Patterns of Neonatal and Neurodevelopmental Comorbidities in Neonates of <29 Weeks' Gestation

Introduction: Multi-morbidity is a known cause of adverse outcomes and resource utilization in adults. Our objective was to describe the co-occurrence of neonatal morbidities and their association with neurodevelopmental outcomes in preterm neonates.

We included 17,438 preterm neonates of <29 weeks' gestation admitted to Canadian neonatal intensive care units between 2010 and 2020, of whom 7,943 children had neurodevelopmental information. Neonatal outcomes were mortality, late-onset sepsis, necrotizing enterocolitis, and severe neurological injury. The outcomes were neurodevelopmental impairments, with significant impairment defined as any of: Bayley Scales of Infant and Toddler Development-third edition (Bayley-III) score of <70, cerebral palsy with Gross Motor Function Classification System (GMFCS) of ≥3, hearing amplification, or bilateral visual impairment; and severe impairment defined as any of: Bayley-III score of <55, cerebral palsy with GMFCS of 4-5, or bilateral blindness.

The mean (standard deviation) gestational age was 26.1 (1.6) weeks and 54.5% were male. Any neonatal mortality/morbidity occurred in 40.1% of children. Among survivors, 16.3% had significant neurodevelopmental impairment and 5.8% had severe neurodevelopmental impairment. However, 51% of children with significant impairment and 43% with severe neurodevelopmental impairment had no neonatal morbidities. Late-onset sepsis (aOR 1.60, 95% CI: 1.36, 1.88), necrotizing enterocolitis (aOR 1.91, 95% CI: 1.36, 2.69), and severe neurological injury (aOR 3.54, 95% CI: 2.85, 4.38) were associated with significant neurodevelopmental impairment among survivors. An increase in the count of neonatal morbidities correlated with a rise in the count of neurodevelopmental impairments.

Sixty percent of infants of <29 weeks' gestation experienced no adverse neonatal outcomes and the majority were free of significant neurodevelopmental impairment. Neonatal morbidities had a direct and combined association with neurodevelopmental impairment.