Corticosteroids for HELLP syndrome in pregnancy

Corticosteroids for HELLP syndrome in pregnancy (Review)
Matchaba P, Moodley J

This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library
2007, Issue 2


Corticosteroids for HELLP syndrome in pregnancy (Review)
Copyright © 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd

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TABLE OF CONTENTS

ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
PLAIN LANGUAGE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
CRITERIA FOR CONSIDERING STUDIES FOR THIS REVIEW . . . . . . . . . . . . . . . . . .
SEARCH METHODS FOR IDENTIFICATION OF STUDIES . . . . . . . . . . . . . . . . . . .
METHODS OF THE REVIEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
DESCRIPTION OF STUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
METHODOLOGICAL QUALITY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
AUTHORS’ CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
POTENTIAL CONFLICT OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . .
ACKNOWLEDGEMENTS
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
SOURCES OF SUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
TABLES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Characteristics of included studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
ANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Comparison 01. Dexamethasone plus standard treatment versus standard treatment alone . . . . . . . . . .
Comparison 02. Dexamethasone versus betamethasone . . . . . . . . . . . . . . . . . . . . . .
INDEX TERMS
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
COVER SHEET . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
GRAPHS AND OTHER TABLES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 01.01. Comparison 01 Dexamethasone plus standard treatment versus standard treatment alone, Outcome 01
Maternal deaths . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 01.02. Comparison 01 Dexamethasone plus standard treatment versus standard treatment alone, Outcome 02
Postpartum sepsis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 01.03. Comparison 01 Dexamethasone plus standard treatment versus standard treatment alone, Outcome 03
Mean platelet counts over 48 hours . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 01.04. Comparison 01 Dexamethasone plus standard treatment versus standard treatment alone, Outcome 04
Mean hospital stay post randomisation (days) . . . . . . . . . . . . . . . . . . . . . . .
Analysis 01.05. Comparison 01 Dexamethasone plus standard treatment versus standard treatment alone, Outcome 05
Neonatal deaths . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 01.06. Comparison 01 Dexamethasone plus standard treatment versus standard treatment alone, Outcome 06
Neonates with intraventricular hemorrhage . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 01.07. Comparison 01 Dexamethasone plus standard treatment versus standard treatment alone, Outcome 07
Neonates with respiratory distress syndrome . . . . . . . . . . . . . . . . . . . . . . .
Analysis 01.08. Comparison 01 Dexamethasone plus standard treatment versus standard treatment alone, Outcome 08
Neonates with 5 minute Apgars less than 7 . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 01.09. Comparison 01 Dexamethasone plus standard treatment versus standard treatment alone, Outcome 09
Weight at birth in grams . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 01.10. Comparison 01 Dexamethasone plus standard treatment versus standard treatment alone, Outcome 10
Neonates with retrolental fibroplasia . . . . . . . . . . . . . . . . . . . . . . . . . .

Analysis 01.11. Comparison 01 Dexamethasone plus standard treatment versus standard treatment alone, Outcome 11
Number of cesarean section deliveries
. . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 01.12. Comparison 01 Dexamethasone plus standard treatment versus standard treatment alone, Outcome 12
Time interval (hours) from randomisation to delivery . . . . . . . . . . . . . . . . . . . .
Analysis 02.01. Comparison 02 Dexamethasone versus betamethasone, Outcome 01 Mean arterial pressure: adjusted
time-averaged change from baseline . . . . . . . . . . . . . . . . . . . . . . . . . .
Corticosteroids for HELLP syndrome in pregnancy (Review)
Copyright © 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd

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Analysis 02.02. Comparison 02 Dexamethasone versus betamethasone, Outcome 02 Urinary output (mL/h): adjusted
time-averaged change from baseline . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 02.03. Comparison 02 Dexamethasone versus betamethasone, Outcome 03 Platelet count (10-9 cells/L):
adjusted time-averaged change from baseline . . . . . . . . . . . . . . . . . . . . . . .
Analysis 02.04. Comparison 02 Dexamethasone versus betamethasone, Outcome 04 LDH activity (U/L mean): adjusted
time-averaged change from baseline . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 02.05. Comparison 02 Dexamethasone versus betamethasone, Outcome 05 AST activity (U/L): adjusted timeaveraged change from baseline . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 02.06. Comparison 02 Dexamethasone versus betamethasone, Outcome 06 Number of mothers with oliguria
(less than 30 ml/hour for 2 hours) . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 02.07. Comparison 02 Dexamethasone versus betamethasone, Outcome 07 Maternal pulmonary edema

.
Analysis 02.08. Comparison 02 Dexamethasone versus betamethasone, Outcome 08 Number of participants needing
acute antihypertensive therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 02.09. Comparison 02 Dexamethasone versus betamethasone, Outcome 09 Neonates with a 5 minute Apgar
less than 7 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 02.10. Comparison 02 Dexamethasone versus betamethasone, Outcome 10 Neonates needing ventilatory
support . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 02.11. Comparison 02 Dexamethasone versus betamethasone, Outcome 11 Neonates with respiratory distress
syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 02.12. Comparison 02 Dexamethasone versus betamethasone, Outcome 12 Neonatal sepsis . . . . . .
Analysis 02.13. Comparison 02 Dexamethasone versus betamethasone, Outcome 13 Neonatal hyperbilirubinemia .
Analysis 02.14. Comparison 02 Dexamethasone versus betamethasone, Outcome 14 Fetal or neonatal death . . .
Analysis 02.15. Comparison 02 Dexamethasone versus betamethasone, Outcome 15 Neonate time to discharge (days:
mean) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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Corticosteroids for HELLP syndrome in pregnancy (Review)
Matchaba P, Moodley J

This record should be cited as:
Matchaba P, Moodley J. Corticosteroids for HELLP syndrome in pregnancy. Cochrane Database of Systematic Reviews 2004, Issue 1.
Art. No.: CD002076. DOI: 10.1002/14651858.CD002076.pub2.
This version first published online: 26 January 2004 in Issue 1, 2004.
Date of most recent substantive amendment: 31 October 2003

ABSTRACT
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 increased perinatal 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 disordered maternal hematological and biochemical features and perhaps perinatal mortality and
morbidity.
Objectives
To summarise the evidence on the effects of corticosteroids on maternal and neonatal mortality and morbidity in women with HELLP
syndrome.
Search strategy
We searched the Cochrane Pregnancy and Childbirth Group trials register (October 2003). We scanned lists of references from review
articles and primary studies.
Selection criteria
Randomised and quasi-randomised trials evaluating the effects of adjunctive corticosteroids in patients diagnosed with HELLP 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 studies randomised
participants to standard therapy or dexamethasone. One study compared dexamethasone with betamethasone.
Dexamethasone versus control
There were no significant differences in the primary outcomes of maternal mortality and morbidity due to placental abruption,
pulmonary oedema and liver hematoma or rupture. Of the secondary maternal outcomes, there was a tendency to a greater platelet
count increase over 48 hours, statistically significantly less mean number of hospital stay 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.
There were no significant differences in perinatal mortality or morbidity due to respiratory distress syndrome, need for ventilatory
support, intracerebral hemorrhage, necrotizing enterocolitis and a five minute Apgar less than seven. The mean birthweight was
significantly greater in the group allocated to dexamethasone (WMD 247.00, 95% CI 65.41 to 428.59).
Dexamethasone versus betamethasone
There were no significant differences in all the maternal and perinatal mortality and in primary morbidity outcomes.
Corticosteroids for HELLP syndrome in pregnancy (Review)
Copyright © 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd

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Women randomised to dexamethasone fared significantly better for: oliguria, mean arterial pressure, mean increase in platelet count,
mean increase in urinary output and liver enzyme elevations.
Authors’ conclusions
There is insufficient evidence to determine whether adjunctive steroid use in HELLP syndrome decreases maternal and perinatal
mortality, major maternal and perinatal morbidity.

