corticosteroids for hellp syndrome in pregnancy

28/08/13 cochrane.bvsalud.org/cochrane/show.php?db=reviews&mfn=1120&id=CD002076&lang=es&dblang=&lib=COC&print=yes

cochrane.bvsalud.org/cochrane/show.php?db=reviews&mfn=1120&id=CD002076&lang=es&dblang=&lib=COC&print=yes 1/12

COCHRANE BVS

BIREME OPASOMS

Imprimir | Cerrar

Copyright: The Cochrane Library

CORTICOSTEROIDS FOR HELLP SYNDROME IN PREGNANCY

Matchaba Patrice T, Moodley Jagidesa

Matchaba Patrice T, Moodley Jagidesa

Cochrane Database of Systematic Reviews, Issue 7, 2013 (Status in this issue: WITHDRAWN FROM PUBLICATION FORREASONS STATED IN THE REVIEW)

Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.DOI: 10.1002/14651858.CD002076.pub1

This review should be cited as: Matchaba Patrice T, Moodley Jagidesa. Corticosteroids for HELLP syndrome inpregnancy. Cochrane Database of Systematic Reviews. In: The Cochrane Library, Issue 7, Art. No. CD002076. DOI:

10.1002/14651858.CD002076.pub1

A B S T R A C T

Background

Hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome is a severe form of pre-eclampsia. Pre-eclampsia is a multi-system disease of pregnancy associated with an increase in blood pressure and increasedperinatal and maternal morbidity and mortality. Eighty per cent of women with HELLP syndrome present before term.There are suggestions from observational studies that steroid treatment in HELLP syndrome may improve disorderedmaternal hematological and biochemical features and perhaps perinatal mortality and morbidity.

Objective

To summarise the evidence on the effects of corticosteroids on maternal and neonatal mortality and morbidity inwomen with HELLP syndrome.

Criteria for considering studies for this review

We searched the Cochrane Pregnancy and Childbirth Group trials register (October 2003). We scanned lists ofreferences from review articles and primary studies.

Selection criteria

Randomised and quasi-randomised trials evaluating the effects of adjunctive corticosteroids in patients diagnosed withHELLP syndrome were sought.

Data collection and analysis

The two authors independently applied inclusion criteria, assessed trial quality and extracted relevant data.

Main results

Of the five studies reviewed (n = 170), three were conducted antepartum and two postpartum. Four of the studiesrandomised participants to standard therapy or dexamethasone. One study compared dexamethasone withbetamethasone.

Dexamethasone versus control There were no significant differences in the primary outcomes of maternal mortality and morbidity due to placentalabruption, pulmonary oedema and liver hematoma or rupture. Of the secondary maternal outcomes, there was atendency to a greater platelet count increase over 48 hours, statistically significantly less mean number of hospitalstay days (weighted mean difference (WMD) -4.50, 95% confidence interval (CI) -7.13 to -1.87), mean interval(hours) to delivery (41 ± 15) versus (15 ± 4.5) (p = 0.0068) in favour of women allocated to dexamethasone.

Authors' conclusions

There is insufficient evidence to determine whether adjunctive steroid use in HELLP syndrome decreases maternal andperinatal mortality, major maternal and perinatal morbidity.

http://www.bireme.br/

http://www.paho.org/

http://www.who.int/



P L A I N L A N G U A G E S U M M A R Y

More research is needed to determine if corticosteroids can improve outcomes for women and babies affected byHELLP syndrome in pregnancy.

Pre-eclampsia, also known as toxaemia, is a potentially life-threatening condition of pregnancy. It involves high bloodpressure (hypertension) and protein in the urine. HELLP syndrome (hemolysis, elevated liver enzymes and lowplatelets) is a severe form of pre-eclampsia, which can cause a tendency to bleed and other complications.Corticosteroids may be able to normalise some of the abnormal biochemical changes caused by HELLP, as well asreduce hypertension. The review of trials of corticosteroids for women with HELLP (both during pregnancy and afterthe birth) found too little evidence to be sure of the effects, but more research is worthwhile.

W H A T ' S N E W

What's newLast assessed as up-to-date: 30 October 2003.

