hemolysis , elevated liver enzymes , and low platelet count ( hellp ) syndrome is a severe manifestation of a hypertensive disorder of pregnancy called pre - eclampsia .
it affects about 10% to 20% of patients with severe pre - eclampsia ( 0.5% to 0.9% of all pregnancies ) and causes significant mortality and morbidity , which increases in accordance with the severity of this syndrome .
this syndrome is associated with increased maternal risk of developing morbidities , including cerebrovascular complications , hemorrhage , pulmonary edema , retinal detachment , hematoma / hepatic rupture , acute renal failure , liver failure , intravascular coagulopathy , placental abruption , and sepsis [ 35 ] .
perinatal / infant morbidity and mortality rates are higher in pregnant women with hellp syndrome .
the preterm delivery rate is about 70% in hellp syndrome patients with about 15% of cases requiring parturition before the 27 week of gestation .
sufferers may refrain from further pregnancies and need psychological support , and those who attempt further pregnancies have higher risk of gestational hypertension .
previously , immediate delivery was indicated for patients diagnosed with hellp syndrome , which often resulted in significant maternal and neonatal morbidity and/or mortality .
later it was recognized that antepartum administration of high - dose corticosteroids can stabilize the disease indicators and prolong the gestation .
although many studies have demonstrated that cort use helps raise the platelet count and reduce elevated liver enzymes , results are not consistent across all studies .
moreover , evidence regarding the role of corticosteroids in improving maternal morbidity and mortality is not clear .
the present study , therefore , carried out a systematic review of the relevant studies and performed a meta - analysis of all related parameters for the sake of evaluating the efficacy of cort therapy observed in studies with controlled designs .
important features of the method used for the present study are summarized in table 1 .
several electronic databases were searched for the acquisition of required study reports by using the most relevant mesh and keywords in different logical combinations and phrases .
the inclusion criterion was  the studies examining the efficacy of cort therapy to treat hellp patients either in a prospective or retrospective controlled design. some studies were , however , excluded by the following exclusion criteria ( table 1 ) .
important information including outcome measures and outcomes , dosage and mode of administration of cort , and obstetric and demographic characteristics were obtained from identified papers and organized on datasheets .
meta - analyses of mean difference and odds ratio were carried out under the random - effects model .
fifteen studies [ 1226 ] fulfilled were eligible and were included in the meta - analysis .
of the included studies , 8 were randomized controlled trials and 7 were retrospective analyses .
the overall population of this meta - analysis is 675 cort treated and 787 control hellp patients .
age of the cort treated and control patients as mean sd ( range ) was 26.945.8 ( 23.2633.54 ) years and 26.355.7 ( 23.1630.93.3 ) years , respectively .
gestation duration was 32.273.7 ( 29.13.535.12.9 ) weeks in cort treated and 32.423.8 ( 27.63.335.52.6 ) weeks in control hellp patients . in the cort treated group ,
least asymmetry was visible from the visual inspection of the funnel plots , indicative of almost no publication bias in this area of research ( figure 2 ) .
the mean difference [ 95% confidence interval ] in the change from baseline between cort treated patients and controls was 38.08 [ 15.71 , 60.45]10/l ; p=0.0009 ( figure 3 ) . on the other hand ,
the mean differences in the changes from baseline between cort treated and controls were 0.44 [ 0.76 , 0.12 ] iu / ml ; p=0.007 for ldh ( figure 4 ) and 143.34 [ 278.69 , 7.99 ] iu / l ; p=0.04 for alt . however , the decrease in ast levels was not statistically significant in cort - treated patients in comparison with controls ( 48.50 [ 114.32 , 17.32 ] iu / l ; p=0.15 ; table 2 ) .
blood transfusion rate was significantly lower in cort - treated patients ( odds ratio [ 95% ci ] : 0.42 [ 0.24 , 0.76 ] ; p=0.004 .
