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Prenatal pregnancy-related anxiety predicts boys' ADHD symptoms via placental C-reactive protein

Shanshan Shao1, Jianqing Wang2, Kun Huang1

  • 1Department of Maternal, Child and Adolescent Health, School of Public Health, Anhui Medical University, No. 81 Meishan Road, Hefei, 230032, Anhui, China; Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People's Republic of China, No. 81 Meishan Road, Hefei, 230032, Anhui, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, No. 81 Meishan Road, Hefei, 230032, Anhui, China; Anhui Provincial Key Laboratory of Population Health and Aristogenics, Anhui Medical University, No. 81 Meishan Road, Hefei, 230032, Anhui, China.

Psychoneuroendocrinology
|July 19, 2020
PubMed

Insights

Pregnancy anxiety increases boys' risk for attention deficit hyperactivity disorder (ADHD), a link mediated by placental inflammation (CRP). This effect was not observed in girls, suggesting a sex-specific mechanism for ADHD development.

Area of Science:

  • Neuroscience
  • Developmental Psychology
  • Immunology

Background:

  • Maternal stress during pregnancy is linked to offspring externalizing behaviors, potentially in a sex-specific manner.
  • The interplay between maternal stress, immune activation, and offspring neurodevelopment in humans remains under-investigated.
  • Pregnancy-related anxiety is a significant stressor with potential implications for child neurodevelopment.

Purpose of the Study:

  • To investigate the association between pregnancy-related anxiety and attention deficit hyperactivity disorder (ADHD) symptoms in offspring.
  • To explore the mediating role of placental inflammatory markers in the relationship between maternal anxiety and ADHD, examining sex differences.
  • To provide direct human evidence on the combined effects of maternal stress, immune activation, and neurodevelopment.

Main Methods:

  • Prospective cohort study of 2926 pregnant women followed from pregnancy to 36 months postpartum.
  • Assessment of pregnancy-related anxiety using the Pregnancy-Related Anxiety Questionnaire at three time points.
  • Measurement of child ADHD symptoms via the Conners' Hyperactivity Index and analysis of nine inflammatory cytokines (including CRP mRNA) in placental tissues.

Main Results:

  • Pregnancy-related anxiety in at least two trimesters significantly increased ADHD risk in boys (aOR=3.37) but not in girls (aOR=1.02).
  • Structural equation modeling indicated that placental C-reactive protein (CRP) mRNA expression mediated the link between maternal anxiety and ADHD in boys (indirect effect: β=0.025, P=0.022).
  • No significant mediation was found for girls (indirect effect: β=0.005, P=0.589), highlighting a sex-specific pathway.

Conclusions:

  • Frequent pregnancy-related anxiety is a risk factor for ADHD symptoms in boys, independent of other confounding factors.
  • Placental inflammation, specifically elevated CRP mRNA expression, partially explains the sex bias in ADHD development linked to maternal anxiety.
  • These findings underscore the importance of maternal mental health during pregnancy for offspring neurodevelopment and suggest targeted interventions may be sex-specific.

Keywords:
ADHDC-reactive proteinPlacental inflammationPregnancy-related anxietySex

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