Mothers working to prevent early stillbirth study (MiNESS 20-28): Case Control Study Protocol

Abstract

Abstract Background: An estimated 1,600 babies die every year before, during or immediately after birth between 20-28 weeks’ gestation in the United Kingdom. Baby loss at this stage of pregnancy has similar impact on parental physical and psychological wellbeing to late stillbirth (>28 weeks gestation). Further, peri-viable (20-22 week) births with signs of life are inconsistently reported as miscarriages or neonatal deaths. Therefore, in this study these legally disparate baby deaths are considered together (“Early Stillbirth”). Observational studies have improved understanding of previously unrecognised potentially modifiable risk factors for late stillbirth (including supine going to sleep position) and have influenced international clinical practice. Evidence is lacking regarding how previously identified and novel exposures may relate to early stillbirth risk. Methods: This study aims to identify modifiable risk factors for early stillbirth that are amenable to public health campaigns or adaptation of antenatal care. The study design will be a case-control study of non-anomalous singleton baby loss 20+0 – 27+6 (n=316) and randomly-selected control pregnancies (2:1 ratio; n=632) at group-matched gestations, based on the local historic gestation distribution of cases. Data will be collected by participant recall via researcher-administered questionnaire and extraction from contemporaneous medical records. Unadjusted and confounder-adjusted odds ratios will be calculated using logistic regression. Exposures associated with early stillbirth at OR ≥1.5 will be detectable (p<0.05, β>0.80) assuming exposure prevalence of 30-60%. Discussion: Dissemination of information about modifiable risk factors for stillbirth in late pregnancy (including #sidetosleep) may be responsible for recent reductions in late stillbirths in the UK. Critically, there has been no reduction in early stillbirth (~40% of UK baby losses). Information about modifiable factors associated with early stillbirth is now urgently required to inform clinical practice, to assist expectant mothers/parents to reduce their baby’s risk of early stillbirth, and to help address inequalities in pregnancy outcome. This study will focus on what portion of early stillbirth risk may be mitigated by facilitating positive health exposures among expectant mothers/parents and their partners, or by adaptation of their environment or healthcare provision. Information obtained from this study will enable development of antenatal care and education to reduce risk of early stillbirth. Trial registration: NCT06005272