# Methylation differences between assisted reproductive technology-conceived and naturally conceived children near BRCA1 and NBR2

## TL;DR

Children conceived via assisted reproductive technology show subtle DNA methylation differences near BRCA1/NBR2 at birth, but these differences fade over time.

## Contribution

This study provides longitudinal evidence on the persistence of ART-associated DNA methylation differences in children over time.

## Key findings

- ART-conceived children showed subtle hypermethylation at the BRCA1/NBR2 promoter at birth.
- The methylation differences diminished over time and were not statistically significant after correction.
- The findings suggest a potential ART-associated epigenetic signature that may fade postnatally.

## Abstract

Recent studies have shown that newborns conceived using assisted reproductive technology (ART) exhibited significantly different DNA methylation (DNAm) profiles at birth compared to those conceived naturally. Of note was the observation of increased DNAm at the promoter region of BRCA1/NBR2 in ART-conceived newborns. However, it remains unclear if these DNAm differences persist after birth. Using the Norwegian Mother, Father, and Child Cohort Study (MoBa), a large-scale population-based pregnancy cohort with extensive longitudinal data collected through biological samples and questionnaires, we generated longitudinal DNAm data for 105 ART-conceived and 250 naturally conceived children at birth and at ages 3–22 years. DNAm differences in the BRCA1/NBR2 promoter between ART- and naturally conceived children, at birth and postnatally, were tested using linear mixed model with adjustment for maternal and newborn covariates. While ART-conceived children showed subtle hypermethylation at birth and postnatally, the differences diminished over time and did not remain statistically significant after multiple testing correction. Our findings suggest that subtle hypermethylation at the BRCA1/NBR2 promoter in ART-conceived children may represent an ART-associated epigenetic signature, although further studies in larger populations are needed to clarify its persistence and significance.