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Neurodevelopmental outcome of preterm infants enrolled in myo-inositol randomized controlled trial

Abstract

Objective

This study evaluates the 24-month follow-up for the NICHD Neonatal Research Network (NRN) Inositol for Retinopathy Trial.

Study design

Bayley Scales of Infants Development-III and a standardized neurosensory examination were performed in infants enrolled in the main trial. Moderate/severe NDI was defined as BSID-III Cognitive or Motor composite score <85, moderate or severe cerebral palsy, blindness, or hearing loss that prevents communication despite amplification were assessed.

Results

Primary outcome was determined for 605/638 (95%). The mean gestational age was 25.8 ± 1.3 weeks and mean birthweight was 805 ± 192 g. Treatment group did not affect the risk for the composite outcome of death or survival with moderate/severe NDI (60% vs 56%, p = 0.40).

Conclusions

Treatment group did not affect the risk of death or survival with moderate/severe NDI. Despite early termination, this study represents the largest RCT of extremely preterm infants treated with myo-inositol with neurodevelopmental outcome data.

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Fig. 1: Consort diagram.
Fig. 2: Kaplan Meier curve through 24-month follow-up.

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Data availability

Data reported in this paper may be requested through a data use agreement. Further details are available at https://neonatal.rti.org/index.cfm?fuseaction=DataRequest.Home.

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Acknowledgements

IA-C died after writing the manuscript. The study team appreciates her efforts in leading the follow-up study, data analysis and completion of the manuscript. She is a very special person and will be missed by all of the team. Mina Chung, MD, was the research ophthalmologist at the University of Rochester and conducted primary outcome examinations for study participants recruited at this center. Dr. Chung provided important contributions to the study concept and design and she performed ophthalmologic evaluations on the 63 infants enrolled at this site. Dr. Chung died prior to preparation of the final manuscript. The study team would like to extend a special acknowledgement of her efforts on this project.

The National Institutes of Health and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) through the Neonatal Research Network, and the National Eye Institute (NEI) provided grant support for the Inositol Trial. While NICHD staff had input into the study design, conduct, analysis, and manuscript drafting, the comments and views of the authors do not necessarily represent the views of NICHD, NEI, the National Institutes of Health, the Department of Health and Human Services, or the U.S. Government.

Participating NRN sites collected data and transmitted it to RTI International, the data coordinating center (DCC) for the network, which stored, managed and analyzed the data for this study. On behalf of the NRN, RTI International had full access to all of the data in the study, and with the NRN Center Principal Investigators, takes responsibility for the integrity of the data and accuracy of the data analysis.

We are indebted to our medical and nursing colleagues and the infants and their parents who agreed to take part in this study. The following investigators, in addition to those listed as authors, participated in this study:

NRN Steering Committee Chair: Richard A. Polin, MD, Division of Neonatology, College of Physicians and Surgeons, Columbia University, (2011-present).

Alpert Medical School of Brown University and Women & Infants Hospital of Rhode Island (UG1 HD27904)—Abbot R. Laptook, MD; Martin Keszler, MD; Elisabeth C. McGowan, MD; Angelita M. Hensman, PhD RNC-NIC; Barbara Alksninis, PNP; Mary Lenore Keszler, MD; Andrea M. Knoll; Theresa M. Leach, MEd Emilee Little, RN BSN; Elisabeth C. McGowan, MD; Michael R. Muller, PharmD; Elisa Vieira, RN BSN; Victoria E. Watson, MS CAS.

Case Western Reserve University, Rainbow Babies & Children’s Hospital (UG1 HD21364)—Michele C. Walsh, MD MS; Anna Maria Hibbs, MD MSCE; Nancy S. Newman, BA RN; Michael Banchy, RPH; Monika Bhola, MD; Jeffrey L. Blumer, MD; Allison H. Payne, MD MS; Bonnie S. Siner, RN; Elizabeth Ross, MS; Eileen K. Stork, MD; H. Gerry Taylor, PhD; Gulgun Yalcinkaya, MD; Arlene Zadell, RN.

