Meta Analysis
Meta Analysis
Outcomes: A Meta-analysis
Ellen O. Boundy, MS, ScD,a Roya Dastjerdi, MPH, MD,b Donna Spiegelman, ScD,a,b,c Wafaie W.
Fawzi, MBBS, DrPH,a,b,d Stacey A. Missmer, ScD,a,e Ellice Lieberman, MD, DrPH,a,f,g Sandhya
Kajeepeta, SM,a Stephen Wall, MD, SM, MSW,h Grace J. Chan, MD, MPH, PhDb,h,i
CONTEXT: Kangaroo mother care (KMC) is an intervention aimed at improving outcomes abstract
among preterm and low birth weight newborns.
OBJECTIVE: Conduct a systematic review and meta-analysis estimating the association between
KMC and neonatal outcomes.
DATA SOURCES: PubMed, Embase, Web of Science, Scopus, African Index Medicus (AIM), Latin
American and Caribbean Health Sciences Information System (LILACS), Index Medicus for
the Eastern Mediterranean Region (IMEMR), Index Medicus for the South-East Asian Region
(IMSEAR), and Western Pacific Region Index Medicus (WPRIM).
STUDY SELECTION: We included randomized trials and observational studies through April 2014
examining the relationship between KMC and neonatal outcomes among infants of any birth
weight or gestational age. Studies with <10 participants, lack of a comparison group without
KMC, and those not reporting a quantitative association were excluded.
DATA EXTRACTION: Two reviewers extracted data on study design, risk of bias, KMC intervention,
neonatal outcomes, relative risk (RR) or mean difference measures.
RESULTS: 1035 studies were screened; 124 met inclusion criteria. Among LBW newborns,
KMC compared to conventional care was associated with 36% lower mortality(RR 0.64;
95% [CI] 0.46, 0.89). KMC decreased risk of neonatal sepsis (RR 0.53, 95% CI 0.34, 0.83),
hypothermia (RR 0.22; 95% CI 0.12, 0.41), hypoglycemia (RR 0.12; 95% CI 0.05, 0.32), and
hospital readmission (RR 0.42; 95% CI 0.23, 0.76) and increased exclusive breastfeeding (RR
1.50; 95% CI 1.26, 1.78). Newborns receiving KMC had lower mean respiratory rate and pain
measures, and higher oxygen saturation, temperature, and head circumference growth.
LIMITATIONS: Lack of data on KMC limited the ability to assess dose-response.
NIH
Departments of aEpidemiology, cBiostatistics, and dNutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Departments of bGlobal Health and Population, and fSocial
and Behavioral Sciences, Harvard School of Public Health, Boston, Massachusetts; eDepartment of Obstetrics, Gynecology, and Reproductive Biology, Brigham and Women’s Hospital, Boston,
Massachusetts; gDepartment of Pediatric Newborn Medicine, Brigham and Women’s Hospital, Boston, Massachusetts; hSave the Children, Washington, DC; and iDepartment of Medicine,
Boston Children’s Hospital, Boston, Massachusetts
Dr Boundy conceptualized and designed the study, conducted the literature review, collected the data, conducted the analyses, created the tables and figures,
and drafted and revised the manuscript; Dr Dastjerdi conducted the literature review, collected and cleaned the data, assisted with table and figure creation,
and critically reviewed the manuscript; Dr Spiegelman contributed to the study design, statistical analyses, and data interpretation and critically reviewed the
manuscript; Drs Fawzi, Missmer, and Lieberman contributed to the study design and data interpretation and critically reviewed the manuscript; Ms Kajeepeta
conducted the literature review, collected the data, assisted with figure creation, and critically reviewed the manuscript;Dr Wall contributed to the conceptualization
and design of the study and data interpretation and critically reviewed the manuscript; Dr Chan conceptualized and designed the study, designed the data collection
To cite: Boundy EO, Dastjerdi R, Spiegelman D, et al. Kangaroo Mother Care and Neonatal Outcomes: A Meta-analysis. Pediatrics. 2016;137(1):e20152238
2 BOUNDY et al
bias, and confounding were all low country-level neonatal mortality studies (61%) had <100 participants.
