Treatment With Inhaled Nitric Oxide and General Intelligence in Preterm Children in Two European Cohorts

Acta Paediatr. 2025 Sep;114(9):2346-2356. doi: 10.1111/apa.70118. Epub 2025 May 6.

Abstract

Aim: To investigate whether treatment with inhaled nitric oxide is associated with cognitive performance at age 5-6 years in preterm-born children.

Methods: We analysed preterm children from two large European cohort studies, the German Neonatal Network (GNN) (N = 3606) and the French EPIPAGE-2 cohort (N = 2579) admitted to neonatal care and followed up at age 5-6 years. Both cohorts had recorded data on iNO treatment. General cognitive ability was tested with IQ tests. Classification and Regression trees analysis was used to identify prenatal, perinatal and neonatal, clinical and social-environmental predictors of IQ.

Results: In both cohorts, treatment with inhaled nitric oxide was not associated with IQ at age 5-6 years. Analysis identified maternal educational level, gestational age at discharge from hospital, intraventricular haemorrhage and maternal country of birth as important factors associated with IQ scores.

Conclusion: Treatment with inhaled nitric oxide was neither negatively nor positively associated with IQ at age 5-6 years. Neonatal and brain health, as well as socioeconomic factors are important for cognitive performance in early childhood.

Keywords: IQ; cognitive function; inhaled nitric oxide; minipuberty; preterm birth.

Publication types

  • Multicenter Study

MeSH terms

  • Administration, Inhalation
  • Child
  • Child, Preschool
  • Cohort Studies
  • Female
  • Humans
  • Infant, Newborn
  • Infant, Premature
  • Intelligence* / drug effects
  • Male
  • Nitric Oxide* / administration & dosage

Substances

  • Nitric Oxide