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

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.

Author information

1
Boston Children's Hospital and Harvard Medical School, Boston, MA, USA. Electronic address: alan.leviton@childrens.harvard.edu.
2
Boston University School of Medicine, Boston, MA, USA.
3
Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.
4
Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
5
University of North Carolina School of Medicine, Chapel Hill, NC, USA.
6
Boston Medical Center and Boston University School of Medicine, Boston, MA, USA.
7
Tufts University School of Medicine, Boston, MA 02111, USA; Perinatal Neuroepidemiology Unit, Department of Gynecology and Obstetrics, Hannover Medical School, 30623 Hannover, Germany.

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: 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

PMID:
29763840
DOI:
10.1016/j.cyto.2018.05.004

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