hospital / icu stay was also significantly lower in cort - treated patients ( mean difference : 1.79 [ 3.54 , 0.05 ] ; p=0.04 ) .
there was no significant difference between cort - treated and control patients in the incidence of cesarean deliveries ( odds ratio [ 95% ci ] : 1.25 [ 0.95 , 1.63 ] ; p=0.11 ) , prevalence of infections ( 0.78 [ 0.19 , 3.15 ] ; p=0.73 ; table 2 ) , birth weight ( mean difference : 0.09 [ 0.11 , 0.28 ] ; p=0.38 ) , infant respiratory distress incidence ( odds ratio : 1.13 [ 0.50 , 2.53 ] ; p=0.78 ) and maternal mortality ( odds ratio : 1.27 [ 0.45 , 3.60 ] ; p=0.65 ) ( table 2 ) . among the included studies , infant mortality was 23% in cort - treated patients and 8.3% in controls   and 4% in cort - treated patients and 0% in controls .
perinatal death was 0% in cort - treated patients and 3% in controls . despite lower frequency of morbid conditions in hellp patients treated with cort ( 318 vs. 418 ) , there was no significant difference in the incidence of overall morbidity between the groups ( odds ratio : 0.79 [ 0.58 , 1.08 ] ; p=0.14 ) .
morbid complications observed in 1 or more studies included pulmonary edema ( 3.6% ) , intraventricular hemorrhage ( 18% , disseminated intravascular coagulation ( 15% ) , endomyometritis ( 9% ) , ascites ( 13.3% ) , hematoma ( 3.3% ) , acute renal failure and other renal pathologies ( 14% , necrotizing colitis ( 12% , bronchopulmonary dysplasia ( 80% ) , intraventricular hematoma ( 20% ) , infant thrombocytopenia ( 13% ) , apgar score less than 7 ( 18% ) , and other hematological ( 36% ) , neurological ( 12% ) , and cardiopulmonary complications ( 33% ) .
this meta - analysis of the studies with variable research designs revealed that in comparison with controls , cort therapy significantly improved the platelet count , ldh , and alt , as well as reducing ast levels non - significantly in patients with hellp syndrome .
moreover , blood transfusion rate and hospital / icu stay were significantly lower in cort - treated patients .
however , there was no significant difference in the maternal mortality , overall morbidity , birth weight , or infant respiratory distress between cort - treated and control patients .
platelet count and serum ldh levels are reliable indicators of hellp severity , and recovery and longer recovery time is required for more severe cases .
corticosteroids are thought to prevent platelet consumption and erythrocyte destruction by stabilizing the vascular endothelium and effectually reducing blood product administration requirements .
the recovery of platelets is reported to start as earlier as 12 hours after cort administration .
the hellp syndrome , especially in the postpartum period , is associated with high maternal morbidity .
class 1 hellp syndrome patients are at higher risk of maternal mortality , and delay in the diagnosis worsens prognosis . despite improvements in biological parameters of hellp syndrome , most of the studies reported that cort treatment does not reduce maternal morbidity .
the present study also found no significant difference between cort - treated and control hellp patients in the incidence of overall morbidity in a meta - analysis of 8 studies presenting 15 morbid conditions .
the morbid conditions observed in the present study were also reported by many studies not included in this meta - analysis .
the morbidities not reported herein include abruptio placentae , retinal detachment , adult respiratory distress syndrome , and hypoxic ischemic encephalopathy .
it is believed that an imbalance between proangiogenic and antiangiogenic factors and increased proinflammatory cytokines play an important role in women with preeclampsia and hellp syndrome .
higher circulating levels of anti - angiogenic proteins secreted by the placenta , such as soluble fms - like tyrosine kinase 1 ( sflt1 ) and soluble endoglin , are found in preeclampsia patients .
dexamethasone has been demonstrated to significantly decrease sflt-1 , soluble endoglin , il-6 , and tnf- after 24 hours of treatment in hellp patients .
