Insulin-Like Growth Factor II and Binding Proteins 1 and 3 from Second Trimester Human Amniotic Fluid Are Associated with Infant Birth Weight

The developing fetus begins to swallow amniotic fluid (AF) early in gestation, a process that results in ingestion of numerous growth factors. Our objectives were 2-fold: 1) to assess the concentration and distribution of insulin-like growth factor II (IGF II) and its binding proteins (BP) 1 and 3 in 2nd trimester amniotic fluid using ELISA, and 2) to establish whether concentrations of AF IGF II and its binding proteins IGF BP1 and 3, measured early in pregnancy, were associated with and predictive of infant birth weight. Birth weights were categorized using recently developed birth-weight-for-gestational-age percentiles for fetal growth in which infants 90% as LGA (large-for-gestational-age). AF samples were collected after routine genetic testing (15.1 ± 0.04 wk, range 12-20 wk) from 543 mother-infant pairs in Montreal, QC, Canada. Maternal and fetal characteristics were obtained from questionnaires and medical chart review. Multivariate regression analysis that controlled for maternal height, prepregnancy weight, smoking behavior, infant gender, gestational age, parity, as well as amniocentesis week showed that higher AF IGF BP1 was associated with lower birth weight (partial r² = 0.0062). Regression analyses revealed that AF IGF BP3 was positively associated with birth weight within LGA and macrosomia subpopulations (partial r² = 0.0283 and 0.0404, respectively). These results show that 2nd trimester AF IGF BP1, BP3, and IGF II may emerge as early indicators of fetal growth.