Fetuin-A in Infants Born Small- or Large-for-Gestational-Age

Fetuin-A is a multifunctional glycoprotein that has been implicated in insulin resistance and bone metabolism. We assessed whether fetuin-A is associated with poor or excessive fetal growth. In the Shanghai Birth Cohort, we conducted a nested case-control study of 60 trios of small-for-gestational-age (SGA, birth weight <10th percentile), optimal-for-gestational-age (OGA, 25–75th, the reference) and large-for-gestational-age (LGA, >90th percentile) infants matched by sex and gestational age. Cord plasma concentrations of fetuin-A and fetal growth factors [insulin, proinsulin, insulin-like growth factor (IGF)-I and IGF-II] were measured. Cord plasma fetuin-A concentrations were higher in SGA (809.4 ± 306.9 μg/ml, P = 0.026) and LGA (924.2 ± 375.9 μg/ml, P < 0.001) relative to OGA (680.7 ± 262.1 μg/ml) newborns, and were not correlated to insulin, proinsulin, IGF-I and IGF-II (all P > 0.2). Higher fetuin-A concentrations were associated with increased risks of SGA [OR = 1.67 (1.08–2.58) per SD increment, P = 0.024] and LGA [OR = 2.36 (1.53–3.66), P < 0.001]. Adjusting for maternal and neonatal characteristics and fetal growth factors, the elevated risk changed little for LGA [adjusted OR = 2.28 (1.29–4.01), P = 0.005], but became non-significant for SGA (P = 0.202). Our study is the first to demonstrate that fetuin-A may be involved in excessive fetal growth. This association is independent of fetal growth factors.