Date Event Description

11 May 2009 Amended Review withdrawn from publication.

B A C K G R O U N D

Hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome is a severe form of pre-eclampsia ( Pritchard1954 ). Pre-eclampsia is a condition associated with an increase in blood pressure, protein loss via the urine, andoedema in pregnancy and occurs in 5% to 8% of all pregnancies. Its cause is not known, but it remains a major causeof perinatal and maternal morbidity and mortality ( Duley 1992 ). HELLP syndrome occurs in about 20% of severelypre-eclamptic women and does so before term in 80% of cases; 10% of these occur before 27 weeks' gestation (Sibai 1993 ). Premature delivery contributes to the very high rate of perinatal morbidity and mortality. About a thirdof the cases are diagnosed for the first time postpartum ( Sibai 1993 ).

Although it is agreed that hemolysis, liver dysfunction and thrombocytopenia must be present to make a diagnosis ofHELLP syndrome, there is disagreement over the specific biochemical and hematological criteria to be used. For thepurposes of this review, the criteria specified by Sibai ( Sibai 1986 ) and Martin ( Martin 1991 ) will be used. Sibai'scriteria include hemolysis as evidenced by an abnormal peripheral smear, lactate dehydrogenase (LDH) greater than600 IU/L or Total Bilirubin (TB) greater than 1.2 ULN; elevated liver enzymes as evidenced by an aspartatetransaminase (AST) greater than 70 IU/L and platelets less than 100 000/mm³. Martin's criteria include hemolysis asevidenced by a falling hematocrit, LDH greater than 164 IU/L or a bleeding diathesis; elevated liver enzymes asevidenced an AST greater than 48 IU/L and alanine transaminase (ALT) greater than 24 IU/L and platelets less than100 000 mm³.

Maternal mortality (1% to 3.5%) and morbidity are increased by the hypertensive complications of pre-eclampsia, thebleeding tendency that results from the low platelets and liver dysfunction ( Sibai 1993 ; Weinstein 1985 ; Martin 1991).

Since HELLP syndrome is common before term, any intervention that prolongs the time from diagnosis to delivery bystabilising the clinical condition, may decrease perinatal morbidity and mortality. Steroids have been shown inobservational studies ( Magann 1993 ; Clark 1986 ; Yeast 1987 ) to improve the deranged maternal biochemical andhaematological indices associated with the syndrome. This benefit has also been shown in HELLP syndrome diagnosedpostpartum ( Martin 1997 ; Yalcin 1998 ). However, it may be argued that delaying delivery may worsen the maternalmorbidity and increase both maternal and fetal mortality.

Glucocorticoids have been shown to improve fetal lung maturation, decreasing the occurrence and severity ofrespiratory distress syndrome and the overall fetal morbidity and mortality after preterm birth ( Crowley 1999 ).Dexamethasone at doses up to a total of 48 mg over a 48 hour period may be given intramuscularly in order toimprove fetal lung function. However, the steroid dosing regimens that have been suggested for HELLP syndrome aredifferent from the one used for fetal lung maturation. The maternal and fetal effects of such a regimen have not beenquantified. Also, the number of women with HELLP syndrome who have been treated with steroids is probably small.

This review therefore aims to summarise existing evidence of the effects of steroids in HELLP syndrome. Any effectsmay be different according to the gestational age, severity of disease, parity and whether the mother is antepartumor postpartum. The effect estimates will be explored for these factors.

O B J E C T I V E S

(1) To evaluate the effects of corticosteroids in women with HELLP syndrome during pregnancy or shortly afterdelivery.

The following primary hypothesis will be tested:



In comparing women given steroids with control/placebo groups, there will be no difference in: (a) maternal morbidity and mortality; (b) perinatal morbidity and mortality.

(2) In addition, we will explore whether the possible effects of steroids on the mother differ according to: (a) gestational age at treatment; and (b) whether the mother is antepartum or postpartum.

M E T H O D S O F T H E R E V I E W

C R I T E R I A F O R C O N S I D E R I N G S T U D I E S F O R T H I S R E V I E W

Types of studies

All randomised controlled trials and trials which used pseudo-randomised methods, such as alternate allocation.

Types of partic ipants

All antepartum and postpartum women diagnosed clinically and by biochemical parameters as having the HELLPsyndrome.

Types of intervention

Any corticosteroid versus placebo or no treatment.

