The effect of histological and subclinical chorioamnionitis and funisitis on breathing effort in premature infants at birth: a retrospective cohort study.

Antenatal inflammation in the form of chorioamnionitis (fetal membranes; HCA) and funisitis (umbilical vessels; FUN) is a major risk factor for preterm birth. Exposure to HCA + FUN affects infants by releasing mediators that may suppress respiratory drive. While the association between clinical chorioamnionitis (CCA) and (depressed) spontaneous breathing has been described, we have investigated the association between breathing and HCA + FUN. Infants born < 30 weeks' gestation with available placental pathology assessments were included. Infants were compared at multiple levels: infants with vs without HCA + FUN (comparison 1) and infants with subclinical HCA + FUN vs infants without any chorioamnionitis (comparison 2). The primary outcome was breathing effort, defined as minute volume (MV) of spontaneous breathing in the first 5 min after birth. We also assessed tidal volume (Vt), respiratory rate (RR), heart rate (HR), oxygen saturation (SpO₂) and oxygen requirement (FiO₂). Regression analyses were performed to control for confounding factors. One hundred eighty-six infants were included (n = 75 infants with HCA + FUN vs. n = 111 infants without HCA + FUN). Comparison 1: Infants with HCA + FUN had lower gestational ages 26⁺⁵ (25⁺⁰-28⁺¹; median (IQR) and lower birthweights (mean ± SD; 943 ± 264) compared to infants without HCA + FUN (28⁺⁴ (27⁺⁰-29⁺¹) weeks, p < 0.001 and 1023 ± 270 g, p = 0.049). Comparison 2: Subclinical HCA + FUN was diagnosed in 46/75 HCA + FUN infants. Infants with subclinical HCA + FUN had lower gestational ages (26⁺⁶ (25⁺¹-28⁺³) vs. 28⁺⁴ (27⁺²-29⁺¹) weeks, p < 0.001) without significant differences for birthweights (987 ± 248 vs. 1027 ± 267 g, p = 0.389) compared to infants without any chorioamnionitis (n = 102 infants). After adjustment, HCA + FUN was associated with lower MV (p = 0.025), but subclinical HCA + FUN was not (p = 0.226). HCA + FUN and subclinical HCA + FUN were associated with lower Vt (p = 0.003; p = 0.014), SpO₂ at 5 min (p = 0.021; 0.036) and SpO₂/FiO₂ ratio (p = 0.028; p = 0.040).

Conclusion: HCA + FUN and subclinical HCA + FUN are associated with reduced oxygenation and parameters that reflect breathing effort in premature infants at birth.

What is known: • Acute antenatal inflammation, in the form of chorioamnionitis (fetal membranes) and funisitis (umbilical vessels), affects a large proportion of premature infants. • Clinical chorioamnionitis is associated with reduced breathing effort and oxygenation in premature infants at birth.

What is new: • Histological and subclinical chorioamnionitis and funisitis are associated with reduced breathing effort parameters and oxygenation in premature infants at birth.