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The state of birth asphyxia in Ethiopia: an umbrella review of systematic review and
meta-analysis reports, 2020
Wubet Alebachew Bayih, Binyam Minuye Birhan, Demeke Mesfin Belay, Metadel
Yibeltal Ayalew, Getachew Yideg Yitbarek, Hailemariam Mekonen Workie, Dr
Misganaw Abie Tassew, Solomon Demis Kebede, Abebaw Yeshambel Alemu, Getnet
Gedefaw, Asmamaw Demis, Ermias Sisay Chanie
PII: S2405-8440(21)02231-3
DOI: https://doi.org/10.1016/j.heliyon.2021.e08128
Reference: HLY 8128
To appear in: HELIYON
Received Date: 13 December 2020
Revised Date: 20 January 2021
Accepted Date: 30 September 2021
Please cite this article as: W.A. Bayih, B.M. Birhan, D.M. Belay, M.Y. Ayalew, G.Y. Yitbarek, H.M.
Workie, D.M. Abie Tassew, S.D. Kebede, A.Y. Alemu, G. Gedefaw, A. Demis, E.S. Chanie, The state
of birth asphyxia in Ethiopia: an umbrella review of systematic review and meta-analysis reports, 2020,
HELIYON, https://doi.org/10.1016/j.heliyon.2021.e08128.
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1
The state of birth asphyxia in Ethiopia: an umbrella review of systematic
review and meta-analysis reports, 2020
*Wubet Alebachew Bayih1, Binyam Minuye Birhan1, Demeke Mesfin Belay1, Metadel Yibeltal
Ayalew2, Getachew Yideg Yitbarek1, Hailemariam Mekonen Workie2, Dr Misganaw Abie
Tassew1, Solomon Demis Kebede1, Abebaw Yeshambel Alemu1, Getnet Gedefaw3, Asmamaw
Demis3, Ermias Sisay Chanie1
Affiliation/s
1Debre Tabor University, Ethiopia
2Bahir Dar University, Ethiopia
3Woldia University, Ethiopia
*Corresponding author; E-mail: wubetalebachew@gmail.com: PO.BOX:272
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Abstract
Background: To this date, there are 4 systematic reviews and meta-analyses studies about the
burden and associated factors of birth asphyxia in Ethiopia. However, findings of these studies
are inconsistent which is difficult to make use of the findings for preventing birth asphyxia in the
country. Therefore, umbrella review of these studies is required to pool the inconsistent findings
into a single summary estimate that can be easily referred by the information users in Ethiopia.
Methods: PubMed, Science direct, web of science, data bases specific to systematic reviews
such as the Cochrane Database of Systematic Reviews and the Database of Abstracts of Reviews
of Effects were searched for systematic reviews and meta-analyses (SRM) studies on the
magnitude and risk factors of perinatal asphyxia in Ethiopia. The methodological quality of the
included studies was assessed using the Assessment of Multiple Systematic Reviews (AMSTAR)
tool. The estimates of the included SRM studies on the prevalence and predictors of perinatal
asphyxia were pooled and summarized with random-effects meta-analysis models. From
checking PROSPERO, this umbrella review wasn’t registered.
Results: We included four SRM studies with a total of 49,417 neonates. The summary estimate
for prevalence of birth asphyxia was 22.52% (95% CI = 17.01%-28.02%; I2=0.00). From the
umbrella review, the reported factors of statistical significance include: maternal illiteracy
[AOR= 1.96; 95% CI: 1.44–2.67], primiparity [AOR= 1.29; 95% CI: 1.03–1.62], antepartum
hemorrhage [AOR= 3.43; 95% CI: 1.74–6.77], pregnancy induced hypertension [AOR= 4.35;
95% CI: 2.98–6.36], premature rupture of membrane [AOR= 12.27; 95% CI: 2.41, 62.38],
prolonged labor [AOR=3.18; 95% CI: 2.75, 3.60], meconium-stained amniotic fluid [AOR=5.94;
95% CI: 4.86, 7.03], instrumental delivery [AOR=3.39; 95% CI: 2.46, 4.32], non-cephalic
presentation [AOR=3.39; 95% CI: 1.53, 5.26], cord prolapse [AOR=2.95; 95% CI: 1.64, 5.30],
labor induction [AOR=3.69; 95% CI: 2.26–6.01], cesarean section delivery [AOR=3.62; 95%
CI: 3.36, 3.88], low birth weight [AOR=6.06; 95% CI: 5.13, 6.98] and prematurity [AOR=3.94;
95% CI: 3.67, 4.21] at 95% CI.
Conclusion: This umbrella review revealed high burden of birth asphyxia in Ethiopia. The study
also indicated significant risk of birth asphyxia among mothers who were unable to read and
write, primiparous mothers, those mothers having antepartum hemorrhage, pregnancy induced
hypertension, premature rupture of membrane, prolonged labor, meconium-stained amniotic
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fluid, instrumental delivery, cesarean section delivery, non-cephalic presentation, cord prolapse
and labor induction. Moreover, low birth weight and premature neonates were more vulnerable
to birth asphyxia compared to their normal birth weight and term counterparts. Therefore,
burden of birth asphyxia should be mitigated through special consideration of these risk mothers
and neonates during antenatal care, labor and delivery. Mitigation of the problem demands the
collaborative efforts of national, regional and local stakeholders of maternal and neonatal health.
Keywords: Birth asphyxia, Umbrella review, Ethiopia
Background
Birth asphyxia is defined as “failure to initiate and sustain spontaneous breathing at birth [1, 2]”.
It is characterized by marked impairment of exchange of respiratory gases (oxygen and carbon
dioxide) resulting in progressive hypoxemia and hypercapnia, accompanied by marked metabolic
acidosis [1-3]. A diagnosis of birth asphyxia can be made when a newborn has fifth minute
Apgar score of < 7 [2, 3]. Besides, a neonate can be labeled as asphyxiated if (a) umbilical cord
arterial blood pH < 7; (b) neonatal neurological manifestations (seizures, coma or hypotonia);
and (c) multisystem organ dysfunction (cardiovascular, gastrointestinal, hematological,
pulmonary or renal system) [4].