Types of outcome measures

Primary outcomes

(1) maternal mortality; (2) perinatal mortality; (3) maternal morbidity, namely:

presence of liver hematoma and rupture;

pulmonary oedema;

renal failure;

abruptio placentae;

(4) perinatal morbidity, namely:

respiratory distress syndrome and ventilatory support required;

intracerebral haemorrhage;

necrotizing enterocolitis.

Secondary outcomes

(1) Maternal

After randomisation, the

average time taken to return to normal biochemical and haematological parameters;

average time taken to return to a normal urine output;

average time taken to return to a normal blood pressure;

average time to delivery;

mode of delivery.

(2) Neonatal

the mean gestational age and weight at birth;

the mean Apgar scores at birth.



S E A R C H M E T H O D S F O R I D E N T I F I C A T I O N O F S T U D I E S

Search methods for identification of studies

Electronic searches

We searched the Cochrane Pregnancy and Childbirth Group trials register (October 2003).

The Cochrane Pregnancy and Childbirth Group's trials register is maintained by the Trials Search Co-ordinator andcontains trials identified from:

quarterly searches of the Cochrane Central Register of Controlled Trials (CENTRAL);

monthly searches of MEDLINE;

handsearches of 30 journals and the proceedings of major conferences;

weekly current awareness search of a further 37 journals.

Details of the search strategies for CENTRAL and MEDLINE, the list of handsearched journals and conferenceproceedings, and the list of journals reviewed via the current awareness service can be found in the 'Searchstrategies for identification of studies' section within the editorial information about the Cochrane Pregnancy andChildbirth Group.

Trials identified through the searching activities described above are given a code (or codes) depending on the topic.The codes are linked to review topics. The Trials Search Co-ordinator searches the register for each review usingthese codes rather than keywords.

D A T A C O L L E C T I O N A N D A N A L Y S I S

Data collection and analysis

The inclusion criteria were applied to all identified trials by the two authors independently. Each included trial wasassessed in terms of adequacy of concealment of allocation, generation of allocation sequence, blinding and follow upof subjects ( Clarke 2000 ).

Data extraction was undertaken by the two reviewers independently, who collected the following information for eachtrial:

number of women;

women's characteristics including ethnic origin, parity, whether the women were antepartum or postpartum,gestational age at diagnosis, number of babies in current pregnancy, the mode of delivery and time from diagnosis todelivery;

the haematological and biochemical results;

morbidity and mortality outcomes;

the type, dose and duration of steroid used;

other medication used.

Babies' characteristics including ethnic origin, gestational age at birth, weight, Apgar scores and morbidity andmortality outcomes.

It was intended to explore whether any heterogeneity of effect was explained by whether the woman was antepartumor postpartum, the gestational age, severity of disease and parity.

M E T H O D O L O G I C A L Q U A L I T Y

R E S U L T S

Results

Description of studies

See: Characteristics of included studies .

Seven published studies were identified that met the inclusion criteria. One of the studies ( Kadanali 1997 ) has notbeen included in the data analysis because it is being translated into English and another ( Isler 2003 ) has not beenincluded because we have asked for the original data. Of the five studies that have been analysed, four have



compared steroid use (dexamethasone) with placebo ( Isler 2001 ; Magann 1994a ; Magann 1994b ; Yalcin 1998 :Vigil-De Gracia 1997 ). One study compared two different steroid regimens ( Isler 2001 ). The total number of trialparticipants in the five studies is 170.

Three of the reviewed studies were conducted antepartum ( Isler 2001 ; Magann 1994b ; Vigil-De Gracia 1997 ). Theother two were conducted postpartum ( Magann 1994a ; Yalcin 1998 ).

Risk of bias in included studies

Three studies employed adequate randomisation and allocation concealment methods ( Isler 2001 ; Magann 1994a ;Magann 1994b ). However, in Magann 1994b , women allocated to standard treatment (control) had higher meanplatelet counts than those allocated to steroid treatment.

In the two other studies ( Yalcin 1998 ; Vigil-De Gracia 1997 ), there was no mention of the randomisation methodused, nor whether allocation concealment was implemented. Furthermore in Vigil-De Gracia 1997 , the groupsrandomly allocated to standard therapy differed in the maternal platelet count when compared with the groupallocated to steroid therapy, the platelet count being lower in the group randomly allocated to receive steroids. Noneof the trials were placebo-controlled.

In none of the five included studies was blinding described in the methods section.

