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.

Routine placental histopathology findings from women testing positive for SARS‐CoV‐2 during pregnancy: Retrospective cohort comparative study

“…The opposite might also be true: that women with FVM are more predisposed to testing positive for COVID‐19. There has been recent evidence that women with FVM might have glucose dysmetabolism, similar to women with distal villous immaturity, yet never receive the diagnosis of GDM 41 . As GDM has been associated with a higher incidence of severe COVID‐19, 42 including possibly in our cohort, the implications are potentially significant 43 .…”

“…There has been recent evidence that women with FVM might have glucose dysmetabolism, similar to women with distal villous immaturity, yet never receive the diagnosis of GDM. 41 As GDM has been associated with a higher incidence of severe COVID-19, 42 including possibly in our cohort, the implications are potentially significant. 43 More study is needed into the association between FVM, undiagnosed GDM and the risk of severe infections.…”

"Multidisciplinary Team Management of a Pregnant Woman With Newly Diagnosed Multiple Pulmonary Embolisms and Foetal Compromise, When to Deliver?"

“…FIR is an important clinical sign among women with pre-existing diabetes, which should alert the clinician to investigate underlying placental dysfunction (Padmanabhan,et al [9]). Moreover, Siassakos, et al [10] report that 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 (Siassakos,et al [10]).…”

“…Conventional tests of foetal wellbeing (umbilical artery doppler ultrasound, cardiotocography and other biophysical tests) have been shown to have poor sensitivity for predicting such events (p.35). Siassakos, et al [10] report that additional placental histopathological lesions also present in women with diabetes in pregnancy. Accelerated villous maturation and distal villous hypoplasia are associated with maternal vascular malperfusion lesions, which represent hypoxic ischaemic damage to the placenta.…”

Stillbirth: prevention and supportive bereavement care

“… 16 Moreover, a study of placental distal villous immaturity recorded an 18% unexplained stillbirth rate, where the only identifiable risk factor in 70% of cases was one or more high glucose results in pregnancy with no gestational diabetes mellitus diagnosis. 11 Although this suggests increased gestational diabetes mellitus diagnoses might prevent adverse outcomes, universal adoption of the International Association of Diabetes and Pregnancy Study Groups criteria would increase gestational diabetes mellitus prevalence an estimated 6–11-fold, 6 potentially overwhelming stretched health services.…”