Worldwide, 2 to 10 per 1000 term newborns faced perinatal asphyxia [5]. According to Gillam-
Krakauer and Gowen, the incidence of birth asphyxia is 2 per 1000 live births in high income
countries, but the rate is up to 10 times higher in low income countries where there may be
limited access to maternal and neonatal care [6]. As of other evidence, birth asphyxia has an
incidence rate of 100 - 250/1000 live births in low income countries compared to 5 - 10/1000
live births in the high income world [7, 8]. Besides, a report titled “Birth Asphyxia
Complications” estimated the presence of 10 million babies with birth asphyxia at birth [9]
which was caused by obstructed labor or acute hemorrhage during birth for which reasons skilled
antenatal attendance and emergency obstetric care were best recommended for prevention of the
problem [10].
Birth asphyxia has a global significance of causing most of the neonatal deaths [11]. In 2009,
more than one million neonatal deaths were attributed to birth asphyxia globally [12, 13]. In
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2015, out of 2.68 million neonatal deaths, 637,000 (23.8%) were attributed to birth asphyxia and
birth trauma [14]. Besides, in 2019, 2.4 million of the under five deaths were accounted for
newborn deaths; and birth asphyxia was blamed to be the leading cause of these deaths [11]. As
of 2014, birth asphyxia contributed to less than 0.1% of newborn deaths in high income
countries. But, in low income nations, the contribution ranged from 4.6/1000 to 26/1000 live
births [15]. In Africa, birth asphyxia accounts for 24.0% of the newborn deaths; and in Sub-
Saharan Africa, 280,000 neonatal deaths are accounted for birth asphyxia [16]. More
specifically, the incidence of asphyxia in East, Central, and Southern Africa was 22.0% [17].
In addition to the aforementioned mortality burden, birth asphyxia contributes to significant neonatal
morbidities due to severe hypoxic-ischemic multi-organ damage, mainly brain damage [18].
These morbidities are of broadly categorized into two types: Immediate and long term. The
immediate effects include neonatal hypoxia, hypercarbia, acidosis, hypotension and ischemia
whereas the long term morbidities are cerebral palsy, epileptic disorder, motor disorders,
developmental delays, speech delays, learning disabilities, mental retardation, hearing
impairments, blindness, feeding impairment, and behavioral and emotional disorders [2, 4]. For
example, the 2005 World Health Organization report revealed likelihood of developing cerebral
palsy, learning difficulties or other disabilities by as many as 1 million survivors of “birth
asphyxia” annually [19]. Furthermore, another study [9] showed 233,000 surviving neonates had
a moderate or severe disability and another 181,000 had learning problems. Gillam-Krakauer and
Gowen also noted that up to 25% of the birth asphyxia survivors are left with permanent
neurologic deficits [6]. On the contrary, many asphyctic babies die before they have the chance
to develop HIE, attributable to other causes including acquired conditions such as congenital
infection, meningitis, hemorrhage, ischemic or hemorrhagic stroke; genetic syndromes or
isolated gene conditions; neuro-metabolic disorders particularly where the stress of delivery
leads to decompensation and ‘double trouble’ pathologies where a primary pathology leads
secondarily to a hypoxic-ischaemic brain injury, like neuromuscular or cardiac disorders.
Moreover, some asphyctic babies survive without having HIE [3]. For instance, as of a
prospective study at Kilimanjaro Christian Medical College in Tanzania among 201 newborns
with birth asphyxia, 14 (6.7%) newborns did not have HIE during the follow up period, and they
survived the asphyxia without complication [18]. In Ethiopia, according to the 2019 Mini-
Ethiopian Demographic and Health survey report, the neonatal mortality rate is 30/1000 live
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births [20], and more than 50% of the neonatal deaths occurred within the first day of life [21].
For these deaths, birth asphyxia is the second leading cause of mortality in the country next to
prematurity [22-26]. As of recent evidence, number of neonatal deaths attributable to birth
asphyxia and birth trauma declined from 45,965 in 2000 to 28,139 in 2017 in Ethiopia [27].
However, 31.6% of the neonatal mortality in the country is still accounted for birth asphyxia
[28], thus contributing to the country’s ‘unfinished agenda’ of reducing neonatal mortality rate to
as low as 12 per 1000 live births by 2030, which is the key target of Sustainable Development
Goal (SDG) [29]. Therefore, it is alarming and warrants an urgent attention of clinicians and
health managers to make necessary strategies for preventing birth asphyxia by ensuring quality
antenatal, intra-natal and postnatal care at the reach of every woman in the community.
To this date, multiple systematic reviews (SRM) [30-33] disclosed inconsistent prevalence of
birth asphyxia ranging from 21.1% [30] to 24.06% [33] with varying degrees of quality score in
Ethiopia. Likewise, there is inconclusive reporting about the effects of different socio-
demographic, antenatal, intra-natal and neonatal factors on birth asphyxia. Besides, this umbrella
review was in response to the call and recommendation of a prior Ethiopian methodological
study [34]. Therefore, the aim of this umbrella review was to summarize the heterogeneous
findings of the 4 SRM studies [30-33] about birth asphyxia into a single comprehensive
document where the results of these reviews can be compared and contrasted. To the best of
authors’ searching effort, this umbrella review is the first of its kind in addressing birth asphyxia
and its predictors in Ethiopia. Hence, evidence from this review will be utilized to guide
clinicians and neonatal health policy makers for preventing birth asphyxia in the country, thereby
enabling achievement of the SDG target of reducing preventable neonatal mortality to less than
12 deaths per 1000 live births by 2030.
Methods
This umbrella review was conducted based on the methodology of umbrella review of multiple
systematic reviews [35]. It was undertaken through systematic synthesis of the eligible SRM
reports on birth asphyxia and its predictors in Ethiopia.
Search strategy
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Five international online databases (PubMed, Science direct, web of science, data bases specific
to systematic reviews such as the Cochrane Database of Systematic Reviews and the Database of
Abstracts of Reviews of Effects) were searched for SRM studies on birth asphyxia in Ethiopia.
