Matthew A Rysavy1, Lei Li2, Jon E Tyson3, Erik A Jensen4, Abhik Das5, Namasivayam Ambalavanan6, Matthew M Laughon7, Rachel G Greenberg8, Ravi M Patel9, Claudia Pedroza3, Edward F Bell10. 1. Stead Family Department of Pediatrics, University of Iowa, Iowa City, IA. Electronic address: matthew-rysavy@uiowa.edu. 2. Biostatistics and Epidemiology Division, RTI International, Research Triangle Park, NC. 3. Center for Clinical Research & Evidence-Based Medicine, University of Texas McGovern Medical School, Houston, TX. 4. Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA. 5. Biostatistics and Epidemiology Division, RTI International, Rockville, MD. 6. Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL. 7. Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC. 8. Department of Pediatrics, Duke University School of Medicine, Durham, NC. 9. Department of Pediatrics, Emory University School of Medicine, Atlanta, GA. 10. Stead Family Department of Pediatrics, University of Iowa, Iowa City, IA.
Abstract
OBJECTIVE: To determine whether infants at higher risk of bronchopulmonary dysplasia (BPD) or death benefit more from vitamin A therapy than those at lower risk. STUDY DESIGN: We conducted a post hoc reanalysis of a landmark phase III randomized controlled trial conducted from January 1996 to July 1997 at 14 university-affiliated neonatal intensive care units in the US. Data analysis was performed from October 2019 to October 2020. Infants born weighing 401-1000 g and receiving respiratory support at 24 hours of age were assigned to intramuscular vitamin A 5000 IU or sham procedure 3 times weekly for 4 weeks. The primary outcome was BPD, defined as use of supplemental oxygen, or death at 36 weeks postmenstrual age. An externally validated model for predicting BPD or death was used to estimate the risk of these outcomes for each infant. RESULTS: As previously reported, 222 of 405 infants (54.8%) assigned vitamin A therapy and 248 of 402 infants (61.7%) in the control group developed BPD or died (relative risk [RR], 0.89 [95% CI, 0.80-0.99]; risk difference [RD], -6.9% [95% CI, -13.0 to -0.7]). The predicted individual risks of BPD or death ranged from 7.1% to 98.6% (median, 61.5%; mean, 60.9%). The effect of vitamin A therapy on BPD or death depended on infants' risk of the primary outcome (P = .03 for interaction): for example, a RR of 0.73 (RD, -14.5%) for infants with a 25% predicted risk and a RR of 0.96 (RD, -1.0%) for infants with a 75% risk. There was no difference in the decrease in vitamin A deficiency across risk groups. CONCLUSIONS: Contrary to expectations, the effect of vitamin A therapy on BPD or death was greater for lower risk than higher risk infants. TRIAL REGISTRATION: ClinicalTrials.gov NCT01203488.
OBJECTIVE: To determine whether infants at higher risk of bronchopulmonary dysplasia (BPD) or death benefit more from vitamin A therapy than those at lower risk. STUDY DESIGN: We conducted a post hoc reanalysis of a landmark phase III randomized controlled trial conducted from January 1996 to July 1997 at 14 university-affiliated neonatal intensive care units in the US. Data analysis was performed from October 2019 to October 2020. Infants born weighing 401-1000 g and receiving respiratory support at 24 hours of age were assigned to intramuscular vitamin A 5000 IU or sham procedure 3 times weekly for 4 weeks. The primary outcome was BPD, defined as use of supplemental oxygen, or death at 36 weeks postmenstrual age. An externally validated model for predicting BPD or death was used to estimate the risk of these outcomes for each infant. RESULTS: As previously reported, 222 of 405 infants (54.8%) assigned vitamin A therapy and 248 of 402 infants (61.7%) in the control group developed BPD or died (relative risk [RR], 0.89 [95% CI, 0.80-0.99]; risk difference [RD], -6.9% [95% CI, -13.0 to -0.7]). The predicted individual risks of BPD or death ranged from 7.1% to 98.6% (median, 61.5%; mean, 60.9%). The effect of vitamin A therapy on BPD or death depended on infants' risk of the primary outcome (P = .03 for interaction): for example, a RR of 0.73 (RD, -14.5%) for infants with a 25% predicted risk and a RR of 0.96 (RD, -1.0%) for infants with a 75% risk. There was no difference in the decrease in vitamin A deficiency across risk groups. CONCLUSIONS: Contrary to expectations, the effect of vitamin A therapy on BPD or death was greater for lower risk than higher risk infants. TRIAL REGISTRATION: ClinicalTrials.gov NCT01203488.
Authors: J E Tyson; L L Wright; W Oh; K A Kennedy; L Mele; R A Ehrenkranz; B J Stoll; J A Lemons; D K Stevenson; C R Bauer; S B Korones; A A Fanaroff Journal: N Engl J Med Date: 1999-06-24 Impact factor: 91.245
Authors: Wes Onland; Thomas P Debray; Matthew M Laughon; Martijn Miedema; Filip Cools; Lisa M Askie; Jeanette M Asselin; Sandra A Calvert; Sherry E Courtney; Carlo Dani; David J Durand; Neil Marlow; Janet L Peacock; J Jane Pillow; Roger F Soll; Ulrich H Thome; Patrick Truffert; Michael D Schreiber; Patrick Van Reempts; Valentina Vendettuoli; Giovanni Vento; Anton H van Kaam; Karel G Moons; Martin Offringa Journal: BMC Pediatr Date: 2013-12-17 Impact factor: 2.125
Authors: Erik A Jensen; Kevin Dysart; Marie G Gantz; Scott McDonald; Nicolas A Bamat; Martin Keszler; Haresh Kirpalani; Matthew M Laughon; Brenda B Poindexter; Andrea F Duncan; Bradley A Yoder; Eric C Eichenwald; Sara B DeMauro Journal: Am J Respir Crit Care Med Date: 2019-09-15 Impact factor: 21.405