MANUSCRIPT CITATION: 

WHO Immediate KMC Study Group, Arya S, Naburi H, Kawaza K, Newton S, Anyabolu CH, Bergman N, Rao SPN, Mittal P, Assenga E, Gadama L, Larsen-Reindorf R, Kuti O, Linnér A, Yoshida S, Chopra N, Ngarina M, Msusa AT, Boakye-Yiadom A, Kuti BP, Morgan B, Minckas N, Suri J, Moshiro R, Samuel V, Wireko-Brobby N, Rettedal S, Jaiswal HV, Sankar MJ, Nyanor I, Tiwary H, Anand P, Manu AA, Nagpal K, Ansong D, Saini I, Aggarwal KC, Wadhwa N, Bahl R, Westrup B, Adejuyigbe EA, Plange-Rhule G, Dube Q, Chellani H, Massawe A. Immediate “Kangaroo Mother Care” and Survival of Infants with Low Birth Weight. N Engl J Med. 2021 May 27;384(21):2028-2038. doi: 10.1056/NEJMoa2026486. PMID: 34038632

REVIEWED BY

Dr Tejo Pratap Oleti
Head, Department of Neonatology,
Fernandez Hospital
Hyderabad

Dr Srinivas Murki
Head and Director of Neonatology,
Paramita children Hospital
Hyderabad

QUESTION

Does initiation of “Kangaroo mother care” (KMC) immediately after birth (Intervention) compared to conventional care in incubator or warmer until their condition stabilized and intermittent kangaroo mother care thereafter (Control) in infants born with birth weight between 1.0 to 1.799 kg (Population) reduce the occurrence of death (Outcome) in neonatal period (first 28 days after birth) and in first 72 hours after birth (Time)?

