Clinical and genetic spectrum of 104 Indian families with central nervous system white matter abnormalities.

Genetic disorders with predominant central nervous system white matter abnormalities (CNS WMAs), also called leukodystrophies, are heterogeneous entities. We ascertained 117 individuals with CNS WMAs from 104 unrelated families. Targeted genetic testing was carried out in 16 families and 13 of them received a diagnosis. Chromosomal microarray (CMA) was performed for three families and one received a diagnosis. Mendeliome sequencing was used for testing 11 families and all received a diagnosis. Whole exome sequencing (WES) was performed in 80 families and was diagnostic in 52 (65%). Singleton WES was diagnostic for 50/75 (66.67%) families. Overall, genetic diagnoses were obtained in 77 families (74.03%). Twenty-two of 47 distinct disorders observed in this cohort have not been reported in Indian individuals previously. Notably, disorders of nuclear mitochondrial pathology were most frequent (9 disorders in 20 families). Thirty-seven of 75 (49.33%) disease-causing variants are novel. To sum up, the present cohort describes the phenotypic and genotypic spectrum of genetic disorders with CNS WMAs in our population. It demonstrates WES, especially singleton WES, as an efficient tool in the diagnosis of these heterogeneous entities. It also highlights possible founder events and recurrent disease-causing variants in our population and their implications on the testing strategy.

Chronic diarrhoea due to trichohepatoenteric syndrome (THES) in an infant.

An infant was admitted with suspected postinfectious malabsorption with watery diarrhoea, fever and failure to thrive. She had dehydration, acute kidney injury and metabolic acidosis, which were corrected with intravenous fluids and managed with empiric antibiotics and prophylactic antifungals. She also developed Escherichia coli sepsis, meningitis and Candida skin infections during hospitalisation, which were treated according to the culture reports. Intrauterine growth restriction, woolly hair and a broad nasal bridge with chronic refractory diarrhoea prompted genetic testing to rule out syndromic diarrhoea. Whole-exome sequencing revealed a pathogenic compound heterozygous mutation causing trichohepatoenteric syndrome. She succumbed to severe infections at 80 days of life. The condition is rare, and no established guidelines or specific treatments exist; the focus is to promote optimal growth through parenteral nutrition, elemental formula and infection control. Early suspicion and molecular genetic testing can help reduce the time to diagnosis, treatment and genetic counselling.

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.

Randomized Controlled Trial on the Effect of the Neonatal Nurse Navigator Program on Maternal Stress and Neonatal Cortisol Levels.

OBJECTIVE: To assess the effect of the Neonatal Nurse Navigator Program (NNNP) compared to usual care on maternal stress and neonatal salivary cortisol level (SCL) in the NICU. DESIGN: Randomized control trial. SETTING: NICU in a tertiary health care hospital in Manipal, Udupi District, Karnataka, India. PARTICIPANTS: Neonates between 34 and 36 weeks gestation and their mothers (N = 120 dyads). METHODS: We used block randomization to assign dyads to the intervention or control group. We measured maternal stress using the Parental Stress Scale: Neonatal Intensive Care Unit, and we estimated neonatal stress by measuring SCLs within 24 hours of NICU admission and before discharge from the unit. We conducted a descriptive analysis on participant characteristics and reported maternal stress levels using means and standard deviations. We used the analysis of covariance change score test to determine the difference in maternal and neonatal stress levels between the intervention and control groups. RESULTS: The NNNP group exhibited significantly lower maternal stress scores before discharge than the control group, and we observed reductions across all three subscales of the Parental Stress Scale: Neonatal Intensive Care Unit. Mean neonatal salivary cortisol levels were significantly lower in the interventional group than in the control group, F(1.117) = 24.03, 95% confidence interval [7.9, 18.6], p < .001. CONCLUSION: Use of the NNNP reduced maternal stress SCLs in high-risk neonates by actively engaging mothers in the care of their neonates in the NICU. We recommend adoption of the NNNP model as a standard care policy in NICUs throughout India.

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.

Bacterial isolates of early-onset neonatal sepsis and their antibiotic susceptibility pattern between 1998 and 2004: an audit from a center in India.

BACKGROUND: Epidemiology and surveillance of neonatal sepsis helps in implementation of rational empirical antibiotic strategy. OBJECTIVE: To study the frequency of bacterial isolates of early onset neonatal sepsis (EONS) and their sensitivity pattern. METHODS: In this retrospective study, a case of EONS was defined as an infant who had clinical signs or born to mothers with potential risk factors for infection, in whom blood culture obtained within 72 hours of life, grew a bacterial pathogen. Blood culture sample included a single sample from peripheral vein or artery. Relevant data was obtained from the unit register or neonatal case records. RESULTS: Of 2182 neonates screened, there were 389 (17.8%) positive blood cultures. After excluding coagulase-negative Staphylococci (160), we identified 229 EONS cases. Preterm neonates were 40.6% and small for gestational age, 18.3%. Mean birth weight and male to female ratio were 2344.5 (696.9) g and 1.16:1 respectively. Gram negative species represented 90.8% of culture isolates. Pseudomonas (33.2%) and Klebsiella (31.4%) were common among them. Other pathogens included Acinetobacter (14.4%), Staphylococcus aureus (9.2%), E.coli (4.4%), Enterobacter (2.2%), Citrobacter (3.1%) and Enterococci (2.2%). In Gram negative group, best susceptibility was to Amikacin (74.5%), followed by other aminoglycosides, ciprofloxacin and cefotaxime. The susceptibility was remarkably low to ampicillin (8.4%). Gram positive group had susceptibility of 42.9% to erythromycin, 47.6% to ciprofloxacin and above 50% to aminoglycosides. Of all isolates, 83.8% were susceptible to either cefotaxime or amikacin CONCLUSION: Gram-negative species especially Pseudomonas and Klebsiella were the predominant causative organisms. Initial empirical choice of cefotaxime in combination with amikacin appeared to be rational choice for a given cohort.

Opsismodysplasia.

Opsismodysplasia is a rare osteochondrodysplasia with micromelia and platyspondyly. We report on a neonate with opsismodysplasia. During the antenatal period, polyhydramnios was noted. This is the first report of opsismodysplasia from India. Significant observation was antenatal polyhydramnios.