There was significant loss to follow up in one study ( Magann 1994a ). Only 25 of the original 40 participantsrandomised were accounted for in the results section. Intention to treat analysis was not performed in this study. Theother studies had no loss to follow up.

Effects of interventions

Five studies involving 170 women are included.

1. Primary outcomes

Trials that compared dexamethasone plus standard therapy versus standard therapy alone

There were four trials that used this study design ( Magann 1994a ; Magann 1994b ; Yalcin 1998 ; Vigil-De Gracia1997 ).

Maternal mortality

There was one maternal death in the group randomised to standard therapy ( Vigil-De Gracia 1997 , n = 34) and thiswas not statistically significant (relative risk (RR) 0.33, 95% confidence interval (CI) 0.01 to 7.65).

Perinatal mortality

There was no statistically significant difference in neonatal deaths (RR 0.36, 95% CI 0.04 to 3.02) in the one study (n= 25).

Maternal morbidity

There were no cases of liver hematoma or rupture, pulmonary oedema, renal failure or placental abruption in eithergroup.

Perinatal morbidity

i) Intraventricular hemorrhage events occurred in one study ( Magann 1994b , n = 25) and the difference was notstatistically significant (RR 7.54, 95% CI 0.43 to 132.35). ii) Respiratory distress syndrome events occurred in one study ( Magann 1994b ) and there was no statisticallysignificant difference (RR 1.00, 95% CI 0.25 to 4.00). iii) Retrolental fibroplasia occurred in one neonate allocated to placebo ( Magann 1994b ) but the difference was notstatistically significant (RR 0.36, 95% CI 0.02 to 8.05). No intracerebral hemorrhagic events nor necrotizing enterocolitis were recorded.

Trial that compared dexamethasone and betamethasone

There was only one study with this design ( Isler 2001 , n = 40).

Maternal mortality

There were no maternal deaths.



Perinatal mortality

There was no significant difference in neonatal deaths when dexamethasone was compared with betamethasone (RR0.95, 95% CI 0.15 to 6.08).

Maternal morbidity

There were no cases of liver hematoma or rupture, pulmonary oedema, or abruptio placentae in either group. Therewas a statistically significant difference in maternal oliguria (RR 0.06, 95% CI 0.00 to 0.93) in favour of participantsrandomised to dexamethasone.

Perinatal morbidity

There was a tendency for fewer neonates allocated to dexamethasone to have ventilatory support or respiratorydistress syndrome when compared with those allocated to betamethasone. However, this was not statisticallysignificant (RR 0.54, 95% CI 0.19 to 1.56). In this study, no cases of intracerebral hemorrhage and necrotizingenterocolitis were recorded.

2. Secondary outcomes

Trials that compared dexamethasone plus standard therapy versus standard therapy alone

Maternal morbidity

i) There was no statistically significant difference in postpartum sepsis (RR 2.00, 95% CI 0.20 to 19.78) in one study(n = 30) and cesarean sections (RR 0.93, 95% CI 0.66 to 1.31) between the two groups (one study, n = 34). ii) There was a tendency to a greater platelet count increase over 48 hours in participants allocated to dexamethasone(weighted mean difference (WMD) 40.60, 95% CI -26.12 to 107.32) but this result must be interpreted with cautionbecause the data are skewed and are derived from only one small study ( Vigil-De Gracia 1997 , n=34). iii) There was a statistically significant difference in the mean number of hospital stay days postrandomisation (WMD-4.50, 95% CI -7.13 to -1.87) in favour of participants allocated to dexamethasone. iv) There was a significant difference in the mean interval (hours) from randomisation to delivery (41 ± 15) versus(15 ± 4.5) (p = 0.0068) in favour of women allocated to dexamethasone in the single study that looked at thisoutcome ( Magann 1994b , n = 25).

Neonatal morbidity

The number of neonates with a five minute Apgar less than seven did not differ significantly (RR 1.00 95% CI 0.25 to4.00): one study, n = 24. The mean weight at birth was significantly greater in the group allocated to steroids (WMD247.00, 95% CI 65.41 to 428.59).

