Assessment of an Antimicrobial Stewardship Program for Enhancing Clinical Knowledge in Neonatal Care Settings With High Antimicrobial Resistance.

INTRODUCTION: Antimicrobial resistance (AMR) is a global problem, which is particularly challenging in developing countries like India. This study attempts to determine the competencies of health care professionals and to update evidence-based policies to address AMR. METHOD: A survey-based educational interventional study was conducted using a validated structured survey and knowledge questionnaire under 3 domains through an antimicrobial stewardship program. Pooled data were analyzed using SPSS version 16.0. RESULTS: Out of 58 participants, 53 (91%) have observed an increasing trend of multidrug-resistant infections over the last 5 years. There is a significant difference between the overall pretest mean scores (8.12 ± 2.10) and posttest mean scores (12.5 ± 1.49) of clinicians' knowledge with a mean difference of 4.38 ± 0.61, 95% CI of 5.003-3.92, t(57) = 16.62, P < .001). DISCUSSION: The antimicrobial stewardship program was effective in improving the competencies of clinical physicians to improve antimicrobial prescribing and reduce AMR. Moreover, improving the knowledge and competencies among health care professionals will minimize neonatal morbidity and mortality.

Amplitude-Integrated Electroencephalogram in Premature Infants: A Prospective Cohort Study.

OBJECTIVE: The study aimed to interpret and establish patterns of amplitude-integrated electroencephalogram (aEEG) in stable preterm neonates and compare the aEEG among different gestational age groups using three standard classifications. METHODS: This prospective cohort study included stable preterm neonates between 240/7 and 366/7 weeks of gestation. aEEG was recorded in the first and second week of life and interpreted using the L. Hellström-Westas, Burdjalov, and Magalhães classification for background pattern, continuity, upper and lower margin amplitude, sleep-wake cycle, bandwidth, and presence of seizures. Subgroup analysis was performed based on ≤30 and >30 weeks' gestation. RESULTS: A total of 76 aEEG recordings were analyzed from 45 preterm neonates. In the first week, 60% of the neonates had normal voltage patterns, which increased to 80% in the second week. All infants ≤30 weeks displayed discontinuous wave patterns during the first week, and half transitioned to continuous waves in the second week. The lower margin amplitude increased, and the upper margin amplitude decreased with increased gestational age. Additionally, 65% of neonates had a mature sleep-wake cycle in the second week compared with 22% in the first week. The median (interquartile range) CFM score in the second week was 12 (4.5) compared with 8 (4) in the first week, and the CFM score positively correlated with gestation (Spearman correlation coefficient, 0.8; 95% confidence interval, 0.7-0.86). Magalhães grading in both groups was predominantly normal. CONCLUSION: aEEG is predominantly a continuous normal voltage pattern in >30 weeks' gestation and discontinuous in ≤30 weeks' gestation. CFM score correlates positively with advancing gestation gestational age.

Gram-Negative Colonization and Bacterial Translocation Drive Neonatal Sepsis in the Indian Setting.

BACKGROUND: The gut microbiota, comprising billions of microorganisms, plays a pivotal role in health and disease. This study aims to investigate the effect of sepsis on gut microbiome of neonates admitted to the Neonatal Intensive Care Unit. METHODS: A prospective cohort study was carried out in the NICU of tertiary care hospital in Karnataka, India, from January 2021 to September 2023. Preterm neonates with birth weight < 1500 g and gestational age < 37 weeks were recruited, excluding those with congenital gastrointestinal anomalies, necrotizing enterocolitis, or blood culture-negative infections. The study population was divided into three groups: healthy neonates (Group A), neonates with drug-sensitive GNB sepsis (Group B), and neonates with pan drug-resistant GNB sepsis (Group C). Stool samples were collected aseptically, snapped in liquid nitrogen, and stored at -80°C for extraction of DNA and microbiome analysis. RESULTS: The gut microbiota of healthy neonates (Group A) was dominated by Proteobacteria (24.04%), Actinobacteria (27.13%), Firmicutes (12.74%), and Bacteroidetes (3%). Predominant genera included Bifidobacterium (55.17%), Enterobacter (12.55%), Enterococcus (50.69%), Streptococcus (7.92%), and Bacteroides (3.58%).Groups B and C, the microbiota exhibited higher Proteobacteria abundance (57.16% and 66.58%, respectively) and reduced diversity of beneficial bacteria. Notably, the presence of sepsis was associated with an increase in pathogenic bacteria and a decrease in beneficial commensal bacteria. CONCLUSION: Neonates with sepsis exhibited significant gut microbiome dysbiosis, characterized by increased Proteobacteria and reduced beneficial bacteria diversity. These findings highlight the potential of microbiome profiling as a diagnostic tool and underscore the importance of gut microbiota modulation in managing neonatal sepsis.

