Atosiban versus placebo in the treatment of threatened preterm birth between 30 and 34 weeks gestation: study protocol of the 4-year APOSTEL 8 follow-up

Introduction Currently, the majority of women worldwide with threatened preterm birth are treated with tocolytics. Although tocolytics can effectively delay birth for 48 hours, no tocolytic drug has convincingly been shown to improve neonatal outcomes and effects on long-term child development are u...

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Main Authors: Martijn A Oudijk, Madelon van Wely, Eva Pajkrt, Job Klumper, Aleid G van Wassenaer-Leemhuis, Emilie V J van Limburg Stirum, Janneke Van 't Hooft, Larissa van der Windt
Format: Article
Language:English
Published: BMJ Publishing Group 2024-07-01
Series:BMJ Open
Online Access:https://bmjopen.bmj.com/content/14/7/e083600.full
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author Martijn A Oudijk
Madelon van Wely
Eva Pajkrt
Job Klumper
Aleid G van Wassenaer-Leemhuis
Emilie V J van Limburg Stirum
Janneke Van 't Hooft
Larissa van der Windt
author_facet Martijn A Oudijk
Madelon van Wely
Eva Pajkrt
Job Klumper
Aleid G van Wassenaer-Leemhuis
Emilie V J van Limburg Stirum
Janneke Van 't Hooft
Larissa van der Windt
author_sort Martijn A Oudijk
collection DOAJ
description Introduction Currently, the majority of women worldwide with threatened preterm birth are treated with tocolytics. Although tocolytics can effectively delay birth for 48 hours, no tocolytic drug has convincingly been shown to improve neonatal outcomes and effects on long-term child development are unknown. The aim of this follow-up study of a placebo controlled randomised trial is to investigate the long-term effects of atosiban administration in case of threatened preterm birth on child’s neurodevelopment and behaviour development, overall health and mortality.Methods and analysis This protocol concerns a follow-up study of the multicentre randomised double-blind placebo controlled APOSTEL 8 trial (NL61439.018.17, EudraCT-number 2017-001007-72). In this trial, women with threatened preterm birth (between 30 and 34 weeks of gestation) defined as uterine contractions with (1) a cervical length of <15 mm or (2) a cervical length of 15–30 mm and a positive fibronectin test or (3) in centres where cervical length measurement is not part of the local protocol: a positive fibronectin test or Actim-Partus test or (4) ruptured membranes, are randomised to atosiban or placebo for 48 hours. The primary outcome is a composite of perinatal mortality and severe neonatal morbidity. Children born to mothers who participated in the APOSTEL 8 study (n=760) will be eligible for follow-up at 4 years of corrected age and assessed using four parent-reported questionnaires. Primary outcomes are neurodevelopment and behaviour problems. Secondary outcomes are on child growth and general health. All outcomes will be compared between the atosiban and placebo group with OR and corresponding 95% CI. Analyses will be performed 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 (Dutch WMO-law) did not apply to our study (W21_386 # 21.431). Results will be published in a peer-reviewed journal and shared with stakeholders and participants. This protocol is published before analysis of the results.
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spelling doaj-art-eba65ee3ca9e48628508f3182568de922025-08-20T02:36:35ZengBMJ Publishing GroupBMJ Open2044-60552024-07-0114710.1136/bmjopen-2023-083600Atosiban versus placebo in the treatment of threatened preterm birth between 30 and 34 weeks gestation: study protocol of the 4-year APOSTEL 8 follow-upMartijn A Oudijk0Madelon van Wely1Eva Pajkrt2Job Klumper3Aleid G van Wassenaer-Leemhuis4Emilie V J van Limburg Stirum5Janneke Van 't Hooft6Larissa van der Windt7Obstetrics, Amsterdam UMC Locatie De Boelelaan, Amsterdam, The Netherlands2 Amsterdam Reproduction and Development Research Institute, Amsterdam, The NetherlandsObstetrics and Gynaecology, Amsterdam UMC Locatie AMC, Amsterdam, The NetherlandsAmsterdam Reproduction and Development research institute, Amsterdam, NetherlandsAmsterdam Reproduction and Development research institute, Amsterdam, NetherlandsObstetrics and Gynaecology, Amsterdam UMC Locatie AMC, Amsterdam, The NetherlandsObstetrics and Gynaecology, Amsterdam UMC Locatie AMC, Amsterdam, The NetherlandsObstetrics and Gynaecology, Amsterdam UMC Locatie AMC, Amsterdam, The NetherlandsIntroduction Currently, the majority of women worldwide with threatened preterm birth are treated with tocolytics. Although tocolytics can effectively delay birth for 48 hours, no tocolytic drug has convincingly been shown to improve neonatal outcomes and effects on long-term child development are unknown. The aim of this follow-up study of a placebo controlled randomised trial is to investigate the long-term effects of atosiban administration in case of threatened preterm birth on child’s neurodevelopment and behaviour development, overall health and mortality.Methods and analysis This protocol concerns a follow-up study of the multicentre randomised double-blind placebo controlled APOSTEL 8 trial (NL61439.018.17, EudraCT-number 2017-001007-72). In this trial, women with threatened preterm birth (between 30 and 34 weeks of gestation) defined as uterine contractions with (1) a cervical length of <15 mm or (2) a cervical length of 15–30 mm and a positive fibronectin test or (3) in centres where cervical length measurement is not part of the local protocol: a positive fibronectin test or Actim-Partus test or (4) ruptured membranes, are randomised to atosiban or placebo for 48 hours. The primary outcome is a composite of perinatal mortality and severe neonatal morbidity. Children born to mothers who participated in the APOSTEL 8 study (n=760) will be eligible for follow-up at 4 years of corrected age and assessed using four parent-reported questionnaires. Primary outcomes are neurodevelopment and behaviour problems. Secondary outcomes are on child growth and general health. All outcomes will be compared between the atosiban and placebo group with OR and corresponding 95% CI. Analyses will be performed 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 (Dutch WMO-law) did not apply to our study (W21_386 # 21.431). Results will be published in a peer-reviewed journal and shared with stakeholders and participants. This protocol is published before analysis of the results.https://bmjopen.bmj.com/content/14/7/e083600.full
spellingShingle Martijn A Oudijk
Madelon van Wely
Eva Pajkrt
Job Klumper
Aleid G van Wassenaer-Leemhuis
Emilie V J van Limburg Stirum
Janneke Van 't Hooft
Larissa van der Windt
Atosiban versus placebo in the treatment of threatened preterm birth between 30 and 34 weeks gestation: study protocol of the 4-year APOSTEL 8 follow-up
BMJ Open
title Atosiban versus placebo in the treatment of threatened preterm birth between 30 and 34 weeks gestation: study protocol of the 4-year APOSTEL 8 follow-up
title_full Atosiban versus placebo in the treatment of threatened preterm birth between 30 and 34 weeks gestation: study protocol of the 4-year APOSTEL 8 follow-up
title_fullStr Atosiban versus placebo in the treatment of threatened preterm birth between 30 and 34 weeks gestation: study protocol of the 4-year APOSTEL 8 follow-up
title_full_unstemmed Atosiban versus placebo in the treatment of threatened preterm birth between 30 and 34 weeks gestation: study protocol of the 4-year APOSTEL 8 follow-up
title_short Atosiban versus placebo in the treatment of threatened preterm birth between 30 and 34 weeks gestation: study protocol of the 4-year APOSTEL 8 follow-up
title_sort atosiban versus placebo in the treatment of threatened preterm birth between 30 and 34 weeks gestation study protocol of the 4 year apostel 8 follow up
url https://bmjopen.bmj.com/content/14/7/e083600.full
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