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Iron Depletion in the Substantia Nigra of Children With Prenatal Alcohol Exposure

Francesca Alves1,2, Amir Fazollahi3, Pawel Kalinowski1

  • 1The Florey Institute of neuroscience and Mental Health, Melbourne, Victoria, Australia.

Journal of Neurochemistry
|March 6, 2026
PubMed

Insights

Prenatal alcohol exposure (PAE) is linked to lower iron levels in specific brain regions, including the substantia nigra, even with first-trimester exposure. These findings suggest iron metabolism is a modifiable factor in fetal alcohol spectrum disorders (FASD).

Area of Science:

  • Neuroscience
  • Developmental Biology
  • Radiology

Background:

  • Prenatal alcohol exposure (PAE) affects 10%-60% of pregnancies, potentially causing fetal alcohol spectrum disorders (FASD) with cognitive, behavioral, and motor deficits.
  • Animal studies indicate PAE disrupts fetal iron homeostasis, but direct human brain evidence is limited.
  • Iron is crucial for neurodevelopment, including myelination and neurotransmitter synthesis; altered iron deposition may link PAE to adverse outcomes.

Purpose of the Study:

  • To investigate the association between PAE and brain iron levels at age 7 years.
  • To determine if the timing of PAE influences brain iron concentrations.
  • To provide the first human evidence of PAE's impact on brain iron homeostasis.

Main Methods:

  • Utilized quantitative susceptibility mapping (QSM), an MRI technique sensitive to iron, to assess regional brain iron in 38 cortical and subcortical areas.
  • Recruited children from the Asking Questions about Alcohol in Pregnancy (AQUA) prospective longitudinal cohort.
  • Categorized participants into unexposed, first-trimester-only exposed (PAE T1), and first-to-third-trimester exposed (PAE T1-3) groups.

Main Results:

  • Children with any PAE showed significantly lower QSM in the substantia nigra compared to unexposed children (p=0.011).
  • Substantia nigra QSM was reduced even with first-trimester-only exposure (p=0.004).
  • PAE was associated with regional cortical iron changes, including reductions in the superior parietal cortex and insula, and elevations in the postcentral gyrus.

Conclusions:

  • PAE is associated with region-specific alterations in brain iron levels in 7-year-old children.
  • Early PAE, particularly in the first trimester, significantly impacts substantia nigra iron.
  • These findings highlight altered iron homeostasis as a potential mechanism linking PAE to the neurodevelopmental challenges of FASD.

Keywords:
PAEQSMalchoholiron

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