We searched PubMed and the Cochrane Library with the terms “pre-eclampsia” and “hypertension and pregnancy”, and cross-referenced them with the following terms: “epidemiology”, “definition”, “prediction”, “prevention”, “management”, “clinical trials”, “preconception care”, and “thrombophilia”. We restricted the search to studies done in humans and published in English. We limited our search to publications between January, 2010, and January, 2015, with a focus on publications after 2012. We
SeminarPre-eclampsia
Introduction
Pre-eclampsia is a pregnancy-specific syndrome that affects 3–5% of pregnancies and is traditionally diagnosed when a pregnant woman presents with increased blood pressure and proteinuria.1 Pre-eclampsia is one of the main causes of maternal, fetal, and neonatal mortality, especially in low-income and middle-income countries.2 In this Seminar, we describe the current management of pre-eclampsia in terms of prediction, prevention, diagnosis, treatment, and long-term consequences. Our aim is to provide a guide for the optimal management of pre-eclampsia, both in low-resource and high-resource settings.
The acute clinical importance of pre-eclampsia lies in its relation to maternal and neonatal mortality and morbidity. When left untreated, pregnant women with pre-eclampsia have severe complications such as eclampsia, liver rupture, stroke, pulmonary oedema, or kidney failure, which can all be lethal.3 Pre-eclampsia is also related to fetal growth restriction and preterm birth, either spontaneous or through iatrogenic delivery. Children born to mothers with pre-eclampsia have an increased risk of bronchopulmonary dysplasia and cerebral palsy, caused by preterm birth and being small for gestational age.4, 5 Pre-eclampsia decreases health-related quality of life and increases the risk of post-partum depression.6, 7
The cause of pre-eclampsia is unclear. Some women are genetically predisposed to developing the disease which may run in families.8 Robust associations have been identified between pre-eclampsia and gene variants involved in thrombophilia, inflammation, oxidative stress and the renin angiotensin system.9, 10 In a meta-analysis of studies to identify gene variants associated with pre-eclampsia, 22 variants were reproducible across studies with 7 remaining significant upon meta-analysis. However, thrombophillic gene variants in F2 and F5 have been consistently associated with the disease.11, 12, 13 Interactions between maternal gene variants and genes encoding fetal HLA-C have been shown to predispose pregnancies to pre-eclampsia in white people, sub-Saharan Africans, and the Chinese Han population, suggesting a role of an impaired immune tolerance in the pathogenesis of pre-eclampsia.14, 15, 16 In women with pre-eclampsia, placental antiangiogenic factors are upregulated and disrupt the maternal endothelium, leading to an antiangiogenic state that can result in clinical signs of pre-eclampsia.17
Section snippets
Definition of pre-eclampsia
The diagnostic criteria for pre-eclampsia were changed by the International Society for the Study of Hypertension in Pregnancy (ISSHP) in 2014.18 ISSHP defines pre-eclampsia as de-novo hypertension present after 20 weeks of gestation combined with proteinuria (>300 mg/day), other maternal organ dysfunction, such as renal insufficiency, liver involvement, neurological or haematological complications, uteroplacental dysfunction, or fetal growth restriction. As proteinuria is no longer required in
Prediction of pre-eclampsia
Although perfect prediction of pre-eclampsia has been a noble but hitherto elusive goal, distinction between women who are at low risk and high risk is possible. Strong risk factors are previous pre-eclampsia or hypertension in pregnancy, chronic kidney disease, hypertension, diabetes (type 1 or type 2), and autoimmune disorders, including systemic lupus erythematosus or antiphospholipid syndrome.20, 26 Moderate risk factors are first pregnancy, age 40 years or more, a pregnancy interval
Prevention of pre-eclampsia
With reliable risk prediction for pre-eclampsia on the horizon, interventions to prevent pre-eclampsia become more important (table 1). Aspirin is the drug of choice for the prevention of pre-eclampsia, based on the findings of an individual patient data (IPD) meta-analysis that showed moderate benefit of aspirin (RR 0·90, 95% CI 0·84–0·97).41 Other pharmacological drugs, such as heparin and dalteparin, show promising effects in women who are at increased risk for pre-eclampsia, but unlike
Clinical presentation of pre-eclampsia
The clinical presentation of pre-eclampsia is varied.1 Women are mostly asymptomatic, and the disease is often diagnosed during routine antenatal care. Maternal adverse outcomes are recorded in 10% of women with pre-eclampsia, whereas this risk increases to 15% in women with early-onset disease.62
The clinical presentation and findings could be indicative of the underlying multisystem morbidity. Women with severe pre-eclampsia might present with symptoms such as headache, visual disturbances
Signs and symptoms
