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Corticosteroids for HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome in pregnancy.

ABSTRACT: BACKGROUND:Pre-eclampsia is a relatively common complication of pregnancy. HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome is a severe manifestation of pre-eclampsia with significant morbidity and mortality for pregnant women and their children. Corticosteroids are commonly used in the treatment of HELLP syndrome in the belief that they improve outcomes. OBJECTIVES:To determine the effects of corticosteroids on women with HELLP syndrome and their children. SEARCH STRATEGY:We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 June 2010). SELECTION CRITERIA:Randomized controlled trials comparing any corticosteroid with placebo, no treatment, or other drug; or comparing one corticosteroid with another corticosteroid or dosage in women with HELLP syndrome. DATA COLLECTION AND ANALYSIS:Two review authors assessed trial quality and extracted data independently. MAIN RESULTS:Eleven trials (550 women) compared corticosteroids with placebo or no treatment. There was no difference in the risk of maternal death (risk ratio (RR) 0.95, 95% confidence interval (CI) 0.28 to 3.21), maternal death or severe maternal morbidity (RR 0.27, 95% CI 0.03 to 2.12), or perinatal/infant death (RR 0.64, 95% CI 0.21 to 1.97). The only clear effect of treatment on individual outcomes was improved platelet count (standardized mean difference (SMD) 0.67, 95% CI 0.24 to 1.10). The effect on platelet count was strongest for women who commenced treatment antenatally (SMD 0.80, 95% CI 0.25 to 1.35).Two trials (76 women) compared dexamethasone with betamethasone. There was no clear evidence of a difference between groups in respect to perinatal/infant death (RR 0.95, 95% CI 0.15 to 6.17) or severe perinatal/infant morbidity or death (RR 0.64, 95% CI 0.27 to 1.48). Maternal death and severe maternal morbidity were not reported. In respect to platelet count, dexamethasone was superior to betamethasone (MD 6.02, 95% CI 1.71 to 10.33), both when treatment was commenced antenatally (MD 8.10, 95% CI 6.23 to 9.97) and postnatally (MD 3.70, 95% CI 0.96 to 6.44). AUTHORS' CONCLUSIONS:There was no clear evidence of any effect of corticosteroids on substantive clinical outcomes. Those receiving steroids showed significantly greater improvement in platelet counts which was greater for those receiving dexamethasone than those receiving betamethasone. There is to date insufficient evidence of benefits in terms of substantive clinical outcomes to support the routine use of steroids for the management of HELLP. The use of corticosteroids may be justified in clinical situations in which increased rate of recovery in platelet count is considered clinically worthwhile.

SUBMITTER: Woudstra DM

PROVIDER: S-EPMC4171033 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature

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Corticosteroids for HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome in pregnancy.

Woudstra Douglas M DM Chandra Sue S Hofmeyr G Justus GJ Dowswell Therese T

The Cochrane database of systematic reviews 20100908 9

<h4>Background</h4>Pre-eclampsia is a relatively common complication of pregnancy. HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome is a severe manifestation of pre-eclampsia with significant morbidity and mortality for pregnant women and their children. Corticosteroids are commonly used in the treatment of HELLP syndrome in the belief that they improve outcomes.<h4>Objectives</h4>To determine the effects of corticosteroids on women with HELLP syndrome and their children.<h4>Sea ...[more]

PMID: 20824872

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Project description:Excessive accumulation of misfolded proteins was recently demonstrated in preeclampsia. We examined levels and activity of circulatory proteasome and immunoproteasome (inflammatory subtype) in preeclampsia and hemolysis, elevated liver enzymes, and thrombocytopenia (HELLP) syndrome. We analyzed samples from women with hypertensive pregnancy disorders (n=115), including preeclampsia with severe features (sPE) and HELLP syndrome, and normotensive controls (n=45). Plasma proteasome and immunoproteasome immunoreactivity were determined by quantifying the α-subunit of the 20S core and β5i (proteasome subunit beta 8 [PSMB8]), respectively. Plasma proteasome activity was analyzed with fluorogenic substrates. MG132, lactacystin, and ONX0914 were used to inhibit the circulating proteasome and immunoproteasome, respectively. Plasma cytokine profiles were evaluated by multiplex immunoassay. Placental expression of β5 (constitutive proteasome) and β5i (immunoproteasome) was interrogated by immunohistochemistry. Women with sPE had increased plasma 20S levels ( P<0.001) and elevated lytic activities (chymotrypsin-like 7-fold, caspase-like 4.2-fold, trypsin-like 2.2-fold; P <0.001 for all) compared with pregnant controls. Women with features of HELLP displayed the highest plasma proteasome levels and activity, which correlated with decreased IFN-γ (interferon-γ), and increased IL (interleukin)-8 and IL-10. In sPE and HELLP, chymotrypsin-like activity was suppressed by proteasome inhibitors including ONX0914. Compared with gestational age-matched controls, sPE placentas harbored increased β5 and β5i immunostaining in trophoblasts. β5i signal was elevated in HELLP with predominant staining in villous core, extravillous trophoblasts in placental islands, and extracellular vesicles in intervillous spaces. Pregnancy represents a state of increased proteostatic stress. sPE and HELLP were characterized by significant upregulation in circulating levels and lytic activity of the proteasome that was partially explained by placental immunoproteasome upregulation.

Project description:Hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome is one of the most severe forms of preeclampsia and aggravates both maternal and perinatal prognosis. The systematic review available in Cochrane Library compared corticosteroid (dexamethasone, betamethasone, or prednisolone) given during pregnancy, just after delivery or in the postnatal period, or both before and after birth, with placebo or no treatment. Those receiving steroids showed significantly greater improvement in platelet counts which was greater for those receiving dexamethasone than those receiving betamethasone. There was no clear evidence of any effect of corticosteroids on substantive clinical outcomes. These benefits appear to be greater in Class I HELLP syndrome.To determine the effectiveness of dexamethasone for accelerating postpartum recovery in patients with Class I HELLP syndrome in a multicenter randomized controlled trial.The study is a triple blind randomized controlled trial including women with class I HELLP syndrome, and exclusion criteria were dexamethasone use in the last 15 days before diagnosis of HELLP syndrome; chronic use of corticosteroids; chronic diseases that alter laboratory parameters of HELLP Syndrome, such as chronic liver disease or purpura, patients unable to consent (coma or critical clinical condition) and without accompanying persons that may consent to study participation.Eligible patients will be invited to participate and those who agree will be included in the study and receive placebo or dexamethasone according to a random list of numbers and subjects will receive the study medication every 12 hours for two days.During the study the women will be subject to strict control of blood pressure and urine output. Laboratory tests will be performed at regular intervals during treatment and 24 hours and 48 hours after its suspension. If worsening of clinical or laboratory variables is observed, a rescue scheme of dexamethasone will be administrated. This proposal has already obtained approval of the local Institutional Review Board of the coordinating center (IMIP, Recife, Brazil), all other participating centers and of the National Council for Ethics in Research (CONEP) of the Brazilian Ministry of Health.Clinical Trials Register under the number NCT00711841.

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Corticosteroids for HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome in pregnancy.

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Corticosteroids for HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome in pregnancy.

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