A prognostic model to guide decision-making on timing of delivery in late preterm pre-eclampsia: the PEACOCK prospective cohort study
Background: Pre-eclampsia affects around 2–3% of all pregnancies, and is associated with potential serious complications for the woman and the baby. Once diagnosed, progression of the syndrome can be unpredictable, and decisions around timing of delivery need to take into account evolving maternal c...
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| Format: | Article |
| Language: | English |
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NIHR Journals Library
2021-05-01
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| Series: | Health Technology Assessment |
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| Online Access: | https://doi.org/10.3310/hta25300 |
| _version_ | 1818437684896464896 |
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| author | Kate Duhig Paul T Seed Anna Placzek Jenie Sparkes Carolyn Gill Anna Brockbank Andrew Shennan Shakila Thangaratinam Lucy C Chappell |
| author_facet | Kate Duhig Paul T Seed Anna Placzek Jenie Sparkes Carolyn Gill Anna Brockbank Andrew Shennan Shakila Thangaratinam Lucy C Chappell |
| author_sort | Kate Duhig |
| collection | DOAJ |
| description | Background: Pre-eclampsia affects around 2–3% of all pregnancies, and is associated with potential serious complications for the woman and the baby. Once diagnosed, progression of the syndrome can be unpredictable, and decisions around timing of delivery need to take into account evolving maternal complications and perinatal morbidity. Novel prognostic models and blood biomarkers for determination of need for delivery in pregnancies with pre-eclampsia are now emerging. Objective: The objective of the study was to establish a prognostic model to inform optimal timing of delivery in women with late preterm pre-eclampsia (34+ 0 to 36+ 6 weeks’ gestation), comparing novel candidate biomarkers (e.g. placental growth factor) with clinical and routinely collected blood/urinary parameters [incorporated into the PREP-S (Prediction models for Risk of Early-onset Pre-eclampsia – Survival) model] to determine clinically indicated need for delivery for pre-eclampsia (or related complications) within 7 days of assessment. Methods: Prospective recruitment of women in whom blood samples for placental growth factor and soluble fms-like tyrosine kinase-1 testing was obtained, alongside clinical data, for use within the PREP-S model. Candidate variables were compared using standard methods (sensitivity, specificity, receiver operator curve areas). Estimated probability of early delivery from PREP-S was compared with actual event rates by calibration. Setting: The PEACOCK (Prognostic indicators of severe disEAse in women with late preterm pre-eClampsia tO guide deCision maKing on timing of delivery) study was a prospective cohort study, nested within the PHOENIX (Pre-eclampsia in HOspital: Early iNductIon or eXpectant management) trial. Participants: Women between 34+ 0 and 36+ 6 weeks’ gestation, with a diagnosis of pre-eclampsia, in whom a plasma (ethylenediaminetetraacetic acid) blood sample for placental growth factor testing was obtained, alongside clinical data for the assessment of variables in a prognostic model. Main outcome measures: Clinically indicated need for delivery for pre-eclampsia within 7 days of assessment. Statistical analysis: both PREP-S and placental growth factor were assessed and compared using standard methods (sensitivity and specificity for placental growth factor thresholds of 100 pg/ml and < 12 pg/ml, and receiver operating characteristic areas for continuous measurements). The estimated probability of early delivery from PREP-S was compared with actual event rates for women with similar probabilities by calibration. Calibration using logistic regression was also used. Results: Between 27 April 2016 and 24 December 2018, 501 women were recruited to the study. Although placental growth factor testing had high sensitivity (97.9%) for delivery within 7 days, the negative predictive value was only 71.4% and the specificity was low (8.4%). The area under the curve for the clinical prediction model (PREP-S) and placental growth factor in this cohort in determining need for delivery within 7 days was 0.64 (standard error 0.03) and 0.60 (standard error 0.03), respectively, and 0.65 (standard error 0.03) in combination. Limitations: A high proportion of women in this cohort already had low placental growth factor concentrations at the time of confirmed diagnosis, which reduced the ability of the biomarker to further predict adverse outcomes. Conclusions: In this group of women with late preterm pre-eclampsia, placental growth factor measurement is not likely to add to the current clinical assessment to help plan care for late preterm pre-eclampsia regarding timing of delivery. Existing models developed in women with early-onset pre-eclampsia to predict complications cannot be used to predict clinically indicated need for delivery in women with late preterm pre-eclampsia. Future work: Further statistical modelling and subgroup analysis is being considered to assess if improved model performance in the whole cohort or a subgroup can be achieved. Addition of other biomarkers to the model may also be of use and will be explored. Trial registration: Current Controlled Trials ISRCTN01879376. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 30. See the NIHR Journals Library website for further project information. |
| first_indexed | 2024-12-14T17:28:36Z |
| format | Article |
| id | doaj.art-d983f691f7c94f2ab75370c896cc7f4e |
| institution | Directory Open Access Journal |
| issn | 1366-5278 2046-4924 |
| language | English |
| last_indexed | 2024-12-14T17:28:36Z |
| publishDate | 2021-05-01 |
| publisher | NIHR Journals Library |
| record_format | Article |
| series | Health Technology Assessment |
