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Abstract
Importance The Cochrane review (2016) on kangaroo mother care (KMC) demonstrated a significant reduction in the risk of mortality in low birth weight infants. New evidence from large multi-centre randomised trials has been available since its publication.
Objective Our systematic review compared the effects of KMC vs conventional care and early (ie, within 24 hours of birth) vs late initiation of KMC on critical outcomes such as neonatal mortality.
Methods Eight electronic databases, including PubMed®, Embase, and Cochrane CENTRAL, from inception until March 2022, were searched. All randomised trials comparing KMC vs conventional care or early vs late initiation of KMC in low birth weight or preterm infants were included.
Data extraction and synthesis The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and was registered with PROSPERO.
Main outcomes and measures The primary outcome was mortality during birth hospitalization or 28 days of life. Other outcomes included severe infection, hypothermia, exclusive breastfeeding rates, and neurodevelopmental impairment. Results were pooled using fixed-effect and random-effects meta-analyses in RevMan 5.4 and Stata 15.1 (StataCorp, College Station, TX).
Results In total, 31 trials with 15 559 infants were included in the review; 27 studies compared KMC with conventional care, while four compared early vs late initiation of KMC. Compared with conventional care, KMC reduces the risks of mortality (relative risk (RR) 0.68; 95% confidence interval (CI) 0.53 to 0.86; 11 trials, 10 505 infants; high certainty evidence) during birth hospitalisation or 28 days of age and probably reduces severe infection until the latest follow-up (RR 0.85, 95% CI 0.79 to 0.92; nine trials; moderate certainty evidence). On subgroup analysis, the reduction in mortality was noted irrespective of gestational age or weight at enrolment, time of initiation, and place of initiation of KMC (hospital or community); the mortality benefits were greater when the daily duration of KMC was at least 8 hours per day than with shorter-duration KMC. Studies comparing early vs late-initiated KMC demonstrated a reduction in neonatal mortality (RR 0.77, 95% CI 0.66 to 0.91; three trials, 3693 infants; high certainty evidence) and a probable decrease in clinical sepsis until 28-days (RR 0.85, 95% CI 0.76 to 0.96; two trials; low certainty evidence) following early initiation of KMC.
Conclusions and relevance The review provides updated evidence on the effects of KMC on mortality and other critical outcomes in preterm and low birth weight infants. The findings suggest that KMC should preferably be initiated within 24 hours of birth and provided for at least 8 hours daily.
- public health
- systematic review
Data availability statement
Data are available upon reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information. Data are available upon reasonable request from the corresponding author.
This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
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WHAT IS ALREADY KNOWN ON THIS TOPIC
Kangaroo mother care (KMC) is a simple and cost-effective intervention that decreases neonatal mortality and the risk of infection in low birth weight infants.
The WHO recommends the initiation of KMC among low birth weight infants after clinical stabilisation.
WHAT THIS STUDY ADDS
Compared with conventional care, KMC initiated either in the hospital or at home reduces mortality during birth hospitalisation or 28 days of age and probably reduces severe infection until the latest follow-up among preterm and low birth weight infants.
KMC provided for at least 8 hours a day probably results in greater benefits than a shorter duration of KMC.
KMC initiated within 24 hours of birth reduces neonatal mortality and may reduce clinical sepsis until 28 days compared with later initiation.
HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY
The results of this updated review will likely influence health providers to initiate KMC in all low birth weight and preterm infants managed in health facilities and at home. Efforts might be undertaken to initiate KMC within 24 hours of birth and to provide it for at least 8 hours a day.
Introduction
Prematurity (gestational age <37 weeks) and low birth weight (defined as <2500 g) are important causes of neonatal and infant mortality and long-term neurodevelopmental disability.1 Low- and middle-income countries (LMIC) have the highest burden of preterm and low birth weight infants. Kangaroo mother care (KMC) is a simple and cost-effective intervention that has been shown to reduce neonatal mortality and the risk of infection in low birth weight infants.2 The Cochrane review on KMC, published in 2016, included 21 studies involving 3042 infants and demonstrated a significant reduction in the risks of mortality and severe infection in low birth weight infants.3
New evidence from large multi-country and community-based randomised trials became available after the publication of the Cochrane review.4 5 A few of these trials examined the effect of early KMC, that is, KMC initiated within the first 24 hours of delivery.5 6 The timing of initiation of KMC is critical because KMC is usually commenced after the infant is stabilised. The WHO guidelines also recommend the initiation of KMC after clinical stabilisation. However, stabilisation of preterm/low birth weight neonates may take anything from hours to days, depending on the gestation, birth weight, and general condition at birth. The median age at initiation of KMC in the facility-based studies included in the Cochrane review varied from 3 to 24 days. KMC initiated after 3 days of life would not naturally reduce the risk of deaths occurring in the first 3 days, which account for about 62% of total neonatal deaths.7 The efficacy and safety of early initiation of KMC – within 24 hours of life – are unknown.
