Intrinsic Gestational Timing Governs Human Cerebellar Development After Preterm Birth

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Abstract
Intrinsic programs govern brain maturation, but whether preterm birth induces a persistent shift in these processes remains unknown. The human cerebellum provides a model of extrauterine development; its most rapid growth and circuit maturation occur during the third trimester, a period disrupted by early delivery. By leveraging multimodal in vivo and postmortem tissue analyses, we show that preterm birth constrains cerebellar maturation. Cerebellar growth and functional outcomes scaled with gestational age at birth, paralleled by cellular and spatial molecular programs marking incomplete granule cell maturation and impaired Purkinje cell structural refinement. These lineage-specific alterations indicate developmental asynchrony in prematurity. Thus, in preterm infants, gestational age at birth establishes a cerebellar maturational ceiling, such that postnatal age does not correspond to biological maturity.
Funding Information
  • Raynor's Cerebellar Project
  • Javits Award (R37NS109478)
  • Common Fund (K12HD001399)
  • Child Health Research Career Development Award (CHRCDA)
  • American SIDS Institute
  • Children‘s National Board of Visitors’ Grant
  • Developmental Disabilities Research Center (P50HD105328)

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