Effect of maternal hyperoxygenation on neonatal outcomes among women in labour with pathological cardiotocography: an open-label randomized controlled trial.

BACKGROUND: Hyperoxygenation has shown promise in improving suspicious fetal heart patterns in women in labor. However, the effect of hyperoxygenation on neonatal outcomes in women in labor with pathologic fetal heart rate tracing has not been studied. OBJECTIVE: This study aimed to evaluate the effect of fractional inspiration of oxygen of 80% compared with fractional inspiration of oxygen of 40% on neonatal outcomes in women with pathologic fetal heart rate tracing. STUDY DESIGN: This randomized, open-label, parallel arm, outcome assessor-blinded clinical trial was conducted in a large tertiary care university hospital. Singleton parturients aged ≥18 years at term gestation in active labor (cervical dilatation of ≥6 cm) with pathologic fetal heart rate tracing were recruited in the study. Pathologic fetal heart rate tracing was defined according to the International Federation of Gynecology and Obstetrics 2015 guidelines. The International Federation of Gynecology and Obstetrics classifies fetal heart rate tracings into 3 categories (normal, suspicious, and pathologic) based on rate, variability, and deceleration. Women in the intervention arm received oxygen at 10 L/min via a nonrebreathing mask, and those in the usual care arm received oxygen at 6 L/min with a simple face mask. Oxygen supplementation was continued until cord clamping. The primary outcome measure was a 5-minute Apgar score. The secondary outcome measures were the proportion of neonatal intensive care unit admission, umbilical cord blood gas variables, level of methyl malondialdehyde in the cord blood, and mode of delivery. RESULTS: Overall, 148 women (74 women in the high fractional inspiration of oxygen arm and 74 in the low fractional inspiration of oxygen arm) with pathologic fetal heart rate tracing were analyzed. The demographic data, obstetrical profiles, and comorbidities were comparable. The median 5-minute Apgar scores were 9 (interquartile range, 8-10) in the hyperoxygenation arm and 9 (interquartile range, 8-10) in the usual care arm (P=.12). Furthermore, the rate of neonatal intensive care unit admission (9.5% vs 12.2%; P=.6) and the requirement of positive pressure ventilation (6.8% vs 8.1%; P=.75) were comparable. Concerning cord blood gas parameters, the hyperoxygenation arm had a significantly higher base deficit in the umbilical vein and lactate level in the umbilical artery. The cesarean delivery rate was significantly lower in women who received hyperoxygenation (4.1% [3/74]) than in women who received normal oxygen supplementation (25.7% [19/74]) (P=.00). In addition, umbilical vein malondialdehyde level in the umbilical vein was lower in the hyperoxygenation group (8.28±4.65 µmol/L) than in the normal oxygen supplementation group (13.44±8.34 µmol/L) (P=.00). CONCLUSION: Hyperoxygenation did not improve the neonatal Apgar score in women with pathologic fetal heart rate tracing. In addition, neonatal intensive care unit admission rate and blood gas parameters remained comparable. Therefore, the results of this trial suggest that a high fractional inspiration of oxygen supplementation confers no benefit on neonatal outcomes in women with pathologic fetal heart rate tracings and normal oxygen saturation.

A quality improvement project to improve voluntary milk donation in a human milk bank in South India.

Background: Mother's milk is the ideal food for a neonate. When mother's milk is unavailable for any reason, pasteurised donor human milk (PDHM) is the next best option. This quality improvement (QI) project aimed at improving voluntary donation in a public human milk bank (HMB) in South India. Methods: Between January 2018 and June 2019, the HMB received an average of 15 L of donor milk per month (0.5 L/day). Our aim was to increase voluntary donation by 50% from the baseline over a period of 8 months from July 2019 to March 2020 using QI methods. Two plan-do-study-act (PDSA) cycles were done during the intervention period (4 months). Interventions included the formation of micro teams in postnatal wards to promote exclusive breastfeeding and to liaison with the core QI team. We created a milk expression area in the postnatal ward, counseled postnatal mothers, and addressed supply chain issues like sterile pumping accessories. Results: The average daily voluntary milk donation to HMB increased from 0.83 L/day in the baseline phase to 1.16 and 1.14 L per day in the intervention and postintervention phases, respectively. The mean (SD) monthly donated volumes increased from 28.2 (6.1) L to 34.1 (3.7) L; mean difference (95% CI) 5.9 (0.33-11.4); P = 0.03. The volume of PDHM disbursed from HMB increased from 26.6 (3.2) L/month to 32.2 (9.2) L/month, although not statistically significant (p = 0.15). The number of mothers donating milk did not increase during the study period. Conclusions: A multipronged QI intervention effort focusing on exclusive breastfeeding improved voluntary milk donation in HMB bank. Multiple micro-teams and local networking facilitated the QI initiative.

