Avon Longitudinal Study Of Parents And Children Research Articles

Parental and child genetic burden of glycaemic dysregulation and early-life cognitive development: an Asian and European prospective cohort study

Insulin resistance and glucose metabolism have been associated with neurodevelopmental disorders. However, in the metabolically more susceptible Asian populations, it is not clear whether the genetic burden of glycaemic dysregulation influences early-life neurodevelopment. In a multi-ethnic Asian prospective cohort study in Singapore (Growing Up in Singapore Towards healthy Outcomes (GUSTO)), we constructed child and parental polygenic risk scores (PRS) for glycaemic dysregulation based on the largest genome-wide association studies of type 2 diabetes and fasting glucose among Asians. We found that child PRS for HOMA-IR was associated with a lower perceptual reasoning score at ~7 years (β = −0. 141, p-value = 0.024, 95% CI −0. 264 to −0. 018) and a lower WIAT-III mean score at ~9 years (β = −0.222, p-value = 0.001, 95% CI −0.357 to −0.087). This association were consistent in direction among boys and girls. These inverse associations were not influenced by parental PRS and were likely mediated via insulin resistance rather than mediators such as birth weight and childhood body mass index. Higher paternal PRS for HOMA-IR was suggestively associated with lower child perceptual reasoning at ~7 years (β = −0.172, p-value = 0.002, 95% CI −0.280 to −0.064). Replication analysis in a European cohort, the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort, showed that higher child PRS for fasting glucose was associated with lower verbal IQ score while higher maternal PRS for insulin resistance was associated with lower performance IQ score in their children at ~8.5 years. In summary, our findings suggest that higher child PRS for HOMA-IR was associated with lower cognitive scores in both Asian and European replication cohorts. Differential findings between cohorts may be attributed to genetic and environmental factors. Further investigation of the functions of the genetic structure and ancestry-specific PRS and a more comprehensive investigation of behavioural mediators may help to understand these findings better.

The dietary approaches to stop hypertension (DASH) dietary pattern in childhood in relation to cardiometabolic risk in adolescence and early adulthood in the ALSPAC birth cohort.

To investigate the relationship between the dietary approaches to stop hypertension (DASH)-style dietary patterns in childhood and cardiometabolic risk (CMR) in adolescence/early adulthood. Data were obtained from the Avon Longitudinal Study of Parents and Children (ALSPAC) prospective cohort. Diet diary data collected at 7, 10 and 13 years were used to calculate DASH-style diet scores (DDS). Multivariable linear regression models were used to investigate the associations between the DDS at 7, 10 and 13 years and CMR scores, calculated at 17 and 24 years. The ALSPAC cohort included children born in south-west England in 1991-1992. Children with complete dietary, covariate and cardiometabolic data at 17 (n 1,526) and 24 years (n 1,524). A higher DDS at 7 and 10 years was negatively associated with CMR scores at 17 years (β = -0·64 (95 % CI -1·27, -0·006), Ptrend=0·027 for fifth v. first DDS quintile at 7 years; β = -0·73 (95 % CI -1·35, -0·12) and Ptrend=0·037 for fifth v. first DDS quintile at 10 years) and at 24 years (β = -0·92 (95 % CI -1·49, -0·34) Ptrend = 0·001 for fifth v. first DDS quintile at 7 years; β = -0·60 (95 % CI -1·20, -0·05) Ptrend = 0·092 for fifth v. first DDS quintile at 10 years). No associations were found between the DDS at 13 years and CMR score at 17 and 24 years. Greater adherence with a DASH-style diet during childhood was associated with better cardiometabolic health in adolescence/adulthood in the ALSPAC cohort. The components of the DASH diet could be recommended to improve children's cardiometabolic health.

Demographic and socioeconomic predictors of religious/spiritual beliefs and behaviours in a prospective cohort study (ALSPAC) in Southwest England: Results from the offspring generation.

