Early and extended erythropoietin monotherapy after hypoxic ischaemic encephalopathy: a multicentre double-blind pilot randomised controlled trial.

OBJECTIVE: To examine the feasibility of early and extended erythropoietin monotherapy after hypoxic ischaemic encephalopathy (HIE). DESIGN: Double-blind pilot randomised controlled trial. SETTING: Eight neonatal units in South Asia. PATIENTS: Neonates (≥36 weeks) with moderate or severe HIE admitted between 31 December 2022 and 3 May 2023. INTERVENTIONS: Erythropoietin (500 U/kg daily) or to the placebo (sham injections using a screen) within 6 hours of birth and continued for 9 days. MRI at 2 weeks of age. MAIN OUTCOMES AND MEASURES: Feasibility of randomisation, drug administration and assessment of brain injury using MRI. RESULTS: Of the 154 neonates screened, 56 were eligible; 6 declined consent and 50 were recruited; 43 (86%) were inborn. Mean (SD) age at first dose was 4.4 (1.2) hours in erythropoietin and 4.1 (1.0) hours in placebo. Overall mortality at hospital discharge occurred in 5 (19%) vs 11 (46%) (p=0.06), and 3 (13%) vs 9 (40.9%) (p=0.04) among those with moderate encephalopathy in the erythropoietin and placebo groups. Moderate or severe injury to basal ganglia, white matter and cortex occurred in 5 (25%) vs 5 (38.5%); 14 (70%) vs 11 (85%); and 6 (30%) vs 2 (15.4%) in the erythropoietin and placebo group, respectively. Sinus venous thrombosis was seen in two (10%) neonates in the erythropoietin group and none in the control group. CONCLUSIONS: Brain injury and mortality after moderate or severe HIE are high in South Asia. Evaluation of erythropoietin monotherapy using MRI to examine treatment effects is feasible in these settings. TRIAL REGISTRATION NUMBER: NCT05395195.

Impact of Kangaroo Mother Care on Skin Microbiome of Very Preterm Infants - A Pilot Study.

OBJECTIVES: To test whether Kangaroo mother care (KMC) aids in transfer of favourable skin microbiome from mother to infant by comparing the microbiome composition before and after KMC. METHODS: A prospective cohort pilot study was conducted in a Level III neonatal intensive care unit (NICU) in South India, recruiting 30 preterm infants with gestation <32 wk from October 2020 through December 2020. Neonatal skin involving the area in contact with the mother during KMC i.e., axilla, chest and abdomen was swabbed at the end of first week of life, prior to initiation of KMC. The 2nd swab involving the same areas was taken following KMC for 7 d for at least 6 h a day. The swabs were analysed using Next Generation Sequencing (NGS) - 16sRNA and abundance of organisms isolated were mapped. Statistical analyses using t-test and PERMANOVA were performed to compare phyla and genera of bacterial abundance pre-KMC and post-KMC. RESULTS: KMC at phyla level increased the relative abundance of Firmicutes (p=0.52) and significantly decreased Proteobacteria (p=0.02). At species level, KMC decreased pathogenic bacterial count of Escherichia (p=0.05), while counts of S. hemolyticus (p=0.01) and S. hominis (p=.002) significantly increased post KMC. CONCLUSIONS: KMC has a potential role in altering the neonatal skin microbiota towards a more favourable microenvironment. The clinical significance of these novel findings needs to be validated with larger studies.

Quality Improvement Study With Low-Cost Strategies to Reduce Neonatal Admission Hypothermia.

