Background

Observational studies have generated conflicting evidence on the effects of moderate maternal alcohol consumption during pregnancy on offspring cognition mainly reflecting problems of confounding. Among mothers who drink during pregnancy fetal alcohol exposure is influenced not only by mother’s intake but also by genetic variants carried by both the mother and the fetus. Associations between children’s cognitive function and both maternal and child genotype at these loci can shed light on the effects of maternal alcohol consumption on offspring cognitive development.

Methods

We used a large population based study of women recruited during pregnancy to determine whether genetic variants in alcohol metabolising genes in this cohort of women and their children were related to the child’s cognitive score (measured by the Weschler Intelligence Scale) at age 8.

Findings

We found that four genetic variants in alcohol metabolising genes in 4167 children were strongly related to lower IQ at age 8, as was a risk allele score based on these 4 variants. This effect was only seen amongst the offspring of mothers who were moderate drinkers (1–6 units alcohol per week during pregnancy (per allele effect estimates were −1.80 (95% CI = −2.63 to −0.97) p = 0.00002, with no effect among children whose mothers abstained during pregnancy (0.16 (95%CI = −1.05 to 1.36) p = 0.80), p-value for interaction  = 0.009). A further genetic variant associated with alcohol metabolism in mothers was associated with their child’s IQ, but again only among mothers who drank during pregnancy.

Objectives

To assess whether the prevalence of growing pains varies with indicators of fatty acid exposure. Growing pains (limb pains of no obvious explanation) have been shown to be strongly linked to a family history of arthritis, and are thought to predict an increased risk of the development of arthritis in adulthood. Much has been made of the possibility of fatty acids, particularly the ω-3 fatty acids, playing a preventive role in the development of arthritis, but little research has been undertaken to determine whether such fatty acids might reduce the risk of growing pains. We aimed to assess whether the prevalence of growing pains varies with indicators of fatty acid exposures.

Design

Case–control study nested within a prospective longitudinal cohort comparing prenatal and postnatal diet, blood measures and variants in fatty acid desaturase (FADS) genes that influence the metabolism of fatty acids. Statistical analysis took account of factors such as gender, smoke exposure, maternal age and education, social class and parity.

Setting

Avon Longitudinal Study of Parents & Children.

Participants

All children born between 1 April 1991 and 31 December 1992 (approximately14 000) within the Avon area (only that part of Avon under the South-West Regional Health Authority). This project compared 1676 children who reported ‘growing pains’ at age 8 with 6155 with no such pain.

Primary outcome

Reported limb pains of no apparent origin.

Results

There was no indication that the affected children had diets that differed with regard to ω-3, plasma levels of fatty acids, or the FADS genetic variants. We also assessed fetal and infant exposure but neither maternal prenatal blood levels nor maternal dietary intake, or duration of breast feeding showed any significant relationships even after adjustment for confounders.

Conclusions

Thus, there is no evidence that ω-3 fatty acid status protects against the development of growing pains in childhood.

Background and Aim

Exposure to stressful life events during pregnancy has been suggested as a potential risk factor for offspring Autism Spectrum Disorders (ASD), but the literature is limited and inconsistent. We tested the hypothesis that maternal exposure to stressful life events would be associated with increased risks of offspring ASD, and that these risks would be highest for exposures during the prenatal period.

Methods and Results

We used prospectively collected data from two large population based studies in Sweden and England. In the Swedish study of 4429 ASD cases and 43277 controls, our exposure comprised the occurrence of any severe life event before and during pregnancy and the child's early life. In the English study (maximum n = 11554, ASD n = 72), we studied the risk of offspring ASD in relation to a combined maternal exposure to multiple (up to 42) common and rare life events, as well as their perceived impact upon the mother during pregnancy and early life. In crude and adjusted regression analyses in both studies, we found no evidence of an association between prenatal life events, or their number and perceived impact and the risk of offspring ASD. Sub-group analysis of ASD with and without intellectual disability in the Swedish study yielded similar results.

Conclusion

We found no evidence to support the hypotheses that exposure to stressful life events during the prenatal period is associated with an increased risk of offspring ASD.

Background

Prenatal loss, the death of a fetus/child through miscarriage or stillbirth, is associated with significant depression and anxiety, particularly in a subsequent pregnancy.

Aims

This study examined the degree to which symptoms of depression and anxiety associated with a previous loss persisted following a subsequent successful pregnancy.