Children’s Mercy Hospital, University of Missouri Kansas City School of Medicine (UG1 HD68284)—William E. Truog, MD; Eugenia K. Pallotto, MD MSCE; Prabhu S. Parimi, MD; Cheri Gauldin, RN BSN CCRC; Lisa Gaetano, MSN RN; Anne M. Holmes, RN MSN MBA-HCM CCRC; Kathy Johnson RN, CCRC; Allison Knutson, BSN RNC-NIC.

Cincinnati Children’s Hospital Medical Center, University of Cincinnati Medical Center, and Good Samaritan Hospital (UG1 HD27853, UL1 TR77)—Kurt Schibler, MD; Cathy Grisby, BSN CCRC; Patricia Cobb, MS; Teresa L. Gratton, PA; Kristin Kirker, CRC; Stacey Tepe, BS; Sandra Wuertz, RN-BSN CCRP CLC; Kimberly Yolton, PhD.

Duke University School of Medicine, University Hospital, University of North Carolina, Duke Regional Hospital, and WakeMed Health and Hospitals (UG1 HD40492, UL1 TR1117)—Ronald N. Goldberg, MD; Joanne Finkle, RN JD; Kimberley A. Fisher, PhD FNP-BC IBCLC; William F. Malcolm, MD; Patricia L. Ashley, MD PHD; Deesha Mago-Shah, MD; Chi Dang-Hornik, PharmD BCPS; Sharon F. Freedman, MD; Kathryn E. Gustafson, PhD; Mary Miller-Bell, PharmD RPh; Sasapin Grace Prakalapakorn, MD MPH; Matthew M. Laughon, MD MPH; Carl L. Bose, MD; Janice Bernhardt, MS RN; Cindy Clark, RN; Diane D. Warner, MD MPH; TMO’S; Janice Wereszczak CPNP-AC/PC; Jennifer Talbert, MS RN; Stephen D. Kicklighter, MD; Sofia Aliaga, MD, MPH; Jeffery Board, MD; KRG; Jerry Magolan, MD; Linda Manor, RPh; Jan Niklas Ulrich, MD; Ginger Rhodes-Ryan, ARNP MSN NNP-BC; Donna White, BSN, RN-BC BSN; Alexandra Bentley, MD; Laura Edwards, MD.

Emory University, Children’s Healthcare of Atlanta, Grady Memorial Hospital, and Emory University Hospital Midtown (UG1 HD27851, UL1 TR454)—David P. Carlton, MD; Barbara J. Stoll, MD; Ellen C. Hale, RN BS CCRC; Yvonne Loggins, RN; Diane I. Bottcher, RN MSN; Sheena L. Carter, PhD; Colleen Mackie, BS RT; Maureen Mulligan LaRossa, RN; Lynn C. Comerford, NNP; Gloria Smike, PNP MSN; Salathiel Kendrick-Allwood, MD; Angela Leon-Hernandez, MD.

Eunice Kennedy Shriver National Institute of Child Health and Human Development—SWA.

Indiana University, Riley Hospital for Children and Methodist Hospital at Indiana University Health (UG1 HD27856)—GMS; SG, NNP CCRC; DEH, RN CCRC; ACH; EHyn, RNC-NIC; L-AP; LS CCRC.

McGovern Medical School at The University of Texas Health Science Center at Houston and Children’s Memorial Hermann Hospital (UG1 HD87229)—JET; KAK; AMK; ADu, RM, EA; JA-M, MSN APRN; SB, RCPhT; AGD; EE; FE-A, RPH; CG, RN BSN; KK; JJ, CPNP; PMJ; MLL, RN BSN; KM, RN; SCM, RN; GEM, RN; SME; HO; SR, RN; DS, RN; EKS, RN BSN; Vu Ta, PharmD; CW; SLW, MT (ASCP).

Nationwide Children’s Hospital and The Ohio State University Wexner Medical Center (UG1 HD68278)—PJS; LDN; SRJ; AEG; PL; CAF; GEB; NAP; DLR; RPG; COJ.

RTI International (U10 HD36790)—DW; MGG; CMB; JO’DA, BS; MMC, BS CCRP; JG, MPH CCRP; CMPH, MS CCRP; JWPII; AMV.