risk, the overall risk of bias was rate in 2013,32 infant gestational age Fifty-five (44%) were RCTs, 8 (6%)
considered low. If any of those 3 and birth weight, KMC components, were randomized crossover trials,
domains was high risk, the overall KMC initiation criteria, SSC duration, and 61 (49%) were observational or
risk was considered high. Otherwise, and study quality classification. In nonrandomized intervention studies.
the overall risk of bias was metaregression analyses, we report Most studies (n = 113, 94%) were in
considered unclear. the residual I2, indicating the amount middle- or high-income countries and
of remaining heterogeneity in the were conducted in health facilities (n
Statistical Analysis effect estimate after adjustment = 118, 98%).
for a given characteristic. The
We used the random effects Among studies reporting gestational
indicator method was used for
estimator to assess the effect of KMC age, the majority (n = 61, 68%) were
missing covariate information in
compared with conventional care among preterm infants <37 weeks’
metaregressions.33
on each neonatal outcome.12 For gestation; 17 (19%) were among full-
dichotomous outcomes, we report We assessed publication bias by term infants, defined as ≥37 weeks,
summary estimates as RR and 95% visual inspection of funnel plots of and 12 (13%) were among infants
CI. For studies that did not report effect size and SE for asymmetry of all gestational ages. Similarly, 47
an RR, we calculated the RR and and by Begg’s rank correlation and studies (58%) were among LBW
SE from the data if available. For Egger’s linear regression tests.34,35 infants (≤2500 g), an additional 15
continuous outcomes, we report We conducted meta-analyses by (19%) were among very LBW infants
summary estimates as MD and using Stata statistical software (≤1500 g), 9 (11%) were among
95% CI. When different units or (version 13.1), and risk of bias figures non-LBW infants, and 10 (12%) were
scales were used across studies, we were created in RevMan software among infants of all birth weights.
calculated the standardized mean (version 5.3). Forty-three studies (35%) did not
difference (SMD).11 When available, specify infants’ birth weight, and 34
estimates adjusted for confounding (27%) did not specify gestational age,
were used rather than crude. RESULTS but all studies reported either birth
Estimates that were presented only Our search identified 2515 records weight or gestational age, except for
as medians rather than means, only (Fig 1). We then identified 29 1.45
as odds ratios without raw data to additional records related to KMC Most studies (n = 71, 68%) defined
calculate the RR, or those with 0 through crosscheck of reference lists, KMC as SSC only, 14 (13%) defined
cells were excluded from summary communication with an author,36 KMC as SSC plus promotion of
measures.13–28 and programmatic reports. After exclusive breastfeeding, 20 (19%)
We performed sensitivity analyses 1006 duplicates were removed, included an early discharge or
by restricting the analyses to RCTs 1035 records underwent abstract follow-up component, and 19 (15%)
and adjusted RR estimates for screening. Of those, 527 did not meet did not describe the components
dichotomous outcomes and by inclusion criteria. Full-text articles for of their KMC intervention. SSC was
restricting the analyses to RCTs the remaining 508 records were then initiated immediately after birth in
and randomized crossover studies assessed and of those, 384 did not 7 studies (8%), whereas 41 (48%)
for continuous outcomes. To assess meet inclusion criteria. This review had stability criteria to be met before
between-study heterogeneity, and meta-analysis includes 124 SSC initiation, and 27 (31%) had