For accessing relevant data about birth asphyxia, a comprehensive search was conducted through
the aforementioned databases using adapted PICO questions. These questions were developed
from the following search key words and/or Medical Subject Headings (MeSH) which were
combined using the “OR” and “AND” Boolean operators::
a. Population: fetus, newborn, and neonate
b. Outcome: Fetal distress, hypoxic-ischaemic encephalopathy, postasphyxial
encephalopathy, intrauterine asphyxia, intra-partum asphyxia, perinatal asphyxia,
perinatal suffocation, neonatal asphyxia, birth asphyxia, postnatal asphyxia, asphyxia
neonatorum, suffocation, APGAR score, determinants, predictors, associated factors,
correlates, and risk factors,
c. Study design: systematic review, meta-analysis of observational studies and
d. Setting (context): Ethiopia
Both published and unpublished studies were searched for this umbrella review. Literature
search was conducted from June 28/2020 until August 5/ 2020. The literature search was
performed by two independent researchers, with discrepancies resolved by discussion and
consensus. A sample of the literature search strategy, PubMed search strategy, developed using a
combination of MeSH terms and free texts is presented as a supplementary file (see Additional
file 1).
Eligibility criteria
Inclusion criteria
Publications in the period January 2015–August 2020 were eligible for inclusion. The time
restriction was aimed to ensure the findings better reflect or relate to the current neonatal health
of the country. The following predefined criteria were considered for a study to be regarded as
systematic review or meta-analysis: (a) presented a defined literature search strategy, (b)
appraised its included studies using a relevant tool, and (c) followed a standard approach in
pooling studies and providing summary estimates.
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Exclusion criteria
Studies were excluded due to any of the following reasons: (a) no report on either the prevalence
or determinants of birth asphyxia for this study, (b) narrative reviews, editorials, correspondence,
abstracts, and methodological studies. Besides, literature reviews that did not have a defined
research question, search strategy or defined process of selecting articles were excluded.
Study screening and selection
Searches were downloaded into Endnote version IX and de-duplicated. Then, the screening and
selection of studies was conducted in two stages. First, title and abstract screening was
conducted. Then, full-text reviewing was done. Through title and abstract screening by two
independent researchers (WAB and DMB), studies that mentioned the prevalence and/or
determinants of birth asphyxia were selected for full text review. Then, from full-text reviewing,
any article classified as potentially eligible by either reviewer was considered as a full text and
screened by both reviewers independently. At times of disagreement where a consensus could
not be reached between the researchers, a third researcher (BMB) reviewed and resolved the
disagreements.
Data extraction
Data from the included SRM studies were extracted using a standardized data abstraction form,
developed in excel spreadsheet. For each SRM study, the following data were extracted: (a)
identification data (first author’s last name and publication year), (b) Review aim (c) prevalence
or proportion of birth asphyxia (d) risk factors for birth asphyxia (e) odds ratio or relative risk
with 95% confidence intervals for the risk factors of birth asphyxia, (f) number of primary
studies included within each SRM study and their respective design type, (g) total number of
sample size included, (h) publication bias assessment methods and scores, (i) quality assessment
methods and scores, (j) data synthesis methods (random or fixed-effects model), and (k) the
authors’ main conclusion of the SRM study [Table 1].
Risk of bias assessment
All the included studies were critically appraised for validity scoring of their results. To ensure
the methodological and evidence quality of the included SRM studies, we used the Assessment
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of Multiple Systematic Reviews (AMSTAR) tool [36, 37]. The tool consists of 11 questions that
measure quality of the approaches used for pooling the empirical studies included in the SRM
studies and summarizing their estimates. The quality scoring was done out of 11, with scores 8–
11, 4–7, and < 3 indicating high, medium, and low qualities, respectively.
Data synthesis
Both narrative (qualitative) and quantitative approaches were used to summarize the estimates of
the included SRM studies. When two or more estimates were provided on the prevalence and
associated factors of birth asphyxia, we presented the range of the estimates and calculated a
summary (pooled) estimate. Choice of the metaanalysis model was guided by the between
studies heterogeneity, which was assessed by Higgin’s I2- Statistics [36]. DerSimonian-Laird
random-effects model was used to pool (summarize) prevalence estimates because there was a
high level of between-studies heterogeneity [37]. It was not possible to assess publication bias
because only four studies were included. A minimum of 10 studies is needed to evaluate
publication bias [38, 39]. Stata version 14.0 software was used for the quantitative analyses. A
summary list of the predictors of birth asphyxia with their respective odds ratios was prepared.
Ethical consideration
In this study, no study participants’ consent or ethical approval was needed because the study
was conducted based on data extracted from SRM studies.
Results
Literature search findings
The database search provided a total of 218 articles, of which only 59 articles remained after
duplicates became removed. Then, 54 of the 59 articles were excluded by title and abstract
screening for not being topics of SRM studies because the objective of this study was to include
only SRM studies on birth asphyxia. After full text review of the rest 5 articles, one SRM study
was excluded because it didn’t consider the required outcome. Thus, a total of 4 SRM studies
[30, 31, 32, 33] were included in the current umbrella review. The study selection and screening
process is shown in Fig. 1.
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Characteristics of the included review studies
All the SRM studies [30-33] included in this umbrella review were based on observational
primary studies (6 cohort, 12 case-control, and 28 cross-sectional studies). They included a total
of 46 studies, providing a total sample of 49,417 neonates. The number of primary studies per
SRM ranged from 9 (lowest) [33] to 15 (highest) [30]. The sample size per meta-analysis ranged
from 2,930 (lowest) [32] to 17,147 (highest) [31]. The 3 SRM studies [31-33] were published in
2020 and addressed both the prevalence and determinants of birth asphyxia. Though published,
Alamneh et al [32] cannot be accessed in PubMed because it was published in a journal (acta
Scientific MEDICAL SCIENCES) which is not indexed by PubMed. The fourth SRM study,
Asemie et al [30], has not been published yet. But, we used to make exhaustive search of both
published (even other than PubMed indexed journals) and unpublished sources to reduce
publication bias. The given list of databases and other searching techniques under the column of
‘search strategy’ in table 1 was considered to look for not only the respective SRM study but also
each of the primary studies included in the corresponding SRM study. According to the included
4 SRM studies, the reported estimate on the prevalence of birth asphyxia ranged from 21.1%
(95%CI: 14.08%, 28.19%), I2= 99.4% [30] to 24.06% (95%CI: 18.1%, 30.01%), I2=93.5% [33].
