Long-term cardiovascular health after stopping pre-eclampsia
Authors: Anne Cathrine Staff
Journal: The Lancet (2019)

Pre-eclampsia kills approximately 76 000 women and 500 000 babies every year.1Poon LC Shennan A Hyett JA et al.The International Federation of Gynecology and Obstetrics (FIGO) initiative on pre-eclampsia: a pragmatic guide for first-trimester screening and prevention.Int J Gynaecol Obstet. 2019; 145: 1-33Crossref PubMed Scopus (127) Google Scholar The mortality rate is high in low-income countries without sufficient antenatal and obstetric care. The only current available pre-eclampsia cure is delivery of the dysfunctional placenta, which sheds excessive proinflammatory substances to the maternal cardiovasculature.2Redman CW Sargent IL Staff AC IFPA Senior Award Lecture. Making sense of pre-eclampsia—two placental causes of preeclampsia?.Placenta. 2014; 35: S20-S25Crossref PubMed Scopus (258) Google Scholar, 3Staff AC The two-stage placental model of preeclampsia: an update.J Reprod Immunol. 2019; 134–135: 1-10Crossref PubMed Scopus (61) Google Scholar High-risk women, identified in the first trimester by screening of clinical risk factors4NICEHypertension in pregnancy.: diagnosis and management. NICE guideline 133. National Institute for Health and Care Excellence, London2019Google Scholar and dysregulated placental function biomarkers,1Poon LC Shennan A Hyett JA et al.The International Federation of Gynecology and Obstetrics (FIGO) initiative on pre-eclampsia: a pragmatic guide for first-trimester screening and prevention.Int J Gynaecol Obstet. 2019; 145: 1-33Crossref PubMed Scopus (127) Google Scholar, 5Rolnik DL Wright D Poon LC et al.Aspirin versus placebo in pregnancies at high risk for preterm preeclampsia.N Engl J Med. 2017; 377: 613-622Crossref PubMed Scopus (730) Google Scholar are recommended low-dose aspirin as prophylaxis against preterm pre-eclampsia. Pre-eclampsia is an unpredictable multifaceted syndrome and can rapidly develop into life-threatening conditions, such as eclampsia.6Brown MA Magee LA Kenny LC et al.The hypertensive disorders of pregnancy: ISSHP classification, diagnosis & management recommendations for international practice.Pregnancy Hypertens. 2018; 13: 291-310Crossref PubMed Scopus (262) Google Scholar Clinical guidelines therefore recommend prompt delivery once the pre-eclamptic pregnancy reaches term—ie, at 37 weeks' gestation. As for very preterm pre-eclampsia (24–34 weeks' gestation), the current evidence suggests fetal health benefits of prolonging the pregnancy, but this in turn requires close clinical surveillance of the woman and fetus.7Churchill D Duley L Thornton JG Moussa M Ali HS Walker KF Interventionist versus expectant care for severe pre-eclampsia between 24 and 34 weeks' gestation.Cochrane Database Syst Rev. 2018; 10CD003106PubMed Google Scholar It has hitherto been uncertain what the best procedure is for late preterm pre-eclampsia diagnosed between 34 and 37 gestational weeks. Lucy Chappell and colleagues' randomised controlled trial8Chappell LC Brocklehurst P Green MA et al.Planned early delivery or expectant management for late preterm pre-eclampsia (PHOENIX): a randomised controlled trial.Lancet. 2019; (published online Aug 28.)http://dx.doi.org/10.1016/S0140-6736(19)31963-4Summary Full Text Full Text PDF Scopus (37) Google Scholar reported in The Lancet is therefore highly welcomed. Previously, a smaller randomised controlled trial showed a non-significant reduction in maternal adverse outcomes if late preterm pre-eclampsia was ended before term,9Broekhuijsen K van Baaren GJ van Pampus MG et al.Immediate delivery versus expectant monitoring for hypertensive disorders of pregnancy between 34 and 37 weeks of gestation (HYPITAT-II): an open-label, randomised controlled trial.Lancet. 2015; 385: 2492-2501Summary Full Text Full Text PDF PubMed Scopus (89) Google Scholar and a recent individual participant data meta-analysis found a likely maternal benefit to delivery before gestational week 37.10Bernardes TP Zwertbroek EF Broekhuijsen K et al.Delivery or expectant management for prevention of adverse maternal and neonatal outcomes in hypertensive disorders of pregnancy: an individual participant data meta-analysis.Ultrasound Obstet Gynecol. 2019; 53: 443-453Crossref PubMed Scopus (24) Google Scholar Chappell and colleagues determined in their appropriately powered PHOENIX trial (protocol published previously)11Chappell LC Green M Marlow N et al.Planned delivery or expectant management for late preterm pre-eclampsia: study protocol for a randomised controlled trial (PHOENIX trial).Trials. 