Oxytocin and early life stress in late preterm newborns: an exploratory study

Oxytocin, a neuropeptide traditionally associated with labor and lactation, has been increasingly recognized for its broader roles, including maintaining physiological stability amidst environmental challenges. Previous studies on preterm infants have reported inconsistent results regarding oxytocin responses to maternal contact. The present study investigated peripheral oxytocin levels in late preterm newborns (34 +0 - 36 +6 weeks gestation), an epidemiologically relevant and neurodevelopmentally vulnerable subgroup of preterm infants. Fifty newborns (males 56%, median gestational age = 36.1 weeks) were enrolled between April 2022 and September 2023. Timing and type of first maternal contact (within the first hour post-birth or later; skin-to-skin or not), maternal mental health, attachment, and tactile interactions during the first two days of life were assessed using self-report questionnaires. Neonatal oxytocin levels were measured from blood samples collected after 48 hours of life. Higher oxytocin levels were observed in twins ( p = 0.05, d = 0.67), newborns delivered by caesarean section ( p = 0.002, d = 1.14), and those who experienced delayed first maternal contact ( p = 0.005, d = 1.18) or lacked skin-to-skin contact ( p = 0.001, d = 1.35). Oxytocin levels were also positively correlated with maternal age ( rho = 0.38, p = 0.02). In multivariate analyses, lack of skin-to-skin contact predicted higher oxytocin levels after 48 hours of life ( p =.019, η²ₚ =.27). Although interpretation is limited by the absence of data on maternal oxytocin administration - which, despite ongoing debate on its placental transfer, may account for the observed differences - our results reinforce previous speculations on the context-dependent nature of oxytocin regulation in preterm infants. Elevated oxytocin levels under stressful conditions may reflect an adaptive neuroendocrine response potentially buffering the developing brain against excessive glucocorticoid exposure. • Oxytocin (OT) regulation in preterm infants is dynamic and context-dependent • OT may rise due to early-life stress and protect the brain from glucocorticoid excess • Lack of skin-to-skin was an independent predictor of higher 48hour-OT • A zero-separation paradigm should be advocated for all late-preterms