Maternal epigenetic age acceleration in early pregnancy, gestational duration, and spontaneous preterm birth among Black women in the NuMom2b study
- 1Columbia University
Abstract
ImportancePreterm birth is a leading cause of neonatal morbidity and mortality and disproportionately affects Black birthing people in the United States. DNA methylation-based measures of biological aging may capture physiologic dysregulation relevant to birth timing. We aim to determine whether maternal epigenetic age acceleration in early pregnancy is associated with gestational duration, spontaneous preterm birth (sPTB), and small for gestational age (SGA) among Black nulliparous pregnant individuals.
MethodsThis is a secondary data analysis of the prospective, multicenter Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be (nuMoM2b). Participants enrolled in eight US clinical research sites from 2010 to 2014 were followed through delivery; DNAm arrays were processed in 2024, and the current analysis was conducted in 2026. Participants were nulliparous individuals with singleton pregnancies who self-identified as Black. Maternal peripheral blood DNA methylation was measured at 6-13 weeks gestation using the Illumina MethylationEPIC array. The primary aging metric was standardized GrimAge2 age acceleration. Principal Components versions of the Horvath, Hannum, PhenoAge, GrimAge, and DNAmTL clocks, and DunedinPACE, were used in additional analyses. Delivery data was abstracted from medical records in the NuMom2b study. Outcomes were gestational duration in days, based on the best obstetric estimate, adjudicated sPTB before 37 completed weeks, and SGA. Primary linear and logistic regression models adjusted for maternal age, smoking, gestational age at blood draw, and estimated blood cell composition. Secondary models added education and body mass index (BMI) as additional covariates. Fetal sex interaction effects were tested.
ResultsAmong 931 participants (mean age = 23.46 [SD=5.33] years), 55 (5.9%) experienced sPTB. Each 1-SD higher GrimAge2 acceleration was associated with 1.32 fewer days of gestation ({beta}, -1.32 days; 95% CI, -2.36 to -0.28; P=.01) and higher odds of sPTB (odds ratio, 1.51; 95% CI, 1.13-2.02; P=.01). Results were slightly attenuated but remained significant for sPTB when controlling for education and BMI. Epigenetic age acceleration was not associated with SGA. Results were not significantly different by fetal sex.
Conclusions and RelevanceGreater first-trimester maternal GrimAge2 acceleration was associated with shorter gestation and 51% higher odds of sPTB but was not associated with SGA among Black nulliparous participants. The association with sPTB persisted after adjustment for socioeconomic and metabolic characteristics, warranting further evaluation of whether GrimAge2 improves early-pregnancy prediction of sPTB value beyond these factors.
Related
- Epigenetic gestational age acceleration and indicators of BMI trajectories in childhood
- Association of third-trimester maternal lipid levels with adverse pregnancy outcomes in women with gestational diabetes mellitus: a retrospective single-center study using intrapartum data
- Maternal serum retinol, vitamin K, and ferritin profiles during pregnancy, gestational diabetes mellitus, and offspring neurodevelopment: a prospective case-control study
- Epigenetic age acceleration enhances prediction of overall survival in early-stage non-small cell lung cancer
- Pregnancy Complicated by Citrin Deficiency and Gestational Diabetes Mellitus: Perioperative Metabolic Management and Postoperative Analgesic Challenges Following Caesarean Delivery
BibTeX
@misc{scorza2026maternal,
title = {{Maternal epigenetic age acceleration in early pregnancy, gestational duration, and spontaneous preterm birth among Black women in the NuMom2b study}},
author = {P. Scorza and H. Wu and P. Reho and Y. Zhao and V. Barcelona},
howpublished = {medRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.22.26366150},
url = {https://www.medrxiv.org/content/10.64898/2026.10.22.26366150v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Maternal epigenetic age acceleration in early pregnancy, gestational duration, and spontaneous preterm birth among Black women in the NuMom2b study
AU - P. Scorza
AU - H. Wu
AU - P. Reho
AU - Y. Zhao
AU - V. Barcelona
PY - 2026
DA - 2026/10/22
PB - medRxiv
DO - 10.64898/2026.10.22.26366150
UR - https://www.medrxiv.org/content/10.64898/2026.10.22.26366150v1
AB - ImportancePreterm birth is a leading cause of neonatal morbidity and mortality and disproportionately affects Black birthing people in the United States. DNA methylation-based measures of biological aging may capture physiologic dysregulation relevant to birth timing. We aim to determine whether maternal epigenetic age acceleration in early pregnancy is associated with gestational duration, spontaneous preterm birth (sPTB), and small for gestational age (SGA) among Black nulliparous pregnant individuals. MethodsThis is a secondary data analysis of the prospective, multicenter Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be (nuMoM2b). Participants enrolled in eight US clinical research sites from 2010 to 2014 were followed through delivery; DNAm arrays were processed in 2024, and the current analysis was conducted in 2026. Participants were nulliparous individuals with singleton pregnancies who self-identified as Black. Maternal peripheral blood DNA methylation was measured at 6-13 weeks gestation using the Illumina MethylationEPIC array. The primary aging metric was standardized GrimAge2 age acceleration. Principal Components versions of the Horvath, Hannum, PhenoAge, GrimAge, and DNAmTL clocks, and DunedinPACE, were used in additional analyses. Delivery data was abstracted from medical records in the NuMom2b study. Outcomes were gestational duration in days, based on the best obstetric estimate, adjudicated sPTB before 37 completed weeks, and SGA. Primary linear and logistic regression models adjusted for maternal age, smoking, gestational age at blood draw, and estimated blood cell composition. Secondary models added education and body mass index (BMI) as additional covariates. Fetal sex interaction effects were tested. ResultsAmong 931 participants (mean age = 23.46 [SD=5.33] years), 55 (5.9%) experienced sPTB. Each 1-SD higher GrimAge2 acceleration was associated with 1.32 fewer days of gestation ({beta}, -1.32 days; 95% CI, -2.36 to -0.28; P=.01) and higher odds of sPTB (odds ratio, 1.51; 95% CI, 1.13-2.02; P=.01). Results were slightly attenuated but remained significant for sPTB when controlling for education and BMI. Epigenetic age acceleration was not associated with SGA. Results were not significantly different by fetal sex. Conclusions and RelevanceGreater first-trimester maternal GrimAge2 acceleration was associated with shorter gestation and 51% higher odds of sPTB but was not associated with SGA among Black nulliparous participants. The association with sPTB persisted after adjustment for socioeconomic and metabolic characteristics, warranting further evaluation of whether GrimAge2 improves early-pregnancy prediction of sPTB value beyond these factors.
ER -