Neonatal hypothermia and its associated factors in East Africa: a systematic review and meta-analysis

doi:10.21203/rs.2.16426/v1

Background : Neonatal hypothermia is a global health problem and a major contributing factor for neonatal morbidity, mortality, and for new-born survival, especially in low and middle-income countries. High prevalence of hypothermia has been reported from countries with the highest burden of neonatal mortality. Therefore, the aim of this systematic review and meta-analysis was to assess the prevalence of neonatal hypothermia and its associated factors in Eastern Africa.

Methods: Using PRISMA guideline, we systematically reviewed and meta-analyzed studies that examined the prevalence and associated factors of neonatal hypothermia from PubMed, Cochrane library, and Google Scholar. Heterogeneity across the studies was evaluated using the Q and the I 2 test. A weighted inverse variance random-effects model was applied to estimate the national prevalence and the effect size of associated factors. The subgroup analysis was conducted by country, study design, and year of publication. A funnel plot and Egger’s regression test were used to see publication bias.

Result: A total of 12 potential studies with 20,911 participants were used for analysis. The pooled prevalence of neonatal hypothermia in East Africa was found to be 57.22% (95%CI; 39.48–74.95).Delay in initiation of breastfeeding (AOR=2.83; 95%CI: 1.398-4.259; I 2 = 49.2%; P=0.097), having neonatal health problem (AOR=2.68; 95%CI: 1.21-4.15; I 2 = 0.0%; P=0.98), being low birth weight (AOR =2.16; 95%CI: 1.03-3.29; I 2 =3.3%; P=0.005), being preterm(AOR=4.01; 95%CI: 3.02-5.00; I 2 = 0.0%; P=0.457), and night time delivery (AOR=4.01; 95%CI:3.02-5.00; I 2 =0.0%; P=0.457) were identified associated factors which significantly increase the risk of neonatal hypothermia.

Conclusions : The prevalence of neonatal hypothermia in Eastern Africa remains high. Delay in initiation of breastfeeding, having neonatal health problem, being low birth weight, preterm, and nighttime delivery were identified associated factors which significantly increase the risk of neonatal hypothermia. It is recommended that early initiation of breast feeding should be promoted and emphasis should be given towards low birth weight, preterm and neonates with neonatal problems to prevent burdens of hypothermia in East Africa.

Pediatrics

Neonates

hypothermia

Eastern Africa

meta-analysis

According to World Health Organization(WHO), neonatal hypothermia is an abnormal thermal state in which the newborn’s body temperature is below 36.5°C [1]. It is a global health problem with higher rate in countries with low resource settings [3]. In sub-Saharan countries, hypothermia increases neonatal death by 80% for every 1 degree Celsius decrease of body temperature [3].

Hypothermia occurs usually with severe infections,prematurity, and asphyxia paying much for the least drop in neonatal death rate of the African regions [6]. It leads to diverse neonatal health consequences, and its prevalence in hospitals varies from 32 to 85% and at homes from 11 to 92%, including in the tropical environments[4]. Hypothermia is one of the important causes for neonatal death and morbidity in developing countries, which rises neonatal mortality by five times. Previous studies had revealed that every 1°c reduction of neonate’s body temperature raises the mortality by 80% [3, 7, 8]. The prevalence is high among countries with the highest burden of neonatal morbidity and mortality. Hence, increasingly, it is documented as a contributor for newborn survival [9, 10].

In developed countries neonatal hypothermia takes for 28% of the world burden. More than 98% of yearly neonatal mortality occur in developing countries [11].Despite this fact only limited progress has been made towards risk for neonatal mortality [11].To solve the major neonatal problems secondary to hypothermia, identifying its determinants is needed; which have greater input to attain sustainable development goal (SDG) 3 of ensuring healthy lives and promote well-being for all at all age.

Indeed, approaches that can prevent and treat neonates with hypothermia are vital to hasten the advancement of newborn survival. In East Africa, variety of studies was conducted to estimate the prevalence of neonatal hypothermia. However, prevalence of neonatal sepsis ranges from 1.3% [14] to 79% [15] which indicated a great inconsistencies across different geographical settings and different time periods. In addition, there are some opposing or inconsistent findings on risk factors and mortality predictors of neonates due to hypothermia. Moreover, there is no regionally denoted pooled data of neonatal hypothermia in East Africa. Therefore, this systematic review and meta-analysis was aimed; to estimate the pooled prevalence of neonatal hypothermia and the effect size of its associated factors in East Africa context.

