Prediction of hypertensive disorders after screening at 36 weeks' gestation: comparison of angiogenic markers with competing‐risks model

Journal article


Schiattarella, A., Magee, L., Wright, A., Syngelaki, A., Akolekar, R., von Dadelszen, P. and Nicolaides, K. H. 2023. Prediction of hypertensive disorders after screening at 36 weeks' gestation: comparison of angiogenic markers with competing‐risks model. Ultrasound in Obstetrics & Gynecology. 62 (3), pp. 345-352. https://doi.org/10.1002/uog.26291
AuthorsSchiattarella, A., Magee, L., Wright, A., Syngelaki, A., Akolekar, R., von Dadelszen, P. and Nicolaides, K. H.
Abstract

Objective
To compare the performance at 35 + 0 to 36 + 6 weeks' gestation of screening for delivery with pre-eclampsia (PE) at various timepoints, using one of three approaches: placental growth factor (PlGF) concentration, soluble fms-like tyrosine kinase-1 (sFlt-1) to PlGF concentration ratio, or the competing-risks model, which combines maternal risk factors with biomarkers to estimate patient-specific risk.

Methods
This was a prospective observational study of women attending for a routine hospital visit at 35 + 0 to 36 + 6 weeks' gestation at one of two maternity hospitals in England between 2016 and 2022. During the visit, maternal demographic characteristics and medical history were recorded and serum PlGF, serum sFlt-1 and mean arterial pressure (MAP) were measured. Detection rates (DRs) were evaluated for delivery with PE (defined as per American College of Obstetricians and Gynecologists 2019 criteria) within 1 week, within 2 weeks or at any time after screening, using the following strategies: (i) low PlGF (< 10th percentile); (ii) high sFlt-1/PlGF ratio (> 90th percentile); or (iii) the competing-risks model, in which maternal factors were combined with multiples of the median values of PlGF (‘single test’), PlGF and sFlt-1 (‘double test’) or PlGF, sFlt-1 and MAP (‘triple test’). Risk cut-offs corresponded to a screen-positive rate of 10%. DRs were compared between tests.

Results
Of 34 782 pregnancies, 831 (2.4%) developed PE. In screening for delivery with PE at any time from assessment, the DR at 10% screen-positive rate was 47% by low PlGF alone, 54% by the single test, 55% by high sFlt-1/PlGF ratio, 61% by the double test and 68% by the triple test. In screening for delivery with PE within 2 weeks from assessment, the respective values were 67%, 74%, 74%, 80% and 87%. In screening for delivery with PE within 1 week from assessment, the respective values were 77%, 81%, 85%, 88% and 91%. For prediction of PE at any time, the DR was significantly higher with the triple test compared to PlGF alone or the sFlt-1/PlGF ratio, with a DR difference (95% CI) of 20.1% (16.7–23.0%) and 12.4% (9.7–15.3%), respectively. Similar results were seen for prediction of PE within 2 weeks (20.6% (14.9–26.8%) and 12.9% (7.7–17.5%), respectively) and prediction of PE within 1 week (13.5% (5.4–21.6%) and 5.4% (0.0–10.8%), respectively). The double test was superior to the sFlt-1/PlGF ratio and the single test was superior to PlGF alone in the prediction of PE within 2 weeks and at any time from assessment, but not within 1 week of assessment.

Conclusion
At 35 + 0 to 36 + 6 weeks' gestation, the performance of screening for PE by the competing-risks model triple test is superior to that of PlGF alone or the sFlt-1/PlGF ratio for the development of disease within 1 week, within 2 weeks and at any time from screening. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

