Prediction of stillbirth: an umbrella review of evaluation of prognostic variables

Abstract

Background Stillbirth accounts for over 2 million deaths a year worldwide and rates remains stubbornly high. Multivariable prediction models may be key to individualised monitoring, intervention or early birth in pregnancy to prevent stillbirth. Objectives To collate and evaluate systematic reviews of factors associated with stillbirth in order to identify variables relevant to prediction model development. Search strategy MEDLINE, Embase, DARE and Cochrane Library databases and reference lists were searched up to November 2019. Selection criteria We included systematic reviews of association of individual variables with stillbirth without language restriction. Data collection and analysis Abstract screening and data extraction were conducted in duplicate. Methodological quality was assessed using AMSTAR and QUIPS criteria. The evidence supporting association with each variable was graded. Results The search identified 1198 citations. Sixty-nine systematic reviews reporting 64 variables were included. The most frequently reported were maternal age (n = 5), body mass index (n = 6) and maternal diabetes (n = 5). Uterine artery Doppler appeared to have the best performance of any single test for stillbirth. The strongest evidence of association was for nulliparity and preexisting hypertension. Conclusion We have identified variables relevant to the development of prediction models for stillbirth. Age, parity and prior adverse pregnancy outcomes had a more convincing association than the best performing tests, which were PAPP-A, PlGF and UtAD. The evidence was limited by high heterogeneity and lack of data on intervention bias.

Predicting singleton antepartum stillbirth by the demographic Fetal Medicine Foundation Risk Calculator—A retrospective case-control study

“…Recent systematic reviews reveal the superiority of maternal characteristics in risk-evaluation [ 13 , 16 ]. They confirm a robust body of evidence for the link of nulliparity, pre-existing hypertension, and increased maternal BMI to antepartum stillbirth [ 16 , 33 ].…”

“…Recent systematic reviews reveal the superiority of maternal characteristics in risk-evaluation [ 13 , 16 ]. They confirm a robust body of evidence for the link of nulliparity, pre-existing hypertension, and increased maternal BMI to antepartum stillbirth [ 16 , 33 ]. The demographic findings from our cohort support these data, as all but nulliparity were significantly more prevalent in women affected by fetal death.…”

“…Townsend et al have proposed that a future robust risk prediction tool for stillbirth should incorporate the following candidate variables: maternal age, BMI, parity, pre-existing hypertension, diabetes, previous stillbirth, nicotine consumption, uterine artery Doppler, pregnancy-associated plasma protein PAPP-A, and placental growth factor PlGF [ 16 ]. The merit of such a clinical model would be twofold: primarily, the accurate discrimination of high- from low-risk pregnant women, and secondarily, recognizing the variables that may require early enough alteration, if they are modifiable.…”

“…To date, 69 prediction models for stillbirth have been described in the literature. A recent systematic review has identified maternal age, body-mass-index (BMI), and diabetes as the three most commonly used variables in such prediction tools [ 16 ]. The best evidence with consistently strong association with stillbirth is documented for maternal obesity, pre-existing hypertension, and nulliparity.…”

Predictive performance for placental dysfunction related stillbirth of the competing risks model for small for gestational age fetuses

“…In a series of previous first and second trimester studies for the prediction of stillbirth we highlighted that the causes of this adverse event are heterogeneous and that the focus of research should be placental dysfunction related stillbirths because they are relatively common and to a great extent potentially preventable [17][18][19][20][21][22] . However, a systematic review of 69 previous systematic reviews which aimed to identify variables that could be relevant to the development of a clinical prediction model for stillbirth treated this adverse event as a homogeneous condition.…”