Comparison of two empiric antibiotic regimen in late onset neonatal sepsis--a randomized controlled trial.

OBJECTIVE: To compare the effectiveness of two antibiotic regimens among neonates with late onset sepsis (LOS). METHODS: This randomized controlled trial conducted in a tertiary care teaching hospital, South India, included 90 babies with LOS. Detailed history, examination and appropriate investigations were done for all the babies. Cloxacillin + Amikacin were administered to 40 and Cefotaxime + Gentamicin to 50 babies. Outcomes including mortality, complications and treatment failure were evaluated. Chi-square test was used for categorical variables and Student's unpaired t-test for continuous variables. RESULTS: LOS had a male preponderance, and median time of onset was 13 days. Mortality was more among low birth weight babies irrespective of the antibiotics. Predominant bacteria isolated were coagulase-negative staphylococci (26.67%), Escherichia coli (13.33%) and Streptococcus pneumoniae (13.33%). Complications, mortality and cost were similar in both regimens. CONCLUSION: There was no significant difference between the two antibiotic regimens with regard to outcome of LOS.

Does the 3C (Counselling, Checking and Certification) Initiative Prevent Hypoglycemia Among At-Risk Stable Late Preterm and Term Neonates? - A Randomized Controlled Trial.

OBJECTIVE: To evaluate whether the 3C (Counselling, Checking, Certification) initiative helps in preventing hypoglycemia among at-risk neonates compared to standard care. METHODS: This randomised controlled trial included 222 mother-newborn dyads with risk factors for neonatal hypoglycemia-Small for gestational age (SGA) babies, infants of diabetic mothers (IDM), large for gestational age (LGA) babies and late preterm infants (LPI). They were randomized to two groups. Group A received standard care while mothers in group B were administered 3C intervention. Early initiation of breastfeeding, incidence of neonatal hypoglycemia within 24 h, and exclusive breastfeeding rate at 6 mo were evaluated. RESULTS: Early initiation of breastfeeding was higher in the 3C group compared to standard care group (94.6% vs. 55.9% p <0.001). The incidence of hypoglycemia within 24 h was lower in the intervention group compared to standard care (3.6% vs. 15.3%, p <0.05). However, there was no significant difference in exclusive breastfeeding rates at 6 mo between the two groups (61% and 66% in group A and B respectively). CONCLUSIONS: The 3C intervention decreases the incidence of hypoglycemia among at-risk neonates. Early initiation of breast-feeding is higher among mothers who receive the 3C intervention.

Morbidity and Treatment-Seeking Pattern among Low Birth Weight Infants: A Community-based Cohort Study from Puducherry.

Background: To compare the morbidity and treatment-seeking pattern of low birth weight (LBW) and normal birth weight (NBW) infants during the first six months. Material and Methods: A prospective cohort study was conducted in the service areas of eight urban primary health centers of Puducherry from October 2019 to July 2021. Details of LBW and sex-matched NBW infants were obtained from the birth registers of selected PHCs. Data were collected using a structured interview schedule on completion of the first, third, and sixth months at their homes. For comparison, Mid-p exact test was used for incidence rates, t-test/Mann-Whitney for continuous variables and the Chi-square/Fisher's exact test for the categorical variables. Results: Ninety-four pairs of LBWS and NBW infants were recruited. The incidence of morbidity during the first six months among LBW and NBW infants was 37.5 and 33.3 episodes per 100 child months, respectively (P value 0.118). Though the incidence of all-cause morbidity was similar, skin infections were significantly higher among LBW (3.10 vs 1.21 per 100 child months, P = 0.04). The incidence of all-cause morbidity was high in LBW infants with poor weight gain. Conclusion: Birth weight was associated with all-cause morbidity during the first three months. However, this association varied in age points and infants' weight gain.

Role of central endpoint adjudication and challenges in trials on neonatal sepsis-a case of ProSPoNS trial.