KeywordsAngiogenic factor; Antiangiogenic factor; Competing-risks model; Mean arterial model; Mean arterial pressure; Placental growth factor; PIGF; Pre-eclampsia; sFlt-1; Soluble fms-like tyrosine kinase-1; Survival model; Third-trimester screening
Year2023
JournalUltrasound in Obstetrics & Gynecology
Journal citation62 (3), pp. 345-352
PublisherWiley
ISSN0960-7692
1469-0705
Digital Object Identifier (DOI)https://doi.org/10.1002/uog.26291
Official URLhttps://obgyn.onlinelibrary.wiley.com/doi/10.1002/uog.26291
FunderFetal Medicine Foundation
Publication dates
Online30 Aug 2023
Publication process dates
Accepted26 May 2023
Deposited10 Oct 2024
Output statusPublished
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Ciobanu, A., Anthoulakis, C., Syngelaki, A., Akolekar, R. and Nicolaides, K.H. 2019. Prediction of small-for-gestational-age neonates at 35-37 weeks' gestation: contribution of maternal factors and growth velocity between 32 and 36 weeks. Ultrasound in Obstetrics and Gynecology. 53 (5), pp. 630-637. https://doi.org/10.1002/uog.20267
Maternal and neonatal complications of fetal macrosomia: cohort study
Beta, J., Khan, N., Fiolna, M., Khalil, A., Ramadan, G. and Akolekar, R. 2019. Maternal and neonatal complications of fetal macrosomia: cohort study. Ultrasound in Obstetrics and Gynecology. 54 (3), pp. 319-325. https://doi.org/10.1002/uog.20279
Procedure-related risk of miscarriage following chorionic villus sampling and amniocentesis
Beta, J., Zhang, W., Geris, S., Kostiv, V. and Akolekar, R. 2019. Procedure-related risk of miscarriage following chorionic villus sampling and amniocentesis. Ultrasound in Obstetrics and Gynecology. 54 (4), pp. 452-457. https://doi.org/10.1002/uog.20293
Biomarkers of impaired placentation at 35-37 weeks' gestation in the prediction of adverse perinatal outcome
Ciobanou, A., Jabak, S., De Castro, H., Frei, L., Akolekar, R. and Nicolaides, K. H. 2019. Biomarkers of impaired placentation at 35-37 weeks' gestation in the prediction of adverse perinatal outcome. Ultrasound in Obstetrics and Gynecology. 54 (1), pp. 79-86. https://doi.org/10.1002/uog.20346
Risk of miscarriage following amniocentesis or chorionic villus sampling: systematic review of literature and updated meta-analysis
Salomon, L. J., Sotiriadis, A., Wulff, C. B., Odibo, A. and Akolekar, R. 2019. Risk of miscarriage following amniocentesis or chorionic villus sampling: systematic review of literature and updated meta-analysis. Ultrasound in Obstetrics and Gynecology. 54 (4), pp. 442-451. https://doi.org/10.1002/uog.20353
Prediction of large-for-gestational-age neonate by routine third-trimester ultrasound
Khan, N., Ciobanu, A., Karampitsakos, T., Akolekar, R. and Nicolaides, K. H. 2019. Prediction of large-for-gestational-age neonate by routine third-trimester ultrasound. Ultrasound in Obstetrics and Gynecology. 54 (2), pp. 326-333. https://doi.org/10.1002/uog.20377
Two-stage approach for prediction of small-for-gestational-age neonate and adverse perinatal outcome by routine ultrasound examination at 35-37 weeks' gestation
Akolekar, R., Panaitescu, A. M., Ciobanu, A., Syngelaki, A. and Nicolaides, K. H. 2019. Two-stage approach for prediction of small-for-gestational-age neonate and adverse perinatal outcome by routine ultrasound examination at 35-37 weeks' gestation. Ultrasound in Obstetrics and Gynecology. 54, pp. 484-491. https://doi.org/10.1002/uog.20391
Prevention of stillbirths: impact of a two-stage screening for vasa previa
Zhang, W., Geris, S., Beta, J., Ramadan, G., Nicolaides, K. H. and Akolekar, R. 2019. Prevention of stillbirths: impact of a two-stage screening for vasa previa. Ultrasound in Obstetrics and Gynecology. 55 (5), pp. 605-612. https://doi.org/10.1002/uog.21953
Impact of prospective measurement of outflow tracts in the prediction of coarctation of the aorta
Vigneswaran, T. V., Zidere, V., Chivers, S., Charakida, M., Akolekar, R. and Simpson, J. M. 2019. Impact of prospective measurement of outflow tracts in the prediction of coarctation of the aorta. Ultrasound in Obstetrics and Gynecology. https://doi.org/10.1002/uog.21957
Diagnosis of major heart defects by routine first-trimester ultrasound examination: association with high nuchal translucency, tricuspid regurgitation and abnormal flow in the ductus venosus
Minnella, G. P., Crupano, F. M., Syngelaki, A., Zidere, V., Akolekar, R. and Nicolaides, K. H. 2019. Diagnosis of major heart defects by routine first-trimester ultrasound examination: association with high nuchal translucency, tricuspid regurgitation and abnormal flow in the ductus venosus. Ultrasound in Obstetrics and Gynecology. 55 (5), pp. 637-644. https://doi.org/10.1002/uog.21956