we report the I2 statistic and the studies that reported an association other non–stability-related initiation
P value for the Q statistic.12,29,30 between KMC and ≥1 neonatal criteria. Eleven studies (14%)
The I2 statistic quantifies the outcome. One hundred eleven looking at pain-related outcomes
amount of variation in the effect (90%) were in English, 7 (6%) in started SSC around the time of an
estimate attributable to between- Portuguese, 4 (3%) in Spanish, and 2 infant procedure. Fifty-two studies
study heterogeneity, reported (2%) in Farsi. We e-mailed 8 authors (66%) promoted <4 hours of SSC per
as a percentage, with a higher I2 to obtain additional information37–44 day, 20 (25%) promoted ≥22 hours
indicating more heterogeneity. We and received a response with data per day, and few studies (n = 7, 9%)
conducted subgroup analyses and from 2.38,39 had a duration between 4 and 21
metaregression for outcomes with hours per day. Thirty-eight studies
Study Characteristics
data from ≥10 studies. We explored (31%) did not specify when SSC
these predetermined subgroups: Of the 124 included studies, 110 was initiated, and 45 studies (36%)
year, study type, sample size, (89%) were published between 2000 did not report the daily duration
location, country-level economy,31 and 2014 (Table 1). Seventy-six of SSC mothers were instructed to
4 BOUNDY et al
at latest follow-up are presented TABLE 1 Characteristics of Included Studies (n = 124)
in Supplemental Table 4. We did Characteristic Number of Studies, n (%)
not find important differences in Year of publication
the effect of KMC on mortality by 1988–1999 14 (11)
location, country-level economy, or 2000–2009 58 (47)
neonatal mortality rate. Two studies 2010–2014 52 (42)
Sample size
whose KMC intervention included
<50 43 (35)
SSC, exclusive breastfeeding, early 50–<100 33 (27)
discharge, and close follow-up 100–<200 21 (17)
showed a stronger protective ≥200 27 (22)
effect of KMC against mortality (RR Study type
RCT 55 (44)
0.43; 95% CI, 0.19 to 0.98) than
Cohort 17 (14)
studies using other KMC definitions. Pre–post 23 (19)
Similarly, when mothers were Intervention trial (nonrandomized) 8 (6)
encouraged to provide SSC plus Randomized crossover 8 (6)
≥1 other component, KMC was Crossover (nonrandomized) 3 (2)
Case–control 2 (2)
protective against mortality (n =
Chart review 5 (4)
9; RR 0.65; 95% CI, 0.48 to 0.89), Facility evaluation 2 (2)
whereas studies where KMC was Interview or survey 1 (1)
defined as SSC alone did not (n = Region (World Health Organization)
5; RR 0.71; 95% CI, 0.33 to 1.52). Africa 11 (9)
Americas 50 (41)
There was no difference in mortality
Eastern Mediterranean 11 (9)
between studies including promotion Europe 19 (16)
of exclusive breastfeeding in their Southeast Asia 20 (17)
KMC definition compared with those Western Pacific 9 (7)
that did not. Multiple 1 (1)
Country-level economy (World Bank)
Studies instructing mothers to Low income 7 (6)
start SSC after stability criteria was Middle income 65 (54)
High income 48 (40)
met showed a similarly protective Multiple 1 (1)
effect against mortality (n = 9, RR Country-level neonatal mortality ratio, deaths/1000 live births
0.57; 95% CI, 0.34 to 0.97) as those <5 52 (43)
that started SSC immediately (n = 5–<15 36 (30)
3, RR 0.51; 95% CI, 0.33 to 0.78) 15–<30 29 (24)
≥30 4 (3)
(Supplemental Fig 3). Eleven studies Setting
promoting ≥22 hours of SSC per day Urban 92 (90)
showed a protective effect of KMC Rural 4 (4)
(RR 0.64; 95% CI, 0.44 to 0.92) on Mixed 6 (6)
Facility type
mortality, whereas there was no
NICU or step-down unit 51 (42)
association in the 1 study promoting Health facility 67 (55)
4 to 8 hours per day or the 4 studies Community or population based 3 (2)