Clinicians routinely obtain information on the presence of symptoms associated with progression to severe disease. However, individual symptoms of pre-eclampsia such as headache (AUC 0·58, 95% CI 0·24–0·86), epigastric pain (0·70, 0·30–0·93), and visual disturbances (0·74, 0·33–0·94) do not adequately predict adverse maternal outcomes.64 Chest pain and dyspnoea also have limited predictive value (0·64, 0·54–0·74) for composite adverse maternal outcomes.62 Authors of a systematic review reported
Laboratory tests
The maternal spot urine estimate of the protein:creatinine ratio is promising for the detection of proteinuria in women with suspected pre-eclampsia. There is insufficient knowledge of how the protein:creatinine ratio should be used in clinical practice because test accuracy and prevalence across studies are heterogeneous.71 The degree of proteinuria is not predictive for placental abruption or HELLP syndrome, whereas data on the capacity of proteinuria to predict eclampsia are conflicting.67,
Prediction models
Because all the above-mentioned tests have limited accuracy individually to predict complications, attempts have been made to integrate these tests into multivariable models. The full pre-eclampsia integrated estimate of risk (PIERS) multivariable model predicts composite adverse maternal outcome within 48 h in women admitted to hospital for pre-eclampsia (AUC ROC 0·88, 95% CI 0·84–0·92). In PIERS, the predictive factors are gestational age, platelet count, chest pain or dyspnoea, oxygen
Clinical management of women diagnosed with pre-eclampsia
Novel therapies for pre-eclampsia target various aspects of pre-eclampsia pathogenesis and are in development, yet the only cure for pre-eclampsia is delivery of the placenta (panel 1).86 On the basis of consensus, severe hypertension or end-organ complications should be managed in an inpatient setting. Subspecialty consultation is advised to address underappreciation of the risks of pre-eclampsia. An early epidural catheter will attenuate pain-induced hypertension and enable neuraxial
When to deliver the woman with pre-eclampsia
Because delivery of the placenta is the only cure for pre-eclampsia, optimal timing of delivery is crucial. The decision to deliver is based on the balance between the maternal and fetal risks of continuing the pregnancy and the neonatal risks of ending the pregnancy. In pre-eclampsia, the main driver is an assessment of the risk to the mother, but sometimes a growth-restricted child can become compromised and necessitate induction.
In a study that compared induction of labour and expectant
Cardiovascular risk after pre-eclampsia
In 1964, Epstein showed that women with pre-eclampsia were at increased risk of developing cardiovascular disease later in life.108 Until recently, women who have had a pregnancy complicated by hypertensive disorders, including pre-eclampsia, were not offered preventive measures. Evidence now overwhelmingly suggests that women who had pregnancy-related complications such as hypertensive disorders, gestational diabetes, intrauterine growth restriction, or preterm delivery have increased risk of
Management of pre-eclampsia in low-resource settings
Pre-eclampsia and its serious consequences, including death, are many times more common in low-resource settings than in well resourced settings.20, 127 This epidemiological finding provides a model for seeking clues to the cause of pre-eclampsia and an obligation to direct global efforts to reduce mortality and morbidity from pre-eclampsia towards low-resource settings. Demographic risk factors for pre-eclampsia include young or advanced maternal age, family or personal history of hypertensive
Future research
Despite the scientific efforts (>17 000 PubMed citations on pre-eclampsia since 2010) to increase knowledge of the aetiological and clinical aspects of pre-eclampsia, the incidence of the disease is not decreasing138 and is still the main cause of maternal mortality, with significant adverse effects mainly in low-income and middle-income countries. Standardisation and collaboration in research will probably improve the use of resources. The Core Outcome Measures in Effectiveness Trials (COMET)
Search strategy and selection criteria
References (142)
- et al.
Moving beyond essential interventions for reduction of maternal mortality (the WHO Multicountry Survey on Maternal and Newborn Health): a cross-sectional study
Lancet
(2013) - et al.
Maternal preeclampsia predicts the development of bronchopulmonary dysplasia
J Pediatr
(2010) - et al.
Determinants of health-related quality of life in the postpartum period after obstetric complications
Eur J Obstet Gynecol Reprod Biol
(2015) - et al.
The genetics of pre-eclampsia and other hypertensive disorders of pregnancy
Best Pract Res Clin Obstet Gynaecol
(2011) - et al.
Molecular genetics of preeclampsia and HELLP syndrome—a review
Biochim Biophys Acta
(2012) - et al.
Association of maternal KIR and fetal HLA-C genes with the risk of preeclampsia in the Chinese Han population
Placenta
(2015) - et al.
The classification, diagnosis and management of the hypertensive disorders of pregnancy: A revised statement from the ISSHP
Pregnancy Hypertens
(2014) - et al.
Early prediction and prevention of pre-eclampsia
Best Pract Res Clin Obstet Gynaecol
(2011) - et al.
