Abnormal placental villous maturity and dysregulated glucose metabolism: Implications for stillbirth prevention

Abstract

Objectives: In the UK one in 250 pregnancies end in stillbirth. Abnormal placental villous maturation, commonly associated with gestational diabetes, is a risk factor for stillbirth. Histopathology reports of placental distal villous immaturity (DVI) are reported disproportionately in placentas from otherwise unexplained stillbirths in women without formal diagnosis of diabetes but with either clinical characteristics or risk factors for diabetes. This study aims to establish maternal factors associated with DVI in relation to stillbirth. Methods: Placental histopathology reports were reviewed for all pregnant women delivering at University College London Hospital between July 2018 to March 2020. Maternal characteristics and birth outcomes of those with DVI were compared to those with other placental lesions or abnormal villous maturation. Results: Of the 752 placental histopathology reports reviewed, 11 (1.5%) were reported as diagnostic of DVI. Eighty cases were sampled for clinical record analysis. All women with DVI had normal PAPP-A (>0.4 MoM), normal uterine artery Doppler studies (UtA-PI) and were normotensive throughout pregnancy. Nearly one in five babies (2/11, 18.5%) with DVI were stillborn and 70% had at least one high glucose test result in pregnancy despite no formal diagnosis of diabetes. Conclusions: These findings suggest that the mechanism underlying stillbirth in DVI likely relates to glucose dysmetabolism, not sufficient for diagnosis using current criteria for gestational diabetes, resulting in placental dysfunction that is not identifiable before the third trimester. Relying on conventional diabetes tests, foetal macrosomia or growth restriction, may not identify all pregnancies at risk of adverse outcomes from glucose dysmetabolism.