RATIONALE: Very preterm infants (i.e. born before 32 weeks of gestation) are at risk of cerebral injury and long-term neurodevelopmental impairment. Cerebral near-infrared spectroscopy (NIRS) enables continuous monitoring of cerebral oxygenation to guide clinical management. Interest in NIRS has grown in recent years, highlighting the need for better evidence to support its clinical efficacy in improving brain development and reducing neurological sequelae. This is an update of a Cochrane review first published in 2017.
OBJECTIVES: To evaluate the beneficial and harmful effects of cerebral near-infrared spectroscopy (NIRS) monitoring versus no NIRS or blinded NIRS monitoring in very preterm infants.
SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, three trial registries, and conference abstracts up to August 2025. We also checked reference lists of included studies and relevant systematic reviews.
ELIGIBILITY CRITERIA: We included randomised clinical trials (RCTs) comparing cerebral NIRS monitoring versus no NIRS or blinded NIRS monitoring (where the treating healthcare professionals were unaware of the oxygenation levels) in very preterm infants.
OUTCOMES: Our critical outcomes included all-cause mortality at longest follow-up, major neurodevelopmental disability in children aged 18 to 24 months (a composite outcome including cerebral palsy, severe neurodevelopmental impairment, blindness, and profound hearing impairment), and major brain injury prior to discharge. Our important outcomes included chronic lung disease at 36 weeks' gestational age, proven necrotising enterocolitis prior to discharge, retinopathy of prematurity (stage ≥ III) prior to discharge, and severe adverse reactions prior to discharge.
RISK OF BIAS: We used Cochrane's original risk of bias tool (RoB 1).
SYNTHESIS METHODS: We conducted meta-analyses using fixed-effect models to calculate risk ratios (RRs) and 95% confidence intervals (CIs) for all outcomes. We summarised the certainty of the evidence according to GRADE methods.
INCLUDED STUDIES: We included five parallel-group RCTs published between 2016 and 2023 that enroled a total of 2415 infants, with sample sizes ranging from 23 to 1600 infants per trial. The mean gestational age ranged from 26.1 weeks to 33.1 weeks. Four trials were conducted in multiple hospitals in high-income countries across North America, Asia, and Europe. The remaining trial took place in a single hospital in Austria. The comparator was no NIRS in two trials and blinded NIRS in three trials. In all trials, infants in the NIRS group were treated according to brain oxygen saturation values with specific preset treatment regimens, while those in the control group received standard or usual care regardless of NIRS monitoring values. The trials involved infants with varying start times and durations of NIRS monitoring. Only one trial reported major neurodevelopmental disability, and two trials reported retinopathy of prematurity (stage ≥ III). All five trials provided data for the other main outcomes of this review. We identified five ongoing trials.
SYNTHESIS OF RESULTS: NIRS monitoring compared with no NIRS or blinded NIRS monitoring likely results in little to no difference in all-cause mortality at longest follow-up (RR 0.99, 95% CI 0.82 to 1.18; I² = 46%; 5 studies, 2415 participants; moderate-certainty evidence) and major brain injury diagnosed by brain ultrasound prior to discharge (RR 0.99, 95% CI 0.84 to 1.17; I² = 13%; 5 studies, 2415 participants; moderate-certainty evidence). The evidence is very uncertain about the effect of NIRS monitoring compared with blinded NIRS monitoring on major neurodevelopmental disability in children aged 18 to 24 months (RR 1.28, 95% CI 0.50 to 3.29; 1 study, 115 participants; very low-certainty evidence). NIRS monitoring compared with no NIRS or blinded NIRS monitoring likely results in little to no difference in chronic lung disease at 36 weeks of gestational age (RR 0.95, 95% CI 0.86 to 1.06; I² = 43%; 5 studies, 2415 participants; moderate-certainty evidence), proven necrosing enterocolitis prior to discharge (RR 1.08, 95% CI 0.85 to 1.37; I² = 0%; 5 studies, 2415 participants; moderate-certainty evidence), retinopathy of prematurity (stage ≥ 3) prior to discharge (RR 1.15, 95% CI 0.86 to 1.54; I² = 0%; 2 studies, 1745 participants; moderate-certainty evidence), and severe adverse reactions prior to discharge (RR 9.41, 95% CI 0.51 to 174.44; I² not applicable; 5 studies, 2415 participants; moderate-certainty evidence).
AUTHORS' CONCLUSIONS: Overall, cerebral NIRS monitoring in very preterm infants likely results in little to no benefit for most measured outcomes. Compared with conventional monitoring, cerebral NIRS monitoring in very preterm infants likely results in little to no difference in all-cause mortality at longest follow-up and in major brain injury diagnosed by brain ultrasound prior to discharge, and we are unsure about its effect on major neurodevelopmental disability in children aged 18 to 24 months. Furthermore, NIRS monitoring likely results in little to no difference in the risk of chronic lung disease at 36 weeks' gestational age, proven necrotising enterocolitis prior to discharge, severe retinopathy of prematurity prior to discharge, and severe adverse reactions prior to discharge. Future randomised trials in very preterm infants should provide continuous NIRS monitoring from birth until cardiorespiratory stability to more accurately assess the potential benefits of the intervention. Further research is needed to understand and quantify performance differences among available NIRS devices and to evaluate their effects on long-term clinical outcomes. Few (if any) vital sign monitoring methods have demonstrated patient-relevant benefits in RCTs. For cerebral oximetry in preterm infants, trials using clinically meaningful endpoints (e.g. neurodevelopment at two years assessed with the Bayley Scales) may be infeasible due to the large sample sizes required. In this context, surrogate outcomes, such as electrophysiological markers of hypoxic brain injury, may offer a feasible alternative, provided they are rigorously validated against clinical endpoints.
FUNDING: This Cochrane review had no dedicated funding.
REGISTRATION: Protocol (2015): doi.org/10.1002/14651858.CD011506 Original review (2017): doi.org/10.1002/14651858.CD011506.pub2 Review update (2025): doi.org/10.1002/14651858.CD011506.pub3.
