Endometrial Origins of Stillbirth (EOS), a case-control study of menstrual fluid to understand and prevent preterm stillbirth and associated adverse pregnancy outcomes: study protocol.

INTRODUCTION: Current research aimed at understanding and preventing stillbirth focuses almost exclusively on the role of the placenta. The underlying origins of poor placental function leading to stillbirth, however, remain poorly understood. There is evidence demonstrating that the endometrial environment in which the embryo implants impacts not only the establishment of pregnancy but also the development of some pregnancy outcomes. Menstrual fluid has recently been applied to the study of menstrual disorders such as heavy menstrual bleeding or endometriosis, however, it has great potential in the study of adverse pregnancy outcomes. This study aims to identify differences in menstrual fluid and menstrual cycle characteristics of women who have experienced preterm stillbirth and other associated adverse pregnancy outcomes, compared with those who have not. The association between menstrual fluid composition and menstrual cycle characteristics will also be determined. METHODS AND ANALYSIS: This is a case-control study of women who have experienced a late miscarriage, spontaneous preterm birth or preterm stillbirth or a pregnancy complicated by placental insufficiency (fetal growth restriction or pre-eclampsia), compared with those who have had a healthy term birth. Cases will be matched for maternal age, body mass index and gravidity. Participants will not currently be on hormonal therapy. Women will be provided with a menstrual cup and will collect their sample on day 2 of menstruation. Primary exposure measures include morphological and functional differences in decidualisation of the endometrium (cell types, immune cell subpopulations and protein composition secreted from the decidualised endometrium). Women will complete a menstrual history survey to capture menstrual cycle length, regularity, level of pain and heaviness of flow. ETHICS AND DISSEMINATION: Ethics approval was obtained from Monash University Human Research Ethics Committee (27900) on 14/07/2021 and will be conducted in accordance with these conditions. Findings from this study will be disseminated through peer-reviewed publications and conference presentations.

Causes of perinatal deaths in Australia: Slow progress in the preterm period.

AIM: The majority of perinatal deaths occur in the preterm period; however, current approaches predominantly focus on prevention in the term period. Reducing perinatal deaths in the preterm period is, therefore, key to reducing the rates of perinatal death overall in Australia. The aim was to understand the classifications of causes of preterm stillbirth and neonatal death in Victoria over time and by gestation. MATERIALS AND METHODS: Retrospective study using state-wide, publicly available data. All births in Victoria between 2010 and 2018 included in the Victorian Perinatal Data Collection, excluding terminations of pregnancy for maternal psychosocial indications, were studied. Differences in causes of preterm perinatal mortality gestation group and over time were determined. RESULTS: Out of 7977 perinatal deaths reported, 85.9% (n = 6849) were in the preterm period. The most common cause of preterm stillbirths was congenital anomalies (n = 1574, 29.8%), followed by unexplained antepartum deaths (n = 557, 14.2%). The most common cause of preterm neonatal death was spontaneous preterm birth (sPTB; n = 599, 38.2%), followed by congenital anomalies (n = 493, 31.4%). The rate of preterm stillbirths due to hypertension (-14.9% (95% CI -27.1% to -2.7%; P = 0.02)), maternal conditions (-24.1% (95% CI -44.2% to -4.0%; P = 0.03)) and those that were unexplained (-5.4% (95% CI -9.8% to -1.2%; P = 0.02)) decreased per annum between 2010 and 2018. All other classifications did not change significantly over time. CONCLUSION: Prevention of congenital anomalies and sPTB is critical to reducing preterm perinatal mortality. Greater emphasis on understanding causes of preterm deaths through mortality investigations may reduce the proportion of those considered 'unexplained'.