Reporting

The results of this review were reported based on the Preferred Reporting Items for Systematic Review and Meta-Analysis statement (PRISMA) guideline (Supplementary file 1: PRISMA checklist) and, it is registered in the Prospero database: (PROSPERO 2019: CRD42019131654) Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID = CRD42019131654.

Searching strategy and selection criteria

We identified studies providing data on the prevalence and/or potential risk factors for neonatal hypothermia with the search focused on Eastern Africa. PubMed, Google Scholar, and Cochrane library were retrieved. The search included keywords and MeSH terms, combinations, and snowball searching in references of relevant papers for linked articles. The core search terms and phrases were “newborn”, “neonate”, “infant”, “hypothermia”, “low body temperature”, “thermoregulation”, Body Temperature Regulation, and Eastern Africa. The search strategies were developed using different Boolean operators. Notably, to fit advanced PubMed database, the following search strategy was applied: (prevalence OR magnitude) AND (causes OR determinants OR associated factors OR predictors) AND (newborn [MeSH Terms] OR neonate OR infant OR child OR children)AND (hypothermia [MeSH Terms] OR low body temperature OR thermoregulation OR Body Temperature Regulation)AND (Eastern Africa). We also screened at the reference lists of the remaining papers to identify additional relevant studies to this review.

Study selection / Eligibility criteria

Retrieved studies were exported to Endnote version 8 reference manager software, to remove duplicate studies. Two investigators (BBA and AMK) independently screened the selected studies using article titles and abstracts before retrieval of full-text papers. We used pre-specified inclusion criteria to further screen the full-text articles. Disagreements were discussed during a consensus meeting with other reviewers (MWK and MAR) for the final selection of studies to be included in the systematic review and meta-analysis.

Inclusion and exclusion criteria

Cross-sectional, case-control, and cohort studies were included. Those studies had reported the prevalence and/or at least one associated factor for neonatal hypothermia and published in English language from 2000 up to 2019 were considered. Citations without abstract and/or full-text, anonymous reports, editorials, and qualitative studies were excluded from the analysis.

Quality assessment

Three authors independently appraised the quality of the studies by using the Joanna Briggs Institute (JBI) quality appraisal checklist was used [16]. The disagreement was resolved by the interference of the fourth reviewer. The following items were used to appraise cohort studies: (1) similarity of groups, (2) similarity of exposure measurement, (3) validity and reliability of measurement, (4) identification of confounder,(5) strategies to deal with confounder, (6) appropriateness of groups/participants at the start of the study(7) validity and reliability of outcome measured, (8) sufficiency of follow-up time, (9) completeness of follow-up or descriptions of reason to loss to follow-up, (10) strategies to address incomplete follow-up, and (11) appropriateness of statistical analysis. The items used to appraise case-control studies were: (1) comparable groups, (2) appropriateness of cases and controls, (3) criteria to identify cases and controls, (4) standard measurement of exposure, (5) similarity in measurement of exposure for cases and controls, (6) handling of confounder (7), strategies to handle confounder, (8) standard assessment of outcome, (9) appropriateness of duration for exposure, and (10) appropriateness of statistical analysis. Studies got 50% and above of the quality scale were considered low risk. The following items were used to appraise cross-sectional studies: (1) inclusion criteria, (2) description of study subject and setting, (3) valid and reliable measurement of exposure, (4) objective and standard criteria used,(5)identification of confounder, (6) strategies to handle confounder, (7) outcome measurement, and (8)appropriate statistical analysis. Studies were considered low risk when it scored 50% and above of the quality assessment indicators.

Data extraction

Two reviewers independently extracted the data using a structured data extraction form. Whenever variations of extracted data observed, the phrase was repeated. If discrepancies between data extractors continued, the third and fourth reviewer was involved. The name of the first author and year of publication, tstudy country, study design, the target population, tsample size, prevalence of neonatal hypothermia, and AOR of associated factors were extracted

Outcome measurement

Neonatal hypothermia was considered, when neonate’s body temperature was less than 36.5 degree centigrade or neonates who are diagnosed as hypothermia by attending physician and fulfill hypothermia criteria within 0–28 days of life.

Statistical analysis

We pooled the overall prevalence estimates of neonatal hypothermia by a random effect meta-analysis model [17]. We examined the heterogeneity of effect size using Q statistic and the I² statistics[17]. In this study, the I²statistic value of zero indicates true homogeneity, whereas the value 25, 50, and 75% represented low, moderate and high heterogeneity respectively [18, 19].