Method

Data were derived from the Avon Longitudinal Study of Parents and Children cohort, a longitudinal cohort study in the west of England that has followed mothers from pregnancy into the postnatal period. A total of 13133 mothers reported on the number and conditions of previous perinatal losses and provided self-report measures of depression and anxiety at 18 and 32 weeks’ gestation and at 8 weeks and 8, 21 and 33 months postnatally. Controls for pregnancy outcome and obstetric and psychosocial factors were included.

Results

Generalised estimating equations indicated that the number of previous miscarriages/stillbirths significantly predicted symptoms of depression (β = 0.18, s.e. = 0.07, P < 0.01) and anxiety (β = 0.14, s.e. = 0.05, P < 0.01) in a subsequent pregnancy, independent of key psychosocial and obstetric factors. This association remained constant across the pre- and postnatal period, indicating that the impact of a previous prenatal loss did not diminish significantly following the birth of a healthy child.

Conclusions

Depression and anxiety associated with a previous prenatal loss shows a persisting pattern that continues after the birth of a subsequent (healthy) child. Interventions targeting women with previous prenatal loss may improve the health outcomes of women and their children.

Background

Prenatal loss, the death of a fetus/child through miscarriage or stillbirth, is associated with significant depression and anxiety, particularly in a subsequent pregnancy.

Aims

This study examined the degree to which symptoms of depression and anxiety associated with a previous loss persisted following a subsequent successful pregnancy.

Method

Data were derived from the Avon Longitudinal Study of Parents and Children cohort, a longitudinal cohort study in the west of England that has followed mothers from pregnancy into the postnatal period. A total of 13 133 mothers reported on the number and conditions of previous perinatal losses and provided self-report measures of depression and anxiety at 18 and 32 weeks’ gestation and at 8 weeks and 8, 21 and 33 months postnatally. Controls for pregnancy outcome and obstetric and psychosocial factors were included.

Results

Generalised estimating equations indicated that the number of previous miscarriages/stillbirths significantly predicted symptoms of depression (β = 0.18, s.e. = 0.07, P<0.01) and anxiety (β = 0.14, s.e. = 0.05, P<0.01) in a subsequent pregnancy, independent of key psychosocial and obstetric factors. This association remained constant across the pre- and postnatal period, indicating that the impact of a previous prenatal loss did not diminish significantly following the birth of a healthy child.

Conclusions

Depression and anxiety associated with a previous prenatal loss shows a persisting pattern that continues after the birth of a subsequent (healthy) child. Interventions targeting women with previous prenatal loss may improve the health outcomes of women and their children.

The Avon Longitudinal Study of Parents and Children (ALSPAC) is a transgenerational prospective observational study investigating influences on health and development across the life course. It considers multiple genetic, epigenetic, biological, psychological, social and other environmental exposures in relation to a similarly diverse range of health, social and developmental outcomes. Recruitment sought to enrol pregnant women in the Bristol area of the UK during 1990–92; this was extended to include additional children eligible using the original enrolment definition up to the age of 18 years. The children from 14 541 pregnancies were recruited in 1990–92, increasing to 15 247 pregnancies by the age of 18 years. This cohort profile describes the index children of these pregnancies. Follow-up includes 59 questionnaires (4 weeks–18 years of age) and 9 clinical assessment visits (7–17 years of age). The resource comprises a wide range of phenotypic and environmental measures in addition to biological samples, genetic (DNA on 11 343 children, genome-wide data on 8365 children, complete genome sequencing on 2000 children) and epigenetic (methylation sampling on 1000 children) information and linkage to health and administrative records. Data access is described in this article and is currently set up as a supported access resource. To date, over 700 peer-reviewed articles have been published using ALSPAC data.

Summary The Avon Longitudinal Study of Children and Parents (ALSPAC) was established to understand how genetic and environmental characteristics influence health and development in parents and children. All pregnant women resident in a defined area in the South West of England, with an expected date of delivery between 1st April 1991 and 31st December 1992, were eligible and 13 761 women (contributing 13 867 pregnancies) were recruited. These women have been followed over the last 19–22 years and have completed up to 20 questionnaires, have had detailed data abstracted from their medical records and have information on any cancer diagnoses and deaths through record linkage. A follow-up assessment was completed 17–18 years postnatal at which anthropometry, blood pressure, fat, lean and bone mass and carotid intima media thickness were assessed, and a fasting blood sample taken. The second follow-up clinic, which additionally measures cognitive function, physical capability, physical activity (with accelerometer) and wrist bone architecture, is underway and two further assessments with similar measurements will take place over the next 5 years. There is a detailed biobank that includes DNA, with genome-wide data available on >10 000, stored serum and plasma taken repeatedly since pregnancy and other samples; a wide range of data on completed biospecimen assays are available. Details of how to access these data are provided in this cohort profile.