Background Admission hypothermia is still an underappreciated major challenge for new-born survival in low-resource settings. The WHO recommends skin-to-skin contact as the simplest and safest way for maintaining the body temperature even during transportation. Quality improvement initiatives for hospitalised new-borns have shown benefits like a reduction in neonatal morbidity and mortality. This study was undertaken in a resource-constrained public hospital in southern India with an aim to reduce neonatal hypothermia at admission to <20%. Method It was a prospective, quality improvement study undertaken over 20 weeks. All neonates born in the selected delivery room (DR), requiring transportation to the neonatal intensive care unit, were included. The primary outcome indicators were the mean axillary temperature of neonates measured upon arrival at the neonatal intensive care unit and the percentage of neonates with hypothermia at admission. Improving the thermoregulatory practices and ambient DR temperature to >25˚C, transportation by the kangaroo method, and a portable infant warmer (PIW) were implemented in three successive Plan-Do-Study-Act (PDSA) cycles. Result In the third PDSA cycle, the mean admission temperature (36.51˚C ±0.82) was significantly (p<0.0001) higher when compared with the baseline phase (35.41˚C ±1.09), and there was a significant (p<0.001) reduction in hypothermia (33.33%). The aim was achieved in the last two weeks of the third cycle with a reduction in hypothermia to 17.6%. Conclusion Implementation of appropriate thermoregulatory practices and low-cost strategies like the kangaroo method and PIW using quality improvement methodology significantly reduced admission hypothermia.

Development and Validation of a Neonatal Physical Maturity Score for Low- and Middle-Income Countries.

OBJECTIVE: Currently available gestational age scoring systems are complex and inaccurate for wider use in low- and middle-income countries (LMIC), particularly in infants with neonatal encephalopathy. Here, we aimed to develop a scoring system based on physical characteristics for identifying late preterm infants from term infants. STUDY DESIGN: This was a prospective observational study conducted in 2 phases- the discovery phase and validation phase. In the first phase, we examined the accuracy of 10 objective physical characteristics in a prospective cohort of 1,006 infants recruited from three hospitals in South India. A weighted scoring system and a photo card were then developed based on the six best performing characteristics which were validated in another prospective cohort of 1,004 infants. RESULTS: The final score had a sensitivity of 66.0% (95% confidence intervals [CIs], 58.4-73.8%), specificity of 80.0% (95% CI, 77.2-82.7%), and a negative predictive value of 93.0% (95% CI, 90.5-94.5%). CONCLUSION: This scoring system may have wider applications in LMIC, particularly in community settings and in infants with neonatal encephalopathy. KEY POINTS: · This is an easily administered scoring system using physical characters to identify late preterm infants.. · The scoring is not affected by neurological injury and can be used in encephalopathic infants.. · Overall accuracy is better than previous scores encompassing the physical criteria alone..

Early congenital syphilis: missed opportunities in a mother owing to many problems during pregnancy - a case report.

Untreated syphilis in pregnancy can result in an adverse outcome for the fetus. A multigravida woman with a previously poor obstetric history of early neonatal death, abortion and stillbirth was admitted in labour in the 7th month of pregnancy. On admission, syphilis screening with the qualitative rapid plasma reagin (RPR) test was negative. The infant had macules on the chest, abdomen and extremities, desquamating bullous skin lesions on the palms and soles, bilateral cataracts, an enlarged liver and spleen, anaemia, thrombocytopenia and conjugated hyperbilirubinaemia. A quantitative RPR test in the infant was positive in a 1:64 dilution and was subsequently positive in the mother in a 1:16 dilution after congenital syphilis was diagnosed. The mother later reported the father's high-risk behaviour and her previous visits to healthcare facilities for genital ulcers. The quantitative RPR test in the father was positive in a 1:32 dilution, and the parents and infant were treated for syphilis. The case demonstrates the importance of timely identification of high-risk pregnant women, early screening, repetition of the non-treponemal test on diluted serum when a routine screening test is negative, proper advice from the laboratory regarding selection of the most appropriate tests, and screening with the treponemal test first (reverse) algorithm utilising an automated enzyme immunoassay/chemiluminescence assay for the initial screening in high-risk cases, even in resource-limited settings to prevent a missed diagnosis.Abbreviations: ANC, antenatal care; BPG, benzathine penicillin G; CS, congenital syphilis; CSF, cerebrospinal fluid; CIA, chemiluminescence assay; EIA, enzyme immunoassay; HIC: high-income countries; IgM, immunoglobulin M; LMIC, low- and middle-income countries; MTCT: mother-to-child transmission; NTT, non-treponemal test; POC, point of care; RPR, rapid plasma reagin; RST, rapid syphilis test; STI, sexually transmitted infections; TT, treponemal test; TPHA, Treponema pallidum haemagglutination assay; VDRL, venereal disease research laboratory; WHO, World Health Organization.

