Severe maternal morbidity in the Asia Pacific: a systematic review and meta-analysis

Background: Monitoring rates of severe maternal morbidity (such as eclampsia and uterine rupture) is useful to assess the quality of obstetric care, particularly in low and lower-middle-income countries (LMICs). Methods: We undertook a systematic review characterising the proportion and causes of severe maternal morbidity in the Asia Pacific region. We searched Medline, Embase, Cochrane CENTRAL library and the World Health Organization Western Pacific Index database for studies in the Asia-Pacific reporting maternal morbidity/near miss using a predefined search strategy. We included cohort, case-control and cross-sectional studies published in English before September 2020. A meta-analysis was performed calculating the overall proportion of near miss events by sub-region, country, near miss definition, economic status, setting and cause using a random-effects model. Findings: We identified 26,232 articles, screened 24,306 and retrieved 454 full text articles. Of these, 197 studies spanning 27 countries were included. 13 countries in the region were not represented. There were 30,183,608 pregnancies and 100,011 near misses included. The total proportion of near miss events was 4•4 (95% CI 4•3-4•5) per 1000 total births. The greatest proportion of near misses were found in the Western Pacific region (around Papua New Guinea) at 11•8 per 1000 births (95% CI 6•6-17•1; I2 96.05%). Low-income countries displayed the greatest proportion of near misses (13•4, 95% CI 6•0-20•7), followed by lower-middle income countries (11•1; 95% CI 10•4 – 11•9). High-income countries had the lowest proportion (2•2, 95% CI 2•1-2•3). Postpartum haemorrhage was the most common near miss event (5•9, 95% CI 4•5-7•2), followed by eclampsia (2•7, 95% CI 2•4 – 2•9). Interpretation: There is a high burden of severe maternal morbidity in the Asia-Pacific. LMICs are disproportionately affected. Most of the common causes are preventable. This provides an opportunity to implement targeted interventions which could have major clinical impact. The systematic review protocol was registered with PROSPERO (CDR42019135672) and conducted per Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidance. [22] Our initial search was conducted in July 2018 for studies investigating maternal morbidity/near miss in the Asia-Pacific region (as defined by the United Nations). We included the electronic databases Medline, Embase, Cochrane CENTRAL Library and the WHO Western Pacific Regional Index database. We also reviewed the reference lists of all included studies. A secondary search was performed prior to data analysis in September 2020 to ascertain any further studies published since our initial search. In consultation with an information specialist, we developed a pre-defined and detailed search strategy using the following terms (Appendix A): Asia, South Asia, East Asia, Southeast Asia, Oceania, North Asia, maternal morbidity, maternal near miss, near miss morbidity, severe acute maternal morbidity, severe maternal morbidity, obstetric near miss, emergency hysterectomy, emergency obstetric hysterectomy, maternal complications, pregnancy complications, severe maternal haemorrhage, severe postpartum haemorrhage, severe sepsis, infection, uterine rupture, hypertensive disorders pregnancy, pre-eclampsia, eclampsia, intensive care unit, critical care unit. Studies which met the following criteria were included: reported near miss incidence, prevalence or data that could be used to calculate these; studies including patients in the Asia-Pacific region, published in the English language. All years of publication were eligible for review. We included case control, cohort and cross-sectional studies and randomised controlled trials which defined maternal near misses using either the WHO near miss criteria (Appendix B), [9] modified WHO criteria (i.e. a local adaptation of the WHO criteria), disease-specific (using disease-based endpoints included in the WHO near miss criteria, such as; eclampsia, massive post-partum haemorrhage [≥ 1.5L estimated blood loss], uterine rupture, sepsis or abruption) or management-based criteria (using any management-based endpoints included in the WHO near miss criteria, such as; ICU admission, massive blood transfusion [transfusion of ≥3 units packed red blood cells], renal dialysis or peripartum hysterectomy). Search results from different databases were merged and duplicates removed using reference manager software (Endnote). Two independent reviewers (RH & MD) screened titles and abstracts retrieved for potentially eligible studies via Covidence. RH and MD sought and retrieved full texts for all potentially eligible studies and recorded all reasons for exclusion. Any disagreements during screening were resolved through discussion, or consulting a third reviewer. MD, RH and AM independently extracted data using a standardized data extraction form including the following: study characteristics, design, level of hospitals participating, funding source, study country and sub-region, methods, participant characteristics, possible confounders, primary outcomes, secondary outcomes. Extracted data were compared to identify any disagreements, which were resolved through discussion. Quality of included studies were independently assessed by the primary reviewers (MD, RH and AM) using the Newcastle-Ottawa Scale (NOS) tool for non-randomised studies. No eligible randomised studies were identified. For quality appraisal, we assessed: study characteristics, study design, level of facility, sampling method, sources of data, ascertainment of exposure, reporting definitions, comparability of cohorts, selection of controls (where applicable), representativeness of the exposed cohort, completeness of follow-up and data, funding source, study country and sub-region, methods, participant characteristics, possible confounders, primary outcomes, secondary outcomes. The NOS broadly scores studies using a points-based system, with a maximum score of 9 stars, based on three categories: the selection of the study groups, the comparability of the groups, and the ascertainment of either the exposure or outcome of interest, for case-control or cohort studies respectively. We used these scores to rank study quality as “high”, “medium” or ‘low” quality. A NOS score of 7 or more is considered of “high” quality, or “low” risk of bias. A NOS score of 3-6 is considered “moderate” quality or “unclear” risk of bias; and a score of <3 is considered “low quality”, or “high” risk of bias. Any disparity in quality assessment was resolved with a third reviewer (AL). We used the United Nations and World Bank classification systems for geographical classification of sub-regions and economic development status (Appendix C). We performed a univariate analysis calculating the overall proportion of near miss events per 1000 total births using a random effects model [23]. We also performed meta-analyses using a random effects model calculating the proportion of near miss by the following sub-groups; near miss definition/criteria used (disease-specific, management-specific, WHO, modified WHO criteria and “other” criteria), sub-region, country, economic status, hospital setting, and cause. The point estimates of proportions and their 95% confidence intervals (CIs) were represented in forest plots. Heterogeneity between studies was represented as I2 when > 3 studies per sub-group were present. We also reported proportions and 95% CIs of maternal mortality and perinatal death proportion, where included. Publication bias, reporting bias and biases related to a small sample size were assessed with the use of the regression asymmetry test of Egger. [24] We used STATA IC version 15 for our statistical analyses. Funding bodies had no role in study design, data collection, data analysis, data representation, or writing of the manuscript. The corresponding author and RH had full access to all the data in the study and had final responsibility for the decision to submit for publication. All authors reviewed the final manuscript before submission for publication.