PMID- 34324880 OWN - NLM STAT- MEDLINE DCOM- 20211123 LR - 20221102 IS - 1097-6833 (Electronic) IS - 0022-3476 (Print) IS - 0022-3476 (Linking) VI - 238 DP - 2021 Nov TI - Enteral Iron Supplementation in Infants Born Extremely Preterm and its Positive Correlation with Neurodevelopment; Post Hoc Analysis of the Preterm Erythropoietin Neuroprotection Trial Randomized Controlled Trial. PG - 102-109.e8 LID - S0022-3476(21)00686-7 [pii] LID - 10.1016/j.jpeds.2021.07.019 [doi] AB - OBJECTIVES: To test whether an increased iron dose is associated with improved neurodevelopment as assessed by the Bayley Scales of Infant Development, third edition (BSID-III) among infants enrolled in the Preterm Erythropoietin (Epo) Neuroprotection Trial (PENUT). STUDY DESIGN: This is a post hoc analysis of a randomized trial that enrolled infants born at 24-28 completed weeks of gestation. All infants in PENUT who were assessed with BSID-III at 2 years were included in this study. The associations between enteral iron dose at 60 and 90 days and BSID-III component scores were evaluated using generalized estimating equations models adjusted for potential confounders. RESULTS: In total, 692 infants were analyzed (355 placebo, 337 Epo). Enteral iron supplementation ranged from 0 to 14.7 mg/kg/d (IQR 2.1-5.8 mg/kg/d) at day 60, with a mean of 3.6 mg/kg/d in infants treated with placebo and 4.8 mg/kg/d in infants treated with Epo. A significant positive association was seen between BSID-III cognitive scores and iron dose at 60 days, with an effect size of 0.77 BSID points per 50 mg/kg increase in cumulative iron dose (P = .03). Greater iron doses were associated with greater motor and language scores but did not reach statistical significance. Results at 90 days were not significant. The effect size in the infants treated with Epo compared with placebo was consistently greater. CONCLUSIONS: A positive association was seen between iron dose at 60 days and cognitive outcomes. Our results suggest that increased iron supplementation in infants born preterm, at the doses administered in the PENUT Trial, may have positive neurodevelopmental effects, particularly in infants treated with Epo. TRIAL REGISTRATION: Clinicaltrials.gov: NCT01378273. CI - Copyright (c) 2021 Elsevier Inc. All rights reserved. FAU - German, Kendell R AU - German KR AD - Department of Pediatrics, University of Washington, Seattle, WA. Electronic address: germank@uw.edu. FAU - Vu, Phuong T AU - Vu PT AD - Department of Biostatistics, University of Washington, Seattle, WA. FAU - Comstock, Bryan A AU - Comstock BA AD - Department of Biostatistics, University of Washington, Seattle, WA. FAU - Ohls, Robin K AU - Ohls RK AD - Department of Pediatrics, University of Utah, Salt Lake City, UT. FAU - Heagerty, Patrick J AU - Heagerty PJ AD - Department of Biostatistics, University of Washington, Seattle, WA. FAU - Mayock, Dennis E AU - Mayock DE AD - Department of Pediatrics, University of Washington, Seattle, WA. FAU - Georgieff, Michael AU - Georgieff M AD - Department of Pediatrics, University of Minnesota, MN. FAU - Rao, Raghavendra AU - Rao R AD - Department of Pediatrics, University of Minnesota, MN. FAU - Juul, Sandra E AU - Juul SE AD - Department of Pediatrics, University of Washington, Seattle, WA. CN - PENUT Consortium LA - eng SI - ClinicalTrials.gov/NCT01378273 GR - U01 NS077953/NS/NINDS NIH HHS/United States GR - U01 NS077955/NS/NINDS NIH HHS/United States PT - Journal Article PT - Randomized Controlled Trial DEP - 20210727 PL - United States TA - J Pediatr JT - The Journal of pediatrics JID - 0375410 RN - 0 (EPO protein, human) RN - 11096-26-7 (Erythropoietin) RN - E1UOL152H7 (Iron) SB - IM MH - Adult MH - Enteral Nutrition MH - Erythropoietin/administration & dosage/pharmacology MH - Female MH - Humans MH - Infant MH - Infant, Extremely Premature/growth & development MH - Infant, Newborn MH - Iron/*administration & dosage/adverse effects/pharmacology MH - Male MH - Neurodevelopmental Disorders/*prevention & control MH - Neuroprotection/*drug effects MH - Pregnancy MH - Prospective Studies PMC - PMC8629150 MID - NIHMS1728193 OTO - NOTNLM OT - Epo OT - erythropoietin OT - extremely low gestational age neonate OT - extremely preterm neonate OT - iron OT - neonate OT - neurodevelopment OT - neurodevelopmental outcomes COIS- The authors declare no conflicts of interest. EDAT- 2021/07/30 06:00 MHDA- 2021/11/24 06:00 PMCR- 2022/11/01 CRDT- 2021/07/29 20:11 PHST- 2021/04/19 00:00 [received] PHST- 2021/06/18 00:00 [revised] PHST- 2021/07/02 00:00 [accepted] PHST- 2021/07/30 06:00 [pubmed] PHST- 2021/11/24 06:00 [medline] PHST- 2021/07/29 20:11 [entrez] PHST- 2022/11/01 00:00 [pmc-release] AID - S0022-3476(21)00686-7 [pii] AID - 10.1016/j.jpeds.2021.07.019 [doi] PST - ppublish SO - J Pediatr. 2021 Nov;238:102-109.e8. doi: 10.1016/j.jpeds.2021.07.019. Epub 2021 Jul 27.