Prediction of post-hemorrhagic ventricular dilatation trajectory using a growth mixture model in preterm infants.

BACKGROUND: Early intervention for post-hemorrhagic ventricular dilatation (PHVD), guided by ventricular size measurements from cranial ultrasound (cUS), is associated with improved neurodevelopmental outcomes in preterm infants but benefits must be balanced against intervention risks. METHODS: Anterior horn width (AHW) and ventricular index (VI) were measured from cUS for preterm infants (<29 weeks) with intraventricular hemorrhage admitted from 2010-2018. PHVD was defined as AHW > 6 mm or VI >97th percentile for postmenstrual age. Individual ventricular size trajectories were plotted, and a growth mixture model (GMM) used to identify latent trajectory classes and compare these to predetermined outcome of neurosurgical intervention. RESULTS: Measurements were obtained from 1543 cUS in 249 infants, of whom 39 had PHVD without and 17 PHVD with neurosurgical intervention based on signs of raised intracranial pressure. The GMM predicted trajectory identified: 93.3% of infants without PHVD, 88.2% and 30.8% of infants with PHVD with and without intervention using AHW; 100% of infants without PHVD, 52.9% and 59.0% of infants with PHVD with and without intervention using VI. CONCLUSIONS: The AHW GMM identified a significant proportion of infants with severe PHVD. Model refinement offers a promising approach for identifying differences in PHVD trajectory at an early stage to guide management. IMPACT: It is difficult to distinguish the trajectory of PHVD in the early stage of development, in particular PHVD that spontaneously arrests from slowly progressive PHVD which eventually requires intervention. We report the first modeling-based evaluation of PHVD trajectory for the prediction of short-term outcome of PHVD progression and neurosurgical intervention. With additional clinical validation and optimization to increase accuracy, predictive modeling has the potential to identify important differences in PHVD trajectory at an early stage in the clinical course, allowing for more individualized data-driven risk-benefit assessments to guide decisions on early intervention.

Risk of gentamicin toxicity in neonates treated for possible severe bacterial infection in low- and middle-income countries: Systematic Review.

OBJECTIVES: To assess the risk of gentamicin toxicity and potential number of neonates exposed annually to this risk, through treatment with WHO-recommended first-line antibiotics (gentamicin with penicillin) for the 6.9 million neonates with possible serious bacterial infection (PSBI). METHODS: Systematic literature review and assessment of the evidence using Cochrane and GRADE criteria. Meta-analysis was undertaken for pooled estimates where appropriate. RESULTS: Eleven studies (946 neonates) were included (nine randomised controlled trials and two prospective cohort studies). Six trials reported consistently measured ototoxicity outcomes in neonates treated with gentamicin, and the pooled estimate for hearing loss was 3% (95% CI 0-7%). Nephrotoxicity could not be assessed due to variation in case definitions used. Estimates of the number of neonates potentially affected by gentamicin toxicity were not undertaken due to insufficient data. CONCLUSION: Given wider scale-up of outpatient-based and lower-level treatment of PSBI, improved data are essential to better assess the risks from neonatal gentamicin treatment without assessment of blood levels, to maximise benefit and reduce harm.

Joubert's syndrome and related disorders and home-based peritoneal dialysis in East Africa: a case report.

BACKGROUND: Joubert's syndrome is a rare condition affecting an estimated 1:80,000-1:100,000 individuals. There is underdevelopment of the cerebellar vermis resulting in a characteristic molar tooth sign on cross sectional axial magnetic resonance imaging. It can occur in association with multi-organ involvement; in such cases it is classified as Joubert's syndrome and related disorders. To date, there are no cases of Joubert's syndrome and related disorders from sub-Saharan Africa described in the literature. CASE PRESENTATION: An 8 year old black Kenyan female child was diagnosed in Joubert's syndrome in her first year of life. She was noted to have dysmorphic facies and hypotonia in the neonatal period and cranial MRI showed dysplasia of the cerebellar vermis and typical molar tooth malformation. She was subsequently lost to follow up for several years and later presented with anaemia. Further investigation revealed bilateral multicystic kidneys and significant renal impairment consistent with a diagnosis of end stage renal failure and polycystic kidney disease. She underwent home peritoneal dialysis for 7 months. CONCLUSIONS: Joubert's syndrome and related disorders is a rare condition. This case report demonstrates that home peritoneal dialysis is feasible in a low resource setting. Although it is scarcely provided in African countries, it is an effective renal replacement strategy for patients with end stage renal disease.