Objective

There is overlap between an autistic and hyperactive-inattentive symptomatology when studied cross-sectionally. This study is the first to examine the longitudinal pattern of association between social-communication deficits and hyperactive-inattentive symptoms in the general population, from childhood through adolescence. We explored the interrelationship between trajectories of co-occurring symptoms, and sought evidence for shared prenatal/perinatal risk factors.

Method

Study participants were 5,383 singletons of white ethnicity from the Avon Longitudinal Study of Parents and Children (ALSPAC). Multiple measurements of hyperactive-inattentive traits (Strengths and Difficulties Questionnaire) and autistic social-communication impairment (Social Communication Disorder Checklist) were obtained between 4 and 17 years. Both traits and their trajectories were modeled in parallel using latent class growth analysis (LCGA). Trajectory membership was subsequently investigated with respect to prenatal/perinatal risk factors.

Results

LCGA analysis revealed two distinct social-communication trajectories (persistently impaired versus low-risk) and four hyperactive-inattentive trait trajectories (persistently impaired, intermediate, childhood-limited and low-risk). Autistic symptoms were more stable than those of attention-deficit/hyperactivity disorder (ADHD) behaviors, which showed greater variability. Trajectories for both traits were strongly but not reciprocally interlinked, such that the majority of children with a persistent hyperactive-inattentive symptomatology also showed persistent social-communication deficits but not vice versa. Shared predictors, especially for trajectories of persistent impairment, were maternal smoking during the first trimester, which included familial effects, and a teenage pregnancy.

Conclusions

Our longitudinal study reveals that a complex relationship exists between social-communication and hyperactive-inattentive traits. Patterns of association change over time, with corresponding implications for removing exclusivity criteria for ASD and ADHD, as proposed for DSM-5.

Background

Apolipoprotein E (APOE) genotype (ε2/ε3/ε4: rs429358 ε4 allele; rs7412 ε2 allele) is strongly associated with both lipid levels and Alzheimer's disease. Although there is also evidence of milder cognitive impairment in later life in carriers of the APOE ε4 allele, there have been few studies investigating the impact of APOE genotype on cognitive function in children.

Methods

We determined APOE genotype in 5995 children from the Avon Longitudinal Study of Parents and Children and investigated associations between APOE genotype and plasma lipids (at age 9), IQ (at age 8), memory (at ages 8 and 10), and performance in school attainment tests (at ages 7, 11, and 14).

Results

Observed genotype group counts were consistent with Hardy–Weinberg equilibrium (χ2p value = .84). There were strong relationships between APOE genotype and low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides, which follow the same patterns as in adults. There was no strong evidence to suggest that APOE genotype was associated with IQ (all p values ≥ .46), memory function (p ≥ .35), or school attainment test results (p ≥ .28).

Conclusion

Although APOE genotype does have strong associations with lipid levels in childhood, there does not seem to be meaningful effects on cognitive performance, suggesting that any detrimental effects of the ε4 allele on cognitive function are not important until later life.

Aims

To assess the feasibility and reproducibility of non-invasive vascular assessment in a childhood population setting and identify the determinants of vascular phenotype in early life.

Methods and results

We studied 7557 children (age 9.8–12.3 years) participating in the Avon Longitudinal Study of Parents and Children (ALSPAC). Six research technicians underwent a 5-month training protocol to enable study of brachial artery endothelial function by flow-mediated dilatation (FMD) and arterial stiffness by carotid to radial pulse wave velocity (PWV) and brachial distensibility [distensibility coefficient (DC)]. Reproducibility studies were performed at the beginning, the middle, and the end of the study. A blinded repeat evaluation of a random selection of 3% of the cohort was also undertaken throughout the study. The effect of anthropometric and environmental factors on each measure was examined. Successful measures were obtained in 88, 95, and 87% of the studied children for FMD, PWV, and DC, respectively. The coefficients of variation between technicians for FMD, PWV, and DC were 10.5, 4.6, and 6.6% at the beginning of the study and reached 7.7, 4.1, and 10% at the end. Baseline vessel diameter and gender were important determinants of all the vascular measures, with a small effect of room and skin temperatures on FMD and PWV. Boys consistently had lower FMD and DC and higher PWV measures (P < 0.01 for all).

Conclusion

Reproducible, high-quality assessments of vascular structure and function in children can be made on a large scale in field studies by suitably trained non-specialist operators. This study provides an invaluable resource for assessing the impact of early influences, genetic, and environmental factors on arterial phenotype.