General characteristics of the included systematic review and meta-analyses studies are shown in
Table 1.
Table 1: Review characteristics
Author
(year)
Review
aim
Search strategy
Included
studies
Sample
size
Risk of
bias
Reported prevalence
Authors’ conclusions
AMSTAR
Quality
Sendeku
et al.
(2020)
[33]
to assess
the pooled
prevalenc
e and
associated
factors of
perinatal
asphyxia
in
Ethiopia
Pub Med, HINARI,
EMBASE, Google Scholar
and African Journals
No search start date.
No last search date
Key search terms not
included
Limitations described
No evidence of hand
searching
Eligibility criteria:
anonymous and editorial
reports excluded
No evidence of reference
checking
Crossectional
=5
Case control
=4
12,249
Clear
quality
appraisal
of the
studies
has been
stated
24.06 (18.11-30.01),
I2=93.5%
Remarkably higher
pooled prevalence of
perinatal asphyxia
determined by
prolonged labor,
meconium-stained
amniotic fluid,
instrumental
deliveries, and low
birth weight
8
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Desalew,
et al
(2020)
[31]
To
estimate
the pooled
magnitude
and
determina
nts of
birth
asphyxia
in
Ethiopia
PubMed, Medline,
CINAHL, EMBASE,
Google, Google Scholar,
and World Health
Organization websites.
No search start date.
Last search date June 2,
2019.
Search terms defined.
No limitations.
Case series and reports
were excluded.
Both published and
unpublished records at any
time.
Crossectional
=7
Case control
= 4
Cohort=1
17,147
Clear
quality
appraisal
of the
studies
has been
stated
using
adapted
NOS
22.8 (13–36.8),
I2=83.7%
Very high pooled
magnitude of birth
asphyxia predicted
by maternal
education, APH,
caesarian section,
instrumental
delivery, prolonged
duration of labor,
induction or
augmentation,
MSAF, and non-
cephalic presentation
10
Yoseph
Merkeb
Alamneh.,
et
al.(2020)
[32]
To
estimate
the pooled
prevalenc
e and
associated
factors of
birth
asphyxia
in
Ethiopia
MEDLINE/PubMed,
EMBASE, Web of Sci-
ences, Scopus, Crossref,
publons, ICMJE, Grey
literature databases,
Google Scholar, Science
Direct, Cochrane
library, reference lists of
identified studies.
No search start date.
Last search date
November 30, 2019.
Search terms defined.
Evidence of hand searching
from local and national
organizations.
Evidence of hand
searching.
Both published and
unpublished records at any
time.
Eligibility criteria: Articles
whose full text not accessed
after emailing the primary
author twice were excluded.
Crossectional
=6
Case control
=4
2,930
The
quality of
included
studies
were
appraised
clearly
22.50(10.77,34.24);
I2=98.0%
Relatively higher
prevalence of birth
asphyxia predicted
by prolonged labor
(> 12 hours),
meconium-stained,
assisted vaginal
delivery (vacuum or
Forceps), C/S
delivery, gestational
age < 37 weeks, non-
cephalic presentation,
cord prolapse and
Premature Rupture of
Membrane
8
Assemie
et al
(2020)
[30]
To
develop
national
consensus
on pooled
prevalenc
e and
associated
factor of
birth
asphyxia
in
Ethiopia
Pub Med/MEDLINE,
Google Scholar, Scopus,
Science Direct databases,
retrieving reference lists of
eligible articles and hand
searches for grey literature.
Search start date January
2019.
Last search date April 2019.
Search terms defined.
Eligibility criteria: Only
studies published from
April 2014 to April 2019.
Crossectional
=10
Cohort
=5
17,091
Clear
evidence
of quality
assessmen
t for the
included
primary
studies
21.1(14.08, 28.19);
I2= 99.4
High pooled
prevalence of
perinatal asphyxia
significantly
influenced by low
birth weight,
prolonged labor
and meconium
stained liquor
9
AMSTAR Assessment of Multiple Systematic Reviews
Primary studies
Primary researches within the included 4 SRM studies were mapped to identify if the reviews
were based on the same primary evidence. As presented above in table 1, there were 46 primary
studies included within the reviews. However, from critical appraisal of the included 4 SRM
studies (column wise) by list of the primary studies (row wise), we found only 23 different
primary articles, thus indicating the inclusion of some primary studies by at least two SRM
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studies. For instance, it is clear that all the four primary studies [42, 44, 45, 53] were included by
each of the 4 SRM studies [30-33]; another four primary studies [40, 43, 46, 47] were considered
by each of the three SRM studies [31-33]; two primary studies [48, 51] belong to each of the 2
SRM studies [30, 31] and one primary study [41] was included by each of the 2 SRM studies[32,
33]. Such an overlap is always expected from any umbrella review; and it has been mentioned
among the limitations of the study. On the contrary, 9 primary studies [54-62] were specific to
only Assemie et al [30], 2 primary studies [49, 50] for only Desalew, et al [31], and 1 primary
study [52] was included by Alamneh, et al [32] alone indicating that there was no overlapping of
data from the aforementioned 12 primary studies [49, 50, 52, 54-62] resulting in different
prevalence of birth asphyxia among the included 4 SRM studies, which in turn necessitated the
conduct of this umbrella review (table 2).
Table 2: Primary studies included in the systematic reviews and meta analyses (SRM)
Primary studies
Review
studies
Yohannes K et al[40]
Abebe A et al[41]
Worku N et al[42]
Lisanu W et al[43]
Zelalem J et al[44]
Gdiom G et al[45]
Alemwork D et al[46]
Hagos T et al[47]
Gudayu [48]
Shitemaw et al[49]
Worku et al[50]
Demisse et al[51]
Sebsibie., et al. [52]
Ibrahim., et al. [53]
Farah et al[54]
Orsido et al. [55]
Weldearegawi et al[56]
Roba et al[57]
Mengesha et al. [58]
Debelew et al[59]
Mehretie et al[60]
Yismaw et al[61]
Demissie et al[62]
Sendeku
et al.
