Abstract

BackgroundAdvanced biological aging, as measured by epigenetic aging indices, is associated with early mortality and morbidity. Associations between maternal epigenetic aging indices in pregnancy and pregnancy outcomes, namely gestational length and birthweight, have not been assessed. The purpose of this study was to examine whether epigenetic age during pregnancy was associated with gestational length and birthweight.ResultsThe sample consisted of 77 women from the Los Angeles, CA, area enrolled in the Healthy Babies Before Birth study. Whole blood samples for DNA methylation assay were obtained during the second trimester (15.6 ± 2.15 weeks gestation). Epigenetic age indices GrimAge acceleration (GrimAgeAccel), DNAm PAI-1, DNAm ADM, and DNAm cystatin C were calculated. Gestational length and birthweight were obtained from medical chart review. Covariates were maternal sociodemographic variables, gestational age at blood sample collection, and pre-pregnancy body mass index. In separate covariate-adjusted linear regression models, higher early second trimester GrimAgeAccel, b(SE) = − .171 (.056), p = .004; DNAm PAI-1, b(SE) = − 1.95 × 10−4 (8.5 × 10−5), p = .004; DNAm ADM, b(SE) = − .033 (.011), p = .003; and DNAm cystatin C, b(SE) = 2.10 × 10−5 (8.0 × 10−5), p = .012, were each associated with shorter gestational length. Higher GrimAgeAccel, b(SE) = − 75.2 (19.7), p < .001; DNAm PAI-1, b(SE) = − .079(.031), p = .013; DNAm ADM, b(SE) = − 13.8 (3.87), p = .001; and DNAm cystatin C, b(SE) = − .010 (.003), p = .001, were also associated with lower birthweight, independent of gestational length.DiscussionHigher maternal prenatal GrimAgeAccel, DNAm PAI-1, DNAm ADM, and DNAm cystatin C were associated with shorter gestational length and lower birthweight. These findings suggest that biological age, as measured by these epigenetic indices, could indicate risk for adverse pregnancy outcomes.

Highlights

  • Advanced biological aging, as measured by epigenetic aging indices, is associated with early mortality and morbidity

  • Independent of covariates, higher early second trimester maternal GrimAgeAccel, DNA methylation (DNAm) plasminogen activator inhibitor (PAI)-1, DNAm ADM, and DNAm cystatin C were significantly associated with shorter gestational length; no other epigenetic clock estimate variables were significant

  • These findings suggest that maternal epigenetic age acceleration indices, GrimAgeAccel, DNAm ADM, and DNAm cystatin, are associated with risk for adverse pregnancy outcomes, and highlight the potential role of maternal biological aging in birth outcomes

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Summary

Introduction

As measured by epigenetic aging indices, is associated with early mortality and morbidity. Associations between maternal epigenetic aging indices in pregnancy and pregnancy outcomes, namely gestational length and birthweight, have not been assessed. The purpose of this study was to examine whether epigenetic age during pregnancy was associated with gestational length and birthweight Adverse pregnancy outcomes, such as preterm birth (< 37 weeks gestation) and low birthweight (< 2500 g), affect approximately 10% and 8.3% of pregnancies in the USA, respectively [1, 2]. Older maternal chronological age is associated with higher rates of adverse birth outcomes, including shortened gestational length and lower birthweight [17,18,19,20,21], suggesting that biological aging might be involved in risk. Minimal research has tested whether maternal biological aging, as opposed to chronological aging, is a prognostic marker

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