ESPE Abstracts

Background: Alterations of pre- and early postnatal growth can have long lasting impact on adult height, body composition and metabolic health throughout life. In monozygotic twins discordant for prenatal growth due to twin-to-twin transfusion syndrome (TTTS), we previously demonstrated lower cord blood IGF-I concentrations and earlier pubertal maturation, indicative of prenatal programming of endocrine systems, to be linked to reduced final height of the former growth restricted twin. The individual capacity of postnatal catch-up growth may also depend on genetic factors, as shown for the growth hormone receptor exon 3 deletion (GHRd3) gene variant in very low birth weight preterm infants or children with GH deficiency.

Methods: We longitudinally analyzed growth patterns from birth to near final height (mean age at last visit 15.0 yrs) in relation to the GRHd3 genotype in a cohort of 62 monozygotic TTTS twin pairs. TTTS had been treated by laser coagulation of communicating vessels before 25 weeks of gestation. At birth, 28 of 62 pairs still showed an intra-twin difference of >1.0 SDS for length and/or weight. GHRd3 genotype (exon 3 deletion vs. full length) was analyzed by multiplex PCR.

Results: Birth parameters including mean intra-twin differences were not different between the GHRd3 genotype groups. Transiently and irrespective of their TTTS status, children carrying at least one GHRd3 allele (fl/d3, d3/d3) had lower height-SDS compared with noncarrier (fl/fl) at ages 12 months (donors: d3-carrier -1.42±1.06 SDS vs. noncarrier -0.50±1.25 SDS, P=0.007; recipients: d3-carrier -0.59 ±1.13 SDS vs. noncarrier 0.00±1.19 SDS, P=0.085) and 2 yrs (donors: d3-carrier -0.96±0.80 SDS vs. noncarrier -0.12±0.96 SDS, P=0.008; recipients: d3-carrier 0.39±0.86 SDS vs. noncarrier 0.43±1.29 SDS, P=0.030). Intra-twin differences, however, were not different between genotypes. Up to the last visit during adolescence, most children (116/124) reached a near final height within normal ranges, while height-SDS (d3-carrier 0.15±1.15 SDS vs. noncarrier 0.37±1.10 SDS, P>0.1) as well as mean intra-twin height-SDS differences (d3-carrier 0.32±0.55 SDS vs. noncarrier 0.31±0.49 SDS, P>0.1) again were not different between genotype groups.

Conclusions: During early postnatal catch-up growth at ages 1 and 2 yrs, GHRd3 carrier were significantly shorter than noncarrier, which is in contrast to previous observations regarding GHRd3 and catch-up growth. However, the GHRd3 genotype does not seem to affect near final height or the degree of long-term height approximation within twin pairs in monozygotic twins discordant for prenatal growth.