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Comparative Study
. 2021 Sep 10;13(1):171.
doi: 10.1186/s13148-021-01164-9.

Prenatal risk factors and neonatal DNA methylation in very preterm infants

Marie Camerota  1   2 , Stefan Graw  3 , Todd M Everson  3   4 , Elisabeth C McGowan  5 , Julie A Hofheimer  6 , T Michael O'Shea  6 , Brian S Carter  7 , Jennifer B Helderman  8 , Jennifer Check  8 , Charles R Neal  9 , Steven L Pastyrnak  10 , Lynne M Smith  11 , Lynne M Dansereau  12 , Sheri A DellaGrotta  12 , Carmen J Marsit  3 , Barry M Lester  13   12   5
Affiliations
Comparative Study

Prenatal risk factors and neonatal DNA methylation in very preterm infants

Marie Camerota et al. Clin Epigenetics. .

Abstract

Background: Prenatal risk factors are related to poor health and developmental outcomes for infants, potentially via epigenetic mechanisms. We tested associations between person-centered prenatal risk profiles, cumulative prenatal risk models, and epigenome-wide DNA methylation (DNAm) in very preterm neonates.

Methods: We studied 542 infants from a multi-center study of infants born < 30 weeks postmenstrual age. We assessed 24 prenatal risk factors via maternal report and medical record review. Latent class analysis was used to define prenatal risk profiles. DNAm was quantified from neonatal buccal cells using the Illumina MethylationEPIC Beadarray.

Results: We identified three latent profiles of women: a group with few risk factors (61%) and groups with elevated physical (26%) and psychological (13%) risk factors. Neonates born to women in higher risk subgroups had differential DNAm at 2 CpG sites. Higher cumulative prenatal risk was associated with methylation at 15 CpG sites, 12 of which were located in genes previously linked to physical and mental health and neurodevelopment.

Conclusion: We observed associations between prenatal risk factors and DNAm in very preterm infants using both person-centered and cumulative risk approaches. Epigenetics offers a potential biological indicator of prenatal risk exposure.

Keywords: Buccal; Epigenetics; Epigenome-wide association study (EWAS); Methylation; Neonatal; Prenatal; Preterm.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Rates of endorsement of 24 prenatal risk factors by latent class membership. Women in class 1 (green; 61%) endorse few prenatal risk factors. Women in class 2 (red; 26%) endorse elevated physical health problems, whereas women in class 3 (blue; 13%) endorse elevated substance use and psychological problems
Fig. 2
Fig. 2
Manhattan plot of epigenetic loci associated with cumulative prenatal risk. The x-axis shows the genomic location of individual CpG sites and the y-axis shows the −log10(p values) from models relating cumulative prenatal risk to CpG methylation, adjusting for child sex, recruitment site, postmenstrual age at collection, sample batch, and cellular heterogeneity. Gene annotations have been added for all CpGs yielding significant associations after Bonferroni adjustment. The horizontal red line depicts the Bonferroni adjusted p-value threshold (α = 0.05/706323). +indicates closest gene
See this image and copyright information in PMC

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