Objective

Recent genome-wide analysis identified a genetic variant on 5p14.1 (rs4307059), which is associated with risk for autism spectrum disorder. This study investigated whether rs4307059 also operates as a quantitative trait locus underlying a broader autism phenotype in the general population, focusing specifically on the social communication aspect of the spectrum.

Method

Study participants were 7,313 children from the Avon Longitudinal Study of Parents and Children. Single-trait and joint-trait genotype associations were investigated for 29 measures related to language and communication, verbal intelligence, social interaction, and behavioral adjustment, assessed between ages 3 and 12 years. Analyses were performed in one-sided or directed mode and adjusted for multiple testing, trait interrelatedness, and random genotype dropout.

Results

Single phenotype analyses showed that an increased load of rs4307059 risk allele is associated with stereotyped conversation and lower pragmatic communication skills, as measured by the Children's Communication Checklist (at a mean age of 9.7 years). In addition a trend toward a higher frequency of identification of special educational needs (at a mean age of 11.8 years) was observed. Variation at rs4307059 was also associated with the phenotypic profile of studied traits. This joint signal was fully explained neither by single-trait associations nor by overall behavioral adjustment problems but suggested a combined effect, which manifested through multiple subthreshold social, communicative, and cognitive impairments.

Conclusions

Our results suggest that common variation at 5p14.1 is associated with social communication spectrum phenotypes in the general population and support the role of rs4307059 as a quantitative trait locus for autism spectrum disorder.

The timing of puberty is highly variable1. We carried out a genome-wide association study for age at menarche in 4,714 women and report an association in LIN28B on chromosome 6 (rs314276, minor allele frequency (MAF) = 0.33, P = 1.5 × 10−8). In independent replication studies in 16,373 women, each major allele was associated with 0.12 years earlier menarche (95% CI = 0.08–0.16; P = 2.8 × 10−10; combined P = 3.6 × 10−16). This allele was also associated with earlier breast development in girls (P = 0.001; N = 4,271); earlier voice breaking (P = 0.006, N = 1,026) and more advanced pubic hair development in boys (P = 0.01; N = 4,588); a faster tempo of height growth in girls (P = 0.00008; N = 4,271) and boys (P = 0.03; N = 4,588); and shorter adult height in women (P = 3.6 × 10−7; N = 17,274) and men (P = 0.006; N = 9,840) in keeping with earlier growth cessation. These studies identify variation in LIN28B, a potent and specific regulator of microRNA processing2, as the first genetic determinant regulating the timing of human pubertal growth and development.

Background

It is increasingly recognised that traits associated with autism reflect a spectrum with no clear boundary between typical and atypical behaviour. Dimensional traits are needed to investigate the broader autism phenotype.

Methods and Principal Findings

Ninety-three individual measures reflecting components of social, communication and repetitive behaviours characterising autistic spectrum disorder (ASD) were identified between the ages of 6 months and 9 years from the ALSPAC database. Using missing value imputation, data for 13,138 children were analysed. Factor analysis suggested the existence of 7 factors explaining 85% of the variance. The factors were labelled: verbal ability, language acquisition, social understanding, semantic-pragmatic skills, repetitive-stereotyped behaviour, articulation and social inhibition. Four factors (1, 3, 5 and 7) were specific to ASD being more strongly associated with this phenotype than other co-morbid conditions while other factors were more associated with learning difficulties and specific language impairment. Nevertheless, all 7 factors contributed independently to the explanation of ASD (p<0.001). Exploration of putative genetic causal factors such as variants in the CNTNAP2 gene showed a varying pattern of associations with these traits. An alternative predictive model of ASD was derived using four individual measures: the coherence subscale of the Children's Communication Checklist (9y), the Social and Communication Disorders Checklist (91 m), repetitive behaviour (69 m) and the sociability subscale of the Emotionality Activity and Sociability measure (38 m). Although univarably these traits performed better than some factors, their combined explanations of ASD were similar (R2 = 0.48).

Conclusions and Significance

These results support the fractional nature of ASD with different aetiological origins for these components despite pleiotropic genetic effects being observed. These traits are likely to be useful in the exploration of ASD.

Background

Breastfeeding is important for child cognitive development. A study by Caspi et al has suggested that rs174575 within the FADS2 gene moderates this effect so that children homozygous in the minor allele (GG genotype) have similar IQs irrespective of feeding method.

Methods and Principal Findings

In our study of 5934 children aged 8 years, no genetic main effect with IQ was found for rs174575. However, an interaction with this polymorphism was observed such that breastfed GG children performed better than their formula fed counterparts by an additional 5.8 points [1.4, 10.1] (interaction p = 0.0091). Interaction results were attenuated by about 10% after adjustment for 7 factors. This study also investigated rs1535, another FADS2 polymorphism in linkage disequilibrium with rs174575, together with performance and verbal IQ, finding similar results although effect sizes were generally reduced.