Trial that compared dexamethasone and betamethasone

Maternal morbidity

There was a statistically significant difference in favour of participants allocated to dexamethasone in the adjustedtime-average change from baseline in the following secondary outcomes: i) The mean arterial pressure decrease (WMD -7.50, 95% CI -8.37 to -6.63). ii) The mean increase in urinary output (WMD 24.80, 95% CI 19.58 to 30.02). iii) The mean increase in platelet count (WMD 8.10, 95% CI 6.23 to 9.97). iv) The mean decrease in lactate dehydrogenase activity (U/L) (WMD -54.20, 95% CI -88.22 to -20.18). v) The mean decrease in aspartate transaminase activity (U/L) (WMD -30.30, 95% CI -36.06 to -24.54).

The number of participants needing acute antihypertensive therapy in the dexamethasone group differed significantlystatistically compared with those allocated to betamethasone (RR 0.29, 95% CI 0.12 to 0.73).

Neonatal morbidity

There were no statistically significant differences between the two groups with regards to the number of neonates witha five minute Apgar less than seven (RR 0.95, 95% CI 0.22 to 4.14), neonatal sepsis (RR 4.76, 95% CI 0.24 to93.19), neonatal hyperbilirubinemia (RR 2.85, 95% CI 0.32 to 25.07) and mean time to discharge in days (WMD-5.40, 95% CI -19.53 to 8.73).

There was no trial that compared betamethasone plus standard therapy versus standard therapy alone.

D I S C U S S I O N

Discussion



Trials that compared participants randomised with steroid (dexamethasone) use and placebo (Magann1994a; Magann 1994b; Vigil-De Gracia 1997; Yalcin 1998).

HELLP syndrome is a severe form of pre-eclampsia ( Pritchard 1954 ), whose cause is unknown and remains a majorcause of perinatal morbidity and mortality ( Duley 1992 ). In this review there was no statistically significantdifference in the primary outcome of maternal mortality (relative risk (RR) 0.33, 95% confidence interval (CI) 0.01 to7.65). There was one maternal death in the group allocated to placebo in a trial with a total of 34 participants ( Vigil-De Gracia 1997 ). Besides the small sample size of this trial, the randomisation method used was not mentioned andthe methodology used for allocation concealment is unclear. Furthermore the postrandomisation patient characteristicsdiffered significantly with regards to platelet count, before treatment was instituted.

There were four neonatal deaths in one small trial ( Magann 1994b , n = 25), which were not statistically significant(RR 0.36, 95% CI 0.04 to 3.02). Although allocation concealment and randomisation were adequate in this trial,maternal platelet levels differed significantly postrandomisation before treatment commenced (p = 0.034) and theratio of black to female participants was 2:1.

Maternal morbidity primary outcomes of pulmonary oedema, presence of a liver hematoma or rupture, renal andabruptio placentae did not differ significantly between the two groups of participants.

None of the primary perinatal morbidity outcomes, respiratory distress syndrome, need for ventilatory support,intracerebral hemorrhage and necrotizing enterocolitis, differed significantly.

The only secondary maternal morbidity outcome that was statistically significant in favour of steroid use was the meannumber of days of hospital stay (weighted mean difference (WMD) -4.50, 95% CI -7.13 to -1.87). The number ofneonates with Apgar scores less than seven after five minutes were not significantly different. The mean weight atbirth differed significantly (WMD 247.00, 95% CI 65.41 to 428.59) in one study ( Magann 1994b ).

In summary, because of the small sample sizes in the trials reviewed, there is no evidence that either supports orrefutes the use of steroids in HELLP syndrome antenatally and in the postpartum period in order to decrease orincrease maternal and perinatal mortality and the primary morbidity outcomes of interest in this review.

One trial compared dexamethasone use with betamethasone (Isler 2001):

There were no maternal or neonatal primary outcome differences with regards to death and maternal morbidity, withthe exception of oliguria (less than 30 ml urine/hour for two hours) (RR 0.06, 95% CI 0.00 to 0.93), in favour ofdexamethasone.

The main findings were in the maternal hematological and biochemical parameters. In all instances of adjusted time-average change from baseline for mean arterial pressure decrease, mean increase in the platelet count, meandecrease in lactate dehydrogenase and aspartate transaminase activity and the need for acute antihypertensivetherapy, women allocated to dexamethasone fared better significantly than those allocated to betamethasone. This issupportive of the observational data referenced above that had similar findings.

There were no significant differences in the secondary neonatal outcomes of Apgar score of less than seven after fiveminutes, neonatal sepsis, hyperbilirubinaemia and time to discharge from hospital.