PLAIN LANGUAGE SUMMARY

More research is needed to determine if corticosteroids can improve outcomes for women and babies affected by HELLP syndrome in
pregnancy
Pre-eclampsia, also known as toxaemia, is a potentially life-threatening condition of pregnancy. It involves high blood pressure (hypertension) and protein in the urine. HELLP syndrome (hemolysis, elevated liver enzymes and low platelets) is a severe form of preeclampsia, 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 as reduce hypertension. The review of trials of corticosteroids for women with HELLP
(both during pregnancy and after the birth) found too little evidence to be sure of the effects, but more research is worthwhile.

BACKGROUND
Hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome is a severe form of pre-eclampsia (Pritchard 1954). Preeclampsia is a condition associated with an increase in blood pressure, protein loss via the urine, and oedema in pregnancy and
occurs in 5% to 8% of all pregnancies. Its cause is not known,
but it remains a major cause of perinatal and maternal morbidity
and mortality (Duley 1992). HELLP syndrome occurs in about
20% of severely pre-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 third of 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 of HELLP syndrome, there is disagreement over the specific biochemical and
hematological criteria to be used. For the purposes of this review, the criteria specified by Sibai (Sibai 1986) and Martin (Martin 1991) will be used. Sibai’s criteria include hemolysis as evidenced by an abnormal peripheral smear, lactate dehydrogenase
(LDH) greater than 600 IU/L or Total Bilirubin (TB) greater
than 1.2 ULN; elevated liver enzymes as evidenced by an aspartate
transaminase (AST) greater than 70 IU/L and platelets less than
100 000/mm³. Martin’s criteria include hemolysis as evidenced by
a falling hematocrit, LDH greater than 164 IU/L or a bleeding
diathesis; elevated liver enzymes as evidenced an AST greater than
48 IU/L and alanine transaminase (ALT) greater than 24 IU/L
and platelets less than 100 000 mm³.
Maternal mortality (1% to 3.5%) and morbidity are increased
by the hypertensive complications of pre-eclampsia, the bleeding

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 by stabilising the
clinical condition, may decrease perinatal morbidity and mortality. Steroids have been shown in observational studies (Magann
1993; Clark 1986; Yeast 1987) to improve the deranged maternal
biochemical and haematological indices associated with the syndrome. This benefit has also been shown in HELLP syndrome
diagnosed postpartum (Martin 1997; Yalcin 1998). However, it
may be argued that delaying delivery may worsen the maternal
morbidity and increase both maternal and fetal mortality.
Glucocorticoids have been shown to improve fetal lung maturation, decreasing the occurrence and severity of respiratory 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 to improve fetal lung function. However, the steroid
dosing regimens that have been suggested for HELLP syndrome
are different from the one used for fetal lung maturation. The maternal and fetal effects of such a regimen have not been quantified.
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 effects may be different according to the gestational age, severity of disease, parity
and whether the mother is antepartum or postpartum. The effect
estimates will be explored for these factors.

Corticosteroids for HELLP syndrome in pregnancy (Review)
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OBJECTIVES
(1) To evaluate the effects of corticosteroids in women with
HELLP syndrome during pregnancy or shortly after delivery.

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.

CRITERIA FOR CONSIDERING
STUDIES FOR THIS REVIEW
Types of studies
All randomised controlled trials and trials which used pseudorandomised methods, such as alternate allocation.
Types of participants
All antepartum and postpartum women diagnosed clinically and
by biochemical parameters as having the HELLP syndrome.
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;

• 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.

SEARCH METHODS FOR
IDENTIFICATION OF STUDIES
See: Cochrane Pregnancy and Childbirth Group methods used
in reviews.
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 and contains trials
identified from:
1. quarterly searches of the Cochrane Central Register of
Controlled Trials (CENTRAL);
2. monthly searches of MEDLINE;
3. handsearches of 30 journals and the proceedings of major
conferences;
4. weekly current awareness search of a further 37 journals.
Details of the search strategies for CENTRAL and MEDLINE,
the list of handsearched journals and conference proceedings,
and the list of journals reviewed via the current awareness service
can be found in the ’Search strategies for identification of studies’
section within the editorial information about the Cochrane
Pregnancy and Childbirth 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 using these codes rather than
keywords.

(4) perinatal morbidity, namely:
• respiratory distress syndrome and ventilatory support required;

METHODS OF THE REVIEW

• intracerebral haemorrhage;
• necrotizing enterocolitis.
Secondary outcomes
(1) Maternal
After randomisation, the
• average time taken to return to normal biochemical and haematological parameters;

The inclusion criteria were applied to all identified trials by the two
authors independently. Each included trial was assessed in terms
of adequacy of concealment of allocation, generation of allocation
sequence, blinding and follow up of subjects (Clarke 2000).
Data extraction was undertaken by the two reviewers
independently, who collected the following information for each
trial:

Corticosteroids for HELLP syndrome in pregnancy (Review)
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• 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 to delivery;
• the haematological and biochemical results;

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 participants randomised were
accounted for in the results section. Intention to treat analysis was
not performed in this study. The other studies had no loss to follow
up.

• morbidity and mortality outcomes;
• the type, dose and duration of steroid used;
• other medication used.

RESULTS
Five studies involving 170 women are included.

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

1. Primary outcomes

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

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 Gracia 1997).

DESCRIPTION OF STUDIES
Seven published studies were identified that met the inclusion
criteria. One of the studies (Kadanali 1997) has not been included
in the data analysis because it is being translated into English
and another (Isler 2003) has not been included 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 trial participants in
the five studies is 170.
Three of the reviewed studies were conducted antepartum (Isler
2001; Magann 1994b; Vigil-De Gracia 1997). The other two were
conducted postpartum (Magann 1994a; Yalcin 1998).

METHODOLOGICAL QUALITY
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 mean platelet 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 method used, nor whether
allocation concealment was implemented. Furthermore in VigilDe Gracia 1997, the groups randomly allocated to standard therapy differed in the maternal platelet count when compared with
the group allocated to steroid therapy, the platelet count being
lower in the group randomly allocated to receive steroids. None

of the trials were placebo-controlled.

