First‐ and second‐trimester tests to predict stillbirth in unselected pregnant women: a systematic review and meta‐analysis

Conde-Agudelo, Agustín; Bird, Susan; Kennedy, S H; Villar, José; Papageorghiou, Aris T.

doi:10.1111/1471-0528.13096

Cited by 59 publications

(60 citation statements)

References 121 publications

(234 reference statements)

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“…89 A test is likely to do poorly when assessed against all stillbirths, but might be more specific for a particular cause of stillbirth. A systematic review 90 of biomarker and ultrasonic tests noted that none of 16 single, or five combined, tests did well as predictors of stillbirth. However, stillbirth attributed to placental dysfunction was moderately to strongly associated (positive likelihood ratios between five and 15) with low first-trimester pregnancy associated plasma protein A and abnormal uterine artery Doppler velocimetry in the second trimester.…”

Section: Ultrasonic and Biochemical Prediction Of Stillbirth Riskmentioning

confidence: 99%

Stillbirths: recall to action in high-income countries

et al. 2016

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Variation in stillbirth rates across high-income countries and large equity gaps within high-income countries persist. If all high-income countries achieved stillbirth rates equal to the best performing countries, 19 439 late gestation (28 weeks or more) stillbirths could have been avoided in 2015. The proportion of unexplained stillbirths is high and can be addressed through improvements in data collection, investigation, and classification, and with a better understanding of causal pathways. Substandard care contributes to 20-30% of all stillbirths and the contribution is even higher for late gestation intrapartum stillbirths. National perinatal mortality audit programmes need to be implemented in all high-income countries. The need to reduce stigma and fatalism related to stillbirth and to improve bereavement care are also clear, persisting priorities for action. In high-income countries, a woman living under adverse socioeconomic circumstances has twice the risk of having a stillborn child when compared to her more advantaged counterparts. Programmes at community and country level need to improve health in disadvantaged families to address these inequities.

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Section: Ultrasonic and Biochemical Prediction Of Stillbirth Riskmentioning

confidence: 99%

Stillbirths: recall to action in high-income countries

et al. 2016

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“…The evidence we present on clinical risk‐factor associations adds to the developing knowledge of other types of prediction models to identify pregnancies at risk of stillbirth, from biomarkers and uterine blood flow studies. For example, there is a suggestion that low serum levels of pregnancy‐associated plasma protein‐A during the first trimester and an increased pulsatility index from Doppler ultrasonography during the second trimester could be good predictors of stillbirth, with a moderate LR+ ranging from 10.0 to 15.0 40. The presence of these risk factors, in addition to the patterns of clinical variables we have reported, could guide decision‐making about the timing of delivery to prevent antepartum stillbirth.…”

Section: Discussionmentioning

confidence: 99%

The antepartum stillbirth syndrome: risk factors and pregnancy conditions identified from the INTERGROWTH‐21^st Project