Despite progress in reducing the infant mortality in India, the neonatal mortality decline has been slower, necessitating concerted efforts to achieve Sustainable Development Goal-3. A promising strategy aiming to prevent neonatal sepsis in high-risk, vulnerable, low birth weight neonates through an innovative intervention includes probiotic supplementation. This article communicates the decision by the ProSPoNS trial investigators to establish a Central Endpoint Adjudication Committee (CEAC) as an addendum to the protocol published in Trials in 2021 for the purpose of clarifying the primary outcome. In the published protocol, the study hypothesis and primary objective are based on "sepsis," the primary outcome has been specified as sepsis/PSBI, whereas the sample size estimation was performed based on the "physician diagnosed sepsis." To align all the three above, the investigators meeting, held on 17th-18th August 2023, at MGIMS Sevagram, Wardha, deliberated and unanimously agreed that "physician diagnosed sepsis" is the primary study outcome which includes sepsis/PSBI. The CEAC, chaired by an external subject expert and members including trial statistician, a microbiologist, and all site principal investigators will employ four criteria to determine "physician diagnosed sepsis": (1) blood culture status, (2) sepsis screen status, (3) PSBI/non-PSBI signs and symptoms, and (4) the clinical course for each sickness event. Importantly, this clarification maintains consistency with the approved study protocol (Protocol No. 5/7/915/2012 version 3.1 dated 14 Feb 2020), emphasizing the commitment to methodological transparency and adherence to predefined standards. The decision to utilize the guidance of a CEAC is recommended as the gold standard in multicentric complex clinical trials to achieve consistency and accuracy in assessment of outcomes.Trial registrationClinical Trial Registry of India (CTRI) CTRI/2019/05/019197. Registered on 16 May 2019.

Effect of therapeutic hypothermia on oxidative stress and outcome in term neonates with perinatal asphyxia: a randomized controlled trial.

OBJECTIVES: To evaluate in term babies with perinatal asphyxia, the effect of therapeutic hypothermia (TH) on oxidative stress and neurological outcome at discharge. METHODS: Babies who satisfied inclusion criteria were randomized to TH, with cooling gel packs to a target temperature of 33-34°C for 72 h or normothermia. Blood sample was collected before and after TH for oxidative stress assessment: total antioxidant status (TAS) and malondialdehyde (MDA). RESULTS: Of 116 babies randomized, there was no statistically significant difference in the baseline TAS and MDA. After 72 h of TH, TAS was significantly higher (p = <0.001) (761.69 ± 114.01 vs. 684.16 ± 88.86) and MDA was significantly lower (p = <0.001) in TH group (1.73 ± 0.66 vs. 5.2 ± 1.06). Risk of developing deficit was lower (p < 0.001) in TH group with relative risk of 0.49 and 95 % confidence interval: 0.29-0.68. CONCLUSION: TH reduces oxidative stress and improves neurological outcome in perinatal asphyxia. TRIAL REGISTRATION NUMBER: CTRI/2011/12/002196.

Impact of Low Birth Weight on the Prevalence and Economic Burden of Common Childhood Illnesses Among Under-Five Children in India: Findings From Nationally Representative Surveys.

Background Common childhood illnesses such as diarrhea, fever, and acute respiratory infection impose substantial health burdens among under-five children, and Low Birth Weight (LBW) has been associated with an increased prevalence of these illnesses. However, the impact of LBW on healthcare utilization and the economic burden of these illnesses remains understudied. Aim To assess the impact of LBW on the prevalence, healthcare utilization, and Out of Pocket Expenditure (OOPE) for outpatient (OP) treatment of selected Common Childhood Illnesses (CCHI) among under-five children in India. Methodology This study utilized data from two nationally representative surveys conducted in India; National Family Health Survey (NFHS-5) (2019-2021) and the National Sample Survey Organization (NSSO) 75th Round Schedule Social Consumption: Health (2017-2018). Data from the NFHS-5 was analyzed to assess the impact of LBW on the prevalence of selected CCHI and healthcare utilization. Comparison of OOPE for OP treatment of selected CCHI between LBW and Normal Birth Weight (NBW) children done using the median OOPE for OP visits of CCHI estimated from the NSSO data. Results The two-week prevalence of selected CCHI among LBW and NBW children was found to be 20.0% (95% CI 19.6 -20.4) and 18.0% (95% CI 17.8 -18.2), respectively. There was no significant difference between LBW and NBW children on healthcare utilization for the treatment of CCHI; both groups had a similar proportion (around 70%) of formal medical treatment utilization for CCHI. The median OOPE spending for OP visits per episode of CCHI was comparable between LBW and NBW children. However, families of LBW children had higher annual OOPE spending for OP visits related to CCHI, with projected estimates of INR 1,446 ($19.56) for LBW children and INR 1,271 ($17.2) for NBW children. Conclusion LBW was associated with a higher prevalence of CCHI. Even though healthcare utilization was similar among LBW and NBW children, a higher prevalence of CCHI among LBW children led to higher OOPE. LBW children have approximately 13% higher annual OOPE spending for the OP visits related to selected CCHI compared to NBW children.

