Calcium supplementation to prevent pre-eclampsia: protocol for an individual participant data meta-analysis, network meta-analysis and health economic evaluation
Taryn Young,
Ana Pilar Betran,
Kym I E Snell,
Hema Mistry,
Richard Riley,
Shakila Thangaratinam,
Guillermo Carroli,
Edgardo Abalos,
Zahida P Qureshi,
John Allotey,
Anna Thorson,
Khalid Saeed Khan,
Mandisa Singata-Madliki,
George Justus Hofmeyr,
Alfredo Palacios,
Thaís Rocha,
Joshua Peter Vogel,
Luc Smits,
Gabriela Cormick,
Juan-Pablo Pena-Rosas,
Koiwah Koi Larbi,
Meghan Bohren,
Helen Moraa,
Rana Zahroh
Affiliations
Taryn Young
South African Cochrane Centre, South African Medical Research Council, Cape Town, South Africa
Ana Pilar Betran
Reproductive Health and Research, World Health Organization, Geneva, Switzerland
Kym I E Snell
Centre for Prognosis Research, School of Medicine, Keele University, Keele, UK
Hema Mistry
Warwick Clinical Trials Unit, University of Warwick, Warwick Medical School, Coventry, UK
Richard Riley
Centre for Prognosis Research, School of Primary, Community and Social Care, Keele University, Staffordshire, UK
Shakila Thangaratinam
WHO Collaborating Centre for Global Women’s Health, Institute of Metabolism and Systems Research, University of Birmingham College of Medical and Dental Sciences, Birmingham, UK
Guillermo Carroli
Centro Rosarino de Estudios Perinatales (CREP), Rosario, Argentina
Edgardo Abalos
5 Maternidad Martin, Secretaría de Salud Pública de la Municipalidad de Rosario, Rosario, Santa Fe, Argentina
Zahida P Qureshi
40 University of Nairobi Department of Obstetrics and Gynecology, Nairobi, Kenya
John Allotey
WHO Collaborating Centre for Global Women’s Health, Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK
Anna Thorson
1 UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR), WHO, Geneva, Switzerland
Khalid Saeed Khan
Public Health, University of Granada Faculty of Medicine, Granada, Spain
Mandisa Singata-Madliki
Effective Care Research Unit (ECRU), East London Hospital Complex, East London, South Africa
George Justus Hofmeyr
Obstetrics and Gynaecology, Frere Hospital, East London, South Africa
Alfredo Palacios
Health Economics, Institute for Clinical Effectiveness and Health Policy, Buenos Aires, Argentina
Thaís Rocha
WHO Collaborating Centre for Global Women’s Health, Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK
Joshua Peter Vogel
Maternal, Child and Adolescent Health Program, Burnet Institute, Melbourne, Victoria, Australia
Luc Smits
Department of Epidemiology, Care and Public Health Research Institute, Maastricht University, Maastricht, The Netherlands
Gabriela Cormick
Department of Health Technology Assessment and Health Economics, Institute for Clinical Effectiveness and Health Policy, Buenos Aires, Argentina
Juan-Pablo Pena-Rosas
Reproductive Health and Research, World Health Organization, Geneva, Switzerland
Introduction Low dietary calcium intake is a risk factor for pre-eclampsia, a major contributor to maternal and perinatal mortality and morbidity worldwide. Calcium supplementation can prevent pre-eclampsia in women with low dietary calcium. However, the optimal dose and timing of calcium supplementation are not known. We plan to undertake an individual participant data (IPD) meta-analysis of randomised trials to determine the effects of various calcium supplementation regimens in preventing pre-eclampsia and its complications and rank these by effectiveness. We also aim to evaluate the cost-effectiveness of calcium supplementation to prevent pre-eclampsia.Methods and analysis We will identify randomised trials on calcium supplementation before and during pregnancy by searching major electronic databases including Embase, CINAHL, MEDLINE, CENTRAL, PubMed, Scopus, AMED, LILACS, POPLINE, AIM, IMSEAR, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform, without language restrictions, from inception to February 2022. Primary researchers of the identified trials will be invited to join the International Calcium in Pregnancy Collaborative Network and share their IPD. We will check each study’s IPD for consistency with the original authors before standardising and harmonising the data. We will perform a series of one-stage and two-stage IPD random-effect meta-analyses to obtain the summary intervention effects on pre-eclampsia with 95% CIs and summary treatment–covariate interactions (maternal risk status, dietary intake, timing of intervention, daily dose of calcium prescribed and total intake of calcium). Heterogeneity will be summarised using tau2, I2 and 95% prediction intervals for effect in a new study. Sensitivity analysis to explore robustness of statistical and clinical assumptions will be carried out. Minor study effects (potential publication bias) will be investigated using funnel plots. A decision analytical model for use in low-income and middle-income countries will assess the cost-effectiveness of calcium supplementation to prevent pre-eclampsia.Ethics and dissemination No ethical approvals are required. We will store the data in a secure repository in an anonymised format. The results will be published in peer-reviewed journals.PROSPERO registration number CRD42021231276.