Abnormal blood biomarkers in early pregnancy are associated with preeclampsia: a meta-analysis
Eur J Obstet Gynecol Reprod Biol
(2014) - et al.
Antiplatelet agents for prevention of pre-eclampsia: a meta-analysis of individual patient data
Lancet
(2007)
A dietary pattern characterized by high intake of vegetables, fruits, and vegetable oils is associated with reduced risk of preeclampsia in nulliparous pregnant Norwegian women
J Nutr
Antepartum dalteparin versus no antepartum dalteparin for the prevention of pregnancy complications in pregnant women with thrombophilia (TIPPS): a multinational open-label randomised trial
Lancet
Low-molecular-weight heparin added to aspirin in the prevention of recurrent early-onset pre-eclampsia in women with inheritable thrombophilia: the FRUIT-RCT
J Thromb Haemost
Prediction of adverse maternal outcomes in pre-eclampsia: development and validation of the fullPIERS model
Lancet
Clinical, psychosocial, and economic effects of antenatal day care for three medical complications of pregnancy: a randomised controlled trial of 395 women
Lancet
The role of platelet counts in the assessment of inpatient women with preeclampsia
J Obstet Gynaecol Can
Diagnosis, evaluation, and management of the hypertensive disorders of pregnancy
Pregnancy Hypertens
OS014. Which first-line drug to control severe hypertension in pregnancy? A pilot study
Pregnancy Hypertens
A randomized, double-blind trial of oral nifedipine and intravenous labetalol in hypertensive emergencies of pregnancy
Am J Obstet Gynecol
Pharmacotherapy for preeclampsia in low and middle income countries: an analysis of essential medicines lists
J Obstet Gynaecol Can
Therapy with both magnesium sulfate and nifedipine does not increase the risk of serious magnesium-related maternal side effects in women with preeclampsia
Am J Obstet Gynecol
Induction of labour versus expectant monitoring for gestational hypertension or mild pre-eclampsia after 36 weeks' gestation (HYPITAT): a multicentre, open-label randomised controlled trial
Lancet
Foley catheter versus vaginal prostaglandin E2 gel for induction of labour at term (PROBAAT trial): an open-label, randomised controlled trial
Lancet
Pre-eclampsia rates in the United States, 1980-2010: age-period-cohort analysis
BMJ
A prospective study of maternal, fetal and neonatal deaths in low- and middle-income countries
Bull World Health Organ
Mediators of the association between pre-eclampsia and cerebral palsy: population based cohort study
BMJ
Perinatal complications increase the risk of postpartum depression. The Generation R Study
BJOG
Angiogenic factors in diagnosis, management, and research in preeclampsia
Hypertension
Genetic variants in pre-eclampsia: a meta-analysis
Hum Reprod Update
Genetic association studies in pre-eclampsia: systematic meta-analyses and field synopsis
Int J Epidemiol
Maternal genotype and severe preeclampsia: a HuGE review
Am J Epidemiol
Combinations of maternal KIR and fetal HLA-C genes influence the risk of preeclampsia and reproductive success
J Exp Med
A KIR B centromeric region present in Africans but not Europeans protects pregnant women from pre-eclampsia
Proc Natl Acad Sci USA
Soluble endoglin contributes to the pathogenesis of preeclampsia
Nat Med
Diagnosis, evaluation, and management of the hypertensive disorders of pregnancy
J Obstet Gynaecol Can
Hypertension in pregnancy. NICE clinical guideline 107
Hypertension in Pregnancy
Obstet Gynecol
Can we use the Omron T9P automated blood pressure monitor in pregnancy?
Hypertens Pregnancy
Validation of the Omron M7 and Microlife 3BTO-A blood pressure measuring devices in preeclampsia
Hypertens Pregnancy
When are randomised trials unnecessary? Picking signal from noise
BMJ
Redefining preeclampsia using placenta-derived biomarkers
Hypertension
Chronic hypertension and pregnancy outcomes: systematic review and meta-analysis
BMJ
Risk of adverse pregnancy outcomes in women with polycystic ovary syndrome: population based cohort study
BMJ
Gestational hypertension and preeclampsia in living kidney donors
N Engl J Med
Clinical risk prediction for pre-eclampsia in nulliparous women: development of model in international prospective cohort
BMJ
Circulating angiogenic factors and the risk of preeclampsia
N Engl J Med
The promise of angiogenic markers for the early diagnosis and prediction of preeclampsia
Clin Chem
Diagnostic accuracy of placental growth factor in women with suspected preeclampsia: a prospective multicenter study
Circulation
First-trimester prediction of hypertensive disorders in pregnancy
Hypertension
First-trimester uterine artery Doppler and adverse pregnancy outcome: a meta-analysis involving 55,974 women
Ultrasound Obstet Gynecol
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