Randomized Controlled Trial

. 2021 Aug;41(8):2072-2087.

doi: 10.1038/s41372-021-01018-5. Epub 2021 Mar 23.

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

Ira Adams-Chapman¹, Kristi L Watterberg², Tracy L Nolen³, Shawn Hirsch³, Carol A Cole⁴, C Michael Cotten⁵, William Oh⁶, Brenda B Poindexter^{7

8}, Kristin M Zaterka-Baxter³, Abhik Das⁹, Conra Backstrom Lacy², Ann Marie Scorsone⁴, Andrea F Duncan¹⁰, Sara B DeMauro¹¹, Ricki F Goldstein⁵, Tarah T Colaizy¹², Deanne E Wilson-Costello¹³, Isabell B Purdy¹⁴, Susan R Hintz¹⁵, Roy J Heyne¹⁶, Gary J Myers⁴, Janell Fuller², Stephanie Merhar⁷, Heidi M Harmon^{12

8}, Myriam Peralta-Carcelen¹⁷, Howard W Kilbride¹⁸, Nathalie L Maitre¹⁹, Betty R Vohr⁶, Girija Natarajan²⁰, Helen Mintz-Hittner²¹, Graham E Quinn²², David K Wallace^{23

24}, Richard J Olson²⁵, Faruk H Orge²⁶, Irena Tsui²⁷, Michael Gaynon²⁸, Amy K Hutchinson²⁹, Yu-Guang He³⁰, Timothy W Winter³¹, Michael B Yang³², Kathryn M Haider²⁴, Martin S Cogen³³, Denise Hug³⁴, Don L Bremer³⁵, John P Donahue³⁶, William R Lucas³⁷, Dale L Phelps⁴, Rosemary D Higgins^{38