| spelling | doaj.art-d983f691f7c94f2ab75370c896cc7f4e2022-12-21T22:53:09ZengNIHR Journals LibraryHealth Technology Assessment1366-52782046-49242021-05-01253010.3310/hta2530015/59/06A prognostic model to guide decision-making on timing of delivery in late preterm pre-eclampsia: the PEACOCK prospective cohort studyKate Duhig0Paul T Seed1Anna Placzek2Jenie Sparkes3Carolyn Gill4Anna Brockbank5Andrew Shennan6Shakila Thangaratinam7Lucy C Chappell8Department of Women and Children’s Health, School of Life Course Sciences, King’s College London, London, UKDepartment of Women and Children’s Health, School of Life Course Sciences, King’s College London, London, UKNational Perinatal Epidemiology Unit Clinical Trials Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UKDepartment of Women and Children’s Health, School of Life Course Sciences, King’s College London, London, UKDepartment of Women and Children’s Health, School of Life Course Sciences, King’s College London, London, UKDepartment of Women and Children’s Health, School of Life Course Sciences, King’s College London, London, UKDepartment of Women and Children’s Health, School of Life Course Sciences, King’s College London, London, UKInstitute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UKDepartment of Women and Children’s Health, School of Life Course Sciences, King’s College London, London, UKBackground: Pre-eclampsia affects around 2–3% of all pregnancies, and is associated with potential serious complications for the woman and the baby. Once diagnosed, progression of the syndrome can be unpredictable, and decisions around timing of delivery need to take into account evolving maternal complications and perinatal morbidity. Novel prognostic models and blood biomarkers for determination of need for delivery in pregnancies with pre-eclampsia are now emerging. Objective: The objective of the study was to establish a prognostic model to inform optimal timing of delivery in women with late preterm pre-eclampsia (34+ 0 to 36+ 6 weeks’ gestation), comparing novel candidate biomarkers (e.g. placental growth factor) with clinical and routinely collected blood/urinary parameters [incorporated into the PREP-S (Prediction models for Risk of Early-onset Pre-eclampsia – Survival) model] to determine clinically indicated need for delivery for pre-eclampsia (or related complications) within 7 days of assessment. Methods: Prospective recruitment of women in whom blood samples for placental growth factor and soluble fms-like tyrosine kinase-1 testing was obtained, alongside clinical data, for use within the PREP-S model. Candidate variables were compared using standard methods (sensitivity, specificity, receiver operator curve areas). Estimated probability of early delivery from PREP-S was compared with actual event rates by calibration. Setting: The PEACOCK (Prognostic indicators of severe disEAse in women with late preterm pre-eClampsia tO guide deCision maKing on timing of delivery) study was a prospective cohort study, nested within the PHOENIX (Pre-eclampsia in HOspital: Early iNductIon or eXpectant management) trial. Participants: Women between 34+ 0 and 36+ 6 weeks’ gestation, with a diagnosis of pre-eclampsia, in whom a plasma (ethylenediaminetetraacetic acid) blood sample for placental growth factor testing was obtained, alongside clinical data for the assessment of variables in a prognostic model. Main outcome measures: Clinically indicated need for delivery for pre-eclampsia within 7 days of assessment. Statistical analysis: both PREP-S and placental growth factor were assessed and compared using standard methods (sensitivity and specificity for placental growth factor thresholds of 100 pg/ml and < 12 pg/ml, and receiver operating characteristic areas for continuous measurements). The estimated probability of early delivery from PREP-S was compared with actual event rates for women with similar probabilities by calibration. Calibration using logistic regression was also used. Results: Between 27 April 2016 and 24 December 2018, 501 women were recruited to the study. Although placental growth factor testing had high sensitivity (97.9%) for delivery within 7 days, the negative predictive value was only 71.4% and the specificity was low (8.4%). The area under the curve for the clinical prediction model (PREP-S) and placental growth factor in this cohort in determining need for delivery within 7 days was 0.64 (standard error 0.03) and 0.60 (standard error 0.03), respectively, and 0.65 (standard error 0.03) in combination. Limitations: A high proportion of women in this cohort already had low placental growth factor concentrations at the time of confirmed diagnosis, which reduced the ability of the biomarker to further predict adverse outcomes. Conclusions: In this group of women with late preterm pre-eclampsia, placental growth factor measurement is not likely to add to the current clinical assessment to help plan care for late preterm pre-eclampsia regarding timing of delivery. Existing models developed in women with early-onset pre-eclampsia to predict complications cannot be used to predict clinically indicated need for delivery in women with late preterm pre-eclampsia. Future work: Further statistical modelling and subgroup analysis is being considered to assess if improved model performance in the whole cohort or a subgroup can be achieved. Addition of other biomarkers to the model may also be of use and will be explored. Trial registration: Current Controlled Trials ISRCTN01879376. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 30. See the NIHR Journals Library website for further project information.https://doi.org/10.3310/hta25300pre-eclampsiahypertension in pregnancyprognostic modelplacental growth factor |
| spellingShingle | Kate Duhig Paul T Seed Anna Placzek Jenie Sparkes Carolyn Gill Anna Brockbank Andrew Shennan Shakila Thangaratinam Lucy C Chappell A prognostic model to guide decision-making on timing of delivery in late preterm pre-eclampsia: the PEACOCK prospective cohort study Health Technology Assessment pre-eclampsia hypertension in pregnancy prognostic model placental growth factor |
| title | A prognostic model to guide decision-making on timing of delivery in late preterm pre-eclampsia: the PEACOCK prospective cohort study |
| title_full | A prognostic model to guide decision-making on timing of delivery in late preterm pre-eclampsia: the PEACOCK prospective cohort study |
| title_fullStr | A prognostic model to guide decision-making on timing of delivery in late preterm pre-eclampsia: the PEACOCK prospective cohort study |
| title_full_unstemmed | A prognostic model to guide decision-making on timing of delivery in late preterm pre-eclampsia: the PEACOCK prospective cohort study |
| title_short | A prognostic model to guide decision-making on timing of delivery in late preterm pre-eclampsia: the PEACOCK prospective cohort study |
| title_sort | prognostic model to guide decision making on timing of delivery in late preterm pre eclampsia the peacock prospective cohort study |
| topic | pre-eclampsia hypertension in pregnancy prognostic model placental growth factor |
| url | https://doi.org/10.3310/hta25300 |
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