[33]
*
#
#
*
#
#
*
*
#
Desalew,
et al [31]
*
#
*
#
#
*
*
#
#
†
#
#
Yoseph
Merkeb
Alamneh
et al.[32]
*
#
#
*
#
#
*
*
#
#
Assemie
et al[30]
#
#
#
#
#
#
†
†
†
*
†
†
*
*
*
NB: *denotes case control studies; # crossecrional and † cohort studies
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Methodological quality of the included SRM studies
Table 3 shows methodological quality of the included SRM studies, evaluated using the
AMSTAR tool for assessment of the methodological quality of SRM studies [36]. The quality
scoring was done out of 11 points and ranged from 8 to 10, with a mean score of 9.1 points,
indicating an overall moderate quality. The AMSTAR criteria most frequently satisfied across
the review studies were those about the priori design, duplicate study selection and data
extraction, appropriateness of methods used to combine studies’ findings and disclosure of
conflict of interest. The AMSTAR criteria less frequently satisfied were the ones about search
comprehensiveness, included and excluded studies provided and scientific quality of the included
studies used appropriately in formulating conclusions (table 3).
Table 3: Methodological quality of the included studies based on the AMSTAR tool
Author, year
Q1
Q2
Q3
Q4
Q5
Q6
Q7
Q8
Q9
Q10
Q11
Total
Sendeku et al.
[2020] [33]
Yes
Yes
Yes
No
No
Yes
Yes
No
Yes
Yes
Yes
8
Desalew, et al
[2020] [31]
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
No
Yes
10
Yoseph Merkeb
Alamneh., et al.
[2020] [32]
Yes
Yes
Yes
Yes
No
No
Yes
No
Yes
Yes
Yes
8
Assemie et al [2020]
[30]
Yes
Yes
Yes
Yes
No
Yes
Yes
No
Yes
Yes
Yes
9
AMSTAR Assessment of Multiple Systematic Reviews
Q1: A priori design; Q2: Duplicate study selection and data extraction; Q3: Search comprehensiveness; Q4: Inclusion of grey literature; Q5:
Included and excluded studies provided; Q6: Characteristics of the included studies provided; Q7: Scientific quality of the p rimary studies
assessed and documented; Q8: Scientific quality of included studies used appropriately in formulating conclusions; Q9: Appropriateness of
methods used to combine studies’ findings; Q10: Likelihood of publication bias was assessed; Q11: Conflict of interest – potential sources of
support were clearly acknowledged in both the systematic review and the included studies
Meta-analysis
Prevalence of birth asphyxia
From umbrella review of the 4 SRM studies [30, 31, 32, 33], the summary (pooled) prevalence
of perinatal asphyxia as defined by fifth minute APGAR score below 7 was 22.52% (95% CI =
17.01%-28.02%; I2=0.00) [Figure 2]. But, the systematic review findings range from 21.1%
(95% CI: 14%, 28%) [30] to 24.06% (95% CI: 18.11%, 30.01%) [33].
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Risk factors of perinatal asphyxia
Four SRM studies [30-33] examined a number of factors associated with perinatal asphyxia. The
reported factors include maternal educational status, parity, Antepartum Hemorrhage (APH),
Pregnancy Induced Hypertension (PIH) , Premature Rupture of Membrane (PROM), prolonged
labor, Meconium-Stained Amniotic Fluid (MSAF), instrumental delivery, non-cephalic
presentation, cord prolapse, induction of labor, cesarean section delivery, low birth weight and
prematurity. For this umbrella review, the aforementioned factors are categorized as socio-
demographic, antepartum, intrapartum and neonatal factors as detailed in the following
subsequent sections.
Socio-demographic factors
There was 1 SRM report [31] that showed statistical significance of maternal educational status
and parity on the burden of birth asphyxia. According to this report, neonates born to mothers
unable to read and write were 2 times (AOR= 1.96, 95% CI: 1.44–2.67) more likely to be
asphyxiated as compared to those neonates born to mothers able to read and write. Besides,
neonates of primiparous mothers were 1.3 times (AOR= 1.29, 95% CI: 1.03–1.62) more likely to
be asphyxiated as compared to neonates of multiparous mothers.
Ante-partum factors
One SRM study [31] revealed that neonates born to mothers having APH were 3 folds (AOR=
3.43, 95% CI: 1.74–6.77) likely to be asphyxiated compared to those born to mothers without
APH. Furthermore, neonates born to mothers having PIH were 4 times (AOR= 4.35, 95% CI:
2.98–6.36) more likely to be asphyxiated than those neonates born to mothers who didn’t have
PIH. Another 1 SRM report [32] showed significance of PROM (AOR= 12.27; 95% CI: 2.41,
62.38) in causing perinatal asphyxia.
Intra-partum factors
There was 1 SRM report [32] about significance of cord prolapse (AOR=2.95, 95% CI: 1.64,
5.30) on birth asphyxia. Besides, Desalew et al showed the relevance of labor induction on birth
asphyxia (AOR=3.69, 95% CI: 2.26–6.01). From all SRM reports included [30, 31, 32, 33], the
pooled odds of prolonged labor (AOR=3.18, 95% CI: 2.75, 3.60) and meconium-stained
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amniotic fluid (AOR=5.94, 95% CI: 4.86, 7.03) had significant association with birth asphyxia.
Three SRM studies [31, 32, 33] also revealed significance of instrumental delivery (AOR=3.39,
95% CI: 2.46, 4.32) on birth asphyxia. Moreover, 2 SRM reports [31, 32] witnessed importance
of the pooled odds of noncephalic presentation (AOR=3.39, 95% CI: 1.53, 5.26) and cesarean
section delivery (AOR=3.62, 95% CI: 3.36, 3.88) to cause birth asphyxia [Figure 3].
Neonatal factors
The pooled odds of 3 SRM reports [30, 31, 33] about the effect of low birth weight on birth
asphyxia showed 6 times higher likelihood of developing birth asphyxia among low birth weight
neonates than normal birth weight neonates (AOR=6.06, 95% CI: 5.13, 6.98). Besides, from 2
SRM studies [31, 32], the pooled odds of having asphyxia among premature neonates were 4
folds higher as compared to term neonates (AOR=3.94, 95% CI: 3.67, 4.21) [Figure4].
