Gestational alloimmune liver disease treated with exchange transfusion and intravenous immunoglobulin: A case study

Gestational alloimmune liver disease (GALD) is a materno-fetal alloimmune disorder that targets the fetal liver and often causes neonatal liver failure. GALD most commonly presents as neonatal hemochromatosis (NH), which is a severe neonatal liver injury confirmed by extra-hepatic iron accumulation at various sites. With the discovery of the alloimmune mechanism of GALD, exchange transfusion and intravenous immunoglobulin (IVIG) administration are being used as novel treatments. Here, we present a rare case of an 11-day-old female infant who presented with marked hyperbilirubinemia. Laboratory findings showed significantly elevated direct and indirect bilirubin, high ferritin and alpha fetoprotein levels, high transferrin saturation, and severe coagulopathy. Abdominal magnetic resonance imaging revealed markedly reduced T2 signal intensity in the liver and pancreas compared to the spleen, suggesting iron deposition. The infant was diagnosed with NH and successfully treated with exchange transfusion and four doses of IVIG.     

Changing populations being treated with ECMO in the neonatal period – who are the others?

Extracorporeal life support via extracorporeal membrane oxygenation (ECMO) has served the sickest of neonates for almost 50 years. Naturally, the characteristics of neonates receiving ECMO have changed. Advances in care have averted the need for ECMO for some, while complex cases with uncertain outcomes, previously not eligible for ECMO, are now considered. Characterizing the disease states and outcomes for neonates on ECMO is challenging as many infants do not fall into classic categories, i.e. meconium aspiration syndrome (MAS), respiratory distress syndrome (RDS), or congenital diaphragmatic hernia (CDH). Since 2017, over one third of neonatal respiratory ECMO runs reported to the Extracorporeal Life Support Organization Registry are grouped as Other, a catch-all that encompasses those with a diagnosis not included in the classic categories. This review summarizes the historical neonatal ECMO population, reviews advances in therapy and technology impacting neonatal care, and addresses the unknowns in the ever-growing category of Other.     

An unreported case of Streptococcus cristatus septic arthritis of wrist in a neonate

Septic Arthritis of the wrist is rare in the paediatric population due to its extraarticular metaphysis. We report here a case of wrist septic arthritis in a neonate caused by an uncommon causative organism, Streptococcus cristatus.A 15 days old male child was referred with the complaint of swelling and decreased movement of the left wrist for 5 days. Local examination revealed warm, tender, erythematous and fluctuant swelling over the dorso-ulnar aspect of the left wrist. Ultrasonography of the affected region was suggestive of focal fluid collection in the wrist and periosteal elevation of the distal ulna. Aspiration followed by arthrotomy of the wrist joint was performed and multiple holes were made in the distal ulnar metaphysis using 0.8mm k-wire. The pus culture was positive for Streptococcus cristatus, sensitive to vancomycin, which was given for a total of 4 weeks. At one year follow up the child had a full, painless range of motion with no functional deficit. Final follow up x rays of the left wrist were normal.Streptococcus cristatus strains are described as Gram-positive, catalase-negative cocci, approximately 1 μm in diameter growing in chains and were originally isolated from the human throat and oral cavities. Its association with bone and joint infections has not been described in the literature. To our knowledge, this is the first case of isolated septic arthritis of wrist in a 15 days old child caused by Streptococcus cristatus.To conclude, wrist septic arthritis in a neonate is a rare entity. With the advanced diagnostics, species-level identification of rare organism like Streptococcus cristatus is possible along with antibiotic sensitivity for appropriate therapy. Early surgical decompression and intravenous culture-directed antibiotics are the mainstays of management.     

Interleukin-8 dysregulation is implicated in brain dysmaturation following preterm birth

BackgroundPreterm birth is associated with dysconnectivity of structural brain networks, impaired cognition and psychiatric disease. Systemic inflammation contributes to cerebral dysconnectivity, but the immune mediators driving this association are poorly understood. We analysed information from placenta, umbilical cord and neonatal blood, and brain MRI to determine which immune mediators link perinatal systemic inflammation with dysconnectivity of structural brain networks.MethodsParticipants were 102 preterm infants (mean gestational age 29⁺¹ weeks, range 23⁺³-32⁺⁰). Placental histopathology identified reaction patterns indicative of histologic chorioamnionitis (HCA), and a customized immunoassay of 24 inflammation-associated proteins selected to reflect the neonatal innate and adaptive immune response was performed from umbilical cord (n = 55) and postnatal day 5 blood samples (n = 71). Brain MRI scans were acquired at term-equivalent age (41⁺⁰ weeks [range 38⁺⁰-44⁺⁴ weeks]) and alterations in white matter connectivity were inferred from mean diffusivity and neurite density index across the white matter skeleton.ResultsHCA was associated with elevated concentrations of C5a, C9, CRP, IL-1β, IL-6, IL-8 and MCP-1 in cord blood, and IL-8 concentration predicted HCA with an area under the receiver operator curve of 0.917 (95% CI 0.841 – 0.993, p < 0.001). Fourteen analytes explained 66% of the variance in the postnatal profile (BDNF, C3, C5a, C9, CRP, IL-1β, IL-6, IL-8, IL-18, MCP-1, MIP-1β, MMP-9, RANTES and TNF-α). Of these, IL-8 was associated with altered neurite density index across the white matter skeleton after adjustment for gestational age at birth and at scan (β = 0.221, p = 0.037).ConclusionsThese findings suggest that IL-8 dysregulation has a role in linking perinatal systemic inflammation and atypical white matter development in preterm infants.     

A case of congenital herpes simplex virus infection diagnosed at 8 months of age

We present the case of an 8-month-old boy with the repeated recurrence of vesicles from the time of birth and who subsequently manifested psychomotor developmental delay. We retrospectively diagnosed the patient with congenital herpes simplex virus (HSV) infection. Computed tomography showed multiple calcifications in the periventricular white matter and thalami. The bilateral deep white matter showed an abnormally high signal intensity on T2-weighted magnetic resonance imaging. The patient required consecutive, suppressive therapy with valacyclovir to prevent the repeated recurrence of vesicles. This case presented a milder phenotype of congenital HSV infection in comparison to previous reports, and highlights the importance of the careful examination for this disease when neonates present with skin lesions.     

Can we back off using antibiotics in the NICU?

Antibiotics are extensively and inconsistently prescribed in neonatal ICUs, and usage does not correlate with rates of culture positive sepsis. There is mounting data describing the short and long-term adverse effects associated with antibiotic overuse in neonates, including the increased burden of multi-drug resistant organisms. Currently there is considerable variation in antibiotic prescribing practice among neonatologists. Applying the practice of antibiotic stewardship in the NICU is crucial for standardizing antibiotic use and improving outcomes in this population.Several approaches have been proposed to identify neonatal sepsis, with the hope of reducing antibiotic utilization. These strategies all have their limitations, and often include laboratory testing and treatment of well-appearing, non-septic, infants. A conservative “watch and wait” algorithm is suggested as an alternative method for when to initiate antibiotics. This observational approach relies on availability of trained personnel able to examine infants at specified intervals, without delaying antibiotics, should signs of sepsis arise.