In summary, because of the small sample size there is no evidence from this trial that indicates that whendexamethasone is given intravenously (10 mg 12 hourly before delivery), that there is a statistically significantdifference in the maternal biochemical and hematological parameters when compared with betamethasone (12 mgintramuscularly every 24 hours).

A U T H O R S ' C O N C L U S I O N S

Implications for practice

Until a large enough study that is adequately designed with sufficient power to detect a significant difference in theprimary maternal and neonatal outcomes of death and severe morbidity, there is no evidence to support the additionof dexamethasone or betamethasone to standard therapy in HELLP syndrome. However, it is important to note thatglucocorticoids have been shown to improve fetal lung maturity and overall fetal mortality and morbidity when theappropriate dosing regimens are used ( Crowley 1999 ).

Implications for research

The high maternal and perinatal mortality and morbidity associated with HELLP syndrome makes it imperative that alarge study with the appropriate design be done to determine the effect of antenatal and postpartum steroids on theprimary and secondary outcomes chosen in this review. Steroids are relatively cheap and if found efficacious indecreasing the primary outcomes sought in the review, they would provide a cost-effective intervention for HELLPsyndrome. Because HELLP syndrome is not very common ( Sibai 1993 ), a global multi-centre study design may bethe most efficient study design to use in order to recruit sufficient patients to adequately answer the review question.



A C K N O W L E D G E M E N T S

Acknowledgements

Contributions: Jim Neilson, Michel Boulvain, the Cochrane Pregnancy and Childbirth Group's panel of consumers.

N O T E S

R E F E R E N C E S

References to studies included in this review

Isler 2001 {published data only}

Isler C, Barrilleaux P, Magann E, Bass J, Martin J. A prospective, randomized trial comparing theefficacy of dexamethasone and betamethasone for the treatment of antepartum HELLP (hemolysis,elevated liver enzymes, and low platelet count) syndrome. Revista Chilena de Obstetricia y Ginecologia2001;66(3):248-50.

Isler CM, Barrilleaux PS, Magann EF, Bass JD, Martin JN. A prospective, randomized trial comparing theefficacy of dexamethasone and betamethasone for the treatment of antepartum HELLP (hemolysis,elevated liver enzymes, and low platelet count) syndrome. American Journal of Obstetrics andGynecology 2001;184:1332-7.

Magann 1994a {published data only}

Magann EF, Perry KG, Meydrech EF, Harris RL, Suneet PC, Martin JN. Postpartum corticosteroids:accelerated recovery from the syndrome of hemolysis, elevated liver enzymes, and low platelets(HELLP). American Journal of Obstetrics Gynecology. 1994;171:1154-8.

Magann 1994b {published data only}

Magann EF, Bass D, Chauhan SP, Sullivan D, Martin RW, Martin JN. Antepartum corticosteroids: diseasestabilization in patients with the syndrome of hemolysis, elevated liver enzymes, and low platelets(HELLP). American Journal of Obstetrics and Gynecology 1994;171:1148-53.

Magann EF, Bass D, Chauhan SP, Sullivan DL, Martin RW, Martin JN. Antepartum corticosteroids: diseasestabilization in patients with HELLP syndrome. American Journal of Obstetrics and Gynecology1994;170:410-.

Vigil-De Gracia 1997 {published data only}

Vigil-De Gracia P, Garcia-Caceres E. Dexamethasone in the post-partum treatment of HELLP syndrome.International Journal of Gynecology & Obstetrics 1997;59:217-21.

Yalcin 1998 {published data only}

Yalcin OT, Sener T, Hassa H, Ozalp S, Okur A. Effects of postpartum corticosteroids in patients withHELLP syndrome. International Journal of Gynecology & Obstetrics 1998;61:141-8.

* indicates the major publication for the study

Additional references

Clark 1986

Clark SL, Phelan JR, Allen SH, Golde SR. Antepartum reversal of hematologic abnormalities associatedwith the HELLP syndrome. A report of three cases. Journal of Reproductive Medicine 1986;31:70-2.

Clarke 2000

Clarke M, Oxman AD. Cochrane Reviewers’ Handbook 4.1 [updated June 2000]. :-.

Crowley 1999

Crowley P. Prophylactic corticosteroids for preterm birth (Cochrane Review). Cochrane Database ofSystematic Reviews 1999:-.

