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Randomized Controlled Trial
. 2025 Dec;29(12):1759-1770.
doi: 10.1007/s10995-025-04186-4. Epub 2025 Oct 24.

Mid-Trimester Allostatic Load and Spontaneous Preterm Birth in a Cohort of Pregnant Women Living with HIV in Zambia

Katelyn J Rittenhouse  1 , Bellington Vwalika  2 , Yuri V Sebastião  3 , Rachel S Resop  3 , Humphrey Mwape  4 , Kristina De Paris  5 , Mwansa K Lubeya  2 , Margaret P Kasaro  4 , Jeffrey S A Stringer  3 , Joan T Price  3
Affiliations
Randomized Controlled Trial

Mid-Trimester Allostatic Load and Spontaneous Preterm Birth in a Cohort of Pregnant Women Living with HIV in Zambia

Katelyn J Rittenhouse et al. Matern Child Health J. 2025 Dec.

Abstract

Objectives: Maternal HIV is associated with preterm birth (PTB). In resource-rich settings, spontaneous preterm birth (SPTB) has been linked to biomarkers of stress. We examined the association between allostatic load and SPTB among women with HIV.

Methods: In a nested case-cohort analysis of a randomized trial of intramuscular progesterone to prevent PTB in women with HIV in Lusaka, Zambia, we measured 15 midtrimester plasma biomarkers from 4 domains: cardiovascular, immune, metabolic, and neuroendocrine. SPTB was defined as delivery <37wks preceded by spontaneous labor or membrane rupture. A composite ALI was calculated by summing Z-scores from all markers (ALI-15); another was calculated from a 7 marker subset (ALI-7) with Z-score differences >0.1 between outcome groups. We estimated SPTB time-to-event curves and hazard ratios (HR) between ALI quartiles.

Results: Of 800 women enrolled in IPOP (2015-2017), 51 (6%) had SPTB. We randomly selected 107 participants, including 6 with SPTB (cases). We then selected all remaining cases (n=45), yielding a final sample of 152. Z-score distributions of systolic blood pressure, heart rate, HDL, triglycerides, hemoglobin A1C, albumin, and 25-OH Vitamin D were included in ALI-7. Participants in the fourth quartile of ALI-7 were more likely to experience SPTB (HR 2.49, 95% CI 1.15-5.40) than participants in the second quartile; this association was attenuated when quartile groups were defined by ALI-15 (HR 1.24, 95% CI 0.59-2.60).

Conclusions: High ALI among women with HIV was associated with SPTB. A seven marker ALI appeared a more meaningful indicator of risk than one composed of all measured markers.

Keywords: Allostatic load; HIV; Pregnancy; Preterm birth; Stress; Zambia.

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Conflict of interest statement

Declarations. Competing Interests: The authors declare no competing interests. Ethical Approval: The IPOP trial is registered with clinicaltrials.gov (NCT03297216) and has ongoing approval by the University of Zambia Biomedical Research Ethics Committee and the University of North Carolina Institutional Review Board. Consent to Participate: All study participants provided written informed consent prior to study enrollment. Consent for Publication: Not applicable.

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