From the Institute for Reproductive and Developmental Biology, Imperial College, London, United Kingdom (F.L.F., G.M., S.C., D.A.M., P.R.B., C.C.L.).
Experimental Medicine and Immunotherapeutics, University of Cambridge, United Kingdom (A.M.M., C.M.M., I.B.W.).
Hypertension. 2018 Aug;72(2):442-450. doi: 10.1161/HYPERTENSIONAHA.118.11092. Epub 2018 Jul 2.
Preeclampsia and fetal growth restriction during pregnancy are associated with increased risk of maternal cardiovascular disease later in life. It is unclear whether this association is causal or driven by similar antecedent risk factors. Clarification requires recruitment before conception which is methodologically difficult with high attrition rates and loss of outcome numbers to nonconception/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, cardiac index, stroke volume, total peripheral resistance, mean arterial pressure, and heart rate before pregnancy. Participants were followed to completion of subsequent pregnancy with repeat longitudinal assessments. Of 356 spontaneously conceived pregnancies, 15 (4.2%) were affected by preeclampsia and fetal growth restriction. Women who subsequently developed preeclampsia/fetal growth restriction had lower preconception cardiac output (4.9 versus 5.8 L/min; =0.002) and cardiac index (2.9 versus 3.3 L/min per meter; =0.031) while mean arterial pressure (87.1 versus 82.3 mm Hg; =0.05) and total peripheral resistance (1396.4 versus 1156.1 dynes sec cm; <0.001) were higher. Longitudinal trajectories for cardiac output and total peripheral resistance were similar between affected and healthy pregnancies, but the former group showed a more exaggerated fall in mean arterial pressure in the first trimester, followed by a steeper rise and a steeper fall to postpartum values. Significant relationships were observed between cardiac output, total peripheral resistance, and mean arterial pressure and gestational epoch. We conclude that in healthy women, an altered prepregnancy hemodynamic phenotype is associated with the subsequent development of preeclampsia/fetal growth restriction.
子痫前期和胎儿生长受限与母亲在以后生活中患心血管疾病的风险增加有关。目前尚不清楚这种关联是因果关系还是由类似的前置风险因素驱动的。在受孕前进行招募以明确这一点在方法学上具有挑战性,因为高退出率和非受孕/流产导致结局数量减少。因此,很少有前瞻性研究有足够的能力来解决这些问题。我们招募了 530 名有怀孕意向的健康女性(平均年龄:35.0 岁),在怀孕前评估心输出量、心指数、每搏输出量、总外周阻力、平均动脉压和心率。参与者随后完成了后续怀孕的随访,并进行了重复的纵向评估。在 356 例自发受孕的妊娠中,有 15 例(4.2%)受到子痫前期和胎儿生长受限的影响。随后发生子痫前期/胎儿生长受限的女性在受孕前心输出量(4.9 与 5.8 L/min;=0.002)和心指数(2.9 与 3.3 L/min/m;=0.031)较低,而平均动脉压(87.1 与 82.3 mm Hg;=0.05)和总外周阻力(1396.4 与 1156.1 dynes sec cm;<0.001)较高。受影响和健康妊娠的心脏输出和总外周阻力的纵向轨迹相似,但前者在孕早期的平均动脉压下降更为明显,随后急剧上升,然后急剧下降至产后值。心输出量、总外周阻力和平均动脉压与妊娠周期之间存在显著的关系。我们的结论是,在健康女性中,妊娠前的血流动力学表型改变与随后发生的子痫前期/胎儿生长受限有关。