Preschool development, temperament and genetic liability as early markers of childhood ADHD: A cohort study.

Background: ADHD is associated with multiple adverse outcomes and early identification is important. The present study sets out to identify early markers and developmental characteristics during the first 30 months of life that are associated with ADHD 6 years later. Methods: 9201 participants from the prospective Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort were included. Outcome measures were parent-rated ADHD symptom scores (Strengths and Difficulties Questionnaire, SDQ) and ADHD diagnosis (Development and Wellbeing Assessment, DAWBA) at age 7. Seventeen putative markers were identified from previous literature and included: pre- and peri-natal risk factors, genetic liability (ADHD polygenic risk scores, PRS), early development, temperament scores and regulatory problems. Associations were examined using regression analysis. Results: Univariable regression analysis showed that multiple early life factors were associated with future ADHD outcomes, even after controlling for sex and socio-economic status. In a multivariable linear regression model; temperament activity scores (B = 0.107, CI = 0.083-0.132), vocabulary delay (B = 0.605, CI = 0.211-0.988), fine motor delay (B = 0.693, CI = 0.360-1.025) and ADHD PRS (B = 0.184, CI = 0.074-0.294) were associated with future symptoms (R 2 = 10.7%). In a multivariable logistic regression model, ADHD PRS (OR = 1.39, CI = 1.10-1.77) and temperament activity scores (OR = 1.09, CI = 1.04-1.16) showed association with ADHD diagnosis. Conclusion: As well as male sex and lower socio-economic status, high temperament activity levels and motor and speech delays in the first 30 months of life, are associated with childhood ADHD. Intriguingly, given that genetic risk scores are known to explain little of the variance of ADHD outcomes, we found that ADHD PRS added useful predictive information. Future research needs to test whether predictive models incorporating aspects of early development and genetic risk scores are useful for predicting ADHD in clinical practice.

Early manifestations of genetic liability for ADHD, autism and schizophrenia at ages 18 and 24 months.

Background: ADHD and autism are neurodevelopmental conditions, for which non-specific precursors or early signs include difficulties with language and motor skills, and differences in temperament in the first and second year of life. These early features have also been linked to later diagnosis of schizophrenia which is widely considered to have neurodevelopmental origins. Given that ADHD, autism and schizophrenia are all highly heritable, we tested the hypothesis that in the general population, measures of toddler language development, motor development and temperament are associated with genetic liability to ADHD, autism and/or schizophrenia. Methods: Data were analysed from the Avon Longitudinal Study of Parents and Children (ALSPAC) which included motor development scores at age 18 months and language development and temperament scores at age 24 months (N=7498). Genetic liability was indexed by polygenic risk scores (PGS) for ADHD, autism and schizophrenia. Results: ADHD PGS were associated with specific temperament scales (higher activity ß=0.07, 95% CI=0.04, 0.09 and lower withdrawal ß=-0.05, 95% CI=-0.07, -0.02) as well as better gross motor scores (ß=0.04, 95% CI=0.01, 0.06). Schizophrenia PGS were associated with one specific temperament scale (negative mood ß=0.04, 95% CI=0.02, 0.07). We did not find strong evidence of association of autism PGS with any of the toddler measures; there was also not strong evidence of association with motor or language delays for any of the PGS. Conclusions: This study suggests that some specific aspects of early temperament and gross motor differences in the general population could represent part of the early manifestation of genetic liability to neurodevelopmental conditions.

Full Breastfeeding and Obesity in Children: A Prospective Study from Birth to 6 Years.

BACKGROUND: Obesity is a major public health crisis among both children and adults and contributes to significant physical, psychological, and economic burden. We aim to investigate the effect of duration of breastfeeding on excessive weight and obesity at 6 years of age. SUBJECTS/METHODS: Data on breastfeeding and child anthropometric measurements were collected in a birth-cohort study in Murcia, Spain (n = 350). Breastfeeding status and body mass index (BMI) were established according to WHO definitions. Other factors potentially related to children's weight were considered. Multiple log-linear and ordinal regressions were used to analyze the effects of breastfeeding on overweight and obesity when considering potential confounders. RESULTS: 33% and 17.3% of children in the study were of excess weight and obesity, respectively. Univariate predictors of BMI in children aged 6 were as follows: pregestational maternal BMI (kg/m2) (R2 = 0.127, p < 0.01); full breastfeeding (weeks) R2 = -0.035, p < 0.01); infant weight gain (kg) (R2 = 0.348, p < 0.01); and maternal alcohol consumption during pregnancy (g/day) (R2 = 0.266, p < 0.01) at age 6. In the ordinal logistic regression, full breastfeeding was associated with a significant decrease in obesity -0.052 (95% CI, -0.10 to -0.003). CONCLUSIONS: The delay of bottle feeding introduction may have a protective effect against obesity at 6 years of age. Our findings reinforce the need for greater support of breastfeeding and to promote a healthy environment and antipoverty interventions during pregnancy and infancy, alongside other strategies for obesity prevention.

Spatial clustering of childhood leukaemia with the integration of the Paediatric Environmental History.

BACKGROUND: Leukaemia remains the most common type of paediatric cancer and its aetiology remains unknown, but considered to be multifactorial. It is suggested that the initiation in utero by relevant exposures and/or inherited genetic variants and, other promotional postnatal exposures are probably required to develop leukaemia. This study aimed to map the incidence and analyse possible clusters in the geographical distribution of childhood acute leukaemia during the critical periods and to evaluate the factors that may be involved in the aetiology by conducting community and individual risk assessments. MATERIALS AND METHODS: We analysed all incident cases of acute childhood leukaemia (<15 years) diagnosed in a Spanish region during the period 1998-2013. At diagnosis, the addresses during pregnancy, early childhood and diagnosis were collected and codified to analyse the spatial distribution of acute leukaemia. Scan statistical test methodology was used for the identification of high-incidence spatial clusters. Once identified, individual and community risk assessments were conducted using the Paediatric Environmental History. RESULTS: A total of 158 cases of acute leukaemia were analysed. The crude rate for the period was 42.7 cases per million children. Among subtypes, acute lymphoblastic leukaemia had the highest incidence (31.9 per million children). A spatial cluster of acute lymphoblastic leukaemia was detected using the pregnancy address (p<0.05). The most common environmental risk factors related with the aetiology of acute lymphoblastic leukaemia, identified by the Paediatric Environmental History were: prenatal exposure to tobacco (75%) and alcohol (50%); residential and community exposure to pesticides (62.5%); prenatal or neonatal ionizing radiation (42.8%); and parental workplace exposure (37.5%) CONCLUSIONS: Our study suggests that environmental exposures in utero may be important in the development of childhood leukaemia. Due to the presence of high-incidence clusters using pregnancy address, it is necessary to introduce this address into the childhood cancer registers. The Paediatric Environmental History which includes pregnancy address and a careful and comprehensive evaluation of the environmental exposures will allow us to build the knowledge of the causes of childhood leukaemia.