Preterm neonates show marked leukopenia and lymphopenia that are associated with increased regulatory T-cell values and diminished IL-7

Abstract

IntroductIon: current advances in neonatology have improved survival among preterm and low-birth-weight infants. however, the risk of neonatal death in preterm infants is much greater than in full-term neonates and is frequently associated with infections. Methods: Little is known about the immune status of preterm neonates; therefore, we analyzed the frequency and absolute counts of different immune populations in 211 cord blood samples taken from very-preterm to full-term neonates. results: We found that absolute counts of all the immune subsets analyzed (i.e., monocytes, granulocytes, B cells, natural killer (NK) cells, cD4 + , and cD8 + T cells) were markedly lower in preterm infants than in full-term infants. surprisingly, we observed that regulatory T cells (Tregs) were the only cell subset that did not decrease in preterm infants, and their frequency was even higher than in full-term infants. dIscussIon: Tregs are crucial to maternal-fetal tolerance, but their suppressive role could be also implicated in the leukopenia observed in preterm infants. We did not observe differences in thymic function, but we found that plasma levels of interleukin (IL)-7 and the frequency of its receptor were significantly decreased in preterm infants. Our results could help to identify leukopenia and to implement immune therapies that significantly diminish mortality in preterm neonates. r ecent developments in neonatology and improvements in technology to manage preterm neonates have significantly increased the survival of very-preterm neonates (less than 28 wk of gestation) and very-low-birth-weight infants (less than 1,500 g) (1). However, the relative risk of neonatal death is much greater for preterm infants than for full-term infants, and prematurity has become the leading cause of perinatal morbidity and mortality (2,3). Along with decreasing gestational age (GA), low birth weight is also associated with increased perinatal morbidity and mortality (4). Among the causes responsible for this increased mortality, neonatal sepsis and bronchopulmonary dysplasia are the most frequent causes of death in premature newborns (3).In fact, the most important factors that predispose to infection are prematurity and/or low birth weight.Little is known about innate immunity in premature neonates and the capacity of their immune systems to fight against infections. Several authors have reported differences in phenotype and function of lymphocytes between healthy newborns, children, and adults (5). The immune response of preterm infants is assumed to be immature, although quantitative data on differences in immune capacity between preterm and full-term infants are scant.The objective of this study was to investigate whether the high incidence of infections in preterm infants could be due to an immunodeficiency and, if so, to identify which immune cell populations are implicated in the absence of an adequate immune response. We performed a comprehensive analysis of the frequency and absolute counts of several cell populations in preter...

Lymphocyte subpopulations in premature infants: an observational study

“…This is consistent with the differences reported between premature and term infants at birth8 9 13 16 as well as in previous preterm infant longitudinal studies 20 22. Berrington et al 22 reported lower total lymphocyte count, T cells, B cells and T helper cells at 2 months of age in 18 preterm infants compared with term infants; some of these populations (total lymphocytes, T cells and T helper cells) remained significantly lower at their final sample at 6 months of age.…”

“…Previous studies analysed cord blood samples, and it may be that any significant effect of antenatal steroids had resolved by 2 months of age 8 13…”

Effect of chorioamnionitis on regulatory T cells in moderate/late preterm neonates

“…This maternal alloantigen stimulus explains the presence of a high percentage of Treg in CB in early preterm (29w) compared to full term infants [33,34,37]. Treg prevalence then gradually decreases with GA, reaching a stable number at birth [34,37]. In our study, Treg frequencies did not differ significantly between moderate/late preterm and term neonates.…”

“…During fetal life a substantial number of maternal cells cross the placenta to reside in lymphoid tissues, inducing the development of Treg that keep maternal-fetal tolerance [35,36]. This maternal alloantigen stimulus explains the presence of a high percentage of Treg in CB in early preterm (29w) compared to full term infants [33,34,37]. Treg prevalence then gradually decreases with GA, reaching a stable number at birth [34,37].…”

Reference Intervals of Platelets, Lymphocytes and Cardiac Biomarkers in Umbilical Cord Blood

“…Preterm infants are highly susceptible to invasive infections, which are leading causes of mortality and longterm morbidity. Treg levels and gestational age inversely correlated in several studies [48][49][50]. Preterm infants have higher Treg levels than full-term newborns.…”