Pre-eclampsia

Chappell, Lucy C; Cluver, Catherine; Kingdom, John; Tong, Stephen

doi:10.1016/s0140-6736(20)32335-7

Cited by 496 publications

(465 citation statements)

References 118 publications

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“…Pre-eclampsia is a leading cause of maternal and neonatal morbidity and mortality 12. In South Africa, hypertensive disorders of pregnancy account for 15% of maternal deaths 3.…”

Section: Introductionmentioning

confidence: 99%

Use of metformin to prolong gestation in preterm pre-eclampsia: randomised, double blind, placebo controlled trial

Cluver

Hiscock

Decloedt

et al. 2021

BMJ

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Objective To evaluate whether extended release metformin could be used to prolong gestation in women being expectantly managed for preterm pre-eclampsia. Design Randomised, double blind, placebo controlled trial. Setting Referral hospital in Cape Town, South Africa. Participants 180 women with preterm pre-eclampsia between 26+0 to 31+6 weeks’ gestation undergoing expectant management: 90 were randomised to extended release metformin and 90 to placebo. Intervention 3 g of oral extended release metformin or placebo daily, in divided doses, until delivery. Main outcome measure The primary outcome was prolongation of gestation. Results Of 180 participants, one woman delivered before taking any trial drug. The median time from randomisation to delivery was 17.7 days (interquartile range 5.4-29.4 days; n=89) in the metformin arm and 10.1 (3.7-24.1; n=90) days in the placebo arm, a median difference of 7.6 days (geometric mean ratio 1.39, 95% confidence interval 0.99 to 1.95; P=0.057). Among those who continued to take the trial drug at any dose, the median prolongation of gestation in the metformin arm was 17.5 (interquartile range 5.4-28.7; n=76) days compared with 7.9 (3.0-22.2; n=74) days in the placebo arm, a median difference of 9.6 days (geometric mean ratio 1.67, 95% confidence interval 1.16 to 2.42). Among those who took the full dosage, the median prolongation of gestation in the metformin arm was 16.3 (interquartile range 4.8-28.8; n=40) days compared with 4.8 (2.5-15.4; n=61) days in the placebo arm, a median difference of 11.5 days (geometric mean ratio 1.85, 95% confidence interval 1.14 to 2.88). Composite maternal, fetal, and neonatal outcomes and circulating concentrations of soluble fms-like tyrosine kinase-1, placental growth factor, and soluble endoglin did not differ. In the metformin arm, birth weight increased non-significantly and length of stay decreased in the neonatal nursery. No serious adverse events related to trial drugs were observed, although diarrhoea was more common in the metformin arm. Conclusions This trial suggests that extended release metformin can prolong gestation in women with preterm pre-eclampsia, although further trials are needed. It provides proof of concept that treatment of preterm pre-eclampsia is possible. Trial registration Pan African Clinical Trial Registry PACTR201608001752102 https://pactr.samrc.ac.za/ .

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“…Pre-eclampsia is a leading cause of maternal and neonatal morbidity and mortality 12. In South Africa, hypertensive disorders of pregnancy account for 15% of maternal deaths 3.…”

Section: Introductionmentioning

confidence: 99%

Use of metformin to prolong gestation in preterm pre-eclampsia: randomised, double blind, placebo controlled trial

Cluver

Hiscock

Decloedt

et al. 2021

BMJ

Self Cite

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“…Hypertensive disorders of pregnancy (HDP) affect up to 10% of pregnant women and remain major causes of maternal and perinatal morbidity and mortality worldwide (1)(2)(3)(4)(5). Identifying women at risk early in the course of such disorders, especially gestational hypertension and preeclampsia would facilitate intensive monitoring and intervention.…”

Section: Introductionmentioning

confidence: 99%

Increased Uric Acid, Gamma-Glutamyl Transpeptidase and Alkaline Phosphatase in Early-Pregnancy Associated With the Development of Gestational Hypertension and Preeclampsia

Chen

Ou²,

Lin³

et al. 2021

Front. Cardiovasc. Med.

