Pre-eclampsia is a syndrome of pregnancy that is marked by proteinuria and hypertension. It is a leading cause of maternal mortality and is also associated with fetal growth restriction, placental abruption and perinatal death 1. Interestingly, there is a well-documented association between maternal smoking during pregnancy and reduced risk of pre-eclampsia. A recent review of epidemiological studies reported a total of 48 studies, consistently reporting a reduction in risk of pre-eclampsia in maternal smokers - up to 50% reduction in heavy smokers 2. However, ascertaining with certainty the causality of this association remains a challenge. Whilst the association has long been observed in the literature, the biological mechanisms for this relationship remain unknown. Indeed, many of the known effects of smoking suggest that prenatal smoking should increase the risk of pre-eclampsia, rather than decrease it.

Furthermore, whilst the association between maternal smoking and pre-eclampsia is well documented, associations with antenatal blood pressure per se are less well established. Few studies have reported on this, with some suggestion that smoking may be associated with increased systolic blood pressure3;4, in constrast to what might be expected from the observed associations with pre-eclampsia. Several of the proposed authors for this project (MacDonald-Wallis; Lawlor) have been analysing trajectories of blood pressure in pregnancy in the ALSPAC mothers, and have observed systematic differences in the trajectories of blood pressure amongst women who were nonsmokers, quitters and continued smokers during pregnancy (manuscript in progress). We would like to extend this work by analysing these trajectories with respect to a maternal genotype known to be associated with smoking during pregnancy, in order to better ascertain the extent of the causal mechanisms involved.

Research Questions:

1) Is maternal prenatal smoking status (as indexed by maternal CHRNA3 genotype) causally related to risk of pre-eclampsia

2)Is maternal prenatal smoking status (as indexed by maternal CHRNA3 genotype) causally related to trajectories of blood pressure during pregnancy.

(1) Sibai B, Dekker G, Kupferminc M. Pre-eclampsia. Lancet 2005; 365(9461):785-799.

(2) England L, Zhang J. Smoking and risk of preeclampsia: a systematic review. Front Biosci 2007; 12:2471-2483.

(3) Bakker R, Steegers EAP, Mackenbach JP, Hofman A, Jaddoe VWV. Maternal smoking and blood pressure in different trimesters of pregnancy: The Generation R Study. Journal of Hypertension 2010; 28.

(4) Matkin CC, Britton J, Samuels S, Esenazi B. Smoking and blood pressure patterns in normotensive pregnant women. Paediatr Perinat Epidemiol 1999; 13:22-34.