INTRODUCTION: The importance of cardiovascular health in relation to pregnancy outcome is increasingly acknowledged. Women who develop certain pregnancy complications, in particular preeclampsia, are at higher risk for future cardiovascular disease. Independent of its outcome, pregnancy requires a substantial adaptive response of the maternal cardiovascular system. In the Hemodynamic Adaptation to Pregnancy and Placenta-related Outcome (HAPPO) study, we aim to examine longitudinal maternal haemodynamic adaptation to pregnancy from the preconception period onwards. We hypothesise that women who will develop adverse pregnancy outcomes have impaired cardiovascular health before conception, leading to haemodynamic maladaptation to pregnancy and diminished uteroplacental vascular development. METHODS AND ANALYSIS: In this prospective cohort study embedded in the Rotterdam periconception cohort, 200 women with a history of placenta-related pregnancy complications (high-risk group) and 100 women with an uncomplicated obstetric history (low-risk group) will be included. At five moments (preconception, first, second and third trimester and postdelivery), women will undergo an extensive examination of the macrocirculatory and microcirculatory system and uteroplacental vascular development. The main outcome measures are differences in maternal haemodynamic adaptation to pregnancy between women with and without placenta-related pregnancy complications. In a multivariate linear mixed model, the relationship between maternal haemodynamic adaptive parameters, (utero)placental vascularisation indices and clinical outcomes (occurrence of pregnancy complications, embryonic and fetal growth trajectories, miscarriage rate, gestational age at delivery, birth weight) will be studied. Subgroup analysis will be performed to study baseline and trajectory differences between high-risk and low-risk women, independent of subsequent pregnancy outcome. ETHICS AND DISSEMINATION: This study protocol was approved by the Medical Ethics Committee of the Erasmus MC, Rotterdam, the Netherlands (MEC 2018-150). Results will be disseminated to the medical community by publications in peer-reviewed journals and presentations at scientific congresses. Also, patient associations will be informed and the public will be informed by dissemination through (social) media. TRIAL REGISTRATION NUMBER: NL7394 (

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BMJ Open
Department of Gynaecology & Obstetrics

Bijl, R.C. (Rianne C.), Cornette, J., van den Bosch, A., Duvekot, H., Molinger, J., Willemsen, S., … Koster, M. (2019). Study protocol for a prospective cohort study to investigate Hemodynamic Adaptation to Pregnancy and Placenta-related Outcome: the HAPPO study. BMJ Open, 9(11). doi:10.1136/bmjopen-2019-033083