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. 2018 Sep 11:9:1253.
doi: 10.3389/fphys.2018.01253. eCollection 2018.

Chorioamnionitis Is a Risk Factor for Intraventricular Hemorrhage in Preterm Infants: A Systematic Review and Meta-Analysis

Eduardo Villamor-Martinez  1 , Monica Fumagalli  2 , Owais Mohammed Rahim  1 , Sofia Passera  2 , Giacomo Cavallaro  2 , Pieter Degraeuwe  1 , Fabio Mosca  2 , Eduardo Villamor  1
Affiliations

Chorioamnionitis Is a Risk Factor for Intraventricular Hemorrhage in Preterm Infants: A Systematic Review and Meta-Analysis

Eduardo Villamor-Martinez et al. Front Physiol. .

Erratum in

Abstract

Although chorioamnionitis (CA) is a well-known risk factor for white matter disease of prematurity, the association with intraventricular hemorrhage (IVH) is controversial and has not been yet systematically reviewed. We performed a systematic review and meta-analysis of studies exploring the association between CA and IVH. A comprehensive literature search was conducted using PubMed/MEDLINE and EMBASE, from their inception to 1 July 2017. Studies were included if they examined preterm infants and reported primary data that could be used to measure the association between exposure to CA and the presence of IVH. A random-effects model was used to calculate odds ratios (OR) and 95% confidence intervals (CI). We found 1,284 potentially relevant studies, of which 85 met the inclusion criteria (46,244 infants, 13,432 CA cases). Meta-analysis showed that CA exposure was significantly associated with all grades IVH (OR 1.88, 95% CI 1.61-2.19), with grades 1-2 IVH (OR 1.69, 95% CI 1.22-2.34), and with grades 3-4 IVH (OR 1.62, 95% CI 1.42-1.85). Both clinical and histological CA were associated with an increased risk for developing IVH in very preterm infants. In contrast, the presence of funisitis did not increase IVH risk when compared to CA in the absence of funisitis (OR 1.22, 95% CI 0.89-1.67). Further meta-analyses confirmed earlier findings that CA-exposed infants have significantly lower gestational age (GA; mean difference [MD] -1.20 weeks) and lower birth weight (BW; MD -55 g) than the infants not exposed to CA. However, meta-regression and subgroup analysis could not demonstrate an association between the lower GA and BW and the risk of IVH in the CA-exposed infants. In conclusion, our data show that CA is a risk factor for IVH, but also a risk factor for greater prematurity and more clinical instability. In contrast to other complications of prematurity, such as patent ductus arteriosus, retinopathy of prematurity, or bronchopulmonary dysplasia, the effect of CA on IVH appears to be independent of CA as causative factor for very preterm birth.

Keywords: chorioamnionitis; intraventricular hemorrhage; meta-analysis; systematic review; very preterm infant.

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Figures

Figure 1
Figure 1
Flow diagram of search process (Moher et al., 2009).
Figure 2
Figure 2
Meta-analyses of the association between chorioamnionitis (CA) and intraventricular hemorrhage (IVH), according to definition of IVH. CI, confidence interval. (A) CA and all grades IVH; (B) CA and grades 2-4 IVH; (C) CA and grades 1–2 IVH; (D) CA and grades 3–4 IVH.
Figure 3
Figure 3
Meta-analysis of the association between histological chorioamnionitis (CA) and all grades intraventricular hemorrhage (IVH). CI, confidence interval.
Figure 4
Figure 4
Meta-analysis of the association between histological chorioamnionitis (CA) and grades 3–4 intraventricular hemorrhage (IVH). CI, confidence interval.
Figure 5
Figure 5
Meta-analysis of the association between clinical chorioamnionitis (CA) and all grades intraventricular hemorrhage (IVH). CI, confidence interval.
Figure 6
Figure 6
Meta-analysis of the association between clinical chorioamnionitis (CA) and grades 3–4 intraventricular hemorrhage (IVH). CI, confidence interval.
Figure 7
Figure 7
Funnel plots assessing publication bias for the association between chorioamnionitis (CA) and intraventricular hemorrhage (IVH).
Figure 8
Figure 8
Meta-analysis of the association between funisitis and intraventricular hemorrhage (IVH). Fun, funisitis; CI, confidence interval.
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