ESPE Abstracts

Introduction: In diabetic pregnancies, data about the interaction between maternal, placental, and fetal IGF1/IGFBP in relation to newborn size is not clear,

Aim: To review research papers published in Pubmed, Google scholar, Research gate, and Scopus in the past 20 years on the relation between placental IGF1/IGFBP-1 and fetal/infantile/childhood growth in pregnancies associated with maternal diabetes.

Results: 28 research papers were selected and reviewed. In 527 GDM patients and 527 healthy pregnant women, the GDM group had higher BMI, fasting blood glucose, blood glucose level at 1 h, 2 h after the meal, and AUCG than the NGT group. IGF-1 and Growth/differentiation factor 15 (GDF-15) levels (a member of the transforming growth factor (TGF)-beta family, is released as a response to oxidative stress and inflammation) of the GDM group were higher than those of the NGT group. IGF-1 levels were positively correlated with maternal FBG. In 30 women with GDM and their 30 macrosomic babies, the serum concentrations of IGF-I and IGF-BP3 were higher in GDM women and their macrosomic babies compared to controls (n= 30).  Maternal IGF-1 levels were positively correlated with the birth weight of GDM newborns. In 27 with GDM, and 277 women maternal and fetal IGF-I levels were significantly higher in GDM than in nondiabetic pregnancies and were associated with larger birth weights. In 157 mothers maternal IGF1 level was significantly correlated with the length and ponderal index of their newborns. In 157 healthy newborns, newborn IGF-1 was positively correlated with placental weight, birth weight, and ponderal index. A positive relationship was detected between maternal IGF-1, fetal IGF1, and birth weight in 339 healthy women. In 50 women with GDM, birth weights were positively correlated to maternal IGF-1. The mRNA expression of three growth factor receptors, (IGF-IR, EGFR, and PDGFR-beta) was upregulated in the placenta of GDM women. The activity of placental IGF-I and mTOR signaling were positively correlated to birth weight. In the placental tissue from T1DM mothers (n= 20), the IGF-1R phosphorylation was significantly increased compared to the NGT women.  Increased maternal blood glucose level during pregnancy was associated with an increased IGF-1R phosphorylation in the placenta (promotes excessive growth). 

Conclusion: Higher maternal IGF1 in diabetic mothers can increase the size of the placenta, and stimulate mTOR signaling which stimulates protein synthesis, and nutrient transport which contributes to fetal overgrowth.