Stanford University and Lucile Packard Children’s Hospital (UG1 HD27880, UL1 TR93)—KPVM; DKS; MBB, BS CCRC; SChi; MSP, RCP; BB, PsychD MSEd; MED; AMD, RN PNP PhD; BE; LCH; CEK; RL; HEW.

University of Alabama at Birmingham Health System and Children’s Hospital of Alabama (UG1 HD34216)—WAC; NA; MVC, RN BSN MaEd; SSC, RN BSN; RJQ; BRD; AMA-B; FJB; KCJ, MSN CRNP; CSP; VAP, RN BSN; SW, MA OTR-L FAOTA.

University of California—Los Angeles, Mattel Children’s Hospital, Santa Monica Hospital, Los Robles Hospital and Medical Center, and Olive View Medical Center (UG1 HD68270)—UD; MGarg; TC, MPH; RG, RN BSN.

University of Iowa (UG1 HD53109, UL1 TR442)—EFB; JEB; KJJ, RN BSN; JRW, RN; CAG, RN; KMJ, BSPharm RPh; AM, BA CPhT; JLN, PharmD BCPS; SQL; AVD; DLE, RN CPNP MA; SAL; KRG; VPB.

University of New Mexico Health Sciences Center (UG1 HD53089, UL1TR41)—RKO; SSB, MSN RNC; TD; MRH, RN BSN; CHH, MPH RN; EK, RN BSN; SJK; JL; NAM, RPh MBA.

University of Oulu, and Oulu University Hospital, Oulu, Finland—MKH.

University of Pennsylvania, Hospital of the University of Pennsylvania, Pennsylvania Hospital, and Children’s Hospital of Philadelphia (UG1 HD68244)—BS; HK; SA; ASC, BS RRT; TM, RN BSN CCRC; WVA; JCB; GB, MD MSCE; NC; SLD; MGerdes; HH; MDM; MR; KRJr; JS, RN BSN; SMY, RPh.

University of Rochester Medical Center, Golisano Children’s Hospital, and the University of Buffalo Women’s and Children’s Hospital of Buffalo (UG1 HD68263, UL1 TR42)—CD’A; SL; AMR, MD MPH; SAB; MFC; PRC; RJ; RSR; AMT; AW, MS Ed; MGS, MAT; HW; JH; AH, LPN; MBo, RN NP; MH-M; WZ; OF; KY; JM, LMSW; CF; KB, BS; CO; PS, MPH.

University of Texas Southwestern Medical Center, Parkland Health & Hospital System, and Children’s Medical Center Dallas (UG1 HD40689)—MHW; LPB; DMV, RNC-NIC; SSA, MS RN CPNP; CC; JC, RN; MMDL, BSN RN; FE, BSN RN; LG, PharmD RPh; LG, RN; AG; EH, PsyD PA-C; LEL, RN; HCL; AM, PharmD RPh; LP; CTB, MS CIMI; RW, RPh.

Wayne State University, Hutzel Women’s Hospital and Children’s Hospital of Michigan (UG1 HD21385)—SS; BGS; RB, RN BSN; PA; MB; SCha; KC, RN BSN; MF; LAG; MEJ, RN BSN; ML-B, RPh; BP; EW, RN MSN.

Data and Safety Monitoring Committee—CAG, MD, chair, University of Washington; MCA, MD, Johns Hopkins University School of Medicine; RJB, MD, University of Virginia Health System; Traci Clemons, PhD, The EMMES Corporation; MED’A, MD, Columbia Ob/Gyn Midtown; ADa (ex officio), PhD, RTI International; DEverett, MA (non-voting member), National Eye Institute; Ralph E. Kauffman, MD, University of Missouri-Kansas City, Medical Research Department at Children’s Mercy Hospital; Menachem Miodovnik, MD, Washington Hospital Center; TMO’S, MD MPH, Wake Forest University School of Medicine; Lois Smith, MD, Harvard University Children’s Hospital; Steven J. Weiner, MS, The George Washington University; Marian Willinger (ex officio), PhD, Eunice Kennedy Shriver National Institute of Child Health and Human Development.

