Quantitative assessment of placental morphology may identify specific causes of stillbirth.

BACKGROUND: Stillbirth is frequently the result of pathological processes involving the placenta. Understanding the significance of specific lesions is hindered by qualitative subjective evaluation. We hypothesised that quantitative assessment of placental morphology would identify alterations between different causes of stillbirth and that placental phenotype would be independent of post-mortem effects and differ between live births and stillbirths with the same condition. METHODS: Placental tissue was obtained from stillbirths with an established cause of death, those of unknown cause and live births. Image analysis was used to quantify different facets of placental structure including: syncytial nuclear aggregates (SNAs), proliferative cells, blood vessels, leukocytes and trophoblast area. These analyses were then applied to placental tissue from live births and stillbirths associated with fetal growth restriction (FGR), and to placental lobules before and after perfusion of the maternal side of the placental circulation to model post-mortem effects. RESULTS: Different causes of stillbirth, particularly FGR, cord accident and hypertension had altered placental morphology compared to healthy live births. FGR stillbirths had increased SNAs and trophoblast area and reduced proliferation and villous vascularity; 2 out of 10 stillbirths of unknown cause had similar placental morphology to FGR. Stillbirths with FGR had reduced vascularity, proliferation and trophoblast area compared to FGR live births. Ex vivo perfusion did not reproduce the morphological findings of stillbirth. CONCLUSION: These preliminary data suggest that addition of quantitative assessment of placental morphology may distinguish between different causes of stillbirth; these changes do not appear to be due to post-mortem effects. Applying quantitative assessment in addition to qualitative assessment might reduce the proportion of unexplained stillbirths.

Vaginal prostaglandin E2 versus double-balloon catheter for induction of labour for vaginal birth after caesarean section: A retrospective cohort study.

OBJECTIVE: To compare the success of the double-balloon catheter (DBC) versus prostaglandin gel (PGE2) for induction of labour in women with one previous caesarean section. DESIGN: Retrospective cohort study using routinely collected maternity data in a Tertiary NHS hospital, North West England, UK. Women with a live singleton cephalic pregnancy induced using DBC or PGE2 after one previous birth by caesarean section from 1st April 2017 to 1st July 2019 were included. The core outcomes assessed were the inability to perform artificial rupture of membranes, requirement of oxytocin, vaginal birth and uterine rupture. RESULTS: 208 women met the inclusion criteria, 127 were induced using the DBC and 81 using PGE2. The two groups were well matched for demographics and characteristics. Women induced for prolonged ruptured membranes with PGE2 were excluded from the study leaving 127 managed with DBC and 69 with PGE2. There were no significant differences observed between the two groups. Vaginal birth rates were 52.7% for the DBC and 66.6% for the PGE2 (relative risk 0.79 (confidence interval 0.63-1.00); P = 0.05). A single uterine rupture was reported following DBC usage. CONCLUSIONS: The DBC and PGE2 appear to be equally effective for induction of labour in women with one previous caesarean section.

The PLANES study: a protocol for a randomised controlled feasibility study of the placental growth factor (PlGF) blood test-informed care versus standard care alone for women with a small for gestational age fetus at or after 32 + 0 weeks' gestation.

BACKGROUND: Stillbirth remains a major concern across the globe and in some high-resource countries, such as the UK; efforts to reduce the rate have achieved only modest reductions. One third of stillborn babies are small for gestational age (SGA), and these pregnancies are also at risk of neonatal adverse outcomes and lifelong health problems, especially when delivered preterm. Current UK clinical guidance advocates regular monitoring and early term delivery of the SGA fetus; however, the most appropriate regimen for surveillance of these babies remains unclear and often leads to increased intervention for a large number of these women. This pilot trial will determine the feasibility of a large-scale trial refining the risk of adverse pregnancy outcome in SGA pregnancies using biomarkers of placental function sFlt-1/PlGF, identifying and intervening in only those deemed at highest risk of stillbirth. METHODS: PLANES is a randomised controlled feasibility study of women with an SGA fetus that will be conducted at two tertiary care hospitals in the UK. Once identified on ultrasound, women will be randomised into two groups in a 3:1 ratio in favour of sFlt-1/PlGF ratio led management vs standard care. Women with an SGA fetus and a normal sFlt-1/PlGF ratio will have a repeat ultrasound and sFlt-1/PlGF ratio every 2 weeks with planned birth delayed until 40 weeks. In those women with an SGA fetus and an abnormal sFlt-1/PlGF ratio, we will offer birth from 37 weeks or sooner if there are other concerning features on ultrasound. Women assigned to standard care will have an sFlt-1/PlGF ratio taken, but the results will be concealed from the clinical team, and the woman's pregnancy will be managed as per the local NHS hospital policy. This integrated mixed method study will also involve a health economic analysis and a perspective work package exploring trial feasibility through interviews and questionnaires with participants, their partners, and clinicians. DISCUSSION: Our aim is to determine feasibility through the assessment of our ability to recruit and retain participants to the study. Results from this pilot study will inform the design of a future large randomised controlled trial that will be adequately powered for adverse pregnancy outcome. Such a study would provide the evidence needed to guide future management of the SGA fetus. TRIAL REGISTRATION: ISRCTN58254381 . Registered on 4 July 2019.