that did not define SSC duration Gestational age at birth
(Supplemental Fig 4). Preterm, <37 wk 34 (38)
Very preterm, <34 wk 27 (30)
Full-term, ≥35–37 wk 17 (19)
Breastfeeding
All gestational ages 11 (12)
KMC increased the likelihood Comparison: preterm vs full term 1 (1)
Birth wt
of exclusive breastfeeding at LBW, ≤2500 g 47 (58)
hospital discharge or 40 to 41 Very LBW, ≤1500 g 15 (19)
weeks postmenstrual age by 50% Normal birth wt, ≥2500 g 9 (11)
(n = 13; 95% CI, 1.26 to 1.78; I2 = All birth weights 10 (12)
93%) (Supplemental Fig 5). KMC KMC components
SSC only 71 (68)
increased the likelihood of exclusive SSC + EBF 14 (13)
breastfeeding across nearly all SSC + EBF + DC 1 (1)
subgroups of study, infant, and KMC SSC + EBF + DC + FU 4 (4)
characteristics (Supplemental Table
6 BOUNDY et al
TABLE 2 RR and 95% CI for the Effect of KMC Compared With Conventional Care on Dichotomous Neonatal Outcomes
Outcome All Studies RCT and Adjusted Observational Studies
n RR (95% CI)a P Test for I2, %b n RR (95% CI)a p Test for I2, %b
Heterogeneity Heterogeneity
(P) (P)
Mortality
Latest follow-up46–61 16 0.77 (0.60 to .05 <.01 67 12 0.95 (0.73 to 1.23) .69 .13 32
0.99)
≤45 d46–55,58 11c 0.79 (0.57 to .17 <.01 77 7 1.16 (0.91 to 1.47) .23 .29 18
1.10)
3–12 mo46,47,56,57,59–61 7c 0.59 (0.43 to <.01 .63 0 6 0.67 (0.47 to 0.96) .03 .88 0
0.82)
LBW <2000 g46–54,56–61 15 0.64 (0.46 to .01 <.01 72 11 0.86 (0.59 to 1.24) .41 .10 38
0.89)
All birth weights50,55 2 1.04 (0.82 to .73 .83 0 1 1.06 (0.80 to 1.41) .70 — —
1.33)
Exclusive breastfeeding
Discharge or 40–41 wk 13 1.50 (1.26 to <.01 <.01 93 8 1.25 (1.10 to 1.42) <.01 <.01 59
PMA28,50,59,62–71 1.78)
1–4 mo old45,62,63,65,69,72–74 8 1.39 (1.11 to .01 .02 60 6 1.53 (1.08 to 2.18) .02 <.01 71
1.74)
Other
Infection15,27,28,48,52,53,58,60,65,67,75,76 12 0.67 (0.43 to .08 <.01 60 10 0.60 (0.36 to 1.01) 0.05 <.01 65
1.05)
Sepsis15,27,28,48,52,53,58,65 8 0.53 (0.34 to .01 .23 25 7 0.44 (0.29 to 0.66) <.01 .49 0
0.83)
NEC49,58,65 3 0.96 (0.45 to .92 .45 0 3 0.96 (0.45 to 2.04) .92 .45 0
2.04)
Hypothermia15,18,36,48,52,58,65,77,78 9 0.22 (0.12 to <.01 <.01 71 7 0.28 (0.15 to 0.53) <.01 .01 65
0.41)
Hyperthermia15,48,52 3 0.77 (0.59 to .06 .88 0 3 0.77 (0.59 to 1.01) .06 .88 0
1.01)
Apnea27,46,48,52,58,65 6 0.39 (0.13 to .09 .12 42 6 0.39 (0.13 to 1.14) .09 .12 42
1.14)
Hypoglycemia27,48 2 0.12 (0.05 to <.01 .53 0 2 0.12 (0.05 to 0.32) <.01 .53 0
0.32)
Readmission60,74 2 0.42 (0.23 to <.01 1.00 0 1 0.42 (0.14 to 1.29) .13 — —
0.76)
NEC, necrotizing enterocolitis; PMA, postmenstrual age.
a Random effects estimates.
b I2 variation in RR or MD attributable to heterogeneity.
c Two studies contributed data to estimates at both follow-up times of ≤45 d and 3–12 mo.15,50
measures of weight gain individually the risk of being malnourished, 88%).122 Studies using the Neonatal
and by combining them using the overweight, or obese at 5 to 6 years Infant Pain Scale123 (n = 3) and the
SMD (Table 3, Supplemental Fig old and found no difference between Neonatal Facial Coding System121,124
12). We did not find a significant the KMC and control groups.121
(n = 2) showed nonsignificant
association between KMC and the
SMD in weight gain or body length Pain decreases in pain among infants
growth. Infants receiving KMC had receiving SSC during painful
head circumference growth 0.19 cm Several studies examined pain- procedures compared with controls.
per week higher than controls in 3 related outcomes, including crying,
When combined across scales using
studies of infants <2000 g at birth heart rate, and pain scores during
and after painful procedures (Table the SMD, a decrease in pain score was
(95% CI, 0.01 to 0.37; I2 = 89%).