The BOOST Study ROP Credentialing site, www.boostnz.info/ROP/[boostnz.info, allowed NRN ophthalmologists to use their online system to certify their ROP training.

Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network

Stephanie Wilson Archer39, Gregory M. Sokol42, Susan Gunn42, Dianne E. Herron42, Abbey C. Hines42, Elizabeth Hynes42, Lu-Ann Papile42, Lucy Smiley42, Jon E. Tyson43, Kathleen A. Kennedy43, Amir M. Khan43, Andi Duncan43, Ricardo Mosquera43, Elizabeth Allain43, Julie Arldt-McAlister43, Shanti Brown43, Allison G. Dempsey43, Elizabeth Eason43, Farida El-Ali43, Carmen Garcia43, Kartik Kumar43, Janice John43, Patrick M. Jones43, M. Layne Lillie43, Karen Martin43, Sara C. Martin43, Georgia E. McDavid43, Shannon McKee EdS43, Hatice Ozsoy43, Shawna Rodgers43, Daniel Sperry43, Emily K. Stephens43, Vu Ta43, Christine Wong43, Sharon L. Wright43, Pablo J. Sánchez44, Leif D. Nelin44, Sudarshan R. Jadcherla44, Amanda E. Graf44, Patricia Luzader44, Christine A. Fortney44, Gail E. Besner44, Nehal A. Parikh44, David L. Rogers44, Richard P. Golden44, Catherine Olson Jordan44, Dennis Wallace45, Marie G. Gantz45, Carla M. Bann45, Jeanette O’ Donnell Auman45, Margaret M. Crawford45, Jenna Gabrio45, Carolyn M. Petrie Huitema45, James W. PickettII45, Annie M. VonLehmden45, Krisa P. Van Meurs46, David K. Stevenson46, M. Bethany Ball46, Steven Chinn46, Melinda S. Proud46, Barbara Bentley46, Maria Elena DeAnda46, Anne M. DeBattista46, Beth Earhart46, Lynne C. Huffman46, Casey E. Krueger46, Ryan Lucash46, Hali E. Weiss46, Waldemar A. Carlo47, Namasivayam Ambalavanan47, Monica V. Collins47, Shirley S. Cosby47, Rebecca J. Quinn47, Brenda Reed Denson47, Ann Marie Arciniegas-Bernal47, Fred J. Biasini47, Kristen C. Johnston47, Cryshelle S. Patterson47, Vivien A. Phillips47, Sally Whitley47, Uday Devaskar48, Meena Garg48, Teresa Chanlaw48, Rachel Geller48, Edward F. Bell49, Jane E. Brumbaugh49, Karen J. Johnson49, Jacky R. Walker49, Claire A. Goeke49, Kristine M. Johnson49, Angela Merriss49, Joanna L. Nohr49, Susannah Q. Longmuir49, Arlene V. Drack49, Diane L. Eastman49, Scott A. Larson49, Kevin R. Gertsch49, Vikki P. Bell49, Robin K. Ohls2, Sandra Sundquist Beauman2, Tara Dupont2, Mary Ruffaner Hanson2, Carol H. Hartenberger2, Elizabeth Kuan2, Susan J. Kunkel2, Jean Lowe2, Nancy A. Morgan2, Mikko K. Hallman50, Barbara Schmidt51, Haresh Kirpalani51, Soraya Abbasi51, Aasma S. Chaudhary51, Toni Mancini51, William V. Anninger51, Judy C. Bernbaum51, Gil Binenbaum51, Noah Cook51, Stefanie L. Davidson51, Marsha Gerdes51, Hallam Hurt51, Monte D. Mills51, Mina Ricciardelli51, Kenneth RockwellJr.51, Jonathan Snyder51, Sze Man Yau51, Carl D’Angio52, Satyan Lakshminrusimha52, Anne Marie Reynolds52, Stephen A. Bean52, Melissa F. Carmen52, Patricia R. Chess52, Rosemary Jensen52, Rajeev S. Ramchandran52, Ann Marie Turner52, Ashley Williams52, Michael G. Sacilowski52, Holly Wadkins52, Julianne Hunn52, Aimee Horan52, Melissa Bowman52, Michele Hartley-McAndrew52, William Zorn52, Osman Farooq52, Kelley Yost52, Joan Merzbach52, Cait Fallone52, Kyle Binion52, Constance Orme52, Premini Sabaratnam52, Myra H. Wyckoff53, Luc P. Brion53, Diana M. Vasil53, Sally S. Adams53, Christine Cha53, Juana Cisneros53, Maria M. De Leon53, Frances Eubanks53, Lynda Godowic53, Laura Grau53, Alicia Guzman53, Elizabeth Heyne53, Lizette E. Lee53, Helen C. Lira53, Azadeh Mozaffari53, Lara Pavageau53, Catherine Twell Boatman53, Reshma Wright53, Seetha Shankaran54, Beena G. Sood54, Rebecca Bara54, Prashant Agarwal54, Monika Bajaj54, Sanjay Chawla54, Kirsten Childs54, Melissa February54, Laura A. Goldston54, Mary E. Johnson54, Mirjana Lulic-Botica54, Bogdan Panaitescu54, Eunice Woldt54, Christine A. Gleason55, Marilee C. Allen55, Robert J. Boyle56, Traci Clemons57, Mary E. D’Alton58, Abhik Das59, Donald Everett45, Ralph E. Kauffman60, Menachem Miodovnik61, T. Michael O’Shea62, Lois Smith63, Steven J. Weiner64, Marian Willinger65

