Title of project

Feto-placental adaptations to increased oxygen demand in pregnancies with pre-gestational diabetes mellitus: a pilot study

Abstract

Placenta and fetus proper form an intimate unit closely cooperating throughout pregnancy to sustain healthy growth and development of the fetus. Understanding how the feto-placental unit copes with challenges posed by adverse maternal influences is important for designing diagnostic and even curative measures. Conditions associated with derangement of maternal glucose-insulin axis, such as T1DM and T2DM, are often associated with fetal hyperglycaemia und hyperinsulinemia. The latter leads to increased fetal metabolism entailing increased oxygen demand. We propose that both placenta and fetus mount adaptive responses to cope with this situation. The present project will test some of these adaptations in pregnant women with or without T1DM or T2DM.

My host just completed a study on placental oxygenation and fetal liver volume, measured at three time points during pregnancy in women with or without T1DM or T2DM. In the placenta samples collected at birth in that study, we will quantify placental vascularization at my home university. This will enable us to test various hypotheses about the association of placental oxygenation and fetal liver volume with placental vascularization at the end of pregnancy. Data on cord blood insulin and haemoglobin levels will provide further insights in potential drivers and indicators of the adaptive responses in the feto-placental unit.

I will help linking the already existing data with new data on placental vascularization. In addition, I will bring in my placenta expertise to put the study results into the context of maternal-placental-fetal dialogue with pregnancy dynamics as a new paradigm in T1DM and T2DM. These combined results will provide novel and unique information on sequence and timing of feto-placental adaptations. Moreover, it will inform my host how to analyse existing data and to design new studies. We will develop a novel mechanistic concept on consequences of adaptive response failure such as in fetal growth restriction.