For the data identified as heterogeneous, we conducted our analysis by random-effects model analysis. Subgroup analysis was done by the study country, design, and year of publication. Sensitivity analysis was employed to see the effect of a single study on the overall estimation.

Publication bias was checked by funnel plot and more objectively through Egger’s regression test.

A total of 3496 studies were identified; 2252 from PubMed, 12 from Cochrane Library, 1210 from Google Scholar and 22 from other sources. After duplication removed, a total of 1034 articles remained. Finally, 201 studies were screened for full-text review and , only 12 articles with (n=20,911 patients) were selected for the prevalence and/ or associated factors analysis (Fig.1)

Characteristics of included studies

Table 1 summarizes the characteristics of the 12 included studies in the systematic review [14, 15, 20-29]. Eight studies were found in Ethiopia [14, 21-27], 2 in Kenya [28, 29], while 2 were from Uganda[15, 20]. Nine studies were cross-sectional , while the others used either case-control (n=1) or cohort (n=2) study design. Most of the studies 8/12(66.7%) were published between 2010 and 2017. The studies included participants, ranging from 136, [29] to 15191[28] (Table1).

Meta-analysis

Prevalence of neonatal hypothermia

Most of the studies (n=10) had reported the prevalence of neonatal hypothermia [14, 15, 20-25, 27, 29]. The prevalence of hypothermia were ranged from 13% [14] up to 79 % [15]. The random-effects model analysis from those studies revealed that, the pooled prevalence of neonatal hypothermia in East Africa was found to be 57.2% (95%CI; 39.48–74.95; I²=99.5%; p<0.001) (Fig.2).

Subgroup analysis of the prevalence of neonatal hypothermia in Eastern Africa

The subgroup analysis was done through stratified by country, study design, and year of publication. Based on this, the prevalence of neonatal hypothermia was found to be 55.3% in Ethiopia, 62.6% in Uganda, and 60.0% in Kenya (Fig 3 and Table 2). Based on the study design, the prevalence of neonatal hypothermia was found to be 63.5% in cross-sectional studies and 32.98% in cohort studies (Fig 4 and Table 2). Based on the year of publication, the prevalence of neonatal hypothermia was found to be 65.06% from 2000-2015, while it was 57.90% from studies conducted from 2016-2019(Fig 5, Table 2).

Publication bias

A funnel plot showed asymmetrical distribution. Egger’s regression test p-value was 0.019, which indicated the presence of publication bias. Due to presence of publication bias we employed a leave-one-out sensitivity analysis to identify the potential source of heterogeneity in the analysis of the prevalence of neonatal hypothermia in Eastern Africa. The results of this sensitivity analysis showed that our findings were not dependent on a single study. Our pooled estimated prevalence of neonatal hypothermia varied between 54.79(36.47–73.12) and 62.26(55.22–69.30) after deletion of a single study. Byaruhanga R, 2005(23), Mekonnen Tilahun, 2018(34) had shown an impact on the overall estimation.

Factors associated with neonatal hypothermia in East Africa

See Table 3.

Delayed initiation of breast feeding

Five studies found significant association between delayed initiation of breast feeding and neonatal hypothermia. Birhanu etal (2017) revealed that neonates with delayed initiation of breast feeding were 4.39 times at risk of having neonatal hypothermia compared to neonates with timely initiation of breast feeding. G/silasea etal revealed that neonates with delayed initiation of breast feeding were 2.42 times at risk of having neonatal hypothermia (95% CI: 1.45, 4.02) compared to neonates with timely initiation of breast feeding. Tewodros et al revealed that neonates with delayed initiation of breast feeding were 7.58 times at risk of having neonatal hypothermia compared to neonates with timely initiation of breast feeding. Hagos et alrevealed that neonates with delayed initiation of breast feeding were 7.23 times at risk of having neonatal hypothermia compared to neonates with timely initiation of breast feeding. Wubet revealed that neonates with delayed initiation of breast feeding were 1.63 times at risk of having neonatal hypothermia (95% CI: 0.88, 2.99) compared to neonates with timely initiation of breast feeding.

Regarding heterogeneity test, galbraith plot showed homogeneity and combining the result of five studies, the forest plot showed the overall estimate of AOR of home delivery was 2.83( 95%C I: 1.398-4.26;I²= 49.2%;P=0.097).I-Squared (I²)and P-value also showed homogeneity (fig 6).