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

Collaborators, Affiliations

Collaborators

Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network:
Stephanie Wilson Archer, Gregory M Sokol, Susan Gunn, Dianne E Herron, Abbey C Hines, Elizabeth Hynes, Lu-Ann Papile, Lucy Smiley, Jon E Tyson, Kathleen A Kennedy, Amir M Khan, Andi Duncan, Ricardo Mosquera, Elizabeth Allain, Julie Arldt-McAlister, Shanti Brown, Allison G Dempsey, Elizabeth Eason, Farida El-Ali, Carmen Garcia, Kartik Kumar, Janice John, Patrick M Jones, M Layne Lillie, Karen Martin, Sara C Martin, Georgia E McDavid, Shannon McKee EdS, Hatice Ozsoy, Shawna Rodgers, Daniel Sperry, Emily K Stephens, Vu Ta, Christine Wong, Sharon L Wright, Pablo J Sánchez, Leif D Nelin, Sudarshan R Jadcherla, Amanda E Graf, Patricia Luzader, Christine A Fortney, Gail E Besner, Nehal A Parikh, David L Rogers, Richard P Golden, Catherine Olson Jordan, Dennis Wallace, Marie G Gantz, Carla M Bann, Jeanette O' Donnell Auman, Margaret M Crawford, Jenna Gabrio, Carolyn M Petrie Huitema, James W Pickett 2nd, Annie M VonLehmden, Krisa P Van Meurs, David K Stevenson, M Bethany Ball, Steven Chinn, Melinda S Proud, Barbara Bentley, Maria Elena DeAnda, Anne M DeBattista, Beth Earhart, Lynne C Huffman, Casey E Krueger, Ryan Lucash, Hali E Weiss, Waldemar A Carlo, Namasivayam Ambalavanan, Monica V Collins, Shirley S Cosby, Rebecca J Quinn, Brenda Reed Denson, Ann Marie Arciniegas-Bernal, Fred J Biasini, Kristen C Johnston, Cryshelle S Patterson, Vivien A Phillips, Sally Whitley, Uday Devaskar, Meena Garg, Teresa Chanlaw, Rachel Geller, Edward F Bell, Jane E Brumbaugh, Karen J Johnson, Jacky R Walker, Claire A Goeke, Kristine M Johnson, Angela Merriss, Joanna L Nohr, Susannah Q Longmuir, Arlene V Drack, Diane L Eastman, Scott A Larson, Kevin R Gertsch, Vikki P Bell, Robin K Ohls, Sandra Sundquist Beauman, Tara Dupont, Mary Ruffaner Hanson, Carol H Hartenberger, Elizabeth Kuan, Susan J Kunkel, Jean Lowe, Nancy A Morgan, Mikko K Hallman, Barbara Schmidt, Haresh Kirpalani, Soraya Abbasi, Aasma S Chaudhary, Toni Mancini, William V Anninger, Judy C Bernbaum, Gil Binenbaum, Noah Cook, Stefanie L Davidson, Marsha Gerdes, Hallam Hurt, Monte D Mills, Mina Ricciardelli, Kenneth Rockwell Jr, Jonathan Snyder, Sze Man Yau, Carl D'Angio, Satyan Lakshminrusimha, Anne Marie Reynolds, Stephen A Bean, Melissa F Carmen, Patricia R Chess, Rosemary Jensen, Rajeev S Ramchandran, Ann Marie Turner, Ashley Williams, Michael G Sacilowski, Holly Wadkins, Julianne Hunn, Aimee Horan, Melissa Bowman, Michele Hartley-McAndrew, William Zorn, Osman Farooq, Kelley Yost, Joan Merzbach, Cait Fallone, Kyle Binion, Constance Orme, Premini Sabaratnam, Myra H Wyckoff, Luc P Brion, Diana M Vasil, Sally S Adams, Christine Cha, Juana Cisneros, Maria M De Leon, Frances Eubanks, Lynda Godowic, Laura Grau, Alicia Guzman, Elizabeth Heyne, Lizette E Lee, Helen C Lira, Azadeh Mozaffari, Lara Pavageau, Catherine Twell Boatman, Reshma Wright, Seetha Shankaran, Beena G Sood, Rebecca Bara, Prashant Agarwal, Monika Bajaj, Sanjay Chawla, Kirsten Childs, Melissa February, Laura A Goldston, Mary E Johnson, Mirjana Lulic-Botica, Bogdan Panaitescu, Eunice Woldt, Christine A Gleason, Marilee C Allen, Robert J Boyle, Traci Clemons, Mary E D'Alton, Abhik Das, Donald Everett, Ralph E Kauffman, Menachem Miodovnik, T Michael O'Shea, Lois Smith, Steven J Weiner, Marian Willinger

