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Objective: Alteration of placental structure may influence fetal overgrowth and complications of
maternal diabetes. We examined the placenta in a cohort of offspring of mothers with type 1
diabetes (OT1DM) to assess structural changes and determine whether these were related to
maternal HbA1c, fetal hematocrit, fetal hormonal or metabolic axes.
Research Design and Methods: Placental samples were analysed using stereological techniques
to quantify volumes and surface areas of key placental components in 88 OT1DM and 39
controls, and results related to maternal HbA1c and umbilical cord analytes (insulin, leptin,
adiponectin, IGF-I, hematocrit, lipids, CRP, IL-6).
Results: Intervillous space volume was increased in OT1DM (OT1DM 250±81 cm3 vs control
217±65cm 3: P=0.02) with anisomorphic growth of villi (p=0.025). The placentae showed a trend
to increased weight (OT1DM 690±19g; control 641±22g: P=0.08) but villous, non-parenchymal,
trophoblast and capillary volumes did not differ. Villous surface area, capillary surface area,
membrane thickness and calculated morphometric diffusing capacity were also similar in T1DM
and controls. HbA1c at 26-34 weeks associated with birthweight (r=0.27, p=0.03), placental
weight (r=0.41, p=0.0009) and intervillous space volume (r=0.38, p=0.0024). In multivariate
analysis of cord parameters in OT1DM, fetal IGF-I emerged as a significant correlate of most
components (intervillous space, villous, trophoblast, capillary volumes all P<0.01). By contrast
fetal insulin was only independently associated with capillary surface area (positive, r 2 6.7%;
P=0.02).
Conclusions: There are minimal placental structural differences between OT1DM and controls.
Fetal IGF-I but not fetal insulin emerges as a key correlate of placental substructural volumes,
thereby facilitating feedback to the placenta regarding fetal metabolic demand.
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