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Background
Several previous research reports have suggested a genetic predisposition to pre-eclampsia but none have demonstrated the effect separately in nulliparous and parous women in the context of other risk or protective factors.
Objective
To assess the magnitude of genetic predisposition to pre-eclampsia with reference to other risk factors in nulliparous and parous women.
Material and Method
The Aberdeen Maternity and Neonatal Databank records all pregnancy and delivery details occurring in Aberdeen, Scotland since 1950. It has now become possible to link pregnancy records of mothers and grandmothers to those of the daughters. Using a nested case control design within this intergenerational cohort, statistical modelling was done with known risk/protective factors for pre-eclampsia, separately for nulliparous and parous women. Conditional logistic regression was used to compare characteristics between parous pre-eclamptics and year and parity matched normotensive controls. In a separate analysis, including all parous women, we used a multilevel approach based on Generalised Estimating Equation (GEE) and specified the link function as binomial. We assumed a working exchangeable correlation of having preeclampsia within a daughter in her pregnancies. Odds ratios (OR) and 95% CI were estimated through GEE with the use of robust standard errors.
Results
There were 34 970 mother-daughter pairs. Of the daughters, there were 1248 nulliparous and 448 parous pre-eclamptics. For nulliparous women, the risk factors remaining in the stepwise model were mother’s history of pre-eclampsia (OR 2.13, 95% CI 1.57 to 2.89), booking BMI >30 kg/m2 (OR 2.06, 95% CI 1.68 to 2.52), age, gestation period, and booking diastolic blood pressure. Smoking ∼10 cigarettes a day was protective against pre-eclampsia (OR 0.52, 95% CI 0.44 to 0.62). For multiparae, the risk factors included pre-eclampsia in the initial pregnancy (OR 8.80, 95% CI 1.54 to 50.23), advanced age at delivery (OR 3.09, 95% CI 1.69 to 5.66) and BMI >30 kg/m2 (OR 2.61, 95% CI 1.62 to 4.20). Smoking 10 or more cigarettes per day was protective (OR 0.57, 95% CI 0.35 to 0.94). A history of maternal pre-eclampsia was not independently associated with an increased risk of development of pre-eclampsia in the multiparae after adjusting for other covariates. Results were similar using the GEE approach.
Conclusion
In nulliparous women, a history of maternal pre-eclampsia was associated with more than doubling of risk of pre-eclampsia. In multiparae, this association was not observed, although a history of pre-eclampsia in a previous pregnancy was strongly associated with increased risk, suggesting genetic susceptibility.