Development of behavioural characteristics is dependent on a complex interaction of genetic and environmental factors. It is also known that neonatal development can be altered by a variety of maternally derived exposures.

Alcohol consumption in pregnancy is an important health issue and the DOH currently advise that 'Pregnant women or women trying to conceive should avoid drinking alcohol' (http://www.dh.gov.uk/en/Publichealth/Healthimprovement/Alcoholmisuse/DH_...). This is due to significant evidence that maternal alcohol consumption has deleterious effects on the development of the unborn infant.

Fetal alcohol syndrome (FAS) is thought to be a leading cause of learning disability in the western world. Characteristics of FAS include; lower IQ, abnormal facial features and behavioural and mental health problems. Whilst FAS is caused by very heavy alcohol consumption for prolonged periods during pregnancy, it is thought that exposure to lower doses of alcohol in utero may cause less severe sub-optimal development, which is largely undetected. However, detecting these effects is problematic since alcohol consumption in the mother is heavily confounded by other lifestyle factors.

Proposed study

ALSPAC has collected information on maternal alcohol consumption through questionnaires at 12, 18 and 32 weeks of gestation as well as data regarding the drinking consumption of the mothers' parents. In addition quantity of maternal alcohol intake data is available related to the timing of fetal development; before pregnancy, first 3 months of pregnancy, at around the time first felt the baby move.

We also have genetic data on these mothers and children, and have shown that a common genetic variant in the ADH1B gene in mothers is associated with alcohol consumption levels during pregnancy. In addition we have shown that 4 genetic variants in ALSPAC children are related to their IQ at age 8, but only among children born to mothers who drank some alcohol during pregnancy. We plan to use these genotypes in an analysis of alcohol and children's behaviour to determine whether maternal alcohol consumption during pregnancy is likely to be causally related to problem behaviour in her offspring.

Children's behaviour problems (conduct problems and hyperactivity) have been assessed repeatedly from ages 4 to 16 years in ALSPAC, using the Strengths and Difficulties Questionnaire (SDQ) and the Development and Wellbeing Assessment (DAWBA). Based on these measures, three types of outcome are available for analyses: symptom scores (on the SDQ), diagnoses (using DAWBA), and longitudinal trajectories of conduct problems between ages 4-13 years (previously created by Barker and Maughan, 2009, using SDQ scores).

We will look at main effects of genotype on children's behaviour, and carry-out a stratified analysis to determine whether effects are due to exposure to alcohol rather than pleiotrophy.

References

Barker ED, Maughan B. Differentiating Early-Onset Persistent Versus Childhood-Limited Conduct Problem Youth. Am J Psychiatry. 2009;166(8):900-8.

Lewis SJ, Zuccolo L, Davey Smith G, Macleod J, Rodriguez S, Draper ES, Barrow M, Alati R, Sayal K, Ring S, Golding J, Gray R.Fetal Alcohol Exposure and IQ at Age 8: Evidence from a Population-Based Birth-Cohort Study.PLoS One. 2012;7(11):e49407. doi: 10.1371/journal.pone.0049407. Epub 2012 Nov 14.

Zuccolo L, Fitz-Simon N, Gray R, Ring SM, Sayal K, Davey Smith G, Lewis SJ. A non-synonymous variant in ADH1B is strongly associated with prenatal alcohol use in a European sample of pregnant women. Hum Mol Genet.2009;18:4457-66.