Genetic and phenotypic landscape of pediatric-onset epilepsy in 142 Indian families: Counseling and therapeutic implications.

The application of genomic technologies has led to unraveling of the complex genetic landscape of disorders of epilepsy, gaining insights into their underlying disease mechanisms, aiding precision medicine, and providing informed genetic counseling. We herein present the phenotypic and genotypic insights from 142 Indian families with epilepsy with or without comorbidities. Based on the electroclinical findings, epilepsy syndrome diagnosis could be made in 44% (63/142) of the families adopting the latest proposal for the classification by the ILAE task force (2022). Of these, 95% (60/63) of the families exhibited syndromes with developmental epileptic encephalopathy or progressive neurological deterioration. A definitive molecular diagnosis was achieved in 74 of 142 (52%) families. Infantile-onset epilepsy was noted in 81% of these families (61/74). Fifty-five monogenic, four chromosomal, and one imprinting disorder were identified in 74 families. The genetic variants included 65 (96%) single-nucleotide variants/small insertion-deletions, 1 (2%) copy-number variant, and 1 (2%) triplet-repeat expansion in 53 epilepsy-associated genes causing monogenic disorders. Of these, 35 (52%) variants were novel. Therapeutic implications were noted in 51% of families (38/74) with definitive diagnosis. Forty-one out of 66 families with monogenic disorders exhibited autosomal recessive and inherited autosomal dominant disorders with high risk of recurrence.

Standardizing Minimally Invasive Tissue Sampling of Postmortem Brain Using Bard Monopty Needle in Newborns with Neurological Injury.

INTRODUCTION: Minimally invasive tissue sampling of the brain in newborns using the Bard Monopty needle helps to diagnose various neurological conditions by obtaining relevant brain cores. We designed a modified procedure to provide maximum diagnostic utility in brain tissue biopsies. METHOD: Twenty newborns underwent postmortem minimally invasive tissue sampling of the brain through the anterior fontanelle and posterior approach, using the engraved lines on the needle labeled from mark 0 to 13. The cores were correlated with conventional autopsy findings. RESULTS: Meninges were best obtained at marks 0 and 1 from the anterior fontanelle and mark 1 from posterior fontenelle in 85% of cases. Periventricular brain parenchyma was best obtained from mark 3 and mark 1 from anterior and posterior fontanel, respectively in 90% cases. The sampling success in obtaining brain cores was 100%. DISCUSSION: This modified technique increases the yield of meninges and brain tissue in newborns and aids in diagnosis.

Comparative Growth Outcomes in Very Low Birth Weight Infants: Evaluating Different Feeding Strategies.

OBJECTIVES: To assess the growth pattern of preterm, very low birth weight (VLBW) appropriate for gestational age (AGA) infants on three different feeding regimens. METHODS: This prospective open label three-arm parallel randomized controlled trial was conducted at neonatal intensive care unit, Kasturba Hospital, Manipal. One hundred twenty VLBW (weight between 1000-1500 g and gestational age 28-32 wk) preterm AGA infants admitted from April 2021 through September 2022 were included. Three feeding regimens were compared: Expressed breast milk (EBM); EBM supplemented with Human milk fortifier (HMF); EBM supplemented with Preterm formula feed (PTF). Primary outcome measure was assessing the growth parameters such as weight, length, head circumference on three different feeding regimens at birth 2, 3, 4, 5 and 6 wk/discharge. Secondary outcomes included incidence of co-morbidities and cost-effectiveness. RESULTS: Of 112 infants analyzed, Group 2 supplemented with HMF showed superior growth outcomes by 6th wk/discharge of intervention, with mean weight of 2053±251 g, mean length of 44.6±1.9 cm, and mean head circumference of 32.9±1.4 cm. However, infants in Group 3, supplemented with PTF, registered mean weight of 1968±203 g, mean length of 43.6±2.0 cm, and mean head circumference of 32.0±1.6 cm. Infants exclusively on EBM presented with mean weight of 1873±256 g, mean length of 43.0±2.0 cm and mean head circumference of 31.4±1.6 cm. CONCLUSIONS: Addition of 1 g of HMF to 25 ml of EBM in neonates weighing 1000-1500 g showed better weight gain and head circumference at 6 wk/discharge, which was statistically significant. However, no significant differences in these parameters were observed at postnatal or 2, 3, 4, and 5 wk.

