Volume 36, June 2024, 101111Author links open overlay panel, , , , , , , , Highlights•

It is unclear whether the sFlt-1/PlGF ratio is of added value to standard-of-care analyses performed in multiple pregnancies.

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The sFlt-1/PlGF cut-off 38 in addition to urine PCr did not enhance pre-eclampsia prediction in multiple pregnancy.

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The sFlt-1/PlGF ratio's impact on morbidity, cost-effectiveness in multiple pregnancies remains debatable.

AbstractObjective

To assess the predictive accuracy of the sFlt-1/PlGF ratio cut-off 38 in addition to the standard-of-care spot urine protein/creatinine ratio (PCr) for multiple pregnancies in women with suspected pre-eclampsia.

Study design

Post-hoc analysis of a prospective cohort study.

Main outcome measures

Primary outcome was the occurrence of pre-eclampsia in one and four weeks after presentation with suspected pre-eclampsia. Test characteristics with 95% confidence intervals (CI) were calculated on pre-eclampsia development in one and four weeks.

Results

Twenty-three multiple pregnancies with suspected pre-eclampsia between 20 and 37 weeks gestation were included for analysis. Women who eventually developed pre-eclampsia had a significantly higher PCr (34.0 vs. 16.5, p = 0.015), sFlt-1 (17033 vs. 5270 pg/ml, p = 0.047) and sFlt-1/PlGF ratio (99 vs. 25, p = 0.033) at baseline. Furthermore, PCr ≥ 30 and sFlt-1/PlGF ratio > 38 was respectively seen in 1/16 (6.3 %) and 3/16 (18.8 %) of the women who did not develop pre-eclampsia. For predicting pre-eclampsia within one week the sFlt-1/PlGF ratio sensitivity was 75.0 % [95 % CI 19.4–99.4] and the negative predictive value 93.8 % [73.0–98.8], while no pre-eclampsia developed when PCr was < 30. Consequently, the combination of these tests did not lead to an improvement in test characteristics, with non-significant differences in positive predictive value (50.0 % [29.5–70.5] versus 80.0 % [37.3–96.4]) compared to PCr alone for pre-eclampsia development in one week.

Conclusions

In addition to standard-of-care spot urine PCr measurements, this study has not been able to demonstrate that the sFlt-1/PlGF ratio cut-off 38 is of added value in the prediction of pre-eclampsia in multiple pregnancy.

Trial registration: Netherlands Trial Register (NL8308).

AbbreviationsPREPARE

PREdiction of Pre-eclampsia and AdveRse Events

LUMC

Leiden University Medical Centre

sFlt-1

Soluble FMS-like tyrosine kinase-1

PIGF

Placental growth factor

PCr

spot urine protein/creatinine ratio

ALT

alanine aminotransferase

AST

aspartate aminotransferase

FGR

fetal growth restriction

NICU

neonatal intensive care-unit

ISSHP

International Society for the Study of Hypertension in Pregnancy

SPSS

Statistical Package for the Social Sciences

Keywords

Pre-eclampsia

Multiple pregnancy

Biomarkers

sFlt-1/PlGF ratio

© 2024 The Author(s). Published by Elsevier B.V. on behalf of International Society for the Study of Hypertension in Pregnancy.