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You are called to help resuscitate a 30-week preterm neonate in the delivery suite. According to a recent meta-analysis on the effects of initial oxygen concentration for the resuscitation of neonates born at less than 32 weeks’ gestation, which of the following outcomes is MOST likely in this neonate if he receives high fraction of inspired oxygen (FIO2 ≥ 0.9) compared with a similar neonate who receives low FIO2 (≤0.3) for initial resuscitation?
(A) Lower rate of all-cause mortality at hospital discharge ✔
(B) Higher rate of morbidities of prematurity X
(C) Lower oxygen saturation (SpO2) at 5 minutes X
Gain insight on this topic, and many others, with Summaries of Emerging Evidence (SEE) 2025 – Volume 41B, now available. The content is aggregated from 30 international medical journals to streamline your learning and improve your practice.
The ideal fraction of inspired oxygen (FIO2) for initial resuscitation of neonates has been an unanswered question for many years. Although, the mortality benefit of using room air for initial resuscitation has been shown for term infants, comparable data are limited for preterm infants. Concerns regarding free radical–induced organ damage from oxidative stress have prevented the recommended use of high FIO2 in the preterm population as it has been linked to multiple morbidities of prematurity. However, it is unclear whether avoiding high FIO2 for initial resuscitation in extremely and very preterm infants (<32 weeks’ gestational age) has any mortality or morbidity benefit.
A group of investigators recently conducted a systematic review and an individual participant data network meta-analysis to evaluate the relative effectiveness of initial FIO2 on reducing mortality, morbidities of prematurity, and oxygen saturation (SpO2) at 5 minutes in preterm infants born at less than 32 weeks’ gestation. Included studies were randomized controlled trials with infants born at less than 32 weeks’ gestation that compared at least 2 initial oxygen concentrations for delivery room resuscitation, defined as low (≤0.3), intermediate (0.5–0.65), or high (≥0.90) FIO2. The authors included studies with interventions using static FIO2 of 1.0 without titration as well as interventions with low and intermediate FIO2 as long as the oxygen was titrated according to the clinical status of the infant. Infants were included regardless of umbilical cord clamping timing; singleton and multiple births were also included. Trials using static low and intermediate FIO2 concentrations were excluded. A total of 13 eligible trials were identified, with studies spanning from 1980 to 2023. Due to the nonavailability of individual participant data, only 12 trials were included in the data analysis (N = 1,055 infants). The primary outcome was all-cause mortality before hospital discharge while secondary outcomes were SpO2 at 5 minutes, SpO2 in a target range of 80% to 85% at 5 minutes, and morbidities of prematurity including severe intraventricular hemorrhage (grade III or IV), retinopathy of prematurity, and bronchopulmonary dysplasia.
A total of 125 deaths (12%) occurred across the 11 studies (N = 1,003 infants) that contributed to the primary outcome of mortality. High initial FIO2 demonstrated lower odds of death compared with low initial FIO2 when used for resuscitation (odds ratio [OR], 0.45; 95% credible interval [CrI], 0.23–0.86; low certainty of evidence) whereas high initial FIO2 possibly reduced mortality compared with intermediate FIO2 (OR, 0.34; 95% CrI, 0.11–0.99; very low certainty of evidence). Probability of reduced mortality with high, intermediate, and low initial FIO2 were 0.97, 0.02, and 0.01, respectively. No differences were found between the 3 intervention groups for morbidities of prematurity (high vs low FIO2): severe intraventricular hemorrhage (OR, 0.56; 95% CrI, 0.10–1.82), retinopathy of prematurity (OR, 1.17; 95% CrI, 0.58–2.20), and bronchopulmonary dysplasia (OR, 1.17; 95% CrI, 0.55–2.52). SpO2 at 5 minutes was higher in the high initial FIO2 group compared with the low initial FIO2 group (mean difference of SpO2, 9.02%; 95% CrI, 2.08–16.31). High initial FIO2 had higher odds of achieving SpO2 of 80% or greater at 5 minutes compared with low initial FIO2 (OR, 3.67; 95% CrI, 1.15–12.21).
In conclusion, a recent meta-analysis demonstrated that high initial FIO2 may be associated with reduced mortality compared with low initial FIO2 for delivery room resuscitation in preterm infants born at less than 32 weeks’ gestation; however, there was a low certainty of evidence. No differences were found in morbidities of prematurity with high initial FIO2 versus low initial FIO2.
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Date of last update: July 9, 2025
