Pessary or progesterone to prevent preterm birth in women with short cervical length: protocol of the 4-6 year follow-up of a randomised controlled trial (Quadruple-P)

Emilie V J van Limburg Stirum; Larissa I van der Windt; Charlotte E van Dijk; Anneloes L van Baar; Aleid G Leemhuis; Madelon van Wely; Marjon A de Boer; Janneke van 't Hooft; Martijn A Oudijk; Eva Pajkrt; Quadruple-P study group

doi:10.1136/bmjopen-2022-064049

Pessary or progesterone to prevent preterm birth in women with short cervical length: protocol of the 4-6 year follow-up of a randomised controlled trial (Quadruple-P)

BMJ Open. 2022 Aug 24;12(8):e064049. doi: 10.1136/bmjopen-2022-064049.

Authors

Emilie V J van Limburg Stirum^{1

2}, Larissa I van der Windt^{3

2}, Charlotte E van Dijk^{3

2}, Anneloes L van Baar⁴, Aleid G Leemhuis^{2

5}, Madelon van Wely^{3

2}, Marjon A de Boer^{2

6}, Janneke van 't Hooft^{3

2}, Martijn A Oudijk^{2

6}, Eva Pajkrt^{3

2}; Quadruple-P study group

Collaborators

Quadruple-P study group:
E S A van den Akker, M N Bekker, K de Boer, I M Evers, S J Gordijn, B B J Hermsen, A B Hooker, N Horrée, J Langenveld, F W van der Made, M Sueters, H Visser, K C Vollebregt, J van Drongelen

Affiliations

¹ Amsterdam UMC location University of Amsterdam, Department of Obstetrics and Gynaecology, Amsterdam, The Netherlands e.v.vanlimburgstirum@amsterdamumc.nl.
² Amsterdam Reproduction & Development, Amsterdam, The Netherlands.
³ Amsterdam UMC location University of Amsterdam, Department of Obstetrics and Gynaecology, Amsterdam, The Netherlands.
⁴ Utrecht University, Child and Adolescent studies, Utrecht, The Netherlands.
⁵ Emma Children's Hospital, Amsterdam UMC location University of Amsterdam, Department of Neonatology and Paediatrics, Amsterdam, The Netherlands.
⁶ Amsterdam UMC location Vrije Universiteit Amsterdam, Department of Obstetrics and Gynaecology, Amsterdam, The Netherlands.

Abstract

Introduction: Vaginal progesterone and a cervical pessary are both interventions that are investigated for the prevention of preterm birth (PTB). Thus far, beneficial or harmful effects of these interventions on long-term child health and development are described, but evidence is not robust enough to draw firm conclusions. With this follow-up study, we intent to investigate if progesterone or a pessary is superior for the prevention of PTB considering the child's health at 4-6 years of corrected age.

Methods and analysis: This study is a follow-up study of the Quadruple-P trial; a multicentre, randomised clinical trial (NL42926.018.13, Eudractnumber 2013-002884-24) which randomises women with an asymptomatic midtrimester short cervix to daily progesterone or a pessary for the prevention of PTB. All children born to mothers who participated in the Quadruple-P study (n=628 singletons and n=332 multiples) will be eligible for follow-up at 4-6 years of corrected age. Children will be assessed using parental questionnaires. Main outcomes are child (neuro)development and behaviour. Other outcomes include child mortality, growth and general health. A composite of adverse child outcomes will be compared between the progesterone and pessary groups reporting OR and the corresponding 95% CI. Analyses will be performed separately for singletons and multiples and using the intention-to-treat approach.

Ethics and dissemination: The Medical Research Ethics Committee from Amsterdam UMC confirmed that de Medical Research Involving Human Subjects Act (WMO) did not apply to our study (W20_481 #20.531). Results will be published in a peer-reviewed journal and shared with stakeholders and participants. This protocol is published before analysis of the results.

Trial registration number: Dutch Trial Register (NL9646).

Keywords: Developmental neurology & neurodisability; Fetal medicine; Maternal medicine.

Publication types

Clinical Trial Protocol
Research Support, Non-U.S. Gov't

MeSH terms

Cervical Length Measurement
Cervix Uteri / diagnostic imaging
Child
Female
Follow-Up Studies
Humans
Infant, Newborn
Multicenter Studies as Topic
Pessaries*
Pregnancy
Premature Birth* / prevention & control
Progesterone / therapeutic use
Randomized Controlled Trials as Topic

Substances

Progesterone