This systematic review aimed to compare the effects of (a) KMC with conventional care and (b) early initiation, that is, KMC within 24 hours of age, with late initiation of KMC on neonatal and infant mortality and severe morbidities among low birth weight and preterm infants. This review would provide critical evidence for policymakers and other stakeholders and may help to formulate clinical practice guidelines.
Methods
Inclusion and exclusion criteria
Our review included individually-randomised and cluster-randomised trials that compared KMC with conventional care or early initiation (ie, in the first 24 hours after birth) of KMC with late-initiated KMC among low birth weight and preterm infants, irrespective of the duration of KMC, infant stability at enrolment, study setting, and breastfeeding patterns. Trials reported as only abstracts were included if sufficient information on study methods was available to assess the eligibility and the risk of bias. We excluded quasi-randomised and crossover trials, studies evaluating KMC among term infants or those with birthweight >2500 g, and studies assessing KMC on only physiological parameters, pain scores, maternal mental health, infant colic, or during neonatal transport or as a part of a package of interventions.
Search strategy
We systematically reviewed the relevant publications by searching the electronic databases of MEDLINE (1966 to March 2022) via PubMed® and OVID, Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1 to March 2022), EMBASE (1988 to March 2022), CINAHL (1981 to March 2022), and the databases PsycINFO, AMED, EMCARE, BNI from inception until March 2022. We used the search terms “kangaroo care,” “kangaroo mother care,” “skin-to-skin care,” and “neonates or infants” in the search strategy. The search was initially conducted until March 2021 (for the presentation of review findings to the WHO Guideline Development Group of the guidelines on the care of low birth weight infants); the search was then updated to March 2022. The search strategy, search results, and the definitions used in the review are provided in online supplemental file 1. We also searched the databases of clinical trials and reference lists of retrieved articles for eligible studies.
Supplemental material
Outcomes
The primary outcome was mortality during birth hospitalisation or by day 28 of life. Other outcomes were mortality by 6–12 months of age, severe infections, infant growth, neurodevelopment, hypothermia, length of hospital stay, readmission to hospital, and exclusive breastfeeding at discharge and at one and 6 months of age.
Data extraction
The two review authors (SS and MJS) extracted data using a standardised and pre-tested data abstraction form. The data included study characteristics, sample size, details of KMC initiation, duration, breastfeeding, time of hospital discharge, study setting (hospital or community), outcomes including neonatal mortality, hypothermia, sepsis, rates of exclusive breastfeeding, and weight gain. Discrepancies, if any, were resolved by mutual discussion between the reviewers.
Quality assessment and statistical analysis
The review authors independently evaluated the quality of studies using Cochrane’s Risk of Bias-1 tool, extracted data, and synthesised the effect estimates – relative risks (RR) or mean difference (MD) – using RevMan version 5.4 (The Cochrane Collaboration, 2020) or Stata 15.1 (StataCorp, College Station, TX, USA). The RR and 95% confidence intervals (CI) were calculated based on the extracted frequencies and denominators. Results were pooled using fixed-effect meta-analyses using the Mantel-Haenszel method. The heterogeneity of the pooled studies was assessed using the test of homogeneity of study-specific effect sizes and the I2 statistic, in addition to visual confirmation from forest plots. If substantial heterogeneity was detected, the reasons for heterogeneity were explored. If there was no critical clinical or methodological heterogeneity among the studies, we pooled their results using the random-effects model. We evaluated the likelihood of potential publication bias using funnel plots.