Maternal mortality
There was one maternal death in the group randomised to standard therapy (Vigil-De Gracia 1997, n = 34) and this was 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 either group.
Perinatal morbidity
i) Intraventricular hemorrhage events occurred in one study (Magann 1994b, n = 25) and the difference was not statistically 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 statistically significant 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 not statistically
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 (RR 0.95, 95%
CI 0.15 to 6.08).

Corticosteroids for HELLP syndrome in pregnancy (Review)

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

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).

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

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

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 caution because 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 this outcome (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 to 4.00): one
study, n = 24. The mean weight at birth was significantly greater
in the group allocated to steroids (WMD 247.00, 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 adjusted time-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).

Neonatal morbidity
There were no statistically significant differences between the two
groups with regards to the number of neonates with a 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 to 93.19), 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.

DISCUSSION
Trials that compared participants randomised with steroid
(dexamethasone) use and placebo (Magann 1994a; 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 major cause of perinatal morbidity and mortality (Duley 1992). In this review there
was no statistically significant difference in the primary outcome
of maternal mortality (relative risk (RR) 0.33, 95% confidence
interval (CI) 0.01 to 7.65). 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 and the
methodology used for allocation concealment is unclear. Furthermore the postrandomisation patient characteristics differed 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 the ratio of black to female participants was 2:1.
Maternal morbidity primary outcomes of pulmonary oedema,
presence of a liver hematoma or rupture, renal and abruptio placentae did not differ significantly between the two groups of participants.

Corticosteroids for HELLP syndrome in pregnancy (Review)
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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 mean number of days of hospital stay (weighted mean difference (WMD)
-4.50, 95% CI -7.13 to -1.87). The number of neonates with Apgar scores less than seven after five minutes were not significantly
different. The mean weight at birth 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 or refutes the use
of steroids in HELLP syndrome antenatally and in the postpartum period in order to decrease or increase 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, with the exception
of oliguria (less than 30 ml urine/hour for two hours) (RR 0.06,
95% CI 0.00 to 0.93), in favour of dexamethasone.
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, mean decrease in lactate dehydrogenase and aspartate transaminase activity and the need for acute antihypertensive therapy, women allocated to dexamethasone fared
better significantly than those allocated to betamethasone. This
is supportive 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 five minutes,
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 when dexamethasone is given
intravenously (10 mg 12 hourly before delivery), that there is a
statistically significant difference in the maternal biochemical and
hematological parameters when compared with betamethasone
(12 mg intramuscularly every 24 hours).

cient power to detect a significant difference in the primary maternal and neonatal outcomes of death and severe morbidity, there
is no evidence to support the addition of dexamethasone or betamethasone to standard therapy in HELLP syndrome. However,
it is important to note that glucocorticoids have been shown to
improve fetal lung maturity and overall fetal mortality and morbidity when the appropriate 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 a large study
with the appropriate design be done to determine the effect of
antenatal and postpartum steroids on the primary and secondary
outcomes chosen in this review. Steroids are relatively cheap and
if found efficacious in decreasing the primary outcomes sought
in the review, they would provide a cost-effective intervention for
HELLP syndrome. Because HELLP syndrome is not very common (Sibai 1993), a global multi-centre study design may be the
most efficient study design to use in order to recruit sufficient patients to adequately answer the review question.

POTENTIAL CONFLICT OF
INTEREST
We certify that we have no affiliations or involvement in any organisation or entity with a direct financial interest in the subject
matter of the review (e.g. employment, consultancy, stock ownership, honoraria and expert testimony). The researchers wrote this
review independently and Novartis Pharmaceuticals has no commercial or intellectual interest in the topic or products reviewed.

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

SOURCES OF SUPPORT
External sources of support

AUTHORS’ CONCLUSIONS

• No sources of support supplied

Implications for practice

Internal sources of support

Until a large enough study that is adequately designed with suffi-

• Medical Research Council SOUTH AFRICA

Corticosteroids for HELLP syndrome in pregnancy (Review)
Copyright © 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd

6


REFERENCES

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 the efficacy of dexamethasone and betamethasone for the treatment of antepartum HELLP (hemolysis,
elevated liver enzymes, and low platelet count) syndrome [Un estudio prospectivo, randomizado que compara la eficacia de la dexametasona y betametasona para el tratamiento anteparto del sindron de
hellp (hemolisis, elevacion de enzimas hepaticas y plaquetopenia)].
Revista Chilena de Obstetricia y Ginecologia 2001;66(3):248–50.
Isler CM, Barrilleaux PS, Magann EF, Bass JD, Martin JN. A prospective, randomized trial comparing the efficacy of dexamethasone and
betamethasone for the treatment of antepartum HELLP (hemolysis,
elevated liver enzymes, and low platelet count) syndrome. American
Journal of Obstetrics and Gynecology 2001;184(7):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(4):
1154–8.

Kadanali 1997
Kadanali S, Kucukozkan T, Bukam B. Helpful effect of high-dose
corticosteroid use on Hellp syndrome. Jinekoloji Ve Obstetrik Dergisi
1997;11:55–8.

Additional references
Clark 1986
Clark SL, Phelan JR, Allen SH, Golde SR. Antepartum reversal of
hematologic abnormalities associated with the HELLP syndrome. A
report of three cases. Journal of Reproductive Medicine 1986;31:70–2.
Clarke 2000
Clarke M, Oxman AD, editors. Cochrane Reviewers’ Handbook 4.1
[updated June 2000]. In: Review Manager (RevMan) [Computer
program]. Version 4.1. Oxford, England: The Cochrane Collaboration, 2000.
Crowley 1999
Crowley P. Prophylactic corticosteroids for preterm birth (Cochrane

Review). In: The Cochrane Library, 4, 1999. Oxford: Update software.
Duley 1992
Duley L. Maternal mortality associated with hypertensive disorders of
pregnancy in Africa, Asia, Latin America and the Caribbean. British
Journal of Obstetrics and Gynaecology 1992;99:547–53.

Magann 1994b {published data only}
Magann EF, Bass D, Chauhan SP, Sullivan D, Martin RW, Martin
JN. Antepartum corticosteroids: disease stabilization 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 1993
Magann EF, Martin RW, Issacs JD, Blake PG, Morrison JC, Martin
JN Jr. Corticosteroids for the enhancement 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.

Magann EF, Bass D, Chauhan SP, Sullivan DL, Martin RW, Martin JN. Antepartum corticosteroids: disease stabilization in patients
with HELLP syndrome. American Journal of Obstetrics and Gynecology 1994;170:410.

Martin 1991
Martin JN Jr, 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 Gynecology 1991;164:1500–9.

Vigil-De Gracia 1997 {published data only}
Vigil-De Gracia P, Garcia-Caceres E. Dexamethasone in the postpartum 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 with HELLP syndrome. International
Journal of Gynecology & Obstetrics 1998;61:141–8.

References to studies awaiting assessment
Isler 2003
Isler C, Magann E, Rinehart B, Terrone D, Bass J, Martin J Jr. Dexamethasone versus betmethasone for postpartum hellp syndrome: a
randomized prospective clinical trial of comparative efficacy. American Journal of Obstetrics and Gynecology 2000;182(1 Pt 2):S87.
Isler CM, Magann EF, Rinehart BK, Terrone DA, Bass JD, Martin JN
Jr. Dexamethasone compared with betamethasone for glucocorticoid
treatment of postpartum hellp syndrome. International Journal of
Gynecology & Obstetrics 2003;80(3):291–7.

