In this systematic review of controlled studies we found that antiphospholipid antibodies, a history of pre-eclampsia, pre-existing diabetes, multiple pregnancy, family history, nulliparity, a raised BMI before pregnancy or at booking, maternal age > 40, renal disease, hypertension, ≥ 10 years since the last pregnancy, and raised blood pressure at booking all increased the risk of a woman developing pre-eclampsia.
We reviewed only published studies, and unpublished studies may contain valid results that conflict with our conclusions. This is of particular concern in a meta-analysis of observational studies as there is a greater tendency towards publication bias than there is with randomised controlled trials.59
Because the peer review process is an important means of ensuring quality, however, possibly only published data and studies should be used.60
Publication bias is always a concern for systematic reviews. Funnel plots for the risk factors where over three studies were included were symmetrical for low maternal age, parity, previous pre-eclampsia, pre-existing diabetes, and body mass index before pregnancy (see figs A-H on bmj.com
). Some researchers may not have reported on variables that they studied but that did not show an association with pre-eclampsia.
Pre-eclampsia was seldom divided into early and late onset, nor were results presented for onset of pre-eclampsia or delivery in relation to gestational age. We may therefore have underestimated the importance of risk factors for early onset pre-eclampsia, a type with considerable maternal and perinatal morbidity and mortality.26,61
Although we examined the role of individual risk factors, little is known about the association between them. For instance, is a low risk multiparous woman under 40 who did not have pre-eclampsia in her first pregnancy at an increased risk of pre-eclampsia because she has a family history? Similarly as most of the studies concerning body mass index did not separate out their results for parity or control for previous history, it is also unclear whether a raised pre-pregnancy or booking weight or body mass index is less of a risk factor in a multiparous woman who has not had pre-eclampsia in her first pregnancy.
Because we did not identify any controlled studies of sufficient quality we cannot draw any conclusions about proteinuria at booking, although the association of proteinuria with renal disease, which is a risk factor, suggests that it is probably important.
The risk factors that we have identified can be used to assess risk at the booking visit, so that a suitable surveillance routine to detect pre-eclampsia can be planned for the rest of the pregnancy, as recommended by the recent NICE guideline on antenatal care5
and the new pre-eclampsia community guideline (PRECOG) guideline.62
What is already known on this topic
Various factors, which can be ascertained at the first antenatal or booking visit, are thought to increase the risk of a woman developing pre-eclampsia during pregnancy
What this study adds
The most significant risk factors for developing pre-eclampsia are a history of pre-eclampsia and the presence of antiphospholipid antibodies
Pre-existing diabetes and a pre-pregnancy BMI of ≥ 35 almost quadruple the risk; nulliparity, a family history of pre-eclampsia, and twin pregnancy almost triple the risk; and maternal age ≥ 40, a booking BMI of ≥ 35, and a systolic blood pressure ≥ 130 at booking double the risk
Pre-existing hypertension, renal disease, chronic autoimmune disease, and ≥ 10 years between pregnancies increase the risk but it is not clear by how much