these soluble factors are known to stimulate angiotensin ii receptor ( at1-aa ) production and increase endothelin 1 , which are known to play a pathophysiological role in gestational hypertension .
these findings suggest that targeting immunomodulators of hellp syndrome pathology may be a novel therapeutic research strategy .
management of hellp syndrome requires earlier diagnosis , mother - fetus status examination , stabilization of the indicators and symptoms , delivery at optimal time , and postpartum care in order to reduce maternal morbidity and mortality .
a rather longer postpartum recovery period may be required for patients with progressively worsening hellp syndrome .
corticosteroid therapy is a cost - effective medication that can be administered via different routes and reduces the length of hospitalization as compared to other treatments , such as platelet transfusion . in the present study , on average , cort therapy reduced hospital / icu
stay by about 3 days in comparison with controls and this difference was statistically significant in the meta - analysis of 7 studies .
thus , corticosteroids can be beneficial in carefully selected hellp patients without apparent adverse effects to mother or fetus / neonate .
firstly , studies with varying designs were included because none of a particular design could make sufficient data available .
secondly , clinical and methodological heterogeneity of the sample population in the form of factors such as the severity of hellp syndrome , time of cort administration , and dosage and duration of cort administration in recruited patients may have affected overall outcomes .
although , the random - effects model was used to interpret the results , but multi - center randomized controlled trials will be required for clarification of these results .
thirdly , the effect of some statistical procedures used to impute missing data may also have had a slight impact , as not all studies provided measures of dispersal values of the effect size of change in indicators following cort / placebo treatments .
corticosteroid administration to hellp patients improves platelet count and the serum levels of ldh , besides reducing hospital / icu stay and blood transfusion rate .
however , these indices are not significantly associated with maternal mortality and overall morbidity prevalence .
 backgroundhemolysis , elevated liver enzymes , and low platelet count ( hellp ) syndrome is a severe condition of pregnancy that is associated with significant morbidity and mortality . 
 corticoteroid ( cort ) therapy is common in the management of hellp syndrome . 
 this study evaluates the efficacy of cort therapy to patients with hellp syndrome.material/methodsa literature search was carried out in multiple electronic databases . 
 meta - analyses of means difference and odds ratio were carried under the random - effects model.resultsfifteen studies ( 675 cort treated and 787 control hellp patients ) were included . 
 cort treatment significantly improved platelet count ( mean difference between cort treated and controls in changes from baseline , md : 38.08 [ 15.71 , 60.45]109 ; p=0.0009 ) , lactic dehydrogenase ( ldh ) levels ( md : 440 [ 760 , 120 ] iu / l ; p=0.007 ) , and alanine aminotransferase ( alt ) levels ( md : 143.34 [ 278.69 , 7.99 ] iu / l ; p=0.04 ) but the decrease in aspartate aminotransferase ( ast ) levels was not statistically significant ( md : 48.50 [ 114.32 , 17.32 ] iu / l ; p=0.15 ) . 
 corticosteroid treatment was also associated with significantly less blood transfusion rate ( odds ratio , or : 0.42 [ 0.24 , 0.76 ] ; p=0.004 ) and hospital / icu stay ( md : 1.79 [ 3.54 , 0.05 ] days ; p=0.04 ) . maternal mortality ( or : 1.27 [ 0.45 , 3.60 ] ; p=0.65 ) , birth weight ( md : 0.09 [ 0.11 , 0.28 ] ; p=0.38 ) and the prevalence of morbid conditions ( or : 0.79 [ 0.58 , 1.08 ] ; p=0.14 ) did not differ significantly between both groups.conclusionscorticosteroid administration to hellp patients improves platelet count , and the serum levels of ldh and alt , and reduces hospital / icu stay and blood transfusion rate , but is not significantly associated with better maternal mortality and overall morbidity . 
Background
Material and Methods
Results
Discussion
Conclusions
Supplementary materials