Influence of genetic variants for birth weight on fetal growth and placental haemodynamics

Objective: To determine the combined effect of 60 genetic variants (single nucleotide polymorphisms, SNPs), previously identified as being associated with birth weight, on fetal growth and placental haemodynamics throughout pregnancy. Design: Prospective birth cohort (Generation R Study). Setting: General multiethnic population. Participants: 5374 singleton liveborn children with genome-wide association arrays and fetal growth data. Methods: Longitudinal and cross-sectional analyses of a genetic score of the total number of birth weight-increasing alleles across the 59 available SNPs and repeated fetal growth and haemodynamic measures. Main outcome measures: SD scores (SDS) of fetal weight, (femur) length, head circumference, umbilical artery pulsatility index, uterine artery mean resistance index and placental weight, in different periods of pregnancy until birth. Results: In longitudinal analyses, the effect of the genetic score on the fetal growth measures increased throughout pregnancy (p<0.001). At 20 weeks of gestation, the genetic score was not associated with any of the fetal growth measures, whereas at 30 weeks it was associated with all. The strongest effects were observed at birth: Per SD increase in genetic score, birth weight increased by 0.15 SDS (95% confidence interval: 0.13 to 0.18), birth length by 0.12 SDS (0.08 to 0.19) and head circumference by 0.08 SDS (0.05 to 0.12). The genetic score was not associated with placental haemodynamics, but was associated with a 14 g (10 to 18) increase in placental weight per SDS increase in genetic score. Conclusions: Our results suggest that genetic variants related to birth weight exert their combined effect on fetal growth from second half of pregnancy onwards and have no effect on placental haemodynamics.

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