Regarding publication bias, a funnel plot showed an asymmetrical distribution. During the Egger’s regression test, the p-value was 0.016, which indicated the presence of publication bias. Due to presence of publication bias trim and fill analysis was done and 2 studies were added, and the total number of studies becomes 7. The pooled estimate of AOR of home delivery was found to be 2.463.

Neonatal health problems

Five studies (G/silasea etal 2019, Tewodros S etal 2015, Hagos T 2018, Wubet A etal 2019 and ANNA BM etal 2005) found significant association between neonatal health problems and neonatal hypothermia. G/silasea et al revealed that neonates with health problem were 2.46 times at risk of having neonatal hypothermia (95% CI: 1.07, 5.66) compared to neonates without health problems. Tewodros et al revealed that neonates with health problem were 3.1 times at risk of having neonatal hypothermia compared to neonates without health problem. Hagos revealed that neonates with health problem were 2.282 times at risk of having neonatal hypothermia compared to neonates without health problem. Wubet A revealed that neonates with health problems were 4.24 times at risk of having neonatal hypothermia (95% CI: 1.92, 9.34) compared to neonates without neonatal health problems. ANNA BM etal revealed that neonates with health problems were 4.24 times at risk of having neonatal hypothermia compared to neonates without health problems(table 3)

Regarding heterogeneity test for neonatal health problems, galbraith plot showed homogeneity and combining the result of five studies the forest plot showed the overall estimate of AOR of home delivery was 2.68( 95%CI: 1.21-4.15;I²= 0.0%;P=0.98).I-Squared (I²)and P-value also showed homogeneity (fig 7)

Regarding publication of bias for neonatal health problems analysis, the funnel plot analysis showed asymmetrical distribution. During the Egger's regression test, the p-value was 0.068, which indicated the absence of publication bias. Trim and fill analysis was done, and 1 study were added and the total number of studies become 6 .the pooled estimate of AOR of preterm becomes 2.49.

We employed a leave-one-out sensitivity analysis to identify the potential source of heterogeneity in the analysis of the prevalence of neonatal hypothermia in Eastern Africa. The results of this sensitivity analysis showed that our findings were not dependent on a single study. Our pooled estimate of neonatal health problems varied between 2.49(95%CI,0.88-4.09) and 2.75(95%CI, 1.15-4.34) after deletion of a single study.

Low birth weight

Five studies (Birhanu W etal 2017, G/silasea etal 2019, Tewodros S etal 2015, Hagos T 2018, Wubet A etal 2019) found significant association between low birth weight and neonatal hypothermia. Birhanu W etal revealed that neonates with low birth weight were 1.33 times at risk of having neonatal hypothermia compared to neonates with normal birth weight. G/silasea etal revealed that neonates with low birth weight were 3.61 times at risk of having neonatal hypothermia (95% CI: 2.1, 6.18) compared to neonates with normal birth weight. Tewodros S etal revealed that neonates with low birth weight were 3.75 times at risk of having neonatal hypothermia compared to neonates with normal birth weight. Hagos T revealed that neonates with low birth weight were 8.51 times at risk of having neonatal hypothermia compared to neonates with normal birth weight. Wubet A revealed that neonates with low birth weight were 1.2 times at risk of having neonatal hypothermia (95% CI: 0.51,2.82) compared to neonates with neonatal birth weight.

Regarding heterogeneity test, galbraith plot showed heterogeneity and combining the result of five studies the forest plot showed the overall estimate of AOR of low birth weight was 2.16( 95%CI: 1.027-3.293;I²= 3.3%;P=0.005).I-Squared (I²)and P-value also showed heterogeneity(fig 8).

Regarding publication bias a funnel plot showed a symmetrical distribution. Egger's regression test p-value was 1.98, which indicated the absence of publication bias.

Trim and fill analysis was done, and 2 studies were added and the total number of studies become 7. The pooled estimate of AOR of low birth weight becomes 1.85.