Conclusions and Significance

This study did not replicate the findings of Caspi et al. In contrast to their study, GG children exhibited the greatest difference between feeding methods such that breastfed children performed similarly irrespective of child genotype whereas formula fed GG children performed worse than other children on formula milk. Further studies are required to replicate these findings.

Data from the Avon Longitudinal Study of Parents and Children were used to describe initiation of secondary sexual characteristic development of girls. Tanner stages of breast and pubic hair and menarche status were self-reported via mailed questionnaires, administered from ages 8–14. Initiation pathway was categorized as breast [thelarche] or pubic hair [pubarche] development alone, or synchronous. Average ages at beginning breast and pubic hair development were estimated using survival analysis. Factors associated with initiation pathway were assessed using logistic regression. Among the 3938 participants, the median ages at beginning breast and pubic hair development were 10.19 (95% CI: 10.14–10.24) and 10.95 (95% CI: 10.90–11.00) years. Synchronous initiation was the most commonly reported pathway (46.3%), followed by thelarche (42.1%). Girls in the pubarche pathway were less likely to be obese or overweight at age 8 or have an overweight or obese mother. Girls in the thelarche pathway were less likely to be of nonwhite race or be the third born or later child.

The potential relationship between daily physical activity and pregnancy outcome remains unclear because of the wide variation in study designs and physical activity assessment measures. We sought to prospectively quantify the potential effects of the various domains of physical activity on selected birth outcomes in a large unselected population. The sample consisted of 11,759 singleton pregnancies from the Avon longitudinal study of parents and children, United Kingdom. Information on daily physical activity was collected by postal questionnaire for self-report measures. Main outcome measures were birth weight, gestational age at delivery, preterm birth and survival. After controlling for confounders, a sedentary lifestyle and paid work during the second trimester of pregnancy were found to be associated with a lower birth weight, while ‘bending and stooping’ and ‘working night shifts’ were associated with a higher birth weight. There was no association between physical exertion and duration of gestation or survival. Repetitive boring tasks during the first trimester was weakly associated with an increased risk of preterm birth (<37 weeks) (adjusted odds ratio [OR] = 1.25, 95% CI 1.04–1.50). ‘Bending and stooping’ during the third trimester was associated with a reduced risk of preterm birth (adjusted OR = 0.73, 95% CI 0.63–0.84). Demanding physical activities do not have a harmful effect on the selected birth outcomes while a sedentary lifestyle is associated with a lower birth weight. In the absence of either medical or obstetric complications, pregnant women may safely continue their normal daily physical activities should they wish to do so.

Background

A number of studies have assessed ages of parents of children with autistic spectrum disorders (ASD), and reported both maternal and paternal age effects. Here we assess relationships with grandparental ages.

Methods and Findings

We compared the parental and grandparental ages of children in the population-based Avon Longitudinal Study of Parents and Children (ALSPAC), according to their scores in regard to 4 autistic trait measures and whether they had been given a diagnosis of ASD. Mean maternal and paternal ages of ASD cases were raised, but this appears to be secondary to a maternal grandmother age effect (P = 0.006): OR = 1.66[95%CI 1.16, 2.37] for each 10-year increase in the grandmother's age at the birth of the mother. Trait measures also revealed an association between the maternal grandmother's age and the major autistic trait–the Coherence Scale (regression coefficient b = 0.142, [95%CI = 0.057, 0.228]P = 0.001). After allowing for confounders the effect size increased to b = 0.217[95%CI 0.125, 0.308](P<0.001) for each 10 year increase in age.

Conclusions

Although the relationship between maternal grandmother's age and ASD and a major autistic trait was unexpected, there is some biological plausibility, for the maternal side at least, given that the timing of female meiosis I permits direct effects on the grandchild's genome during the grandmother's pregnancy. An alternative explanation is the meiotic mismatch methylation (3 M) hypothesis, presented here for the first time. Nevertheless the findings should be treated as hypothesis generating pending corroborative results from other studies.

Making sense of rapidly evolving evidence on genetic associations is crucial to making genuine advances in human genomics and the eventual integration of this information in the practice of medicine and public health. Assessment of the strengths and weaknesses of this evidence, and hence the ability to synthesize it, has been limited by inadequate reporting of results. The STrengthening the REporting of Genetic Association studies (STREGA) initiative builds on the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement and provides additions to 12 of the 22 items on the STROBE checklist. The additions concern population stratification, genotyping errors, modeling haplotype variation, Hardy–Weinberg equilibrium, replication, selection of participants, rationale for choice of genes and variants, treatment effects in studying quantitative traits, statistical methods, relatedness, reporting of descriptive and outcome data, and the volume of data issues that are important to consider in genetic association studies. The STREGA recommendations do not prescribe or dictate how a genetic association study should be designed but seek to enhance the transparency of its reporting, regardless of choices made during design, conduct, or analysis.