Martin 1997
Martin JN, Perry KG Jr, Blake PG, May WA, Moore A, Robinette
L. Better maternal outcomes are achieved with dexamethasone therapy for postpartum HELLP (hemolysis, elevated liver enzymes and
thrombocytopenia) 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 other haematologic abnormalities associated with severe toxemia of pregnancy. New England Journal of Medicine 1954;250:89–98.
Sibai 1986
Sibai BM, Taslimi MM, el-Nazer A, Aman E, Mabie BC, Ryan GM.
Maternal-perinatal outcome associated with the syndrome of hemolysis, elevated liver enzymes, and low platelets in severe pre-eclampsiaeclampsia. 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 in 442 pregnancies with

Corticosteroids for HELLP syndrome in pregnancy (Review)
Copyright © 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd

7


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 with HELLP 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 of three cases. Journal of Reproductive
Medicine 1987;32:781–4.

TABLES

Characteristics of included studies
Study

Isler 2001

Methods

Randomisation:
random number tables used.
Allocation concealment:
sealed, opaque envelopes.

Blinding:
not mentioned.
Loss to follow up:
none.
Intention to treat analysis done.

Participants

Randomisation antepartum done into dexamethasone and betamethasone groups.
N = 41 (19 in the dexamethasone group and 21 in the betamethasone group).
No differences in the participant characteristics postrandomisation.
All participants had labor induced after stabilisation unless a cesarean section was indicated.

Interventions

All groups:
1. Intravenous magnesium sulphate for seizure prophylaxis at study enrolment and continued for 24 hours
postpartum.
2. Intravenous fluids.
3. Hydralazine or labetalol used to control acute hypertensive episodes.
Betamethasone group:
In addition to the above, this group was given combination 12 mg betamethasone acetate and betamethasone
sodium phosphate intramuscularly every 24 hours until criteria for discontinuation met (see criteria). On
the other hand, the dexamethasone group was given:
10 mg dexamethasone sodium phosphate intravenously every 12 hours.

Outcomes

Primary endpoint was considered to be:

Corticosteroids for HELLP syndrome in pregnancy (Review)
Copyright © 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd

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Characteristics of included studies (Continued )
1. The impact of the steroid on laboratory values (platelet count, LDH activity, AST activity) MAP and
urinary output, using adjusted time averaged change from baseline.
Kaplan-Meier were generated to illustrate the cumulative distribution of time to delivery.
2. Ancillary analyses considered the frequency of additional medications and treatments for patient stabilization.
Both maternal and neonatal mortality and morbidity data were captured.
Notes

Adequate allocation concealment and randomisation method.

Allocation concealment

A – Adequate

Study

Magann 1994a

Methods

Randomisation:
random number tables used.
Allocation concealment:
sealed, opaque envelopes.

Blinding:
not mentioned.
Loss to follow up:
none.
Intention to treat analysis done.

Participants

Randomisation postpartum done into steroid and control groups after ’disease remission was believed to
present’.
At randomisation N = 40. There were no statistical differences in participants’ characteristics postrandomisation between the two groups.
At analysis of results, 15 participants not accounted for (lost to follow up). Only 12 in the steroid group and
13 in the control group accounted for.

Interventions

Control group:
Magnesium sulphate 2 gm/hr intravenous infusion for 36 hours.
No mention of antihypertensive therapy used.
Treatment group:
1. Magnesium sulphate regimen as the control group.
2. Dexamethazone 10 mg intravenously as a stat dose then, 10 mg after 12 hours, followed by 5 mg 12
hourly at 24 hours and 36 hours. Total steroid given 30 mg of Dexamethazone.

Outcomes

Data reported on 25 participants only instead of 40 (steroid: 12, and control: 13).
No tables of dichotomous or continuous data provided. Only charted graphs provided.
Conclusions:
1. No primary maternal or neonatal outcomes recorded or mentioned.

2. Secondary outcomes: compared with the control group, in the steroid group:
i) The MAP became significantly decreased by 22 hours postpartum (p < 0.03) significantly different.
ii) The urinary output increased significantly by 36 hours postpartum (p < 0.02).
iii) The platelet count had significantly increased by 24 hours postpartum (p < 0.05).
iv) Both the LDH and the aspartate aminotransferase decreased significantly by 36 hours (p < 0.04 and p <
0.05) respectively.
v) There were no differences in:
postpartum infectious morbidity;
abnormal uterine bleeding;
alanine aminotransferase and hematocrit values between the steroid treated group and placebo.

Corticosteroids for HELLP syndrome in pregnancy (Review)
Copyright © 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd

9


Characteristics of included studies (Continued )
Notes

Adequate allocation concealment.
Loss to follow up greater than 37%.
No blinding.

Allocation concealment

A – Adequate

Study

Magann 1994b

Methods

Randomisation:
computer generated with card enclosed in sealed opaque envelope.
Allocation concealment: adequate.
Blinding: not mentioned.
Loss to follow up: none.
Intention to treat analysis done.

Participants

Antepartum randomisation of participants between 27 and 34 weeks gestation.
N = 25 (steroid group = 12 and control group = 13).
1. Participant characteristics differed on the level of the maternal platelet count (p = 0.034). The authors
speculate that the steroid group was perhaps a sicker group. The other participant characteristics were not
significantly different.
2. The ratio of black to white participants was 2:1 in the placebo group compared with 1:1 in the placebo
group.

Interventions

Control group:
Managed with standard HELLP protocol (drugs not mentioned).
Steroid group:
In addition to the above management, dexamethazone was administered intravenously at rate of 10 mg, 12
hourly until delivery.

Outcomes

Maternal primary outcomes:
No maternal primary outcomes occurred (death, liver heamatoma or rupture, pulmonary oedema, renal
failure, abruptio placentae).
Maternal secondary outcomes:
Simple linear regression technique was used to model the hourly rates of change for the following parameters:
1. Mean urinary output increased in the steroid treated group compared with the control group (p < 0.0006).
2. Platelets significantly increased in the steroid treated group compared with the control group (p < 0.006).
3. LDH in the treatment group decreased significantly (p < 0.03) compared with the control group. 4.
Aspartate aminotransferase decreased significantly in the treatment group (p < 0.005) compared with the
control group, ’over time’.
Postpartum maternal secondary outcomes were noted and the authors concluded that:
1. There was a significant difference in the time to delivery after randomisation.
2. There was an immediate deterioration in the disease process in all patients (no significant differences
between the two groups).
2. There was resolution of the HELLP syndrome process by 96 hours postpartum and again there was no
significant differences between the two groups.
Neonatal primary outcomes:
1. Neonatal deaths were recorded in both groups.
2. Neonatal morbidity (respiratory distress syndrome, intraventricular hemorrhage and retrolental fibroplasia)
were recorded.
3. Birthweight, and
4. Apgar scores after 5 minutes were also recorded.