Preterm

Five studies (Birhanu W etal 2017, G/silasea etal 2019, Tewodros S etal 2015, Hagos T 2018, Wubet A etal 2019) found significant association between preterm and neonatal hypothermia. Birhanu W etal revealed that preterm neonates were 4.39 times at risk of having neonatal hypothermia compared to term neonates. G/silasea etal revealed that preterm neonates were 4.61times at risk of having neonatal hypothermia (95% CI: 2.1, 8.18) compared to term neonates. Tewodros etal revealed that term neonates were 1.5 times at risk of having neonatal hypothermia compared to preterm neonates. Hagos revealed that term neonates were 3.689 times at risk of having neonatal hypothermia compared to preterm neonates. Wubet revealed that term neonates 3.37 times at risk of having neonatal hypothermia (95% CI: 1.53, 7.44) compared to preterm neonates (Table 3).

Regarding heterogeneity test, the galbraith plot analysis showed homogeneity and combining the result of five studies the forest plot showed the overall estimate of AOR of home delivery was 4.01( 95%C I: 3.02,5.00;I²= 0.0%;P=0.457).I-Squared (I²)and P-value also showed homogeneity(figure 9)

Regarding publication bias a funnel plot showed a symmetrical distribution. Egger's regression test p-value was 0.131, which indicated the presence of publication bias.

Nighttime delivery

Five studies (Birhanu W etal 2017, G/silasea etal 2019, Tewodros S etal 2015, Hagos T 2018, Wubet A etal 2019) found significant association between night delivery and neonatal hypothermia. Birhanu W etal revealed that neonates delivered at night were 1.32 times at risk of having neonatal hypothermia compared to neonates who delivered at day. G/silasea etal revealed that neonates delivered at night 1.68 times at risk of having neonatal hypothermia (95% CI: 1.01, 2.83) compared to neonates who delivered at day. Tewodros etal revealed that neonates delivered at night 6.61 times at risk of having neonatal hypothermia compared to neonates who delivered at day. Hagos revealed that neonates delivered at night 6.25 times at risk of having neonatal hypothermia compared to neonates delivered at day.

Wubet revealed that neonates delivered at night were 3.18 times at risk of having neonatal hypothermia (95% CI: 0.51, 2.82) compared to neonates delivered at day.

Regarding heterogeneity test, the galbraith plot showed homogeneity and combining the result of five studies the forest plot showed the overall estimate of AOR of low birth weight was 4.01( 95%C I: 3.018-5.002;I²= 0.0%;P=0.457).I-Squared (I²)and P-value also showed homogeneity(figure 10).

Regarding publication bias, the funnel plot analysis showed a symmetrical distribution. During the Egger's regression test, the p-value was 0.131, which indicated the absence of publication bias.

In this systematic review and meta-analysis, we explored the prevalence and determinants of neonatal hypothermia in Eastern Africa. 14 studies were included in the final analysis. Based on the meta-analysis a significant proportion (more than 1 in 2) of neonates had neonatal hypothermia in Eastern Africa. This shows that neonatal hypothermia is a significant public health problem in Eastern Africa. We also identified factors that were significantly associated with neonatal hypothermia in Eastern Africa. In this study, the pooled prevalence of neonatal hypothermia in Eastern Africa was 57.22 %( 95%CI; 39.48–74.95). The results of this meta-analysis were in line with other systematic review, prevalence of hypothermia ranges from 32% to 85% (33).

The results of this meta-analysis were higher than review conducted in Iran which was 7.48 to 53.3 percent (34).

Lower than a review in sub Saharan Africa, a prevalence rate of 62% (35).These differences might be due to the socioeconomic and cultural differences between the countries. Moreover, the other obvious reason for the various might be the sample size, a collection of data from different settings (community and institution setting) as well as different study periods.

Delay in initiation of breastfeeding, having neonatal health problem, being low birth weight, being preterm, and night time delivery were identified factors which significantly increase the risk of neonatal hypothermia. Similar finding was also reported from the meta-analysis [30–32].

The prevalence of neonatal hypothermia in Eastern Africa remains high. Delay in initiation of breastfeeding, having neonatal health problem, being low birth weight, being preterm, and nighttime delivery were identified factors which significantly increase the risk of neonatal hypothermia. It is recommended that early initiation of breast feeding should be promoted and emphasis should be given towards low birth weight, preterm and neonates with neonatal problems to prevent burdens of hypothermia in East Africa.

This review may help policy-makers and program officers to design neonatal sepsis preventive interventions.

Strength and limitations

This study has several strengths: First, we used a pre-specified protocol for search strategy and data abstraction and conducted quality assessment two independent investigators to lessen the possible assessor bias; second, we employed subgroup and sensitivity analysis based on study country, study design, and publication year to identify the small study effect and the risk of heterogeneity. Nevertheless, this review had some limitations: The result in this meta-analysis is derived from studies conducted in hospital settings, and this limits the generalizability of the review findings.

