Maternal sleep deprivation and developmental programming of brain aging trajectories in offspring

Maternal sleep deprivation (MSD) is a common but usually unnoticed issue during pregnancy, and in recent years, it has been increasingly recognised as an important prenatal stressor that may adversely influence maternal physiology, placental function, and fetal neurodevelopment. Sleep disturbances during pregnancy, including reduced sleep duration, fragmented sleep, poor sleep quality, circadian disruption, and rapid eye movement sleep restriction, have been associated with altered hypothalamic-pituitary-adrenal axis activity, systemic inflammation, oxidative stress, and impaired circadian regulation. Emerging evidence from clinical and preclinical studies suggests that these alterations may affect fetal neurogenesis, synaptic development, neuroimmune signaling, and maturation of brain circuits involved in cognition and emotional regulations. Within the framework of the Developmental Origins of Health and Disease, maternal sleep disturbances may contribute to epigenetic modifications, mitochondrial dysfunction, microglial activation, and altered neuroplasticity-related pathways, which are increasingly implicated in long-term neurological vulnerability. Experimental findings further indicate that prenatal sleep disruption may impair offspring cognitive performance, emotional behavior, and stress responsiveness, while potentially influencing biological pathways associated with brain aging-related processes. However, the extent to which MSD directly contributes to pathological brain aging in humans remains incompletely understood. Factors such as timing and duration of exposure, sex-specific responses, and postnatal environmental conditions may further influence offspring outcomes. Therefore, this narrative review critically summarizes current evidence regarding MSD and examines the molecular, cellular, and neurodevelopmental mechanisms through which prenatal sleep disturbances may influence long-term neurological health and vulnerability to brain aging-associated alterations in offspring.This graphical abstract illustrates the mechanistic framework connecting maternal sleep deprivation to the developmental programming of brain aging in offspring. [ MSD: maternal sleep deprivation; DOHaD: Developmental Origins of Health and Disease; 11β HSD2: 11β hydroxysteroid dehydrogenase type 2; ROS: reactive oxygen species; REM: rapid eye movement; HPA axis: hypothalamic pituitary adrenal axis; BDNF: brain derived neurotrophic factor].