Preterm Infant Outcomes after Randomization to Initial Resuscitation with FiO2 0.21 or 1.0

Valerie Thamrin; Ola D Saugstad; William Tarnow-Mordi; Yueping Alex Wang; Kei Lui; Ian M Wright; Koert De Waal; Javeed Travadi; John P Smyth; Paul Craven; Rowena McMullan; Elisabeth Coates; Meredith Ward; Parag Mishra; Kwee Ching See; Irene G S Cheah; Chin Theam Lim; Yao Mun Choo; Azanna Ahmad Kamar; Fook Choe Cheah; Ahmed Masoud; Ju Lee Oei

doi:10.1016/j.jpeds.2018.05.053

Preterm Infant Outcomes after Randomization to Initial Resuscitation with FiO₂ 0.21 or 1.0

J Pediatr. 2018 Oct:201:55-61.e1. doi: 10.1016/j.jpeds.2018.05.053. Epub 2018 Jul 6.

Authors

Valerie Thamrin¹, Ola D Saugstad², William Tarnow-Mordi³, Yueping Alex Wang⁴, Kei Lui⁵, Ian M Wright⁶, Koert De Waal⁷, Javeed Travadi⁷, John P Smyth⁸, Paul Craven⁷, Rowena McMullan⁹, Elisabeth Coates¹⁰, Meredith Ward⁵, Parag Mishra⁵, Kwee Ching See¹¹, Irene G S Cheah¹², Chin Theam Lim¹³, Yao Mun Choo¹³, Azanna Ahmad Kamar¹³, Fook Choe Cheah¹⁴, Ahmed Masoud¹⁵, Ju Lee Oei¹⁶

Affiliations

¹ School of Women's and Children's Health, The University of New South Wales, Sydney, NSW, Australia.
² Department of Pediatric Research, The University of Oslo, Oslo, Norway.
³ NHMRC Clinical Trials Centre, The University of Sydney, Sydney, NSW, Australia; Westmead International Network for Neonatal Education and Research, Sydney, NSW, Australia.
⁴ Faculty of Health, University of Technology Sydney, Sydney, NSW, Australia.
⁵ School of Women's and Children's Health, The University of New South Wales, Sydney, NSW, Australia; Department of Newborn Care, The Royal Hospital for Women, Sydney, NSW, Australia.
⁶ Illawarra Health and Medical Research Institute and Graduate School of Medicine, The University of Wollongong, Wollongong, NSW, Australia; Hunter Medical Research Institute, University of Newcastle, Newcastle, NSW, Australia.
⁷ Hunter Medical Research Institute, University of Newcastle, Newcastle, NSW, Australia; Department of Neonatology, The John Hunter Hospital, Newcastle, NSW, Australia.
⁸ School of Women's and Children's Health, The University of New South Wales, Sydney, NSW, Australia; Department of Pediatric Research, The University of Oslo, Oslo, Norway.
⁹ Department of Neonatology, Royal Prince Alfred Hospital, Sydney, NSW, Australia.
¹⁰ NHMRC Clinical Trials Centre, The University of Sydney, Sydney, NSW, Australia.
¹¹ Department of Neonatology, Sungai Buloh Hospital, Selangor, Malaysia.
¹² Department of Neonatology, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia.
¹³ Department of Neonatology, University of Malaya Medical Centre, Kuala Lumpur, Malaysia.
¹⁴ Department of Paediatrics, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia.
¹⁵ Hamad Medical Corporation, Doha, Qatar.
¹⁶ School of Women's and Children's Health, The University of New South Wales, Sydney, NSW, Australia; NHMRC Clinical Trials Centre, The University of Sydney, Sydney, NSW, Australia; Department of Newborn Care, The Royal Hospital for Women, Sydney, NSW, Australia. Electronic address: j.oei@unsw.edu.au.

PMID: 30251639
DOI: 10.1016/j.jpeds.2018.05.053

Abstract

Objective: To determine rates of death or neurodevelopmental impairment (NDI) at 2 years corrected age (primary outcome) in children <32 weeks' gestation randomized to initial resuscitation with a fraction of inspired oxygen (FiO₂) value of 0.21 or 1.0.

Study design: Blinded assessments were conducted at 2-3 years corrected age with the Bayley Scales of Infant and Toddler Development, Third Edition or the Ages and Stages Questionnaire by intention to treat.

Results: Of the 290 children enrolled, 40 could not be contacted and 10 failed to attend appointments. Among the 240 children for whom outcomes at age 2 years were available, 1 child had a lethal congenital anomaly, 1 child had consent for follow-up withdrawn, and 23 children died. The primary outcome, which was available in 238 (82%) of those randomized, occurred in 47 of the 117 (40%) children assigned to initial FiO₂ 0.21 and in 38 of the 121 (31%) assigned to initial FiO₂ 1.0 (OR, 1.47; 95% CI, 0.86-2.5; P = .16). No difference in NDI was found in 215 survivors randomized to FiO₂ 0.21 vs 1.0 (OR, 1.26; 95% CI, 0.70-2.28; P = .11). In post hoc exploratory analyses in the whole cohort, children with a 5-minute blood oxygen saturation (SpO₂) <80% were more likely to die or to have NDI (OR, 1.85; 95% CI, 1.07-3.2; P = .03).

Conclusions: Initial resuscitation of infants <32 weeks' gestation with initial FiO₂ 0.21 had no significant effect on death or NDI compared with initial FiO₂ 1.0. Further evaluation of optimum initial FiO₂, including SpO₂ targeting, in a large randomized controlled trial is needed.

Trial registration: Australian and New Zealand Clinical Trials Network Registry ACTRN 12610001059055 and the National Malaysian Research Registry NMRR-07-685-957.

Keywords: death; neurodevelopmental injury; oxygen; preterm; resuscitation.

Publication types

Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Aptitude Tests
Child, Preschool
Female
Follow-Up Studies
Gestational Age
Humans
Infant, Newborn
Infant, Premature*
Male
Neurodevelopmental Disorders / epidemiology*
Oxygen / administration & dosage*
Oxygen / blood
Oxygen Inhalation Therapy / methods*
Resuscitation*

Substances

Oxygen