Notes

Adequate allocation concealment.

Corticosteroids for HELLP syndrome in pregnancy (Review)
Copyright © 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd

10


Characteristics of included studies (Continued )
Patient characteristics after randomisation not the same, mainly steroid allocated patients had a statistically
significant lower platelet count.
The racial distribution (black and white) was unequal between the two groups).
Allocation concealment

A – Adequate

Study

Vigil-De Gracia 1997

Methods

Randomisation:
no mention of method used.
Allocation concealment:
not mentioned.
Blinding:
not mentioned.
Loss to follow up: nil.
Intention to treat analysis done.

Participants

Randomisation done antepartum.

N = 34.
Participant demographics after randomisation:
The two groups are not significantly different except in the platelet count which was statistically significant
(p < 0.05); with lower counts in the treatment group.

Interventions

Control group:
1. Hydralazine boluses given to control blood pressure.
2. No MgSO4 given to prevent or control fits.
Treatment groups:
1. Given the same treatment as the control group and
2. Dexamethazone 10 mg intravenously stat then 12 hourly until 30 mg dose given after 24 hours.
3. All patients monitored for 72 hours and after delivery.

Outcomes

Maternal primary outcomes:
1. Death was the only primary outcome noted in the study.
Maternal secondary outcomes:
1. The authors noted there was no significant differences between the steroid treated group and control for
the postpartum sepsis, metabolic disorders, blood pressure control, urinary output, LDH, AST and ALT
values post delivery.
2. Platelet count resolution was recorded and the rate of increase was found to be significantly different in
favour of the steroid treated group at 30 hours postpartum (p < 0.01).

Notes

Unclear allocation concealment.
Randomisation method not stated.

Post randomisation patient platelet levels significantly different.

Allocation concealment

B – Unclear

Study

Yalcin 1998

Methods

N = 30.
Postpartum patients with HELLP syndrome
randomised (method not stated).
Allocation concealment not mentioned. Blinding not stated.

Corticosteroids for HELLP syndrome in pregnancy (Review)
Copyright © 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd

11


Participants

Randomisation done antepartum.
N = 34.
Participant demographics after randomisation:
The two groups are not significantly different except in the platelet count which was statistically significant
(p < 0.05); with lower counts in the treatment group.

Interventions

Control group given magnesium sulphate regimen for eclampsia prevention, nifedipine to decrease acute
blood pressure and methyl dopa as maintenance antihypternsive medication.
Steroid group given the above treatment and: dexamethazone 10 mg intravenously as a stat dose, then 10
mg after 12 hours, followed by 5 mg at 24 and 36 hours respectively. Total dexamethazone dose given was
30 mg in 36 hours.

Outcomes

The authors provided mean data without standard deviations but concluded that:
1. Following initiation of dexamethazone therapy the mean arterial pressure and mean serum level aspartate
aminotransferase of the study group became significantly decreased by 28 hours and 36 hours respectively (p
< 0.05) and that compared with the control group, it was observed that both the mean platelet count and the
mean urine output per hour of the study group increased significantly by 36 hours and 20 hours postpartum
respectively (p < 0.05). These differences in effects lasted beyond the 48 hour observation period.
2. They also concluded that there were no significant differences in the mean hematocrit values, serum alanine
aminotransferase and uric acid levels between the two groups at any time interval during the first 48 hours
postpartum. No data were provided.
None of the primary outcomes (death, liver hematoma or rupture, pulmonary oedema, renal failure and
abruptio) were noted in the two treatment groups postrandomisation.
4. Maternal infectious morbidity postrandomisation was recorded and was not significant.
5. Mean hospital length stay in days (with SD) was given and ranges. 6.0 +/- 4.1 days (4-15) for the steroid
treated group and 10.5 +/- 3.2 days (6-21) for the control group (p < 0.01).
Neonatal outcomes were not recorded.

Notes

Allocation concealment unclear. Randomisation method not stated. No mention of blinding method or

whom was blinded.

Allocation concealment

B – Unclear

ALT: alanine transaminase
AST: aspartate transaminase
LDH: lactate dehydrogenase
MAP: mean arterial pressure
N: number
SD: standard deviation
stat: daily

ANALYSES

Comparison 01. Dexamethasone plus standard treatment versus standard treatment alone
Outcome title
01 Maternal deaths
02 Postpartum sepsis
03 Mean platelet counts over 48
hours
04 Mean hospital stay post
randomisation (days)
05 Neonatal deaths

No. of
studies
1
1

1

No. of
participants
34
30
34

Relative Risk (Fixed) 95% CI
Relative Risk (Fixed) 95% CI
Weighted Mean Difference (Fixed) 95% CI

1

30

Weighted Mean Difference (Fixed) 95% CI

0.33 [0.01, 7.65]
2.00 [0.20, 19.78]
40.60 [-26.12,
107.32]
-4.50 [-7.13, -1.87]

1

25

Relative Risk (Fixed) 95% CI

0.36 [0.04, 3.02]

Statistical method

Corticosteroids for HELLP syndrome in pregnancy (Review)
Copyright © 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd

Effect size

12


06 Neonates with intraventricular
hemorrhage
07 Neonates with respiratory
distress syndrome
08 Neonates with 5 minute Apgars
less than 7
09 Weight at birth in grams
10 Neonates with retrolental
fibroplasia
11 Number of cesarean section
deliveries
12 Time interval (hours) from
randomisation to delivery

1

25

Relative Risk (Fixed) 95% CI

7.54 [0.43, 132.35]

1

24

Relative Risk (Fixed) 95% CI

1.00 [0.25, 4.00]

1

24

Relative Risk (Fixed) 95% CI

1.00 [0.25, 4.00]

1

25

Weighted Mean Difference (Fixed) 95% CI

1

25

Relative Risk (Fixed) 95% CI

247.00 [65.41,
428.59]
0.36 [0.02, 8.05]

1

34

Relative Risk (Fixed) 95% CI

0.93 [0.66, 1.31]

Weighted Mean Difference (Fixed) 95% CI

Totals not selected

Comparison 02. Dexamethasone versus betamethasone

Outcome title
01 Mean arterial pressure: adjusted
time-averaged change from
baseline
02 Urinary output (mL/h):
adjusted time-averaged change
from baseline
03 Platelet count (10-9 cells/L):
adjusted time-averaged change
from baseline

04 LDH activity (U/L mean):
adjusted time-averaged change
from baseline
05 AST activity (U/L): adjusted
time-averaged change from
baseline
06 Number of mothers with
oliguria (less than 30 ml/hour
for 2 hours)
07 Maternal pulmonary edema
08 Number of participants
needing acute antihypertensive
therapy
09 Neonates with a 5 minute
Apgar less than 7
10 Neonates needing ventilatory
support
11 Neonates with respiratory
distress syndrome
12 Neonatal sepsis
13 Neonatal hyperbilirubinemia
14 Fetal or neonatal death

No. of
studies

No. of
participants

1

40

Weighted Mean Difference (Fixed) 95% CI

-7.50 [-8.37, -6.63]

1

40

Weighted Mean Difference (Fixed) 95% CI

24.80 [19.58, 30.02]

