{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T14:13:36Z","timestamp":1788444816052,"version":"build-2803163510"},"reference-count":22,"publisher":"BMJ","issue":"7","license":[{"start":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:00:00Z","timestamp":1782950400000},"content-version":"unspecified","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001826","name":"ZonMw","doi-asserted-by":"publisher","award":["10390032310044"],"award-info":[{"award-number":["10390032310044"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Dutch Organisation for Health Research and Development. Roche Diagnostics"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2026,5,27]]},"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>The soluble FMS-like tyrosine kinase-1 and placental growth factor (sFlt-1\/PlGF) ratio has demonstrated impressive predictive test characteristics in women with suspected pre-eclampsia. However, it remains a matter of debate whether the introduction of this novel test can indeed translate to a reduction in pre-eclampsia-related hospital admissions, outpatient visits and can consequently lower overall healthcare costs. The PREPARE II study aims to investigate whether the sFlt-1\/PlGF ratio, along with digital self-monitoring, can reduce pre-eclampsia-related healthcare utilisation in the first week following the test for women with suspected pre-eclampsia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>This is a randomised controlled trial across six centres which includes women (\u226516 years old) between 20 and 37 weeks of gestation with suspected pre-eclampsia due to one or more identified symptoms. For power calculation, we assumed that the sFlt-1\/PlGF ratio including a telemonitoring strategy leads to a de-escalation of care by cumulatively reducing the frequency of pre-eclampsia-related hospital admissions and\/or outpatient visits in the first week from 50% in the control group to 35% in the intervention group. Considering a loss to follow-up of 5%,\u2009a sample size of approximately 470\u2009women is required with 235\u2009women per arm (\u03b1=5%; power=90%). The intervention is an algorithm based on the urine protein\/creatinine ratio (PCr)+sFlt-1\/PlGF ratio, along with a telemonitoring strategy. The algorithm incorporates a PCr cut-off of 30 (mg\/mmol) and a sFlt-1\/PlGF ratio cut-off of 38 for risk classification. Subsequent clinical follow-up recommendations are stratified based on this classification: low risk entails no additional follow-up, returning to routine antenatal care; intermediate risk includes telemonitoring; high risk necessitates immediate admission. The primary outcome is the occurrence of pre-eclampsia-related healthcare utilisation in the first week after testing. Secondary outcomes are maternal\/perinatal adverse events, total healthcare usage, pre-eclampsia diagnosis, quality of life and productivity losses. A cost-effectiveness analysis from a societal perspective will be performed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>Ethical approval was obtained from the Medical Ethics Committee of Leiden University Medical Centre (METC LDD) on 21 July 2025 (reference NL-009295). The results will be disseminated through peer-reviewed publications and presentations at international conferences.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>NL88527.058.24.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2025-113516","type":"journal-article","created":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T11:41:37Z","timestamp":1782992497000},"page":"e113516","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Cost-effectiveness of the sFlt-1\/PlGF ratio and telemonitoring in managing suspected pre-eclampsia: protocol for the PREPARE II randomised controlled trial"],"prefix":"10.1136","volume":"16","author":[{"given":"M","family":"Wind","sequence":"first","affiliation":[{"name":"Department of Obstetrics, Leiden University Medical Center, Leiden, Zuid-Holland, the 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Bodegom-Vos","sequence":"additional","affiliation":[{"name":"Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, Zuid-Holland, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F","family":"Boekhorst","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Groene Hart Hospital, Gouda, Zuid-Holland, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C M","family":"Cobbaert","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry, Leiden University Medical Center, Leiden, Zuid-Holland, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W","family":"Hermes","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Haaglanden Medical Center, The Hague, Zuid-Holland, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M E","family":"Van 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