Highlights • Postnatal hydrocortisone alters growth factors and reduces rat body and organ growth. • High doses of postnatal hydrocortisone results in delayed memory in adult rats. • High-dose hydrocortisone causes adverse metabolic events in adult rats. Abstract Background and purpose Hydrocortisone (HC), at different dosages, is used in critically ill newborns for lung stability, blood pressure support, and prevention of chronic lung disease (CLD). Its long-term effects on postnatal growth are not well studied. We hypothesized that early exposure to high doses of HC adversely affects growth, growth factors, metabolic hormones, and neurological outcomes, persisting in adulthood. Experimental design Rat pups received a single daily intramuscular dose of HC (1 mg/kg/day, 5 mg/kg/day, or 10 mg/kg/day on days 3, 4 & 5 postnatal age (P3, P4, P5). Age-matched controls received equivalent volume saline. Body weight, linear growth, and neurological outcomes were monitored. Animals were sacrificed at P21, P45, and P70 for blood glucose, insulin, IGF-I, GH, leptin, and corticosterone levels. Liver mRNA expression of IGFs and IGFBPs were determined at P21 and P70. Memory and learning abilities were tested using the Morris water maze test at P70. Results HC suppressed body weight and length at P12, P21 and P45, but by P70 there was catchup overgrowth in the 5 and 10 mg/kg/day groups. At P70 blood insulin, IGF-I, GH, and leptin levels were low, whereas blood glucose, and liver IGFs and IGFBPs were high in the high dose groups. High HC also caused delayed memory and learning abilities at P70. Conclusions These data demonstrate that while higher doses of HC may be required for hemodynamic stability and prevention of CLD, these doses may result in growth deficits, as well as neurological and metabolic sequelae in adulthood. [ABSTRACT FROM AUTHOR]