Conceptual frame work
In Ethiopia, umbrella review of the existing SRM studies showed birth asphyxia is a resultant of
different factors in the category of maternal socio-demography, antenatal, intra-natal and
neonatal components [Figure 5].
Discussion
To this date, there are four SRM reports about birth asphyxia in Ethiopia. In fact, SRM studies
are thought to denote a high level of evidence for decision making in health programs. However,
it could be exhausting for the information users when the number of individual reviews increases
[35]. Therefore, this umbrella review was conducted to summarize the four SRM studies on birth
asphyxia into a single document, and found that birth asphyxia was highly prevalent and a
problem of significant public health concern in Ethiopia. Moreover, different factors falling in
the category of maternal socio-demography, antenatal period, intra-partum period and neonatal
related characteristics were summarized to be of statistical significance in determining the
burden of birth asphyxia in the country.
Umbrella review of the included 4 SRM studies on the burden of birth asphyxia in Ethiopia
revealed a summary estimate of 22.52% (95% CI: 17.01%, 28.02%) which concurs with its
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incidence in East Africa 18.0% (95% CI: 11.4%, 26.7%), but higher than in Central African
countries 9.1% (95%CI: 2.0%, 16.2%) [63]. The variation in birth asphyxia between Ethiopia
and Central African countries may be due to relatively poor maternal socio-demographic
characteristics, low antenatal care visits (62%), high home delivery (74%), high prevalence of
low birth weight and preterm births in Ethiopia than in Central African countries [9, 11, 14].
Besides, our study involved only Ethiopia while the study in Central Africa included several
countries whose prevalence of birth asphyxia was averaged hence relatively lower burden in the
region than in Ethiopia. The burden of asphyxia in Ethiopia was; however, lower than in Iran
(58.8%) [64] which may be due to difference in case definition; for example, our study was
based on only fifth minute APGAR score less than 7 whereas that of the Iranian study used to
have a flexible diagnostic criteria of birth asphyxia including: umbilical cord pH<7 or 5 min
Apgar score <6 or 20 minute Apgar score less than 7 or multi organs failure in the first 72 hours
or convulsion in the first 24 hours of life.
Birth asphyxia accounts for 24.0% of the neonatal deaths in Africa [16]. Moreover, it comprises
31.6% of the neonatal deaths in Ethiopia [28] indicating its severity in the country. The severity
could be due to lack of costly neonatal care of asphyxiated neonates like miracradle, a
specialized neonatal bed designed for providing therapeutic hypothermia for neonates suffering
from birth asphyxia [2]. As birth asphyxia is a multifactorial condition, concerted efforts should
be made in its prevention through mainly skilled emergency obstetrics care [7, 8, 11]. The
Ethiopian government is implementing different strategies to reduce birth asphyxia such as
accessibility of maternity waiting homes for improving antenatal service usage and institutional
delivery rate [20]. But, further work is still needed to reduce neonatal deaths attributable to birth
asphyxia. Therefore, obstetric measures that are specific and sensitive to feto-neonatal health
should always be emphasized.
Neonates born to mothers unable to read and write were 2 times (AOR= 1.96, 95% CI: 1.44–
2.67) more likely to be asphyxiated as compared to those born to mothers able to read and write.
Our finding was consistent with studies in southern Nepal [66] and Pakistan [67]. This may be
due to the more educated a mother is, the more likely to utilize maternal and neonatal services
during pregnancy, labor and postnatal times hence minimizing risk of asphyxia [68]. Thus,
unable to read and write mothers should be continuously given health education about
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optimizing feto-neonatal health during pregnancy at health facilities and even in the community
through community health education by encouraging health extension workers.
Besides, neonates of primiparous mothers were 1.3 times (AOR= 1.29, 95% CI: 1.03–1.62) more
likely to be asphyxiated as compared to neonates of multiparous mothers and this finding
concurred with a Kenyan study [65]. This may be due to primigravidous mothers have a
relatively stronger and more vigorous uterine contractions leading to compromised oxygen
supply to the fetus hence birth asphyxia [69]. Besides, primigravidous mothers are often subject
to induction, which is a known possible risk factor of birth asphyxia from the hyperuterotonic
and antidiuretic adverse effects of oxytocin resulting in uterine rupture, water intoxication hence
fetoplacental insufficiency and birth asphyxia [70]. Umbilical cord entanglement (nuchal cord) is
also more likely among primigravidous mothers hence fetal hypoxia from cord accidents [71,
72]. Thus, primigravida mothors should always be at the forefront of receiving special antenatal
and intranatal follow up to prevent or minimize the possible intrapartum related complications as
early as possible.
Neonates born to mothers having antepartum derangements (antepartum hemorrhage, pregnancy
induced hypertension and premature rupture of membranes) and intrapartum risk factors
(prolonged labor, noncephalic presentation and cord prolapse) were more risked for birth
asphyxia than their counterparts which accords with findings from Kenya [65], East and Central
Africa [63], Pakistan [67] and Iran [64] which could be due to uteroplacental insufficiency hence
compromised fetal oxygenation and birth asphyxia. As a result, the existing efforts of health
extension workers, health care providers and health policy makers should be pooled to improve
the utilization of maternal and child health services during pregnancy and labor, thus optimizing
neonatal lives.
Preterm babies were 4 times (AOR=3.94, 95% CI: 3.67, 4.21) more likely to be asphyxiated than
term babies. This study is in line with studies conducted in Jordan [73] and Jakarta [74] which
discovered that preterm babies had more risk of developing birth asphyxia than the term
counterparts. This may be due to premature infants are more susceptible to ischemia due to
incomplete blood brain barrier formation. Moreover, it may be due to the fact that preterm babies
face multiple morbidities including organ system immaturity especially lung immaturity causing
respiratory failure.
