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The Lancet Regional Health - Western Pacific 14 (2021) 100217
Contents lists available at ScienceDirect
The Lancet Regional Health - Western Pacific
journal homepage: www.elsevier.com/locate/lanwpc
Research paper
Severe maternal morbidity in the Asia Pacific: a systematic review and
meta-analysis
Manarangi De Silva, MD
a , b , Leeanne Panisi, MD
c , Anthea Lindquist, DPhil a , b , Catherine Cluver, PhD
a , b , d , Anna Middleton, MPH
a , b , Benjamin Koete, MD
c , Joshua P. Vogel, PhD
5 , 6 , Susan Walker, PhD
a , b , Stephen Tong, PhD
a , b , † , Roxanne Hastie, PhD
a , b , ∗
a Translational Obstetrics Group, Department of Obstetrics and Gynaecology, University of Melbourne, Heidelberg, Victoria, Australia, 3084 b Mercy Perinatal, Mercy Hospital for Women, and Department of Obstetrics and Gynaecology, University of Melbourne, Mercy Hospital, Heidelberg,
Australia, 3084 c Department of Obstetrics and Gynaecology, National Referral Hospital, Honiara, Solomon Islands d Department of Obstetrics and Gynaecology, Tygerberg Hospital, Stellenbosch University, Cape Town, South Africa 5 Maternal, Child and Adolescent Health Program, Burnet Institute, Melbourne, Australia 6 School of Population and Global Health, University of Melbourne, Melbourne, Australia
a r t i c l e i n f o
Article history:
Received 9 May 2021
Revised 27 June 2021
Accepted 29 June 2021
Available online 20 July 2021
Maternal morbidity
Near-miss
Asia-Pacific
LMIC
Maternal death
a b s t r a c t
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 mater-
nal 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 cal-
culating 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 10 0 0 total births. The greatest proportion of near misses were found in the
Western Pacific region (around Papua New Guinea) at 11 • 8 per 10 0 0 births (95% CI 6 • 6-17 • 1; I 2 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 pro-
portion (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 dis-
proportionately affected. Most of the common causes are preventable. This provides an opportunity to
implement targeted interventions which could have major clinical impact.
M. De Silva, L. Panisi, A. Lindquist et al. The Lancet Regional Health - Western Pacific 14 (2021) 100217
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Research in context
Evidence before this study
Many pregnant women continue to suffer severe mater- nal morbidity (or a maternal “near miss” event) around the world. While causes and risk factors for maternal deaths have been extensively investigated, severe maternal morbidity has not had the same focus, particularly in low and lower-and- middle-income countries (LMIC). In settings where absolute numbers of maternal deaths are low or underreported, moni- toring rates of severe maternal morbidity/near misses can be used to better assess the quality of health systems. The Asia- Pacific region is diverse with a high number of LMICs, each
with unique sociocultural and geographical challenges that have the potential to contribute to poor maternal outcomes. Assessing maternal morbidity is essential to improving ma- ternal health in this region.
Added value of this study
Our systematic review is the first to characterise severe maternal morbidity across the entire Asia Pacific. 30,183,608 pregnancies and 100,011 near miss cases were included. The total proportion of near misses was 4 • 4 cases (95% CI 4 • 3 - 4.5) per 10 0 0 total births across 27 countries, with significant variation among subregions and individual countries. Unfor- tunately, there were many countries in the region that were underrepresented, or entirely missing. LMICs had the great- est proportion of near-miss cases, with the Western Pacific subregion (the area including Papua New Guinea and Timor Leste) having the highest overall proportions of near misses. Massive haemorrhage and eclampsia were the main causes of maternal near miss in the Asia Pacific region.
Implications of all the evidence available
There are a disproportionate number of women who ex- perience adverse consequences of pregnancy and childbirth
in LMICs in the Asia Pacific. Massive postpartum haemor- rhage and eclampsia are major contributors to adverse mater- nal outcomes, though both are largely preventable. Our find- ings further demonstrate the utility of near miss in evaluat- ing quality of maternal health services. These results should
help policy makers and leaders understand the main causes of maternal morbidity and which areas are most heavily bur- dened within the Asia-Pacific region. This evidence can be used to inform targeted interventions to help reduce the number of preventable maternal deaths and near misses in
the Asia Pacific region.