METHODS

• Design: Muti-centre Randomized control trial
• Randomization: Randomization was performed with the use of computer-generated blocks. The blocks were variable in size and were stratified according to site and birth weight (1.0 to 1.499 kg or 1.5 to 1.799 kg).
• Allocation: Assignments were sealed in serially numbered, opaque envelopes.
• Blinding: Not blinded
• Follow-up period:
  • Primary outcome: mortality from enrolment to 28 days of age and mortality from enrolment to 72 hours of age
  • Secondary outcomes: Morbidities, breastfeeding outcomes and maternal satisfaction and maternal depression (till 28 days of age)
• Setting: Five tertiary -level hospitals situated in low resource countries located in Ghana, India, Malawi, Nigeria and Tanzania. To conduct the study, the settings made changes in infrastructure and hospital personnel. This study was conducted in a controlled environment under the supervision of multiple teams.
• Patients:
  • Inclusion criteria: 
    • Infants born alive in the participating hospitals with a birth weight from 1.0kg to less than 1.8 kg, regardless of their gestational age, were eligible for participation in this trial with their mothers.
    • The mother–infant dyad is eligible even if the infants are twins or are born by caesarean section or if the mother experiences some complications during labor and delivery that are expected to be resolved within 3 days
  • Exclusion criteria: 
    • Mother is younger than 15 years of age,
    • Mother (or her guardian if the mother is 15–17 years old) is unable or unwilling to provide consent
    • Baby is unable to breathe spontaneously within 1 hour of birth
    • Baby has a congenital malformation that interferes with the intervention or the intervention interferes with the required care for the congenital malformation
    • The place of residence is not a part of the defined study area (the study area has been defined to make 28-day follow-up home visit feasible)
    • If for any reason the mother–infant pair cannot be enrolled within 2 h of the birth of the infant.
• Intervention: Kangaroo Mother Care was defined as continuous Skin to Skin Contact (SSC) with the mother or her surrogate aiming for at least 20 hours per day, support for infant’s exclusive breastfeeding and required medical care without separation from the mother as much as possible. The surrogate is a female relative or friend identified by the mother to provide SSC when she is unable to do so. The surrogate chosen was a female relative to ensure privacy for mothers in the perinatal area.
  • • • Intervention (iKMC) group: Intervention (KMC) was executed by 3 principles:
        • Promotion and support for continuous SSC initiated as soon as possible after birth
        • Health care for mother and infant provided without separation
        • Promotion and support for early and exclusive breastfeeding.
    • Structural changes are made to create new Neonatal Intensive Care Unit(NICU)s (Mother-NICU). Mother-NICUs were equipped with sufficient staff, equipment and space to provide continuous KMC.
      • Control group: Existing standard practice at the site was continued and neonates randomized to group were shifted to NICU. Mothers provided expressed breast milk and participated in brief KMC sessions once their neonates have recovered from preterm birth related complications and at least of 24 hours age.
    • Hospital personnel provided care for infants in both the groups according to the WHO-minimum package for small infants(1). In both the groups, infants were transferred from Mother-NICU or control NICU to KMC ward once they were clinically stable for 24 hours. In the KMC ward, KMC was practiced till discharge.
• Outcomes:
  • Primary outcome: The proportion of:
    • Neonatal deaths between enrollment and 72 h of age measured through vital status records every 12 h during hospital stay
    • Neonatal deaths between enrollment and 28 days of age measured through vital status records every 12 h during hospital stay and at a home visit on day 29 of age.
  • Secondary outcomes: The proportion of:
    • Infants receiving exclusive breastfeeding (or exclusive breast-milk feeding) at discharge and at the end of the neonatal period measured by 24-h feeding recall at a home visit on day 29 of age. (Exclusive breastfeeding is defined as an infant receiving only breast milk and no other liquid or solid, with the exception of vitamin or mineral supplements, medicines, or oral rehydration solution, (if prescribed))
    • Infants with clinically suspected sepsis as per 12-hourly records during hospital stay.
    • Infants with hypothermia defined as any axillary temperature of less than 36 °C from 2 h after randomization until discharge (or 28 days of age if not discharged before then).
    • Infants with hypoglycemia defined as any blood glucose of less than 45 mg/dL (2.6 mmol/L) at mandatory measures at 6, 12, 18, and 24 h of age or at any other time.
    • Time to being fully breastfed: age at which the baby could feed fully by suckling on the breast without requiring any feeding by cup or nasogastric tube as per 12-hourly records.
    • Time to clinical stabilization: age at which the baby is considered to be clinically stable as per 12-hourly records and defined stability criteria.
    • Maternal satisfaction with health care in the hospital as per interviews.
    • Maternal depression defined as a score of 15 points or more in the Patient Health Questionnaire 9 (PHQ-9) administered to mothers at the day-29 home visit.
• Analysis and Sample Size:
  • Sample size: They estimated that 4200 infants were needed to detect 20% lower mortality in the intervention group than in the control group (16.8% vs. 21.1%), with a 95% confidence level, 90% power,and a 10% loss to follow-up. The data and safety monitoring board conducted interim analyses when 50% and 75% of the participants were enrolled. After the second interim analysis, the data and safety monitoring board recommended stopping enrollment in the trial because of the clear benefit in neonatal survival in the infants receiving immediate kangaroo mother care. Total 2944 mothers and 3211 infants were randomized.
  • Statistical analysis: Intention to treat analysis was used to assess primary and secondary outcomes.
• Patient follow-up:
  • Intervention group: 1470 mothers and 1609 infants were assigned while 1596 were included in final analysis.
  • Control group: 1474 mothers and 1602 infants were assigned while 1587 were included in final analysis.

MAIN RESULTS

Mean gestational age (32.6±3.0 vs. 32.6±2.8 weeks) and birth weight (1.5±0.2 vs 1.5±0.2 kgs) of infants enrolled neonates was similar in both the groups. Near to 27% of the infants enrolled were born to mother with twin pregnancy. Maternal age, mode of delivery, educational level, and socio-economic status of included pregnant women were similar across the groups.

Nearly 87% of the mothers included in intervention group have initiated skin to skin contact within 6 hours. Mean duration of SSC in NICU or MNICU in intervention and control groups was 16.9 (13.0–19.7) and 1.5 (0.3–3.3) hours per day respectively.   Duration of SSC in KMC ward was similar in both the groups (20.2 (18.6–21.3) vs.19.0 (16.3–20.4) hours).

Primary and secondary outcomes are shown in table 1.

N=Total number; n= number of events; IQR: Interquartile range;

*Maternal satisfaction score ranges from 1-10. Higher scores indicate greater satisfaction with care

CONCLUSION

Continuous kangaroo mother care initiated immediately after birth in infants with a birth weight between 1.0 and 1.799 kg resulted in a significantly lower risk of neonatal death than the currently recommended initiation of kangaroo mother care after stabilization. On post-hoc analysis, the benefit was seen across the categories of birth weight, gestation, weight for gestational age, type of delivery and singleton or twins.

