We will conduct an individually randomised, controlled, superiority trial with two parallel groups; an intervention arm allocated to receive KMC and a control arm receiving 'standard' care. The primary aim is to examine the impact of KMC initiated before stabilisation on mortality within 7 days relative to standard care amongst neonates ≤2000g at four hospitals in Uganda. We hypothesise that neonates in the arm allocated to receive KMC before stabilisation will have a 25% overall reduction in mortality within 7 days compared to neonates allocated to receive standard care.
METHODS Study setting, design, and participants The OMWaNA trial was an individually randomised, controlled, superiority trial with two parallel arms allocated in a 1:1 ratio to receive KMC initiated before stabilisation (intervention) or standard care (control). The trial was conducted in the neonatal units (WHO level-2) of five government hospitals in Uganda (appendix p 5). Infrastructure and equipment improvements as well as training were required prior to trial initiation, as described previously.10 All hospitals were provided with essential equipment and supplies to support the provision of KMC and level-2 newborn care. Details regarding study context and methods have been published in the trial protocol9 and are briefly summarised here. Ugandan practice is that maternity and newborn care should be provided free of charge in government health facilities;11 however, families are expected to support caregivers to meet essential needs such as meals. The trial is reported here in accordance with the CONSORT guidelines. All live-born neonates, aged 1 to \<48 hours and weighing 700-2000g, who were admitted to participating hospitals and for whom the indication for KMC was "uncertain" according to WHO guidance concerning clinical stability, defined as receiving ≥1 therapy (oxygen, continuous positive airway pressure \[CPAP\] where available, intravenous \[IV\] fluids, therapeutic antibiotics, anti-seizure medication), were eligible for inclusion. Exclusion criteria included triplet or higher multi-fetal pregnancy (unless pregnancy resulted in demise of ≥1 fetus) and parent/caregiver being unable/unwilling to provide either consent, KMC, and/or attend follow-up visits. Neonates with life-threatening instability, severe jaundice requiring immediate management, active seizures, or major congenital malformations were also excluded. The study was approved by the Research Ethics Committees of Uganda Virus Research Institute (GC/127/19/06/717), Uganda National Council of Science and Technology (HS 2645), and London School of Hygiene \& Tropical Medicine (LSHTM, 16972). The trial was overseen by a steering committee and an independent data and safety monitoring board (DSMB). Screening and informed consent All admitted neonates weighing ≤2000g were screened for eligibility by study staff. Stable neonates (meeting WHO 2019 criteria for KMC eligibility) were excluded and remaining neonates were assessed for eligibility. Those who met criteria for 'life-threatening instability' or who had conditions precluding KMC (e.g., seizures, jaundice), were reassessed every 3 hours up to 48 hours, after which they were excluded. Written informed parental consent was obtained for all participants. Randomisation, allocation concealment and masking A random allocation sequence was computer-generated using permuted blocks of varying sizes stratified by birthweight (\<1000g, 1000-1499g, ≥1500g) and recruitment site. Allocation concealment was done by programming the allocation sequence into the screening database and revealing treatment group only when screening of eligible neonates was complete. Neonates from multiple births (twins or triplets) were allocated to the same arm according to first-born allocation.14 Masking of parents, caregivers, or healthcare workers was not possible due to the nature of the KMC intervention. Procedures In the intervention arm, KMC was initiated soon after randomisation. Neonates were naked except for hat and diaper, placed prone and skin-to-skin on caregiver's chest, and secured using a KMC wrap. Adjustable beds were provided to facilitate continuous skin-to-skin care. KMC duration was charted by caregivers and verified by study staff. When not in KMC (e.g., during maternal bathing), incubator or radiant heater care was commenced. Study personnel, in addition to hospital staff, provided continuous KMC counselling throughout the hospitalisation. Control arm neonates were cared for in an incubator or radiant heater, as per hospital practice. Caregivers could have physical contact with their newborn but skin-to-skin contact was not initiated until stability criteria were met.9 Once stable, newborns were transferred to routine (intermittent) KMC. Neonates in both arms received standard clinical care according to hospital guidelines.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
2,221
Skin-to-skin care (target: at least 18 hours per day)
Incubator or radiant warmer until neonate meets stability criteria; once stable (WHO indication for KMC certain), the baby can transition to routine (intermittent) KMC
Entebbe
Entebbe, Uganda
Iganga District Hospital
Iganga, Uganda
Jinja Regional Referral Hospital
Jinja, Uganda
Masaka Regional Referral Hospital
Masaka, Uganda
Mortality Within 7 Days
early neonatal mortality at 7 days
Time frame: 7 days
Prevalence of Hypothermia at 24 Hours Post-randomisation
Prevalence of hypothermia at 24 hours post-randomisation using axillary temperature was assessed using a digital thermometer.
Time frame: 24 hours
Time From Intervention/Control Procedures Starting to Clinical Stabilisation
Time-to-stabilization was defined as the first time at which a neonate had met all of the following criteria for a continuous period of at least 24 hours: breathing spontaneously with SpO2 \>90% in room air; no need for supplemental oxygen or CPAP; respiratory rate 40-59 breaths per minute; no apneic episodes; heart rate 80-179 beats per minute; axillary temperature 36.0-37.4 °C; and no need for intravenous fluids.
Time frame: 30 days
Time From Starting Intervention/Control Procedures to Death
The date and time of death were prospectively recorded from the death certificate for in-hospital deaths. For deaths occurring after discharge, the date was recorded based on parent/caregiver verbal report. Median and IQR of time-to-event calculated as the 50th and 25th to 75th percentile of the distribution of event times among those who experienced the event.
Time frame: 30 days
Mean Duration of Hospital Stay in Days
The date and time of hospital admission and discharge were documented prospectively for the first admission episode.
Time frame: 30 days
Proportion of Neonates Exclusively Breastmilk Feeding at Discharge
Proportion of neonates who were exclusively breastmilk feeding at discharge, from the breast or by other means
Time frame: 30 days
Mortality Within 28 Days
All-cause mortality within 28 days. Vital status was documented at the 28-30-day follow-up visit. If participants did not attend, a telephone call was made the same day to ascertain outcome.
Time frame: 28 days
Frequency of Readmission
Episodes in which a neonate was readmitted to the index hospital were prospectively recorded. Episodes in which a neonate was readmitted to a different hospital were recorded based on parent/caregiver verbal report.
Time frame: 30 days
Daily Weight Gain at 28 Days
Mean daily weight gain was calculated as the difference between weight at enrollment and 28-30-day follow-up, as measured by the study scale.
Time frame: 28 days
Infant-caregiver Attachment at 28 Days
The intention-to-treat analysis assessed the mean difference in Maternal Infant Responsiveness Instrument score between the two arms. Scores range from 0 to 110, with higher scores indicating greater attachment.
Time frame: 28 days
Women's Well-being at 28 Days
The intention-to-treat analysis assessed the mean difference in Women's Capabilities Index (WCI) score between the two arms. The WCI has a scale of 0 to 1, with higher scores indicating greater wellbeing. The analysis excluded duplicate entries for mothers of enrolled twins/triplets.
Time frame: 28 days
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