TY - JOUR
T1 - Long-term outcomes following antenatal exposure to low-dose aspirin
T2 - study protocol for the 4-year follow-up of the APRIL randomised controlled trial
AU - Landman, Anadeijda J. E. M. C.
AU - van Limburg Stirum, Emilie V. J.
AU - van 't Hooft, Janneke
AU - Leemhuis, Aleid G.
AU - Finken, Martijn J. J.
AU - van Baar, Anneloes L.
AU - Roseboom, Tessa J.
AU - Ravelli, Anita C. J.
AU - van Wely, Madelon
AU - Oosterlaan, Jaap
AU - Painter, Rebecca C.
AU - Pajkrt, Eva
AU - Oudijk, Martijn A.
AU - de Boer, Marjon A.
N1 - Funding Information: This work was supported by Amsterdam Reproduction & Development (AR&D) research institute ( https://www.amsterdamumc.org/en/research/institutes/amsterdam-reproductiondevelopment.htm ). AR&D has no influence on study design, data collection, management, analysis, and interpretation of data, writing of the report and the decision to submit the report for publication. They do not have ultimate authority over any of these activities. Publisher Copyright: ©
PY - 2022/8/1
Y1 - 2022/8/1
N2 - INTRODUCTION: The use of low-dose aspirin by pregnant women to prevent preterm pre-eclampsia is gradually increasing. The administration of aspirin during pregnancy improves perinatal outcome, which could translate into improved child outcome in the long term. However, antenatal exposure to aspirin could have adverse effects on child development that may manifest later in life. The aim of this follow-up study is to assess the long-term effects of antenatal exposure to low-dose aspirin compared with placebo on survival, (neuro)development, behaviour and general health at 4 years corrected age. METHODS AND ANALYSIS: This is a follow-up study of the Dutch double-blind randomised controlled APRIL trial which assessed the effectiveness of treatment with aspirin (80 mg daily) compared with placebo for the prevention of preterm birth in women with a previous spontaneous preterm birth. Treatment was initiated before 16 weeks of gestation and continued until 36 weeks or birth. We aim to follow-up all 379 children born to women who participated in the APRIL trial and survived the neonatal period, at the corrected age of 4 years. The main outcomes are (neuro)development as assessed by the Ages and Stages Questionnaire, and behaviour as assessed by the Strength and Difficulties Questionnaire. Additional outcomes include mortality, growth and general health from birth up to 4 years, and a composite outcome including mortality, abnormal (neuro)development and problem behaviour. Analyses will be performed by intention-to-treat using a superiority design. ETHICS AND DISSEMINATION: Institutional Review Board approval was obtained from the Medical Research Ethics Committee from Amsterdam Medical Center (no. W20 289#20.325). The results will be published in a peer-reviewed journal and presented at conferences. TRIAL REGISTRATION NUMBER: The APRIL trial (NTR5675, NL5553; EudraCT number 2015-003220-31) and the APRIL follow-up study (NL8950) are registered in the Dutch trial register. The study is funded by the Amsterdam Reproduction & Development research institute.
AB - INTRODUCTION: The use of low-dose aspirin by pregnant women to prevent preterm pre-eclampsia is gradually increasing. The administration of aspirin during pregnancy improves perinatal outcome, which could translate into improved child outcome in the long term. However, antenatal exposure to aspirin could have adverse effects on child development that may manifest later in life. The aim of this follow-up study is to assess the long-term effects of antenatal exposure to low-dose aspirin compared with placebo on survival, (neuro)development, behaviour and general health at 4 years corrected age. METHODS AND ANALYSIS: This is a follow-up study of the Dutch double-blind randomised controlled APRIL trial which assessed the effectiveness of treatment with aspirin (80 mg daily) compared with placebo for the prevention of preterm birth in women with a previous spontaneous preterm birth. Treatment was initiated before 16 weeks of gestation and continued until 36 weeks or birth. We aim to follow-up all 379 children born to women who participated in the APRIL trial and survived the neonatal period, at the corrected age of 4 years. The main outcomes are (neuro)development as assessed by the Ages and Stages Questionnaire, and behaviour as assessed by the Strength and Difficulties Questionnaire. Additional outcomes include mortality, growth and general health from birth up to 4 years, and a composite outcome including mortality, abnormal (neuro)development and problem behaviour. Analyses will be performed by intention-to-treat using a superiority design. ETHICS AND DISSEMINATION: Institutional Review Board approval was obtained from the Medical Research Ethics Committee from Amsterdam Medical Center (no. W20 289#20.325). The results will be published in a peer-reviewed journal and presented at conferences. TRIAL REGISTRATION NUMBER: The APRIL trial (NTR5675, NL5553; EudraCT number 2015-003220-31) and the APRIL follow-up study (NL8950) are registered in the Dutch trial register. The study is funded by the Amsterdam Reproduction & Development research institute.
KW - EPIDEMIOLOGY
KW - Fetal medicine
KW - Maternal medicine
KW - PAEDIATRICS
KW - PERINATOLOGY
UR - http://www.scopus.com/inward/record.url?scp=85135551507&partnerID=8YFLogxK
U2 - https://doi.org/10.1136/bmjopen-2021-060632
DO - https://doi.org/10.1136/bmjopen-2021-060632
M3 - Article
C2 - 35940829
SN - 2044-6055
VL - 12
SP - e060632
JO - BMJ Open
JF - BMJ Open
IS - 8
M1 - e060632
ER -