Funding

Funded by the National Institutes of Health, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (U10 HD36790, UG1 HD27904, UG1 HD21364, UG1 HD68284, UG1 HD27853, UG1 HD40492, UG1 HD27851, UG1 HD27856, UG1 HD87229, UG1 HD68278, UG1 HD27880, UG1 HD34216, UG1 HD68270, UG1 HD53109, UG1 HD53089, UG1 HD68244, UG1 HD68263, UG1 HD40689, UG1 HD21385), the National Eye Institute (via co-funding to NICHD), and the National Center for Advancing Translational Sciences (UL1 TR41, UL1 TR42, UL1 TR77, UL1 TR93, UL1 TR442, UL1 TR454, UL1 TR1117).

Author information

Authors and Affiliations

Authors

Consortia

Contributions

This manuscript represents a Phase III study of myo-Inositol for treatment of retinopathy of prematurity conducted within the NICHD Neonatal Research Network (NRN). The Inositol Subcommittee members had monthly conference calls during protocol development and early implementation, and regular teleconferences during implementation, data analysis, and manuscript drafting. The following authors have made significant contributions as determined by the Uniform Requirements for Manuscripts Submitted to Biomedical Journals: • IA-C, was the NRN Follow-up Principal Investigator (FU PI) at the Emory University, and oversaw participant follow-up in the study, which saw 13 infants for follow-up. She drafted the manuscript and received input from the coauthors below as part of manuscript revision. • KLW, was the NRN PI at the University of New Mexico and the Vice Chair of the Inositol Protocol Subcommittee. As the subcommittee vice chair, she helped develop the protocol and monitor implementation. As the PI, she oversees recruitment at the site, which enrolled 10 infants into this study. She also provided critical revision to this study’s concept and to the draft manuscript, and approved the final version of the manuscript. • TLN, served as a statistician for this study and completed the statistical analyses for the paper. She developed the tables for the paper and provided critical revision to the manuscript and approved the final version of the manuscript. • SH, served as a statistician for this study and completed the statistical analyses for the paper. He provided critical revision to the manuscript and approved the final version of the manuscript. • CAC, RPh, was a member of the Inositol Protocol Subcommittee, and a research pharmacist at the University of Rochester. As a site research pharmacist, she helped implement the study at the site, which enrolled 63 infants. She contributed critical revisions of the manuscript and approved the final manuscript for submission • CMC, was the NRN Co-PI at Duke University and a member of the Inositol Protocol Subcommittee. As the site investigator, he oversaw recruitment at the site, which enrolled 75 infants into this study. He contributed critical revisions of the manuscript and approved the final manuscript for submission. • WO, was a member of the Inositol Protocol Subcommittee, and a site investigator at Brown University. As the site investigator, he helped with recruitment at the site, which enrolled 37 infants into this study. He contributed critical revisions of the manuscript and approved the final manuscript for submission. • BBP, was the NRN PI at Indiana University, co-PI for enrollment at Cincinnati Children’s Hospital Medical Center, and a member of the Inositol Protocol Subcommittee. As the PI, she oversaw recruitment at Indiana University, which enrolled 39 infants into this study. As the co-PI, she oversaw recruitment at Cincinnati Children’s, assisted with participant recruitment and protocol implementation, which enrolled 50 infants into the study. She contributed critical revisions of the manuscript and approved the final manuscript for submission. • KMZ-B, RN BSN, served a critical role as the main coordinator at the Data Coordinating Center. She helped develop and train the NRN PIs and coordinators for the study, and provided day-to-day assistance with protocol and procedural questions as well as data form entry. She also maintained administrative documents for certification, and organized face-to-face subcommittee meetings and monthly teleconferences with investigators. She provided critical revision of the manuscript as well as approval of the final manuscript. • ADa, was the PI for NRN Data Coordinating Center at RTI International. He provided overall statistical and analytical guidance for the trial and served on the Inositol Subcommittee. He contributed to conception and design of the project, designed data collection instruments, supervised data collection for the NRN, performed data analysis and interpretation of data, revised the manuscript for intellectual content. He provided critical revision to this study’s concept and to the