Association of pre-pregnancy cardiovascular function with subsequent pregnancy outcome of pre-eclampsia or fetal growth restriction

Abstract

Pre-eclampsia (PE) and fetal growth restriction (FGR) are pregnancy-specific disorders associated with increased risk of maternal cardiovascular disease (CVD) later in life. It is unclear if this association is causal, or driven by similar antecedent risk factors. Clarification requires recruitment prior to conception which is methodologically difficult with high attrition rate and loss of outcome numbers to non-conception / miscarriage. Few prospective studies have therefore been adequately powered to address these questions. We recruited 530 healthy women (mean age: 35.0 years) intending to conceive, and assessed cardiac output (CO), cardiac index (CI), stroke volume (SV), total peripheral resistance (TPR), mean arterial pressure (MAP) and heart rate (HR) prior to pregnancy. Participants were followed to completion of pregnancy with repeat longitudinal assessments. Of 356 spontaneously conceived pregnancies, 15 (4.2%) were affected by PE and/or FGR. Women who subsequently developed PE/FGR had lower pre-conception CO (4.5 vs 5.8 L/min; p = 0.002) and CI (3.0 vs 3.3 L/min/m2; p = 0.031), while MAP (87.1 vs 82.3 mmHg; p = 0.05) and TPR (1432.3 vs 1392.6 dynes.sec.cm-5; p <0.001) were higher. Longitudinal trajectories for CO and TPR were similar between affected and healthy pregnancies, but the former group showed a more exaggerated fall in MAP in the first trimester, followed by a steeper rise and a steeper fall to postpartum values. Highly significant relationships were observed between CO, TPR and MAP and gestational epoch. We conclude that in healthy women, an altered pre-pregnancy haemo-dynamic phenotype is associated with the subsequent development of PE/FGR.