Maternal vascular - placental axis in the third trimester in women with gestational diabetes mellitus, hypertensive disorders and unaffected pregnancies.

Objectives: The objectives of the study were first, to compare different markers of maternal vascular function in women with gestational diabetes mellitus (GDM), preeclampsia (PE), or gestational hypertension (GH) and women whose pregnancies were unaffected by these complications. Second, to assess the association between maternal vascular function and markers of placental perfusion, maternal vascular - placental axis, in these four groups of women.

Study design: This was a prospective observational study of women attending for a routine hospital visit at 35 + 0 to 36 + 6 weeks' gestation at King's College Hospital, London, UK. This visit included recording of maternal demographic characteristics and medical history, ultrasound examination for fetal anatomy and growth, Doppler studies of the uterine arteries and ophthalmic arteries, carotid-femoral pulse-wave velocity (PWV) measurements, estimation of augmentation index (AIx) and total peripheral resistance and measurements of serum placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFLT-1). Linear regression was performed for the outcomes of uterine artery pulsatility index (UtA-PI) multiples of median (MoM), PLGF MoM and sFLT-1 MoM. Ophthalmic artery peak systolic velocity (PSV) ratio, PWV , AIx and total peripheral vascular resistance were assessed as potential predictors. This analysis was carried out in all women and separately in the different groups.

Results: The study population of 6502 women included 614 (9.4%) with GDM, 140 (2.1%) who subsequently developed PE and 129 (2.0%) who developed GH. Women with GDM, compared to those with pregnancies unaffected by GDM, PE or GH, had increased PWV. Women with PE or GH, compared to those with unaffected pregnancies, had lower PlGF MoM and higher UtA-PI MoM, sFLT1 MoM, AIx, PWV, total peripheral resistance and ophthalmic artery PSV ratio. In unaffected pregnancies, ophthalmic artery PSV ratio was predictive of UtA-PI MoM, and ophthalmic artery PSV ratio, AIx, total peripheral resistance, and PWV were predictive of PLGF MoM and sFLT-1 MoM. In women with GDM, ophthalmic artery PSV ratio was predictive of UtA-PI MoM and ophthalmic artery PSV ratio, total peripheral resistance, and PWV were predictive of PLGF MoM, and total peripheral resistance was predictive of sFLT-1 MoM. In women with PE, ophthalmic artery PSV ratio was predictive of UtA-PI MoM, PLGF MoM and sFLT-1 MoM. In women unaffected by GDM, PE or GH, ophthalmic artery PSV ratio was predictive of UtA-PI MoM and AIx, total peripheral resistance, PWV and ophthalmic artery PSV ratio were predictive of PLGF MoM and sFLT-1 MoM.

Conclusions: In the third trimester of pregnancy, women with PE, GH, and GDM present with increased arterial stiffness. In addition, those diagnosed with hypertensive complications show increased peripheral vascular resistance. Ophthalmic artery PSV ratio provides predictive information for placental perfusion and function for all pregnant women, whereas vascular indices are more informative for placental function in women with unaffected pregnancy and those with GDM, than in those with PE or GH. These data suggest that vascular assessment in women during pregnancy may not only provide information about maternal vascular health but can be used to offer information about individual risk for development of placental insufficiency. The selection of vascular index will have to be tailored according to maternal profile and pregnancy complication.