Mycobacterium Species on the Cutaneous Microbiome of Very Preterm Neonates.

The neonatal skin microbiome consists of all the genomes and genetic products of microorganisms harboring on an infant's skin. Host and the microbiota develop a harmonious environment resulting in symbiosis. Any disruption of this environment could lead to pathological disease. This study was conducted to understand the neonatal skin microbiome of very preterm neonates (under 32 weeks) admitted to the Neonatal Intensive Care Unit(NICU) at a tertiary healthcare setting before and after kangaroo mother care (KMC), using next-generation sequencing (NGS). Skin swabs were collected on two different occasions and analyzed using the NGS technique after amplification via polymerase chain reaction. The results showed relative abundance for Mycobacterium tuberculosis in 83.33% and 66.67% (p = 0.29) and Mycobacteroides abscessus in 100% and 93.33% (p = 0.30) of the very preterm neonates on the skin microbiome before and after KMC, respectively as an incidental finding. The mere presence of these bacilli as commensals or as potential pathogens is alarming due to the risk of early exposure and incidence of tuberculosis from birth. These findings, in our view, are the first findings to be established in such a setting.

Exploring the Skin Mycobiome in Very Preterm babies during the early neonatal period in a Neonatal Intensive Care Unit of India.

The neonatal skin microbiome consists of all the genomes and genetic products of micro-organisms harbouring the skin of babies. Host and the microbiota develop a harmonious environment resulting in symbiosis. Any disruption of this environment could lead to pathological disease. Our study was conducted to explore the neonatal skin fungal microbiome of very preterm neonates admitted to Neonatal Intensive Care Unit at a tertiary health care setting using Next Generation Sequencing of the18S rRNA gene. The most abundant genera found in 22/30 samples were Candida followed by Bipolaris & Cladosporium on the skin microbiome of these neonates. The presence of these fungi, whether just as commensals or as potential pathogens, is currently under research, owing to the risk of early exposure and incidence of infection right from birth.

Decreasing antibiotic over-use by implementation of an antibiotic stewardship programme in preterm neonates in resource limited settings - a quality improvement initiative.

BACKGROUND: Antibiotics play a critical role in neonatal sepsis but excessive use is associated with adverse outcomes and the current prescribing rates of antibiotics are unacceptably high. AIM: To reduce antibiotic over-use in preterm neonates by implementing an antibiotic stewardship programme using a quality improvement (QI) initiative. METHODS: This study was conducted at a neonatal intensive care unit in a resource-limited setting. The reasons for antibiotic over-use were analysed and an antibiotic stewardship programme was implemented by using a QI initiative. The duration of the QI was a 1-month baseline phase followed by 3 months of implementation which was undertaken in the form of Plan-Do-Study-Act (P-D-S-A) cycles. The sustainment phase was observed for 2 months. All neonates admitted to the preterm unit were included. The outcome measure was the antibiotic usage expressed as days of therapy (DOT)/1000 patient days. RESULTS: In the baseline phase, DOT/1000 patient days was 1464 which fell to 706, 511, and 442 DOT/1000 patient days, respectively, over 3 months, resulting in a 65% reduction in antibiotic usage. This was achieved by a combination of efforts directed towards defining the conditions for no antibiotics, revising existing antibiotic policy, stopping orders at 48 hours, de-escalation to the narrowest spectrum antibiotic, stopping prophylactic antifungal agents and limited use of broad-spectrum antibiotics. The results were achieved without an increase in culture-positive sepsis or mortality. CONCLUSIONS: Implementation of a tailored antibiotic stewardship programme through a QI initiative was effective and safe in reducing antibiotic use in preterm neonates in a resource-limited setting. ABBREVIATIONS: AIIMS, All India Institute of Medical Sciences; DOT, days of therapy; HIC, high-income countries; ICMR, Indian Council of Medical Research; LMIC, low- to middle-income countries; LOS, late-onset sepsis; NICU, neonatal intensive care unit; NNF, National Neonatology Forum; P-D-S-A, plan-do-study-act; QI, quality improvement; SNCU, Special newborn care unit.