We used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach8 to assess the quality of evidence for critical outcomes such as mortality at discharge, severe infection/sepsis at the latest follow-up, weight gain, exclusive breastfeeding, and neurodevelopmental outcomes. Evidence from randomised controlled trials was considered high quality; still, it could be downgraded by one or two levels for serious and very serious limitations, respectively, based on the risk of bias, imprecision, inconsistency, indirectness of study results, and publication bias. The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and was registered in PROSPERO (CRD42021240336).
Planned subgroup analyses
For the comparison of KMC vs conventional care, we performed subgroup analyses according to different gestational and birth weight categories and by median duration KMC in hours (<8 hours, 8–16 hours, and >16 hours); time of initiation of KMC – early (≤24 hours of life) vs late initiation; stable vs unstable neonates; health facility vs community settings; and countries (high income vs LMIC settings).
Patient and public involvement
The study is a systematic review of the existing literature on the efficacy of KMC in preterm and low birth weight infants. No subjects were enrolled in the review. Therefore, parents, parent advisors, or the public were not involved in developing the research question and outcome measures.
Role of the funding source
The WHO, Geneva, funded the review. The WHO staff helped finalise the protocol and the manuscript; they had no role in the literature search, data extraction, or data analysis. The corresponding author had the final responsibility for the decision to submit for publication.
Results
Of the 3458 records identified from the database and bibliographic searches, 314–6 9–35 studies enrolling 15 559 infants were included in the review (figure 1); 25 studies were conducted in LMIC (two from multiple countries5 14 while seven were conducted in high-income countries12 20 24 26 29 30 34 (Appendix). Twenty-seven studies compared KMC with conventional care, while four compared early with late initiation of KMC.5 6 24 25 KMC was initiated in the health facility in 29 studies and at home (community) in two trials.4 11 While the sample sizes of earlier hospital-based studies ranged from 28 to 777, the most recent facility-based study – WHO iKMC study5 – had a sample size of 3211. Of the two community-based studies, one trial had enrolled around 8400 infants.4 Only six studies included infants with birthweight <1500 g.12 13 19 28 30 34 Figure 2 depicts the risk of bias in the included studies in specific domains. Many studies had an unclear or high risk of selection bias (due to a lack of information on allocation concealment) and detection bias (because the outcomes assessors were not masked to the intervention group).
Flow chart of search results (adapted from PRISMA 2009 flow diagram).
Risk of bias in included studies. Green circle indicates low-risk, red indicates high-risk and yellow, unclear-risk of bias.
KMC versus conventional newborn care
The comparison included 27 studies that enrolled 11 956 infants. The characteristics of included studies are provided in table 1. All but one study enrolled infants after stabilisation (variably defined in different studies as cardiorespiratory stability, off oxygen or any form of respiratory support, or off intravenous fluids). KMC was started within 24 hours after birth in two studies, between 1 and 7 days in 10 studies, and after 7 days in 12 studies (3 studies did not report the time of initiation). The duration of KMC was <8 hours in 9 studies, 8–16 hours in 9 studies, and >16 hours in 4 studies (5 studies did not report the duration).
KMC vs conventional newborn care – characteristics of included studies
Pooled analysis revealed a 32% reduction in mortality during birth hospitalisation or by 28 days after birth or 40 weeks of postmenstrual age (risk ratio (RR) 0.68; 95% CI (CI) 0.53 to 0.86; I2=0%; 12 studies; 10 505 infants; fixed-effect model; high certainty evidence; figure 3). The funnel plot did not show any evidence of a potential publication bias (online supplemental efigure 1). The benefits of KMC in the primary outcome of mortality during birth hospitalisation or by 28 days of age were observed in all subgroup analyses: gestational age category (≤34 weeks vs. >34 weeks), weight at birth/enrolment (≤2000 g vs. >2000 g), setting (health facility vs. community) and time of initiation of KMC (within 24 hours after birth vs later); the benefits were greater when the daily duration of KMC was at least 8 hours per day than with shorter duration (online supplemental efigure 2). Pooled analysis of 4 studies that had reported mortality by 6 months of age showed a 25% reduction in mortality (RR 0.75; 95% CI 0.62 to 0.92; fixed-effect model; high certainty of evidence).
Supplemental material
Kangaroo mother care (KMC) vs. conventional care –Risk ratio of mortality during birth hospitalisation or 28 days of life.
