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

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.

Chorioamnionitis as a risk factor for retinopathy of prematurity: An updated systematic review and meta-analysis

“…Two broad pathological conditions have been identified to lead to very preterm birth: (i) infection/inflammation and (ii) placental dysfunction resulting from vascular malfunction [ 88 , 89 ]. As discussed elsewhere [ 11 , 90 ], in addition to distinct pathophysiological pathways, baseline and clinical characteristics are different between these two groups [ 88 , 91 ]. Accordingly, our analyses showed that the infants exposed to CA were born significantly earlier (~1.15 weeks), were lighter (~35 g), had a higher rate of exposure to antenatal corticosteroids, had a lower rate of cesarean section, were less often SGA, had a higher rate of PROM, had a higher rate of EOS and LOS, and had a higher mortality.…”

Placental Pathology Findings and the Risk of Intraventricular and Cerebellar Hemorrhage in Preterm Neonates

“…In the last decades, several studies have explored the contribution of the prenatal environment to the development of preterm brain lesions (11). In particular, the role of placental pathology in prematurity-related complications has been widely investigated but is still a matter of debate (12,13). The heterogeneous results in different studies could be explained by the multiplicity of both placental lesion definition and classification.…”

Machine learning models for identifying preterm infants at risk of cerebral hemorrhage

“…The association between these variables and the development of IVH in preterm neonates has been reported in several previous studies [22][23][24][25][26][27][28][29][30][31]. Occurrence of IVH is strongly associated with thrombocytopenia (lower number of thrombocytes in blood) [22], and, in very low birth weight infants, with an increase in leukocyte count [23].…”

“…Occurrence of IVH is strongly associated with thrombocytopenia (lower number of thrombocytes in blood) [22], and, in very low birth weight infants, with an increase in leukocyte count [23]. Moreover, leukocyte count and CPR were found to be associated with histological chorioamnionitis [24], which in turn has also been identified as a risk factor of IVH [25]. Low initial Ht-levels in preterm infants with < 28 WG were shown to be associated with occurrence of IVH [26], with initial values of Ht < 45% having been associated with a 2-fold increase in cerebral hemorrhage probability in extremely low birth weight neonates [27].…”