ABSTRACT
BACKGROUND: Epigenetic clocks use CpG DNA methylation to estimate biological age. Acceleration is associated with cancer, heart disease, and shorter life span. Few studies evaluate DNA methylation age and pregnancy outcomes. AgeAccelGrim is a novel epigenetic clock that combines 7 DNA methylation components. OBJECTIVE: This study aimed to determine whether maternal biological aging (via AgeAccelGrim) is associated with early preterm birth. STUDY DESIGN: A prospective cohort of patients with singleton pregnancies and at high risk of spontaneous preterm birth delivering at a tertiary university hospital were included in this study. Genome-wide CpG methylation was measured using the Illumina EPIC BeadChip (Illumina, Inc, San Diego, CA) from maternal blood samples obtained at <28 weeks of gestation. AgeAccelGrim and its 7 DNA methylation components were estimated by the Horvath DNA methylation age online tool. Positive values are associated with accelerated biological aging, whereas negative values are associated with slower biological aging relative to each subject's age. The primary outcome was preterm birth at <34 weeks of gestation (any indication). The secondary outcomes were preterm birth at <37 and <28 weeks of gestation. AgeAccelGrim was analyzed as a continuous variable and in quartiles. Exploratory analyses evaluated each of the 7 DNA methylation components included in the composite AgeAccelGrim. Data were analyzed by chi-square test, t test, rank-sum test, logistic regression (controlling a priori for maternal age, cell counts, low socioeconomic status, and gestational age at the time of sample collection), and Kaplan-Meier survival analyses. The log-rank test was used to test the equality of the survival functions. RESULTS: Overall, 163 patients met the inclusion criteria. Of the patients, 48%, 39%, and 21% delivered at <37, <34, and <28 weeks of gestation, respectively. The median AgeAccelGrim was -0.35 years (interquartile range, -2.24 to 1.31) for those delivering at term. Those delivering preterm had higher AgeAccelGrim values that were inversely proportional to delivery gestational age (preterm birth at <37 weeks of gestation: +0.40 years [interquartile range: -1.21 to +2.28]; preterm birth at <34 weeks of gestation: +0.51 years [interquartile range: -1.05 to +2.67]; preterm birth at <28 weeks of gestation: +1.05 years [interquartile range: -0.72 to +2.72]). Estimated DNA methylation of the 7 epigenetic clock component values was increased among those with preterm birth at <34 weeks of gestation, although the differences were only significant for DNA methylation of plasminogen activation inhibitor 1. In regression models, AgeAcccelGrim was associated with an elevated risk of preterm birth with increasing magnitude for increasing severity of preterm birth. For each 1-year increase in the AgeAccelGrim value (ie, each 1-year increase in biological age compared with chronologic age), the adjusted odds of preterm birth were 11% (adjusted odds ratio, 1.11; 95% confidence interval, 1.00-1.24), 13% (adjusted odds ratio, 1.13; 95% confidence interval, 1.01-1.26), and 18% (adjusted odds ratio, 1.18; 95% confidence interval, 1.04-1.35) higher for preterm birth at <37, <34, and <28 weeks of gestation, respectively. Similarly, individuals with accelerated biological aging (≥75th percentile AgeAccelGrim) had more than double the odds of preterm birth at <34 weeks of gestation (adjusted odds ratio, 2.36; 95% confidence interval, 1.10-5.08) and more than triple the odds of preterm birth at <28 weeks of gestation (adjusted odds ratio, 3.89; 95% confidence interval, 1.61-9.38). The adjusted odds ratio for preterm birth at <37 weeks of gestation was 1.73 but spanned the null (adjusted odds ratio, 1.73; 95% confidence interval, 0.81-3.69). In Kaplan-Meier survival analyses, those in the highest AgeAccelGrim quartile delivered the earliest (log-rank P value of <.001). CONCLUSION: Accelerated biological aging was associated with preterm birth among high-risk patients. Future research confirming these findings and elucidating factors that slow biological aging may improve birth outcomes.
ABSTRACT
This expert review aimed to assess current literature on the effect and tracking of physical activity during pregnancy and associated outcomes. Self-reported physical activity may be inaccurate given the subjective nature of the questionnaires. The accelerometer ActiGraph is considered the "gold standard" to objectively measure physical activity. However, other more user-friendly wearable devices are now widely available and may accurately track physical activity. Conclusive data from both validated activity questionnaires and accelerometers indicate that physical activity is safe during pregnancy. In addition, studies of physical activity during pregnancy that evaluate pregnancy outcomes have found reduced risks of preterm birth, preeclampsia, and gestational diabetes mellitus and improved mental health among individuals who regularly engage in physical activity. In the United States, approximately 48% of pregnant individuals gain more than the recommended amount of weight during pregnancy; excessive gestational weight gain is associated with an increased risk of maternal and fetal complications, including preterm birth, preeclampsia, and gestational diabetes mellitus, and corresponding higher adverse short- and long-term maternal and offspring health outcomes. Although physical activity is safe during pregnancy and may reduce excessive gestational weight gain and resultant pregnancy complications, further research is needed to determine the frequency and duration of specific types of physical activity during pregnancy. Providers should encourage physical activity before and during pregnancy and educate patients regarding the benefits and safety of physical activity.
