244 - PDA Treatments and Hydrocortisone exposure in extremely preterm infants: A secondary analysis of the Hydrocortisone Trial.

Friday, April 28, 2023

5:15 PM – 7:15 PM ET

Poster Number: 244
Publication Number: 244.127

Meera N. Sankar, Stanford University School of Medicine, Palo Alto, CA, United States; Valerie Y. Chock, Stanford University School of Medicine, Sunnyvale, CA, United States; Faith Myers, Stanford University School of Medicine, Palo Alto, CA, United States; Alexis Davis, Stanford University School of Medicine, Palo Alto, CA, United States; Scott A. McDonald, RTI International, Raleigh, NC, United States; Matthew Rysavy, McGovern Medical School at the University of Texas Health Science Center at Houston, Houston, TX, United States; Matthew Laughon, The University of North Carolina at Chapel Hill, Chapel Hill, NC, United States; Shazia Bhombal, Emory University and Children's Healthcare of Atlanta, Atlanta, GA, United States; Krisa P. Van Meurs, Stanford University School of Medicine, Menlo Park, CA, United States; Abhik Das, RTI International, Rockville, MD, United States; William E. Benitz, Stanford University, Palo Alto, CA, United States; Kristi Watterberg, University of New Mexico School of Medicine, Albuquerque, NM, United States; NICHD Neonatal Research Network, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD, United States

Presenting Author(s)

Meera N. Sankar, MD (she/her/hers)

Clinical Professor, Pediatrics/Neonatal/Perinatal Medicine
Stanford University School of Medicine
Stanford University
Palo Alto, California, United States

Background:

Although prior trials of early hydrocortisone (HC) supplementation for preterm infants found reduction in both moderate to severe BPD or death and in treatment for patent ductus arteriosus (PDA), neither of these effects were observed with HC treatment initiated at 14-28 days of age in the NICHD NRN Hydrocortisone Trial. Heterogeneity in patient characteristics, such as cortisol insufficiency, have been suggested as explanations for failure of PDA treatment to reduce BPD or death. Whether later HC and PDA treatment together decrease BPD or death has not been examined.

Objective: We hypothesize that combined exposure to HC and PDA treatment will decrease the outcome of moderate to severe BPD or death compared to infants who received only PDA treatment in the HC Trial.

Design/Methods:

We performed a secondary analysis of infants enrolled in the NICHD NRN Hydrocortisone Trial. The primary outcome was moderate to severe BPD or death. Secondary outcomes included moderate to severe BPD, death, moderate to severe cerebral palsy (CP), neurodevelopmental impairment (NDI), necrotizing enterocolitis (NEC), late onset sepsis (LOS), days of mechanical ventilation, oxygen supplementation, z-scores for growth, home oxygen, and any grade of BPD. Robust Poisson, linear and cumulative logistic regression analyses adjusted for center and gestational age were performed. Separate analyses adjusting for prophylactic indomethacin or for interaction between PDA treatments and hydrocortisone were performed for the primary and secondary outcomes.

Results:

Treatments for PDA were used in 198 infants who received HC and in 197 who received placebo (Table 1). The interaction between PDA treatment and HC was not statistically significant for moderate to severe BPD or death (p=0.93). PDA treatment alone was associated with a significant increase in moderate to severe BPD or death at 36 weeks, moderate to severe CP or death, home oxygen, duration of ventilatory support, oxygen supplementation at 36 weeks, and BPD severity, and with decreased weight-for-age z-score at 36 weeks. HC did not modify the effect of PDA treatment on these outcomes. LOS was less frequent among those who received HC and PDA treatment and more frequent among those who received only HC or only PDA treatment (Table 2).

Conclusion(s):

In preterm infants in the NICHD NRN Hydrocortisone Trial, the relationship between PDA treatment and BPD or death was not altered by HC exposure after the second postnatal week. PDA treatment remained a significant risk factor for several adverse neonatal outcomes regardless of HC exposure.