Duley 1992

Duley L. Maternal mortality associated with hypertensive disorders of pregnancy in Africa, Asia, LatinAmerica and the Caribbean. British Journal of Obstetrics and Gynaecology 1992;99:547-53.



Magann 1993

Magann EF, Martin RW, Issacs JD, Blake PG, Morrison JC, Martin JN. Corticosteroids for theenhancement of fetal lung maturity: impact on the gravida with preeclampsia and the HELLP syndrome.Australian and New Zealand Journal of Obstetrics and Gynaecology 1993;33:127-31.

Martin 1991

Martin JN, Blake PG, Perry KG, McCaul JF, Hess LW, Martin RW. The natural history of HELLP syndrome:patterns of disease progression and regression. American Journal of Obstetrics and Gynecology1991;164:1500-9.

Martin 1997

Martin JN, Perry KG, Blake PG, May WA, Moore A, Robinette L. Better maternal outcomes are achievedwith dexamethasone therapy for postpartum HELLP (hemolysis, elevated liver enzymes andthrombocytopenia) syndrome. American Journal of Obstetrics and Gynecology 1997;177:1011-7.

Pritchard 1954

Pritchard J, Weisman R, Ratnoff O, Vosburgh G. Intravascular haemolysis, thrombocytopenia and otherhaematologic abnormalities associated with severe toxemia of pregnancy. New England Journal ofMedicine 1954;250:89-98.

Sibai 1986

Sibai BM, Taslimi MM, el-Nazer A, Aman E, Mabie BC, Ryan GM. Maternal-perinatal outcome associatedwith the syndrome of hemolysis, elevated liver enzymes, and low platelets in severe pre-eclampsia-eclampsia. American Journal of Obstetrics and Gynecology 1986;155:501-9.

Sibai 1993

Sibai BM, Ramadan MK, Usta I, Salama M, Mercer BM, Friedman SA. Maternal morbidity and mortality in442 pregnancies with heamolysis, elevated liver enzymes, and low platelets (HELLP syndrome).American Journal of Obstetrics and Gynecology 1993;169:1000-6.

Weinstein 1985

Weinstein L. Preeclampsia/eclampsia with heamolysis, elevated liver enzymes and thrombocytopenia.Obstetrics and Gynecology 1985;66:657-60.

Yalcin 1998

Yalcin OT, Sener T, Hassa H, Ozalp S, Okur A. Effects of postpartum corticosteroids in patients withHELLP syndrome. International Journal of Gynecology and Obstetrics 1998;61:141-8.

Yeast 1987

Yeast JD, Coronado S. Hepatic dysfunction, thrombocytopenia and late onset preeclampsia. A report ofthree cases. Journal of Reproductive Medicine 1987;32:781-4.

G R A P H S

Graphs and Tables

To view a graph or table, click on the outcome title of the summary table below.

Dexamethasone plus standard treatment versus standard treatment alone

Outcome titleNo. of

studiesNo. of

participantsStatistical method Effect size

1 Maternal deaths 1 34 Risk Ratio (M-H, Fixed,95% CI)

0.33 [0.01,7.65]

2 Postpartum sepsis 1 30 Risk Ratio (M-H, Fixed,95% CI)

2.0 [0.20,19.78]

3 Mean platelet counts over 48 hours 1 34 Mean Difference (IV,Fixed, 95% CI)

40.60 [-26.12,107.32]

4 Mean hospital stay post randomisation Mean Difference (IV, -4.5 [-7.13,

http://cochrane.bvsalud.org/cochrane/img_data/CD002076/image_n/nCD002076-CMP-001-01.png






(days) 1 30 Fixed, 95% CI) -1.87]

5 Neonatal deaths 1 25 Risk Ratio (M-H, Fixed,95% CI)

0.36 [0.04,3.02]

6 Neonates with intraventricularhemorrhage

1 25 Risk Ratio (M-H, Fixed,95% CI)

7.54 [0.43,132.35]

7 Neonates with respiratory distresssyndrome


1.0 [0.25, 4.00]

8 Neonates with 5 minute Apgars lessthan 7


1.0 [0.25, 4.00]

9 Weight at birth in grams 1 25 Mean Difference (IV,Fixed, 95% CI)

247.0 [65.41,428.59]

10 Neonates with retrolental fibroplasia 1 25 Risk Ratio (M-H, Fixed,95% CI)

0.36 [0.02,8.05]