Recommendations

Hypothermia prevention messages and interventions into evidence-based, cost-effective packages for maternal and newborn care should be introduced. Attention is needed for thermal care of newborn especially those preterm, low birth weight and newborns with health problems on early initiation of breastfeeding immediately after delivery. It is also important to give attention babies delivered during nighttime.

WHO: World Health Organization; CI: Confidence interval; DHS: Demographic and Health Surveys; EDHS: Ethiopian Demographic and Health Survey; AOR: Adjusted odds ratio; ENBC: Essential newborn care; RR: Relative risk; SDG: Sustainable development goal; SPSS: Statistical Package for Social Sciences

Ethics approval and consent to participate

Not applicable because no primary data were collected

Consent for publication

Note applicable.

Availability of data and materials

Data is available and it can be accessed from the corresponding author when asked with a reasonable inquiry.

Competing interests

The authors declare that they have no competing interests.

Funding

None

Authors’ contributions

BBA conceives the study idea, and conducted the data analysis; AMK, MWK and MAR established the search strategy, and involve the meta-analysis. All authors read the and approve the manuscript for publication.

Acknowledgments

Not applicable

Authors’ information

¹Woldia University, Faculty of Health Sciences, Department of Nursing, P. O. Box 400, Woldia, Ethiopia; ²Department of Medical Laboratory Science, Faculty of Health Sciences, Woldia University, P. O.Box 400 Woldia, Ethiopia; ³Department of Medical Microbiology, Faculty of Health Sciences, University of Pretoria, South Africa.

1.Organization WH: Thermal control of the newborn: a practical guide. In.: Geneva: World Health Organization; 1993.

2.Organization WH: Thermal protection of the newborn: a practical guide. Maternal and Newborn Health. Safe motherhood unit WHO/RHT/MSM/972 1997.

3.Onalo R: Neonatal hypothermia in sub-Saharan Africa: a review. Nigerian journal of clinical practice 2013, 16(2):129–138.

4.Mullany LC, Katz J, Khatry SK, LeClerq SC, Darmstadt GL, Tielsch JM: Neonatal hypothermia and associated risk factors among newborns of southern Nepal. BMC medicine 2010, 8(1):43.

5.Zayeri F, Kazemnejad A, Ganjali M, Babaei G, Nayeri F: Incidence and risk factors of neonatal hypothermia at referral hospitals in Tehran, Islamic Republic of Iran. 2007.

6.Mekonnen Y, Tensou B, Telake DS, Degefie T, Bekele A: Neonatal mortality in Ethiopia: trends and determinants. BMC public health 2013, 13(1):483.

7.Sodemann M, Nielsen J, Veirum J, Jakobsen MS, Biai S, Aaby P: Hypothermia of newborns is associated with excess mortality in the first 2 months of life in Guinea‐Bissau, West Africa. Tropical Medicine & International Health 2008, 13(8):980–986.

8.Mullany LC, Katz J, Khatry SK, LeClerq SC, Darmstadt GL, Tielsch JM: Risk of mortality associated with neonatal hypothermia in southern Nepal. Archives of pediatrics & adolescent medicine 2010, 164(7):650–656.

9.Kumar V, Shearer J, Kumar A, Darmstadt G: Neonatal hypothermia in low resource settings: a review. Journal of Perinatology 2009, 29(6):401.

10.Lawn Je O, Adler A, Cousens S: Europe Funders Group. Four million neonatal deaths: counting and attribution of cause of death 2012, 22(5):2012.

11.Mullany LC: Neonatal hypothermia in low-resource settings. In: Seminars in perinatology: 2010: Elsevier; 2010: 426–433.

12.Liu L, Johnson HL, Cousens S, Perin J, Scott S, Lawn JE, Rudan I, Campbell H, Cibulskis R, Li M: Global, regional, and national causes of child mortality: an updated systematic analysis for 2010 with time trends since 2000. The Lancet 2012, 379(9832):2151–2161.

13.Lunze K, Bloom DE, Jamison DT, Hamer DH: The global burden of neonatal hypothermia: systematic review of a major challenge for newborn survival. BMC medicine 2013, 11(1):24.

