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Meta-Analysis
. 2019 May 9;19(1):163.
doi: 10.1186/s12884-019-2268-9.

Potential biological therapies for severe preeclampsia: a systematic review and meta-analysis

Sophia Grimes  1 , Kira Bombay  1 , Andrea Lanes  1   2 , Mark Walker  1   2   3 , Daniel J Corsi  4   5   6   7
Affiliations
Meta-Analysis

Potential biological therapies for severe preeclampsia: a systematic review and meta-analysis

Sophia Grimes et al. BMC Pregnancy Childbirth. .

Abstract

Background: Preeclampsia remains a significant danger to both mother and child and current prevention and treatment management strategies are limited. The objective of this systematic review was to investigate the current literature on evidence for the use of the regenerative capacity of mesenchymal stem cell (MSC) therapy, the anticoagulant activity of antithrombin (AT), or the free radical scavenging activity of alpha-1-microglobulin (A1M) as potential novel treatments for severe preeclampsia and Hemolysis, Elevated Liver enzymes, Low Platelet count (HELLP).

Method: We conducted a systematic review of potential biological therapies for preeclampsia. We screened MEDLINE and Embase from inception through May 2017 for studies using AT, A1M or MSCs as potential treatments for preeclampsia and/or HELLP. A meta-analysis was performed to pool data from randomized control trials (RCTs) with homogenous outcomes using the inverse variance method. The Newcastle-Ottawa Scale, the Cochrane risk of bias tool for RCTs, and SYRCLE's risk of bias tool for animal studies were used to investigate potential bias of studies.

Results: The literature search retrieved a total of 1015 articles, however, only 17 studies met the selection criteria: AT (n = 9, 8 human and 1 animal); A1M (n = 4, 3 animal and 1 ex-vivo); and, MSCs (n = 4, 3 animal and 1 ex-vivo). A meta-analysis of AT therapy versus placebo and a meta-analysis for AT therapy with heparin versus heparin alone did not show significant differences between study groups. Animal and ex-vivo studies demonstrated significant benefits in relevant outcomes for A1M and MSCs versus control treatments. Most RCT studies were rated as having a low risk of bias across categories with some studies showing an unclear risk of bias in some categories. The two cohort studies both received a total of four out of nine stars (a rating of "poor" quality). Most animal studies had an unclear risk of bias across most categories, with some studies having a low risk of bias in some categories.

Conclusions: The findings of this review are strengthened by rigorous systematic search and review of the literature. Results of our meta-analyses do not currently warrant further exploration of AT as a treatment of preeclampsia in human trials. Results of animal and ex-vivo studies of A1M and MSCs were encouraging and supportive of initiating human investigations.

Keywords: Alpha-1-microglobulin; Antithrombin; Gestational hypertension; Mesenchymal stem cells; Meta-analysis; Preeclampsia; Systematic review.

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Conflict of interest statement

Ethics approval and consent to participate

Not applicable.

Consent for publication

All authors have consented to the publication of this systematic review.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram showing study selection process
Fig. 2
Fig. 2
AT as a potential therapy for PE, Outcome: Gestational age at delivery
Fig. 3
Fig. 3
AT as a potential therapy for PE, Outcome: Gestational age at delivery in patients treated with AT and heparin, versus patients treated with heparin alone
See this image and copyright information in PMC

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