Correlation of Insulin-Like Growth Factor-I and -II Concentrations at Birth Measured by Mass Spectrometry and Growth from Birth to Two Months

Abstract

Background: Immunoassays used to measure insulin-like growth factor (IGF)-I and -II concentrations are susceptible to interference from IGF-binding proteins. The aim of this study was to investigate the association of IGF-I and -II concentrations at birth with neonatal anthropometry using a liquid chromatography/mass spectrometry (LCMS) assay. Methods: LCMS was used to measure IGF-I and -II concentrations in umbilical cord blood of term, healthy infants enrolled in the Cork BASELINE Birth Cohort Study. Weight, length, and occipitofrontal head circumference (OFC) were measured at birth and 2 months. Results: Cord blood IGF-I and -II concentrations were measured in 1,100 infants. Mean (SD) IGF-I and -II concentrations were 52.5 (23.9) ng/mL and 424.3 (98.2) ng/mL, respectively. IGF-I and -II concentrations at birth were associated (p < 0.05) with weight (R² = 0.19, R² = 0.01), length (R² = 0.07, R² = 0.004), and OFC (R² = 0.03, R² = 0.04) at birth. Low IGF-I concentrations at birth were associated with increases in weight (p < 0.001) and OFC (p < 0.01) Z-scores in the first 2 months. Conclusion: Using an LCMS assay, we have shown that anthropometric parameters at birth are associated with IGF-I and weakly with IGF-II concentrations. This indicates that, at the time of birth, IGF-I is the more important growth factor for regulating infant growth.

The relationship between IGF-I and -II concentrations and body composition at birth and over the first 2 months

“…The relationship between IGF-I concentration at birth and adiposity is not surprising. There are strong associations between IGF-I concentrations and birth weight( 14 , 28 ) and nutritional status( 11 ). IGF-II is an important prenatal growth factor.…”

“…The change in Z-score between birth and two months was calculated by subtracting the age- and sex-specific Z-score at birth from the two months Z-score. Gestational age- and sex-specific Z-scores for IGF-I and –II concentrations were also used in this analysis, and the development of these reference data are described elsewhere( 14 ). The LCMS assay cannot detect IGF-I concentrations below 16 ng/ml or IGF-II concentrations below 32 ng/ml.…”

“…Regulation of IGF-I and -II in utero appears to be more dependent on nutrition( 11 ) than growth hormone (GH). Infants with GH deficiency have normal size at birth( 12 ) whereas infants with intrauterine growth restriction have reduced concentrations of IGF-I and –II( 13 , 14 ). This correlation with weight at birth is stronger for IGF-I than for IGF-II concentrations( 14 ).…”

“…Infants with GH deficiency have normal size at birth( 12 ) whereas infants with intrauterine growth restriction have reduced concentrations of IGF-I and –II( 13 , 14 ). This correlation with weight at birth is stronger for IGF-I than for IGF-II concentrations( 14 ). Animal models also show that expression of IGF-I and –II is reduced in response to intrauterine nutritional deprivation( 15 ).…”

Impact of the Choice of IGF-I Assay and Normative Dataset on the Diagnosis and Treatment of Growth Hormone Deficiency in Children

“…Well-derived pediatric normative data for the iSYS IGF-I assay are lacking and are, considering the clinical relevance, highly desirable. Analysis of IGF-I with mass spectrometry can circumvent some of the problems that are inherent to immunoassays, e.g., interference of IGF-binding proteins or cross-reactivity of IGF-II [29, 30]. Mass spectrometry might be a promising technique to reduce variability in IGF-I analysis and to improve standardization across platforms, provided that calibration procedures are harmonized [31].…”