BackgroundPrenatal serotonin reuptake inhibitor (SRI) antidepressant exposure is associated with newborn neurobehavioural disturbances, but it remains unclear whether this reflects a transient pharmacologic condition or an altered neurodevelopmental trajectory emerging in utero from sustained gestational SRI exposure. AimThis study explored longitudinal relationships between third-trimester fetal physiology and newborn neurobehaviour, and determined whether early neurobehavioural continuity is shaped by prenatal SRI or depression exposure. MethodsParticipants were 127 pregnant mothers and their fetal-newborn offspring. Four groups were defined based on antenatal depressive symptoms and SRI treatment: Control (n = 51), Depressed (unmedicated; n = 35), SRI-Depressed (n = 26) and SRI-Non-Depressed (n = 15). Doppler measures of fetal heart rate (fHR), motor activity and vascular hemodynamics were obtained at 36-weeks' gestation, then newborn neurobehavioural maturity was evaluated at postnatal day-7. Partial least squares analysis was used to identify latent correlations between fetal-newborn measures; associations were further studied with hierarchical regression testing group moderation. ResultsTwo dimensions described 74 % of the covariance between fetal physiologic and newborn neurobehavioural measures (permuted p < 0.05). Three latent fetal-newborn relationships were significantly moderated by group: (1) lower fHR variability, and (2) greater fHR decelerations, predicted lower alertness/orientation scores but only in SRI-Depressed-group newborns; and (3) lower fetal cerebrovascular resistance predicted lower motor scores in Depressed-group newborns. SRI treatment to euthymia was not associated with fetal-newborn neurobehavioural disturbances. ConclusionsMaternal depression, both unmedicated and SRI-treated with persistent/poorly-managed mood symptoms, differentially shaped fetal-newborn neurobehavioural continuity. These findings suggest that neurobehavioural disturbances may predate birth, and underscore the importance of effective mental health management during pregnancy.