Normal lymphocyte responses to mitogens in term and premature neonates following normal and abnormal intrauterine growth

Abstract

Cord blood lymphocyte responses to a panel of four mitogens were studied in 242 neonates using a whole blood technique. The patient population was divided into five gestational-age groups: 20–27.9, 28–32.9, 33–37.9, 38–41.9, and 42–44 weeks. Neonatal lymphocytes undergo a continuous reduction in proliferative responsiveness to the polyclonal ligands phytohemaglutinin (PHA) and concanavalin A (Con A) as gestation progresses from 20 to 44 weeks postconception. This is consistent with their change in unstimulated in vitro blastogenesis which when measured over the same developmental period is greatest in more immature neonates. Neonatal lymphocyte proliferative responsiveness to pokeweed mitogen (PWM) and staphylococcus protein A (SpA), however, was unrelated to gestational age. The influence of intrauterine nutritional deprivation on lymphocyte proliferative responses was studied in clinically uninfected newborns and compared to gestational age-matched controls with a normal nutritional status. Intrauterine nutritional deprivation was not associated with a decrease in mitogen-induced lymphocyte proliferation. Further, we explored the influence of several perinatal clinical settings commonly associated with fetal distress on cord blood lymphocyte responses to mitogens. Although perinatal stress in the form of low Apgar scores, meconium-stained amniotic fluid, and prolonged rupture of the amniotic membranes was not related to differences in mitogen induced lymphocyte proliferation, mode of delivery was. Cesarean section delivery as compared to vaginal delivery was associated with a significantly greater PHA-, Con A-, and SpA-induced neonatal lymphocyte response. Several alternative explanations for this finding are explored. Lastly, the purified protein thymosin fraction 5 was not associated with alteration in either neonatal or adult mitogen-induced lymphocyte proliferation.