. Introduction
Although progress has been made in reducing global maternal
ortality, it is estimated that 295,0 0 0 maternal deaths still occur
ach year. [1] Much of this burden is shouldered by low and lower-
iddle income countries (LMICs) [2-6] The maternal mortality ra-
io (MMR) has been used to evaluate healthcare quality and guide
olicy, however this is difficult to use in settings where absolute
umbers of maternal deaths are low, such as in high-income coun-
ries; or unreported, such as in many LMICs. [7-9] Severe mater-
al morbidity occurs 20 to 30 times more frequently than mater-
al death and most cases share underlying risk factors with those
omen who do not survive.[ 5 , 7 , 9-13 ] Thus, there is growing con-
ensus in the utility of monitoring rates of severe maternal mor-
idity as a complementary or alternative tool for assessing the
uality of maternal health care, particularly in LMICs. [ 3 , 13-16 ]
In 2004 the World Health Organisation (WHO) performed a sys-
ematic review of global maternal morbidity and found significant
2
eterogeneity in the prevalence of morbidity and how it is defined,
r measured. [13] This led to the development of WHO’s stan-
ard definition for severe maternal morbidity, or maternal “near
iss” – ‘a woman who nearly died but survived a complication
hat occurred during pregnancy, childbirth or within 42 days of
ermination of pregnancy’. [9] The WHO criteria to define mater-
al near miss includes clinical endpoints (such as massive post-
artum haemorrhage), management-based endpoints (such as in-
ensive care admission, organ-dysfunction endpoints (such as re-
al failure) and laboratory-based endpoints (e.g, severe thrombo-
ytopaenia) (Appendix A).
The use of standardised near miss criteria allows more reli-
ble comparisons within, and across regions and countries. How-
ver, many of the endpoints in the WHO criteria focus on facility-
ased births or depend on information that is not reliably avail-
ble or obtained in LMICs (such as many laboratory-based criteria)
17] . As a result, maternal near miss is often measured in LMICs
sing 1) WHO criteria that have been modified by local centres,
) management-based criteria such as the number of women re-
eiving massive blood transfusion or 3) disease-based criteria such
s the number of women suffering from uterine rupture, eclamp-
ia or massive post-partum haemorrhage. [ 18 , 19 ] Despite the chal-
enges arising from varied criteria used to define near miss in the
iterature, measuring and comparing rates of maternal near miss
an still provide a more comprehensive and objective assessment
f health services compared to examining of maternal mortality
lone.
The Asia-Pacific region encompasses many countries with
nique sociocultural, geographical and economic barriers to the de-
ivery of high-quality maternal health care. Most are LMICs with
Data shown are proportions per 10 0 0 births with corresponding 95% confidence intervals
Table 3
Near miss proportions and 95% confidence intervals in each sub-region for most common outcome criteria overall.
Criteria Total # n Western
Pacific
n South Asia n South-East
Asia
n North-East
Asia
n China &
Hong Kong
n Australia &
New Zealand
n Western
Asia
n
WHO Near Miss 14 • 8 (13 • 3,
16 • 3)
32 13 • 9 (5 • 9,
21 • 8)
3 23 • 2 (18 • 7,
27 • 7)
21 2 • 3 (1 • 6,
2 • 9)
2 - 0 7 • 2 (5 • 6,
8 • 8)
4 5 • 9 (4 • 2, 7 • 6) 3 5 • 1 (4 • 3,
6 • 0)
1
Other criteria 30.5
(28.1,
33.0)
23 8.8
(8.3, 9.3)
2 46.1
(17.9, 74.3)
