average verbal IQ seems to confer protection against social communication impairments in female subjects but not in male subjects.

Association of the KIAA0319 Dyslexia Susceptibility Gene With Reading Skills in the General Population

OBJECTIVE The authors previously identified a haplotype on chromosome 6p22 defined by three single-nucleotide polymorphisms (SNPs) that was associated with dyslexia (reading disability) in two independent samples of families that included at least one sibling with severe reading impairment. The authors also showed that this haplotype is associated with a reduction in expression of the KIAA0319 gene. In addition, a completely independent study detected an association between KIAA0319 markers and reading disability. In the current study, the authors tested whether the KIAA0319 gene influences reading skills in the general population, rather than having an effect restricted to reading disability. METHOD The authors genotyped four SNPs that previously showed association with reading disability in the population of 7-9-year-old children in the Avon Longitudinal Study of Parents and Children (ALSPAC), a large longitudinal cohort for which reading-related phenotypes were available for more than 6,000 individuals. The authors conducted quantitative analysis for both single markers and haplotypes. RESULTS The rs2143340 SNP, which effectively tags the three-SNP risk haplotype, was significantly associated with a test for reading ability. The risk haplotype itself also showed association with poor reading performance, and as in previous research, the association was stronger when the analysis was controlled for IQ. CONCLUSIONS These results both support a role of the KIAA0319 gene in the development of dyslexia and suggest that this gene influences reading ability in the general population. Moreover, the data implicate the three-SNP haplotype and its tagging SNP rs2143340 as genetic risk factors for poor reading performance.

Genetic variation in polyunsaturated fatty acid metabolism and its potential relevance for human development and health

Blood and tissue contents of polyunsaturated fatty acid (PUFA) and long-chain PUFA (LC-PUFA) are related to numerous health outcomes including cardiovascular health, allergies, mental health and cognitive development. Evidence has accumulated to show that in addition to diet, common polymorphisms in the fatty acid desaturase (FADS) gene cluster have very marked effects on human PUFA and LC-PUFA status. Recent results suggest that in addition to fatty acid desaturase 1 and fatty acid desaturase 2, the gene product of fatty acid desaturase 3 is associated with desaturating activity. New data have become available to show that FADS single nucleotide polymorphisms (SNPs) also modulate docosahexaenoic acid status in pregnancy as well as LC-PUFA levels in children and in human milk. There are indications that FADS SNPs modulate the risk for allergic disorders and eczema, and the effect of breastfeeding on later cognitive development. Mechanisms by which FADS SNPs modulate PUFA levels in blood, breast milk and tissues should be explored further. More studies are required to explore the effects of FADS gene variants in populations with different ethnic backgrounds, lifestyles and dietary habits, and to investigate in greater depth the interaction of gene variants, diet and clinical end points, including immune response and developmental outcomes. Analyses of FADS gene variants should be included into all sizeable cohort and intervention studies addressing biological effects of PUFA and LC-PUFA in order to consider these important confounders, and to enhance study sensitivity and precision.

High levels of depressive symptoms in pregnancy with low omega-3 fatty acid intake from fish

Background: Depression during pregnancy has adverse consequences for both mother and child. Although common in western countries, depression appears to be virtually absent in countries with high seafood intake. We test the hypothesis that low seafood intake during pregnancy is associated with increased prevalence of depressive symptoms. Methods: This study used data prospectively collected from women participating in the Avon Longitudinal Study of Parents and Children in the period 1991–1992. At 32 weeks’ gestation, the mother completed a questionnaire that included symptoms of depression and a food frequency questionnaire from which the amount of omega-3 fatty acids from fish was calculated. Statistical analysis took social and lifestyle factors into account. Results: Unadjusted and adjusted analyses showed lower maternal intake of omega-3 from seafood was associated with high levels of depressive symptoms. Compared with women consuming more than 1.5 g omega-3 from seafood per week, those consuming none were more likely to have high levels of depressive symptoms at 32 weeks’ gestation (adjusted odds ratios = 1.54; 95% confidence interval = 1.25–1.89). Conclusions: These observational data support an association between low omega-3 intake from seafood and increased risk of high levels of depressive symptoms during pregnancy. Eating seafood during pregnancy may have beneficial effects on mental well-being.