Screening for pre-eclampsia using sFlt-1/PlGF ratio cut-off of 38 at 30-37 weeks' gestation
Dragan, I., Georgiou, T., Prodan, N., Akolekar, R. and Nicolaides, K. H. 2017. Screening for pre-eclampsia using sFlt-1/PlGF ratio cut-off of 38 at 30-37 weeks' gestation. Ultrasound in Obstetrics and Gynecology. 49 (1), pp. 73-77. https://doi.org/10.1002/uog.17301
Uterine artery pulsatility index at 30-34 weeks' gestation in the prediction of adverse perinatal outcome
Valiño, N., Giunta, G., Gallo, D. M., Akolekar, R. and Nicolaides, K. H. 2016. Uterine artery pulsatility index at 30-34 weeks' gestation in the prediction of adverse perinatal outcome. Ultrasound in Obstetrics and Gynecology. 47 (3), pp. 308-315. https://doi.org/10.1002/uog.14898
Biophysical and biochemical markers at 30-34 weeks' gestation in the prediction of adverse perinatal outcome
Valiño, N., Giunta, G., Gallo, D. M., Akolekar, R. and Nicolaides, K. H. 2016. Biophysical and biochemical markers at 30-34 weeks' gestation in the prediction of adverse perinatal outcome. Ultrasound in Obstetrics and Gynecology. 47 (2), pp. 194-202. https://doi.org/10.1002/uog.14928
Screening for trisomies by cell-free DNA testing of maternal blood: consequences of a failed result
Revello, R., Sarno, L., Ispas, A., Akolekar, R. and Nicolaides, K. H. 2016. Screening for trisomies by cell-free DNA testing of maternal blood: consequences of a failed result. Ultrasound in Obstetrics and Gynecology. 47 (6), pp. 698-704. https://doi.org/10.1002/uog.15851
Metformin versus placebo in obese pregnant women without diabetes mellitus
Syngelaki, A., Nicolaides, K. H., Balani, J., Hyer, S., Akolekar, R., Kotecha, R., Pastides, A. and Shehata, H. 2016. Metformin versus placebo in obese pregnant women without diabetes mellitus. New England Journal of Medicine. 374, pp. 434-43. https://doi.org/10.1056/NEJMoa1509819
Prospective first-trimester screening for trisomies by cell-free DNA testing of maternal blood in twin pregnancy
Sarno, L., Revello, R., Hanson, E., Akolekar, R. and Nicolaides, K. H. 2016. Prospective first-trimester screening for trisomies by cell-free DNA testing of maternal blood in twin pregnancy. Ultrasound in Obstetrics and Gynecology. 47 (6), pp. 705-11. https://doi.org/10.1002/uog.15913
Prediction of stillbirth from biochemical and biophysical markers at 11-13 weeks
Mastrodima, S., Akolekar, R., Yerlikaya, G., Tzelepis, T. and Nicolaides, K. H. 2016. Prediction of stillbirth from biochemical and biophysical markers at 11-13 weeks. Ultrasound in Obstetrics and Gynecology. 48 (5), pp. 613-617. https://doi.org/10.1002/uog.17289
Prediction of stillbirth from maternal demographic and pregnancy characteristics
Yerlikaya, G., Akolekar, R., McPherson, K., Syngelaki, A. and Nicolaides, K. H. 2016. Prediction of stillbirth from maternal demographic and pregnancy characteristics. Ultrasound in Obstetrics and Gynecology. 48 (5), pp. 607-612. https://doi.org/10.1002/uog.17290
Endoscopic placental laser coagulation in dichorionic and monochorionic triplet pregnancies
Peeva, G., Chaveeva, P., Gil Guevara, E., Akolekar, R. and Nicolaides, K. H. 2016. Endoscopic placental laser coagulation in dichorionic and monochorionic triplet pregnancies. Fetal Diagnosis and Therapy. 40 (3), pp. 174-180. https://doi.org/10.1159/000443792
Prediction of stillbirth from maternal factors, fetal biometry and uterine artery Doppler at 19-24 weeks
Akolekar, R., Tokunaka, M., Ortega, N., Syngelaki, A. and Nicolaides, K. H. 2016. Prediction of stillbirth from maternal factors, fetal biometry and uterine artery Doppler at 19-24 weeks. Ultrasound in Obstetrics and Gynecology. 48 (5), pp. 624-630. https://doi.org/10.1002/uog.17295
Prediction of stillbirth from placental growth factor at 11-13 weeks
Akolekar, R., Machuca, M., Mendes, M., Paschos, V. and Nicolaides, K. H. 2016. Prediction of stillbirth from placental growth factor at 11-13 weeks. Ultrasound in Obstetrics and Gynecology. 48 (5), pp. 618-623. https://doi.org/10.1002/uog.17288
Prediction of stillbirth from placental growth factor at 19-24 weeks
Aupont J. E., Akolekar, R., Illian, A., Neonakis, S. and Nicolaides, K. H. 2016. Prediction of stillbirth from placental growth factor at 19-24 weeks. Ultrasound in Obstetrics and Gynecology. 48 (5), pp. 631-635. https://doi.org/10.1002/uog.17229
Biophysical and biochemical markers at 35-37 weeks' gestation in the prediction of adverse perinatal outcome
Valiño, N., Giunta, G., Gallo, D. M., Akolekar, R. and Nicolaides, K. H. 2015. Biophysical and biochemical markers at 35-37 weeks' gestation in the prediction of adverse perinatal outcome. Ultrasound in Obstetrics and Gynecology. 47 (2), pp. 203-209. https://doi.org/10.1002/uog.15663