Antenatal Steroids and Neonatal Outcome After Chorioamnionitis

8/3/2019 Antenatal Steroids and Neonatal Outcome After Chorioamnionitis

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A NTENATAL STEROIDS AND

NEONATAL OUTCOME AFTER

CHORIOAMNIONITIS: A METAANALYSIS

Journal Report :

Karen Kristy U. Quiñanola, ,MD1st Year OB Resident SHH



DR. JV BEEN

PL DEGRAEUWE BW KRAMER LJI ZIMMERMAN

Department of Pediatrics School of Oncology andDevelopmental Biology Maastricht University MedicalCenter Netherlands

Accepted 06 September 2010.Published online 04 November 2010



Background

There is debate concerning the safety and efficacy ofantenatal steroids in preterm labour with suspectedintrauterine infection (chorioamnionitis)

Objectives They performed a systematic literature review and

meta-analysis aimed at evaluating the efficacy andsafety of antenatal steroids in clinical and histological

chorioamnionitis.



Search Strategy

MEDLINE, EMBASE, BioMed Central and the CochraneDatabases were searched using the terms‘chorioamnionitis’ OR ‘intrauterine infection’ and

‘steroids’ OR ‘corticoids’. Selection Criteria

Studies that reported selected neonatal outcomemeasures in preterm infants with clinical or histologicalchorioamnionitis, according to antenatal steroidexposure were eligible.



Data collection and analysis

Study selection, data extraction and data analysis wereperformed by two independent investigators.

The meta-analysis techniques used included: Mantel-

Haenszel analysis-an assessment of studyheterogeneity using the Q statistic; and Egger’s

regression test and funnel plots- to assess publicationbias.



INTRODUCTION

Maternal administration of corticosteroids is aneffective therapy to reduce respiratory distress andimprove neurological morbidity and mortality.



This approach has become the standard care incases of imminent or anticipated preterm delivery.

However, general concern exists regarding theadministration of antenatal steroids in cases ofsuspected intrauterine infection as confirmed by arecent survey among Dutch perinatologists.



Available guidelines delineate chorioamnionitis as acontraindication for antenatal steroids, although thescientific basis for this recommendation remainsobscure.



Accordingly, pregnant women exhibiting signssuggestive of intrauterine infection –ClinicalChorioamnionitis have often been excluded fromrandomised clinical trial investigating the effect of

antenatal steroids on neonatal outcome.



As a consequence, there is an important lack ofdata regarding the effects of antenatal steroids onneonatal outcome in the setting of suspectedintrauterine infection.



Antenatal infection or inflammation can bediagnosed in various ways. The diagnosis based onthe histological examination of the placenta andassociated tissues is probably the most reliable and

valid marker of intrauterine infection.



METHODS

1.) Sources:

A systematic literature search was performedindependently by two investigators (JVB and PLD) inAugust 2010 using online databases for medical

literature from 1966 onwards (MEDLINE, EMBASE,BioMed Central, Cochrane Database of SystematicReviews).



In order to maximize the probability of identifyingpotentially relevant articles, broad search termswere used ( chorioamnionitis or intrauterineinfection) and ( steroids or corticoids) without

additional restrictions.



2.) Study Selection:

Articles in any language were eligible for inclusion in themeta-analysis if they reported one or more neonataloutcome measures of interest with regard to antenatal

steroid status in preterm infants with either histologic orclinical chorioamnionitis.



The neonatal outcome measures of interest werethe following:

Neonatal mortality

Respiratory distress syndrome RDS

Bronchopulmonary dysplasia

Intraventricular hemorrhage

Severe IVH

Periventricular leucomalacia PVL

Necrotising enterocolitis

Patent ductus arteriosus

Culture-proven early onset sepsis within 72hrs of birth



3.) Analyses

Aggregate odds ratios and 95% confidence intervalswere calculated using Mantel-Haenszel analysis (fixed-effects model)

The heterogeneity of studies was examined using bothqualitative and quantitative assessment ( Q Statistic).



When important heterogeneity was present, arandomised effects model was applied.

Study quality was assessed independently by twoinvestigators (JVB and PLD) using the Newcastle-

Ottawa Scale for cohort studies. Any disagreement was resolved by consensus.



RESULTS

Study selection and characteristics

Eight studies were identified that reported one or moreoutcome measures of interest for infants exposed tochorioamnionitis, with regard to antenatal steroid

administration.



All studies were observational cohort studies. No RCTsaddressing the effect of antenatal steroids within thechorioamnionitis-exposed infants were identified.



E

Eligible for systematic review8

Potentially relevant articles187

Articles identified by search1094

Deemed irrelevant based on

the title and/or abstract 907

Excluded 179-No original data presented 55-Not about preterm infants 2

-Outcome not reportedaccording to chorioamnionitis/

Steroid exposure 99

Included in systematic review 7

Excluded to serious concerns

regarding bias 1



In all of the studies, consecutively born preterminfants were studied and essential maternalperinatal and neonatal characteristics weredocumented, although data collection was

retrospective in most studies.



Meta-analysis: Histological Chorioamnionitis

Administration of antenatal steroids was associated withsignificant reductions in neonatal mortality, RDS, PDA,IVH and Severe IVH after histological chorioamnionitis.

No significantly increased risk for any adverse outcomewas detected after antenatal steroids.

For early onset sepsis, a random-effects model wasapplied because of study heterogeneity.



No stastical indications for publication bias were presentfor any outcome measure.

