Key Points• GATA1 mutations are common in neonates with Down syndrome but are often unsuspected and detectable only with sensitive methods.• Multilineage blood abnormalities in all Down syndrome neonates in the absence of GATA1 mutations suggests that trisomy 21 itself perturbs hemopoiesis.Transient abnormal myelopoiesis (TAM), a preleukemic disorder unique to neonates with Down syndrome (DS), may transform to childhood acute myeloid leukemia (ML-DS). Acquired GATA1 mutations are present in both TAM and ML-DS. Current definitions of TAM specify neither the percentage of blasts nor the role of GATA1 mutation analysis.To define TAM, we prospectively analyzed clinical findings, blood counts and smears, and GATA1 mutation status in 200 DS neonates. All DS neonates had multiple blood count and smear abnormalities. Surprisingly, 195 of 200 (97.5%) had circulating blasts. GATA1 mutations were detected by Sanger sequencing/denaturing high performance liquid chromatography (Ss/DHPLC) in 17 of 200 (8.5%), all with blasts >10%. Furthermore lowabundance GATA1 mutant clones were detected by targeted next-generation resequencing (NGS) in 18 of 88 (20.4%; sensitivity ∼0.3%) DS neonates without Ss/DHPLC-detectable GATA1 mutations. No clinical or hematologic features distinguished these 18 neonates. We suggest the term "silent TAM" for neonates with DS with GATA1 mutations detectable only by NGS. To identify all babies at risk of ML-DS, we suggest GATA1 mutation and blood count and smear analyses should be performed in DS neonates. Ss/DPHLC can be used for initial screening, but where GATA1 mutations are undetectable by Ss/DHPLC, NGS-based methods can identify neonates with small GATA1 mutant clones. (Blood. 2013;122(24):3908-3917)

The incidence of bacterial meningitis in young infants remains unchanged since the 1980s and is associated with significant case fatality. Prevention strategies and guidelines to improve the early management of cases should be prioritized.

ABSTRACTGroup BStreptococcus(GBS) is a leading cause of neonatal meningitis and septicemia. The ability of this organism to survive inside phagocytic cells is poorly understood but thought to be an important step for the establishment of disease in the host. Here, we demonstrate that GBS shows prolonged survival within J774 macrophages and that the capacity to survive is not significantly changed across a diverse range of strains representing different serotypes, multilocus sequence types (MLST), and sites of clinical isolation. Using staining for the lysosome-associated membrane protein (LAMP) and by pharmacological inhibition of phagosome acidification, we demonstrate that streptococci reside in a phagosome and that acidification of the phagosome is required for GBS to survive intracellularly. Moreover, we show that the GBS two-component system CovS/CovR, which is the major acid response regulator in this organism, is required for survival inside the phagosome.

Rates of invasive fungal infection are highest among neonates, especially those of low birthweight. This study aimed to describe the current epidemiology of invasive neonatal fungal infections in a UK neonatal infection surveillance network. From 2004 to 2010 prospective multicentre surveillance was conducted by 14 neonatal units using a web-based database. Clinicians then completed a standardized pro forma for each positive fungal blood and/or cerebrospinal fluid culture. The overall incidence was 2.4/1000 neonatal unit admissions and was highest among babies <1000 g (extreme low birthweight, 18.8/1000). Only five infants (6%) were >1500 g. The majority of infections were caused by Candida albicans (59; 69%) and Candida parapsilosis (17; 20%); 33% of infants had received antifungal prophylaxis. Known risk factors (use of central venous catheter, parenteral nutrition, previous antibiotic use) were common among cases. The attributable case fatality rate was 21% (18/84). Extreme low birthweight infants remain at highest risk of invasive fungal infection and prophylaxis should be particularly considered for this group. The number needing to receive prophylaxis to prevent one case varies significantly among units, hence unit-specific decisions are required. Further research is still needed into the optimal empiric and therapeutic strategies.

De novo guidance on the management of Gram-negative bacteria outbreaks in UK neonatal units was developed in 2012 by a Department of Health, England Antimicrobial Resistance and Healthcare Associated Infection working group. The recommendations included activation of an organisational response and establishing a control team when an outbreak is suspected; screening for the specific organism only during an outbreak; undertaking multidisciplinary reviews of cleaning routines, hand hygiene and Gram-negative bacteria transmission risks; considering deep-cleaning; cohorting colonised and infected babies preferably but not necessarily in isolation cubicles; and considering reducing beds or closing a unit to new admissions as a way of improving spacing and staff:patient ratios until the outbreak is under control. The group advised establishing mechanisms to communicate effectively across the network; informing parents of the outbreak as early as possible, and providing prewritten 'infection outbreak' information sheets. For prevention of outbreaks, the group advised meeting national staffing and cot-spacing requirements; following a Water Action Plan; using infection reduction care bundles and benchmarking; and introducing breast milk early and limiting antibiotic use.