ESPE Yearbook of Paediatric Endocrinology

To read the full abstract: Clin Endocrinol (Oxf) 2020 May 13. doi: 10.1111/cen.14221. Online ahead of print.

Children born either small for gestational age (SGA) or preterm usually do not achieve a final height (FH) in the mid-parental target height (MPTH) range, despite showing catch-up growth in the first years of life (1). The influence of intrauterine metabolic and hormonal factors has been proposed and, in particular, IGF-I plays a key role in both pre and post-natal growth (2), (3), (4). This paper stems from a longitudinal study in monozygotic twins who suffered from twin to twin transfusion syndrome (TTTS). These children shared the same genetic, prenatal environmental and family background, but differed in intrauterine nutrient availability. 28 twin pairs were selected and analyzed at 1 year, 4 years and pubertal age up to near FH (height velocity <2 cm/year). Anthropometry and cord blood IGF-I were assessed. Subjects were defined as discordant (10) or concordant (18) according to intra-twin birth weight difference more or less than 1 S.D., respectively.

Significant intra-twin length/height differences remained for 26/28 (93%) of all twins and for all initially discordant twins. Mean difference in intra-twin height among concordant birth weight twin pairs was 0.18 SDS, corresponding to an absolute mean intra-twin difference at FH of only 1.31 cm. In the discordant birth weight group, all the initially smaller twins remained substantially shorter than their respective co-twin (mean difference 1.23 SDS). This corresponded to an absolute mean difference in intra-twin height at FH of 7.9 cm. A strong correlation between intra-twin difference in FH and differences in birth weight and birth length was observed. A significant correlation between cord blood concentrations of IGF-I and FH for both twin cohorts was observed. The greater the intra-twin difference in IGF-I cord blood concentrations, the larger the intra-twin difference in FH.

The results of this powerful long-term follow-up study suggest that IGF-I levels in cord blood are predictive for FH. Whether IGF-I concentrations are the drivers or just a mirror of the biological/environmental mechanisms regulating the differing growth outcomes in twins has to be established.

References:

1. Saenger P, Czernichow P, Hughes I, Reiter EO. Small for gestational age: short stature and beyond. Endocr Rev. 2007 Apr;28(2):219–51.

2. Gohlke BC, Huber A, Hecher K, Fimmers R, Bartmann P, Roth CL. Fetal Insulin-Like Growth Factor (IGF)-I, IGF-II, and Ghrelin in Association with Birth Weight and Postnatal Growth in Monozygotic Twins with Discordant Growth. J Clin Endocrinol Metab. 2005 Apr;90(4):2270–4.

3. Napoli F, Di Iorgi N, Bagnasco F, Cangemi G, D’Amico B, Boschetti M, Allegri AE, Bruzzone Ichim IA, Traggiai C, Allodi A, Polo Perucchin P, Ghezzi M, Noli S, Giaccardi M, Roviglione B, De Miglio L, Calcagno A, Lorini R, Maghnie M. Growth factors and metabolic markers in cord blood: relationship to birth weight and length. J Biol Regul Homeost Agents. 2014 Apr–Jun;28(2):237–49.

4. Chellakooty M, Juul A, Boisen KA, Damgaard IN, Kai CM, Schmidt IM, J H Petersen, N E Skakkebaek, K M Main. A Prospective Study of Serum Insulin-Like Growth Factor I (IGF-I) and IGF-Binding Protein-3 in 942 Healthy Infants: Associations with Birth Weight, Gender, Growth Velocity, and Breastfeeding. J Clin Endocrinol Metab. 2006 Mar 1;91(3):820–6.