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

Cytokine. 2018 Oct;110:181-188. doi: 10.1016/j.cyto.2018.05.004. Epub 2018 May 12.


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: What is not known: What this study adds.

Keywords: Autism spectrum disorder; Developmental outcome; Inflammation; Interleukin-10; Interleukin-4; Neurodevelopment; Reading; Spelling; Very premature infant.

Publication types

  • Multicenter Study
  • Observational Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Autism Spectrum Disorder / blood
  • Child
  • Cytokines / blood
  • Female
  • Gestational Age
  • Humans
  • Infant, Extremely Premature / blood*
  • Infant, Newborn
  • Inflammation / blood
  • Interleukin-10 / blood*
  • Interleukin-4 / blood*
  • Male
  • Neurodevelopmental Disorders / blood*
  • Parturition / blood
  • Pregnancy
  • Prospective Studies
  • Risk


  • Cytokines
  • IL10 protein, human
  • IL4 protein, human
  • Interleukin-10
  • Interleukin-4