The goal of this study is to investigate the relationship between the Val66Met polymorphism in the brain-derived neurotrophic factor (BDNF) and body mass index (BMI) in two sizable and well-characterized populations of British women: the British Women's Heart and Health Study (BWHHS) (age 60–79 years) and the mothers from the Avon Longitudinal Study of Parents and Children (age 16–44 years). We genotyped the Val66Met polymorphism (rs6265) in these two populations, and conducted a linear regression analysis to test for an association between this polymorphism and BMI. Both study populations indicated an association between BMI and the Val66Met polymorphism, with individuals carrying the Met–Met genotype having a lower mean BMI than those with the Val–Met or Val–Val genotypes (in the BWHHS): mean BMI difference=−0.911 kg/m2, 95% confidence interval (CI): −1.70 to −0.12, P=0.023; in the mothers from the Avon Longitudinal Study of Parents and Children (ALSPAC): mean BMI difference=−0.57 kg/m2, 95%CI: −1.08 to −0.054, P=0.03). In a pooled analysis of these two studies, together with one further published study that provided data in a suitable format for inclusion in our meta-analysis, we found a pooled difference of −0.76 (95% CI: −1.16, −0.036) for adult women; I2–test for heterogeneity=51%, P=0.13. Our study indicated an association between BDNF and BMI in two general population studies of women. The exact role of BDNF in weight regulation merits further investigation.

Background

Depression is a prevalent health problem among women during the childbearing years. To obtain a more accurate global picture of maternal postnatal depression, studies that explore maternal depression with comparable measurements are needed. The aims of the study are: (1) to compare the prevalence of maternal depression in the first and second year postpartum between a UK and Brazilian birth cohort study; (2) to explore the extent to which variations in the rates were explained by maternal and infant characteristics, and (3) to investigate income-related inequalities in maternal depression after childbirth in both settings.

Methods

Population-based birth cohort studies were carried out in Avon, UK in 1991 (ALSPAC) and in the city of Pelotas, Brazil in 2004, where 13 798 and 4109 women were analysed, respectively. Self-completion questionnaires were used in the ALSPAC study while questionnaires completed by interviewers were used in the Pelotas cohort study. Three repeated measures of maternal depression were obtained using the Edinburgh Postnatal Depression Scale in the first and second year after delivery in each cohort. Unadjusted and adjusted analyses were carried out. The Relative index of Inequality was used for the analysis of income-relate inequalities so that results were comparable between cohorts.

Results

At both the second and third time assessments, the likelihood of being depressed was higher among women from the Pelotas cohort study. These differences were not completely explained by differences in maternal and infant characteristics. Income-related inequalities in maternal depression after childbirth were high and of similar magnitude in both cohort studies at the three time assessments.

Conclusion

The burden of maternal depression after childbirth varies between and within populations. Strategies to reduce income-related inequalities in maternal depression should be targeted to low-income women in both developed and developing countries.

Background

Developed and developing countries are facing rapid increases in overweight and obesity among children and adolescents. The patterns of overweight/obesity differ by age, sex, rural or urban residence and socioeconomic position (SEP) and vary between and within countries.

Methods

We investigated patterns of SEP – overweight status association among adolescents from the UK (ALSPAC) and Brazil (the 1982 and 1993 Pelotas birth cohort studies).

All analyses were performed separately for males and females. Logistic regression analysis was used to examine the relationships between overweight status and two SEP indicators – family income and maternal education.

Results

A strong positive association was observed in 11-year-old boys from the 1993 Pelotas cohort, with higher prevalence of overweight among the least poor and among those whose mothers had more years of schooling (x2 for linear trend p < 0.001). In ALSPAC study higher prevalence of overweight was seen among boys whose mothers had lower educational achievement (x2 for linear trend p = 0.006). Among 11 year-old girls from 1993 Pelotas cohort study there was a positive association (higher prevalence of overweight in the higher socioeconomic and educational strata, x2 for linear trend p < 0.001 and p = 0.01, respectively) while an inverse association was found in the ALSPAC study (x2 for linear trend p < 0.001). Among males from the 1982 cohort study, overweight at 18 years of age showed a positive association with both SEP indicators while among females, the reverse association was found.

