Neuro-immuno-teratogenicity of drugs used in neonatal pharmacotherapy in relation to the ontogenic stage at the time of their administration

The risk of functional teratogenicity of two drugs used in neonatal pharmac otherapy was studied: indomethacin (INDO) and dexamethasone (DEX). Model ex periments were carried out in Wistar strain rats, breed Konarovice, which r eceived single subcutaneous drug injection (INDO 2 mg/kg, DEX 1 mg/kg) on p ostnatal day 4 (PD:4; model of human fetus/preterm newborn of 6-7-month-ges tational age) or on postnatal day 9 (PD:9; model of full-term human neonate ). The rats were followed up during development (body weight, maturation) t ill late adult;hood (age 6-8 months) using tests of cognition, immune react ivity and biochemical brain analysis. The results evaluated by comparing tr eated and control litter-mates indicated that the functional teratogenic ri sk was significantly higher in DEX than in INDO. DEX-rats revealed disorgan ization of developmental processes: retardation of body growth, but acceler ation of sensory development (pinna and eye opening), retarded male sexual maturation. Adult DEX-rats (age 6 months) of both series (PD:4, PD:9) had d eficit of short-term memory (social recognition test). Disturbances of immu ne reactivity (decrease of humoral and rise of cell-mediated immune respons e) appeared both in adult INDO and DEX-rats (age 7 months), but only in the PD:9 series i.e. when the drugs were administered at a higher stage of the ontogenic development simulating neonatal period in humans. This finding m ay be warning from the clinical point of view for the neonatological practi ce.