KMC probably results in a 15% reduction in severe infection/sepsis at the latest follow-up (RR 0.85, 95% CI 0.79 to 0.92; 9 trials, 9847 infants; moderate certainty evidence) and 68% reduction in the risk of hypothermia (RR 0.32, 95% CI 0.19 to 0.53; 11 trials, 1169 infants; moderate-certainty evidence). Infants in the KMC arm had a higher gain in anthropometric parameters, namely weight gain per day and length and head circumference gain per week (table 2). The exclusive breastfeeding rates were higher at discharge/28 days of life (RR 1.48, 95% CI 1.44 to 1.52; 9 trials, 9983 infants, very low certainty evidence), but the evidence was uncertain; also, there was no difference in breastfeeding rates at 1–3 months of age. KMC may result in little to no difference in the Griffith Quotients or the risk of cerebral palsy at 12 months of corrected age36 or IQ scores at 20 years of age.
KMC vs conventional newborn care: key outcomes
Early-initiated versus late-initiated KMC
The evidence was derived from 4 trials that enrolled 3603 infants. One study was done in a high-come country (Sweden), 2 studies were done in low-income countries (Madagascar and The Gambia), and 1 study was multi-country conducted in LMICs (Ghana, India, Malawi, Nigeria, and Tanzania). All trials were conducted in health facilities. Infant stability at enrolment, duration of KMC achieved, and time of initiation of KMC in the included studies are provided in table 3. In two studies (Mörelius et al 24 and WHO iKMC)5 KMC was initiated in the delivery room. Brotherton et al 6 enrolled moderately unstable infants in the early KMC arm and stable infants after >24 hour of admission in the control arm. Nagai et al began KMC within 24 hours of birth in the early arm and after 24 hours in the late arm.
Early vs late-initiated KMC – characteristics of included studies
Early-initiated KMC showed a reduction in the risks of mortality by 28 days of age (RR 0.78, 95% CI 0.66 to 0.92; 3 trials, 3533 infants, high certainty evidence; online supplemental efigure 3) and hypothermia by discharge or at 28 days (RR 0.74, 95% CI 0.61 to 0.90; high certainty evidence). It probably reduces the risk of clinical sepsis until 28-day follow-up (RR 0.85, 95% CI 0.76 to 0.96; table 4; low certainty evidence) and improves exclusive breastfeeding at discharge (RR 1.1.2, 95% CI 1.10 to 1.19; moderate certainty evidence). There was also a decrease in the length of hospital stay (table 4).
Early vs late-initiated KMC – critical outcomes
On subgroup analysis, there was evidence of a reduction in 28-day mortality for infants with GA ≤34 weeks and BW ≤2000, but there was little data for infants >34 weeks and weighing >2000 g at birth. The mortality reduced with a duration of KMC of at least >16 hours per day, with little data for daily KMC duration of <8 hours or 8–16 hours per day.
Quality of the evidence
For the comparison of KMC vs conventional newborn care, the certainty of the evidence was assessed as high for neonatal mortality and moderate for sepsis/severe infection and hypothermia (table 5). For early vs late-initiated KMC, the certainty of the evidence was high for neonatal mortality and hypothermia, moderate for exclusive breastfeeding at discharge, and low for nosocomial clinical sepsis (table 6). A few outcomes, such as weight gain, breastfeeding, and length of hospital stay, showed a high degree of heterogeneity, partly due to clinical and methodological heterogeneity among the studies (varied definitions of hypothermia and time points of assessment; different methods of breastfeeding assessment, etc.).
Summary of findings – KMC vs conventional newborn care
Summary of findings – early initiated KMC vs late-initiated KMC in preterm or low-birth weight infants
Discussion
The systematic review showed that KMC reduces mortality during birth hospitalisation or by 28 days of age and probably reduces severe infection at the latest follow-up in preterm and low birth weight infants in health facilities and at home. KMC may result in a slight increment in growth parameters (weight and length) and exclusive breastfeeding rates at discharge. KMC may result in little to no difference in neurodevelopmental outcomes at 12 months compared with conventional care. Compared with delayed initiation (>24 hours) of KMC, early-initiated KMC (<24 hours) results in a 33% reduction in mortality by 28 days and a slight reduction in clinical sepsis by 28 days.
