Association of Funisitis with Short-Term Outcomes of Prematurity: A Frequentist and Bayesian Meta-Analysis

Abstract

The fetal systemic inflammatory response associated with intra-amniotic inflammation may play a key role in the pathogenesis of complications of preterm birth. Funisitis is the histologic equivalent of the fetal inflammatory response, whereas chorioamnionitis represents a maternal inflammatory response. We conducted a frequentist and Bayesian model average (BMA) meta-analysis of studies investigating the effects of funisitis on short-term outcomes of prematurity. Thirty-three studies (12,237 infants with gestational age ≤ 34 weeks) were included. Frequentist meta-analysis showed that funisitis was associated with an increased risk of any bronchopulmonary dysplasia (BPD), moderate/severe BPD, retinopathy of prematurity (ROP), intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), any sepsis, early-onset sepsis (EOS), and mortality. However, Bayesian meta-analysis showed that the evidence in favor of the alternative hypothesis (i.e., funisitis is associated with an increased risk of developing the outcome) was strong for any IVH, moderate for severe IVH and EOS, and weak for the other outcomes. When the control group was restricted to infants having chorioamnionitis without funisitis, the only outcome associated with funisitis was any IVH. In conclusion, our data suggest that the presence of funisitis does not add an additional risk to preterm birth when compared to chorioamnionitis in the absence of fetal inflammatory response.

Keywords: bronchopulmonary dysplasia; chorioamnionitis; complications of preterm birth; funisitis; intrauterine infection; intraventricular hemorrhage; mortality; periventricular leukomalacia; retinopathy of prematurity; sepsis.

Figure 2

Summary of frequentist random-effects meta-analyses comparing infants with funisitis (Fun+) vs. infants who had neither funisitis nor chorioamnionitis (Fun−/CA−) or infants without funisitis but with chorioamnionitis (Fun−/CA+). BPD: bronchopulmonary dysplasia; EOS: early-onset sepsis; IVH: intraventricular hemorrhage; K: number of studies included in the meta-analysis; LOS: late-onset sepsis; NEC: necrotizing enterocolitis; PDA: patent ductus arteriosus; PVL: periventricular leukomalacia; Req.: requiring, ROP: retinopathy of prematurity.

Figure 1

Summary of frequentist random-effects meta-analyses on the association between funisitis and short-term outcomes of prematurity. BPD: bronchopulmonary dysplasia; EOS: early-onset sepsis; IVH: intraventricular hemorrhage; K: number of studies included in the meta-analysis; LOS: late-onset sepsis; NEC: necrotizing enterocolitis; PDA: patent ductus arteriosus; PVL: periventricular leukomalacia; ROP: retinopathy of prematurity.