Death, Hypothermia, Newborn, Infection, Bacterial, Kangaroo Mother Care, Preterm Infant
Conditions
Brief summary
The mortality effect of kangaroo mother care in stable newborns \<2000g is well established but mortality effect in unstable newborns is not conclusively known. This pragmatic clinical trial aims to investigate the mortality and clinical effects of early continuous Kangaroo Mother Care (KMC) compared to standard care in mild-moderately unstable neonates \<2000g in a resource limited hospital setting.
Detailed description
This individually randomised controlled trial will compare 2 parallel groups of hospitalised mild-moderately unstable neonates \<2000g and aged \<24h at time of screening who receive either early continuous kangaroo mother care (KMC) (started at \<24h of admission) or standard care with continuous KMC at \>24h of admission and when stable. The intervention will be un-blinded to participants and researchers with blinding of outcomes where possible. If participants clinically deteriorate and meet "stopping criteria" they will be temporarily withdrawn from the intervention arm and re-start KMC when clinically stable, as per the control arm. Intention to treat analysis will be used. Duration of time spent in KMC will be documented and compared between arms. All other hospital management will be provided as per a Standardised Preterm Management Protocol, based on current standard care at the study site and compliance to this protocol will be monitored in both arms. Underlying protective mechanisms for early KMC will also be explored, focusing on causal pathways such as thermal control, cardio-respiratory stability, infection prevention control and gastro-intestinal stability pathways.
Interventions
Continuous skin-to-skin contact between baby and mother/caregiver started within 24h of hospital admission
OTHERStandard care
Incubator or radiant heater care until stable, off oxygen and \>24h of admission, at which point will start intermittent or continuous kangaroo mother care
Sponsors
London School of Hygiene and Tropical Medicine
Wellcome Trust
Medical Research Council Unit, The Gambia
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Individually randomised controlled superiority trial
Eligibility
Sex/Gender
ALL
Age
1 Years to 24 Years
Healthy volunteers
No
Inclusion criteria
* New admission to study site during study period * Admission weight \<2000g * Age 1 - 24h at start of screening * Alive at enrolment * Availability of study bed * Written informed consent from parent or caregiver * Parent or caregiver available and willing to provide intervention, if necessary
Exclusion criteria
* Congenital malformation incompatible with life or needing immediate surgical correction * Severe jaundice needing immediate management * Seizures * Clinically stable as assessed over pre-defined period of cardio-respiratory monitoring * Severely unstable as assessed over pre-defined period of cardio-respiratory monitoring * Completed triplet admission * Mother and/or neonate enrolled in another research study at time of hospital admission
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| All-cause Mortality | 28 days | All neonatal deaths within 28 postnatal days |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Death | 28 days of age | Time from start of intervention/control procedures to death |
| Cardio-respiratory Stability | At 24 hours after start of intervention/control procedures | The 'Stability of Cardio-Respiratory in Preterm' infants is a scale to quantify the cardio-respiratory stability of preterm infants. It is composed of three parameters: Heart rate; Respiratory rate and breathing pattern and oxygen saturation (including whether is in oxygen). Scores between 0 and 2 are allocated for each parameter, with minimum total score 0 and maximum total score 6. The highest score (6) represents a better outcome, with all parameters within normal range whilst not receiving oxygen. |
| Number and Proportion of Participants With Hypothermia | At 24 hours after start of intervention/control procedures | Number and proportion of participants with hypothermia (Temperature \<36.5 degrees Celsius) |
| Weight Gain | At 28 days of age | Average daily weight gain compared to admission weight |
| Exclusive Breastfeeding | At time of hospital discharge, within study period, on average 2 weeks of age | Number of babies who are exclusively breastfed (defined as only receiving breast milk with no infant formula supplementation) |
| Suspected Infection Between 3d to 28d of Age | Within 28 days of age | Number and proportion of participants with suspected infection between 3d to 28d of age, or age at latest follow up |
| Neonatal Intestinal Carriage of Extended Spectrum Beta-Lactamase-producing Klebsiella Pneumoniae | At day 28 of age | Number and proportion of participants with intestinal carriage of Extended Spectrum Beta-Lactamase-Klebsiella pneumoniae |
| Duration of Hospital Admission | Within 28 days of age or at latest follow-up | Mean length of admission (first admission only if re-admitted) |
Countries
The Gambia
Contacts
PRINCIPAL_INVESTIGATORHelen C Brotherton, MBChB
London School of Hygiene and Tropical Medicine
Participant flow
Recruitment details
Recruitment took place from 23rd May 2018 - 19th March 2020 at the neonatal unit of the only teaching hospital in The Gambia, providing WHO level 2+ newborn care.