3). According the Premature Infant again noted in infants receiving SSC
Among studies reporting weight gain
Pain Profile scale, with a range from compared with conventional care
outcomes, there were no important
differences in the effect of KMC by 0 to 21, infants receiving SSC during (SMD −0.63; 95% CI, −1.09 to −0.16;
subgroups of study, infant, or KMC a painful procedure had a mean pain I2 = 89%) (Supplemental Fig 13). This
characteristics (Supplemental Table score 0.83 points lower than controls effect was similar across subgroups
12). One additional study examined (n = 7; 95% CI, −1.53 to −0.13; I2 = (Supplemental Table 13).
Temperature, °C65,78–83,85–87,89,93–95 14 0.24 (0.15 to 0.33) <.01 <.01 82 3 0.24 (0.04 to 0.44) .02 <.01 91
Breastfeeding initiation time, 4 −1.07 (−2.30 to 0.17) .09 <.01 97 4 −1.07 (−2.30 to 0.17) .09 <.01 97
SMD48,52,96,97
Growth
Wt change, g14,18,53,59,98 5 3.29 (−4.95 to 11.52) .43 .02 67 2 8.30 (1.16 to 15.43) .02 .31 3
Wt change, g/day28,48,58,99,100 5 2.58 (−0.51 to 5.67) .10 <.01 81 4 3.04 (−1.35 to 7.43) .18 <.01 84
Wt change, g/kg/day49,99 2 −0.84 (−3.39 to 1.70) .52 .02 81 0 — — — —
Wt change, SMD14,18,28,48,49,53,58,59,98– 11 0.16 (−0.08 to 0.40) .21 <.01 81 6 0.33 (−0.05 to 0.70) .09 <.01 83
100
Length change, cm/wk18,96 2 0.15 (−0.09 to 0.39) 0.21 .03 79 2 0.15 (−0.09 to 0.39) .21 .03 79
Length change, SMD18,48,58 3 0.24 (−0.02 to 0.49) .07 .26 25 3 0.24 (−0.02 to 0.49) .07 .26 25
Head circumference change, cm/ 3 0.19 (0.01 to 0.37) .04 <.01 89 3 0.19 (0.01 to 0.37) .04 <.01 89
wk18,28,48
Head circumference change, 4 0.61 (0.20 to 1.02) <.01 <.01 77 4 0.61 (0.20 to 1.02) <.01 <.01 77
SMD18,28,48,58
Pain
Pain score, SMD38,101–109 10 −0.63 (−1.09 to −0.16) .01 <.01 89 8 −0.75 (−1.28 to −0.22) .01 <.01 89
Premature Infant Pain Profile 7 −0.83 (−1.53 to −0.13) .02 <.01 88 5 −0.98 (−1.83 to −0.13) .02 <.01 91
score, 0–2138,103–105,107–109
Neonatal Infant Pain Scale score, 3 −1.14 (−2.34 to 0.05) .06 <.01 85 2 −1.21 (−2.88 to 0.45) .15 <.01 91
0–738,102,106
Neonatal Facial Coding System 2 −1.40 −3.08 to 0.28) .10 <.01 91 2 −1.40 (−3.08 to 0.28) .10 <.01 91
score, 0–10101,102
Crying duration after painful 3 −11.30(-19.79 to-2.80) .01 .80 0 3 −11.30(−19.79 to −2.80) .01 .80 0
stimulus, s110–112
Heart rate during painful stimulus, 3 −7.46 (−12.98 to −1.93) .01 .25 29 3 −7.46 (−12.98 to −1.93) .01 .25 29
beats/min111–113
Heart rate after painful stimulus, 4 −4.00 (−8.93 to 0.93) .11 <.01 87 3 −7.52 (−8.47 to −6.58) <.01 .54 0
beats/min101,103,114,115
Other
Length of hospital stay, days14,18,48,4 12 −0.68 (−2.11 to 0.75) .35 <.01 95 5 −0.38 (−2.99 to 2.23) .78 <.01 91
9,52,53,68,71,99,100,116,117
Cortisol, SMD38,95,107 3 −0.44 (−0.94 to 0.06) .08 .12 54 2 −0.58 (−0.88 to −0.29) <.01 .33 0
SMD, standardized mean difference.
a Random effects MD.
b I2: variation in RR or MD attributable to heterogeneity.
