A new collaborative consortium for the study of pregnancy treatments.
Research stage: Ongoing study (June 2018 - May 2023)
Fifty percent of pregnant women are prescribed drugs in pregnancy, but there are significant knowledge gaps about the safety, optimum dosage and long-term effects of medications in pregnancy. The Consortium for the Study of Pregnancy Treatments (Co-OPT) is a collaboration designed to investigate this.
We have formed the Consortium for the Study of Pregnancy Treatments (Co-OPT) collaboration with cross-disciplinary expertise, to investigate the effects of treatments given in pregnancy. Co-OPT will address knowledge gaps through individual patient data meta-analysis and linkage studies using data extracted from electronic health records, birth registries, cohort studies and randomised controlled trials. We anticipate that the methods developed will serve as a platform for future studies of other preterm birth treatments and medications used in pregnancy.
The initial focus of Co-OPT is antenatal corticosteroids (ACS), which are given to pregnant women in threatened preterm labour to reduce perinatal and neonatal death and respiratory distress syndrome. The current Co-OPT study combines data from Scottish Health Records with anonymised, routinely-collected population data from international birth registries, to undertake a robust evaluation of the short- and long-term benefits and harms of ACS exposure. This will be used to determine who antenatal corticosteroids should be offered to, and in what form, and will help contribute towards improving the health of pregnant women and their babies.
The primary objective is to determine the safety of ACS in women and babies who receive inappropriately timed ACS (birth >7 days after administration, when benefits are minimal), or who are treated unnecessarily (preterm administration of ACS, but birth occurs at term) or who receive questionably appropriate ACS (given at ≥ 36 weeks gestation, before early term birth, where there is less clear evidence of benefit).
The secondary objective is to determine characteristics that influence maternal and infant outcomes following ACS, develop predictive models for their use and determine best formulation and dose regimens.
The principal research questions which Co-OPT will address include:
- What is the incidence of ACS that is a) inappropriately timed, b) unnecessary and c) questionably appropriate, based on the above definitions?
- Does inappropriately timed and/or unnecessary or early term ACS exposure increase perinatal morbidity and/or mortality?
- What are the effects of ACS on maternal morbidity?
- What is the effect of ACS on childhood neurodevelopment and health?
- How do pregnancy characteristics (e.g. gestation at administration or birth, multiple gestation, growth restriction, chorioamnionitis, other treatments) influence outcomes following ACS?
- Do different dose schedules and formulations of ACS affect outcomes?
This work will be complimented by a separate, but related systematic review and meta-analysis of randomised controlled trial data.
Infographic on Antenatal Corticosteroids
We have established a Parental Advisory Board (PAB) group, with assistance from the European Foundation for the Care of Newborn Infants (EFCNI) with members from European countries contributing data. EFCNI is a pan-European organisation, representing the interests of preterm and newborn infants and their families.
With members of the PAB group and a graphic designer (Tom Harris), Dr Emily Frier has created an infographic on use of antenatal corticosteroids before planned caesarean birth at term.
This infographic is supported by the Royal College of Obstetricians & Gynaecologists, and is designed to be used by patients and clinicians. It accompanies the recently published Royal College of Obstetricians and Gynaecologists Green-top Guideline 'Antenatal corticosteroids to reduce neonatal morbidity and mortality'.
Dr Chun Lin
Dr Emily Frier
Clinical Research Fellow
Stock SJ, Thomson A, Papworth S. Royal College of Obstetricians, Gynaecologists. Antenatal corticosteroids to reduce neonatal morbidity and mortality. BJOG 2022; doi: 10.1111/1471-0528.17027, 00: 1-26.