Sustaining extended Kangaroo mother care in stable low birthweight babies in NICU: a quality improvement collaborative of six centres of Karnataka.

BACKGROUND: Kangaroo mother care (KMC) is a proven intervention for intact survival in preterms. Despite evidence, its adoption has been low. We used a point of care quality improvement (QI) approach to implement and sustain KMC in stable low birthweight babies from a baseline of 1.5 hours/baby/day to above 4 hours/baby/day through a series of plan-do-study-act (PDSA) cycles over a period of 53 weeks. METHODS: All babies with birth weight <2000 g not on any respiratory support or phototherapy and or umbilical lines were eligible. The key quantitative outcome was KMC hours/baby/day. A QI collaborative was formed between six centres of Karnataka mentored by a team with a previous QI experience on KMC. The potential barriers for extended KMC were evaluated using fishbone analysis. Baseline data were collected over 3 weeks. A bundled approach consisting of a variety of parent centric measures (such as staff awareness, making KMC an integral part of treatment order, foster KMC, awareness sessions to parents weekly, recognising KMC champions) was employed in multiple PDSA cycles. The data were aggregated biweekly and the teams shared their implementation experiences monthly. RESULTS: A total of 1443 parent-baby dyads were enrolled. The majority barriers were similar across the centres. Bundled approach incorporating foster KMC helped in the quick implementation of KMC even in outborns. Parental involvement and empowering nurses helped in sustaining KMC. Two centres had KMC rates above 10 hours/baby/day, while remaining four centres had KMC rates sustained above 6 hours/baby/day. Cross-learnings from team meetings helped to sustain efforts. Extended KMC could be implemented and sustained by low intensity training and QI collaboration. CONCLUSIONS: Formation of a QI collaborative with mentoring helped in scaling implementation of extended KMC. Extended KMC could be implemented by parent centric best practices in all the centres without any additional need of resources.

Probiotic effect in preterm neonates with sepsis - A systematic review protocol.

Background: The microbiota in the intestine is made up of trillions of living bacteria that coexist with the host. Administration of antibiotics during neonatal infection causes depletion of gut flora resulting in gut dysbiosis. Over the last few decades, probiotics have been created and promoted as microbiota management agents to enrich gut flora. Probiotics decrease the overgrowth of pathogenic bacteria in the gut of preterm neonates, reducing the frequency of nosocomial infections in the Neonatal Intensive Care Unit (NICUs). Methods: The systematic review will include randomized control trials (RCTs) of premier neonates with sepsis. Studies will be retrieved from global databases like Cochrane CENTRAL, CINAHL Plus via EBSCO host, MEDLINE via PubMed, EMBASE, SCOPUS, Ovid, Web of Science, ProQuest Medical Library, Microsoft academic, and DOAJ by utilizing database-specific keywords. Screening, data extraction, and critical appraisal of included research will be carried out separately by two review writers. Findings will be reported in accordance with the PRISMS-P 2020 guidelines. Conclusions: The findings of this systematic review will help to translate the evidence-based information needed to encourage the implementation of potential research output in the field of neonatal intensive care, guide best clinical practise, assist policy making and implementation to prevent gut dysbiosis in neonates with sepsis by summarising and communicating the evidence on the topic. PROSPERO registration number: This systematic review protocol has been registered in PROSPERO (Prospective Register of Systematic Reviews) on 10 th March 2022. The registration number is CRD42022315980.

Cause of Death in Neonates With Neurological Insults in the Neonatal Intensive Care Unit: Insights From A MITS Pilot Study.

