Maternal plasma fatty acid patterns in mid-pregnancy and offspring epigenetic gestational age at birth

ABSTRACT

Maternal pregnancy fatty acid status is associated with child health. Epigenetic gestational age acceleration, referring to a discrepancy between chronological and epigenetic gestational age, may underlie these associations. Previous research suggests that analysing fatty acid patterns rather than individual fatty acids may overcome the caveat of missing synergistic or additive effects. Among 1226 mother-newborn pairs from the population-based Generation R Study, we examined the associations of three maternal plasma mid-pregnancy fatty acid patterns, identified by principal component analysis, with offspring epigenetic gestational age acceleration. This was estimated from cord blood DNA methylation data using the method developed by Bohlin. As a secondary analysis, we used the method developed by Knight to estimate epigenetic gestational age. The identified ‘high n-6 polyunsaturated fatty acid,’ ‘monounsaturated and saturated fatty acid’ and ‘high n-3 polyunsaturated fatty acid’ patterns were not associated with epigenetic gestational age acceleration in the main analyses. In sensitivity analyses restricted to 337 children born to mothers with more accurate pregnancy dating based on a regular menstrual cycle, a one standard-deviation-score higher maternal plasma ‘high n-3 polyunsaturated fatty acid’ pattern was associated with an epigenetic gestational age acceleration of 0.20 weeks (95% CI 0.06, 0.33), but only when using the Knight method. Thus, we found some evidence that a maternal plasma fatty acid pattern characterized by higher concentrations of n-3 polyunsaturated fatty acids may be associated with accelerated epigenetic gestational ageing. These findings depended on the method used and the accuracy of pregnancy dating and therefore need confirmation.

KEYWORDS:

• Fatty acids
• pregnancy
• child
• DNA methylation
• epigenetic clock
• epigenetic age
• gestational age acceleration
• cohort study

Abbreviations

CI, confidence interval

MUFA, monounsaturated fatty acid

LC-PUFA, polyunsaturated fatty acid

PUFA, long-chain polyunsaturated fatty acid

SD, standard deviation

SFA, saturated fatty acid

SDS, standard deviation score

Acknowledgments

The Generation R Study is conducted by the Erasmus Medical Center in close collaboration with the School of Law and Faculty of Social Sciences of the Erasmus University Rotterdam, the Municipal Health Service Rotterdam area, Rotterdam, the Rotterdam Homecare Foundation, Rotterdam and the Stichting Trombosedienst & Artsenlaboratorium Rijnmond (STAR-MDC), Rotterdam. We gratefully acknowledge the contribution of children and parents, general practitioners, hospitals, midwives and pharmacies in Rotterdam. The generation and management of the Illumina 450K methylation array data (EWAS data) for the Generation R Study was executed by the Human Genotyping Facility of the Genetic Laboratory of the Department of Internal Medicine, Erasmus MC, and the Netherlands. We thank Mr Michael Verbiest, Ms Mila Jhamai, Ms Sarah Higgins, Mr Marijn Verkerk and Dr Lisette Stolk for their help in creating the EWAS database. We thank Dr Alexander Teumer for his work on the quality control and normalization scripts.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data sharing

Data described in the manuscript are available from the corresponding author on reasonable request, subject to the Generation R Study data access procedures.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/15592294.2022.2076051.

Additional information

Funding

This work was supported by the Erasmus MC, University Medical Centre Rotterdam, Erasmus University Rotterdam; the Netherlands Organization for Health Research and Development (ZonMw); the Netherlands Organization for Scientific Research (NWO); the Ministry of Health, Welfare and Sport; the Ministry of Youth and Families; the Netherlands Genomics Initiative (NGI)/Netherlands Organization for Scientific Research (NWO) Netherlands Consortium for Healthy Aging (NCHA) under Grant 050-060-810; the Genetic Laboratory of the Department of Internal Medicine, Erasmus MC; the National Institute of Child and Human Development under Grant R01HD068437; the European Union’s Horizon 2020 research and innovation programme under Grants 733206 (LifeCycle) and 874739 (LongITools); the European Joint Programming Initiative ‘A Healthy Diet for a Healthy Life’ (JPI HDHL) under Grants 529051022 (NutriPROGRAM project, ZonMw the Netherlands) and 529051023 (PREcisE project, ZonMw the Netherlands)