Quality improvement initiative to improve the duration of kangaroo mother care for twin preterm neonates born at a tertiary care hospital in resource-limited settings.

AIM: Kangaroo mother care (KMC) can be challenging in multiple births and more so in resource-limited settings. This study aims at increasing the mean duration of KMC with early initiation in twin preterm neonates born at a tertiary care hospital using a quality improvement (QI) initiative. METHODS: Barriers for poor KMC practice in twin preterm neonates born at the tertiary care hospital were analysed and baseline data were collected over a period of 4 months using a predesigned proforma. A QI team was formed and suggested solutions were prioritised through focus group discussions in the form of Plan-Do-Study-Act (P-D-S-A) cycles. Each cycle was of one-month duration and three cycles were implemented, followed by the sustenance phase studied at 1-month post-implementation. RESULTS: There were a total of 238 twin deliveries in the study period, of which 169 twin pairs were included in the study. At the end of implementation, the average day of initiation of KMC improved from 8th to 3rd day of life and the duration of KMC increased significantly from an average of 2.70 h/infant/day to 7.88 h/infant/day. CONCLUSION: This QI project focused on the improvement of KMC practice in twin preterm neonates in a tertiary care hospital where results were achieved with maximal utilisation of available hospital resources and low-cost interventions. This study design is generalizable to other hospitals in resource-limited settings where family participatory care can be strengthened to overcome the challenges of KMC in multiple births.

Newborn Screening for Five Conditions in a Tertiary Care Government Hospital in Bengaluru, South India-Three Years Experience.

PURPOSE: Newborn screening is the need of the hour in a developing country like India as there is paucity of data from studies conducted in government hospitals with large sample size. The purpose of the study is to estimate incidence rate and recall rates for five conditions screened in the neonatal period namely congenital hypothyroidism, congenital adrenal hyperplasia, glucose-6-phosphate dehydrogenase (G6PD) deficiency, galactosemia and phenyl ketonuria (PKU). METHODS: The study was conducted at VaniVilas Hospital attached to Bangalore Medical College and Research Institute. A retrospective analysis of the results of newborn screening programme during a 3-year period between January 2016 and December 2018 was done. There were 47 623 livebirths during this period out of which 41 027 babies were screened (coverage-86% of total livebirths). Heelprick samples after 48 h of life and prior to discharge were analysed by quantitative assessment. Neonates having positive screening results were recalled by telephonic call for repeat screening and confirmatory tests. RESULTS: G6PD deficiency was the most common disorder with an incidence of 1:414, followed by congenital hypothyroidism and Congenital Adrenal Hyperplasia with an incidence of 1:2735 and 1:4102, respectively. Galactosemia and PKU were found to be rare in our population. The overall average recall rate was 0.6% which meant that 24 normal newborns were recalled for testing for one confirmed case. The recall rate was relatively higher for galactosemia and G6PD deficiency which was at 0.25% each compared to the other conditions where it was below 0.05%. CONCLUSION: The results of the study emphasize the need for universal newborn screening especially in all government hospitals with large birth cohorts.