Fetal Genotype and Maternal Glucose have Independent and Additive Effects on Birth Weight
American Diabetes Association
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Maternal glycemia is a key determinant of birth weight but recent large-scale genome wide-association studies demonstrated an important contribution of fetal genetics. It is not known whether fetal genotype modifies the impact of maternal glycemia, or whether it acts through insulin-mediated growth. We tested the effects of maternal fasting plasma glucose (FPG) and a fetal genetic score for birth weight on birth weight and fetal insulin in 2,051 European mother-child pairs from the Exeter Family Study of Childhood Health (EFSOCH) and Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study. The fetal genetic score influenced birth weight independently of maternal FPG and impacted on growth at all levels of maternal glycemia. For mothers with FPG in the top tertile, the frequency of large for gestational age (LGA, birth weight ≥90thcentile) was 31.1% for offspring with the highest tertile genetic score and only 14.0% with the lowest tertile genetic score. Unlike maternal glucose, the fetal genetic score was not associated with cord insulin or C-peptide. Similar results were seen for HAPO participants of non-European ancestry (n=2,842 pairs). This work demonstrates that for any level of maternal FPG, fetal genetics have a major impact on fetal growth and act predominantly through independent mechanisms.
A.E.H. was an Academic Foundation Year 2 Doctor funded by the National Institute of Health Research (NIHR). R.N.B. and R.M.F. are funded by the Wellcome Trust and Royal Society, grant 104150/Z/14/Z. A.T.H. is a Wellcome Trust Senior Investigator and NIHR senior investigator. The Exeter Family Study of Childhood Health (EFSOCH) was supported by South West NHS Research and Development, Exeter NHS Research and Development, the Darlington Trust and the Peninsula National Institute of Health Research (NIHR) Clinical Research Facility at the University of Exeter. The opinions given in this paper do not necessarily represent those of NIHR, the NHS or the Department of Health. Genotyping of the EFSOCH study samples was funded by the Welcome Trust and Royal Society grant 104150/Z/14/Z. HAPO was supported by grants from Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Diabetes and Digestive and Kidney Diseases, the National Centre for Research Resources and the American Diabetes Association.
This is the author accepted manuscript. The final version is available from American Diabetes Association via the DOI in this record
Published online 20 February 2018
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