Reply

We thank Gupta and Sundaram for their interest in our work. Our point-by-point response is outlined below. Because of the seemingly contradictory report of decreased respiratory distress syndrome (RDS) and increased bronchopulmonary dysplasia (BPD) incidence after chorioamnionitis, investigators have been intrigued by this association. Ongoing evidence from animal and human studies shows that chorioamnionitis indeed decreases RDS through enhanced lung maturation. The association with BPD appears to be more complex and highly modulated by ‘‘secondary hits’’ to the lung.
In our article, the response to surfactant was evaluated by the clinical variables of oxygen need and time to extubation. Our study was nested within a cohort study to evaluate the association between chorioamnionitis and neonatal outcome. The parent study was originally powered to detect clinically relevant differences in BPD and periventricular leukomalacia between infants with and without chorioamnionitis. Thus no power calculation was performed for surfactant responses, which were secondary outcomes.
No infants with chorioamnionitis who were given surfactant were initially on nasal continuous airway pressure (nCPAP), and several who did not need surfactant were treated with nCPAP. This simply indicates that surfactanttreated infants were the sickest group. Although the preferential use of nCPAP for initial respiratory management is increasing, it was not standard in our unit at the time of this study. Moreover, the debate of nCPAP versus early surfactant in this setting continues.
The difference in FiO2 after the first dose and before the second dose of surfactant is not due to an error, it is the result of patient selection. All infants who received a first dose of surfactant are in the graph depicting the response after the first dose. As stated in the methods section, only infants who still met the criteria for surfactant administration 6 to 8 hours after the first dose were given a second dose. Only these are included in the second dose graph. This subgroup was composed of sicker infants, with higher FiO2 before the second surfactant dose, as shown.
We thank Gupta and Sundaram for giving us the opportunity to clarify some issues, although we believe they do not change the conclusions from our study. Even though antenatal exposure to chorioamnionitis may enhance lung maturation, our results indicate that surfactant efficacy is decreased when severe inflammation is present, providing a novel link between chorioamnionitis, ‘‘secondary hits,’’ and development of BPD.