We explored associations between possible demographic and socioeconomic causes of religious/spiritual beliefs and behaviours (RSBB) in the offspring generation of the Avon Longitudinal Study of Parents and Children (ALSPAC). We examined approximately 4,450 offspring aged 28 years with RSBB data from a prospective birth cohort study (ALSPAC) in Southwest England. Three RSBB outcome measures were assessed: religious belief (belief in God/a divine power; yes/not sure/no), religious affiliation (Christian/none/other) and religious attendance (frequency of attendance at a place of worship). We explored age- and sex-adjusted associations between 35 demographic and socioeconomic exposures and each of the three RSBB outcomes using multinomial regression. Exposure-sex interactions were also examined. Some sociodemographic factors were associated with RSBB in this cohort; for instance, being female and from an ethnicity other than White were associated with increased religiosity across all domains. For many other exposures, however, associations were frequently null or inconsistent, often depending on the specific exposure and outcome combination. As an example, higher educational attainment was associated with higher rates of religious attendance, but not with religious belief or affiliation; in contrast, higher income was associated with lower levels of religiosity. No consistent interactions between sex and the exposures on RSBB were found. Effect sizes were also rather weak, with most pseudo- R 2 values below 0.5% and a maximum of 1.2%. The results highlight that several demographic and socioeconomic factors are associated with RSBB in this cohort. However, the number of these associations, and their magnitude, is smaller than comparable results from the parental generation of these offspring, suggesting that patterns of sociodemographic factors associated with RSBB differ between these generations. In addition to describing these associations, this paper will help inform future studies using these data, particularly regarding the choice of potential sociodemographic confounders.

Increasing lipids with risk of worsening cardiac damage in 1595 adolescents: A 7-year longitudinal and mediation study

Background and aimsLongitudinal evidence on the associations of changes in lipids level with changes in cardiac structure and function in youth is limited due to few repeated echocardiography measures. This study examined whether changes in lipid levels from adolescence through young adulthood associate with the risk of cardiac damage progression and potential mechanistic pathways. MethodsFrom the Avon Longitudinal Study of Parents and Children (ALSPAC), UK birth cohort, 1595 adolescents aged 17 years who had fasting plasma total cholesterol, triglyceride, high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), and non-HDL-c measured at 17- and 24-year clinic visit were included. Echocardiography measured left ventricular mass indexed for height2.7 (LVMI2.7), and LV diastolic function from mitral E/A ratio (LVDF). LVMI2.7 ≥51 g/m2.7 and LVDF<1.5 were categorized as LV hypertrophy and LVD dysfunction, respectively. Multivariable adjusted associations were examined using generalized logit mixed-effect models and structural equation models for mediation analyses. ResultsThe prevalence of LV hypertrophy increased from 3.6% at baseline to 11.6% at follow-up in males and increased from 1.6% to 4.0% in females. The prevalence of LVD dysfunction increased from 7.8% at baseline to 16.6% at follow-up in males and increased from 10.3% to 15.4% in females. Each 1 mmol increase in total cholesterol (OR, 1.18; [95% CI, 1.09–1.27]), triglyceride (2.89; [1.54–5.43]), LDL-c (1.19; [1.08–1.32]), and non-HDL-c (1.21; [1.11–1.33]) was associated with higher odds of worsening LV hypertrophy progression over 7 years. Increased triglyceride was associated with the odds of progressively worsening LVD dysfunction (1.98; [1.06–3.71]). Increased HDL-c was not associated with the odds of cardiac structural and functional damage. Systolic blood pressure (12% mediation) and fat mass (25% mediation) partly mediated the associations of LDL-c with increased LVMI2.7. ConclusionsIncreased lipids may independently associate with the risk of progressively worsening structural and functional cardiac damage in youth but increased systolic blood pressure and fat mass explained circa forty percent of the relationship.

Prenatal Exposure to Androgens and Gender Socialisation Effects on Children’s Academic Interests

Previous studies have documented gender differences in fields of study as well as interest in school subjects. Boys are on average more interested in mathematics, and girls show greater interest in languages. The extent to which these disparities are the result of biological or environment influences is still an open debate. On the one hand, brain organisation theory suggests that physiological and behavioural differences may be linked to prenatal hormone levels. On the other hand, sociological and psychological perspectives highlight the importance of gender socialisation. This paper combines biological, psychological, and sociological perspectives to examine the emergence of gendered academic interests in children.The study draws on data from 9‑year-old children from the Avon Longitudinal Study of Parents and Children (ALSPAC). Our results suggest that for both boys and girls, medium to high compared with low prenatal exposure to circulating maternal testosterone might increase children’s interests in mathematics relative to English, although results vary depending on how prenatal testosterone exposure is measured. As the distributions of prenatal androgen exposure and the relationships with maths versus English interests are very similar for boys and girls, prenatal androgen exposure does not contribute to explaining gender differences in academic interests. However, we find some evidence that the relationship with parental gender socialisation varies by prenatal androgen exposure. A more gender-equal parental division of domestic work is more strongly associated with less gendered academic interests for girls with low prenatal androgen exposure and for boys with medium to high androgen exposure.

