Objective: To study associations between established risk factors for pre-eclampsia and different clinical manifestations of the disease.

Design: A population-based, nested case-control study.

Setting: Information from 12,804 consecutive deliveries that took place over three years at a birth clinic, which alone serves a population of nearly 240,000 in Rogaland county, Norway.

Subjects: Cases of pre-eclampsia (n = 323) and healthy controls (n = 650) were selected. Pre-eclampsia was defined as increase in diastolic blood pressure (> or = 25 mmHg to > or = 90 mmHg) and proteinuria (> or = 1+ by dipstick testing) after 20 weeks of pregnancy.

Main study measures: Parity, previous pre-eclampsia, blood pressure, maternal weight, and maternal smoking were included as study variables. Women with pre-eclampsia were grouped according to clinical manifestations of the disease (i.e. severity [mild, moderate or severe]) and time of onset (early or late gestation). Associations with the study factors were estimated as relative risks (odds ratio, OR).

Results: Both nulliparity and hypertension increased pre-eclampsia risk, with no clear preference for any clinical subtype. High maternal weight was related to a higher risk of mild and moderate, but not severe, pre-eclampsia. Previous pre-eclampsia strongly increased the risk for pre-eclampsia in the current pregnancy, and the risk of early onset disease was especially high (OR 42.4; 95% CI 11.9-151.6). Overall, smoking was associated with a reduced risk for pre-eclampsia (OR 0.6; 95% CI 0.4-0.9). However, no effect of smoking was observed in the early onset disease group and among women with repeated pre-eclampsia.

Conclusion: Nulliparity and hypertension increased the risk for each subgroup of pre-eclampsia, but high maternal weight, previous pre-eclampsia and smoking were not consistently associated with each clinical subtype. This observation may suggest that heterogeneous clinical manifestations of pre-eclampsia may be preceded by different pathological mechanisms.