Conclusion

The results of this study demonstrate that the social patterning of overweight varies between and within populations over time. Specific approaches should be developed within populations in order to contain the obesity epidemic and reduce disparities.

Julian Little and colleagues present the STREGA recommendations, which are aimed at improving the reporting of genetic association studies.

Background

Early menarche tends to be preceded by rapid infancy weight gain and is associated with increased childhood and adult obesity risk. As age at menarche is a heritable trait, we hypothesised that age at menarche in the mother may in turn predict her children's early growth and obesity risk.

Methods and Findings

We tested associations between mother's age at menarche, mother's adult body size and obesity risk, and her children's growth and obesity risk in 6,009 children from the UK population-based Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort who had growth and fat mass at age 9 y measured by dual-energy X-ray absorptiometry. A subgroup of 914 children also had detailed infancy and childhood growth data. In the mothers, earlier menarche was associated with shorter adult height (by 0.64 cm/y), increased weight (0.92 kg/y), and body mass index (BMI, 0.51 kg/m2/y; all p < 0.001). In contrast, in her children, earlier mother's menarche predicted taller height at 9 y (by 0.41 cm/y) and greater weight (0.80 kg/y), BMI (0.29 kg/m2/y), and fat mass index (0.22 kg/m2/year; all p < 0.001). Children in the earliest mother's menarche quintile (≤11 y) were more obese than the oldest quintile (≥15 y) (OR, 2.15, 95% CI 1.46 to 3.17; p < 0.001, adjusted for mother's education and BMI). In the subgroup, children in the earliest quintile showed faster gains in weight (p < 0.001) and height (p < 0.001) only from birth to 2 y, but not from 2 to 9 y (p = 0.3–0.8).

Conclusions

Earlier age at menarche may be a transgenerational marker of a faster growth tempo, characterised by rapid weight gain and growth, particularly during infancy, and leading to taller childhood stature, but likely earlier maturation and therefore shorter adult stature. This growth pattern confers increased childhood and adult obesity risks.

Earlier age at menarche may be a transgenerational marker of faster growth, particularly during infancy, leading to taller childhood stature but earlier maturation and hence shorter adult stature.

Editors' Summary

Background.

Childhood obesity is a rapidly growing problem. Twenty-five years ago, overweight children were rare. Now, 155 million of the world's children are overweight and 30–45 million are obese. Overweight and obese children—those having a higher than average body mass index (BMI; weight divided by height squared) for their age and sex—are at increased risk of becoming obese adults. Such people are more likely to develop heart disease, diabetes, and other health problems than lean people. Many factors are involved in the burgeoning size of children. Parental obesity, for example, predisposes children to being overweight. In part, this is because parents influence the eating habits of their offspring and the amount of exercise they do. In addition, though, children inherit genetic factors from their parents that make them more likely to put on weight.

Why Was This Study Done?

To prevent childhood obesity, health care professionals need ways to predict which infants are likely to become obese so that they can give parents advice on controlling their children's weight. In girls, early menarche (the start of menstruation) is associated with an increased risk of childhood and adult obesity and tends to be preceded by rapid weight gain in the first two years of life. Because age at menarche is inherited, the researchers in this study have investigated whether mothers' age at menarche predicts rapid growth in infancy and childhood obesity in their offspring using data from the Avon Longitudinal Study of Parents and Children (ALSPAC). In 1991–1992, this study recruited nearly 14,000 children born in Bristol, UK. Since then, the children have been regularly examined to investigate how their environment and genetic inheritance interact to affect their health.

What Did the Researchers Do and Find?

The researchers measured the growth and fat mass of 6,009 children from ALSPAC at 9 years of age. For 914 of these children, the researchers had detailed data on their growth during infancy and early childhood. They then looked for any associations between the mother's age at menarche (as recalled during pregnancy), mother's adult body size, and the children's growth and obesity risk. In the mothers, earlier menarche was associated with shorter adult height and increased weight and BMI. In the children, those whose mothers had earlier menarche were taller and heavier than those whose mothers had a later menarche. They also had a higher BMI and more body fat. The children whose mothers had their first period before they were 11 were twice as likely to be obese as those whose mothers did not menstruate until they were 15 or older. Finally, for the children with detailed early growth data, those whose mothers had the earliest menarche had faster weight and height gains in the first two years of life (but not in the next seven years) than those whose mothers had the latest menarche.

What Do These Findings Mean?