14.Mekonnen T, Tenu T, Aklilu T, Abera T: Assessment of Neonatal Death and Causes among Admitted Neonates in Neonatal Intensive Care Unit of Mizan Tepi University Teaching Hospital, Bench Maji Zone, South-West Ethiopia, 2018. Clinics Mother Child Health 2018, 15(305):2.

15.Byaruhanga R, Bergstrom A, Okong P: Neonatal hypothermia in Uganda: prevalence and risk factors. Journal of tropical pediatrics 2005, 51(4):212–215.

16.Peters MD, Godfrey CM, McInerney P, Soares CB, Khalil H, Parker D: The Joanna Briggs Institute reviewers’ manual 2015: methodology for JBI scoping reviews. 2015.

17.Borenstein M, Hedges LV, Higgins JP, Rothstein HR: A basic introduction to fixed‐effect and random‐effects models for meta‐analysis. Research synthesis methods 2010, 1(2):97–111.

18.Ioannidis JP: Interpretation of tests of heterogeneity and bias in meta‐analysis. Journal of evaluation in clinical practice 2008, 14(5):951–957.

19.Higgins JP, Thompson SG: Quantifying heterogeneity in a meta‐analysis. Statistics in medicine 2002, 21(11):1539–1558.

20.Bergström A, Byaruhanga R, Okong P: The impact of newborn bathing on the prevalence of neonatal hypothermia in Uganda: a randomized, controlled trial. Acta Paediatrica 2005, 94(10):1462–1467.

21.Mengesha HG, Sahle BW: Cause of neonatal deaths in Northern Ethiopia: a prospective cohort study. BMC public health 2017, 17(1):62.

22.Demisse AG, Alemu F, Gizaw MA, Tigabu Z: Patterns of admission and factors associated with neonatal mortality among neonates admitted to the neonatal intensive care unit of University of Gondar Hospital, Northwest Ethiopia. Pediatric health, medicine and therapeutics 2017, 8:57.

23.Demissie BW, Abera BB, Chichiabellu TY, Astawesegn FH: Neonatal hypothermia and associated factors among neonates admitted to neonatal intensive care unit of public hospitals in Addis Ababa, Ethiopia. BMC pediatrics 2018, 18(1):263.

24.Ukke GG, Diriba K: Prevalence and factors associated with neonatal hypothermia on admission to neonatal intensive care units in Southwest Ethiopia–A cross-sectional study. PloS one 2019, 14(6):e0218020.

25.Dheresa M, Assefa N, Bayih WA: Neonatal Hypothermia and Associated Factors within Six Hours of Delivery at Public Health Institutions of Harar city, Eastern Ethiopia. Haramaya University; 2018.

26.Tasew H, Gebrekristos K, Kidanu K, Mariye T, Teklay G: Determinants of hypothermia on neonates admitted to the intensive care unit of public hospitals of Central Zone, Tigray, Ethiopia 2017: unmatched case–control study. BMC research notes 2018, 11(1):576.

27.Bayih WA, Assefa N, Dheresa M, Minuye B, Demis S: Neonatal hypothermia and associated factors within six hours of delivery in eastern part of Ethiopia: a cross-sectional study. BMC pediatrics 2019, 19(1):252.

28.Talbert A, Atkinson S, Karisa J, Ignas J, Chesaro C, Maitland K: Hypothermia in children with severe malnutrition: low prevalence on the tropical coast of Kenya. Journal of tropical pediatrics 2009, 55(6):413–416.

29.Switchenko N KE, Fassl B.: PREVALENCE OF NEONATAL HYPOTHERMIA IN A REFERRAL HOSPITAL’S NEWBORN UNIT IN KENYA. . 2017.

30.Shruti MurthyID MAG, Vasudeva Guddattu ID, Leslie Edward, Simon Lewis NSN: Risk factors of neonatal sepsis in India: A systematic review and meta-analysis 2019.

31.Chan GJ1 LA, Baqui AH, Tan J, Black RE.: Risk of early-onset neonatal infection with maternal infection or colonization: a global systematic review and meta-analysis.. 2013.

32.Shruti MurthyID MAG, Vasudeva Guddattu ID, Leslie Edward: Risk factors of neonatal sepsis in India: A systematic review and meta-analysis. 2019.

33.Karsten Lunze, David E Bloom, Dean T Jamison and Davidson H Hamer:The global burden of neonatal hypothermia: systematic review of a major challenge for newborn survival

34.Roya Farhadi, Mohammad Sadegh Rezai,Maryam Nakhshab,Incidence of neonatal hypothermia at birth in hospitals of Islamic Republic of Iran: A review

35.R Onalo: Neonatal hypothermia in sub-Saharan Africa: A review

Table 1: Distribution of studies on the prevalence and determinants of neonatal hypothermia in East Africa,2000-2019.

