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.
Highlights
We analyzed a subgroup of studies where the CA-group had a mean difference (MD) in gestational age (GA) of ≤0.5 weeks, and we found that CA was a risk factor for all grades intraventricular hemorrhage (IVH)
We found through additional meta-analyses that CA-exposed infants had significantly lower GA and birth weight (BW) than infants not exposed to CA
We have previously reported that funisitis is not an additional risk factor for developing patent ductus arteriosus (PDA) (Behbodi et al, 2016) but the presence of funisitis significantly increased the risk of developing severe retinopathy of prematurity (ROP) (Villamor-Martinez et al, 2018a)
Summary
Germinal matrix hemorrhage–intraventricular hemorrhage (GMH-IVH) is one of the most common complications of prematurity (Ballabh, 2010; Volpe, 2015; Inder et al, 2018). As assessed by Inder et al (2018) not all the pathogenetic factors are present in every IVH and the clinical circumstances determine which factors are most relevant in each infant Among these clinical circumstances, very preterm birth, generally defined as birth before 32 completed weeks of gestation, is the most consistently associated with the development of IVH. A number of risk factors including, among others, absent antenatal corticosteroid (ACS) treatment, vaginal delivery, peri- and postnatal hypoxicischemic events, severe respiratory distress syndrome (RDS), pneumothorax, hypercapnia, hemodynamic disturbances (either systemic hypertension or hypotension), rapid volume expansion, decreased hematocrit, glucose and/or electrolyte disturbances, seizures, patent ductus arteriosus (PDA), thrombocytopenia, inherited thrombophilia, and infection may predispose to the development of IVH (Ballabh, 2010; Ramenghi et al, 2011; Volpe, 2015; Bermick et al, 2016; Romantsik et al, 2017; Inder et al, 2018; Poryo et al, 2018)
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