Association of Poor Family Functioning From Pregnancy Onward With Preadolescent Behavior and Subcortical Brain Development

Yllza Xerxa, Scott W Delaney, Leslie A Rescorla, Manon H J Hillegers, Tonya White, Frank C Verhulst, Ryan L Muetzel, Henning Tiemeier

16 Citations (Scopus)


Importance: The association of poor family functioning, a potent stressor, with child behavior is potentially long term and relevant for a person's well-being later in life. Whether changes in brain development underlie the associations with preadolescent behavior and help identify periods of vulnerability is unclear.

Objective: To assess the associations of poor family functioning from pregnancy onward with cortical, white matter, and subcortical volumes, and to examine the extent to which, in particular, hippocampal volume mediates the association of prenatal parental environmental exposures with child problem behavior in preadolescence.

Design, Setting, and Participants: This population-based cohort study, conducted from April 2002 to January 2006, was embedded in Generation R, a multiethnic population-based cohort from fetal life onward. All pregnant women living in Rotterdam, the Netherlands, with an expected delivery date between April 2002 and January 2006 were invited to participate. Of the 8879 pregnant women enrolled during pregnancy, 1266 mothers with no partner data and 490 with missing family functioning data were excluded, as well as 1 sibling of 32 twin pairs. After excluding an additional 657 children with poor imaging data quality or incidental findings, the final sample consisted of 2583 mother-child pairs. Data analysis was performed from March 1, 2019, to June 28, 2019.

Exposures: Mother- and father-rated poor family functioning was repeatedly measured by the General Functioning subscale of the Family Assessment Device.

Main Outcomes and Measures: Our primary hypothesis, formulated after data collection but before analysis, was that poor prenatal family functioning would be associated with smaller hippocampal and amygdala volumes in late childhood. High-resolution structural neuroimaging data of children aged 10 years were collected with a single 3-T magnetic resonance imaging system. Child emotional and behavioral problems were assessed with the Child Behavior Checklist.

Results: Data were available for 2583 children (mean [SD] age, 10.1 [0.6] years; 1315 girls [50.9%]). Data for parents included 2583 mothers (mean [SD] age, 31.1 [4.7] years; 1617 Dutch race/ethnicity [62.6%]) and 1788 fathers (mean [SD] age, 33.5 [5.3] years; 1239 Dutch race/ethnicity [69.3%]). Children exposed to prenatal maternal-reported poor family functioning had smaller hippocampal (B = -0.08; 95% CI, -0.13 to -0.02) and occipital lobe (B = -0.70; 95% CI, -1.19 to -0.21) volumes in preadolescence. There was no evidence for an association of exposure to poor family functioning at mid- or late childhood with brain morphology. Hippocampal volumes partially mediated the association of prenatal maternal-reported poor family functioning with preadolescent problem behavior (B = 0.08; 95% CI, 0.03-0.13), even after adjusting for prior child problems at age 1.5 years. Analyses of combined maternal and paternal family functioning ratings showed similar results, but associations were largely driven by maternal family functioning reports.

Conclusions and Relevance: In this population-based cohort study, prenatal maternal-reported poor family functioning was associated with a smaller hippocampus in preadolescents. This difference in brain structure may underlie behavioral problems and is a possible neurodevelopmental manifestation of the long-term consequences of poor family functioning for the child.

Original languageEnglish
JournalJAMA Psychiatry
Issue number1
Pages (from-to)29-37
Number of pages9
Publication statusPublished - 1 Jan 2021


  • Adult
  • Adverse Childhood Experiences
  • Amygdala/anatomy & histology
  • Child
  • Child Behavior/physiology
  • Family
  • Female
  • Gray Matter/anatomy & histology
  • Hippocampus/anatomy & histology
  • Humans
  • Longitudinal Studies
  • Magnetic Resonance Imaging
  • Male
  • Netherlands
  • Occipital Lobe/anatomy & histology
  • Pregnancy
  • Prenatal Exposure Delayed Effects/etiology
  • Problem Behavior
  • Stress, Psychological/complications
  • White Matter/anatomy & histology


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