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 May 12;110:181-188. doi: 10.1016/j.cyto.2018.05.004.
Leviton A, Joseph RM, Allred EN, Fichorova RN, O’Shea TM, Kuban KKC, Dammann O7.
Boston Children’s Hospital and Harvard Medical School, Boston, MA, USA.
Boston University School of Medicine, Boston, MA, USA.
Boston Children’s Hospital and Harvard Medical School, Boston, MA, USA.
Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA.
University of North Carolina School of Medicine, Chapel Hill, NC, USA. Boston Medical Center and Boston University School of Medicine, Boston, MA, USA. 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.
