Rationale There is a high burden of neonatal sepsis and mortality in level II neonatal units in India. Although iKMC has been shown to reduce neonatal mortality in a large RCT, the overall evidence for reduction of sepsis and mortality remains equivocal. There is a need to evaluate if iKMC can reduce the incidence of all-cause neonatal mortality or culture-positive sepsis in LBW neonates admitted to level-2 neonatal units of district hospitals with a high baseline incidence of sepsis and high case-fatality rates. Also, it is pertinent to examine the feasibility of implementing the intervention in these facilities with limited resources. Research question Among low birth weight neonates (1000-1799 g at birth) admitted to the special care newborn units (SNCU) of the district hospitals (P), does immediate kangaroo mother care (iKMC) initiated within 12 hours of life (I) reduce the incidence of all-cause neonatal mortality or culture-positive sepsis (O) compared to the conventional care (C) i.e., care in a radiant warmer/incubator until their condition is stabilized and initiating KMC after that? Sites randomization and participant enrolment In a stepped-wedge study, the intervention is gradually rolled out in steps at the participating clinical sites. The sequence of rolling of intervention will be determined using a computer-generated random sequence placed in sequentially numbered opaque sealed envelopes kept at the nodal center. The 36 months will be divided into 10 steps, with each step of 3 months’ duration. We will have 6 months as baseline period before randomizing the first unit. Before each step, the envelope will be opened, and the clinical site randomly selected for that step will be informed about initiating iKMC and ensuring care of the neonate in the mother newborn care unit (MNCU). A five- to seven-day training session will be held for the research staff before the intervention is rolled out. Thus, the clinical sites will know about the initiation of intervention at their site 14 days before the scheduled step. By the end of the 10 steps, all 10 clinical sites will have the intervention. The duration of each step will be three months.
Participants: Screening and enrolment The healthcare staff of the hospital or the research nurse (RN) will weigh every neonate born in the hospital or admitted to the SNCU. After weighing, the RN will assess the mother-newborn dyad’s eligibility for the study. If the mother and baby are eligible, neonates will be enrolled after obtaining informed written consent from the mother/guardian. Mothers who are minors will be eligible for enrollment in this study if they are at least 18 years of age and their consent is confirmed by the guardian (parent or husband). Control and Intervention After enrollment, all neonates enrolled during the control period will receive standard care, adhering to the usual practices at the sites, which involve separation of the mother and infant and admission to the SNCU until the baby achieves clinical stability. Apart from immediate kangaroo mother care (KMC) and care of the neonate in the MNCU, all other interventions will remain consistent across both intervention and control groups. Feeding will begin based on the neonate’s clinical condition, with expressed breast milk initially administered via orogastric tube or cup/paladai, transitioning to direct breastfeeding when the baby is deemed ready. Brief KMC sessions will commence in the control period once the neonates are stable, typically after meeting specific criteria such as being off CPAP, requiring less than 30% oxygen, and tolerating partial enteral feeds, usually at least 24 hours old. The mother will visit the SNCU to provide these short KMC sessions several times a day during feeding times. Continuous KMC will be initiated in the control period once the neonates meet stability criteria for at least 24 hours and can be transferred to the KMC ward. Monitoring of enrolled newborns The research nurses will be divided into two teams – the implementation team (5 nurses) and the outcome assessor team (3 nurses). The implementation team shall be responsible for enrolling the neonates and supporting mothers in providing continuous skin-to-skin contact. The outcome assessor team will monitor the enrolled neonates for the specified outcomes during their stay in the SNCU/MNCU/KMC and record the information regarding vital parameters every 12 hours up to hospital discharge/death. In neonates with suspected sepsis (based on pre-specified criteria), sepsis workup, including cultures of blood and other body fluids, will be performed by the outcome assessor team with the support of the clinical team as per the Standard Operating Procedures. Sample collection Blood culture samples (1 mL) will be collected from the eligible neonates in BacT/ALERT bottles at suspicion. The bottles with samples will be kept in an incubator at 37° C. The runner (field worker) from the SNCU site will transport the samples (in a carrier bag) to the state transport bus, where he will hand over the bag to the bus conductor. The location of the bus is tracked, and the runner from AIIMS Raipur will collect the samples from the conductor. The same bus will collect samples from all the SNCUs on the bus route. The samples collected at AIIMS, Raipur, will be processed at the microbiology laboratory. Microbiome sample collection In each period from three randomly selected sites, sample collection (skin swabs and fecal samples) from the neonates will be done on day 3 (±24 hrs) and day 7 (±24 hrs) after enrolment. For a neonate, four samples will be collected. In each period, 30 neonates will be sampled from three sites. 16S rRNA sequencing will be done to understand the microbiome in a sample from the neonate. Alpha- and beta-diversity will be calculated to understand the microbial diversity within a sample and between the samples collected during two periods. Data collection The research nurses in the assessing team will evaluate outcomes during intervention and control periods using identical methods and procedures. A separate team of research nurses from the implementation team will assist with implementing iKMC. However, they will not participate in routine newborn care provided by the regular nursing and medical staff employed at the SNCUs. During the hospital stay, outcomes will be assessed by reviewing medical records (including notes and treatment/feeding charts), observing care provision, and conducting baby assessments every 12 hours in the Special Newborn Care Unit (SNCU) and Maternal and Neonatal Intensive Care Unit (MNCU) wards. Measures will be taken to ensure participant retention and complete follow-up. A phone call will be made by the outcome assessment nurse on day 29 of age to determine outcomes at the end of the neonatal period. If unable to contact for three days by phone, a home visit will be made at the address provided at the time of enrolment. All the neonatal and maternal data will be entered into the standardized case record forms by the research nurses and subsequently entered into an electronic data capture system/platform. The database application access will be provided to the staff through a laptop/desktop as determined by the project administrator. The site research officers will ensure the timely completion of the data and conduct random checks on the forms for validation purposes. A secure login password will be used for data extraction, and the access rights to delete it will remain with the principal investigator.
Training and standardization The healthcare staff in the Special Newborn Care Units (SNCUs) are trained to deliver neonatal care using the basic care package for newborns and mothers. All relevant staff in the neonatal unit are trained to support Kangaroo Mother Care (KMC) for very small infants. This includes the proper technique for safely wrapping and positioning the baby’s head during KMC, especially when the baby is asleep. As outlined in the WHO manual for small infants, the standard of care includes monitoring, maintaining body temperature, supporting breastfeeding, and ensuring hygiene for all infants. It also involves providing access to intravenous fluids, antibiotics, and respiratory support with safe oxygen therapy and bubble Continuous Positive Airway Pressure (CPAP) if needed. To enhance the implementation of WHO Essential Care for Small Babies, all participating SNCUs will receive support. All research team members involved in the study will be highly qualified and receive thorough initial training for five to seven days before site initiation. The first three training sessions will be conducted at Safdarjung Hospital/AIIMS New Delhi. The training for nurses at the remaining sites will be conducted at these initial (three) SNCUs under the supervision of a trained person from AIIMS Raipur/AIIMS Delhi. Further, during implementation, their activities will be overseen by competent research officers who will ensure adherence to Standard Operating Procedures (SOPs). Research nurses will also receive training in screening and enrolling participants, providing KMC support, and measuring outcomes. The teams will also undergo regular training using a standardized study operations manual. Furthermore, all research staff will receive training in building rapport and communicating effectively with mothers and families. The monitoring team and site Principal Investigators (PIs) will conduct internal checks to maintain the study’s quality. These checks will consist of supervised observations and random independent assessments. Supervised observations will involve weekly supervision of the activities implemented by the monitoring team/PI. Independent checks will involve 5% of observations reviewed independently by the nodal team.
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