Three recent systematic reviews examined the effect of KMC compared with conventional care on infant clinical outcomes.3 37 38 The Cochrane review in 2016 found 21 studies enrolling 3042 low birth weight infants.3 Our systematic review used a similar search strategy and inclusion criteria and included studies until 2022. We found 10 newer studies that provided data on 12 517 additional infants with similar gestation and birth weight range. The Cochrane review reported a similar decrease in mortality at discharge or 40 weeks of postmenstrual age (RR 0.60, 95% CI 0.39 to 0.92; 8 trials, 1736 infants) and similar effects on infection, hypothermia, and anthropometry. However, the certainty of the evidence was graded as moderate to very low in the Cochrane review. The addition of information from 12,000-odd infants has improved the precision and certainty of the evidence of the critical outcomes in the current review. In 2020, a systematic review of 416 preterm neonates reported that KMC significantly reduced apneic events in preterm neonates.38 Another review in 2019 concluded that KMC had a significant positive impact on growth and breastfeeding rates in very low birth weight (VLBW) neonates.37
We investigated the effect of mean duration KMC in hours and prespecified three categories (<8 hours, 8–16 hours, and >16 hours). The effects on mortality were comparable in the >16 hour and 8–16 hour groups, but there was insufficient data in the <8 hours group. The Cochrane review (2016) explored the effects of the duration of KMC in three different categories; <2 hours and 6–15 hours, and >20 hours per day, and found benefits only when KMC was done for 20 hours or more. We found beneficial effects of KMC in prespecified subgroups of ≤2.0 kg and >2.0 kg and infants with gestational age ≤34 and >34 weeks at birth. The two community-based studies that enrolled infants at home also showed significant benefits on mortality. We found no additional trials – other than the study by Worku et al included in the Cochrane review – that compared KMC with conventional care in unstable infants.
Only one systematic review – the Cochrane review published in 2016 – has evaluated the effects of early vs late initiation of KMC in low birth weight infants. It also used a cut-off of 24 hours to define early initiation but found only one study of 73 relatively stable low birth weight infants.25 Our review included three additional studies that recruited 3530 preterm/low birth weight infants and found significant beneficial effects with early initiation of KMC.5 6 24
The results of our review have substantial implications for policymaking, particularly in LMIC. First, KMC should be provided to all low birth weight and preterm infants irrespective of the settings – both health facilities and at home. Second, given the probable dose-effect response, KMC should preferably be practiced for at least 8 hours a day for optimal benefits. Third, KMC should be initiated within the first 24 hours of life. Indeed, our findings have helped to make recommendations on KMC in the new WHO guidelines on the care of preterm and low birth weight neonates.39
The strengths of the current review include a comprehensive and systematic search of the literature with updated evidence to March 2022. Compared with the existing Cochrane reviews on KMC, our review identified additional studies that had enrolled almost 13 000 low birth weight infants, which resulted in high precision of estimates and improved the certainty of the evidence. The review also had some limitations. The included studies were not blinded, although outcome assessors were blinded in many studies. However, the risk of bias in the included studies was generally low, and the certainty of the evidence for the primary outcomes was moderate to high. Very low birth weight, extremely preterm neonates, and severely unstable neonates were often excluded from studies. More evidence is needed before extrapolating the study results in these high-risk groups.
To conclude, our findings support the practice of KMC for preterm and low birth weight infants as soon as possible after birth and for at least 8 hours a day. Future research should focus on overcoming barriers and facilitators to large-scale implementation of KMC in facility and community settings. Data on long-term neurodevelopmental outcomes are also needed.
Data availability statement
Data are available upon reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information. Data are available upon reasonable request from the corresponding author.
Ethics statements
Patient consent for publication
Ethics approval
Not applicable.
Acknowledgments
We acknowledge the support and guidance provided by Dr. Rajiv Bahl, Dr. Karen Edmond, and Dr. Shuchita Gupta from the WHO, Geneva, in finalising the protocol and interpreting the results.
References
Supplementary materials
Supplementary Data
This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.
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Footnotes
Handling editor Seema Biswas
Contributors Both authors, MJS and SS, contributed equally to protocol development, literature search, data extraction and analysis and interpretation. SS drafted the manuscript with inputs from MJS. Both authors reviewed and approved the final manuscript. MJS acts as the guarantor of the paper.
Funding The World Health Organization. Grant number- not applicable.
Competing interests None declared.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Provenance and peer review Not commissioned; externally peer reviewed.
Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.