Longitudinal changes in hormonal and immune profiles associated with preterm birth among pregnant women in Zambia

Abstract Background Spontaneous preterm birth (SPTB) remains a major cause of neonatal morbidity and mortality, particularly in sub-Saharan Africa. Although endocrine and immune pathways are implicated in the initiation of preterm labour, longitudinal evidence from African populations remains limited. This study investigated longitudinal changes in maternal hormonal and systemic immune profiles associated with SPTB in Zambia. Methods A prospective longitudinal cohort study was conducted under Preventing Preterm Births in Zambia (ZAPPs) among pregnant women attending the Women and New-born Hospital, Lusaka, Zambia, between January 2023 and December 2024. Women were enrolled during the first trimester and followed until delivery, with maternal serum collected during the first, second, and third trimesters. Concentrations of progesterone, estradiol, insulin-like growth factor-1 (IGF-1), corticotropin-releasing hormone (CRH), cortisol, and eight cytokines were measured using enzyme-linked immunosorbent assays and multiplex immunoassays, respectively. Participants were classified according to delivery outcome as SPTB (< 37 completed weeks) or term birth (≥ 37 weeks). Results Of 100 women enrolled, 65 with complete longitudinal data were included in the analysis, comprising 31 SPTB and 34 term births. Estradiol concentrations were significantly higher in the SPTB group during the second trimester (median 14,934.5 vs. 6,483.8 pg/mL; p = 0.042). IGF-1 concentrations were significantly lower among women with SPTB during the second (37.25 vs. 61.96 ng/mL; p = 0.006) and third trimesters (6.76 vs. 22.07 ng/mL; p = 0.018). Progesterone was significantly lower in the SPTB group during the third trimester (63.47 vs. 246.72 ng/mL; p = 0.010). CRH and cortisol did not differ significantly between groups. None of the measured cytokines showed statistically significant between-group differences at any trimester, although MIP-1α showed a trend toward higher concentrations in the SPTB group during the third trimester (p = 0.074). Conclusions SPTB was associated with distinct trimester-specific endocrine alterations, particularly increased second-trimester estradiol and reduced IGF-1 and late-pregnancy progesterone. In contrast, maternal circulating cytokines showed limited differentiation between SPTB and term pregnancies. Larger longitudinal studies are warranted to validate these endocrine trajectories and determine their potential value for early identification of women at risk of SPTB.