2019; 20: 85Crossref PubMed Scopus (2) Google Scholar that planned delivery within the subsequent 48 h after randomisation in women with late preterm pre-eclampsia reduced severe maternal adverse outcomes without substantially worsening neonatal outcomes compared with the current practice of expectant management until 37 weeks' gestation. However, the planned delivery group did have a higher occurrence of neonatal unit referrals, in line with expected clinical challenges associated with neonatal lung immaturity. It was, however, reassuring that the frequency of true neonatal morbidities was not increased for this planned delivery group. Women in the expectant management group had a median of 5 days additional prolongation of pregnancy, yet more than half of them delivered before 37 weeks' gestation, with three-quarters progressing to severe forms of pre-eclampsia. The planned delivery group had a higher rate of vaginal deliveries compared with the expectant management group, which has positive implications for future obstetric history, including less risk for uterine ruptures and invasive placentas. Furthermore, the total health costs of planned delivery were lower than for expectant management in this UK setting, in line with the shorter observation time for predelivery, less severe maternal morbidities, and no increase in neonatal morbidity. Chappell and colleagues' wisely suggest shared decision making with late preterm pre-eclamptic women (34–37 weeks' gestation), offering initiation of delivery with the aim of reducing maternal morbidity and severe hypertension, balanced against the increased risk of neonatal unit admissions, albeit without increasing newborn respiratory or other morbidities. Women with a history of pre-eclampsia are at increased risk for several non-communicable disorders, including cardiovascular disease. The associations strengthen with repeated pre-eclampsia, fetal growth restriction, and preterm onset.12Staff AC Redman CW Williams D et al.Pregnancy and long-term maternal cardiovascular health: progress through harmonization of research cohorts and biobanks.Hypertension. 2016; 67: 251-260Crossref PubMed Scopus (75) Google Scholar The mechanisms behind these associations are not clear. One theory, in addition to the shared risk theory, is that stress signals from the dysfunctional placenta to the maternal cardiovasculature might aggravate cardiovascular dysfunction and promote premature cardiovascular disease.12Staff AC Redman CW Williams D et al.Pregnancy and long-term maternal cardiovascular health: progress through harmonization of research cohorts and biobanks.Hypertension. 2016; 67: 251-260Crossref PubMed Scopus (75) Google Scholar Initiating delivery in late preterm pre-eclampsia rather than waiting until term might theoretically reduce the stress on the woman's cardiovasculature. Whether a change to active delivery of women with late preterm pre-eclampsia will also benefit maternal cardiovascular health in the long term should be addressed in future follow-up studies. The PHOENIX trial8Chappell LC Brocklehurst P Green MA et al.Planned early delivery or expectant management for late preterm pre-eclampsia (PHOENIX): a randomised controlled trial.Lancet. 2019; (published online Aug 28.)http://dx.doi.org/10.1016/S0140-6736(19)31963-4Summary Full Text Full Text PDF Scopus (37) Google Scholar findings are likely to be generalisable to similar health-care settings. A more active delivery procedure in late preterm pre-eclampsia would probably be beneficial in other high and middle income countries that have a high level of care available to preterm infants with immaturity challenges. In low-income settings without adequate pregnancy, delivery, and neonatal follow-up, the risks to the premature infant must be weighed against the reduction in adverse maternal outcomes before recommending active delivery over expectant surveillance for the late preterm pre-eclampsia group. The high global rates of maternal and fetal deaths due to pre-eclampsia are unacceptable. Access to adequate antenatal and delivery care in low-income settings is essential to prevent deaths and to improve maternal and offspring health outcomes globally. I declare no competing interests. Planned early delivery or expectant management for late preterm pre-eclampsia (PHOENIX): a randomised controlled trialThere is strong evidence to suggest that planned delivery reduces maternal morbidity and severe hypertension compared with expectant management, with more neonatal unit admissions related to prematurity but no indicators of greater neonatal morbidity. This trade-off should be discussed with women with late preterm pre-eclampsia to allow shared decision making on timing of delivery. Full-Text PDF Open Access