draft manuscript, and approved the final version of the manuscript. • CBL, RN, was the NRN Coordinator for the University of New Mexico. She served on the Inositol Subcommittee, helping to develop the protocol, and monitor implementation. She contributed to the conception and design of the project, designed data collection instruments, and served as the resource for data collection related activity for the other NRN sites. As the research coordinator, she assisted with recruitment at the site, which enrolled 10 infants into this study. She provided critical revision to this study’s concept and to the draft manuscript, and approved the final version of the manuscript. • AMS, was the NRN Coordinator for the University of Rochester. She served on the Inositol Subcommittee, helping to develop the protocol, and monitor implementation. She contributed to the conception and design of the project, designed data collection instruments, and served as the resource for data collection related activity for the other NRN sites. As the research coordinator, she assisted with recruitment at the site, which enrolled 63 infants into this study. She provided critical revision to this study’s concept and to the draft manuscript, and approved the final version of the manuscript. • AFD, MD MSClinRes, was the NRN FU PI at the McGovern Medical School at The University of Texas Health Science Center at Houston and oversaw participant follow-up in the study, which saw 64 infants for follow-up in the study. She provided critical revision to this study’s concept and to the draft manuscript, and approved the final version of the manuscript. • SBD, MD MSCE, was the NRN site investigator and FU PI at the University of Pennsylvania, and oversaw participant follow-up in the study, which saw 25 infants for follow-up in the study. She provided critical revision to this study’s concept and to the draft manuscript, and approved the final version of the manuscript. • RFG, was the NRN FU PI at Duke University, and oversaw participant follow-up in the study, which saw 60 infants for follow-up in the study. She provided critical revision to this study’s concept and to the draft manuscript, and approved the final version of the manuscript. • TTC, was the NRN FU PI at the University of Iowa, and oversaw participant follow-up in the study, which saw 43 infants for follow-up in the study. She provided critical revision to this study’s concept and to the draft manuscript, and approved the final version of the manuscript. • DEW-C, was the NRN FU PI at Case Western Reserve University, and oversaw participant follow-up in the study, which saw 31 infants for follow-up in the study. She provided critical revision to this study’s concept and to the draft manuscript, and approved the final version of the manuscript. • IBP, PhD CPNP, was the NRN FU PI at the University of California—Los Angeles, and oversaw participant follow-up in the study, which saw 18 infants for follow-up in the study. She provided critical revision to this study’s concept and to the draft manuscript, and approved the final version of the manuscript. • SRH, MD MS Epi, was the NRN FU PI at Stanford University, and oversaw participant follow-up in the study, which saw 17 infants for follow-up in the study. She provided critical revision to this study’s concept and to the draft manuscript, and approved the final version of the manuscript. • RJH, was the NRN FU PI at the University of Texas Southwestern, and oversaw participant follow-up in the study, which saw 11 infants for follow-up in the study. He provided critical revision to this study’s concept and to the draft manuscript, and approved the final version of the manuscript. • GJM, was the FU PI at the University of Rochester, and oversaw participant follow-up in the study, which saw 50 infants for follow-up in the study. He provided critical revision to this study’s concept and to the draft manuscript, and approved the final version of the manuscript. • JF, was the NRN FU PI at the University of New Mexico, and oversaw participant follow-up in the study, which saw 7 infants for follow-up in the study. She provided critical revision to this study’s concept and to the draft manuscript, and approved the final version of the manuscript. • SM, was the NRN FU PI at Cincinnati Children’s Hospital Medical Center, and oversaw participant follow-up in the study, which saw 33 infants for follow-up. She provided critical revision to this study’s concept and to the draft manuscript, and approved the final version of the manuscript. • HMH, was the NRN FU PI at Indiana University, and oversaw participant follow-up in the study, which saw 29 infants for follow-up. She provided critical revision to this study’s concept and to the draft manuscript, and