Protocol for the development and validation of a risk prediction model for stillbirths from 35 weeks gestation in Australia

Abstract: Background: Despite advances in the care of women and their babies in the past century, an estimated 1.7 million babies are born still each year throughout the world. A robust method to estimate a pregnant woman’s individualized risk of late-pregnancy stillbirth is needed to inform decision-making around the timing of birth to reduce the risk of stillbirth from 35 weeks of gestation in Australia, a high-resource setting. Methods: This is a protocol for a cross-sectional study of all late-pregnancy births in Australia (2005–2015) from 35 weeks of gestation including 5188 stillbirths among 3.1 million births at an estimated rate of 1.7 stillbirths per 1000 births. A multivariable logistic regression model will be developed in line with current TransparentReporting of a multivariable prediction model forIndividualPrognosis orDiagnosis (TRIPOD) guidelines to estimate the gestation-specific probability of stillbirth with prediction intervals. Candidate predictors were identified from systematic reviews and clinical consultation and will be described through univariable regression analysis. To generate a final model, elimination by backward stepwise multivariable logistic regression will be performed. The model will be internally validated using bootstrapping with 1000 repetitions and externally validated using a temporally unique dataset. Overall model performance will be assessed with R2, calibration, and discrimination. Calibration will be reported using a calibration plot with 95% confidence intervals (α = 0.05). Discrimination will be measured by the C-statistic and area underneath the receiver-operator curves. Clinical usefulness will be reported as positive and negative predictive values, and a decision curve analysis will be considered. Discussion: A robust method to predict a pregnant woman’s individualized risk of late-pregnancy stillbirth is needed to inform timely, appropriate care to reduce stillbirth. Among existing prediction models designed for obstetric use, few have been subject to internal and external validation and many fail to meet recommended reporting standards. In developing a risk prediction model for late-gestation stillbirth with both providers and pregnant women in mind, we endeavor to develop a validated model for clinical use in Australia that meets current reporting standards

Protocol for the development and validation of a risk prediction model for stillbirths from 35 weeks gestation in Australia

Abstract: Background: Despite advances in the care of women and their babies in the past century, an estimated 1.7 million babies are born still each year throughout the world. A robust method to estimate a pregnant woman’s individualized risk of late-pregnancy stillbirth is needed to inform decision-making around the timing of birth to reduce the risk of stillbirth from 35 weeks of gestation in Australia, a high-resource setting. Methods: This is a protocol for a cross-sectional study of all late-pregnancy births in Australia (2005–2015) from 35 weeks of gestation including 5188 stillbirths among 3.1 million births at an estimated rate of 1.7 stillbirths per 1000 births. A multivariable logistic regression model will be developed in line with current TransparentReporting of a multivariable prediction model forIndividualPrognosis orDiagnosis (TRIPOD) guidelines to estimate the gestation-specific probability of stillbirth with prediction intervals. Candidate predictors were identified from systematic reviews and clinical consultation and will be described through univariable regression analysis. To generate a final model, elimination by backward stepwise multivariable logistic regression will be performed. The model will be internally validated using bootstrapping with 1000 repetitions and externally validated using a temporally unique dataset. Overall model performance will be assessed with R2, calibration, and discrimination. Calibration will be reported using a calibration plot with 95% confidence intervals (α = 0.05). Discrimination will be measured by the C-statistic and area underneath the receiver-operator curves. Clinical usefulness will be reported as positive and negative predictive values, and a decision curve analysis will be considered. Discussion: A robust method to predict a pregnant woman’s individualized risk of late-pregnancy stillbirth is needed to inform timely, appropriate care to reduce stillbirth. Among existing prediction models designed for obstetric use, few have been subject to internal and external validation and many fail to meet recommended reporting standards. In developing a risk prediction model for late-gestation stillbirth with both providers and pregnant women in mind, we endeavor to develop a validated model for clinical use in Australia that meets current reporting standards

Stillbirths in High-Income Countries: Lifestyle, Environmental and Sociodemographic Risk Factors

Background Stillbirth rates in high-income countries have shown little improvement over the last decade. However, many lifestyle, sociodemographic and environmental factors are modifiable, and may help reduce stillbirth rates. Systematic review, meta-analysis and cohort studies identifying lifestyle, sociodemographic and environmental factors are powerful methods for guiding stillbirth prevention in high-income countries. Better understanding of potentially modifiable risk factors of stillbirth at a global level as well as a local level will enable more effective prevention of stillbirth. Aims 1. To systematically review case-control and cohort studies to identify lifestyle, environmental and sociodemographic risk factors, and their association with stillbirth within high-income countries. 2. To use data contained with the perinatal dataset of South Australia (SA) to identify lifestyle, environmental and sociodemographic risk factors of stillbirth relevant to the Australian population. 3. To inform and recommend individual, local community, national policy, and practice changes to prevent stillbirths. Methods To following methods were employed to address the identified aims of this research; 1. Systematic review of cohort and case-control studies published between 1998-2020 examining factors of interest associated with stillbirth were identified through database searches. The primary outcome of interest, stillbirth, is defined as a birth with no signs of life ≥20 weeks gestational age (GA) or ≥400 grams birthweight. Adjusted odds ratios were calculated through random effects meta-analysis for individual risk factors and stratified by GA where possible. 2. All births registered in the SA routine data collection over the period of 1998-2016 were included in a cohort study of stillbirth risk in SA. Associations between stillbirth risk and lifestyle, environmental and social determinant factors were explored, using multivariable logistic regression. Population Attributable Fractions (PAF) were calculated for factors demonstrating the strongest associations with stillbirth in SA. Results 1. The systematic review and meta-analysis included 390 studies assessing relevant risk factors of stillbirth in high-income countries. Strongest associations with stillbirth were seen for inadequate or no antenatal care, maternal assault during pregnancy, supine sleep position, maternal age ≥45 years, maternal body mass index ≥40, and pre-existing diabetes. Other factors showing an increase in stillbirth risk were; unmarried status, low household income, advanced paternal age, pre-existing hypertension, nulliparity or ≥3 previous births, small or large interpregnancy interval, drug, alcohol, caffeine or cigarette use, unplanned place of birth, parental occupation, maternal ethnicity or country of birth, high exposure to tap water pollution, public or uninsured insurance status and remote/regional living. Maternal university education, H1N1 vaccination, and residential segregation, showed preventative associations with stillbirth odds. 2. From the SA perinatal database, a total of 363,959 births were included in a large cohort study investigating stillbirth risk factors. An inadequate number of antenatal visits was associated with the strongest odds of stillbirth. Other factors found to have important associations with stillbirth odds were: pregnant plant or machine operators, maternal age ≥40 years, paternal pensioners, South Asian country of birth and Aboriginal/Torres Strait Islander women. Odds of stillbirth were increased in regional and remote areas in association with inadequate antenatal care visits, maternal age 35-40 years, Aboriginal and/or Torres Strait Islander women, paternal occupations; tradesperson or unemployed. Discussion and conclusion Comprehensive systematic review and detailed SA cohort data have identified risk factors that potential actions and strategies can target to prevent stillbirth and to decrease rates within high-income countries. Although there is a lack of global consensus on definitions of stillbirth, it is clear that the identified risk factors need to be addressed at local and national policy levels. Risk factors found to have the largest impact on stillbirth odds such as maternal assault, inadequate antenatal care, supine sleep position, and occupation are all factors that may be modified to mitigate the risk of stillbirth. Knowledge of these preventive factors will help families to decrease their risk of stillbirth and to also address and reduce inequity.Thesis (Ph.D.) -- University of Adelaide, Adelaide Medical School, 202