Mol BW, Li W, Lai S, Stock SJ. Effectiveness of antenatal corticosteroids at term: Can we trust the data that “inform” us? Eur J Obstet Gynaecol Repro Biol. 2021 Jun; 261:144-147. doi: 10.1016/j.ejogrb.2021.04.031. Epub 2021 Apr 24. PMID: 33940424
Wastnedge E, Vogel J, Been JV et al. An evaluation of the benefits and harms of antenatal corticosteroid treatment for women at risk of imminent preterm birth or prior to elective Caesarean-section: Study protocol for an individual participant data meta-analysis [version 1; peer review: 2 approved]. Wellcome Open Res 2020. 4:38. doi: 10.12688/wellcomeopenres.15661.1
Hrabalkova L, Takahashi T, Kemp MW, Stock SJ. Antenatal Corticosteroids for Fetal Lung Maturity - Too Much of a Good Thing? Curr Pharm Des. 2019; 25(5):593-600. doi: 10.2174/1381612825666190326143814. PMID: 30914016
Stock SJ and Norman JE. Medicines in pregnancy [version 1; peer review: 3 approved]. F1000Research 2019, 8(F1000 Faculty Rev):911. doi: 10.12688/f1000research.17535.1
Kemp MW, Jobe AH, Usuda H, Nathanielsz PW, Li C, Kuo A, Huber HF, Clarke GD, Saito M, Newnham JP, Stock SJ. Efficacy and Safety of Antenatal Steroids. Am J Physiol Regul Integr Comp Physiol. 2018 Apr 11. doi: 10.1152/ajpregu.00193.2017
Agnew EJ, Ivy JR, Stock SJ, Chapman KE. Glucocorticoids, antenatal corticosteroid therapy and fetal heart maturation. J Mol Endocrinol. 2018 Jul; 61(1):R61-R73. doi: 10.1530/JME-18-0077. Epub 2018 May 2.
Kemp MW, Newnham JP, Challis JG, Jobe AH, Stock SJ. The clinical use of corticosteroids in pregnancy. Hum Reprod Update. 2015 Nov 20. doi: 10.1093/humupd/dmv047
Professor Karel Allergaert (KU Leuven, Belgium)
Associate Professor C Bannerman-Gyamfi (Columbia University, USA)
Dr Jasper Been (Erasmus MC, Netherlands)
Dr S Bhattacharya (University of Aberdeen, UK)
Associate Professor Kristjana Einarsdottir (Centre for Health Sciences, University of Iceland)
Dr Abigail Fraser (University of Bristol, UK)
Professor Mika Gissler (National Institute of Health and Welfare, Finland)
Professor Lani Florian (University of Edinburgh, UK)
Professor B Jacobsson (Sahlgrenska Academy, University of Gothenburg, Sweden)
Professor S Kuhle (Dalhousie University, Canada)
Professor B Mol (University of Adelaide, Australia)
Professor Jane Norman (University of Bristol, UK)
Associate Professor Lars Henning Pedersen (Aarhus University, Denmark)
Professor Rebecca Reynolds (University of Edinburgh, UK)
Professor Richard Riley (University of Keele, UK)
Dr Sarah Murray (University of Edinburgh)
Dr Devender Roberts (Liverpool Women's Hospital, UK)
Assistant Professor E Schuit (UMC Utrecht, the Netherlands)
Professor Aziz Sheikh (University of Edinburgh, UK)
Dr Elizabeth Wastnedge (University of Edinburgh, UK)
Dr Joshua Vogel (Maternal and Perinatal Health, WHO)
Dr Rachael Wood (University of Edinburgh, UK)
Professor John Wright (Bradford Institute for Health Research, UK)
Professor Helga Zoega (Centre for Big Data Research in Health, UNSW Australia)
Dr Eyal Krispin (Tel Aviv University, Israel)
Dr Ting Shi (University of Edinburgh)
Dr Christy Woolcott (Dalhousie University, Nova Scotia)
Dr Jessica Miller (Murdoch Children’s Research Institute, Australia)
Dr Kate Duhig (King’s College London)
Professor Ashraf Nabhan (Ain Shams University, Egypt)
Dr Jeeva John (University of Edinburgh, UK)
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