310 - Exposure to pre-eclampsia is associated with altered neonatal adaptive and innate immune phenotype.

Poster Number: 310
Publication Number: 310.124

Mariana Brewer, Cohen Children's Medical Center, Forest Hills, NY, United States; Shanika Uduwana, Stamford Health, Bronx, NY, United States; Toni P. Iurcotta, NewYork-Presbyterian Morgan Stanley Children's Hospital, Oakland Gardens, NY, United States; Clifford S. Deutschman, Cohen Children's Medical Center, Lake Success, NY, United States; Matthew D. Taylor, Northwell Health, Manhasset, NY, United States

Background: Preeclampsia (PEC) affects 3-17% of pregnancies & has serious consequences for the mother & fetus. Maternal immunopathology in PEC is well studied but less is known regarding the immunological effects on newborns.

Objective: Our objective was to assess innate & adaptive immune cells in premature infants w. & w.o. exposure to PEC.

Design/Methods: Infants born at < 29 wks & ≥ 500 gms admitted to two level 3 & 4 NICUs in NY were recruited. Mothers w. PEC were identified per the EMR. Controls were born to mothers w.o. PEC, chronic hypertension, or chorioamnionitis. Blood samples were collected on day 0-7 & at 3-4 wks. Peripheral blood mononuclear cells were isolated & stained for flow cytometry. Two-tailed Mann-Whitney Test, Fisher’s exact test, 2-way repeated measures ANOVA, & mixed-effects repeated measures analysis w. Sidak correction for multiple comparisons were used. Differences were defined as statistically significant at the level of p < 0.05.

Results: 9 PEC-exposed babies & 9 age-matched controls were included in the analysis. The PEC group had a higher incidence of intrauterine growth restriction. Controls had more preterm labor. In the 1st wk there was no difference in proportions of innate cells between the 2 groups. PEC-exposed babies had a significant increase in the proportion of CD11b+ cells between 1 wk & 3-4 wks, primarily due to an increase in monocytes (Fig 1A). The proportion of B cells was not different between the 2 groups at birth, but PEC-exposed babies had a lower proportion at 3-4 wks (Fig 1B). The proportion of total T cells & CD4 T cells was low at birth & normalized at 3-4 wks in the PEC group. The proportion of CD8 T cells in the control group increased at 3-4 wks & was significantly higher than in the PEC group. The proportion of regulatory CD4 T cells (Tregs), was higher at birth in the PEC group (Fig 1C). The PEC group had lower CD4 & CD8 central memory (CM) & CD8 effector memory (EM) T cells in the 1st wk. Over time, the proportion of CD4 EM, CD8 EM, & CD8 CM T cells increased. This was associated in an increase in CD4 & CD8 effector T cells at 3-4 wks in the PEC group (Fig 2A). Stimulated expression of IL4 by CD4 & CD8 T cells was higher in the PEC group at 1 wk. By 3-4 wks, there was no difference in IL4 production between the 2 groups (Fig 2B).Conclusion(s): PEC-exposed premature babies have an altered immune phenotype w. greater Th2 skewing at birth & persistent alterations in immune cells at 3-4 wks, which may have significant implications for their risk of neonatal inflammatory disorders including bronchopulmonary dysplasia, necrotizing enterocolitis, & sepsis.
Innate and adaptive immune cells in PEC-exposed premature babies over time.PEC-exposed premature babies are born with low T cells and CD4 T cells which normalized at 3-4 weeks. In contrast T reg cells are increased at birth in PEC-exposed babies. Although there are no differences at birth, PEC-exposed babies have increased CD11b+ cells and low B cells at 3-4 weeks GA.
CD4 and CD8 T cell subsets and IL4 expression.The PEC group had lower CD4 & CD8 central memory (CM) & CD8 effector memory (EM) T cells in the 1st wk which normalized over time. Stimulated expression of IL4 by CD4 & CD8 T cells was higher in the PEC group at 1 wk.