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Original Investigation
September 16, 2020

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

Author Affiliations
  • 1The Generation R Study Group, Erasmus University Medical Center, Rotterdam, the Netherlands
  • 2Department of Child and Adolescent Psychiatry, Erasmus University Medical Center, Rotterdam, the Netherlands
  • 3Department of Social and Behavioral Sciences, Harvard T. H. Chan School of Public Health, Boston, Massachusetts
  • 4Department of Psychology, Bryn Mawr College, Bryn Mawr, Pennsylvania
  • 5Department of Radiology, Erasmus University Medical Center, Rotterdam, the Netherlands
  • 6Child and Adolescent Mental Health Center, Mental Health Services, the Capital Region of Denmark, Copenhagen, Denmark
  • 7Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
JAMA Psychiatry. Published online September 16, 2020. doi:10.1001/jamapsychiatry.2020.2862
Key Points

Question  To what extent is the persistent association of poor prenatal family functioning with preadolescent problem behavior mediated by subcortical brain development?

Findings  In this population-based cohort study of 2583 children with neuroimaging data, smaller hippocampal volumes were found in preadolescents exposed to prenatal maternal-reported poor family functioning. Smaller hippocampal volumes partially mediated the association of prenatal maternal-reported poor family functioning with preadolescent problem behavior.

Meaning  Subcortical brain characteristics found after more than 10 years of follow-up may help clinicians understand why poor family functioning is associated with child neurodevelopment and well-being.


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.

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