approved the final version of the manuscript. • MP-C, was the NRN Follow-up Principal Investigator (FU PI) at the University of Alabama at Birmingham, and oversaw participant follow-up in the study, which saw 16 infants for follow-up. She provided critical revision to this study’s concept and to the draft manuscript, and approved the final version of the manuscript. • HWK, was the NRN FU PI at Children’s Mercy Hospital, and oversaw participant follow-up in the study, which saw 20 infants for follow-up. He provided critical revision to this study’s concept and to the draft manuscript, and approved the final version of the manuscript. • NLM, was the FU PI at the Nationwide Children’s Hospital, and oversaw participant follow-up in the study, which saw 21 infants for follow-up. She provided critical revision to this study’s concept and to the draft manuscript, and approved the final version of the manuscript. • BRV, was the NRN FU PI at Brown University, and oversaw participant follow-up in the study, which saw 27 infants for follow-up. She provided critical revision to this study’s concept and to the draft manuscript, and approved the final version of the manuscript. • GN, was the NRN FU PI at Wayne State University and oversaw participant follow-up in the study, which saw 8 infants for follow-up. She provided critical revision to this study’s concept and to the draft manuscript, and approved the final version of the manuscript. • HM-H, was a research ophthalmologist at the McGovern Medical School at The University of Texas Health Science Center at Houston and conducted primary outcome examinations for study participants recruited at this center, which enrolled 71 infants into the study. She provided critical revision to this study’s concept and to the draft manuscript, and approved the final version of the manuscript. • GEQ, MD MSCE, was the research ophthalmologist at University of Pennsylvania and conducted primary outcome examinations for study participants recruited at this center, which enrolled 28 infants into the study. He provided critical revision to this study’s concept and to the draft manuscript, and approved the final version of the manuscript. • DKW, was the research ophthalmologist at Duke University and conducted primary outcome examinations for study participants recruited at this center, which enrolled 75 infants into the study. He provided critical revision to this study’s concept and to the draft manuscript, and approved the final version of the manuscript. • RJO, was the research ophthalmologist at the University of Iowa and conducted primary outcome examinations for study participants recruited at this center, which enrolled 48 infants into the study. He provided critical revision to this study’s concept and to the draft manuscript, and approved the final version of the manuscript. • FH, was the research ophthalmologist at Case Western Reserve University and conducted primary outcome examinations for study participants recruited at this center, which enrolled 41 infants into the study. He provided critical revision to this study’s concept and to the draft manuscript, and approved the final version of the manuscript. • IT, was the research ophthalmologist at University of California—Los Angeles and conducted primary outcome examinations for study participants recruited at this center, which enrolled 17 infants into the study. She provided critical revision to this study’s concept and to the draft manuscript, and approved the final version of the manuscript. • MG, was the research ophthalmologist at Stanford University and conducted primary outcome examinations for study participants recruited at this center, which enrolled 19 infants into the study. He provided critical revision to this study’s concept and to the draft manuscript, and approved the final version of the manuscript. • AKH, was the research ophthalmologist at Emory University and conducted primary outcome examinations for study participants recruited at this center, which enrolled 18 infants into the study. She provided critical revision to this study’s concept and to the draft manuscript, and approved the final version of the manuscript. • Y-GH, was the research ophthalmologist at University of Texas Southwestern and conducted primary outcome examinations for study participants recruited at this center, which enrolled 15 infants into the study. He provided critical revision to this study’s concept and to the draft manuscript, and approved the final version of the manuscript. • Mina Chung, MD, was the research ophthalmologist at the University of Rochester and conducted primary outcome examinations for study participants recruited at this center, which enrolled 63 infants into the study. She provided critical revision to this