Dynamic Changes in Serum IGF-I and Growth During Infancy: Associations to Body Fat, Target Height, and PAPPA2 Genotype

Emmie N Upners; Marie Lindhardt Ljubicic; Alexander S Busch; Margit Bistrup Fischer; Kristian Almstrup; Jørgen H Petersen; Rikke Beck Jensen; Casper P Hagen; Anders Juul

doi:10.1210/clinem/dgab653

Dynamic Changes in Serum IGF-I and Growth During Infancy: Associations to Body Fat, Target Height, and PAPPA2 Genotype

J Clin Endocrinol Metab. 2022 Jan 1;107(1):219-229. doi: 10.1210/clinem/dgab653.

Authors

Emmie N Upners^{1

2}, Marie Lindhardt Ljubicic^{1

2}, Alexander S Busch^{1

2}, Margit Bistrup Fischer^{1

2}, Kristian Almstrup^{1

2}, Jørgen H Petersen^{1

2}, Rikke Beck Jensen^{1

2}, Casper P Hagen^{1

2}, Anders Juul^{1

2

3}

Affiliations

¹ Department of Growth and Reproduction, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.
² International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.
³ Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.

PMID: 34476481
DOI: 10.1210/clinem/dgab653

Abstract

Context: IGF-I is important for postnatal growth and may be of diagnostic value in infants suspected of pituitary disease; however, little is known about the impact of IGF-I and its determinants on infant growth. Importantly, detailed reference ranges for IGF-I and IGF binding protein-3 (IGFBP-3) concentrations during infancy are lacking.

Objective: To evaluate the rapid changes in weight and length as well as their determinants in healthy infants, and to establish age- and sex-specific reference curves for IGF-I and IGFBP-3 in children aged 0 to 1 years.

Design: Prospective longitudinal study.

Setting: Cohort study.

Participants: A total of 233 healthy children (114 girls) with repeated blood samples during the first year of life.

Main outcome measure(s): Serum concentrations of IGF-I and IGFBP-3, length velocity, weight velocity, and PAPPA2 (rs1325598) genotype.

Results: Individual trajectories of length and weight velocities were sex specific. We provide detailed reference curves based on longitudinal data for IGF-I and IGFBP-3 during infancy. In both girls and boys, IGF-I decreased during infancy, whereas IGFBP-3 remained stable. IGF-I and IGFBP-3, but not PAPPA2 genotype, were positively associated with weight gain, but not with longitudinal growth. When stratified by sex, the association between weight gain and IGF-I only remained significant in girls.

Conclusions: Interestingly, we found a significant association between IGF-I and infant weight gain in girls, but not with longitudinal growth in the first year of life. Our findings highlight the role of IGF-I as an important anabolic hormone that is not limited to linear growth.

Keywords: IGF-I; IGFBP-3; PAPP-A2; growth; growth velocity; infancy.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Body Height
Body Weight
Child Development*
Female
Genotyping Techniques
Healthy Volunteers
Humans
Infant
Infant, Newborn
Insulin-Like Growth Factor Binding Protein 3 / blood*
Insulin-Like Growth Factor Binding Protein 3 / metabolism
Insulin-Like Growth Factor I / analysis*
Insulin-Like Growth Factor I / metabolism
Longitudinal Studies
Male
Polymorphism, Single Nucleotide
Pregnancy-Associated Plasma Protein-A / genetics*
Prospective Studies
Reference Values
Sex Factors
Weight Gain

Substances

IGF1 protein, human
IGFBP3 protein, human
Insulin-Like Growth Factor Binding Protein 3
Insulin-Like Growth Factor I
PAPPA2 protein, human
Pregnancy-Associated Plasma Protein-A