Context: A common polymorphism in the growth hormone receptor (GHR) gene has been linked to increased growth response in GH treated patients. No former study has focused on the association to prenatal growth.

Objective: To evaluate the association between the d3-GHR isoforms and spontaneous pre- and postnatal growth

Design: A prospective study on third trimester fetal growth velocity (FGV), birth weight (BW), birth length (BL) and postnatal growth

Setting: Copenhagen University Hospital

Participants: 115 healthy adolescents were divided into those born small for gestational age (SGA) and appropriate for gestational age (AGA) with or without intrauterine growth restriction (IUGR).

Main outcome measures: FGV measured by serial ultrasonography, BW, BL and adolescent height. Isoforms of the d3-GHR gene (fl/fl, d3/fl, d3/d3) were determined.

Results: The prevalence of the d3-GHR isoforms was 50%, but differed among the groups (p=0.006), in the SGA-IUGR group the prevalence was 88% and in SGA subjects carriers of the d3-GRH allele was associated with decreased third trimester FGV (P=0.05).

In the entire cohort carriers of the d3-GHR allele had a significantly increased height (-0.10 SDS vs. 0.34 SDS, P=0.017) and change in height from birth to adolescence compared to carriers of the fl-GHR allele (0.57 SDS vs. -0.02 SDS, P=0.005).

Conclusion: This study showed an increased spontaneous postnatal growth velocity in the carriers of the d3-GHR allele. Interestingly, we found the opposite effect on prenatal growth in the SGA group with a decreased fetal growth velocity in carriers of the d3-GHR allele.