Environmental and genetic predictors of whole blood mercury and selenium concentrations in pregnant women in a UK birth cohort

There is evidence that tissue concentrations of mercury (Hg) and selenium (Se) are predicted by numerous dietary, sociodemographic, environmental, and genetic factors. This study aimed to estimate the relative importance of predictors of Hg and Se concentrations in blood samples taken from pregnant women. The Avon Longitudinal Study of Parents and Children (ALSPAC) in the UK measured whole blood Hg and Se concentrations in 3,972 pregnant women. We identified 30 potential predictors of Hg and 24 of Se, which were evaluated using cross-validated random forests to identify the optimal models for predictive power. The relative importance of individual variables was estimated by averaging the added-R2 per predictor. Linkage disequilibrium score regression was used to estimate the variance explained by genotype. A multivariable model of 14 predictors explained 22.4% of Hg variance (95% CI: 13.0 to 37.1), including 6.9% from blood Se and 3.2% from white fish consumption. There were 11 predictors which explained 15.3% of Se variance (CI: 8.9 to 25.9), including 6.4% from blood Hg, 1.3% from blood lead, and 1.3% from oily fish. Measured genetic variation explained 30% of Hg variance (CI: 8.4 to 51.5) and 37.5% of Se (CI: 10.4 to 64.5). A high proportion of Hg and Se variance could be explained from dietary, sociodemographic, metabolic, and genetic factors. Seafood consumption was less predictive of Hg than may be expected and other factors should be considered when determining risk of exposure. There was tentative evidence that genotype is a major contributor to Hg and Se variation, possibly by modifying the efficacy of internal metabolism.

Prevalence and recurrence of pica behaviors in early childhood within the ALSPAC birth cohort.

The present study examined prevalence and correlates of pica behaviors during childhood using data from the Avon Longitudinal Study of Parents and Children (ALSPAC) study. Data on 10,109 caregivers from the ALSPAC study who reported pica behavior at 36, 54, 65, 77, and 115 months on their child were included. Autism was obtained through clinical and education records, while DD was derived from the Denver Developmental Screening Test. A total of 312 parents (3.08%) reported pica behaviors in their child. Of these, 19.55% reported pica at least at two waves (n = 61). Pica was most common at 36 months (N = 226; 2.29%) and decreased as children aged. A significant association was found between pica and autism at all five waves (p < .001). There was a significant relationship between pica and DD, with individuals with DD more likely to experience pica than those without DD at 36 (p = .01), and 54 (p < .001), 65 (p = .04), 77 (p < .001), and 115 months (p = .006). Exploratory analyses examined pica behaviors with broader eating difficulties and child body mass index. This study enhances understanding of childhood pica behaviors, addressing a significant gap in knowledge. Pica occurrence in the general population is poorly understood due to few epidemiological studies. Findings from the present study indicate pica is an uncommon behavior in childhood; however, children with DD or autism may benefit from pica screening and diagnosis between ages 36 and 115 months. Children who exhibit undereating, overeating, and food fussiness may also engage in pica behaviors.

Associations of Sedentary Time and Physical Activity From Childhood With Lipids: A 13-Year Mediation and Temporal Study.

Among children, evidence on long-term longitudinal associations of accelerometer-measured sedentary time, light physical activity (LPA), and moderate to vigorous PA (MVPA) with lipid indices are few. The mediating role of body composition and other metabolic indices in these associations remains unclear and whether poor movement behavior precedes altered lipid levels is unknown. This study examined the associations of sedentary time, LPA, and MVPA from childhood through young adulthood with increased lipids, the mediating role of body composition, and whether temporal interrelations exist. Data from 792 children (58% female; mean [SD] age at baseline, 11.7 [0.2] years), drawn from the Avon Longitudinal Study of Parents and Children (ALSPAC) UK birth cohort, who had at least 2 time-point measures of accelerometer-based sedentary time, LPA, and MVPA during clinic visits at ages 11, 15, and 24 years and complete fasting plasma high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride, and total cholesterol measured during follow-up visits at ages 15, 17, and 24 years were analyzed. Total fat mass partly mediated the inverse associations of LPA with low-density lipoprotein cholesterol by 13%, triglyceride by 28%, and total cholesterol by 6%. Total fat mass mediated the inverse associations of MVPA with low-density lipoprotein cholesterol by 37% and total cholesterol by 48%, attenuating the effect on total cholesterol to nonsignificance (P = .077). In the temporal path analyses, higher MVPA at age 15 years was associated with lower low-density lipoprotein cholesterol at 24 years (β = -0.08, SE, 0.01, P = .022) but not vice versa. Sedentary time worsens lipid indices, but increased LPA had a 5- to 8-fold total cholesterol-lowering effect and was more resistant to the attenuating effect of fat mass than MVPA.