5 91.0
(60.9,
121.2)
5 22.9
(22.2, 23.6)
2 9.1
(8.5, 9.6)
2 5.4
(3.0, 7.9)
7 - -
Severe maternal
complication/
disease specific
3 • 5 (3 • 3,
3 • 6)
147 9 • 1 (3 • 9,
14 • 3)
4 9 • 3 (8 • 5,
10 • 0)
69 3 • 9 (3 • 4,
4 • 4)
19 0 • 2 (0 • 1,
0 • 3)
7 6 • 4 (5 • 2,
7 • 6)
12 2 • 6 (2 • 4, 2 • 9) 28 7 • 7 (5 • 0,
10 • 4)
6
Eclampsia 2 • 7 (2 • 4,
2 • 9)
44 1 • 8 (0 • 2,
2 • 7)
1 13 • 0 (9 • 9,
16 • 0)
21 3 • 3 (2 • 4,
4 • 3)
9 0 • 7 (0 • 6,
0 • 8)
1 0 • 7 (0 • 5,
0 • 9)
4 0 • 3 (0 • 06, 0 • 5) 5 0 • 8 (0 • 5,
1 • 2)
3
Uterine rupture 0 • 9 (0 • 8,
1 • 0)
66 0 • 8 (0 • 3,
1 • 3)
2 3 • 7 (3 • 1,
4 • 2)
35 0 • 3 (0 • 1,
0 • 4)
8 0 • 1 0 • 01,
0 • 2)
3 0 • 3 (0 • 2,
0 • 5)
5 0 • 5 (0 • 3, 0 • 7) 12 0 • 5 (0 • 3,
0 • 7)
2
Abruption 0 • 6 (0 • 5,
0 • 8)
14 - 0 0 • 9 (0 • 1,
1 • 7)
5 2 • 7 (1 • 0,
4 • 3)
4 - 0 0 • 2 (0 • 05,
0 • 4)
3 - 0 1 • 2 (0 • 9,
1 • 5)
2
Post-partum
haemorrhage ∗5 • 9 (4 • 5,
7 • 2)
35 4 • 1 (1 • 3,
6 • 9)
3 3 • 2 (2 • 3,
4 • 0)
13 21 • 1 (11 • 0,
31 • 1)
4 - 0 9 • 1 (3 • 0,
15 • 2)
4 4 • 1 (0 • 01, 8 • 2) 8 2 • 6 (1 • 4,
3 • 8)
3
Sepsis 1 • 5 (1 • 2,
1 • 7)
43 1 • 0 (0 • 6,
1 • 4)
2 2 • 2 (1 • 7,
2 • 7)
25 4 • 5 (4 • 3,
4 • 8)
2 - 0 0 • 14 (0 • 14,
0 • 15)
2 1 • 1 (0 • 03, 2 • 3) 9 0 • 5 (0 • 1,
1 • 2)
3
Management
specific
3 • 6 (3 • 3,
3 • 9)
83 0 • 2 (0 • 07,
0 • 7)
1 4 • 6 (3 • 9,
5 • 2)
33 1 • 5 (1 • 1,
1 • 9)
10 0 • 9 (0 • 2,
1 • 7)
5 5 • 2 (3 • 4,
7 • 0)
14 3 • 8 (2 • 7, 4 • 8) 17 6 • 3 (3 • 3,
3 • 8)
3
Peripartum
hysterectomy
1 • 0 (0 • 8,
1 • 1)
56 0 • 2 (0 • 07,
0 • 7)
1 1 • 6 (1 • 3,
2 • 0)
22 0 • 8 (0 • 5,
1 • 1)
8 0 • 9 (0 • 2,
1 • 7)
5 0 • 7 (0 • 5,
0 • 9)
8 0 • 8 (0 • 5, 1 • 0) 12 0 • 5 (0 • 3,
1 • 0)
1
ICU 4 • 1 (3 • 4,
4 • 8)
43 - 0 4 • 3 (3 • 1,
5 • 4)
14 2 • 9 (1 • 5,
4 • 4)
5 - 0 4 • 8 (2 • 9,
6 • 7)
10 3 • 2 (2 • 0, 4 • 5) 12 4 • 5 (4 • 0,
5 • 1)
2
Massive
transfusion ∗∗2 • 8 (1 • 8,
3 • 7)
16 - 0 5 • 2 (2 • 8,
7 • 5)
5 1 • 3 (0 • 9,
1 • 9)
1 - 0 2 • 0 (0 • 3,
3 • 7)
5 1 • 0 (0 • 6, 1 • 4) 4 6 • 4 (5 • 3,
7 • 7)
1
Data shown are near miss proportions per 1,0 0 0 births with corresponding 95% confidence intervals • n = number of studies ∗ ≥ 1 • 5L estimated blood loss ∗∗ ≥ 3 units packed red blood cells # data of Central Asia (includes > 1 subregion) included in total but not shown individually as only one study each
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HO review of maternal near miss. [13] The largest proportion
f studies prior to 2004 in the Asia Pacific region used disease-
pecific criteria (n = 37). This was also the case after 2004 (n = 110),
owever there was an increase in the number of studies using
anagement-based criteria (n = 68) and the WHO criteria (n = 32).
There was significant variation in the proportion of near misses
mong the various criteria used to define it ( Table 3 ). The high-
st proportion of near misses was seen among studies that used
ther non-WHO based criteria (30.5 per 10 0 0 births, 95% CI 28.1,
3.0, 23 studies) ( Table 3 , Table S3). These criteria included those
eveloped prior to the WHO criteria [25-27] and those using other
6
ommon near miss criteria, such as the CDC-endorsed surveillance
lgorithm [28] . Interestingly, the proportion of near misses in stud-
es that used The WHO criteria ( Figure 3 , Table 3 , Table S3) were
uch lower at 14.8 per 10 0 0 births (95% CI 13.3 - 16.3, 32 studies).
he lowest proportion was seen among studies reporting disease
pecific criteria (3.5 per 10 0 0 births, 95% CI 3.3 - 3.6, 147 studies).
