Clinical Guidelines for Management of Infants Born before 25 Weeks of Gestation: How Representative Is the Current Evidence?

Objective: To determine whether management guidelines for infants born extremely preterm are representative for those infants <25 weeks of gestation.

Study design: Three guidelines were reviewed: the 2022 European Consensus Guidelines on the Management of Respiratory Distress Syndrome, the 2017 American Academy of Pediatrics Guidelines for Perinatal Care, and the 2020/2021 International Liaison Committee on Resuscitation guidelines. All referenced studies for overlapping recommendations were reviewed. Data extracted included the total number and proportion of infants <25 weeks of gestation in the original articles referred in the guidelines. Where the exact number of infants <25 weeks of gestation was unobtainable, this was conservatively estimated by statistical deduction.

Results: Eight recommendations were included in 2 or more guidelines: (1) antenatal corticosteroids, (2) antenatal magnesium sulfate, (3) delayed cord clamping, (4) thermoregulation at birth, (5) initial oxygen concentration at birth, (6) continuous positive airway pressure, (7) surfactant, and (8) parenteral nutrition. In total, 519 studies (n = 409 986) informed these 8 recommendations, of which 335 (64.5%) were randomized controlled trials (n = 78 325). Across all studies, an estimated 59 360 (14.5%) infants were <25 weeks of gestation. Within randomized controlled trials alone, an estimated 5873 (7.5%) infants were <25 weeks of gestation. A total of 196 (37.8%) studies did not include any infants <25 weeks of gestation.

Conclusions: Infants born <25 weeks of gestation are not well-represented in the evidence used to develop major clinical guidelines for infants born extremely preterm. Future studies should provide evidence for this population as a distinct cohort.