The risk of neurodevelopmental disorders at age 10 years associated with blood concentrations of interleukins 4 and 10 during the first postnatal month of children born extremely preterm

Background: Interleukin (IL)-4 and IL-10 are viewed mainly as anti-inflammatory cytokines. Yet, high concentrations have also been associated with inflammation-related diseases in newborns. Methods: We measured the concentrations of IL-4 and IL-10, as well as IL-8 and ICAM-1 in blood specimens collected on postnatal day 21 (N = 555), day 28 (N = 521), and both days 21 and 28 (N = 449) from children born extremely preterm (EP) (< 28 weeks gestation) who at age 10 years had a DAS-II IQ Z-score >2 (which approximates a score of > 70) and the following assessments, CCC-2, and CSI-4, DAS-II, NEPSY-II, SCQ, and WIAT-III. Selected children also were assessed with the ADI-R and the ADOS-2. We modeled the risk of low scores or dysfunctions associated with top quartile concentrations of IL-4 and IL-10 on each day and on both days. Results: The risks of low scores on the Animal Sorting and Arrows components of the NEPSY-II, both components of the OWLS-II, and the PseudoWord and Spelling components of the WIAT-III were heightened among children who had top quartile concentrations of IL-4 on postnatal days 21 and 28. Children who had high concentrations of IL-10 on days 21 and 28, individually and collectively, were at increased risk of low scores on the WIAT-III Spelling component. High concentrations of IL-4 on day 28 were associated with autism spectrum disorder (ASD). High concentrations of IL-10 on day 28 were also associated with a doubling of ASD risk, but this did not achieve statistical significance. Top quartile concentrations of IL-4 and IL10 on both days were not associated with increased risk of social, language, or behavioral dysfunctions. Conclusion: Among children born EP, those who had top quartile concentrations of IL-4 and/or IL-10 on postnatal days 21 and/or 28 were more likely than their peers to have low scores on components of the NEPSY-II, OWLS-II, and WIAT-III assessments, as well as identification as having an ASD. What is known: center dot IL-4 and IL-10 are viewed as predominantly anti-inflammatory proteins. center dot Less commonly, high concentrations of IL-4 and IL-10 have been associated with adverse health outcomes. What is not known: center dot We do not know to what extent elevated concentrations of IL-4 and IL-10 during the third and fourth postnatal weeks are associated with increased risk of neurocognitive, behavioral, language, and social dysfunctions among children born very preterm. What this study adds: center dot Children born very preterm who have elevated concentrations of IL-4, but not IL-10, on both postnatal days 21 and/or 28 are at increased risk of low scores on assessments of processing speed, visuospatial skills, listening comprehension, oral expression, and reading and spelling achievement.