BOUNDY et al
FIGURE 2
Forest plot for effect of KMC compared with conventional care on mortality at latest follow-up time, grouped by follow-up time. BW, birth weight.
After a painful stimulus, infants into a summary measure. Those Several studies also examined the
receiving SSC cried on average 11 outcomes related to illness included effect of KMC on neurocognitive
seconds less than control group retinopathy, bronchopulmonary outcomes. These data were reported
infants (n = 3; 95% CI, −19.79 to dysplasia, regurgitation, across different scales with endpoints
−2.80; I2 = 0%) (Table 3). Among respiratory tract disease, at different ages and thus could
studies using infant heart rate during diarrhea, and intraventricular not be combined into summary
painful stimulus as a proxy pain hemorrhage.48,49,58,60,125 measures. They included
measure, mean heart rate was 7 beats Other outcomes included assessments of behavior, mental
per minute slower in the SSC groups hyperbilirubinemia, blood pressure, and psychomotor development,
than controls (n = 3; 95% CI, −12.98 reflexes, temperament,
stratum corneum hydration, oxygen
to −1.93; I2 = 29%). brain maturation, and
requirement, carbon dioxide
sleep.16,61,77,90,91,95,110,113,115,140–151
production, low-frequency/high-
Other Outcomes
frequency ratio, thyroid measures,
A variety of other neonatal water loss, home observation of Risk of Bias
outcomes were reported in a single the environment, stabilization After evaluating 5 domains of bias
study or in different ways across of cardiopulmonary system, and among the 55 RCTs, we classified
studies that could not be combined cost of care.13,44,71,79,80,89,125–139 25 (45%) as overall low risk of bias,
10 BOUNDY et al
analyses, and we found that variation provides support for widespread
in duration did not appear to have implementation of KMC as standard
ABBREVIATIONS
an important impact on the effect of care for newborns. Additional AIM: African Index Medicus
of KMC in these data. We could research is needed to determine the CI: confidence interval
not adequately assess the impact ideal duration and components IMEMR: Index Medicus for the
of number of days of SSC because of KMC. Successful strategies for Eastern Mediterranean
the majority of studies promoted a KMC implementation in various Region
similar duration of 1 to contexts should be disseminated IMSEAR: Index Medicus for the
5 days. among clinicians and South-East Asian Region
policymakers. KMC: kangaroo mother care
LBW: low birth weight
LILACS: Latin American and
CONCLUSIONS Caribbean Health
ACKNOWLEDGMENTS Sciences Information
KMC is protective against a wide
System
variety of adverse neonatal outcomes The authors would like to
MD: mean difference
and has not shown evidence of harm. acknowledge the contributions to
RCT: randomized controlled trial
This safe, low-cost intervention data abstraction and referencing
RR: relative risk
has the potential to prevent many by Stacie Constantian, Tobi
SMD: standardized mean
complications associated with Skotnes, Ilana Bergelson, Rodrigo
difference
preterm birth and may also provide Kuromoto and Eduardo Toledo.
SSC: skin-to-skin contact
benefits to full-term newborns. The We acknowledge Kate Lobner
WPRIM: Western Pacific Region
consistency of these findings across for developing the search
Index Medicus
study settings and infant populations strategy.
instruments, conducted the literature review, coordinated and supervised data collection and analyses, and critically reviewed the manuscript; and all authors
approved the final manuscript as submitted.
DOI: 10.1542/peds.2015-2238
Accepted for publication Oct 20, 2015
Address correspondence to Grace J. Chan, MD, MPH, PhD, Boston Children's Hospital, 300 Longwood Ave, Boston, MA 02115. E-mail: [Link]@childrens.
[Link]
PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).
Copyright © 2016 by the American Academy of Pediatrics
FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose.
FUNDING: This study was supported by the Saving Newborn Lives initiative (SNL) of Save the Children. Dr Boundy received support from training grant
T32HD060454 in reproductive, perinatal, and pediatric epidemiology from the National Institute of Child Health and Human Development, National Institutes of
Health, and training grant T76MC00001 from the Maternal and Child Health Bureau. Funded by the National Institutes of Health (NIH).
POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.
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