Meta-analysis: Clinical Chorioamnionitis

In these infants, antenatal steroids were associated with

significant reductions in Severe IVH and PVL Again, no significant association between antenatal

steroid administration and any adverse outcomemeasure was observed.

No indications for publications bias were present.



Meta-analysis :sensitivity analysis

The low number of studies and almost completeabsence of subgroup-specific data reports did not allowfor subgroup analyses to be performed.

Application of a random-effects model did notimportantly affect the size or significance level for mostoutcome measures.



However, regarding the effect of antenatal steroidson severe IVH and PVL in infants with clinicalchorioamnionitis, the random-effects model resultedin a loss of significance, although the point

estimate remained essentially the same.



DISCUSSION

The current meta-analysis of observational studiesindicates that in patients with chorioamnionitis ,antenatal steroids may be safe and effective inreducing adverse neonatal outcome.



In patients with histological chorioamnionitis,antenatal steroid administration was associatedwith important reductions in mortality, RDS, PDA,Total IVH and Severe IVH.

To their knowledge, no previous attempt was madeto systematically review the available evidence onthe efficacy and safety of antenatal steroids inchorioamnionitis.



They believed that the relative uniformity ofinclusion criteria and outcome parameters used,and the separation of analyses for histological andclinical chorioamnionitis, justify performing a meta-

analysis by statistically aggregating the data.



The absence of statistical indications for publicationbias and study heterogeneity (except for early-onset sepsis after clinical chorioamnionitis) furthersupports the validity of the results; Although a meta-

analysis may substantiate the conclusions drawnfrom the available evidence, several importantlimitations should be acknowledged.



Overall the number of studies suitable for inclusionwas low. Although individual cohorts were ofconsiderable size, this may introduce bias mainlythrough differences in the inclusion and exclusion

criteria between studies.



Aspects regarding the administration of antenatalsteroids need additional consideration. Differencesbetween studies are present in the type of drugused, in drug dosing and timing, and whether or not

multiple courses were allowed.



In some instances, steroids may not be have beengiven because delivey ensued quickly afteradmission, leading to potential bias.

Moreover, antenatal steroid administration was

scored as positive by some authors only when a fullcourse was administered, whereas others alsoincluded infants that received incomplete courses.



Thus, differences between studies may arise fromwhether infants who received an incomplete coursewere assigned to the treatment group or controlgroup.

Another source of variation between studies isintroduced by differences in diagnostic criteriarelated to both chorioamnionitis and outcomedefinitions.



Comparison of random-effects and fixed-effectsmodel suggests that the effect of heterogeneity islimited for most outcomes.

However, in infants with clinical chorioamnionitis,the random-effects model resulted in the loss ofsignificance of the beneficial effect of antenatalsteroids, suggesting that study heterogeneity could

account for part of the observed effect.



In summary, although the meta-analysis clearlysuggests that antenatal steroids may be beneficialin both histological and clinical chorioamnionitis,the results should be interpreted with great care

given these methodological considerations.



Certain additional issues should be taken intoaccount when interpreting the data. Mostimportantly, there is lack of information on thetiming of steroid administration relative to the

emergence of signs suggestive of intrauterineinfection.



As stressed by Goldenberg et al., steroids mayhave been administered before the occurrence ofclinical chorioamnionitis in the majority of cases.Outcome measures of these infants obviously are

not very helpful in guiding the use of antenatalsteroids when intrauterine infection is clinicallyapparent.



Thus, although antenatal steroids are associatedwith improved short-term neurological outcome ininfants with clinical chorioamnionitis in the currentmeta-analysis, one should be prudent in

extrapolating these findings in clinical situationdirectly.



Also, the identification of potential maternal adverseeffects of steroid administration in the setting ofsuspected intrauterine infection was beyond thescope of this review, none were reported in the

studies. In this respect it is important to note that antenatal

steroid administration in itself has been shown notto increase the risk of developing chorioamnionitis.



The efficacy of antenatal steroids in histologicalchorioamnionitis may not seem clinically relevant,as placental histology is not available to theObstetrician when deciding whether or not to give

antenatal steroids.



However, the beneficial effect of antenatal steroidsafter histological chorioamnionitis indicates thattreatment may indeed be safe and effective,regardless of whether subclinical inflammation is

present.



Moreover, a meta-analysis of RCTs showingparticular benefit of antenatal steroids in pregnantwomen with preterm labor rupture of membranessupports their potential when intrauterine infection

is imminent.



Despite these potential sources of bias, theabsence of any association between antenatalsteroid treatment and adverse outcome inchorioamnionitis-exposed infants is reassuring.



CONCLUSION

In conclusion, the current meta-analysis ofobservational studies suggests that antenatalsteroids are safe and effective in preterm infantsborn before 33weeks of gestation with subclinical

chorioamnionitis.



However, when chorioamnionitis is clinicallyapparent, the evidence is less obvious and moresensitive to bias. Retrospective subgroup analysisof observational studies and RCTs in which data on

chorioamnionitis and antenatal steroid exposure areavailable, may further increase their knowledge onthis important topic.



They would favor an RCT to assess the efficacyand safety of antenatal steroids in clinicalchorioamnionitis.

Both maternal and neonatal outcome must be

evaluated, and include long-term follow-up.

Until such a trial has been carried out, one shouldbe cautious to make any clinical recommendationregarding this issue.

Antenatal Steroids and Neonatal Outcome After Chorioamnionitis

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