Participants by arm
| Arm | Count |
|---|---|
| Early KMC Continuous kangaroo mother care started within 24h of hospital admission, aiming for minimum 18h/day and until hospital discharge with encouragement of KMC at home
Early Kangaroo Mother Care: Continuous skin-to-skin contact between baby and mother/caregiver started within 24h of hospital admission | 138 |
| Standard Care Standard care under radiant heater or incubator until clinical stability criteria are met then intermittent or continuous Kangaroo mother care started at \>24h of hospital admission until hospital discharge with encouragement of KMC at home
Standard care: Incubator or radiant heater care until stable, off oxygen and \>24h of admission, at which point will start intermittent or continuous kangaroo mother care | 141 |
| Total | 279 |
Baseline characteristics
| Characteristic | Standard Care | Total | Early KMC |
|---|---|---|---|
| Admission weight | 1436 grams | 1450 grams | 1459 grams |
| Admission weight <1200g | 39 Participants | 73 Participants | 34 Participants |
| Age, Categorical <=18 years | 141 Participants | 279 Participants | 138 Participants |
| Age, Categorical >=65 years | NA Participants | NA Participants | NA Participants |
| Age, Categorical Between 18 and 65 years | NA Participants | NA Participants | NA Participants |
| Age, Continuous | 2.3 hours | 2.3 hours | 2.3 hours |
| Gestational age | 32 weeks | 33 weeks | 33 weeks |
| Race/Ethnicity, Customized Gambian | 141 Participants | 279 Participants | 138 Participants |
| Region of Enrollment Gambia | 141 participants | 279 participants | 138 participants |
| Sex: Female, Male Female | 82 Participants | 161 Participants | 79 Participants |
| Sex: Female, Male Male | 59 Participants | 118 Participants | 59 Participants |
| Stable at baseline | 5 Participants | 19 Participants | 14 Participants |
| Twin, both enrolled | 24 Participants | 48 Participants | 24 Participants |
| Twin pregnancy | 45 Participants | 86 Participants | 41 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 29 / 138 | 34 / 141 |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 30 / 138 | 28 / 141 |
Outcome results
Primary
All-cause Mortality
All neonatal deaths within 28 postnatal days
Time frame: 28 days
Population: All recruited neonates with primary outcome data at 28 days were included in the analysis. This consisted of all (n=138) neonates allocated to the intervention arm and 139 neonates in the control arm, as two control participants were lost to follow up.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Early KMC | All-cause Mortality | 29 Participants |
| Standard Care | All-cause Mortality | 34 Participants |
Secondary
Cardio-respiratory Stability
The 'Stability of Cardio-Respiratory in Preterm' infants is a scale to quantify the cardio-respiratory stability of preterm infants. It is composed of three parameters: Heart rate; Respiratory rate and breathing pattern and oxygen saturation (including whether is in oxygen). Scores between 0 and 2 are allocated for each parameter, with minimum total score 0 and maximum total score 6. The highest score (6) represents a better outcome, with all parameters within normal range whilst not receiving oxygen.
Time frame: At 24 hours after start of intervention/control procedures
Population: Only neonates with outcome data available at 24h after enrolment were included in the analysis, hence the number of participants analysed is less than 279. This was principally due to mortality during first 24h of trial.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Early KMC | Cardio-respiratory Stability | 5 units on a scale |
| Standard Care | Cardio-respiratory Stability | 5 units on a scale |
Secondary
Duration of Hospital Admission
Mean length of admission (first admission only if re-admitted)
Time frame: Within 28 days of age or at latest follow-up
Population: Only neonates with outcome data available at time of discharge were included in the analysis, hence the number of participants analysed is less than 279. Neonates were died during first hospital admission were not included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Early KMC | Duration of Hospital Admission | 16.6 Days | Standard Deviation 11.1 |
| Standard Care | Duration of Hospital Admission | 16.3 Days | Standard Deviation 10 |
Secondary
Exclusive Breastfeeding
Number of babies who are exclusively breastfed (defined as only receiving breast milk with no infant formula supplementation)
Time frame: At time of hospital discharge, within study period, on average 2 weeks of age
Population: Only neonates with outcome data available at discharge were included in the analysis, hence the number of participants analysed is less than 279. The missing data was principally due to mortality prior to discharge.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Early KMC | Exclusive Breastfeeding | 107 Participants |
| Standard Care | Exclusive Breastfeeding | 105 Participants |
Secondary
Neonatal Intestinal Carriage of Extended Spectrum Beta-Lactamase-producing Klebsiella Pneumoniae
Number and proportion of participants with intestinal carriage of Extended Spectrum Beta-Lactamase-Klebsiella pneumoniae
Time frame: At day 28 of age
Secondary
Number and Proportion of Participants With Hypothermia
Number and proportion of participants with hypothermia (Temperature \<36.5 degrees Celsius)
Time frame: At 24 hours after start of intervention/control procedures
Population: Only neonates with outcome data available at 24h after enrolment were included in the analysis, hence the number of participants analysed is less than 279. This was principally due to mortality during first 24h of trial.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Early KMC | Number and Proportion of Participants With Hypothermia | 51 Participants |
| Standard Care | Number and Proportion of Participants With Hypothermia | 55 Participants |
Secondary
Suspected Infection Between 3d to 28d of Age
Number and proportion of participants with suspected infection between 3d to 28d of age, or age at latest follow up
Time frame: Within 28 days of age
Population: All randomised participants were included in the analysis
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Early KMC | Suspected Infection Between 3d to 28d of Age | 28 Participants |
| Standard Care | Suspected Infection Between 3d to 28d of Age | 21 Participants |
Secondary
Time to Death
Time from start of intervention/control procedures to death
Time frame: 28 days of age
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Early KMC | Time to Death | 90.0 hours |
| Standard Care | Time to Death | 98.5 hours |
Secondary
Weight Gain
Average daily weight gain compared to admission weight
Time frame: At 28 days of age
Population: Only neonates with outcome data available at age 28d were included in the analysis, hence the number of participants analysed is less than 279. This was principally due to mortality, loss to follow up and small number of participants with missing data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Early KMC | Weight Gain | 10.3 grams/day | Standard Deviation 10.1 |
| Standard Care | Weight Gain | 12.5 grams/day | Standard Deviation 12.1 |