Neuroanatomical Correlates Underlying the Association Between Maternal Interleukin 6 Concentration During Pregnancy and Offspring Fluid Reasoning Performance in Early Childhood

Jerod M Rasmussen; Alice M Graham; Lauren E Gyllenhammer; Sonja Entringer; Daniel S Chow; Thomas G O'Connor; Damien A Fair; Pathik D Wadhwa; Claudia Buss

doi:10.1016/j.bpsc.2021.03.007

Neuroanatomical Correlates Underlying the Association Between Maternal Interleukin 6 Concentration During Pregnancy and Offspring Fluid Reasoning Performance in Early Childhood

Biol Psychiatry Cogn Neurosci Neuroimaging. 2022 Jan;7(1):24-33. doi: 10.1016/j.bpsc.2021.03.007. Epub 2021 Mar 23.

Authors

Jerod M Rasmussen¹, Alice M Graham², Lauren E Gyllenhammer³, Sonja Entringer⁴, Daniel S Chow⁵, Thomas G O'Connor⁶, Damien A Fair², Pathik D Wadhwa⁷, Claudia Buss⁸

Affiliations

¹ Development, Health and Disease Research Program, University of California, Irvine, California; Department of Pediatrics, University of California, Irvine, California. Electronic address: rasmussj@hs.uci.edu.
² Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, Oregon.
³ Development, Health and Disease Research Program, University of California, Irvine, California; Department of Pediatrics, University of California, Irvine, California.
⁴ Development, Health and Disease Research Program, University of California, Irvine, California; Department of Pediatrics, University of California, Irvine, California; Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Medical Psychology, Berlin, Germany.
⁵ Department of Radiology, University of California, Irvine, California.
⁶ Departments of Psychiatry, Psychology, Neuroscience and Obstetrics & Gynecology, University of Rochester Medical Center, Rochester, New York.
⁷ Development, Health and Disease Research Program, University of California, Irvine, California; Department of Pediatrics, University of California, Irvine, California; Departments of Psychiatry and Human Behavior, Obstetrics & Gynecology, Epidemiology, University of California, Irvine, California.
⁸ Development, Health and Disease Research Program, University of California, Irvine, California; Department of Pediatrics, University of California, Irvine, California; Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Medical Psychology, Berlin, Germany. Electronic address: claudia.buss@charite.de.

Abstract

Background: Maternal inflammation during pregnancy can alter offspring brain development and influence risk for disorders commonly accompanied by deficits in cognitive functioning. We therefore examined associations between maternal interleukin 6 (IL-6) concentrations during pregnancy and offspring cognitive ability and concurrent magnetic resonance imaging-based measures of brain anatomy in early childhood. We further examined newborn brain anatomy in secondary analyses to consider whether effects are evident soon after birth and to increase capacity to differentiate effects of pre- versus postnatal exposures.

Methods: IL-6 concentrations were quantified in early (12.6 ± 2.8 weeks), mid (20.4 ± 1.5 weeks), and late (30.3 ± 1.3 weeks) pregnancy. Offspring nonverbal fluid intelligence (Gf) was assessed at 5.2 ± 0.6 years using a spatial reasoning task (Wechsler Preschool and Primary Scale of Intelligence-Matrix) (n = 49). T1-weighted magnetic resonance imaging scans were acquired at birth (n = 89, postmenstrual age = 42.9 ± 2.0 weeks) and in early childhood (n = 42, scan age = 5.1 ± 1.0 years). Regional cortical volumes were examined for a joint association between maternal IL-6 and offspring Gf performance.

Results: Average maternal IL-6 concentration during pregnancy was inversely associated with offspring Gf performance after adjusting for socioeconomic status and the quality of the caregiving and learning environment (R² = 13%; p = .02). Early-childhood pars triangularis volume was jointly associated with maternal IL-6 and childhood Gf (p_corrected < .001). An association also was observed between maternal IL-6 and newborn pars triangularis volume (R² = 6%; p = .02).

Conclusions: These findings suggest that the origins of variation in child cognitive ability can, in part, trace back to maternal conditions during the intrauterine period of life and support the role of inflammation as an important component of this putative biological pathway.

Keywords: Fluid intelligence; Fluid reasoning; Inferior frontal gyrus; Inflammation; Interleukin 6; Longitudinal MRI; Newborn; Pars triangularis.

Published by Elsevier Inc.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Brain
Child
Child, Preschool
Cognition*
Female
Humans
Infant
Infant, Newborn
Interleukin-6 / blood*
Magnetic Resonance Imaging
Pregnancy
Prenatal Exposure Delayed Effects*

Substances

IL6 protein, human
Interleukin-6

Abstract

Publication types

MeSH terms

Substances

Grants and funding