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et al. 2016

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ObjectivesTo identify risk factors for antepartum stillbirth, including fetal growth restriction, among women with well‐dated pregnancies and access to antenatal care.DesignPopulation‐based, prospective, observational study.SettingEight international urban populations.PopulationPregnant women and their babies enrolled in the Newborn Cross‐Sectional Study of the INTERGROWTH‐21st Project.MethodsCox proportional hazard models were used to compare risks among antepartum stillborn and liveborn babies.Main outcome measuresAntepartum stillbirth was defined as any fetal death after 16 weeks’ gestation before the onset of labour.ResultsOf 60 121 babies, 553 were stillborn (9.2 per 1000 births), of which 445 were antepartum deaths (7.4 per 1000 births). After adjustment for site, risk factors were low socio‐economic status, hazard ratio (HR): 1.6 (95% CI, 1.2–2.1); single marital status, HR 2.0 (95% CI, 1.4–2.8); age ≥40 years, HR 2.2 (95% CI, 1.4–3.7); essential hypertension, HR 4.0 (95% CI, 2.7–5.9); HIV/AIDS, HR 4.3 (95% CI, 2.0–9.1); pre‐eclampsia, HR 1.6 (95% CI, 1.1–3.8); multiple pregnancy, HR 3.3 (95% CI, 2.0–5.6); and antepartum haemorrhage, HR 3.3 (95% CI, 2.5–4.5). Birth weight <3rd centile was associated with antepartum stillbirth [HR, 4.6 (95% CI, 3.4–6.2)]. The greatest risk was seen in babies not suspected to have been growth restricted antenatally, with an HR of 5.0 (95% CI, 3.6–7.0). The population‐attributable risk of antepartum death associated with small‐for‐gestational‐age neonates diagnosed at birth was 11%.ConclusionsAntepartum stillbirth is a complex syndrome associated with several risk factors. Although small babies are at higher risk, current growth restriction detection strategies only modestly reduced the rate of stillbirth.Tweetable abstractInternational stillbirth study finds individual risks poor predictors of death but combinations promising.

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“…The function of PAPP-A is not completely clear, but it is suggested to be important for placental development. In fetuses with normal chromosome number, low levels of PAPP-A have been associated with the development of PE, intrauterine growth restriction (IUGR), placental abruption and stillbirth [31,32]. As a single biomarker for PE, PAPP-A only predicts 22 % of the ePE cases in the first trimester of pregnancy at an FPR of 5 %.…”

Section: Biochemical Markersmentioning

confidence: 99%

First Trimester Prediction of Preeclampsia

et al. 2015

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Preeclampsia (PE) is a serious pregnancy-related condition that causes severe maternal and fetal morbidity and mortality. Within the recent years, there has been an increasing focus in predicting PE at the end of the first trimester of pregnancy. In this review, literature published between 2011 and 2015 was evaluated. In a total of six biomarker algorithms, for first and early second trimester, the prediction of preeclampsia is discussed. In addition, one randomized clinical trial was included. Several algorithms were based on placental biomarkers such as pregnancy-associated plasma protein A (PAPP-A), placental growth factor (PLGF), and soluble FMS-like tyrosine kinase 1 (s-FLT-1). The algorithms containing these biomarkers showed a high prediction rate (PR) for early onset PE, ranging from 44 to 92 % at 5 % false positive rate (FPR). New biomarkers suggest an alternative model based on free HbF and the heme scavenger alpha-1-microglobulin (A1M) with a prediction rate of 69 % at an FPR of 5 %. Interestingly, this model performs well without uterine artery Doppler pulsatility index (UtAD-PI), which is an advantage particularly if the screening method were to be implemented in developing countries. The randomized clinical trial showed a clear reduction in early onset PE as well as reducing preterm PE if identified high-risk pregnancies were treated with low-dose aspirin. In conclusion, PE prediction is now possible through several prediction algorithms and prophylaxis is beneficial in high-risk cases.

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First‐ and second‐trimester tests to predict stillbirth in unselected pregnant women: a systematic review and meta‐analysis

Cited by 59 publications

References 121 publications

Stillbirths: recall to action in high-income countries

Stillbirths: recall to action in high-income countries

The antepartum stillbirth syndrome: risk factors and pregnancy conditions identified from the INTERGROWTH‐21^st Project

First Trimester Prediction of Preeclampsia

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First‐ and second‐trimester tests to predict stillbirth in unselected pregnant women: a systematic review and meta‐analysis

Cited by 59 publications

References 121 publications

Stillbirths: recall to action in high-income countries

Stillbirths: recall to action in high-income countries

The antepartum stillbirth syndrome: risk factors and pregnancy conditions identified from the INTERGROWTH‐21st Project

First Trimester Prediction of Preeclampsia

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The antepartum stillbirth syndrome: risk factors and pregnancy conditions identified from the INTERGROWTH‐21^st Project