The overall proportion of near miss cases secondary to man-
gement specific criteria was 3.6 cases per 10 0 0 births (95% CI 3.3
3.8), with China and Hong Kong having the highest proportion
5.2 per 10 0 0 births (95% CI 3.4 - 7.0, 14 studies. Table 3 ). Inten-
ive care unit admission was the endpoint which gave the high-
M. De Silva, L. Panisi, A. Lindquist et al. The Lancet Regional Health - Western Pacific 14 (2021) 100217
Figure 3. Near Miss by WHO criteria.
e
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st proportion of near misses using management criteria (4.1 per
0 0 0 births, 95% 3.4-4.8, 43 studies) and these were also highest
n China and Hong Kong (4.8 per 10 0 0 births, 95% CI 2.9-6.7, 10
tudies,)
.4. Maternal death
We also examined maternal death. Of the studies that we in-
luded, 117 (60%) also reported maternal mortality and among
hese, 49 studies recorded maternal mortality relative to all births.
cross these 49 studies the maternal mortality ratio was 80 per
0 0,0 0 0 births (95% CI 70 - 90). South Asia had the highest pro-
ortion of maternal deaths at 510 per 10 0,0 0 births (95% CI 410 -
10) and in keeping with our near miss findings, Australia and New
ealand had the lowest maternal mortality ratio (5 per 10 0,0 0 0
irths (95% CI 2 - 9) ( Table 2 ).
.5. Quality of the included studies
There was a considerable degree of heterogeneity among the
tudies included, as demonstrated by the high I 2 values in sub-
roup analysis. This reflects the large variation in study design,
ample size and near miss definitions used. Overall, most stud-
es had a low risk of bias (Supplementary Figure 1). The high-
st area of intermediate risk for cohort studies was in the ade-
uacy of follow-up. Of the 6 case control studies, the highest area
7
f risk was in the ascertainment of controls and cases. Addition-
lly, there were some studies with potential ascertainment bias in-
luding three from the same authorship team that reported poten-
ially implausibly high proportions of near-miss ranging from 117
179 cases per 10 0 0 births. This data suggests that close to 20%
f women suffer a near miss in these centres. Supplementary Fig-
re 2 illustrates asymmetry in the precision of all studies included,
hich is likely attributed to publication bias and small study ef-
ects.
. Discussion
This is the first systematic review to document rates of serious
aternal morbidity across the Asia-Pacific region. We found the
otal proportion of near misses in the Asia Pacific was 4.4 cases
95% CI 4.3-4.5) per 10 0 0 total births across 27 countries. There
s a clear association with economic status, with the highest rates
een in LMICs in the region. The Western Pacific and South Asian
ub-regions showed the highest proportions, compared to the low-
st in Australia and New Zealand. As expected, there was consid-
rable heterogeneity across the studies, reflecting the large variety
n study design and sample size. The primary causes of maternal
ear miss were in keeping with global data on the leading causes
f maternal deaths, including haemorrhage and hypertensive dis-
rders. [5] These findings provide a more comprehensive picture
f the burden of severe maternal outcomes which can be used to
M. De Silva, L. Panisi, A. Lindquist et al. The Lancet Regional Health - Western Pacific 14 (2021) 100217
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R
irect targeted improvements in health services in the Asia-Pacific
egion.
Unsurprisingly, the risk of maternal near miss is disproportion-
tely high in LMICs. However, there is a concerning lack of near
iss data from many LMICs, particularly in the Western Pacific and
entral Asian subregions, despite extremely high maternal mortal-
ty rates in these sub-regions. [ 5 , 6 , 29 ] Of more concern, the major-
ty of studies included in our review predated the COVID-19 pan-
emic. COVID-19 has likely disrupted health systems and diverted
unding from maternal and child health programs. We anticipate
hat this will increase rates of severe maternal outcomes, especially
n LMICs. [30]
The leading cause of maternal near miss overall was major
aemorrhage, an adverse outcome where there are effective treat-
ents that are inexpensive. Major haemorrhage was highest in
ub-regions containing a high number of LMICs, such as South-
ast Asia. This is in keeping with global data on maternal death
nd morbidity. [ 5 , 29 ] Many women in the Asia Pacific suffer from
naemia, thus making them particularly vulnerable to the grave
isks posed by postpartum haemorrhage. [ 6 , 13 , 31 ] Despite this, the
roportion of near misses classified by massive transfusion was
ower overall. [5] It is plausible that many women who are not
epresented as a near miss classified by massive transfusion is ex-
lained by the fact that blood products are not readily available, or
ragically, they may have suffered a maternal death instead.