COMMENTARY

Kangaroo mother care (KMC) is one of the low-cost interventions known to reduce mortality, infections, duration of hospitalization and cost of care among low-birth-weight infants (LBW)(2). Previous QI initiatives (3,4) provide insights into the gaps in infrastructure, hospital personnel, patient factors in implementing continuous KMC and in improving the duration of SSC hours. In this study, researchers made changes to the neonatal intensive care unit (NICU) environment (Mother-NICU) to facilitate immediate and continuous KMC and hospital personnel were trained to initiate and sustain skin to skin contact (SSC), promote exclusive breast feeding, provide clinical care and to reduce mother-infant dyad separation.

Nearly 10% of eligible (n=494) mothers not approached for enrolment. This may have created a selection bias in this study. Although baseline characteristics of the study groups were comparable, missing data on sickness scoring, need for CPAP, HFNC, ventilation and use of surfactant or caffeine limit the external validity. Data on preventive strategies such as antenatal steroids and magnesium sulphate which improve the perinatal outcomes would add value to the study.

The authors report a high duration of SSC in the NICU/MNICU among infants in the intervention group and among all the enrolled infants when shifted to the KMC ward (19 to 20 hours). Including feeding time to the SSC hours and involving KMC surrogates may be the reasons for this higher mean duration of SSC.(5)

The study reports reduction in one death (birth till day 28) for every 27 infants subjected to immediate KMC (NNT 27; 95% CI: 17 to 77). On sub-group analysis, the benefit was noted across all birth weight and gestation categories, but benefit was not consistent across the sites. The authors did not address the reasons for this variation. The mortality rates reported in this study sites are very high (6,7).

Most previous studies with similar study objectives reported higher cardio-respiratory stabilization scores in infants given iKMC compared with those given conventional care.(8,9)  Missing data on time to regain birth weight, weight gain and incidence of IVH, PVL and CLD could raise concerns on the safety of this intervention in similar study settings. Descriptions of the structural changes, trainings of hospital personnel, identification of barriers and strategies to overcome them and improve duration of SSC, cost evaluations would help implementation of iKMC in similar neonatal care settings. Future studies should evaluate implementation difficulties in iKMC and effectiveness in different settings, especially in low-mortality settings, in hospitals with maternity units without NICU facilities and in low delivery rate hospitals.

Kangaroo mother care with all its components is known to improve outcomes of preterm infants and earlier KMC is implemented, longer the duration of KMC, higher are the benefits. Immediate KMC is likely to better infant mother bonding and improve colonization with friendly microbiota. However, feasibility of iKMC when babies are likely to require respiratory support and intensive care management, compromise on the maternal privacy when implementing iKMC, ethical issues of replacing the standard intensive care management with iKMC and risking the newborn for possible morbidities are questions that linger in the reader’s mind.

REFERENCES

1. WHO recommendations on newborn health: guidelines approved by the WHO Guidelines Review Committee [Internet]. [cited 2021 Sep 4]. Available from: https://www.who.int/publications-detail-redirect/WHO-MCA-17.07
2. Conde-Agudelo A, Díaz-Rossello JL. Kangaroo mother care to reduce morbidity and mortality in low birthweight infants. Cochrane Database Syst Rev. 2016 Aug 23;(8):CD002771.
3. Joshi M, Sahoo T, Thukral A, Joshi P, Sethi A, Agarwal R. Improving Duration of Kangaroo Mother Care in a Tertiary-care Neonatal Unit : A Quality Improvement Initiative. Indian Pediatr. 2018 Sep 15;55(9):744–7.
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5. Sharma D, Murki S, Pratap OT. The effect of kangaroo ward care in comparison with “intermediate intensive care” on the growth velocity in preterm infant with birth weight <1100 g: randomized control trial. Eur J Pediatr. 2016 Oct;175(10):1317–24.
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7. Schindler T, Koller-Smith L, Lui K, Bajuk B, Bolisetty S, New South Wales and Australian Capital Territory Neonatal Intensive Care Units’ Data Collection. Causes of death in very preterm infants cared for in neonatal intensive care units: a population-based retrospective cohort study. BMC Pediatr. 2017 Feb 21;17(1):59.
8. Bergman NJ, Linley LL, Fawcus SR. Randomized controlled trial of skin-to-skin contact from birth versus conventional incubator for physiological stabilization in 1200- to 2199-gram newborns. Acta Paediatr Oslo Nor 1992. 2004 Jun;93(6):779–85.
9. Chi Luong K, Long Nguyen T, Huynh Thi DH, Carrara HPO, Bergman NJ. Newly born low birthweight infants stabilise better in skin-to-skin contact than when separated from their mothers: a randomised controlled trial. Acta Paediatr Oslo Nor 1992. 2016 Apr;105(4):381–90.