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. (October 2018)

• Record Type: Journal Article
• Authors: Leviton, Alan; Joseph, Robert M.; Allred, Elizabeth N.; Fichorova, Raina N.; O'Shea, T. Michael; Kuban, Karl K.C.; Dammann, Olaf
• Is Part Of: Cytokine. Volume 110(2018)
• Page Start: 181
• Page End: 188
• Publication Date: 2018-10
• Subjects: Developmental outcome -- Neurodevelopment -- Reading -- Spelling -- Autism spectrum disorder -- Inflammation -- Very premature infant -- Interleukin-4 -- Interleukin-10; ADI-R Autism Diagnostic Interview-Revised -- ADOS-2 Autism Diagnostic Observation Schedule, Second edition -- ASD Autism Spectrum Disorder -- CCC-2 Children's Communication Checklist-2 (CCC-2) -- CSI-4 Child Symptom Inventory-4 -- DAS-II Differential Ability Scales, Second Edition -- ELGAN Extremely Low Gestational Age Newborn -- ICAM-1 Intercellular Adhesion Molecule-1 (CD54) -- IL-4 Interleukin-4 -- IL-8 Interleukin-8 (CXCL-8) -- IL-10 Interleukin-10 -- NEPSY-II A Developmental NEuroPSYchological Assessment, Second Edition -- OWLS Oral and Written Language Scales, Second Edition -- SCQ Social Communication Questionnaire -- SRS-2 Social Responsiveness Scale, Second Edition -- WIAT-III Wechsler Individual Achievement Test, Third Edition -- WM Working memory; Cytokines -- Periodicals; 571.844
• DOI: 10.1016/j.cyto.2018.05.004
• Languages: English
• ISSNs: 1043-4666

Abstract

Highlights: IL-4 and IL-10 are viewed as predominantly anti-inflammatory proteins. Extremely preterm (EP) newborns are at high risk of developmental limitations. These risks are heightened if they have systemic inflammation shortly after birth. The risks are heightened if they have high concentrations of IL-4 and IL-10. Abstract: 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, OWLS-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: IL-4 and IL-10 are viewed as predominantly anti-inflammatory proteins. Less commonly, high concentrations of IL-4 and IL-10 have been associated with adverse health outcomes. What is not known: 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: 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.