The impact of routines on emotional and behavioural difficulties in children and on parental anxiety during COVID-19

BackgroundThe Covid-19 pandemic and related public health measures, including lockdowns and school closures, have impacted on mental health of children.Aims and hypothesisWe hypothesised that there would be an association between maintaining a routine during lockdown and both lower emotional and behavioural difficulties in children and lower parental anxiety. Routine was taken as keeping to the same basic activities such as mealtimes and bedtimes. We also hypothesised that children of ‘keyworker’ parents would have fewer emotional and behavioural symptoms due to having maintained more normal routines. The key reason was that children of keyworkers still attended school or nursery and parents would have been getting up and coming home at the same times as pre-Covid. Keyworker status was defined as those whose work was essential to Covid-19 response, including work in health and social care and other key sectors.MethodsWe used data from the Avon Longitudinal Study of Parents and Children (ALSPAC) to explore associations between maintaining a routine, and emotional and behavioural difficulties in children, using linear regression models. All eligible ALSPAC-G2 participants were sent the survey and the responders are representative of the eligible G2 population. We included measures of parental anxiety. We separately explored associations with having a keyworker parent. We used the Carey Infant Temperament Questionnaire and the Revised Rutter Parent Scale for Preschool Children to establish levels of emotional and behavioural difficulties. The measures were chosen to match previous waves in multi-generations in ALSPAC where they had been shown to be predictive of later mental health in children. The scales measure emotional and behavioural problems.ResultsTwo hundred eighty-nine parents completed questionnaires about their 411 children. Keeping a routine was associated with emotional and behavioural difficulty scores 5.0 points lower (95% CI −10.0 to −0.1), p = 0.045 than not keeping a routine. Parents who reported keeping a routine had anxiety scores 4.3 points lower (95% CI −7.5 to −1.1), p = 0.009 than those who did not. Children of keyworkers tended to have lower emotional and behavioural difficulty scores [−3.1 (95%CI −6.26 to 0.08), p = 0.056] than children of non-keyworkers. All models were adjusted for relevant potential confounders.ConclusionMaintaining a routine may be beneficial for both child emotional wellbeing and parental anxiety, although it is also possible that lower parental anxiety levels made maintaining a routine easier. Being the child of a keyworker parent during lockdown may have been protective for child emotional wellbeing.

Effects of accelerometer-based sedentary time and physical activity on DEXA-measured fat mass in 6059 children

Globally, childhood obesity is on the rise and the effect of objectively measured movement behaviour on body composition remains unclear. Longitudinal and causal mediation relationships of accelerometer-based sedentary time (ST), light physical activity (LPA), and moderate-to-vigorous physical activity (MVPA) with dual-energy X-ray absorptiometry-measured fat mass were examined in 6059 children aged 11 years followed-up until age 24 years from the Avon Longitudinal Study of Parents and Children (ALSPAC), UK birth cohort. Over 13-year follow-up, each minute/day of ST was associated with 1.3 g increase in fat mass. However, each minute/day of LPA was associated with 3.6 g decrease in fat mass and each minute/day of MVPA was associated with 1.3 g decrease in fat mass. Persistently accruing ≥60 min/day of MVPA was associated with 2.8 g decrease in fat mass per each minute/day of MVPA, partly mediated by decrease insulin and low-density lipoprotein cholesterol. LPA elicited similar and potentially stronger fat mass-lowering effect than MVPA and thus may be targeted in obesity and ST prevention in children and adolescents, who are unable or unwilling to exercise.

Maternal prenatal paracetamol ingestion and scholastic attainments of the offspring.

Background: Fetal exposure to paracetamol (acetaminophen) has been shown to be associated with asthma and other atopic disorders, as well as behavioural problems including hyperactivity, in childhood. However, there is little information on scholastic abilities among children exposed to paracetamol in pregnancy. Objectives: To determine whether there are any differences in scholastic abilities among the offspring of women who ingested paracetamol during pregnancy compared with non-exposed children. Methods: Mothers enrolled in the Avon Longitudinal Study of Parents and Children (ALSPAC) had recorded the frequency with which they had taken the medication over two time periods during pregnancy: i) the first 18weeks and ii) 18-32weeks. The offspring have been followed up ever since. For this study we use as outcomes: a) 14 tests of ability at reading and 2 of spelling using the study's tests and the national education system test results; b) 6 of mathematical abilities including tests of arithmetic and mathematical reasoning, and c) 1 of scientific understanding. Multiple regression was used, adjusting for 15 different exposures including reasons for taking the medication as well as demographic features. Results: Almost all unadjusted and adjusted mean differences were negative (i.e., those exposed to maternal intake of paracetamol did less well), but negative associations for exposures between 18 and 32weeks of gestation were much more evident than for exposures earlier in pregnancy. Of the later exposures, after adjustment, 12 of the 23 scholastic tests were associated with prenatal exposure to paracetamol at p < 0.05. These negative effects were found in the girls (12 tests at p < 0.05) but not boys (0 tests at p < 0.05). Conclusion: Evidence from this longitudinal study suggests that maternal exposure to paracetamol is associated with disadvantages to the offspring in scholastic abilities such as mathematics and reading at secondary school ages. This raises the question as to whether there are longer-lasting effects on educational attainment from age 15years onwards, including at university level. Clearly these results should be tested in other settings, but meanwhile they add to a growing accumulation of known adverse effects of exposure to paracetamol in pregnancy.

