Neurodevelopmental outcomes at age 5 years among children born very preterm and surviving after persistent pulmonary hypertension of the newborn: EPIPAGE-2 cohort study

Abstract

Objective

To determine whether pulmonary hypertension (PH) is associated with higher risk of adverse neurodevelopmental outcome at age 5 in a population-based cohort of 22–31⁺⁶ preterm children.

Study design

In the EPIPAGE-2 French prospective population-based cohort of preterm children born in 2011, the neurodevelopmental outcome of children with PH was collected at 5 years. The primary outcome was a composite measure with four levels of neurodevelopmental disabilities: severe, moderate, mild, no disability, based on cerebral palsy, visual, hearing or cognitive deficiencies, behavioral difficulties and developmental coordination disorders. Secondary outcomes were autism spectrum disorders and school attendance. Missing data were multiply imputed. Developmental measures were compared using generalized estimating equations models.

Results

Of the 3007 eligible children, 1825 were analyzed, of whom 79 (4.3 %) were PH+. At age 5, 36.9 % (95 % CI, 26.0–47.8) of PH + children had moderate to severe overall neurodevelopmental disabilities compared with 17.9 % (95 % CI, 16.1–19.8) of PH–children, P < 0.001. Significant differences at 5 years between the PH+ and PH– groups were observed for cerebral palsy (CP) (6 % versus 2.3 % for severe CP, P = 0.003), cognitive deficiency (31.7 % versus 15.0 %, P < 0.001) and developmental coordination disorders (27.1 % versus 11.7 %, P < 0.001). There were no significant differences in behavioral difficulties and autism spectrum disorders. Normal school was attended by 69.2 % of PH + children versus 88.3 % of PH– children.

Conclusion

In this nationwide population-based cohort of extremely preterm and very preterm infants, moderate to severe overall neurodevelopmental disability at age 5 was significantly associated with neonatal PH.