Protocol for a randomised trial of early kangaroo mother care compared to standard care on survival of pre-stabilised preterm neonates in The Gambia (eKMC)

Abstract

Background: Complications of preterm birth cause more than 1 million deaths each year, mostly within the first day after birth (47%) and before full post-natal stabilisation. Kangaroo mother care (KMC), provided as continuous skin-to-skin contact for 18 h per day to fully stabilised neonates ≤ 2000 g, reduces mortality by 36-51% at discharge or term-corrected age compared with incubator care. The mortality effect of starting continuous KMC before stabilisation is a priority evidence gap, which we aim to investigate in the eKMC trial, with a secondary aim of understanding mechanisms, particularly for infection prevention.

Methods: We will conduct a single-site, non-blinded, individually randomised, controlled trial comparing two parallel groups to either early (within 24 h of admission) continuous KMC or standard care on incubator or radiant heater with KMC when clinically stable at > 24 h of admission. Eligible neonates (n = 392) are hospitalised singletons or twins < 2000 g and 1-24 h old at screening who are mild to moderately unstable as per a trial definition using cardio-respiratory parameters. Randomisation is stratified by weight category (< 1200 g; ≥ 1200 g) and in random permuted blocks of varying sizes with allocation of twins to the same arm. Participants are followed up to 28 ± 5 days of age with regular inpatient assessments plus criteria-led review in the event of clinical deterioration. The primary outcome is all-cause neonatal mortality by age 28 days. Secondary outcomes include the time to death, cardio-respiratory stability, hypothermia, exclusive breastfeeding at discharge, weight gain at age 28 days, clinically suspected infection (age 3 to 28 days), intestinal carriage of extended-spectrum beta-lactamase producing (ESBL) Klebsiella pneumoniae (age 28 days), and duration of the hospital stay. Intention-to-treat analysis will be applied for all outcomes, adjusting for twin gestation.

Discussion: This is one of the first clinical trials to examine the KMC mortality effect in a pre-stabilised preterm population. Our findings will contribute to the global evidence base in addition to providing insights into the infection prevention mechanisms and safety of using this established intervention for the most vulnerable neonatal population.

Trial registration: ClinicalTrials.gov NCT03555981. Submitted 8 May 2018 and registered 14 June 2018. Prospectively registered.

Keywords: Infection; Kangaroo care; Kangaroo mother care; Neonate; Pragmatic; Preterm; Randomised controlled trial; Skin-to-skin contact; Survival.

Conflict of interest statement

The authors declare that they have no competing interests. The funder (Wellcome Trust) played no role in the design of the trial or writing of the manuscript.

Figures

Fig. 1

eKMC trial schedule of enrolment, interventions and assessments [16] 1. The start of study procedures (Time 0) is defined as when the pulse oximeter is attached for baseline continuous cardio-respiratory assessment, immediately prior to the intervention/control procedures commencing. 2. Participants are reviewed daily until KMC unit admission, after which they are reviewed on days 7, 14, 21, and 28 of age whilst inpatients and on day 28 as outpatients. Daily reviews are re-started if the baby is transferred back to the neonatal unit. 3. Stability definitions used during eligibility screening and routine assessments are detailed in Fig. 2. 4. Weight at 5 days of age is taken on calibrated digital scales and then is taken daily until either discharge or KMC unit admission, after which it is obtained on days 7, 14, 21, and 28 whilst an in-patient and at the day 28 follow-up if discharged. 5. Skin swab samples are taken from the first person to provide skin-to-skin contact and the mother (if different) as soon as possible and prior to any skin-to-skin contact. The relationship of the KMC provider to the participant is documented and correlated with swabs using unique, anonymised identification codes. 6. Outcomes such as feeding method and duration of stay are recorded at the time of discharge, including for participants hospitalised for > 28 days

Fig. 2

eKMC trial definitions of cardio-respiratory instability and eligibility status. 1. Criteria for starting CPAP is a Silverman-Anderson score ≥ 4 that does not improve with oxygen therapy and the absence of the following: heart rate 

Fig. 3

An eKMC participant receiving the intervention of ocntinuous skin-to-skin contact at the same time as other standard care treatments (H.Brotherton with caregiver consent for publication)

Fig. 4

Overview of eKMC routine procedures and assessment of clinical deterioration including key trial criteria. 1. New or changed PSBI definitions to increase relevance for hospitalised preterm neonates. 2. Spontaneous apnoea with no identifiable reason, e.g., not associated with milk aspiration or end-stage respiratory failure. 3. Re-start criteria also apply to neonates in control arm at the initiation of KMC

Fig. 5

Trial flow diagram, as per CONSORT guidelines 2010 [27]