Impact of early kangaroo mother care versus standard care on survival of mild-moderately unstable neonates Helen Brotherton  1   2 , Abdou Gai  2 , Bunja Kebbeh  2 , Yusupha Njie  2 , Georgia Walker  1 , Abdul K Muhammad  2 , Saffiatou Darboe  2 , Mamadou Jallow  2 , Buntung Ceesay  2 , Ahmadou Lamin Samateh  3 , Cally J Tann  1   4   5 , Simon Cousens  1 , Anna Roca  2 , Joy E Lawn  1 Affiliations Expand Affiliations 1 Department of Infectious Disease Epidemiology and MARCH Centre, London School of Hygiene and Tropical Medicine (LSHTM), Keppel Street, London, UK. 2 MRC Unit The Gambia at LSHTM, Atlantic Road, Fajara, Gambia. 3 Ministry of Health, Gambia Government, Banjul, Gambia. 4 MRC/UVRI and LSHTM Uganda Research Unit, Nakiwogo Road, Entebbe, Uganda. 5 Neonatal Medicine, University College London Hospitals NHS Trust, Euston Rd, London, UK. PMID: 34401686 PMCID: PMC8358420 DOI: 10.1016/j.eclinm.2021.101050 Free PMC article Item in Clipboard

Abstract

Background: Understanding the effect of early kangaroo mother care on survival of mild-moderately unstable neonates <2000 g is a high-priority evidence gap for small and sick newborn care.

Methods: This non-blinded pragmatic randomised clinical trial was conducted at the only teaching hospital in The Gambia. Eligibility criteria included weight <2000g and age 1-24 h with exclusion if stable or severely unstable. Neonates were randomly assigned to receive either standard care, including KMC once stable at >24 h after admission (control) versus KMC initiated <24 h after admission (intervention). Randomisation was stratified by weight with twins in the same arm. The primary outcome was all-cause mortality at 28 postnatal days, assessed by intention to treat analysis. Secondary outcomes included: time to death; hypothermia and stability at 24 h; breastfeeding at discharge; infections; weight gain at 28d and admission duration. The trial was prospectively registered at www.clinicaltrials.gov (NCT03555981).

Findings: Recruitment occurred from 23rd May 2018 to 19th March 2020. Among 1,107 neonates screened for participation 279 were randomly assigned, 139 (42% male [n = 59]) to standard care and 138 (43% male [n = 59]) to the intervention with two participants lost to follow up and no withdrawals. The proportion dying within 28d was 24% (34/139, control) vs. 21% (29/138, intervention) (risk ratio 0·84, 95% CI 0·55 - 1·29, p = 0·423). There were no between-arm differences for secondary outcomes or serious adverse events (28/139 (20%) for control and 30/139 (22%) for intervention, none related). One-third of intervention neonates reverted to standard care for clinical reasons.

Interpretation: The trial had low power due to halving of baseline neonatal mortality, highlighting the importance of implementing existing small and sick newborn care interventions. Further mortality effect and safety data are needed from varying low and middle-income neonatal unit contexts before changing global guidelines.

Keywords: CFR, (Case-fatality rate); CI, (confidence interval); CLSI, (Clinical & Laboratory Standards Institute); CONSORT, (Consolidated Standards of Reporting Trials); CSF, (Cerebral-Spinal Fluid); DSMB, (Data Safety Monitoring Board); EFSTH, (Edward Francis Small Teaching Hospital); GEE, (Generalized Estimating Equation); HR, (Hazard Ratio); ICH-GCP, (International Conference on Harmonisation – Good Clinical Practice); IQR, (Inter Quartile Range); ISO, (International organisation for standardisation); IV, (intravenous); KMC, (Kangaroo mother care); Kangaroo Mother Care; Kangaroo method; LMIC, (Low and middle-income countries); LSHTM, (London School of Hygiene & Tropical Medicine); MDR, (Multi-drug resistant); MRCG, (Medical Research Council Unit The Gambia at London School of Hygiene & Tropical Medicine); Mortality; NA, (not applicable); NNU, (Neonatal Unit); Neonate; Newborn; Premature; RCT, (Randomised controlled trial); RD, (Risk difference); RDS, (Respiratory Distress Syndrome); RR, (Risk Ratio); SAE, (Serious Adverse Event); SD, (Standard Deviation); SDG, (Sustainable Development Goal); SSA, (Sub-Saharan Africa); Skin-to-skin contact; Survival; WHO, (World Health Organisation); aPSBI, (adapted Possible Severe Bacterial Infection); aSCRIP, (adapted Stability of Cardio-respiratory in Preterm infants); bCPAP, (bubble Continuous Positive Airway Pressure); eKMC trial, (early Kangaroo Mother Care before Stabilisation trial).

Conflict of interest statement

We declare no competing interests.

© 2021 The Authors.

Figures

Fig. 1

Definitions of stability used in eKMC trial. Originally published by BMC . a. Criteria for starting bCPAP were: Silverman-Anderson score ≥4 with no apnoea and/or heart rate 2, respiratory rate and heart rate were recorded every minute for a 10 min period and classified according to most frequent category of observations present for >5 min. c. Upper limit of SPO2 for providing oxygen therapy was 95%. Abbreviations: bCPAP= Bubble continuous positive airway pressure; RR=Respiratory rate; h=hours; HR=Heart rate; SPO2=oxygen saturation.

Fig. 2

Overview of enrolment, randomisation & inclusion in intention to treat analysis of primary outcome. a. Other reasons for non-recruitment were weight ≥2000 g on trial scales (6); planned team retraining (5); seizures (3); political protests leading to temporary halt to recruitment (1) and not known (1). b. Reasons for not receiving early KMC in the intervention arm were clinical deterioration between screening and start of intervention procedures (2); no study bed available (1); no caregiver available (1). Abbreviations: h=hours; KMC = Kangaroo mother care.

Fig. 3

Cumulative incidence of survival over time from start of intervention/control procedures.