Author	Year	Country	Study design	Sample size	Prevalence (%)	Quality status	Reference
Byaruhanga R,	2005	Uganda	cross-sectional	300	79	Low risk	[15]
Bergstrom A,	2005	Uganda	case-control	249	46	Low risk	[20]
Hayelom Gebrekirstos ,	2017	Ethiopia	cross-sectional	1152	53	Low risk	[21]
Abayneh Girma Demisse,	2017	Ethiopia	cross-sectional	769	71	Low risk	[22]
Birhanu Wondimeneh Demissie,	2018	Ethiopia	cross-sectional	356	64	Low risk	[23]
Gebresilasea Gendisha,	2019	Ethiopia	cross-sectional	354	50.3	Low risk	[24]
Tewodros Seyum,	2015	Ethiopia	cohort	421	69.8	Low risk	[25]
Hagos Tasew	??	Ethiopia	cross-sectional	264	???	Low risk	[27]
Wubet Alebachew Bayih ,	2019	Ethiopia	cross-sectional	403	66.3	Low risk	[14]
Mekonnen Tilahun,	2018	Ethiopia	cross-sectional	1316	13	Low risk	[14]
Alison Talbert	2009	Kenya	cohort	15 191	-	Low risk	[28]
Switchenko N,	2017	Kenya	cross-sectional	136	60	Low risk	[29]

Table 2: Subgroup analysis of the prevalence of neonatal hypothermia in Eastern Africa by country, design and year of publication

Variables	Characteristics	Pooled prevalence (95% CI)	I²(P-value)
By country	Ethiopia	55.32(33.74-76.90)	99.6%(<0.001)
	Uganda	62.57(30.23-94.91)	98.6%(<0.001)
	Kenya	60.00(51.77-68.23)	99.5%(<0.001)
By design	Cross-sectional	63.49(56.42-70.57)	94.2% (<0.001)
By design	Cohort	32.98(6.22-72.18)	99.8%(<0.001)
By year of publication	2000-2015	65.06(47.89-82.23)	97.2% (<0.001)
By year of publication	2016-2019	57.90(32.41-75.40)	99.6%(<0.001)

Table 3: Identified associated factors for neonatal hypothermia from studies in East Africa, January 2000 - 2019.

Determinants	Odds ratio (AOR)	Author	Year of publication	Reference
Delay in initiation of breastfeeding	4.39	Birhanu et al	2017	[23]
	2.42	G/silasea et al	2019	[24]
	7.58	Tewodros et al	2015	[25]
	7.23	Hagos et al	2018	[26]
	1.63	Wubet et al	2019	[27]
Neonatal health problem OR	2.46	G/silasea et al	2019	[24]
	3.1	Tewodros et al	2015	[25]
	2.28	Hagos et al	2018	[26]
	4.24	Wubet et al	2019	[27]
	4.24	ANNA et al	2005	[20]
Low birth weight	1.33	Birhanu et al	2017	[23]
	3.61	G/silasea et al	2019	[24]
	3.75	Tewodros et al	2015	[25]
	8.51	Hagos et al	2018	[26]
	1.2	Wubet et al	2019	[27]
Preterm	4.81	Birhanu et al	2017	[23]
	4.61	Gebresilasea et al	2019	[24]
	1.5	Tewodros et al	2015	[25]
	3.69	Hagos et al	2018	[26]
	3.37	Wubet et al	2019	[27]
Nighttime delivery	1.32	Birhanu et al	2017	[23]
	1.68	G/silasea et al	2019	[24]
	6.61	Tewodros et al	2015	[25]
	6.25	Hagos et al	2018	[26]
	3.18	Wubet et al	2019	[27]

fFPRISMAchecklistHYPOTHERMIA.doc

Neonatal hypothermia and its associated factors in East Africa: a systematic review and meta-analysis

Status:

Version 1

Abstract

Figures

Introduction

Methods and Materials

Reporting

Searching strategy and selection criteria

Study selection / Eligibility criteria

Inclusion and exclusion criteria

Quality assessment

Data extraction

Outcome measurement

Statistical analysis

Results

Discussion

Conclusion

Abbreviations and Acronyms

Declarations