Objective. To evaluate the rate of preterm birth and low birth weight in the newborns of pregnant women with early and late onset pre-eclampsia according to folic acid supplementation. Study design. Birth outcomes of newborns were evaluated in 1,017 (2.7%) pregnant women with medically recorded pre-eclampsia and 37,134 pregnant women without pre-eclampsia as reference in the Hungarian Case-Control Surveillance System of Congenital Abnormalities, 1980–1996, in addition these study groups were differentiated according to the supplementation of high dose of folic acid alone from early pregnancy. Results. Pregnant women with pre-eclampsia associated with a higher rate of preterm birth (10.2% versus 9.1%) and low birthweight (7.9% versus 5.6%). There was a lower risk of preterm birth (6.8%) of newborn infants born to pregnant women with early onset pre-eclampsia after folic acid supplementation from early pregnancy though the rate of low birthweight was not reduced significantly. There was no significant reduction in the rate of preterm birth and low birthweight in pregnant women with late onset pre-eclampsia after folic acid supplementation. Conclusion. The rate of preterm birth in pregnant women with early onset pre-eclampsia was reduced moderately by high doses of folic acid supplementation from early pregnancy. 1. Introduction Pre-eclampsia (PE) is frequent (2–8%) and severe complications of pregnancy, and this multisystem disorder of pregnancy is characterized by pregnancy-induced hypertension and new-onset proteinuria during the second half of pregnancy [1–3]. PE is a major contributor to maternal mortality if associates with eclampsia and HELLP syndrome [4, 5]. Furthermore, since delivery is the only cure of PE, there is a higher risk of preterm birth up to 15% [6] and intrauterine growth retardation [7] with an increase in infant mortality and morbidity. Two important hypotheses have been generated for the pathogenesis of PE during the last decades. The first hypothesis was based on the differentiation of early and late onset PE [3] or on the two-stage model of PE [8]. The second hypothesis was based on PE associated with placental insufficiency due to hyperhomocysteinemia-related vasculopathy because 3.2–7.7-fold higher risk of PE was found in pregnant women with elevated homocysteine levels [9–16]. Folic acid supplementation lowers plasma homocysteine in general [17] and in patients with PE [18], thus folic acid containing multivitamins was tested in pregnant women with gestational hypertension [19] and in pregnant women with PE [20, 21] with
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