Affiliations

¹ Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA, USA.
² University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
³ Social, Statistical and Environmental Sciences Unit, RTI International, Research Triangle Park, North Carolina, NC, USA.
⁴ University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
⁵ Department of Pediatrics, Duke University, Durham, NC, USA.
⁶ Department of Pediatrics, Women & Infants' Hospital, Brown University, Providence, RI, USA.
⁷ Department of Pediatrics, Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, OH, USA.
⁸ Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, USA.
⁹ Social, Statistical and Environmental Sciences Unit, RTI International, Rockville, MD, USA.
¹⁰ Department of Pediatrics, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, TX, USA.
¹¹ Department of Pediatrics, The Children's Hospital of Philadelphia and The University of Pennsylvania, Philadelphia, PA, USA.
¹² Department of Pediatrics, University of Iowa, Iowa City, IA, USA.
¹³ Department of Pediatrics, Rainbow Babies & Children's Hospital, Case Western Reserve University, Cleveland, OH, USA.
¹⁴ Department of Pediatrics, University of California, Los Angeles, CA, USA.
¹⁵ Department of Pediatrics, Division of Neonatal and Developmental Medicine, Stanford University School of Medicine and Lucile Packard Children's Hospital, Palo Alto, CA, USA.
¹⁶ Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX, USA.
¹⁷ Division of Neonatology, University of Alabama at Birmingham, Birmingham, AL, USA.
¹⁸ Department of Pediatrics, Children's Mercy Hospital and University of Missouri Kansas City School of Medicine, Kansas City, MO, USA.
¹⁹ Department of Pediatrics, Nationwide Children's Hospital, The Ohio State University College of Medicine, Columbus, OH, USA.
²⁰ Department of Pediatrics, Wayne State University, Detroit, MI, USA.
²¹ Department of Ophthalmology and Visual Science, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, TX, USA.
²² Department of Ophthalmology, The Children's Hospital of Philadelphia and The University of Pennsylvania, Philadelphia, PA, USA.
²³ Department of Ophthalmology, Duke University, Durham, NC, USA.
²⁴ Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, IN, USA.
²⁵ Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, IA, USA.
²⁶ Department of Ophthalmology, Rainbow Babies & Children's Hospital, Case Western Reserve University, Cleveland, OH, USA.
²⁷ Department of Ophthalmology, University of California, Los Angeles, CA, USA.
²⁸ Department of Ophthalmology, Division of Neonatal and Developmental Medicine, Stanford University School of Medicine and Lucile Packard Children's Hospital, Palo Alto, CA, USA.
²⁹ Department of Ophthalmology, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA, USA.
³⁰ Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
³¹ Division of Ophthalmology/Department of Surgery, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
³² Department of Ophthalmology, Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, OH, USA.
³³ Department of Ophthalmology, University of Alabama at Birmingham, Birmingham, AL, USA.
³⁴ Department of Ophthalmology, Children's Mercy Hospital and University of Missouri Kansas City School of Medicine, Kansas City, MO, USA.
³⁵ Department of Ophthalmology, Nationwide Children's Hospital, Columbus, OH, USA.
³⁶ Alpert Medical School of Brown University and Consulting Staff, Women & Infants Hospital of Rhode Island, Providence, RI, USA.
³⁷ Department of Ophthalmology, Wayne State University, Detroit, MI, USA.
³⁸ Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA. rhiggin@gmu.edu.
³⁹ College of Health and Human Services, George Mason University, Fairfax, VA, USA. rhiggin@gmu.edu.

PMID: 33758387
PMCID: PMC8349854
DOI: 10.1038/s41372-021-01018-5

Randomized Controlled Trial

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

Ira Adams-Chapman et al. J Perinatol. 2021 Aug.

. 2021 Aug;41(8):2072-2087.

doi: 10.1038/s41372-021-01018-5. Epub 2021 Mar 23.