Sexual Orientation Identity Change, Developmental Trajectories of Depressive Symptoms, and Childhood Abuse From Adolescence to Young Adulthood

PurposeThis study tested differences between youths who reported being heterosexual at ages 15.5 and 21, and those who changed from reporting being heterosexual at age 15.5 to nonheterosexual at age 21, in the developmental trajectories of depressive symptoms from age 22–24 years, and whether these longitudinal patterns were explained by childhood and adolescent abuse. MethodsThe Avon Longitudinal Study of Parents and Children (ALSPAC) was used (849 male youths and 1,455 female youths). Youths' self-reported sexual orientation was measured at ages 15.5 and 21, and depressive symptoms were measured at ages 22, 23, and 24. Childhood and adolescent abuse between birth and 17 years were reported by youths and their mothers. ResultsMale and female youths who changed from reporting being heterosexual to nonheterosexual reported significantly more depressive symptoms than their consistently heterosexual counterparts at all 3 ages (except the association for male youths at age 24), with total effects (unstandardized regression coefficients) ranging from 2.00 to 5.27. These associations were weakened but remained statistically significant when childhood and adolescent abuse was controlled for, with direct effects ranging from 1.50 to 4.68. These associations were mediated through childhood and adolescent abuse, with indirect effects ranging from 0.48 to 0.58. Differences between youths who consistently reported being heterosexual and those who changed from reporting being heterosexual to nonheterosexual in depressive symptoms decreased from age 22–24 years, possibly due to the success of identity integration. DiscussionChildhood and adolescent abuse may partially explain these developmental disparities.

Atopic dermatitis, cognitive function and psychiatric comorbidities across early childhood and adolescence in a population-based UK birth cohort.

Atopic dermatitis (AD) may affect cognitive function, but studies are limited and inconsistent. The effect of AD severity on cognition remains underexplored and few previous studies have examined clinically validated or repeated measures of cognition throughout childhood. To evaluate the relationship of AD activity and severity with validated measures of general cognition in a longitudinal birth cohort. We conducted cross-sectional analyses using data from the Avon Longitudinal Study of Parents and Children (ALSPAC), a UK cohort of 14 975 individuals followed prospectively since their birth in 1991-92. AD was assessed 11 times between the age of 6 and 166 months. Mothers were asked if their child had an 'itchy, dry skin rash in the joints and creases', and AD status was time-updated accordingly as 'never', 'maybe', 'inactive', 'active/mild' or 'active/moderate-severe'. General cognition [i.e. intelligence quotient (IQ)] was measured at 18, 49, 103 and 186 months of age using the Griffiths Mental Development Scales (GMDS), Wechsler Preschool and Primary Scale of Intelligence (WPPSI), Wechsler Intelligence Scale for Children (WISC) and Wechsler Abbreviated Scale of Intelligence (WASI), respectively. Multivariable linear regression was used to compare IQ with respect to nearest time-updated AD status. Secondary analyses were stratified by the presence or absence of psychiatric or learning disorders. An exploratory longitudinal analysis of IQ across all four outcome assessments was conducted using generalized estimating equations. No significant associations between AD status and full-scale IQ scores on the GMDS, WPPSI, WISC and WASI were observed after adjustment for sociodemographic factors, atopic comorbidities and sleep characteristics. However, at 8 years of age, WISC Performance IQ was slightly, although statistically significantly, lower among children with active/moderate-severe AD [β coefficient -2.16, 95% confidence interval (CI) -4.12 to -0.19] and Verbal IQ was slightly, but statistically significantly, higher among those with inactive AD (β coefficient 1.31, 95% CI 0.28-2.34) compared with those without AD. Analyses stratified by psychiatric or learning disorders, and exploratory longitudinal analyses of cognition revealed similar findings. We did not find any clinically meaningful associations between AD activity and severity and general cognitive function during early childhood and adolescence. Future studies should incorporate objective measures of AD severity and investigate outcomes beyond IQ.

Genome-Wide Analyses of Vocabulary Size in Infancy and Toddlerhood: Associations With Attention-Deficit/Hyperactivity Disorder, Literacy, and Cognition-Related Traits

BackgroundThe number of words children produce (expressive vocabulary) and understand (receptive vocabulary) changes rapidly during early development, partially due to genetic factors. Here, we performed a meta–genome-wide association study of vocabulary acquisition and investigated polygenic overlap with literacy, cognition, developmental phenotypes, and neurodevelopmental conditions, including attention-deficit/hyperactivity disorder (ADHD). MethodsWe studied 37,913 parent-reported vocabulary size measures (English, Dutch, Danish) for 17,298 children of European descent. Meta-analyses were performed for early-phase expressive (infancy, 15–18 months), late-phase expressive (toddlerhood, 24–38 months), and late-phase receptive (toddlerhood, 24–38 months) vocabulary. Subsequently, we estimated single nucleotide polymorphism–based heritability (SNP-h2) and genetic correlations (rg) and modeled underlying factor structures with multivariate models. ResultsEarly-life vocabulary size was modestly heritable (SNP-h2 = 0.08–0.24). Genetic overlap between infant expressive and toddler receptive vocabulary was negligible (rg = 0.07), although each measure was moderately related to toddler expressive vocabulary (rg = 0.69 and rg = 0.67, respectively), suggesting a multifactorial genetic architecture. Both infant and toddler expressive vocabulary were genetically linked to literacy (e.g., spelling: rg = 0.58 and rg = 0.79, respectively), underlining genetic similarity. However, a genetic association of early-life vocabulary with educational attainment and intelligence emerged only during toddlerhood (e.g., receptive vocabulary and intelligence: rg = 0.36). Increased ADHD risk was genetically associated with larger infant expressive vocabulary (rg = 0.23). Multivariate genetic models in the ALSPAC (Avon Longitudinal Study of Parents and Children) cohort confirmed this finding for ADHD symptoms (e.g., at age 13; rg = 0.54) but showed that the association effect reversed for toddler receptive vocabulary (rg = −0.74), highlighting developmental heterogeneity. ConclusionsThe genetic architecture of early-life vocabulary changes during development, shaping polygenic association patterns with later-life ADHD, literacy, and cognition-related traits.

Epigenetic age acceleration and reproductive outcomes in women

Life history theory applied to human development stipulates that humans have evolved to detect and encode information from the early developmental environment that entrain coordinated development pathways. One possible mechanism is epigenetic age acceleration but few studies have prospectively examined associations between epigenetic aging and life-history related phenotypes. The purpose of this study was to examine the relations between epigenetic age acceleration when children were age 7 years and indices of reproductive development during adolescence using a sample of N = 512 youth from the Avon Longitudinal Study of Parents and Children (ALSPAC). A path model was used to test direct and indirect associations between epigenetic age acceleration and age at menarche (AAM), age at first sex, and lifetime and past year sexual partner number. Results showed epigenetic age acceleration was directly associated with earlier age at first sex and increased sexual partner number. There were further indirect associations with sexual partner number via age at first sex. Epigenetic age acceleration was not associated with AAM. Follow-up analyses to determine if aspects of the early developmental environment were associated with age acceleration were null. Implications for life history theory and the need for additional research are discussed.

A novel approach to risk exposure and epigenetics—the use of multidimensional context to gain insights into the early origins of cardiometabolic and neurocognitive health

BackgroundEach mother–child dyad represents a unique combination of genetic and environmental factors. This constellation of variables impacts the expression of countless genes. Numerous studies have uncovered changes in DNA methylation (DNAm), a form of epigenetic regulation, in offspring related to maternal risk factors. How these changes work together to link maternal-child risks to childhood cardiometabolic and neurocognitive traits remains unknown. This question is a key research priority as such traits predispose to future non-communicable diseases (NCDs). We propose viewing risk and the genome through a multidimensional lens to identify common DNAm patterns shared among diverse risk profiles.MethodsWe identified multifactorial Maternal Risk Profiles (MRPs) generated from population-based data (n = 15,454, Avon Longitudinal Study of Parents and Children (ALSPAC)). Using cord blood HumanMethylation450 BeadChip data, we identified genome-wide patterns of DNAm that co-vary with these MRPs. We tested the prospective relation of these DNAm patterns (n = 914) to future outcomes using decision tree analysis. We then tested the reproducibility of these patterns in (1) DNAm data at age 7 and 17 years within the same cohort (n = 973 and 974, respectively) and (2) cord DNAm in an independent cohort, the Generation R Study (n = 686).ResultsWe identified twenty MRP-related DNAm patterns at birth in ALSPAC. Four were prospectively related to cardiometabolic and/or neurocognitive childhood outcomes. These patterns were replicated in DNAm data from blood collected at later ages. Three of these patterns were externally validated in cord DNAm data in Generation R. Compared to previous literature, DNAm patterns exhibited novel spatial distribution across the genome that intersects with chromatin functional and tissue-specific signatures.ConclusionsTo our knowledge, we are the first to leverage multifactorial population-wide data to detect patterns of variability in DNAm. This context-based approach decreases biases stemming from overreliance on specific samples or variables. We discovered molecular patterns demonstrating prospective and replicable relations to complex traits. Moreover, results suggest that patterns harbour a genome-wide organisation specific to chromatin regulation and target tissues. These preliminary findings warrant further investigation to better reflect the reality of human context in molecular studies of NCDs.Graphical

Menstrual cycle features in mothers and daughters in the Avon Longitudinal Study of Parents and Children (ALSPAC)

Problematic menstrual cycle features, including irregular periods, severe pain, heavy bleeding, absence of periods, frequent or infrequent cycles, and premenstrual symptoms, are experienced by high proportions of females and can have substantial impacts on their health and well-being. However, research aimed at identifying causes and risk factors associated with such menstrual cycle features is sparse and limited. This data note describes prospective, longitudinal data collected in a UK birth cohort, the Avon Longitudinal Study of Parents and Children (ALSPAC), on menstrual cycle features, which can be utilised to address the research gaps in this area. Data were collected across 21 timepoints (between the average age of 28.6 and 57.7 years) in mothers (G0) and 20 timepoints (between the average age of 8 and 24 years) in index daughters (G1) between 1991 and 2020. This data note details all available variables, proposes methods to derive comparable variables across data collection timepoints, and discusses important limitations specific to each menstrual cycle feature. Also, the data note identifies broader issues for researchers to consider when utilising the menstrual cycle feature data, such as hormonal contraception, pregnancy, breastfeeding, and menopause, as well as missing data and misclassification.

Childhood socioeconomic position and sex-specific trajectories of metabolic traits across early life: prospective cohort study

Socioeconomic inequalities in cardiovascular disease risk begin early in life and are more pronounced in females than males later in life. Causal atherogenic traits explaining this are not well understood. We explored sex-specific associations between childhood socioeconomic position (SEP) and molecular measures of systemic metabolism across early life. Data were from the Avon Longitudinal Study of Parents and Children (ALSPAC), a population-based birth cohort in southwest England. Pregnant women with an expected delivery date between 1991 and 1992 were invited to participate. Maternal education was the primary indicator of SEP. Concentrations of 148 metabolic traits from targeted metabolomics (nuclear magnetic resonance spectroscopy) from research clinics at ages 7, 15, 18 and 25years were analysed. The sex-specific slope index of inequality (SII) in trajectories of metabolic traits was estimated using multilevel models. Total number of participants included was 6537 (12,543 repeated measures). Lower maternal education was associated with more adverse levels of several atherogenic lipids and key metabolic traits among females at age 7years, but not males. For instance, SII for very small very-low-density lipoprotein (VLDL) concentrations was 0.16SD (95% CI: 0.01, 0.30) among females and-0.02SD (95% CI:-0.16, 0.13) among males. Between 7and 25years, inequalities widened among females and emerged among males particularly for VLDL particle concentrations, apolipoprotein-B concentrations, and inflammatory glycoprotein acetyls. For instance, at 25years, SII for very small VLDL concentrations was 0.36SD (95% CI: 0.20, 0.52) and 0.22SD (95% CI: 0.04, 0.40) among females and males respectively. Prevention of socioeconomic inequalities in cardiovascular disease risk requires a life course approach beginning at the earliest opportunity, especially among females. The UK Medical Research Council and Wellcome (grant ref: 217065/Z/19/Z) and the University of Bristol provide core support for ALSPAC. A comprehensive list of grants funding is available on the ALSPAC website (http://www.bristol.ac.uk/alspac/external/documents/grant-acknowledgements.pdf). KON is supported by a Health Research Board (HRB) of Ireland Investigator Led Award (ILP-PHR-2022-008). JB, GDS and KT work in a unit funded by the UK MRC (MC_UU_00011/1 and MC UU 00011/3) and the University of Bristol. OR is supported by a UKRI Future Leaders Fellowship (MR/S03532X/1). These funding sources had no role in the design and conduct of this study. This publication is the work of the authors and KON will serve as guarantor for the contents of this paper.

