Use of intravenous immunoglobulin in antiphospholipid antibody positive patients with high risk of miscarriage: a systematic review and meta-analysis

Abstract

Objective: The purpose of the present study was to evaluate whether intravenous immunoglobulin (IVIG) increases live birth rates and improves neonatal results in patients with antiphospholipid antibodies (aPL) at high-risk for miscarriage.

Background: Positivity of aPL in pregnant women is a high-risk factor for miscarriage, and IVIG treatment has emerged as a potential intervention.

Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was employed to search multiple electronic databases for articles published until August 20, 2023, including PubMed, Web of Science, Embase, Scopus and Medline. The inclusion criteria encompassed studies assessing the efficacy of IVIG in aPL-positive patients with a high risk of miscarriage. Relevant articles were assessed for the quality and data were extracted for analysis. Two independent reviewers performed study selection, data extraction, and quality assessments. The risk of bias was evaluated according to the Cochrane risk of bias tool. All analyses were conducted using Review Manager 5.3.

Results: This systematic review included nine randomized controlled trials, with 366 aPL-positive women at high risk of miscarriage. These studies included in this review were randomized controlled trials. The primary outcome measures were successful pregnancy outcomes and live birth rates. The secondary outcomes included obstetric complications, and neonatal outcomes (such as birth weight and live-birth rate). The comparison between the intervention and control groups revealed no significant differences in terms of obstetric complications and neonatal outcomes. The group receiving IVIG treatment had a higher prevalence of preterm deliveries than controls (OR = 2.05, I² = 46%, 95% CI [0.58-5.24]), but also exhibited a partial improvement in live birth rates (OR = 2.86, I² = 52%, 95% CI [1.04-7.90]), because it reduced the number of miscarriages (OR = 0.35, I² = 52%, 95% CI [0.13-0.96]).

Conclusion: Based on the available evidence, IVIG intervention appears to be a potentially effective approach for managing of aPL-positive pregnant women with high risk of miscarriage. While IVIG shows significant potential in tripling the chances of having a live-born child, further large-scale randomized controlled trials are necessary, preferably comparing IVIG with hydroxychloroquine or lifestyle and dietary interventions, to refine treatment protocols and ensure the most effective application.

Keywords: Antiphospholipid antibodies; Intravenous immunoglobulin; Miscarriage; Systematic review.

Figure 1. Literature screening flowchart.

Figure 2. Assessment for risk of bias in included studies.

Above: The bias assessment conducted for the included studies. Below: The Cochrane Collaboration Risk of Bias Assessment Tool evaluates the risk of bias.

Figure 3. Forest plots of included studies.

(A) Live birth rates (six comparisons, n = 317). (B) Miscarriage rates (six comparisons, n = 317). (C) Preterm delivery rates (nine comparisons, n = 307). (D) Obstetric complications (three comparisons, n = 135). (E) Neonatal outcome (four comparisons, n = 112). (CI, confidence interval; MH, Mantel–Haenszel method) (Branch et al., 2000; Dendrinos, Sakkas & Makrakis, 2009; Heilmann, von Tempelhoff & Kuse, 2001; Mahmoud et al., 2004; Perricone et al., 2008; Stricker et al., 2000; Vaquero et al., 2001; Triolo et al., 2003; Yamada et al., 2022).

Figure 4. Forest plots of birth weight (five RCTs, n = 155).

(CI, confidence interval; IV, inverse variance method) (Branch et al., 2000; Dendrinos, Sakkas & Makrakis, 2009; Perricone et al., 2008; Stricker et al., 2000; Triolo et al., 2003; Yamada et al., 2022).