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Background: Previous studies have reported that biomarkers of liver injury and renal dysfunction were associated with hypertensive disorders of pregnancy (HDP). However, the associations of these biomarkers in early pregnancy with the risk of HDP and longitudinal blood pressure pattern during pregnancy were rarely investigated in prospective cohort studies.Methods: A total of 1,041 pregnant women were enrolled in this prospective cohort study. BP was assessed in four stages throughout pregnancy. The following biomarkers were measured at early pregnancy before 18 weeks gestation: lactate dehydrogenase (LDH), aspartate aminotransferase to alanine aminotransferase ratio (AST/ALT), gamma-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP), uric acid (UA), and estimated glomerular filtration rate (eGFR). Linear mixed-effects and logistic regression models were used to examine the associations of these biomarkers with longitudinal BP pattern during pregnancy and HDP incidence, respectively.Results: In unadjusted models, higher serum UA, GGT, ALP, and LDH levels, as well as lower eGFR and AST/ALT, were associated with higher BP levels during pregnancy and an increased risk of HDP. After adjustment for maternal age, pre-pregnancy BMI and other potential confounders, UA, GGT, ALP, and LDH remained positively associated with both BP and HDP. However, eGFR and AST/ALT were not associated with HDP after adjusting for potential confounders. When including all 6 biomarkers simultaneously in multivariable analyses, increased UA, GGT, and ALP significantly associated with gestational hypertension and preeclampsia.Conclusion: This study suggests that increased UA, GGT, and ALP in early-pregnancy are independent risk factors of gestational hypertension and preeclampsia.

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“…Hypertension after week 20 of pregnancy is one of the major symptoms of preeclampsia. The current concept considers defective placentation with ensuing insufficient uteroplacental perfusion as an initiating event of preeclampsia and preeclampsia hypertension [4,[57][58][59]. Dysfunctional placentation is thought to develop as a result of insufficient cytotrophoblast invasion of spiral arterioles [59].…”

Section: The Interrelationship Between Impaired Arterial Function Dysfunctional Placentation and Hypertensionmentioning

confidence: 99%

“…Monitoring of blood pressure during pregnancy is an important measure of diagnosis because high blood pressure which exceeds 140/90 mm Hg is a common symptom of preeclampsia [3]. Currently, the only treatment of preeclampsia is (premature) delivery of the infant [4].…”

Section: Introductionmentioning

confidence: 99%

Pathological AT1R-B2R Protein Aggregation and Preeclampsia

Quitterer

AbdAlla

2021

Cells

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Preeclampsia is one of the most frequent and severe complications of pregnancy. Symptoms of preeclampsia usually occur after 20 weeks of pregnancy and include hypertension and kidney dysfunction with proteinuria. Up to now, delivery of the infant has been the most effective and life-saving treatment to alleviate symptoms of preeclampsia because a causative treatment does not exist, which could prolong a pregnancy complicated with preeclampsia. Preeclampsia is a complex medical condition, which is attributed to a variety of different risk factors and causes. Risk factors account for insufficient placentation and impaired vasculogenesis and finally culminate in this life-threatening condition of pregnancy. Despite progress, many pathomechanisms and causes of preeclampsia are still incompletely understood. In recent years, it was found that excessive protein complex formation between G-protein-coupled receptors is a common sign of preeclampsia. Specifically, the aberrant heteromerization of two vasoactive G-protein-coupled receptors (GPCRs), the angiotensin II AT1 receptor and the bradykinin B2 receptor, is a causative factor of preeclampsia symptoms. Based on this knowledge, inhibition of abnormal GPCR protein complex formation is an experimental treatment approach of preeclampsia. This review summarizes the impact of pathological GPCR protein aggregation on symptoms of preeclampsia and delineates potential new therapeutic targets.

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Pre-eclampsia

Cited by 496 publications

References 118 publications

Use of metformin to prolong gestation in preterm pre-eclampsia: randomised, double blind, placebo controlled trial

Use of metformin to prolong gestation in preterm pre-eclampsia: randomised, double blind, placebo controlled trial

Increased Uric Acid, Gamma-Glutamyl Transpeptidase and Alkaline Phosphatase in Early-Pregnancy Associated With the Development of Gestational Hypertension and Preeclampsia

Pathological AT1R-B2R Protein Aggregation and Preeclampsia

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