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Male fetus susceptibility to maternal inflammation: C-reactive protein and brain development

Published online by Cambridge University Press:  02 December 2019

Sharon K Hunter ,
M. Camille Hoffman Open the ORCID record for M. Camille Hoffman [Opens in a new window] ,
Angelo D'Alessandro ,
Kathleen Noonan ,
Anna Wyrwa ,
Robert Freedman Open the ORCID record for Robert Freedman [Opens in a new window]  and
Amanda J. Law Open the ORCID record for Amanda J. Law [Opens in a new window]
Sharon K Hunter*
Affiliation:
Departments of Psychiatry, University of Colorado Denver School of Medicine, Aurora, Colorado80045, USA
M. Camille Hoffman
Affiliation:
Departments of Psychiatry, University of Colorado Denver School of Medicine, Aurora, Colorado80045, USA Obstetrics and Gynecology, Division of Maternal and Fetal Medicine, University of Colorado Denver School of Medicine, Aurora, Colorado80045, USA
Angelo D'Alessandro
Affiliation:
Biochemistry and Molecular Genetics, University of Colorado Denver School of Medicine, Aurora, Colorado80045, USA
Kathleen Noonan
Affiliation:
Departments of Psychiatry, University of Colorado Denver School of Medicine, Aurora, Colorado80045, USA
Anna Wyrwa
Affiliation:
Departments of Psychiatry, University of Colorado Denver School of Medicine, Aurora, Colorado80045, USA
Robert Freedman
Affiliation:
Departments of Psychiatry, University of Colorado Denver School of Medicine, Aurora, Colorado80045, USA
Amanda J. Law
Affiliation:
Departments of Psychiatry, University of Colorado Denver School of Medicine, Aurora, Colorado80045, USA Cell and Developmental Biology, University of Colorado Denver School of Medicine, Aurora, Colorado80045, USA
*
Author for correspondence: Sharon K. Hunter, E-mail: [email protected]
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Abstract

Background

Maternal inflammation in early pregnancy has been identified epidemiologically as a prenatal pathogenic factor for the offspring's later mental illness. Early newborn manifestations of the effects of maternal inflammation on human fetal brain development are largely unknown.

Methods

Maternal infection, depression, obesity, and other factors associated with inflammation were assessed at 16 weeks gestation, along with maternal C-reactive protein (CRP), cytokines, and serum choline. Cerebral inhibition was assessed by inhibitory P50 sensory gating at 1 month of age, and infant behavior was assessed by maternal ratings at 3 months of age.

Results

Maternal CRP diminished the development of cerebral inhibition in newborn males but paradoxically increased inhibition in females. Similar sex-dependent effects were seen in mothers' assessment of their infant's self-regulatory behaviors at 3 months of age. Higher maternal choline levels partly mitigated the effect of CRP in male offspring.

Conclusions

The male fetal-placental unit appears to be more sensitive to maternal inflammation than females. Effects are particularly marked on cerebral inhibition. Deficits in cerebral inhibition 1 month after birth, similar to those observed in several mental illnesses, including schizophrenia, indicate fetal developmental pathways that may lead to later mental illness. Deficits in early infant behavior follow. Early intervention before birth, including prenatal vitamins, folate, and choline supplements, may help prevent fetal development of pathophysiological deficits that can have life-long consequences for mental health.

Keywords

Child developmentcholineC-reactive proteinpregnancyprenatal exposure delayed effectssensory gating
Type
Original Articles
Information
Psychological Medicine , Volume 51 , Issue 3 , February 2021 , pp. 450 - 459
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Copyright
Copyright © Cambridge University Press 2019

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