345 - Effect Modification of Late Surfactant Treatment by Patent Ductus Arteriosus Status in Ventilated Preterm Infants Receiving Inhaled Nitric Oxide

Publication Number: 345.4719

Patrick J. Peebles, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States; Nicolas Bamat, Childrens Hospital of Philadelphia, Swarthmore, PA, United States; Jens Eickhoff, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States; Tim G. Elgin, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States; Roberta Keller, UCSF Benioff Children's Hospital San Francisco, San Francisco, CA, United States; Jonathan M. Klein, University of Iowa, Iowa City, IA, United States; Patrick J. McNamara, University of Iowa Stead Family Children's Hospital, IOWA CITY, IA, United States; Anudeepa Sharma, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States; Dinushan Kaluarachchi, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States

Background: Bronchopulmonary dysplasia (BPD) is a significant source of morbidity among extremely preterm infants. The Trial of Late Surfactant (TOLSURF) investigated the effect of late surfactant, administered in the second postnatal week, to infants born < 28 0/7 weeks gestation receiving mechanical ventilation on 1) survival without BPD at 36 and 2) 40 weeks postmenstrual age (PMA). Although late surfactant did not improve survival without BPD at 36 or 40 weeks PMA, infants that received late surfactant required less home respiratory support. The study included co-administration of inhaled nitric oxide, which may increase pulmonary blood flow in patients with patent ductus arteriosus (PDA); recent data show that the presence of PDA was associated with a negative response to late surfactant, measured by respiratory severity score.

Objective: To determine whether the effect of late surfactant is modified by PDA status with respect to the following outcomes as defined in TOLSURF: 1) survival without BPD at 36 weeks PMA, 2) survival without BPD at 40 weeks PMA, 3) persistent pulmonary morbidity by 1 year corrected age, and 4) no pulmonary morbidity by 1 year corrected age.

Design/Methods: Secondary analysis of data from TOLSURF. A formal test of interaction between the presence of a PDA and late surfactant with respect to the above outcomes was performed by including an interaction term in a multivariable logistic regression model adjusting for baseline differences and variables known to impact BPD risk. The presence of the PDA was defined by PDA treatment, either medical or a ligation, during or after the late surfactant dosing period (PDA definition 1). An alternative PDA definition classified PDA presence as a PDA ligation during or after the late surfactant dosing period (PDA definition 2).

Results: Baseline characteristics of the 511 included infants, stratified by PDA status, are shown in Table 1. An interaction between the presence of a PDA and late surfactant did not exist for any of the four prespecified study outcomes (Table 2). Defining PDA presence as receiving a ligation had similar results (Table 3).

Conclusion(s): Among extremely preterm infants enrolled in TOLSURF, the presence of a PDA did not modify the effect of receipt of late surfactant for the evaluated long-term outcomes. This study was limited by defining PDA presence by treatment, rather than echocardiography, which may have misclassified the presence of a PDA. Our results do not suggest that PDA presence will impact long term outcomes among infants receiving late surfactant.

Table 1
Baseline Characteristics, Stratified by PDA Status (PDA Definition 1)

Table 2
Interaction between PDA (PDA Definition 1) and Study Outcomes

Table 3
Interaction between PDA Ligation (PDA Definition 2) and Study Outcomes