BACKGROUND: Minimally invasive tissue sampling (MITS) of organs has been used as an alternative to complete diagnostic autopsy in countries where refusal for autopsy in newborns is common for sociocultural reasons. There is a paucity of literature regarding the diagnostic utility of MITS of the brain after death in neonates with neurological insults, especially in India. METHODS: This was a prospective, preliminary single-center tertiary care hospital study in India, focused specifically on MITS of the brain after neonatal death as a diagnostic tool to identify the various neurological insults. All neonatal deaths with neurological symptoms occurring within the first 30 days of life were enrolled, irrespective of the suspected clinical diagnosis. RESULTS: Sixteen neonates were enrolled after death for MITS of the brain, performed for diagnostic purposes, during the study period from February 2020 to March 2021. Their gestational ages ranged from 26 to 38 weeks. All neonates had either a history of seizures and/or respiratory distress or clinical evidence of sepsis and were on ventilator support. Histopathology in all 16 neonates showed evidence of anoxia, with or without reactive astrogliosis or microgliosis. In 5 neonates with cranial ultrasound evidence of brain hemorrhage, MITS of the brain showed intraventricular hemorrhage, subdural hemorrhage, or intraparenchymal white matter microhemorrhages. Premortem blood culture-proven sepsis was seen in 9 neonates. In all cases (100%), MITS had a good diagnostic yield and was useful to establish the neurological insult in the brain. CONCLUSIONS: MITS of the brain provides an accurate and adequate diagnosis and can be an alternative to complete diagnostic autopsy for establishing the cause of death due to neurological insults, especially in low-resource settings where obtaining consent for more invasive procedure is often challenging.

Vitamin D Levels in Neonates With and Without Seizures: A Single Center Cross-Sectional Study.

OBJECTIVE: To study the serum vitamin D levels in neonatal seizures and vitamin D status of the mothers whose babies had vitamin D deficiency. METHODS: For this cross-sectional study, vitamin D levels were studied in term and late preterm neonates admitted to NICU with seizures at our tertiary care center. Controls were term and late preterm healthy neonates admitted in the postnatal ward with the mothers in the same center. RESULTS: 30 cases and 30 controls were enrolled. The mean (SD) serum vitamin D was 19.33 (7.76) ng/mL among cases and 16.83 (6.74) ng/mL among controls (P=0.18). We tested maternal vitamin D levels in babies with seizures and low vitamin D levels. The mean (SD) serum vitamin D level among these mothers (n=11) was 13.25 (6.17) ng/mL. CONCLUSIONS: There was no statistically significant association between serum vitamin D levels and seizures among neonates in our study.

Acute hemodynamic effects of methylxanthine therapy in preterm neonates: Effect of variations in subgroups.

BACKGROUND: Methylxanthines have cardiac stimulant effects. The current study aimed to compare acute hemodynamic changes between caffeine and aminophylline in ≤34 weeks' preterm neonates. METHODS: The study was performed using information on echocardiography measurements from preterm neonates recruited for apnea of prematurity (75 of 240) and preventing extubation failure (113 of 156) studies. The neonates were randomized either to the caffeine or aminophylline groups. Neonates with no maintenance followed by loading doses with both the methylxanthines (caffeine and aminophylline) and incomplete echocardiography examination were excluded. RESULTS: Cardiac parameters were found to be similar between groups. The heart rate was higher among the aminophylline-treated neonates (p < 0.001) than among the caffeine-treated ones. End-systolic volume was higher among both caffeine- (p < 0.001) and aminophylline-treated neonates (p = 0.001) when compared with pretreatment values. End-diastolic volume was statistically higher in both groups' neonates (p = 0.01). The odds of increase in cardiac output was higher; however, increase in ejection fraction was less in caffeine-treated small-for-gestation-age neonates. CONCLUSION: Caffeine has similar effects on cardiac parameters as aminophylline; however, caffeine-treated small-for-gestation stratification gave rise to significant cardiac variations.

Development and Validation of Educational Leaflet for Caregivers of Preterm Infants.