1

40

Weighted Mean Difference (Fixed) 95% CI

8.10 [6.23, 9.97]

1

40

Weighted Mean Difference (Fixed) 95% CI

-54.20 [-88.22,

-20.18]

1

40

Weighted Mean Difference (Fixed) 95% CI

-30.30 [-36.06,
-24.54]

1

40

Relative Risk (Fixed) 95% CI

0.06 [0.00, 0.93]

1
1

40
40

Relative Risk (Fixed) 95% CI
Relative Risk (Fixed) 95% CI

Not estimable
0.29 [0.12, 0.73]

1

39

Relative Risk (Fixed) 95% CI

0.95 [0.22, 4.14]

1

39

Relative Risk (Fixed) 95% CI

0.54 [0.19, 1.56]

1

39

Relative Risk (Fixed) 95% CI

0.54 [0.19, 1.56]

1
1
1

39

39
39

Relative Risk (Fixed) 95% CI
Relative Risk (Fixed) 95% CI
Relative Risk (Fixed) 95% CI

4.76 [0.24, 93.19]
2.85 [0.32, 25.07]
0.95 [0.15, 6.08]

Statistical method

Corticosteroids for HELLP syndrome in pregnancy (Review)
Copyright © 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd

Effect size

13


15 Neonate time to discharge
(days: mean)

1

39

Weighted Mean Difference (Fixed) 95% CI

-5.40 [-19.53, 8.73]

INDEX TERMS
Medical Subject Headings (MeSH)
Adrenal Cortex Hormones [∗ therapeutic use]; Betamethasone [therapeutic use]; Dexamethasone [therapeutic use]; HELLP Syndrome
[∗ drug therapy]; Randomized Controlled Trials
MeSH check words
Female; Humans; Pregnancy

COVER SHEET
Title

Corticosteroids for HELLP syndrome in pregnancy

Authors

Matchaba P, Moodley J

Contribution of author(s)

PT Matchaba conceived the idea, and wrote the protocol and review. J Moodley assisted
with the writing of the protocol and the review.

Issue protocol first published

2000/2

Review first published

2004/1

Date of most recent amendment

24 August 2005

Date of most recent
SUBSTANTIVE amendment

31 October 2003

What’s New

Information not supplied by author

Date new studies sought but
none found

Information not supplied by author

Date new studies found but not
yet included/excluded

31 October 2003

Date new studies found and
included/excluded

18 July 2002

Date authors’ conclusions

section amended

Information not supplied by author

Contact address

Dr Patrice Tinaye Matchaba
Medical Director
Novartis Pharmaceutical Corporation
CD and MA, Building 122
One Health Plaza
East Hanover
New Jersey
NJ 07936 - 108
USA
E-mail:
Tel: +1 862 7788443
Fax: +1 973 7813579

DOI

10.1002/14651858.CD002076.pub2

Corticosteroids for HELLP syndrome in pregnancy (Review)
Copyright © 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd

14


Cochrane Library number

CD002076

Editorial group

Cochrane Pregnancy and Childbirth Group

Editorial group code

HM-PREG
GRAPHS AND OTHER TABLES

Analysis 01.01.
Review:

Comparison 01 Dexamethasone plus standard treatment versus standard treatment alone,
Outcome 01 Maternal deaths

Corticosteroids for HELLP syndrome in pregnancy

Comparison: 01 Dexamethasone plus standard treatment versus standard treatment alone
Outcome: 01 Maternal deaths
Study

Vigil-De Gracia 1997
Total (95% CI)

Dexamethasone

Control

Relative Risk (Fixed)

Weight

Relative Risk (Fixed)

n/N

n/N

95% CI

(%)

95% CI

0/17

1/17

100.0

0.33 [ 0.01, 7.65 ]

17

17

100.0

0.33 [ 0.01, 7.65 ]

Total events: 0 (Dexamethasone), 1 (Control)
Test for heterogeneity: not applicable
Test for overall effect z=0.69

p=0.5

0.1 0.2

0.5

1

Favour Dexamethasone

Analysis 01.02.
Review:

2

5

10

Favour control

Comparison 01 Dexamethasone plus standard treatment versus standard treatment alone,
Outcome 02 Postpartum sepsis

Corticosteroids for HELLP syndrome in pregnancy

Comparison: 01 Dexamethasone plus standard treatment versus standard treatment alone
Outcome: 02 Postpartum sepsis
Study

Yalcin

1998

Total (95% CI)

Dexamethasone

Control

Relative Risk (Fixed)

Weight

Relative Risk (Fixed)

n/N

n/N

95% CI

(%)

95% CI

2/15

1/15

100.0

2.00 [ 0.20, 19.78 ]

15

15

100.0

2.00 [ 0.20, 19.78 ]

Total events: 2 (Dexamethasone), 1 (Control)
Test for heterogeneity: not applicable
Test for overall effect z=0.59

p=0.6

0.1 0.2

0.5

1

Favour Dexamethasone

Corticosteroids for HELLP syndrome in pregnancy (Review)
Copyright © 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd

2

5

10

Favour control

15


Analysis 01.03.
Review:

Comparison 01 Dexamethasone plus standard treatment versus standard treatment alone,
Outcome 03 Mean platelet counts over 48 hours

Corticosteroids for HELLP syndrome in pregnancy

Comparison: 01 Dexamethasone plus standard treatment versus standard treatment alone
Outcome: 03 Mean platelet counts over 48 hours
Study

Dexamethasone

Vigil-De Gracia 1997
Total (95% CI)

Control

N

Mean(SD)

N

Mean(SD)

17

110.26 (118.00)

17

69.66 (76.00)

17

Weighted Mean Difference (Fixed)

Weight

95% CI

(%)

17

Weighted Mean Difference (Fixed)
95% CI

100.0

40.60 [ -26.12, 107.32 ]

100.0

40.60 [ -26.12, 107.32 ]

Test for heterogeneity: not applicable
Test for overall effect z=1.19

p=0.2

-100.0

-50.0

0

50.0

Favour control

Analysis 01.04.
Review:

100.0

Favour Dexamethasone

Comparison 01 Dexamethasone plus standard treatment versus standard treatment alone,
Outcome 04 Mean hospital stay post randomisation (days)

Corticosteroids for HELLP syndrome in pregnancy

Comparison: 01 Dexamethasone plus standard treatment versus standard treatment alone
Outcome: 04 Mean hospital stay post randomisation (days)
Study

Yalcin

Dexamethasone

1998

Total (95% CI)

Control

N

Mean(SD)

N

Mean(SD)

15

6.00 (4.10)

15

10.50 (3.20)

15

Weighted Mean Difference (Fixed)

Weight

Weighted Mean Difference (Fixed)

95% CI

(%)

95% CI

15

100.0

-4.50 [ -7.13, -1.87 ]

100.0

-4.50 [ -7.13, -1.87 ]

Test for heterogeneity: not applicable
Test for overall effect z=3.35

p=0.0008

-10.0

-5.0

Favour Dexamethasone

0

5.0

10.0

Favour control

Corticosteroids for HELLP syndrome in pregnancy (Review)
Copyright © 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd

16

Analysis 01.05.
Review:

Comparison 01 Dexamethasone plus standard treatment versus standard treatment alone,
Outcome 05 Neonatal deaths

Corticosteroids for HELLP syndrome in pregnancy

Comparison: 01 Dexamethasone plus standard treatment versus standard treatment alone
Outcome: 05 Neonatal deaths
Study

Magann 1994b
Total (95% CI)

Dexamethasone

Control

Relative Risk (Fixed)

Weight

Relative Risk (Fixed)

n/N

n/N

95% CI

(%)

95% CI

1/12

3/13

100.0

0.36 [ 0.04, 3.02 ]

12

13

100.0

0.36 [ 0.04, 3.02 ]

Total events: 1 (Dexamethasone), 3 (Control)
Test for heterogeneity: not applicable
Test for overall effect z=0.94

p=0.3

0.1 0.2

0.5

1

Favour Dexamethasone

Analysis 01.06.
Review:

2

5

10

Favour control

Comparison 01 Dexamethasone plus standard treatment versus standard treatment alone,
Outcome 06 Neonates with intraventricular hemorrhage

Corticosteroids for HELLP syndrome in pregnancy

Comparison: 01 Dexamethasone plus standard treatment versus standard treatment alone
Outcome: 06 Neonates with intraventricular hemorrhage
Study

Magann 1994b
Total (95% CI)

Dexamethasone

Control

Relative Risk (Fixed)

Weight

Relative Risk (Fixed)

n/N

n/N

95% CI

(%)

95% CI

3/12

0/13

100.0

7.54 [ 0.43, 132.35 ]

12

13

100.0

7.54 [ 0.43, 132.35 ]

Total events: 3 (Dexamethasone), 0 (Control)
Test for heterogeneity: not applicable
Test for overall effect z=1.38

p=0.2

0.001 0.01 0.1

1

Favour Dexamethasone

Corticosteroids for HELLP syndrome in pregnancy (Review)
Copyright © 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd

10 100 1000
Favour control

17


Analysis 01.07.
Review:

Comparison 01 Dexamethasone plus standard treatment versus standard treatment alone,

Outcome 07 Neonates with respiratory distress syndrome

Corticosteroids for HELLP syndrome in pregnancy

Comparison: 01 Dexamethasone plus standard treatment versus standard treatment alone
Outcome: 07 Neonates with respiratory distress syndrome
Study

Magann 1994b
Total (95% CI)

Dexamethasone

Control

Relative Risk (Fixed)

Weight

n/N

n/N

95% CI

(%)

Relative Risk (Fixed)
95% CI

3/12

3/12

100.0

1.00 [ 0.25, 4.00 ]

12

12

100.0

1.00 [ 0.25, 4.00 ]

Total events: 3 (Dexamethasone), 3 (Control)
Test for heterogeneity: not applicable
Test for overall effect z=0.00

p=1

0.1 0.2

0.5

1

Favour Dexamethasone

Analysis 01.08.
Review:

2

5

10

Favour control

Comparison 01 Dexamethasone plus standard treatment versus standard treatment alone,
Outcome 08 Neonates with 5 minute Apgars less than 7

Corticosteroids for HELLP syndrome in pregnancy

Comparison: 01 Dexamethasone plus standard treatment versus standard treatment alone
Outcome: 08 Neonates with 5 minute Apgars less than 7
Study

Magann 1994b
Total (95% CI)

Dexamethasone

Control

Relative Risk (Fixed)

Weight

Relative Risk (Fixed)

n/N

n/N

95% CI

(%)

95% CI

3/12

3/12

100.0

1.00 [ 0.25, 4.00 ]

12

12

100.0

1.00 [ 0.25, 4.00 ]

Total events: 3 (Dexamethasone), 3 (Control)

Test for heterogeneity: not applicable
Test for overall effect z=0.00

p=1

0.1 0.2

0.5

1

Favour Dexamethasone

Corticosteroids for HELLP syndrome in pregnancy (Review)
Copyright © 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd

2

5

10

Favour control

18


Analysis 01.09.
Review:

Comparison 01 Dexamethasone plus standard treatment versus standard treatment alone,
Outcome 09 Weight at birth in grams

Corticosteroids for HELLP syndrome in pregnancy

Comparison: 01 Dexamethasone plus standard treatment versus standard treatment alone
Outcome: 09 Weight at birth in grams
Study

Magann 1994b
Total (95% CI)

Dexamethasone

Control

N

Mean(SD)

N

Mean(SD)

12

1758.00 (230.00)

13

1511.00 (233.00)

12

Weighted Mean Difference (Fixed)

Weight

95% CI

(%)

13

Weighted Mean Difference (Fixed)
95% CI

100.0

247.00 [ 65.41, 428.59 ]

100.0

247.00 [ 65.41, 428.59 ]

Test for heterogeneity: not applicable
Test for overall effect z=2.67

p=0.008

-1000.0 -500.0

0

500.0 1000.0

Favour control

Analysis 01.10.
Review:

Favour Dexamethasone

Comparison 01 Dexamethasone plus standard treatment versus standard treatment alone,
Outcome 10 Neonates with retrolental fibroplasia

Corticosteroids for HELLP syndrome in pregnancy

Comparison: 01 Dexamethasone plus standard treatment versus standard treatment alone
Outcome: 10 Neonates with retrolental fibroplasia
Study

Magann 1994b
Total (95% CI)

Dexamethasone

Control

Relative Risk (Fixed)

Weight

Relative Risk (Fixed)

n/N

n/N

95% CI

(%)

95% CI

0/12

1/13

100.0

0.36 [ 0.02, 8.05 ]

12

13

100.0

0.36 [ 0.02, 8.05 ]

Total events: 0 (Dexamethasone), 1 (Control)
Test for heterogeneity: not applicable
Test for overall effect z=0.65

p=0.5

0.1 0.2

0.5

1

Favour Dexamethasone

Corticosteroids for HELLP syndrome in pregnancy (Review)
Copyright © 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd

2

5

10

Favour control

19


Analysis 01.11.

