Hypertension; Maternal medicine; OBSTETRICS; FLT1 protein, human; Vascular Endothelial Growth Factor Receptor-1; Placenta Growth Factor; Biomarkers; Infant, Newborn; Pregnancy; Female; Humans; Cesarean Section; Predictive Value of Tests; Randomized Controlled Trials as Topic; Multicenter Studies as Topic; Pre-Eclampsia/diagnosis; Pre-Eclampsia/prevention & control; Pre-Eclampsia/epidemiology; Pre-Eclampsia; Medicine (all)
Abstract :
[en] [en] INTRODUCTION: Pre-eclampsia affects ~5%-7% of pregnancies. Although improved obstetric care has significantly diminished its associated maternal mortality, it remains a leading cause of maternal morbidity and mortality in the world. Term pre-eclampsia accounts for 70% of all cases and a large proportion of maternal-fetal morbidity related to this condition. Unlike in preterm pre-eclampsia, the prediction and prevention of term pre-eclampsia remain unsolved. Previously proposed approaches are based on combined third-trimester screening and/or prophylactic drugs, but these policies are unlikely to be widely implementable in many world settings. Recent evidence shows that the soluble fms-like tyrosine kinase-1 (s-Flt-1) to placental growth factor (PlGF) ratio measured at 35-37 weeks' gestation predicts term pre-eclampsia with an 80% detection rate. Likewise, recent studies demonstrate that induction of labour beyond 37 weeks is safe and well accepted by women. We hypothesise that a single-step universal screening for term pre-eclampsia based on sFlt1/PlGF ratio at 35-37 weeks followed by planned delivery beyond 37 weeks reduces the prevalence of term pre-eclampsia without increasing the caesarean section rates or worsening the neonatal outcomes.
METHODS AND ANALYSIS: We propose an open-label randomised clinical trial to evaluate the impact of a screening of term pre-eclampsia with the sFlt-1/PlGF ratio followed by planned delivery in asymptomatic nulliparous women at 35-37 weeks. Women will be assigned 1:1 to revealed (sFlt-1/PlGF known to clinicians) versus concealed (unknown) arms. A cut-off of >90th centile is used to define the high risk of subsequent pre-eclampsia and offer planned delivery from 37 weeks. The efficacy variables will be analysed and compared between groups primarily following an intention-to-treat approach, by ORs and their 95% CI. This value will be computed using a Generalised Linear Mixed Model for binary response (study group as fixed effect and the centre as intercept random effect).
ETHICS AND DISSEMINATION: The study is conducted under the principles of Good Clinical Practice. This study was accepted by the Clinical Research Ethics Committee of Hospital Clinic Barcelona on 20 November 2020. Subsequent approval by individual ethical committees and competent authorities was granted. The study results will be published in peer-reviewed journals and disseminated at international conferences.
TRIAL REGISTRATION NUMBER: NCT04766866.
Disciplines :
Reproductive medicine (gynecology, andrology, obstetrics)
Author, co-author :
Llurba, Elisa; Obstetrics and Gynecology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
Crispi, Fatima; BCNatal, Fetal Medicine Research Center, Hospital Clínic and Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain
Crovetto, Francesca ; Hospital Clinic de Barcelona, Barcelona, Spain
Youssef, Lina; IDIBAPS, Barcelona, Spain
Delgado, Juan Luis; Unidad Medicina Fetal Murcia, IMIB Arrixaca, Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, Spain
Puig, Isabel; Unidad Medicina Fetal Murcia, IMIB Arrixaca, Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, Spain
Mora, Josefina; Biochemistry, Hospital Sant Pau, Barcelona, Spain
Krofta, Ladislav; Institute for the Care of Mother and Child, Third Faculty of Medicine, Charles University, Prague, Czech Republic
Mackova, Katerina; Institute for the Care of Mother and Child, Third Faculty of Medicine, Charles University, Prague, Czech Republic
Martinez-Varea, Alicia; Hospital Politécnico y Universitario La Fe, Valencia, Spain
Tubau, Albert ; Obstetrician, Son Llàtzer Hospital, Palma de Mallorca, Illes Balears, Spain
Ruiz, Aina; Obstetrician, Son Llàtzer Hospital, Palma de Mallorca, Illes Balears, Spain
Paya, Antoni; Hospital del Mar, Barcelona, Spain
Prat, Maria; Hospital del Mar, Barcelona, Spain
Chantraine, Frédéric ; Université de Liège - ULiège > Département des sciences cliniques
Comas, Carmina; Hospital Germans Trias i Pujol, Badalona, Spain
Kajdy, Anna; Centre of Postgraduate Medical Education, Obstetrics and Gynecology and Perinatal Medicine, Warsaw, Poland
Lopez-Tinajero, Maria Fernanda; Hospital Clinic de Barcelona, Barcelona, Spain
Figueras, Francesc ; BCNatal, Fetal Medicine Research Center, Hospital Clínic and Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain FFIGUERA@clinic.cat
Gratacos, Eduard; Hospital Clinic de Barcelona, Barcelona, Spain
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