Accelerated biological aging linked to increased preterm birth risk

There is an association between accelerated biological aging and preterm birth (PTB), according to a recent study published in the American Journal of Obstetrics & Gynecology.¹

PTB is the leading cause of morbidity and mortality among US neonates, with a rate of 10.47% reported in 2021. However, information about the pathophysiology of PTB remains lacking. However, data has indicated a potential link between histologic patterns and preterm birth.²

Currently established risk factors are associated with chronic stress which often leads to increased allostatic load.¹ This can cause accelerated biological aging. However, it is unclear whether accelerated biological aging is directly linked to PTB.

Epigenetic modifications such as Cytosine-guanine nucleotide methylation (CpG DNA methylation [DNAm]) can be used to measure biological age. Health outcomes associated with biological age include heart disease, cancer, and reduced lifespan, indicating a need to understand this biological process.

To determine the association between accelerated biological aging and PTB, investigators conducted a prospective cohort study. Participants included singleton, nonanomalous pregnancies with high spontaneous preterm birth risk, determined by historical factors or current pregnancy complications.

Exclusion criteria included fetal aneuploidy or lethal fetal anomalies in pregnancy, multiple pregnancy, and being unable to provide consent in English or Spanish. The last menstrual period and ultrasound were used to determine gestational age.

Blood samples were obtained at enrollment and stored using a PAXgene blood DNA tube (Thermo Fisher Scientific Inc, Waltham, MA). Additional data collected included maternal demographics, medical and obstetrical history, antenatal course, and pregnancy outcomes.

The AllPrep DNA/RNA/miRNA Universal Kit (Qiagen, Valencia, CA) was used to isolate genomic DNA from frozen samples. Density distributions were utilized to visualize data. Biological aging was measured using the composite biomarker AgeAccelGrim.

DNAm beta values, female sex, and patient chronological age data was recorded. PTB at under 34 weeks’ gestation was reported as the primary outcome of the analysis.

Secondary outcomes included PTB at under 37 and 28 weeks’ gestation. The models included factors associated with PTB, such as low socioeconomic status, chronological age, estimated peripheral cell counts, and gestational age at blood sampling.

There were 163 individuals included in the final analysis, delivering at a median 37 weeks’ gestation. Rates of delivery under 37 weeks’ gestation, under 34 weeks’ gestation, and under 28 weeks’ gestation were 47.9%, 38.7%, and 20.9%, respectively. Of PTBs, 11.5% were medically indicated

The odds of self-identifying as White and having a hypertensive disorder of pregnancy were reduced among patients delivering under 34 weeks’ gestation. These patients were also more likely to have their blood sampled later. However, other demographic and baseline characteristics did not significantly differ between groups.

A transvaginal cervical length assessment was reported in 84.6% of participants. The midtrimester transvaginal cervical length was shorter in pateints delivering under 34 weeks’ gestation, and these patients were more likely to have a cervical length under 25 mm.

The overall cohort had a median AgeAccelGrim of -0.044 years. For patients delivering at term, the median AgeAccelGrim was -0.35 years, with AgeAccelGrim values inversely proportional to delivery gestational age. At under 37 weeks, under 34 weeks, and under 28 weeks, the median AgeAccelGrim values were 0.40 years, 0.51 years, and 1.05 years, respectively.

All 7 individual clock components were higher among patients delivering under 34 weeks’ gestation. However, only the estimated DNAm of plasminogen activation inhibitor 1 reached statistical significance.

Participants with accelerated biological aging delivered at a median 31 weeks’ gestation. The odds of delivering at under 37 weeks’, under 34 weeks’, and under 28 weeks’ gestation were increased in these patients, at 58.5%, 53.7%, and 36.6%, respectively, vs 44.3%, 33.6%, and 15.6%, respectively.

These results indicated an association between accelerated biological aging and PTB. Investigators recommended validation of these findings through intervention-based randomized controlled trials before and after treatment.

References

1. Gascoigne EL, Roell KR, Eaves LA, et al. Accelerated epigenetic clock aging in maternal peripheral blood and preterm birth. Am J Obstet Gynecol. 2024;230:559.e1-9. doi:10.1016/j.ajog.2023.09.003
2. Krewson C. Understanding histologic patterns in spontaneous preterm birth recurrence. Contemporary OB/GYN. April 22, 2024. Accessed May 24, 2024. https://www.contemporaryobgyn.net/view/understanding-histologic-patterns-in-spontaneous-preterm-birth-recurrence