Early Postnatal Hypocapnia and Hypercapnia in Ventilated Preterm Infants: Incidence and Associations with Adverse Outcomes

Background/Objectives: Abnormalities in the partial pressure of carbon dioxide (PCO₂) can occur during respiratory support and may contribute to adverse neonatal outcomes. This study aimed to assess the incidence of early hypocapnia and hypercapnia in mechanically ventilated preterm infants and their major associated outcomes. Methods: A single-center retrospective cohort study (2017–2024) was conducted in preterm infants < 32 weeks’ gestation who required >24 hours of invasive ventilation within the first 3 days of life. Perinatal-neonatal data were retrieved from the medical database. Admission blood gas values (arterial and capillary-venous) and the maximum and minimum PCO₂ in the first 72 hours were evaluated. Normocapnia was defined as PCO₂ 35–45 mmHg, hypocapnia 45 mmHg. Primary outcomes were the incidence of PCO₂ abnormalities; secondary outcomes included death or severe brain injury (SBI), SBI alone, and bronchopulmonary dysplasia (BPD) among survivors. Logistic regression identified independent predictors of the secondary outcomes. Results: Among the 134 infants evaluated, most experienced both hypercapnia and hypocapnia. Hypercapnia occurred in 81.3% of infants, and hypocapnia in 93.2%. Death or SBI was observed in 51.5%, and SBI alone in 42.5%. Gestational age < 28 weeks, air-leak syndromes, and pulmonary hemorrhage were independent predictors of death or SBI. Among survivors, hypercapnia and gestational age < 28 weeks independently predicted BPD. Infants with adverse outcomes had higher maximum PCO₂ values and greater PCO₂ variability, although these were not independent predictors of SBI or death. Conclusions: PCO₂ instability is highly prevalent in ventilated preterm infants necessitating personalized ventilation management. Extreme prematurity remains the strongest risk factor for adverse outcomes, while hypercapnia independently predicts BPD.