11 Number of cesarean sectiondeliveries


0.93 [0.66,1.31]

12 Time interval (hours) fromrandomisation to delivery

1 Mean Difference (IV,Fixed, 95% CI)

Totals notselected

Dexamethasone versus betamethasone

Outcome titleNo. of

studiesNo. of

participantsStatistical method Effect size

1 Mean arterial pressure: adjusted time-averaged change from baseline

1 40 Mean Difference (IV,Fixed, 95% CI)

-7.50 [-8.37,-6.63]

2 Urinary output (mL/h): adjusted time-averagedchange from baseline


24.8 [19.58,30.02]

3 Platelet count (10-9 cells/L): adjusted time-averaged change from baseline


8.1 [6.23,9.97]

4 LDH activity (U/L mean): adjusted time-averaged change from baseline


-54.20[-88.22,-20.18]

5 AST activity (U/L): adjusted time-averagedchange from baseline


-30.30[-36.06,-24.54]

6 Number of mothers with oliguria (less than 30ml/hour for 2 hours)


0.06 [0.00,0.93]

7 Maternal pulmonary edema 1 40 Risk Ratio (M-H, Fixed,95% CI)

Not estimable

8 Number of participants needing acuteantihypertensive therapy


0.29 [0.12,0.73]

9 Neonates with a 5 minute Apgar less than 7 1 39 Risk Ratio (M-H, Fixed,95% CI)

0.95 [0.22,4.14]

10 Neonates needing ventilatory support 1 39 Risk Ratio (M-H, Fixed,95% CI)

0.54 [0.19,1.56]

11 Neonates with respiratory distress syndrome 1 39 Risk Ratio (M-H, Fixed,95% CI)

0.54 [0.19,1.56]

12 Neonatal sepsis 1 39 Risk Ratio (M-H, Fixed,95% CI)

4.76 [0.24,93.19]

13 Neonatal hyperbilirubinemia 1 39 Risk Ratio (M-H, Fixed,95% CI)

2.85 [0.32,25.07]

14 Fetal or neonatal death 1 39 Risk Ratio (M-H, Fixed,95% CI)

0.95 [0.15,6.08]

15 Neonate time to discharge (days: mean) 1 39 Mean Difference (IV, -5.40 [-19.53,



























Fixed, 95% CI) 8.73]

C O V E R S H E E T

Corticosteroids for HELLP syndrome in pregnancy

Reviewer(s) Matchaba Patrice T, Moodley Jagidesa

Contribution of Reviewer(s)

Issue protocol first published 2000 issue 2

Issue review first published 2004 issue 1

Date of last minor amendment Information not supplied by reviewer

Date of last substantive amendment Information not supplied by reviewer

Most recent changes

Date new studies sought but none found Information not supplied by reviewer

Date new studies found but not yetincluded/excluded

Information not supplied by reviewer

Date new studies found and included/excluded Information not supplied by reviewer

Date reviewers' conclusions section amended Information not supplied by reviewer

Contact address HendersonFirst Floor, Liverpool Women's NHS FoundationTrustCrown StreetOne Health PlazaPrivate Bag 7CongellaLiverpoolEast HanoverDurban

UKUSASouth AfricaL8 7SSNJ 07936-10804013Telephone: Facsimile: E-mail: [email protected]

Cochrane Library number CD002076

Editorial group Cochrane Pregnancy and Childbirth Group

Editorial group code HM-PREG

S O U R C E S O F S U P P O R T

External sources of support

No sources of support supplied

Internal sources of support

Medical Research Council, South Africa.

mailto:[email protected]

http://cochrane.bvsalud.org/cochrane/show.php?id=_ID_PREG&lang=es&lib=COC&backto=review



K E Y W O R D S

Female; Humans; Pregnancy; Adrenal Cortex Hormones [*therapeutic use] ; Betamethasone [therapeutic use] ;Dexamethasone [therapeutic use] ; HELLP Syndrome [*drug therapy] ; Randomized Controlled Trials as Topic

H I S T O R Y

HistoryProtocol first published: Issue 2, 2000Review first published: Issue 1, 2004

Date Event Description

16 June 2008 Amended Converted to new review format.

Imprimir | Cerrar

Copyright: The Cochrane Library

corticosteroids for hellp syndrome in pregnancy

Documents