These findings indicate that earlier mother's menarche predicts a faster growth tempo (the speed at which an individual reaches their adult height) in their offspring, which is characterized by rapid weight and height gain during infancy. This faster growth tempo leads to taller childhood stature, earlier sexual maturity, and—because age at puberty determines adult height—shorter adult stature. An inherited growth pattern like this, the researchers write, confers an increased risk of childhood and adult obesity. As with all studies that look for associations between different measurements, these findings will be affected by the accuracy of the measurements—for example, how well the mothers recalled their age at menarche. Furthermore, because puberty, particularly in girls, is associated with an increase in body fat, a high BMI at age nine might indicate imminent puberty rather than a risk of long-standing obesity—further follow-up studies will clarify this point. Nevertheless, the current findings provide a new factor—earlier mother's menarche—that could help health care professionals identify which infants require early growth monitoring to avoid later obesity.

Additional Information.

Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0040132.

The Avon Longitudinal Study of Parents and Children has a description of the study and results to date

The US Centers for Disease Control and Prevention provides information on overweight and obesity (in English and Spanish)

US Department of Health and Human Services's program, Smallstep Kids, is an interactive site for children about healthy eating (in English and Spanish)

The International Obesity Taskforce has information on obesity and its prevention

The World Heart Federation's Global Prevention Alliance provides details of international efforts to halt the obesity epidemic and its associated chronic diseases

The Child Growth Foundation has information on childhood growth and its measurement

Objective

To follow mothers' mood through pregnancy and after childbirth and compare reported symptoms of depression at each stage.

Design

Longitudinal cohort study.

Setting

Avon.

Participants

Pregnant women resident within Avon with an expected date of delivery between 1 April 1991 and 31 December 1992.

Main outcome measures

Symptom scores from the Edinburgh postnatal depression scale at 18 and 32 weeks of pregnancy and 8 weeks and 8 months postpartum. Proportion of women above a threshold indicating probable depressive disorder.

Results

Depression scores were higher at 32 weeks of pregnancy than 8 weeks postpartum (difference in means 0.88, 95% confidence interval 0.79 to 0.97). There was no difference in the distribution of total scores or scores for individual items at the four time points. 1222 (13.5%) women scored above threshold for probable depression at 32 weeks of pregnancy, 821 (9.1%) at 8 weeks postpartum, and 147 (1.6%) throughout. More mothers moved above the threshold for depression between 18 weeks and 32 weeks of pregnancy than between 32 weeks of pregnancy and 8 weeks postpartum.

Conclusions

Symptoms of depression are not more common or severe after childbirth than during pregnancy. Research and clinical efforts need to be moved towards understanding, recognising, and treating antenatal depression.

Objectives

To investigate whether the accelerated immunisation programme in the United Kingdom is associated, after adjustment for potential confounding, with the sudden infant death syndrome.

Design

Population based case-control study, February 1993 to March 1996. Parental interviews were conducted for each death and for four controls matched for age, locality, and time of sleep. Immunisation status was taken from records held by the parents.

Setting

Five regions in England with a combined population of over 17 million.

Subjects

Immunisation details were available for 93% (303/325) of infants whose deaths were attributed to the sudden infant death syndrome (SIDS); 90% (65/72) of infants with explained sudden deaths; and 95% (1515/1588) of controls.

Results

After all potential confounding factors were controlled for, immunisation uptake was strongly associated with a lower risk of SIDS (odds ratio 0.45 (95% confidence interval 0.24 to 0.85)). This difference became non-significant (0.67 (0.31 to 1.43)) after further adjustment for other factors specific to the infant's sleeping environment. Similar proportions of SIDS deaths and reference sleeps (corresponding to the time of day during which the index baby had died) among the controls occurred within 48 hours of the last vaccination (5% (7/149) v 5% (41/822)) and within two weeks (21% (31/149) v 27% (224/822)). No longer term temporal association with immunisation was found (P=0.78). Of the SIDS infants who died within two weeks of vaccination, 16% (5/31) had signs and symptoms of illness that suggested that medical contact was required, compared with 26% (16/61) of the non-immunised SIDS infants of similar age. The findings for the infants who died suddenly and unexpectedly but of explained causes mirrored those for SIDS infants.

Conclusions

Immunisation does not lead to sudden unexpected death in infancy, and the direction of the relation is towards protection rather than risk.

What is already known on this topicSome studies have suggested a link between the sudden infant death syndrome and primary immunisation, but most have failed to show a linkPotential bias in the studies includes lack of a comparative control group with similar low immunisation uptake and misclassification of cause of deathWhat this study addsThis study investigated explained sudden infant deaths as well as the sudden infant death syndrome and took into account potential biasAfter confounding was controlled for, immunisation uptake was lowest among the infants who died, with no temporal relation or correlation with signs and symptoms of illness