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

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.

FIGURE 1

Flow diagram of the participant recruitment and selection process for the GNN 2009–2016 cohort study.

FIGURE 2

Flow diagram of the participant recruitment and selection process for the EPIPAGE‐2 cohort study.

FIGURE 3

Classification tree resulting from RPART analysis of early predictors and risk factors associated with IQ at the age of 5–6 years based on GNN 2009–2016 data. Note: Important early factors associated with IQ at age 5–6 years were gestational age at discharge of less than 39 weeks, maternal postsecondary school education and higher, no IVH (intraventricular haemorrhage) or IVH Grade 1 or 2. That is, those children that were discharged from the NICU before 39 weeks of gestational age, whose mother achieved an educational level of postsecondary school and who had no or a mild IVH were more likely to have an above average IQ score of 105 at age 5–6 years.

FIGURE 4

Classification tree resulting from RPART analysis of early predictors and risk factors associated with IQ at the age of 5–6 years based on EPIPAGE‐2 data. Note: Important early factors associated with IQ at age 5–6 years were maternal education of at least postsecondary school level, a gestational age at discharge of less than 42 weeks and France as the mother's country of birth. That is, children whose mother had a high educational level, who were discharged from the NICU before 42 weeks of gestational age and whose mother was born in France were more likely to have an above average IQ score of 103 at age 5–6 years.