Neonatal handling modifies maternal care and lactational adaptations to gestational protein restriction

Prenatal nutritional conditions influence offspring metabolic health and may also program maternal physiology and caregiving during lactation. Early postnatal experience can modify maternal-infant interactions and thus modulate maternal physiological and behavioral adaptations induced by gestational undernutrition. Although species differences must be considered, this early postnatal window in rodents approximates human early infancy. We tested whether neonatal handling, an early-life manipulation that increases maternal care, modifies the effects of maternal protein restriction during gestation and early lactation on maternal behavior, milk composition, and lactogenic hormones. Wistar rat dams received a control (22% protein) or low-protein (8%, isoenergetic) diet throughout gestation and the first week of lactation. Litters were assigned to either neonatal handling (10 min/day, postnatal days 1-6) or undisturbed rearing with their dams. We measured maternal caloric intake, gestational weight gain, pup growth, maternal licking and grooming, milk macronutrients on postnatal day 6, and maternal serum prolactin, corticosterone, and insulin. Thirty-seven dams were included (8-10 per treatment group), and litter size did not differ between groups. Maternal low-protein diet significantly reduced pup body weight and milk protein content, while neonatal handling significantly increased maternal licking/grooming in low-protein dams and reversed the reduction in milk protein concentration. Additionally, neonatal handling decreased insulin levels in control dams, but had no effect in low protein dams, while prolactin and corticosterone were not altered between groups. Together, these findings indicate that early postnatal experience can modify a maternal phenotype induced by gestational undernutrition, including maternal care and lactational composition, with a metabolic signature involving insulin.