Non-pregnant circulatory volume status predicts subsequent pregnancy outcome in normotensive thrombophilic formerly preeclamptic women

Abstract

Background: Preeclampsia seems to be superimposed upon a preexisting hemodynamic, hemostatic, autoimmune or metabolic disorder. We tested the hypothesis that in normotensive thrombophilic formerly preeclamptic subjects, the non-pregnant circulatory volume status predicts the development of subsequent hypertensive pregnancy and/or fetal growth restriction.

Methods: In 250 non-diabetic formerly preeclamptic women and 15 normal parous controls, we measured and calculated the following variables at least 5 months postpartum at day 5 (+/-2) of the menstrual cycle: mean arterial pressure, body mass index, plasma volume and the clotting function. In the subsequent pregnancy we determined, birth weight, birth-weight centile and the incidence of preterm birth, fetal growth restriction, pregnancy-induced hypertension, preeclampsia and HELLP-syndrome. We only included in the final analysis normotensive subjects with a thrombophilic phenotype at the time of the pre-pregnant screening, who had a subsequent singleton pregnancy, ongoing beyond 16 weeks gestation within 1 year after pre-pregnant evaluation. As a consequence, 23 formerly preeclamptic women and 12 controls were eligible for final analysis. The thrombophilic formerly preeclamptic participants received aspirin in combination with low-molecular-weight heparin throughout pregnancy. If thrombophilia was diagnosed on the basis of hyperhomocysteinemia, the treatment consisted of aspirin, pyridoxine and folic acid, instead.

Results: Among 250 formerly preeclamptic 131/250 (52%) had a normotensive thrombophilic phenotype. Only 23 (18%) of these 131 participants had an ongoing pregnancy within 1 year. They were allocated to subgroup THROMB. None of the controls had hypertension or thrombophilia. In contrast, 12/15 (80%) controls had an ongoing pregnancy within a year. The observations in the THROMB subgroup were compared with those in the control group. None of the baseline demographic and blood pressure variables differed between THROMB and controls. With respect to pregnancy outcome, the incidence of the following pregnancy complications were observed in THROMB subjects: preterm birth: 9%, pregnancy-induced hypertension: 44%, preeclampsia: 13%, HELLP-syndrome: 13%, and fetal growth restriction: 30%. A low non-pregnant plasma volume was found to predispose for hypertensive complications in a subsequent pregnancy.

Conclusion: Pre-pregnant plasma volume in normotensive thrombophilic formerly preeclamptic women have predictive value with respect to hypertensive complications in the subsequent pregnancy.