Maternal and perinatal outcome of women with early-onset severe pre-eclampsia before 28 weeks: Is expectant management beneficial in a low-resource country? A prospective observational study.

OBJECTIVE: To study the maternal and perinatal outcomes in women with severe pre-eclampsia before 28 weeks of pregnancy. METHODS: A descriptive study from a tertiary care center. All consecutive women with severe pre-eclampsia withonset before 28 weeks of pregnancy were included. The details were collected in a predesigned structured proforma prospectively. RESULTS: The study cohort included 145 women with a mean maternal age of 26.97 ± 5.36 years (range 19-47 years). The mean duration of prolongation of pregnancy was 13.04 ± 10.57 days (range 1-51 days). A total of 29.7% (n = 43) of women had at least one major adverse maternal outcome, and the most common was HELLP (hemolysis, elevated liver enzymes, low platelet count) syndrome (n = 24,16.6%), followed by eclampsia (n = 12,8.3%). The stillbirth rate was high (n = 103,68.7%), and most occurred in the antepartum period. Of 47 (31.3%) neonates born alive, only eight (17.02%;8/47) survived up to 28 days of life. Fetal growth restriction with Doppler abnormalities and neonatal sepsis were the most common reasons for perinatal mortality. CONCLUSION: Expectant management should not be considered routinely when the onset of severe pre-eclampsia is before 25+6 weeks of pregnancy. Between 26 and 27+6 weeks it can be offered under close monitoring and the perinatal survival depends on the neonatal services available in their facility.

Congenital rubella syndrome surveillance in India, 2016-21: Analysis of five years surveillance data.

Background: In India, facility-based surveillance for congenital rubella syndrome (CRS) was initiated in 2016 to estimate the burden and monitor the progress made in rubella control. We analyzed the surveillance data for 2016-2021 from 14 sentinel sites to describe the epidemiology of CRS. Method: We analyzed the surveillance data to describe the distribution of suspected and laboratory confirmed CRS patients by time, place and person characteristics. We compared clinical signs of laboratory confirmed CRS and discarded case-patients to find independent predictors of CRS using logistic regression analysis and developed a risk prediction model. Results: During 2016-21, surveillance sites enrolled 3940 suspected CRS case-patients (Age 3.5 months, SD: 3.5). About one-fifth (n = 813, 20.6%) were enrolled during newborn examination. Of the suspected CRS patients, 493 (12.5%) had laboratory evidence of rubella infection. The proportion of laboratory confirmed CRS cases declined from 26% in 2017 to 8.7% in 2021. Laboratory confirmed patients had higher odds of having hearing impairment (Odds ratio [OR] = 9.5, 95% confidence interval [CI]: 5.6-16.2), cataract (OR = 7.8, 95% CI: 5.4-11.2), pigmentary retinopathy (OR = 6.7, 95 CI: 3.3-13.6), structural heart defect with hearing impairment (OR = 3.8, 95% CI: 1.2-12.2) and glaucoma (OR = 3.1, 95% CI: 1.2-8.1). Nomogram, along with a web version, was developed. Conclusions: Rubella continues to be a significant public health issue in India. The declining trend of test positivity among suspected CRS case-patients needs to be monitored through continued surveillance in these sentinel sites.

Neonatal Sepsis-Newer Insights.

Sepsis is one of the leading causes of mortality and morbidity among neonates worldwide and especially affects the preterm neonates in resource-restricted settings. The infection may be acquired in utero, from the mother's genital tract or postnatally from the community or hospital environment and personnel. Factors including the time of exposure, size of the inoculum, immunity in the host, and virulence of the infectious agent affect the severity and course of illness. Culture-independent diagnostics, sepsis prediction scores, antibiotic stewardship, and preventive strategies including hand hygiene are ongoing efforts for reducing the neonatal sepsis burden.

Global DNA hypomethylation and the expression profile of DNA methyltransferase genes in late-onset neonatal sepsis.

