Birth weight variants are associated with variable fetal intrauterine growth from 20 weeks of gestation

TY - JOUR

T1 - Birth weight variants are associated with variable fetal intrauterine growth from 20 weeks of gestation

AU - Engelbrechtsen, L.

AU - Gybel-brask, D.

AU - Mahendran, Y.

AU - Crusell, M.

AU - Hansen, T. H.

AU - Schnurr, T. M.

AU - Hogdall, E.

AU - Skibsted, L.

AU - Hansen, T.

AU - Vestergaard, H.

PY - 2018/12/1

Y1 - 2018/12/1

N2 - Fetal intrauterine growth is influenced by complex interactions between the maternal genes, environment and fetal genes. The aim of this study was to assess the effect of GWAS-identified genetic variants associated with birth weight on intrauterine fetal growth in 665 children. Fetal growth was estimated by two-dimensional ultrasound scans at 20, 25 and 32 weeks of gestation and growth trajectories were modeled using mixed linear regression. A genetic risk score (GRS) of birth weight-raising variants was associated with intrauterine growth showing an attenuating effect on the unconditional daily reduction in proportional weight gain of 8.92 × 10-6 percentage points/allele/day (p = 2.0 × 10-4), corresponding to a mean difference of 410 g at 40 weeks of gestation between a child with lowest and highest GRS. Eight variants were independently associated with intrauterine growth throughout the pregnancy, while four variants were associated with fetal growth in the periods 20-25 or 25-32 weeks of gestation, indicating that some variants may act in specific time windows during pregnancy. Four of the intrauterine growth variants were associated with type 2 diabetes, hypertension or BMI in the UK Biobank, which may provide basis for further understanding of the link between intrauterine growth and later risk of metabolic disease.

AB - Fetal intrauterine growth is influenced by complex interactions between the maternal genes, environment and fetal genes. The aim of this study was to assess the effect of GWAS-identified genetic variants associated with birth weight on intrauterine fetal growth in 665 children. Fetal growth was estimated by two-dimensional ultrasound scans at 20, 25 and 32 weeks of gestation and growth trajectories were modeled using mixed linear regression. A genetic risk score (GRS) of birth weight-raising variants was associated with intrauterine growth showing an attenuating effect on the unconditional daily reduction in proportional weight gain of 8.92 × 10-6 percentage points/allele/day (p = 2.0 × 10-4), corresponding to a mean difference of 410 g at 40 weeks of gestation between a child with lowest and highest GRS. Eight variants were independently associated with intrauterine growth throughout the pregnancy, while four variants were associated with fetal growth in the periods 20-25 or 25-32 weeks of gestation, indicating that some variants may act in specific time windows during pregnancy. Four of the intrauterine growth variants were associated with type 2 diabetes, hypertension or BMI in the UK Biobank, which may provide basis for further understanding of the link between intrauterine growth and later risk of metabolic disease.

U2 - 10.1038/s41598-018-26752-3

DO - 10.1038/s41598-018-26752-3

M3 - Journal article

C2 - 29849051

SN - 2045-2322

VL - 8

JO - Scientific Reports

JF - Scientific Reports

M1 - 8376

ER -