It was reassuring that the overall proportions of uterine rupture
ere low in our review. Uterine rupture was significantly higher in
he South-Asian sub-region, where there has been a rise in the in-
idence of caesarean sections (a major risk factor for uterine rup-
ure). [32] Eclampsia was the second most common cause of mor-
idity and was the highest cause of near miss in the South Asian
ub-region. This is also in keeping with hypertensive disorders be-
ng the second most common cause of maternal death and of re-
ional and global estimates of the prevalence of hypertensive disor-
ers of pregnancy. [ 5 , 33 ] As expected, we found consistently lower
ates of haemorrhage and eclampsia in high-income countries. Tar-
eting the prevention and prompt treatment of postpartum haem-
rrhage and eclampsia may be an important strategy to reduce
aternal morbidity and maternal death. [ 5 , 29 ]
This review is the first to characterise severe maternal mor-
idity for the whole Asia-Pacific region, where the current rates
f maternal mortality are high. The Asia-Pacific region provided a
nique opportunity to directly compare severe maternal morbid-
ty between LMICs and high- and middle-income countries within
he same region, which is not possible in many other regions.
ur search strategy was detailed, as evidenced by the large num-
er of studies identified. Additionally, we included several near
iss/severe maternal morbidity definitions. Given most countries
n this region are LMICs and absolute numbers of documented
aternal deaths are low, our assessment of severe maternal mor-
idity is timely and provides an important adjunct to maternal
eath data, providing a more comprehensive picture of maternal
ealth in the Asia-Pacific. Our review has some limitations, in-
luding those that are inherent to meta-analyses [ 34 , 35 ]. We only
dentified published data on severe maternal morbidity and deaths,
hilst there may have been some important unpublished data
issed, particularly in LMICs. There was a very high level of het-
rogeneity between studies, with variation in study design, disease
efinitions and criteria used to define maternal morbidity amongst
he studies included. Not all countries in the Asia Pacific were rep-
esented in our review with many countries lacking published data
f severe maternal outcome. Furthermore, many of the studies in
his review recorded severe maternal outcomes in facilities only,
owever many births in the Asia-Pacific, particularly in LMICs, oc-
ur outside of facilities.
8
. Conclusion
There is a high burden of severe maternal morbidity in the
sia-Pacific region, predominantly in LMICs. The main causes of
evere maternal morbidity we identified – particularly haemor-
hage and hypertensive disorders - are largely preventable. We
ave highlighted the utility and strength of maternal near miss
s a tool to measure the quality of maternal health care, partic-
larly in LMICs where maternal mortality data is lacking or de-
cient. These findings should be used to inform maternal health
olicy and direct resources to improve maternal outcomes in this
egion.
. Contributors
MD and RH conceived and designed this study. MD conducted
he database search and reviewed the reference lists of articles in-
luded in screening. MD and RH performed initial screening and
eview of full texts for eligibility. MD, RH and AM extracted the
ata and completed quality assessment. AL resolved any conflicts
n quality assessment. RH & MD conducted the data analysis, data
nterpretation, drafted the final manuscript and prepared the tables
nd figures. RH, SW, ST and AL, CC, JPV and SB, LP and BK provided
ritical analysis and made revisions of the manuscript and impor-
ant intellectual contributions. All authors reviewed the manuscript
efore final submission.
eclaration of Competing Interest
We declare no competing interests. The authors alone are re-
ponsible for the views expressed in this article and they do not
ecessarily represent the views, decision, or policies of the institu-
ion with which they are affiliated.
cknowledgments
We are grateful to the staff at the Bailieu Library, The University
f Melbourne, for assistance in development of the search strategy
nd Mr. Naveen De Silva for his generous assistance in creating the
gures for this manuscript.
unding
Funding bodies had no role in study design, data collection,
ata analysis, data representation, or writing of the manuscript.
ata sharing
Data is available upon reasonable request to the corresponding
uthor.
ditor note
The Lancet Group takes a neutral position with respect to terri-
orial claims in published maps and institutional affiliations
upplementary materials
Supplementary material associated with this article can be
ound, in the online version, at doi: 10.1016/j.lanwpc.2021.100217 .
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M. De Silva, L. Panisi, A. Lindquist et al. The Lancet Regional Health - Western Pacific 14 (2021) 100217
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