Authors

Collaborators

Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network:
Stephanie Wilson Archer, Gregory M Sokol, Susan Gunn, Dianne E Herron, Abbey C Hines, Elizabeth Hynes, Lu-Ann Papile, Lucy Smiley, Jon E Tyson, Kathleen A Kennedy, Amir M Khan, Andi Duncan, Ricardo Mosquera, Elizabeth Allain, Julie Arldt-McAlister, Shanti Brown, Allison G Dempsey, Elizabeth Eason, Farida El-Ali, Carmen Garcia, Kartik Kumar, Janice John, Patrick M Jones, M Layne Lillie, Karen Martin, Sara C Martin, Georgia E McDavid, Shannon McKee EdS, Hatice Ozsoy, Shawna Rodgers, Daniel Sperry, Emily K Stephens, Vu Ta, Christine Wong, Sharon L Wright, Pablo J Sánchez, Leif D Nelin, Sudarshan R Jadcherla, Amanda E Graf, Patricia Luzader, Christine A Fortney, Gail E Besner, Nehal A Parikh, David L Rogers, Richard P Golden, Catherine Olson Jordan, Dennis Wallace, Marie G Gantz, Carla M Bann, Jeanette O' Donnell Auman, Margaret M Crawford, Jenna Gabrio, Carolyn M Petrie Huitema, James W Pickett 2nd, Annie M VonLehmden, Krisa P Van Meurs, David K Stevenson, M Bethany Ball, Steven Chinn, Melinda S Proud, Barbara Bentley, Maria Elena DeAnda, Anne M DeBattista, Beth Earhart, Lynne C Huffman, Casey E Krueger, Ryan Lucash, Hali E Weiss, Waldemar A Carlo, Namasivayam Ambalavanan, Monica V Collins, Shirley S Cosby, Rebecca J Quinn, Brenda Reed Denson, Ann Marie Arciniegas-Bernal, Fred J Biasini, Kristen C Johnston, Cryshelle S Patterson, Vivien A Phillips, Sally Whitley, Uday Devaskar, Meena Garg, Teresa Chanlaw, Rachel Geller, Edward F Bell, Jane E Brumbaugh, Karen J Johnson, Jacky R Walker, Claire A Goeke, Kristine M Johnson, Angela Merriss, Joanna L Nohr, Susannah Q Longmuir, Arlene V Drack, Diane L Eastman, Scott A Larson, Kevin R Gertsch, Vikki P Bell, Robin K Ohls, Sandra Sundquist Beauman, Tara Dupont, Mary Ruffaner Hanson, Carol H Hartenberger, Elizabeth Kuan, Susan J Kunkel, Jean Lowe, Nancy A Morgan, Mikko K Hallman, Barbara Schmidt, Haresh Kirpalani, Soraya Abbasi, Aasma S Chaudhary, Toni Mancini, William V Anninger, Judy C Bernbaum, Gil Binenbaum, Noah Cook, Stefanie L Davidson, Marsha Gerdes, Hallam Hurt, Monte D Mills, Mina Ricciardelli, Kenneth Rockwell Jr, Jonathan Snyder, Sze Man Yau, Carl D'Angio, Satyan Lakshminrusimha, Anne Marie Reynolds, Stephen A Bean, Melissa F Carmen, Patricia R Chess, Rosemary Jensen, Rajeev S Ramchandran, Ann Marie Turner, Ashley Williams, Michael G Sacilowski, Holly Wadkins, Julianne Hunn, Aimee Horan, Melissa Bowman, Michele Hartley-McAndrew, William Zorn, Osman Farooq, Kelley Yost, Joan Merzbach, Cait Fallone, Kyle Binion, Constance Orme, Premini Sabaratnam, Myra H Wyckoff, Luc P Brion, Diana M Vasil, Sally S Adams, Christine Cha, Juana Cisneros, Maria M De Leon, Frances Eubanks, Lynda Godowic, Laura Grau, Alicia Guzman, Elizabeth Heyne, Lizette E Lee, Helen C Lira, Azadeh Mozaffari, Lara Pavageau, Catherine Twell Boatman, Reshma Wright, Seetha Shankaran, Beena G Sood, Rebecca Bara, Prashant Agarwal, Monika Bajaj, Sanjay Chawla, Kirsten Childs, Melissa February, Laura A Goldston, Mary E Johnson, Mirjana Lulic-Botica, Bogdan Panaitescu, Eunice Woldt, Christine A Gleason, Marilee C Allen, Robert J Boyle, Traci Clemons, Mary E D'Alton, Abhik Das, Donald Everett, Ralph E Kauffman, Menachem Miodovnik, T Michael O'Shea, Lois Smith, Steven J Weiner, Marian Willinger

