Epigenetic gestational age and the relationship with developmental milestones in early childhood

Kristen J. Polinski, Sonia L. Robinson, Diane L. Putnick, Weihua Guan, Jessica L. Gleason, Sunni L. Mumford, Rajeshwari Sundaram, Pauline Mendola, Stephanie London, Edwina H. Yeung

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


Shorter gestational age (GA) is a risk factor of developmental delay. GA is usually estimated clinically from last menstrual period and ultrasound. DNA methylation (DNAm) estimates GA using sets of cytosine-guanine-sites coupled with a clock algorithm. Therefore, DNAm-estimated GA may better ref lect biological maturation. A DNAm GA greater than clinical GA, known as gestational age acceleration (GAA), may indicate epigenetic maturity and holds potential as an early biomarker for developmental delay risk. We used data from the Upstate KIDS Study to examine associations of DNAm GA and developmental delay within the first 3 years based on the Ages & Stages Questionnaire® (n = 1010). We estimated DNAm GA using two clocks specific to the Illumina Methylation EPIC 850K, the Haftorn clock and one developed from the Effects of Aspirin in Gestation and Reproduction study, in which women were followed to detect pregnancy at the earliest time possible. Among singletons, each week increase in DNAm GA was protective for overall delay (odds ratio:0.74; 95% confidence interval:0.61–0.90) and delay in all domains except for problem-solving skills. Among twins, we observed similar point estimates but lower precision. Results were similar for clinical GA. GAA was largely not associated with developmental delays. In summary, either DNAm GA or clinical GA at birth, but not epigenetic maturity (i.e. GAA), was associated with decreased odds of developmental delay in early childhood. Our study does not support using DNAm GA or GAA as separate risk factors for future risk of developmental delay within the first 3 years of age.

Original languageEnglish (US)
Pages (from-to)1565-1574
Number of pages10
JournalHuman molecular genetics
Issue number9
StatePublished - May 1 2023

Bibliographical note

Funding Information:
Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development [contract numbers HHSN267200603423, HHSN267200603424, HHSN267200603426, HHSN275201300023I—HHSN2750008, HHSN 275201200005C, HHSN267200700019C, HHSN275201400013C, HHSN275201300026I/27500004 and HHSN275201300023I/275000 17]. S.J.L. is supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences.

Publisher Copyright:
© 2023 Authors. All rights reserved.

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Intramural
  • Research Support, N.I.H., Extramural


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