INTRODUCTION: Facilitation of child development is usually emphasized in the form of early intervention classes and practical demonstrations. However, non-adherence to home program for such interventions has been reported due to various reasons. AIM: To develop and validate an educational leaflet as a supplement guide for caregivers to promote better development of their child during 4-6 months of age. MATERIALS AND METHODS: An in-depth literature review and focus group discussion with the experts was conducted to formulate the content of leaflet. Initial framework consisted of introduction, main text with pictorial representation and instructions about facilitation of various milestones, do's-don'ts and disclaimer. Validation was done through a questionnaire consisting of 9 questions pertaining to completeness, understandability, legibility, clarity and utility of educational material for caregivers and a section for comments. Leaflet with enclosed questionnaire was distributed to 14 validators (2 neonatologists, 4 paediatricians and 8 physiotherapists), along with a covering letter stating the purpose and relevance of this educational material, and the importance of their participation in validation process. Scoring was done on 5 point Likert scale for each item in the material. RESULTS: Responses from the 14 evaluators were collected and analysed. Item level content validity index (I-CVI) was calculated for individual items which ranged from 0.73 - 1. Scale level Content Validity Index (S-CVI) was calculated for complete nine items and it was found to be 0.91. Validators expressed their views to include a column on normal milestones across 4-6 months of age and also to highlight the significance of performing each activity mentioned in the leaflet. These suggestions were incorporated in consensus with the subject experts and the final draft was made. CONCLUSION: Educational leaflet for caregivers of 4-6 months preterm infants has been developed and validated. It can be provided as a supplement guide to the caregivers to facilitate better development of their child.

Feasibility and Safety of Therapeutic Hypothermia and Short Term Outcome in Neonates with Hypoxic Ischemic Encephalopathy.

Therapeutic hypothermia is well known for neuroprotection in asphyxiated neonates with hypoxic ischemic encephalopathy. The authors aimed to study the feasibility and safety of therapeutic hypothermia and short term outcome in neonates with hypoxic ischemic encephalopathy (HIE). Total 31 neonates with moderate to severe HIE were enrolled in the study. Continuous temperature recording was noted in 31 neonates; 17 neonates were studied prospectively while 14 neonates were studied retrospectively. Rectal temperature was monitored in 31 neonates and maintained between 33 and 34 °C by switching off the warmer and using ice packs. Reusable ice packs were used which were inexpensive. Therapeutic hypothermia was maintained for 72 h and babies were then rewarmed 0.5 °C every hour. Therapeutic hypothermia was feasible and inexpensive. There was no major complication during the study. MRI was done in 17 neonates; 52 % were found to have normal MRI at the end of first week. Among the study neonates (n = 31) 64.5 % were neurologically normal at the time of discharge. To conclude, therapeutic hypothermia is feasible in a low resource setting and is a safe way of neuroprotection. Short term outcome was also favourable in these neonates.

Neonatal meningitis and sepsis by Chryseobacterium indologenes: a rare and resistant bacterium.

Early neonatal meningitis with non-fermenting Gram negative bacilli (NFGNB) is rare, and whenever it occurrs, inanimate environment is usually implicated as the source. The authors report a case of neonatal meningitis and sepsis with Chryseobacterium indologenes, a rare non fermenting Gram negative bacterium with unusual antimicrobial susceptibility. Despite resistance to all the beta lactams, carbapenems and aminoglycosides, therapy with ciprofloxacin led to a favorable outcome.

Analysis of prenatal and postnatal risk factors of retinopathy of prematurity in a tertiary care hospital in South India.

CONTEXT: Recent advances in neonatology have influenced the incidence and severity of ROP in a dichotomous fashion. AIMS: To determine the incidence of ROP and to analyse its risk factors. SETTINGS AND DESIGN: Prospective clinical case series. MATERIALS AND METHODS: 282 preterm infants with birthweight < 1500 g and/or gestational age ≤ 32 weeks and also those with gestational age > 32 weeks, with birthweight between 1500-2000 g, who were at risk for ROP were selected. Weight gain proportion was measured as weight at 6 weeks minus birthweight divided by birthweight. STATISTICAL ANALYSIS: Univariate and multivariate logistic regression. RESULTS: Incidence of any ROP was 21.6% while severe ROP was 6.7%. Prenatal factors like multiple gestation (P = 0.510) and antenatal steroids (P = 0.104) were not significantly associated with ROP. On multivariate analysis, postnatal factors like weight at birth < 1250 g (P = 0.01) and gestational age between 31-32 weeks (P = 0.02) were independent risk factors for any ROP, while intraventricular hemorrhage (P = 0.03) was the only independent risk factor for severe ROP. Mean birthweight of infants with severe ROP was 1056 µ 207 g (P = 0.004), which was significantly low. After logistic regression, the mean weight gain proportion at 6 weeks, of those neonates with severe ROP was 30%. CONCLUSIONS: Low birthweight and prematurity were the most important risk factors for developing any ROP, while intraventricular hemorrhage was the independent risk factor for developing severe ROP. The mean postnatal weight gain at 6 weeks was not statistically significant in neonates with severe ROP.