Estrogen and progesterone in immune dysfunction at childhood follow up of preterm infants

Philip Stewart; Dearbhla Byrne; Aoife Branagan; Johana Isaza-Correa; Lynne Kelly; Judith Meehan; Eleanor Molloy

P1-282

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ESPE Abstracts (2024) 98 P1-282

ESPE2024 Poster Category 1 Sex Endocrinology and Gonads 3 (6 abstracts)

Estrogen and progesterone in immune dysfunction at childhood follow up of preterm infants

Philip Stewart ¹ , Dearbhla Byrne ¹ , Aoife Branagan ¹ , Johana Isaza-Correa ^1,2 , Lynne Kelly ^1,2 , Judith Meehan ¹ & Eleanor Molloy ^1,2,3

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¹Trinity University College, Dublin, Ireland. ²TTMI, Dublin, Ireland. ³CHI Dublin, Dublin, Ireland

Background and Aims: Infants born prematurely have increased risk of multi-organ dysfunction and death throughout their lives. Males are particularly higher risk and susceptible to the adverse effects of infection related inflammation with poorer clinical outcomes. Immune function, hormone exposure and genetic factors play contributory roles. Physiological concentrations of female hormones hypothesised to have a role in immune development, could affect the expression of CD11b and TLR4 on previously premature neonates. We aimed to assess the influence of sex hormones on innate immune responses.

Methods: A prospective cohort study recruited ex preterm infants born <1500g and <32weeks, now aged 5 years old. Blood samples were treated with LPS, oestrogen (E2) and progesterone (PG) and compared with aged matched controls. Using flow cytometry, Toll-like receptor (TLR)-4 (recognition of lipopolysaccharide (LPS)) and CD11b (cell activation, migration) was analysed as a marker of innate immune function in neutrophils (CD66b+) and monocytes (CD14/16).

Results: In ex preterm children and age-matched controls (n = 25), there was significant upregulation of neutrophil CD11b expression when exposed to LPS (p value 0.001), E2 and LPS (p value 0.001), PG and LPS (p value 0.02) and E2, PG and LPS in combination (p value 0.0022). Classical monocyte CD11b was similarly upregulated by LPS (p value 0.02) E2 and LPS (p value 0.01), PG and LPS (p value 0.47) and combination of the three (p value (0.02)

Conclusion: Immune function is altered in ex preterm children and these dysregulated responses may increase risk of infection and complications. Immunomodulation has potential as a treatment for multiple end organ issues.