Meng-Nan Yang1,2, Guang-Hui Zhang3, Kun Du3, Wen-Juan Wang1,2, Yu Dong1, Hua He1, Huei-Chen Chiu2, Yu-Na Guo4, Fengxiu Ouyang1, Jun Zhang1, Xiao-Lin Hua5,6, Zhong-Cheng Luo7,8. 1. Ministry of Education-Shanghai Key Laboratory of Children's Environmental Health, and Department of Obstetrics, Xinhua Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, 200092, China. 2. Department of Obstetrics and Gynecology, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, and Institute of Health Policy, Management and Evaluation, Dalla Lana School of Public Health, University of Toronto, Toronto, M5G 1X5, Canada. 3. Department of Clinical Assay Laboratory, Xinhua Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, 200092, China. 4. Department of Obstetrics and Gynecology, International Peace Maternity and Child Health Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, 200030, China. 5. Ministry of Education-Shanghai Key Laboratory of Children's Environmental Health, and Department of Obstetrics, Xinhua Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, 200092, China. huaxiaolin_sh@163.com. 6. Department of Obstetrics and Gynecology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, 200040, China. huaxiaolin_sh@163.com. 7. Ministry of Education-Shanghai Key Laboratory of Children's Environmental Health, and Department of Obstetrics, Xinhua Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, 200092, China. zcluo@lunenfeld.ca. 8. Department of Obstetrics and Gynecology, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, and Institute of Health Policy, Management and Evaluation, Dalla Lana School of Public Health, University of Toronto, Toronto, M5G 1X5, Canada. zcluo@lunenfeld.ca.
Abstract
BACKGROUND: Retinol-binding protein 4 (RBP-4) is an adipokine involved in regulating insulin sensitivity which would affect fetal growth. It is unclear whether RBP-4 is associated with fetal overgrowth, and unexplored which fetal growth factor(s) may mediate the association. METHODS: In the Shanghai Birth Cohort, we studied 125 pairs of larger-for-gestational-age (LGA, birth weight >90th percentile, an indicator of fetal overgrowth) and optimal-for-gestational-age (OGA, 25-75th percentiles) control infants matched by sex and gestational age. We measured cord blood concentrations of RBP-4, insulin, proinsulin, insulin-like growth factor-I (IGF-I), and IGF-II. RESULTS: Cord blood RBP-4 concentrations were elevated in LGA vs. OGA infants (21.9 ± 6.2 vs. 20.2 ± 5.1 µg/ml, P = 0.011), and positively correlated with birth weight z score (r = 0.19, P = 0.003), cord blood proinsulin (r = 0.21, P < 0.001), IGF-I (r = 0.24, P < 0.001), and IGF-II (r = 0.15, P = 0.016). Adjusting for maternal and neonatal characteristics, each SD increment in cord blood RBP-4 was associated with a 0.28 (0.12-0.45) increase in birth weight z score (P < 0.001). Mediation analyses showed that IGF-I could account for 31.7% of the variation in birth weight z score in association with RBP-4 (P = 0.01), while IGF-II was not an effect mediator. CONCLUSIONS: RBP-4 was positively associated with fetal overgrowth. IGF-I (but not IGF-II) may mediate this association.
BACKGROUND:Retinol-binding protein 4 (RBP-4) is an adipokine involved in regulating insulin sensitivity which would affect fetal growth. It is unclear whether RBP-4 is associated with fetal overgrowth, and unexplored which fetal growth factor(s) may mediate the association. METHODS: In the Shanghai Birth Cohort, we studied 125 pairs of larger-for-gestational-age (LGA, birth weight >90th percentile, an indicator of fetal overgrowth) and optimal-for-gestational-age (OGA, 25-75th percentiles) control infants matched by sex and gestational age. We measured cord blood concentrations of RBP-4, insulin, proinsulin, insulin-like growth factor-I (IGF-I), and IGF-II. RESULTS: Cord blood RBP-4 concentrations were elevated in LGA vs. OGA infants (21.9 ± 6.2 vs. 20.2 ± 5.1 µg/ml, P = 0.011), and positively correlated with birth weight z score (r = 0.19, P = 0.003), cord blood proinsulin (r = 0.21, P < 0.001), IGF-I (r = 0.24, P < 0.001), and IGF-II (r = 0.15, P = 0.016). Adjusting for maternal and neonatal characteristics, each SD increment in cord blood RBP-4 was associated with a 0.28 (0.12-0.45) increase in birth weight z score (P < 0.001). Mediation analyses showed that IGF-I could account for 31.7% of the variation in birth weight z score in association with RBP-4 (P = 0.01), while IGF-II was not an effect mediator. CONCLUSIONS:RBP-4 was positively associated with fetal overgrowth. IGF-I (but not IGF-II) may mediate this association.