Aim: Infectious organisms tend to cause DNA methylation changes. Thus, this paper aims to study global DNA methylation and the expression of DNA methyltransferase (DNMT) genes in late-onset neonatal sepsis (LONS). Methods: Global and Alu DNA methylation and expression levels of DNMT were performed using 5mc ELISA, methylation-specific PCR and quantitative real-time-PCR, respectively for LONS and controls. Results: Significant hypomethylation of global DNA and Alu DNA methylation and lower expression of DNMT1 and DNMT3a were observed in LONS compared with controls. Receiver operating characteristic analysis of global and Alu DNA methylation showed good discrimination for the identification of LONS. Conclusion: The hypomethylation of global DNA and Alu elements is evident in neonates with LONS. This may be clinically useful for the prognosis of LONS.

Incidence of Sepsis and Its Determinants among Neonates Admitted in Level III Neonatal Unit - A Prospective Observational Study.

Introduction: Neonates are prone for sepsis due to their immature immune system. Sepsis is preventable if we aware of the maternal and neonatal risk factors. This study aimed to identify the incidence of sepsis and its risk factors. Methods: A prospective observational study was carried out among 288 neonates in level III Neonatal unit. Convenience sampling technique was used to enroll the neonates who met the inclusion criteria. Data pertaining to neonatal and maternal demographic and clinical characteristics, incidence of sepsis, risk factors of sepsis were collected by direct observation and from medical record. Data regarding number of skin pricks for blood sample and intravenous cannulation and number of handling of the baby were collected from Tally counters. Data were analysed using chi square test, t-test and logistic regression with SPSS software version 25. Results: The incidence of sepsis was 34.7% in level III neonatal unit. Culture positive sepsis constituted 7.3%, urinary tract infection 0.3%, meningitis 7 % and probable sepsis 26.4%. Neonatal factors like extreme preterm, extreme low birth weight, gestational age, birth weight, duration of stay in level III neonatal unit, number of handling, number of skin pricks, duration of intravenous line, duration of tube feeds, mechanical ventilation and maternal premature rupture of membrane were associated with neonatal sepsis significantly. Conclusion: Incidence of neonatal sepsis can be minimized by concentrating on modifiable risk factors and implementing the protocol of minimum handling and minimal skin pricks for the neonates.

A Systematic Review of Antenatal Risk Scoring Systems in India to Predict Adverse Neonatal Outcomes.

Background: The purpose of antenatal care (ANC) is to identify 'at-risk' pregnant women, to provide quality care for all, and maximize the allocation of resources for those who need them the most. To address the synergistic effect of risk factors, clinicians across the globe developed antenatal scoring systems. Objective: This review aims to investigate various antenatal risk scoring systems developed and used in India to predict adverse neonatal outcome. Methods: We reviewed articles published between January 2000 and April 2020, which have either developed a scoring system or used a scoring system, among the Indian population. This systematic review is reported based on Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Prediction model study Risk Of Bias Assessment Tool (PROBAST) was employed for the assessment of the quality of included studies. Data sources such as Embase, MEDLINE/Pubmed, APA PsycExtra, PsycINFO, CINHAL Plus, Cochrane Library, IndMED, LILACS, Scopus, WHO Reproductive Health Library and Web of science were searched. Results: An initial search retrieved a total of 6246 articles. This systematic review identified six studies, of which one study developed an antenatal scoring system and the other five studies used two antenatal systems for predicting adverse neonatal outcome. The study which developed a risk scoring system had a high risk of bias (ROB) and concern for applicability. The overall sensitivity of the antenatal scoring system was high (77.4%), but the specificity was low (45%). Similarly, the positive predictive value is low (15.3%), and the negative predictive value is high (94.2%). A meta-analysis was not conducted due to the heterogeneity of the studies and insufficient data. Conclusions: There is a need for a systematically developed antenatal scoring system for India. Such scoring systems can be promising in public health, proposing a paradigm shift in the implementation of effective mother and child health programmes locally as well as nationally. Supplementary Information: The online version contains supplementary material available at 10.1007/s13224-021-01484-z.

Implementing Family-Centered Care in the Neonatal Intensive Care Unit - A Quality Improvement Initiative.

