The association between environmental factors early in life and Attention-Deficit Hyperactivity Disorder in Childhood– epidemiological studies to improve preventive efforts

Introduction

During the last decades a trend towards an increase in diagnosis of ADHD has been observed with a current estimated prevalence of 1-8% among children and adolescents. The same tendency has been observed for many other childhood psychiatric disorders such as etc. Autism Spectrum Disorders. It has been debated, whether this increase in diagnosis of childhood psychiatric disorders reflects a true increase, or more likely is related to changes in diagnostic criteria, earlier age at diagnosis, increased clinical awareness, or media attention. Also genetic and environmental factors have been suggested responsible for part of the increase with an enormous amount of research into the aetiology of ADHD taking steps forward.

It is evident that undetected mental problems tend to increase in severity with age, and in recent years it has become known that 50-75% of children with ADHD continue to have problems into adulthood, with increased risk of antisocial behaviour and substance misuse, poor educational attainment and unemployment, friendship difficulties and social problems. Therefore, identification of potential preventable causes to ADHD is of public health relevance, with early identification of children with ADHD being crucial. As a result of the increased incidence of some childhood mental disorders, a greater focus on potential pre- and perinatal factors as predictors of mental health in the offspring has occurred, trying to establish, whether risk factors acting in early life play a major role in the pathogenesis of mental problems.

The nature of the relationship between obstetric and genetic risk factors is uncertain, but it is parsimonious to assume that they confer risk by acting either additively or multiplicatively on common neurodevelopmental processes.

A foetal programming effect has been suggested contributing to the aetiology of many neurological disorders, including ADHD, by altering the foetal brain development. Foetal programming occurs when normal foetal development is disrupted by an abnormal stimulus or insult applied to a critical point in intrauterine life with gestational conditions representing important determinants of future health.

Several environmental factors have been suggested as potential risk factors of ADHD, but it remains unclear whether or not the associations are causal. The overall objective of this thesis is, in an epidemiological setting, to study associations between pregnancy related risk factors and offspring behavioural problems and to interpret whether associations are due to a foetal programming effect or rather caused by social or genetic conditions.

Results (edited)

Maternal characteristics

The results suggest that low maternal age, high maternal pre-pregnancy BMI, and high maternal coffee consumption at 15 weeks of gestation are likely to be markers of genetic traits with associations with offspring ADHD partly representing genetic confounding. Genetic factors causing a genetic predisposition in offspring might exert indirect risk effects through interplay with maternal characteristics and lifestyle factors with effects of a gene-environment interaction contributing to the aetiology of ADHD. Focus on delaying fertility, weight loss among obese pre-pregnant and pregnant women or reduced caffeine intake without ameliorating the background risks experienced by these mothers may not be fully effective in reducing offspring ADHD. It appeared that most of the associations between the combined effects of umbilical artery cord blood pH value and gestational age or Apgar score on ADHD are driven by gestational age or the Apgar score.

Perinatal factors

A pH value below 7.10 was significantly associated with an increased risk of ADHD. The strongest risks were observed among children with a pH value <7.15 and a gestational age of <32 weeks. The pH value did not contribute much to the risk among children with an Apgar score of 0-3 From a clinical point of view the trend of higher risk of ADHD estimated among children with both gestational age <32 weeks and an umbilical artery cord blood pH value below 7.15 is important to be aware of, even though the relative importance of low umbilical cord pH value as a predictor of ADHD in preterm infants compared to term infants is still unclear.