The effects and mechanisms of primiparity on the risk of pre‐eclampsia: a systematic review

Pre-eclampsia has been dubbed as 'a disease of primiparity'. However, the effects and mechanisms of the association of primiparity with pre-eclampsia have not been clearly defined. We conducted a systematic review of studies evaluating the effect of primiparity on the risk of pre-eclampsia, and studies (published between January 1966 and July 2005) on the mechanisms underlying such an association. A total of 26 original studies were identified and a meta-analysis carried out for the risk of pre-eclampsia among primiparous vs. multiparous women. Variably (1.4-5.5 times) higher risks of pre-eclampsia were observed in primiparous women in all studies, with a summary odds ratio (OR) of 2.42 95% CI 2.16, 2.71. The adjusted ORs were larger than crude ORs in all but one study after various adjustments. Except for abundant epidemiological evidence in support of the immune maladaptation theory, only four original studies examined the actual mechanisms of such primiparity-associated risk. Two (small) studies suggested differences in immunological responses in the aetiology of pre-eclampsia in primiparous vs. multiparous women. Two recent studies indicated that differences in angiogenic factor profile or reactivity to insulin resistance in early pregnancy may explain the elevated pre-eclampsia risk in first pregnancies. In conclusion, primiparity is associated with approximately 2.4-fold elevated risk of pre-eclampsia. Although immune maladaptation is generally considered as the basis to explain such an elevated risk, few data are available on immune maladaptation parameters in primiparous vs. multiparous pregnancies. Available data are insufficient to interpret the mechanisms of such primiparity-associated excess risk of pre-eclampsia.