OBJECTIVE: The present study aims to implement family-centered care (FCC) in neonatal intensive care unit (NICU). FCC facilitates mother-infant bonding with benefits for both families and health system. The authors used quality-improvement (QI) methods to implement FCC in level-2 NICU from an existing baseline of 30% to 80% over a period of 6 mo. METHODS: Using the Institute of Healthcare model for improvement, the authors implemented strategies for family participation in caregiving activities, oral feeding and kangaroo care for neonates admitted in level-2 NICU. Eligibility criteria included the availability of at least one family member, preferably the mother for at least 6 h/d and a stable neonate based on physiological criteria irrespective of gestational age. The key interventions were: (1) adoption of a unit protocol for FCC with expanded visitation hours; (2) parental education through audio-visual aids, and (3) capacity building through training and peer support. RESULT: Between August 2019 and January 2020, 1587 neonates were admitted to the NICU and 505 admitted in level-2 were enrolled. The proportion of eligible mother-infant dyads participating in FCC increased from a baseline of 32% to 44% during intervention and to 66% in the postintervention phase. The number of days per month FCC was tracked increased from 67% in the baseline to 82% in postintervention phase. There was no increase in the incidence of sepsis after implementation of FCC. CONCLUSION: Orientation of parents to FCC using audio-visual aids, provision of hands-on training and peer-support facilitated them to become active participants in their neonates' care.

Is SARS-CoV-2 Transmitted Through Breastfeeding?

There are concerns regarding the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from mother to child during this COVID pandemic. This descriptive study was done to check the possible transmission of the virus through breastfeeding in the Indian context. RT-qPCR for SARS-CoV-2 was done in breast milk samples from 30 COVID-positive mothers. Paired oropharyngeal swabs of the same neonates were also sent for RT-PCR at 48 h and on day 5 of life. All the breast milk samples were negative for SARS-CoV-2 except one. A repeat sample of breast milk from the same mother was also negative when rechecked the next day. All the paired neonatal oropharyngeal swabs were also negative for SARS-CoV-2. The authors could not find evidence for transmission of SARS-CoV-2 from mother to child through breastmilk in the population studied.

Evaluating the efficacy of a multistrain probiotic supplementation for prevention of neonatal sepsis in 0-2-month-old low birth weight infants in India-the "ProSPoNS" Study protocol for a phase III, multicentric, randomized, double-blind, placebo-controlled trial.

BACKGROUND: Progress has been made in the reduction of under-five mortality in India; however, neonatal mortality is reducing at a slower rate. Efforts are required to bring down neonatal mortality in order to attain the Sustainable Development Goal-3. Prevention of sepsis among the high-risk, vulnerable low birth weight neonates by a newer intervention with probiotic supplementation is promising. METHODS: A phase III, multicenter, randomized, double-blind, placebo-controlled study is being conducted at six sites in India. A total of 6144 healthy low birth weight (LBW) infants fulfilling the eligibility criteria would be enrolled within the first week of life, after obtaining written informed consent from the parents of the infant. Randomization in 1:1 ratio, stratified by site, sex, and birth weight, would be done through an interactive web response system (IWRS) using a standard web browser and email service. Vivomixx®, a probiotic containing a mix of 8 strains of bacteria, in a suspension form standardized to deliver 10 billion CFU/ml, or an organoleptically similar placebo would be fed to enrolled infants in a 1-ml/day dose for 30 days. The follow-up of enrolled infants for 60 days would take place as per a pre-specified schedule for recording morbidities and outcome assessments at the six participating sites. Screening for morbidities would be conducted by trained field workers in the community, and sick infants would be referred to designated clinics/hospitals. A physician would examine the referred infants presenting with complaints and clinical signs, and blood samples would be collected from sick infants for diagnosis of neonatal sepsis by performing sepsis screen and blood culture. Appropriate treatment would be provided as per hospital protocol. The study would be implemented as per the MRC guideline for the management of Global Health Trials in accordance with ICH-GCP and Indian Regulatory guidelines. A contract research organization would be engaged for comprehensive monitoring and quality assurance. The final analysis would be conducted in a blinded manner as per the statistical analysis plan (SAP) to estimate the primary outcomes of sepsis, possible serious bacterial infection (PSBI), and secondary outcomes. The codes will be broken after DMC permission. The protocol has been reviewed by the Research Ethics Committee of the Liverpool School of Tropical Medicine (REC-LSTM), from Research Ethics Committees of the six subject recruitment participating sites. DISCUSSION: This adequately powered and well-designed trial would conclusively answer the question whether probiotics can prevent neonatal sepsis in the high-risk group of low birth weight infants as indicated by a pilot study in 1340 LBW infants, evidence from systematic reviews of hospital-based studies, and a primary study on healthy newborns in Orissa. Results of the study would be generalizable to India and other low-middle-income countries. TRIAL REGISTRATION: Clinical Trial Registry of India (CTRI) CTRI/2019/05/019197 . Registered on 16 May 2019.