Is pre‐eclampsia more than one disease?

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Abstract
Objectives The clinical characteristics of pre-eclampsia (gestational hypertension and proteinuria) may represent separate pathogenetic conditions. Pre-eclampsia accompanied by restricted fetal growth may originate from abnormal implantation, and appropriate or high birthweights may indicate a mixture of conditions, ranging from mild pre-eclampsia with modest placental involvement to hypertensive conditions without placental disease. Design Prospective, observational study. Setting General population. Population We used data from the Medical Birth Registry of Norway, a population-based registry that has recorded births since 1967. For this study, we used information on length of gestation and presence of pre-eclampsia among 1,679,205 singletons born between 1967 and 1998. Pre-eclampsia was diagnosed in 44,220 (2.6%) pregnancies. Methods We studied the risk of pre-eclampsia in relation to standardised measures (z scores) of birthweight, adjusted for length of gestation, and stratified by term and preterm delivery. We also explored whether gestational diabetes was more prevalent in conjunction with preterm than term pre-eclampsia. Main outcome measures Pre-eclampsia diagnosed at term or preterm. Results For pre-eclampsia diagnosed around term, there was a U-shaped association with birthweight. Compared with appropriate birthweights for gestation, the risk of term pre-eclampsia was more than fourfold higher (relative risk [RR] 4.5, 95% confidence interval [CI], 4.3 to 4.7) if the baby's birthweight was lower than two standard deviations under the mean. For birthweights three standard deviations or higher than the mean, pre-eclampsia was more than twice as likely (RR 2.6, 95% CI 2.2–2.9). In contrast, the risk of preterm pre-eclampsia displayed an L-shaped association with birthweight. Low birthweight (less than −2 standard deviations) was associated with greatly increased risk (RR 9.9, 95% CI 9.1–10.9), but for high birthweights (≥3 standard deviations), there was no association with the risk of preterm pre-eclampsia (RR 1.2, 95% CI 0.7–2.1). The prevalence of gestational diabetes was three times (prevalence ratio 3.3, 95% CI 2.6–3.6) higher in preterm than term pre-eclampsia. Conclusion Whereas pre-eclampsia with preterm delivery associated with low birthweight may be caused by underlying placental abnormality, pre-eclampsia delivered at term may represent a mixture of conditions, ranging from mild pre-eclampsia with moderate placental affection to hypertensive conditions in pregnancy without placental dysfunction.