Recently two studies from the Menorca cohort have investigated the role of genes associated with detoxification (1, 2). These studies have reported interactions between GSTM1 with maternal smoking in pregnancy and GSTP1 with indoor NO2 exposure at 3 months of age on child cognitive development at 4 years as measured by the McCarthy scale. Similar analyses of smoking with GSTT1 found no interaction. As far as we know no other studies have examined these issues. The Menorca cohort was relatively small (N~400) and currently has no DNA from mothers.

Early in 1993, about 1000 families from the ALSPAC cohort participated in a study to assess indoor air quality. Passive diffusion tubes were left exposed, usually in the child's bedroom, over a two week period from which average NO2 concentrations (parts per billion) were obtained. These families also completed a questionnaire about the use of gas appliances, portable heaters (gas or paraffin), smoking, ventilation in the home, and external sources of NO2 (level of traffic outside home). Similar questions were asked in pregnancy and at 8 months for the whole cohort.

Maternal cigarette smoking is assessed at multiple times during pregnancy.

Child cognitive development was assessed at 49 months using WPPSI but only for Children in Focus subsample and at 8 years using WISC for the whole cohort.

It is proposed to follow a similar strategy as adopted in the Menorca studies. In respect of NO2 exposure, both actual and indirect measures of exposure are possible. Indirect assessments could involve using questionnaire data on the use of gas appliances or alternatively creating a predictive model of actual exposure based upon gas usage, other sources of NO2 and ventilation. Both these methods would permit the use of larger numbers whereas analyses on actual exposures would be restricted to the 1000 families involved in the indoor air study. For smoking, exposure can be assessed as a continuous variable (assuming linearity) or as a categorical variable.

Unlike the Menorca studies, we propose to extend the analyses to consider cognition at 8y (to investigate the attenuation with age) and the maternal genotype. The maternal genotype may affect the child during pregnancy. The metabolites of environmental toxins can cross the placenta with the potential to disrupt the developing fetus (3). Consequently, the ability of the mother to metabolise these toxins may have a direct impact on the fetus.

1.MoralesE, SunyerJ, JulvezJ, Castro-GinerF, EstivillX, TorrentM, de Cid R.GSTM1 polymorphisms modify the effect of maternal smoking during pregnancy on cognitive functioning in

preschoolers. Int J Epidem (in press)

2.MoralesE, JulvezJ, TorrentM, de Cid R, Guxens M, Bustamante M, SunyerJ. Association of early life exposure to household gas appliances and indoor NO2 with cognition and attention behavior in preschoolers. Am J Epidem (submitted)

3. Perera FP, Jedrychowski W, Rauh V, Whyatt RM. Molecular epidemiologic research on the

effects of environmental pollutants on the fetus. Environ Health Perspect 1999;107:451-60.

Data required

Concept

Specific measure

Person

Source

Time point(s)

IQ

WPPSI, WISC

Child

Clinic

49m, 8y

Air Quality

NO2

Substudy

Environmental

Exposures

Smoking, gas usage, etc

Mother

Questionnaire

Pregnancy to 8m