Child maltreatment and parental domestic violence and abuse, co-occurrence and the effect on lifetime outcomes in the Avon Longitudinal Study of Parents and Children (ALSPAC)

Exposure to child maltreatment (CM), and parental domestic violence and abuse (DVA), impose considerable adverse life outcomes in both the short and long term, yet, the extent and effects of their co-occurrence on outcomes have not been comprehensively quantified. This study describes the analysis of data from the Avon Longitudinal Study of Parents and Children, quantifying the prevalence of CM, parental DVA, co-occurrence rates, and the impact of different combinations of childhood exposures on life outcomes (health, economic, and likelihood of perpetrating intimate partner violence as a young person).Childhood exposure prevalences were estimated at 41.7% for any form of CM, 19.3% for parental DVA, and 49.0% for exposure to at least one form of CM and/or parental DVA. Co-occurring parental DVA was reported in 21%–42% of CM-exposed households. Sexual abuse was reported in 2% of parental DVA-exposed households, whilst co-occurrence of other forms of CM ranged between 19% and 41%.Co-occurring CM and parental DVA exposures were associated with increased risks of drug use, anxiety, depression, smoking, unemployment, social welfare use, and perpetration of intimate partner violence as a young person – highlighting the intergenerational effects of exposure. Increased risks across a wider range of adverse outcomes were associated with child-reported awareness of parental DVA, compared to parent-reported DVA exposure.The high cumulative prevalence of childhood exposure to CM and/or parental DVA, and the scale of the resulting adverse impacts emphasise the need for policies and family interventions sensitive to the possibility of co-occurring forms of abuse.

Independent Prediction of Child Psychiatric Symptoms by Maternal Mental Health and Child Polygenic Risk Scores

Prenatal maternal symptoms of depression and anxiety are associated with an increased risk for child socioemotional and behavioral difficulties, supporting the fetal origins of mental health hypothesis. However, to date, studies have not considered specific genomic risk as a possible confound. The Avon Longitudinal Study of Parents and Children (ALSPAC) cohort (n= 5,546) was used to test if child polygenic risk score for attention-deficit/hyperactivity disorder (ADHD), schizophrenia, or depression confounds or modifies the impact of prenatal maternal depression and anxiety on child internalizing, externalizing, and total emotional/behavioral symptoms from age 4 to 16 years. Longitudinal child and adolescent symptom data were analyzed in the ALSPAC cohort using generalized estimating equations. Replication analyses were done in an independent cohort (Prevention of Preeclampsia and Intrauterine Growth Restriction [PREDO] cohort; n= 514) from Finland, which provided complementary measures of maternal mental health and child psychiatric symptoms. Maternal depression and anxiety and child polygenic risk scores independently and additively predicted behavioral and emotional symptoms from childhood through mid-adolescence. There was a robust prediction of child and adolescent symptoms from both prenatal maternal depression (generalized estimating equation estimate= 0.093, 95% CI 0.065-0.121, p= 2.66× 10-10) and anxiety (generalized estimating equation estimate= 0.065, 95% CI 0.037-0.093, p= 1.62× 10-5) after adjusting for child genomic risk for mental disorders. There was a similar independent effect of maternal depression (B= 0.156, 95% CI 0.066-0.246, p= .001) on child symptoms in the PREDO cohort. Genetically informed sensitivity analyses suggest that shared genetic risk only partially explains the reported association between prenatal maternal depression and offspring mental health. These findings highlight the genomic contribution to the fetal origins of mental health hypothesis and further evidence that prenatal maternal depression and anxiety are robust in utero risks for child and adolescent psychiatric symptoms. Depression and anxiety affect approximately 15% of pregnant women, and children exposed to maternal depression or anxiety during pregnancy are at higher risk of developing mental health problems. However, the degree to which shared genetics explains the association between maternal and child mental health is unknown. In this study the authors generated polygenic risk scores (PRS), which provide a single measure of genetic risk for complex traits, to investigate the impact of shared genetic risk on the development of childhood mental health problems. Utilizing two longitudinal studies (n = 6,060), the authors found that PRS only partially explained the association between prenatal maternal depression and childhood mental health problems. These analyses show prenatal maternal depression remained a significant predictor of childhood mental health problems after accounting for shared genetic risk, further highlighting that prenatal maternal mental health is a robust predictor of child and adolescent mental health problems.