Development of pre-eclampsia within 4 weeks of sFlt-1/PlGF ratio > 38: comparison of performance at 31-34 vs 35-37 weeks' gestation.
OBJECTIVE
To compare the performance of screening by soluble fms-like tyrosine kinase 1 (sFlt-1) to placental growth factor (PlGF) ratio > 38 for the prediction of delivery with pre-eclampsia (PE) at < 1 week and < 4 weeks from assessment when the test is carried out at 31-34 vs 35-37 weeks' gestation.


METHODS
This was a prospective observational study in women attending a third-trimester ultrasound scan as part of routine pregnancy care; the visit was at 30-34 weeks' gestation in the first phase of the study and at 35-37 weeks in the second phase. Serum sFlt-1 and PlGF were measured and their ratio calculated. We estimated the detection rate (DR) and false-positive rate (FPR) of sFlt-1/PlGF ratio > 38 for predicting delivery with PE at < 1 week and < 4 weeks after assessment and compared the performance of screening when the test was carried out at 31 + 0 to 33 + 6 vs 35 + 0 to 36 + 6 weeks' gestation.


RESULTS
The study population included 8063 singleton pregnancies that were examined at 31-34 weeks and 3703 at 35-37 weeks. Delivery with PE occurred at < 1, < 4 and ≥ 4 weeks from assessment in five (0.1%), 29 (0.4%) and 202 (2.5%) women assessed at 31-34 weeks, respectively, and in seven (0.2%), 39 (1.1%) and 21 (0.6%) of those assessed at 35-37 weeks. In women without PE, the median sFlt-1/PlGF ratio increased with gestational age at screening and a ratio of 38 was just below the 99thpercentile at 32 weeks' gestation and just below the 90thpercentile at 36 weeks. In the two gestational windows, the DR of PE delivering < 4 weeks from assessment was similar (75.9% (95% CI, 56.5-89.7%) vs 79.5% (95% CI, 63.5-90.7%)), but the FPR was substantially lower at 31-34 weeks than at 35-37 weeks (1.7% (95% CI, 1.4-2.0%) vs 9.6% (95% CI, 8.7-10.6%)). The number of cases with PE delivering < 1 week from assessment was small, but similarly, in the two gestational windows, the DR was comparable (80.0% (95% CI, 28.4-99.5%) vs 85.7% (95% CI, 42.1-99.6%)), and the FPR was substantially lower at 31-34 weeks than at 35-37 weeks (1.9% (95% CI, 1.6-2.2%) vs 10.2% (95% CI, 9.3-11.3%)).


CONCLUSIONS
The performance of sFlt-1/PlGF ratio > 38 in the prediction of delivery with PE at < 1 and < 4 weeks from assessment is substantially different when the assessment is at 31-34 weeks' gestation compared to at 35-37 weeks. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.
Harris Birthright Research Centre for Fetal Medicine, King's College Hospital, London, UK.
I
I
Dragan
Institute of Health Research, University of Exeter, Exeter, UK.
D
D
Wright
Harris Birthright Research Centre for Fetal Medicine, King's College Hospital, London, UK.
M
M
Fiolna
Harris Birthright Research Centre for Fetal Medicine, King's College Hospital, London, UK.
G
G
Leipold
Harris Birthright Research Centre for Fetal Medicine, King's College Hospital, London, UK.
K H
KH
Nicolaides
D000328:Adult; D005260:Female; D005865:Gestational Age; D006801:Humans; D000072483:Placenta Growth Factor / Q000097:blood*; D011225:Pre-Eclampsia / Q000175:diagnosis* / Q000378:metabolism; D011237:Predictive Value of Tests; D011247:Pregnancy; D011263:Pregnancy Trimester, Third / Q000097:blood*; D011296:Prenatal Diagnosis; D011446:Prospective Studies; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood*
C000608036:PGF protein, human; D000072483:Placenta Growth Factor; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1
placental growth factor; pre-eclampsia; pyramid of antenatal care; soluble fms-like tyrosine kinase-1