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Low birth weight neonates (AOR=6.06, 95% CI: 5.13, 6.98) had 6 times more likelihood of
being asphyxiated as compared to their normal birth weight counterparts Kenya [65], Mulago
Hospital, Uganda [75], Dr Soetomo Hospital Surabaya, Indonesia[76], Vali-eAsr Hospital,
Tehran-Iran[77], Civil Hospital in Karachi, Pakistan[78], Pattani Hospital, Thailand[79] and
Phramongkutklao Hospital, Thailand [80]. This could be explained by the fact that low birth
weight babies might be pre-term that they might not have enough surfactant which might lead to
suffering from difficulty of breathing and developing difficulty in cardiopulmonary transition
and subsequent birth asphyxia. Moreover, small babies have low brown fat tissue which
increases their risk of being hypothermic thus increasing the severity of asphyxia. Consequently,
low birth weight neonates should be provided with immediate respiratory support, calorie gain
and thermal care support to help them adapt the extra uterine environment [1, 2]
Implications of the study
This study was in response to the call and recommendation of a prior Ethiopian methodological
study [34] that urged summary evidence on a certain health problem when there is more than one
systematic review on that problem. Being the first of its kind in synthesizing the existing SRM
reports about birth asphyxia in Ethiopia, this umbrella review has brought a comprehensive
summary estimate of the problem. Therefore, this national summary estimate of birth asphyxia
and its associated factors can be used by clinicians, policy makers and all other bodies at the
stake of optimizing neonatal health in the country.
Strength and limitation
The risk of bias was tried to be minimized through exhaustive searching of multiple databases,
and study selection was undertaken by two researchers, with involvement of a third researcher as
a tie breaker. Once more, risk of bias of the SRM studies was assessed using the AMSTAR tool.
Primary researches within the SRM reports were also mapped to identify the overlap of data
among the included SRM studies. Despite the aforementioned strengths, summarizing multiple
meta-analyses data that include overlapping primary studies has the potential to overestimate the
strength of the findings. Also, usage of the fifth minute Apgar score alone, compared to AAP and
ACOG definition of birth asphyxia, does not give a complete picture of measuring birth
asphyxia, which might have caused an overestimated prevalence of birth asphyxia in Ethiopia.
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Therefore, future studies in the country should complement fifth minute Apgar score with
immediate newborns’ umblical cord blood pH and bio-chemical results of arterial blood gas analyses
(indicative of neonatal hypoxemia and hypercarbia). Moreover, regarding outcome measurement, 2 of
the 23 primary articles, namely Necho AW et al [42] and Meshesha AD et al [46] considered the first
minute Apgar score < 7, unlike the rest 21 primary articles that considered the fifth minute Apgar score <
7. This discordance in measuring birth asphyxia might have influenced the generalization and
interpretations of our pooled estimate. Most importantly, confounding factors that can affect birth
asphyxia were not identified due to the nature of meta-analysis in using aggregated group data,
which could have affected the pooled estimate. Because of all the above mentioned reasons, our
pooled estimate may not actually represent the national figure of birth asphyxia in Ethiopia.
Therefore, we would like to forward our earnest reminder for the readers to be mindful of
interpreting and using this finding in the context of both inherent limitations of the included
primary studies and the current umbrella analysis.
Overall, since this meta-analysis has systematically identified all the aforementioned limitations,
the design of future studies can be substantially improved.
Conclusions
In this umbrella review, the quality of individual reviews (SRM) were first appraised and then
evidence were highlighted and brought together in a single document, providing definitive
summaries of birth asphyxia that could be used to inform clinical practice.
From the umbrella review, birth asphyxia is still burdensome in Ethiopia. Besides, maternal
illiteracy, primiparity, antepartum hemorrhage, pregnancy induced hypertension, premature
rupture of membrane, prolonged labor, meconium-stained amniotic fluid, instrumental delivery,
non-cephalic presentation, cord prolapse, labor induction, cesarean section delivery, low birth
weight and preterm babies are positively associated with birth asphyxia. All of these factors can
be optimized through the collaborative efforts of national, regional and local stakeholders of
neonatal health in Ethiopia. As advanced cares like miracradle aren’t present for asphyxiated
neonates in the country, prevention is unquestionably urged. Thus, health care providers should
make exhaustive investment of their efforts for early detection and management of obstetrical
deviations during pregnancy, labor and delivery. Most importantly, strict partographic follow ups
of feto-maternal health should be made during the intrapartum time supported by different
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diagnostics (E.g. ultrasound), accompanied with immediate emergency obstetrics and newborn
care interventions.
Acronyms
AOR: Adjusted Odds Ratio; APGAR: Appearance, Pulse, Grimace, Activity, Respiration; APH:
Ante Partum Hemorrhage; CI: Confidence Interval; FMOH: Federal Ministry of Health; MSAF:
Meconium-Stained Amniotic Fluid; LBW: low birth weight; PIH: Pregnancy Induced
Hypertension; PROM: Premature Rupture of Membrane; prolonged labor; PRISMA: Preferred
Reporting Items for Systematic Reviews and Meta-Analyses; SRM: Systematic Reviews and
Meta-analysis; AMSTAR:Assessment of Multiple Systematic Reviews and Meta-analysis; NOS:
Newcastle Ottawa Scale; SDG: Sustainable Development Goal; SNNP: Southern Nations,
Nationalities and Peoples; WHO: World Health Organization.
Declarations
Ethics approval and consent to participate
Not applicable.
Consent for publication
Not applicable.
Availability of data and materials
The data analyzed during the current systematic review and meta-analysis is public and
contained within the manuscript.
Competing interests
The authors declare that they have no competing interests.
Funding: Not applicable.
Authors’ contributions
WAB, BMB, DMB, MYA, AD and GYY developed the protocol and involved in the design and
searching of literature. HMW, Dr MAT and SDK contributed in screening and selection of
articles. AYA, GG and AD extracted data from the included studies. AYA and ESC analyzed the
extracted data and developed initial draft of the manuscript. All authors prepared, read and
approved the final draft of the manuscript.
Acknowledgements
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We would like to thank all authors of the studies included in this systematic review and meta
analysis.