Affiliations

¹ Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA, USA.
² University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
³ Social, Statistical and Environmental Sciences Unit, RTI International, Research Triangle Park, North Carolina, NC, USA.
⁴ University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
⁵ Department of Pediatrics, Duke University, Durham, NC, USA.
⁶ Department of Pediatrics, Women & Infants' Hospital, Brown University, Providence, RI, USA.
⁷ Department of Pediatrics, Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, OH, USA.
⁸ Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, USA.
⁹ Social, Statistical and Environmental Sciences Unit, RTI International, Rockville, MD, USA.
¹⁰ Department of Pediatrics, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, TX, USA.
¹¹ Department of Pediatrics, The Children's Hospital of Philadelphia and The University of Pennsylvania, Philadelphia, PA, USA.
¹² Department of Pediatrics, University of Iowa, Iowa City, IA, USA.
¹³ Department of Pediatrics, Rainbow Babies & Children's Hospital, Case Western Reserve University, Cleveland, OH, USA.
¹⁴ Department of Pediatrics, University of California, Los Angeles, CA, USA.
¹⁵ Department of Pediatrics, Division of Neonatal and Developmental Medicine, Stanford University School of Medicine and Lucile Packard Children's Hospital, Palo Alto, CA, USA.
¹⁶ Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX, USA.
¹⁷ Division of Neonatology, University of Alabama at Birmingham, Birmingham, AL, USA.
¹⁸ Department of Pediatrics, Children's Mercy Hospital and University of Missouri Kansas City School of Medicine, Kansas City, MO, USA.
¹⁹ Department of Pediatrics, Nationwide Children's Hospital, The Ohio State University College of Medicine, Columbus, OH, USA.
²⁰ Department of Pediatrics, Wayne State University, Detroit, MI, USA.
²¹ Department of Ophthalmology and Visual Science, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, TX, USA.
²² Department of Ophthalmology, The Children's Hospital of Philadelphia and The University of Pennsylvania, Philadelphia, PA, USA.
²³ Department of Ophthalmology, Duke University, Durham, NC, USA.
²⁴ Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, IN, USA.
²⁵ Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, IA, USA.
²⁶ Department of Ophthalmology, Rainbow Babies & Children's Hospital, Case Western Reserve University, Cleveland, OH, USA.
²⁷ Department of Ophthalmology, University of California, Los Angeles, CA, USA.
²⁸ Department of Ophthalmology, Division of Neonatal and Developmental Medicine, Stanford University School of Medicine and Lucile Packard Children's Hospital, Palo Alto, CA, USA.
²⁹ Department of Ophthalmology, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA, USA.
³⁰ Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
³¹ Division of Ophthalmology/Department of Surgery, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
³² Department of Ophthalmology, Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, OH, USA.
³³ Department of Ophthalmology, University of Alabama at Birmingham, Birmingham, AL, USA.
³⁴ Department of Ophthalmology, Children's Mercy Hospital and University of Missouri Kansas City School of Medicine, Kansas City, MO, USA.
³⁵ Department of Ophthalmology, Nationwide Children's Hospital, Columbus, OH, USA.
³⁶ Alpert Medical School of Brown University and Consulting Staff, Women & Infants Hospital of Rhode Island, Providence, RI, USA.
³⁷ Department of Ophthalmology, Wayne State University, Detroit, MI, USA.
³⁸ Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA. rhiggin@gmu.edu.
³⁹ College of Health and Human Services, George Mason University, Fairfax, VA, USA. rhiggin@gmu.edu.

PMID: 33758387
PMCID: PMC8349854
DOI: 10.1038/s41372-021-01018-5

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.

PubMed Disclaimer

Conflict of interest statement

Conflicts of Interest and Disclosures

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.

Figures

**Figure 2:**
Kaplan Meier Curve through 24 month follow-up

See this image and copyright information in PMC

References

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1. Hallman M, Järvenpää AL, Pohjavuori M. Respiratory distress syndrome and inositol supplementation in preterm infants. Archives of Disease in Childhood. 1986;61(11):1076–1083. - PMC - PubMed
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1. Phelps DL, Watterberg KL, Nolen TL, Cole CA, Cotten CM, Oh W, et al. Effects of Myo-inositol on Type 1 Retinopathy of Prematurity Among Preterm Infants <28 Weeks’ Gestational Age: A Randomized Clinical Trial. JAMA. 2018;320(16):1649–1658. - PMC - PubMed

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

Collaborators

Affiliations

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

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical