Chorioamnionitis and response to surfactant in preterm infants

Chorioamnionitis, which affects up to 60% of extremely preterm infants, represents a major cause of preterm birth. It is defined as an antenatal inflammatory state associated with bacterial invasion of the uterus and subsequent neutrophil invasion of the placenta. More severe cases may exhibit signs of a fetal inflammatory response. Of note, antenatal inflammation enhances lung maturation and increases surfactant production. Correspondingly, chorioamnionitis was associated with decreased incidence of RDS in many studies. However, despite accelerating lung maturation, antenatal inflammation is also associated with adverse lung development. Clinical and experimental evidence suggests that the efficacy of exogenous surfactant may be reduced after antenatal inflammation. Despite the growing body of evidence linking inflammation to decreased surfactant function, studies investigating the association between antenatal inflammation and the subsequent response to surfactant are still lacking.
On this basis, a Dutch group has conducted a prospective observational study to evaluate the relationship between histological chorioamnionitis (HC) with or without fetal involvement and the response to exogenous surfactant.
In total, 301 preterm infants ≤ 32.0 weeks gestational age were evaluated, 146 of whom received surfactant according to standardized criteria. Fraction of inspired oxygen (FiO₂) requirement and time to extubation were compared between groups based on the presence of HC with or without fetal involvement (HC-, n=88; HC+F-, n=25; HC+F+, n=33) and between infants who developed bronchopulmonary dysplasia (BPD) or died (n=57) and BPD-free survivors (n=89).
The results showed that, after adjustment for gestational age and birth weight, HC+F+ infants had significantly greater FiO₂ requirement and prolonged time to extubation postsurfactant compared with HC- infants. Infants with BPD/death had a strikingly similar pattern of increased FiO₂ requirement postsurfactant. Moreover, in infants who received surfactant, HC+F+ status was associated with increased risk for BPD (odds ratio [OR]=3.40; 95% confidence interval [CI]=1.02-11.3; p=0.047) and for BPD/death (OR=2.72; 95% CI=1.00-7.42; p=0.049). Overall, these findings suggest that antenatal exposure to inflammation alters the response to postnatal surfactant therapy and that this mechanism may be an important modulator of the association between chorioamnionitis and development of BPD due to increased mechanical ventilation. In fact, surfactant was less effective in decreasing the FiO₂ requirement in HC+ infants, associated with a prolonged need for mechanical ventilation. These effects were most prominent in the HC+F+ cohort, generally considered as the most severely affected. Moreover, the consequent increased need for respiratory support may explain, at least in part, the predisposition to BPD in HC+ infants.
Increased surfactant clearance or inactivation are likely explanations for reduced response to surfactant therapy. Possible approaches to increase surfactant efficiency in infants with chorioamnionitis include higher surfactant dosing, different methods of administration, or enrichment with additives protecting from inactivation.

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