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Figure Legend
Figure 1: Literature search, screening and selection process (PRISMA flow diagram)
Figure 2: Umbrella review of systematic reviews and met analysis studies on the burden of
perinatal asphyxia in Ethiopia
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27
Figure 3: Umbrella review about the pooled effects of intrapartum risk factors on birth asphyxia
Figure 4: Umbrella review about the pooled effects of neonatal characteristics on birth asphyxia
Figure 5: Conceptual framework on the umbrella review of the risk factors for perinatal
asphyxia in Ethiopia
Supplementary files
Supplementary file 1: PUBMED search strategy
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Science direct
searching
(n=69 records)
*Other data
bases searching
(n=17 records)
PUBMED
searching
(n=94 records)
Records after duplicates removed (n=59)
Records screened
(n=59)
Full text articles assessed
for eligibility
(n=5)
Included in the umbrella review
(n=4)
Records excluded by title and abstract
(n=54)
1 Full text article was excluded for not
including the required outcome
Web of science
searching
(n=38 records)
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Umbrella review of the prevalence of perinatal asphyxia
NOTE: Weights are from random effects analysis
Overall (I-squared = 0.0%, p = 0.987)
Author/year
Yoseph Merkeb Alamneh., et al.[2020]
Assemie et al [2020]
Sendeku et al. [2020]
Desalew, et al [2020]
22.52 (17.01, 28.02)
ES (95% CI)
22.50 (0.99, 22.50)
21.10 (0.31, 21.10)
24.06 (0.41, 24.06)
22.80 (0.32, 22.80)
100.00
Weight
26.22
28.08
%
21.69
24.01
22.52 (17.01, 28.02)
ES (95% CI)
22.50 (0.99, 22.50)
21.10 (0.31, 21.10)
24.06 (0.41, 24.06)
22.80 (0.32, 22.80)
100.00
Weight
26.22
28.08
%
21.69
24.01
0
-28
0
28
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NOTE: Weights are from random effects analysis
.
.
.
.
.
Overall (I-squared = 97.6%, p = 0.000)
Desalew et al [2020]
MSAF
Yoseph Merkeb Alamneh et al [2020]
Desalew et al [2020]
Yoseph Merkeb Alamneh et al [2020]
Subtotal (I-squared = 97.1%, p = 0.000)
Yoseph Merkeb Alamneh et al [2020
Sendeku et al [2020]
Assemie et al [2020]
Desalew et al [2020]
Noncephalic presentation
Subtotal (I-squared = 94.5%, p = 0.000)
Subtotal (I-squared = 0.0%, p = 0.511)
Prolonged labor
Desalew et al [2020]
Study
Subtotal (I-squared = 96.1%, p = 0.000)
Yoseph Merkeb Alamneh et al [2020]
Assemie et al [2020]
Desalew et al [2020]
Yoseph Merkeb Alamneh et al [2020]
Instrumental delivery
Cesarean section delivery
Subtotal (I-squared = 85.3%, p = 0.000)
ID
Sendeku et al [2020]
Sendeku et al [2020]
4.03 (3.43, 4.62)
3.66 (3.38, 3.94)
2.43 (1.87, 2.99)
3.09 (2.83, 3.35)
3.42 (2.76, 4.08)
3.39 (1.53, 5.26)
3.42 (2.76, 4.08)
2.79 (2.50, 3.08)
3.70 (3.42, 3.98)
4.33 (4.03, 4.63)
3.39 (2.46, 4.32)
3.62 (3.36, 3.88)
2.74 (2.50, 2.98)
5.94 (4.86, 7.03)
6.80 (5.89, 7.71)
6.60 (6.23, 6.97)
4.59 (4.28, 4.90)
3.10 (2.47, 3.73)
3.18 (2.75, 3.60)
ES (95% CI)
4.04 (3.69, 4.39)
5.91 (5.49, 6.33)
100.00
6.85
6.55
6.86
6.41
13.38
6.41
6.84
6.85
6.83
20.07
13.25
6.87
%
26.29
5.97
6.77
6.82
6.45
27.00
Weight
6.79
6.72
4.03 (3.43, 4.62)
3.66 (3.38, 3.94)
2.43 (1.87, 2.99)
3.09 (2.83, 3.35)
3.42 (2.76, 4.08)
3.39 (1.53, 5.26)
3.42 (2.76, 4.08)
2.79 (2.50, 3.08)
3.70 (3.42, 3.98)
4.33 (4.03, 4.63)
3.39 (2.46, 4.32)
3.62 (3.36, 3.88)
2.74 (2.50, 2.98)
5.94 (4.86, 7.03)
6.80 (5.89, 7.71)
6.60 (6.23, 6.97)
4.59 (4.28, 4.90)
3.10 (2.47, 3.73)
3.18 (2.75, 3.60)
ES (95% CI)
4.04 (3.69, 4.39)
5.91 (5.49, 6.33)
100.00
6.85
6.55
6.86
6.41
13.38
6.41
6.84
6.85
6.83
20.07
13.25
6.87
%
26.29
5.97
6.77
6.82
6.45
27.00
Weight
6.79
6.72
0-7.71 0 7.71
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Neonatal factors
NOTE: Weights are from random effects analysis
.
.
Overall (I-squared = 97.6%, p = 0.000)
Subtotal (I-squared = 0.0%, p = 0.494)
Desalew et al [2020]
Study ID
Assemie et al [2020]
Desalew et al [2020]
Yoseph Merkeb Alamneh et al [2020]
Sendeku et al [2020]
Low birth weight
Prematurity
Subtotal (I-squared = 94.5%, p = 0.000)
5.19 (4.07, 6.31)
3.94 (3.67, 4.21)
5.17 (4.84, 5.50)
ES (95% CI)
6.50 (6.13, 6.87)
3.98 (3.69, 4.27)
3.72 (3.03, 4.41)
6.52 (6.08, 6.96)
6.06 (5.13, 6.98)
100.00
39.52
20.28
Weight
20.19
20.36
19.16
20.01
60.48
%
5.19 (4.07, 6.31)
3.94 (3.67, 4.21)
5.17 (4.84, 5.50)
ES (95% CI)
6.50 (6.13, 6.87)
3.98 (3.69, 4.27)
3.72 (3.03, 4.41)
6.52 (6.08, 6.96)
6.06 (5.13, 6.98)
100.00
39.52
20.28
Weight
20.19
20.36
19.16
20.01
60.48
%
0
-6.98
0
6.98
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Socio-demographic
factors
Primiparity
Illiteracy
Antenatal
factors
APH
PIH
PROM
Intranatal
factors
Prolonged labor
MSAF
instrumental
delivery
non-cephalic
presentation
cord prolapse
induction of labor
cesarean section
Neonatal factors
Low birth weight
Prematurity
Birth asphyxia
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