Objectives: To identify and map all trials in maternal health conducted in low- and middle-income countries (LMIC) over the 10-year period 2010-2019, to identify geographical and thematic trends, as well as compare to global causes of maternal death and pre-identified priority areas.

Design: Systematic scoping review.

Primary and secondary outcome measures: Extracted data included location, study characteristics and whether trials corresponded to causes of mortality and identified research priority topics.

Results: Our search identified 7,269 articles, 874 of which were included for analysis. Between 2010 and 2019, maternal health trials conducted in LMICs more than doubled (50 to 114). Trials were conducted in 61 countries – 231 trials (26.4%) were conducted in Iran. Only 225 trials (25.7%) were aligned with a cause of maternal mortality. Within these trials, pre-existing medical conditions, embolism, obstructed labour, and sepsis were all under-represented when compared with number of maternal deaths globally. Large numbers of studies were conducted on priority topics such as labour and delivery, obstetric haemorrhage, and antenatal care. Hypertensive disorders of pregnancy, diabetes, and health systems and policy – despite being high-priority topics – had relatively few trials.

Conclusion: Despite trials conducted in LMICs increasing from 2010 to 2019, there were significant gaps in geographical distribution, alignment with causes of maternal mortality, and known research priority topics. The research gaps identified provide guidance and insight for future research conducted in low-resource settings.

With support from an information specialist, a search strategy was devised to capture eligible studies (Supplemental Table 1). Search terms for maternal and perinatal health were derived from search strategies used by Cochrane Pregnancy and Childbirth to maintain and update their specialised register. We consulted the search filters developed by Cochrane EPOC to identify search terms relating to LMICs. The search strategy was applied to the Cochrane Central Register of Controlled Trials (CENTRAL), which retrieves records from PubMed/MEDLINE, Embase, CINAHL, ClinicalTrials.gov, WHO’s International Clinical Trials Registry Platform (ICTRP), KoreaMed, Cochrane Review Group’s Specialised Registers, and hand-searched biomedical sources. Searching CENTRAL directly had the benefit of restricting search results to trials only, keeping the volume of citations to screen to a manageable level. Trial register records from ClinicalTrials.gov and WHO ICTRP were not included in the records retrieved from CENTRAL. The search was conducted on 1 May 2020.

Citation management, identification of duplicates, and screening articles for eligibility were conducted using EndNote and Covidence. Two reviewers independently screened titles and abstracts of all retrieved citations to identify those that were potentially eligible. Full texts for these articles were accessed and assessed by two independent reviewers according to the eligibility criteria. At both steps, any disagreements were resolved through discussion or consulting a third author.

Data collection and analysis

For each included trial we extracted information on title, author, year of publication, location where the trial was conducted (country and SDG region), unit of randomisation (individual or cluster), category of intervention, intervention level (public health, community, primary care, hospital, and health system), and category of the primary outcome(s). The intervention and outcome categories were adapted from Cochrane’s list of ‘higher-level categories for interventions and outcomes’. For trials with more than one primary outcome, we identified a single, most appropriate outcome category through discussion and consensus amongst review authors. The level of intervention was determined based on the level of the healthcare system that the trial was primarily targeting – for example, trials recruiting women at an antenatal clinic were classified as primary care level. Public health and preventative care were defined as interventions for those in the community who were well, while home; and community care was defined as interventions for those in the community who were unwell. Based on the trial’s primary objective, we tagged each trial to one of 35 maternal health topics, as well as classified them by relevance to a cause of maternal death identified by Say et al in their global systematic analysis (Box 1).

Included trials were additionally categorised into global research priority topics identified by Souza et al and Chapman et al. The research priorities identified by Souza et al were ranked based on the distribution of maternal health themes across the 190 priority research questions – i.e., the theme with the most research questions was considered the highest-ranked priority topic. This mirrored the process used by Chapman et al, where research topics with the greatest representation within the 100 research questions, based on percentage, were given the highest rank. For each trial identified in our review, we used the variables extracted to classify it according to priority topics identified in Souza et al or Chapman et al, where possible (Box 1). All data were extracted by two independent reviewers, with results compared to ensure consistency and any disputes resolved through discussion or consultation with a third author. As this was a scoping review, we did not perform quality assessments on individual trials.

We conducted descriptive analyses using Excel to determine frequencies of extracted variables and used line graphs to explore trends. We assessed trends over time using proportions of each variable within studies available for a given year. While we initially planned to look at trends in individual countries and interventions, many had few or no data points.

This dataset captures all maternal health trials published to the Cochrane CENTRAL database from 2010-2019. It was used to determine trends in the data regarding location, the field of interest, and relation to both causes of maternal death and research priorities.

Parameters (Row 1) can be divided into three distinct fields:

- Paper details (columns A-G)

- Study details (columns H-O)

- Classifications (Columns P-S)

Drop-down options were used for parameters where possible. The lists of drop-down options can be found in the following:

- Geographical parameters: Sheet 2

- Paper details parameters: Sheet 3

- Classification lists: Sheet 4

The following parameter lists were based on the references mentioned below:

Intervention and Outcome categories:

Cochrane Linked Data. Metadata and vocabularies London, UK: The Cochrane Collaboration; 2020 [cited 2020 June 15]. Available from: https://linkeddata.cochrane.org/linked-data-project/metadata-and-vocabularies

Global causes of maternal death:

Say L, Chou D, Gemmill A, et al. Global causes of maternal death: a WHO systematic analysis. The Lancet Global health 2014; 2(6): e323-33. DOI: https://dx.doi.org/10.1016/S2214-109X(14)70227-X

Souza et. al. 2014

Souza JP, Widmer M, Gulmezoglu AM, et al. Maternal and perinatal health research priorities beyond 2015: an international survey and prioritization exercise. Reprod Health 2014; 11:61. DOI: 10.1186/1742-4755-11-61

Chapman et. al. 2014

Chapman E, Reveiz L, Sangalang S, et al. A survey study identified global research priorities for decreasing maternal mortality. Journal of Clinical Epidemiology 2014; 67(3): 314-24. DOI: https://doi.org/10.1016/j.jclinepi.2013.10.007