study’s concept and to the draft manuscript, and approved the final version of the manuscript. • TWW, was the research ophthalmologist at University of New Mexico and conducted primary outcome examinations for study participants recruited at this center, which enrolled 10 infants into the study. He provided critical revision to this study’s concept and to the draft manuscript, and approved the final version of the manuscript. • MBY, was the research ophthalmologist at Cincinnati Children’s Hospital Medical Center and conducted primary outcome examinations for study participants recruited at this center, which enrolled 50 infants into the study. He provided critical revision to this study’s concept and to the draft manuscript, and approved the final version of the manuscript. • KMH, was the research ophthalmologist at Indiana University and conducted primary outcome examinations for study participants recruited at this center, which enrolled 39 infants into the study. She provided critical revision to this study’s concept and to the draft manuscript, and approved the final version of the manuscript. • MSC, was the research ophthalmologist at University of Alabama at Birmingham and conducted primary outcome examinations for study participants recruited at this center, which enrolled 40 infants into the study. He provided critical revision to this study’s concept and to the draft manuscript, and approved the final version of the manuscript. • DH, was the research ophthalmologist at Children’s Mercy Hospital and conducted primary outcome examinations for study participants recruited at this center, which enrolled 25 infants into the study. She provided critical revision to this study’s concept and to the draft manuscript, and approved the final version of the manuscript. • DLB, was the research ophthalmologist at Nationwide Children’s Hospital and conducted primary outcome examinations for study participants recruited at this center, which enrolled 30 infants into the study. He provided critical revision to this study’s concept and to the draft manuscript, and approved the final version of the manuscript. • JPD, the research ophthalmologist at Brown University and conducted primary outcome examinations for study participants recruited at this center, which enrolled 37 infants into the study. He provided critical revision to this study’s concept and to the draft manuscript, and approved the final version of the manuscript. • WRL, was the research ophthalmologist at Wayne State University and conducted primary outcome examinations for study participants recruited at this center, which enrolled 12 infants into the study. He provided critical revision to this study’s concept and to the draft manuscript, and approved the final version of the manuscript. • DLP, was the Lead Principal Investigator for the Inositol Study for the NRN and the Chair of the protocol subcommittee. She designed the Inositol trial with the Inositol Subcommittee and was involved in all stages of its development, implementation, and analysis, including training the NRN PIs and coordinators. She provided critical revision to this study’s concept and to the draft manuscript, and approved the final version of the manuscript. • RDH, served as the Program Scientist for the NICHD NRN and a member of the Inositol Protocol Subcommittee. She helped developed the protocol, oversaw recruitment and follow-up compliance, and assisted with data edits from the sites. She also provided critical revision to the manuscript and approved and submitted the final version of the manuscript.

Corresponding author

Correspondence to Rosemary D. Higgins.

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Conflict of interest

None of the authors report any commercial, proprietary, or financial interest in any of the products described in this article. NICHD is the sponsor of the study and holds the investigational new drug (IND) application. Abbott Nutrition Division, Abbott Laboratories, Columbus, OH, provided the inositol product. They had no role in the: design of the trial; the analyses, interpretation, or writing of the manuscript; or the decision to submit the manuscript for publication. They provided on-site monitoring to assist in quality assurance of the data collection.

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Members of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network are listed below Acknowledgements

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Adams-Chapman, I., Watterberg, K.L., Nolen, T.L. et al. Neurodevelopmental outcome of preterm infants enrolled in myo-inositol randomized controlled trial. J Perinatol 41, 2072–2087 (2021). https://doi.org/10.1038/s41372-021-01018-5

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