Review:

Comparison 01 Dexamethasone plus standard treatment versus standard treatment alone,
Outcome 11 Number of cesarean section deliveries

Corticosteroids for HELLP syndrome in pregnancy

Comparison: 01 Dexamethasone plus standard treatment versus standard treatment alone
Outcome: 11 Number of cesarean section deliveries
Study

Vigil-De Gracia 1997
Total (95% CI)

Dexamethasone

Control

Relative Risk (Fixed)

Weight

Relative Risk (Fixed)

n/N

n/N

95% CI

(%)

95% CI

13/17

14/17

100.0

0.93 [ 0.66, 1.31 ]

17

17

100.0

0.93 [ 0.66, 1.31 ]

Total events: 13 (Dexamethasone), 14 (Control)
Test for heterogeneity: not applicable
Test for overall effect z=0.42

p=0.7

0.1 0.2

0.5

1

Favour Dexamethasone

Analysis 01.12.
Review:

2

5

10

Favour control

Comparison 01 Dexamethasone plus standard treatment versus standard treatment alone,
Outcome 12 Time interval (hours) from randomisation to delivery

Corticosteroids for HELLP syndrome in pregnancy

Comparison: 01 Dexamethasone plus standard treatment versus standard treatment alone
Outcome: 12 Time interval (hours) from randomisation to delivery
Study

Dexamathasone

Magann 1994b

Control

N

Mean(SD)

N

Mean(SD)

12

41.00 (15.00)

13

15.00 (4.50)

Weighted Mean Difference (Fixed)

Weighted Mean Difference (Fixed)

95% CI

95% CI
26.00 [ 17.17, 34.83 ]

-100.0

-50.0

Favour control

Analysis 02.01.
Review:

0

50.0

100.0

Favour Dexamethasone

Comparison 02 Dexamethasone versus betamethasone, Outcome 01 Mean arterial pressure:
adjusted time-averaged change from baseline

Corticosteroids for HELLP syndrome in pregnancy

Comparison: 02 Dexamethasone versus betamethasone
Outcome: 01 Mean arterial pressure: adjusted time-averaged change from baseline
Study

Isler 2001
Total (95% CI)

Dexamethasone

Betamethasone

N

Mean(SD)

N

Mean(SD)

19

-15.60 (1.40)

21

-8.10 (1.40)

19

Weighted Mean Difference (Fixed)

Weight

Weighted Mean Difference (Fixed)

95% CI

(%)

95% CI

21

100.0

-7.50 [ -8.37, -6.63 ]

100.0

-7.50 [ -8.37, -6.63 ]

Test for heterogeneity: not applicable
Test for overall effect z=16.92

p<0.00001

-10.0

-5.0

Favour Dexamethasone

0

5.0

10.0

Favour Betamethasone

Corticosteroids for HELLP syndrome in pregnancy (Review)
Copyright © 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd

20


Analysis 02.02.
Review:

Comparison 02 Dexamethasone versus betamethasone, Outcome 02 Urinary output (mL/h):
adjusted time-averaged change from baseline

Corticosteroids for HELLP syndrome in pregnancy

Comparison: 02 Dexamethasone versus betamethasone
Outcome: 02 Urinary output (mL/h): adjusted time-averaged change from baseline
Study

Dexamethasone

Isler 2001
Total (95% CI)

Betamethasone

N

Mean(SD)

N

Mean(SD)

19

12.90 (8.60)

21

-11.90 (8.20)

19

Weighted Mean Difference (Fixed)

Weight

95% CI

(%)

95% CI

100.0

24.80 [ 19.58, 30.02 ]

100.0

24.80 [ 19.58, 30.02 ]

21

Weighted Mean Difference (Fixed)

Test for heterogeneity: not applicable
Test for overall effect z=9.31

p<0.00001

-100.0

-50.0

0

Favour Betamethasone

Analysis 02.03.
Review:

50.0

100.0

Favour Dexamethasone

Comparison 02 Dexamethasone versus betamethasone, Outcome 03 Platelet count (10-9
cells/L): adjusted time-averaged change from baseline

Corticosteroids for HELLP syndrome in pregnancy

Comparison: 02 Dexamethasone versus betamethasone

Outcome: 03 Platelet count (10-9 cells/L): adjusted time-averaged change from baseline
Study

Dexamethasone

Isler 2001
Total (95% CI)

Betamethasone

N

Mean(SD)

N

Mean(SD)

19

13.10 (3.10)

21

5.00 (2.90)

19

Weighted Mean Difference (Fixed)

Weight

Weighted Mean Difference (Fixed)

95% CI

(%)

95% CI

21

100.0

8.10 [ 6.23, 9.97 ]

100.0

8.10 [ 6.23, 9.97 ]

Test for heterogeneity: not applicable
Test for overall effect z=8.51

p<0.00001

-10.0

-5.0

0

5.0

Favour Betamethasone

Analysis 02.04.
Review:

10.0

Favour Dexamethasone

Comparison 02 Dexamethasone versus betamethasone, Outcome 04 LDH activity (U/L
mean): adjusted time-averaged change from baseline

Corticosteroids for HELLP syndrome in pregnancy

Comparison: 02 Dexamethasone versus betamethasone
Outcome: 04 LDH activity (U/L mean): adjusted time-averaged change from baseline
Study

Isler 2001
Total (95% CI)

Dexamethasone

Betamethasone

N

Mean(SD)

N

Mean(SD)

19

-81.20 (56.60)

21

-27.00 (52.80)

19

Weighted Mean Difference (Fixed)

Weight

Weighted Mean Difference (Fixed)

95% CI

(%)

95% CI

21

100.0

-54.20 [ -88.22, -20.18 ]

100.0

-54.20 [ -88.22, -20.18 ]

Test for heterogeneity: not applicable
Test for overall effect z=3.12

p=0.002

-100.0

-50.0

Favour Dexamethasone

0

50.0

100.0

Favour Betamethasone

Corticosteroids for HELLP syndrome in pregnancy (Review)
Copyright © 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd

21


Analysis 02.05.
Review:

Comparison 02 Dexamethasone versus betamethasone, Outcome 05 AST activity (U/L):
adjusted time-averaged change from baseline

Corticosteroids for HELLP syndrome in pregnancy

Comparison: 02 Dexamethasone versus betamethasone
Outcome: 05 AST activity (U/L): adjusted time-averaged change from baseline
Study

Dexamethasone

Isler 2001
Total (95% CI)

Betamethasone

N

Mean(SD)

N

Mean(SD)

19

-20.40 (9.60)

21

9.90 (8.90)

19

Weighted Mean Difference (Fixed)

Weight

95% CI

(%)

21

Weighted Mean Difference (Fixed)
95% CI

100.0

-30.30 [ -36.06, -24.54 ]

100.0

-30.30 [ -36.06, -24.54 ]

Test for heterogeneity: not applicable
Test for overall effect z=10.32

p<0.00001

-100.0

-50.0

0

Favour Dexamethasone

Analysis 02.06.
Review:

50.0

100.0

Favour Betamethasone

Comparison 02 Dexamethasone versus betamethasone, Outcome 06 Number of mothers
with oliguria (less than 30 ml/hour for 2 hours)

Corticosteroids for HELLP syndrome in pregnancy

Comparison: 02 Dexamethasone versus betamethasone
Outcome: 06 Number of mothers with oliguria (less than 30 ml/hour for 2 hours)

Study

Isler 2001
Total (95% CI)

Dexamethasone

Betamethasone

Relative Risk (Fixed)

Weight

Relative Risk (Fixed)

n/N

n/N

95% CI

(%)

95% CI

0/19

9/21

100.0

0.06 [ 0.00, 0.93 ]

19

21

100.0

0.06 [ 0.00, 0.93 ]

Total events: 0 (Dexamethasone), 9 (Betamethasone)
Test for heterogeneity: not applicable
Test for overall effect z=2.01

p=0.04

0.5

0.7

Favour Dexamethasone

Corticosteroids for HELLP syndrome in pregnancy (Review)
Copyright © 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd

1

1.5

2

Favour Betamethasone

22