Intermittent hypoxia and maxillary growth restriction: evidence from a neonatal rat model

Abstract

Purpose: Intermittent hypoxia (IH), a recurring episodes of oxygen deprivation followed by reoxygenation, is a hallmark of sleep-disordered breathing (SDB), including obstructive sleep apnoea (OSA). IH has been implicated in various neonatal complications: neurodevelopmental impairments, cardiovascular dysfunction, and growth restriction. However, its effects on craniofacial development remain underexplored. Given the rapid postnatal craniofacial growth in both humans and animals in early age, this study investigates the impact of IH exposure on maxillary development in neonatal rats. Materials and Methods: Eighteen 5-day-old male Sprague–Dawley rats were randomly assigned to normoxia (N) or IH groups. From postnatal day 7 (PND7) to PND14, the IH group was exposed to 20 cycles of hypoxia per hour (4%O₂ nadir, 21%O₂ peak) for 8 hours daily. Maxillary dimensions were evaluated using lateral and dorsoventral cephalometric radiographs. Data were analysed via multiple linear regression, adjusting for body weight (p < 0.05). Results: IH exposure significantly reduced maxillary height, length, and intermolar width at the first molars. However, the maxilla-to-mandible length ratio remained unchanged, suggesting preserved proportional jaw growth. These changes resembled craniofacial features seen in paediatric OSA, such as maxillary constriction and palatal narrowing. Conclusion: One week of IH exposure during a critical developmental window impaired maxillary growth in neonatal rats. These findings highlight a possible link between early-life hypoxia and altered craniofacial development, with potential relevance to paediatric OSA. Further studies incorporating angular, histological, and molecular assessments are needed to better understand underlying mechanisms.