Prevalence of Invasive Bacterial Infection in Hypothermic Young Infants: A Multisite Study.

OBJECTIVE: To determine the prevalence of bacteremia and meningitis (invasive bacterial infection [IBI]) in hypothermic young infants, and also to determine the prevalence of serious bacterial infections (SBI) and neonatal herpes simplex virus and to identify characteristics associated with IBI. STUDY DESIGN: We conducted a retrospective cohort study of infants ≤90 days of age who presented to 1 of 9 hospitals with historical or documented hypothermia (temperature ≤36.0°C) from September 1, 2017, to May 5, 2021. Infants were identified by billing codes or electronic medical record search of hypothermic temperatures. All charts were manually reviewed. Infants with hypothermia during birth hospitalization, and febrile infants were excluded. IBI was defined as positive blood culture and/or cerebrospinal fluid culture treated as a pathogenic organism, whereas SBI also included urinary tract infection. We used multivariable mixed-effects logistic regression to identify associations between exposure variables and IBI. RESULTS: Overall, 1098 young infants met the inclusion criteria. IBI prevalence was 2.1% (95% CI, 1.3-2.9) (bacteremia 1.8%; bacterial meningitis 0.5%). SBI prevalence was 4.4% (95% CI, 3.2-5.6), and neonatal herpes simplex virus prevalence was 1.3% (95% CI, 0.6-1.9). Significant associations were found between IBI and repeated temperature instability (OR, 4.9; 95% CI, 1.3-18.1), white blood cell count abnormalities (OR, 4.8; 95% CI, 1.8-13.1), and thrombocytopenia (OR, 5.0; 95% CI, 1.4-17.0). CONCLUSIONS: IBI prevalence in hypothermic young infants is 2.1%. Further understanding of characteristics associated with IBI can guide the development decision tools for management of hypothermic young infants.

Variation in Care of Well-Appearing Hypothermic Young Infants: A Multisite Study.

BACKGROUND AND OBJECTIVES: Numerous decision tools have emerged to guide management of febrile infants, but limited data exist to guide the care of young infants presenting with hypothermia. We evaluated the variation in care for well-appearing hypothermic young infants in the hospital and/or emergency department setting between participating sites. METHODS: This is a retrospective cohort study of well-appearing infants ≤90 days old across 9 academic medical centers from September 1, 2016 to May 5, 2021. Infants were identified via billing codes for hypothermia or an initial temperature ≤36.0°C with manual chart review performed. Primary outcomes included assessment of variation in diagnostic evaluation, disposition, empirical antimicrobial therapy, and length of stay. RESULTS: Of 14 278 infants originally identified, 739 met inclusion criteria. Significant interhospital variation occurred across all primary outcomes. Across sites, a full serious bacterial illness evaluation was done in 12% to 76% of hypothermic infants. Empirical antibiotics were administered 20% to 87% of the time. Performance of herpes simplex viral testing ranged from 7% to 84%, and acyclovir was empirically started 8% to 82% of the time. Hospital admission rates ranged from 45% to 100% of patients. CONCLUSIONS: Considerable variation across multiple aspects of care exists for well-appearing young infants presenting with hypothermia. An improved understanding of hypothermic young infants and their risk of infection can lead to the development of clinical decision tools to guide appropriate evaluation and management.

Identification of the bruton tyrosine kinase (BTK) gene mutations in 20 Australian families with X-linked agammaglobulinemia (XLA).

X-linked agammaglobulinemia (XLA) is an immunodeficiency caused by mutations in the Bruton tyrosine kinase (BTK) gene. Twenty Australian patients with an XLA phenotype, from 15 unrelated families, were found to have 14 mutations. Five of the mutations were previously described c.83G>A (p.R28H), c.862C>T (p.R288W), c.904G>A (p.R302G), c.1535T>C (p.L512P), c.700C>T (p.Q234X), while nine novel mutations were identified: four missense c.82C>A (p.R28S), c.494G>A (p.C165Y), c.464G>A (p.C155Y), c.1750G>A (p.G584E), one deletion c.142_144delAGAAGA (p.R48_G50del), and four splice site mutations c.241-2A>G, c.839+4A>G, c.1350-2A>G, c.1566+1G>A. Carrier analysis was performed in 10 mothers and 11 female relatives. The results of this study further support the notion that molecular genetic testing represents an important tool for definitive and early diagnosis of XLA and may allow accurate carrier status and prenatal diagnosis.

Identification of WASP mutations in 10 Australian families with Wiskott-Aldrich syndrome and X-linked thrombocytopenia.

UNLABELLED: Mutations of the gene encoding the Wiskott-Aldrich syndrome protein (WASP) have been previously shown to be responsible for classical Wiskott-Aldrich syndrome (WAS), isolated X-linked thrombocytopenia (XLT) and severe congenital X-linked neutropenia. AIMS: Identification of WASP mutations in 10 unrelated Australian families presenting with clinical features of WAS/XLT. METHODS: Mutation analysis was performed by PCR and sequence analysis. RESULTS AND CONCLUSIONS: Two novel mutations and seven mutations which have previously been reported were identified. The novel mutations consisted of a missense mutation in exon 2 (C290A) associated with the phenotype of XLT and a mutation in intron 10 (1372+1G>A) in the mother of two boys presenting with a classical WAS phenotype.