Prenatal therapy in transient abnormal myelopoiesis: a systematic review.

OBJECTIVE: To systematically review current evidence regarding prenatal diagnosis and management of transient abnormal myelopoiesis (TAM) in fetuses with trisomy 21. A novel case of GATA1-positive TAM, in which following serial in utero blood transfusion clinical improvement and postnatal remission were observed, is included. SEARCH STRATEGY AND DATA COLLECTION: A systematic search of electronic databases (inception to October 2014) and reference lists, hand-searching of journals and expert contact. All confirmed cases of prenatal TAM were included for analysis. Data on study characteristics, design and quality were obtained. RESULTS: Of 73 potentially relevant citations identified, 22 studies were included, describing 39 fetuses. All studies included comprised single case or small cohort studies; overall quality was 'very low'. Fetal/neonatal outcome was poor; 12 stillbirths (30.8%), 4 neonatal deaths (10.2%) and 7 infant deaths (17.9%). In two cases, the pregnancy was terminated (5.1%). TAM was primarily detected in the third trimester (79.4%), and in 14 a retrospective diagnosis was made postpartum. Ultrasound features indicative of TAM included hepatomegaly±splenomegaly (79.5%), hydrops fetalis (30.8%), pericardial effusion (23.1%) and aberrant liquor volume (15.4%). When performed, liver function tests were abnormal in 91.6% of cases. CONCLUSIONS: Prenatal TAM presents a challenging diagnosis, and prognosis is poor, with consistently high mortality. A low threshold to measure haematological and biochemical markers is advised when clinical features typical of TAM are detected in the context of trisomy 21. Larger prospective studies are warranted to accurately ascertain the role of GATA1 analysis and potential value of prenatal therapy.

Early onset neonatal sepsis: diagnostic dilemmas and practical management.

Early onset neonatal sepsis is persistently associated with poor outcomes, and incites clinical practice based on the fear of missing a treatable infection in a timely fashion. Unnecessary exposure to antibiotics is also hazardous. Diagnostic dilemmas are discussed in this review, and suggestions offered for practical management while awaiting a more rapidly available 'gold standard' test; in an ideal world, this test would be 100% sensitive and 100% specific for the presence of organisms.

A trial of recombinant human granulocyte colony stimulating factor for the treatment of very low birthweight infants with presumed sepsis and neutropenia.

OBJECTIVES: The primary objective was to investigate the safety of recombinant human granulocyte colony stimulating factor (rhG-CSF) for the treatment of very low birthweight infants (VLBW) with sepsis and relative neutropenia, specifically with regard to worsening of respiratory distress and thrombocytopenia and all cause mortality. Secondary objectives were to evaluate duration of ventilation, intensive care, and antibiotic use as markers of efficacy. DESIGN: Neonates (< or = 28 days) in intensive care, with birth weights of 500-1500 g, absolute neutrophil count (ANC) of < or = 5 x 10(9)/l, and clinical evidence of sepsis, were randomly assigned to receive either rhG-CSF (10 microg/kg/day) administered intravenously (n = 13), or placebo (n = 15) for a maximum of 14 days, in addition to standard treatment and antibiotics. All adverse events, oxygenation index, incidence of thrombocytopenia, all cause mortality, duration of ventilation, intensive care and antibiotic treatment, and ANC recovery were compared between the two groups. RESULTS: Adverse events and oxygenation index were not increased by, and thrombocytopenia was not attributable to, treatment with rhG-CSF. At 6 and 12 months postmenstrual age, there were significantly fewer deaths in the group receiving rhG-CSF (1/13 v 7/15; p < or = 0.038). There was a non-significant trend towards a reduction in duration of ventilation, intensive care, and antibiotic use in the rhG-CSF group. There was a significantly more rapid increase in ANC in the rhG-CSF treated babies (p < 0.001). CONCLUSIONS: In a small randomised placebo controlled trial in a highly selected group of neonates, adjuvant treatment with rhG-CSF increased ANC rapidly, and no treatment related adverse events were identified. Mortality at 6 and 12 months postmenstrual age was significantly lower in the treatment group. A large trial investigating efficacy in a similar group of neonates is warranted.

Prevention of respiratory syncytial virus infection with palivizumab.

Respiratory syncytial virus (RSV) infects virtually all children by the age of 2 yrs. Premature infants with chronic lung disease (CLD) are at risk of greater morbidity due to RSV infection. However, these infants represent a small proportion of all infants admitted to hospital with RSV infection, and hospitalization rates for this group appear to have decreased over the past decade. Prophylaxis against RSV infection has recently become available in the form of palivizumab, a humanized monoclonal antibody preparation. The IMpact trial demonstrated a 39% relative risk reduction in hospital admissions for RSV in cases in which palivizumab was administered to premature infants with CLD. However, palivizumab is a very expensive drug and cost-effectiveness analyses do not support its use in the majority of premature infants with or without CLD. The only group in which palivizumab should even be considered for use is premature infants with chronic lung disease at home on oxygen during their first respiratory syncytial virus season. In this group of infants, a detailed postlicensing audit needs to be performed to determine efficacy.

Engaging children and parents in service design and delivery.

The involvement of all user groups, including children, young people (CYP) and their parents, encourages people to take responsibility for healthier lifestyle behaviours, improves treatment compliance and leads to more appropriate use of healthcare resources. Initiatives to engage CYP in the UK are gathering momentum, but significant improvements are still needed. There is a national drive from the department of health (DH) and NHS England, strategic clinical networks, operational delivery networks (including newborn networks), charities, parent groups and a number of other bodies to embed CYP involvement in service design and delivery. User engagement and patient choice, is underpinned by the NHS outcomes framework, and a myriad of other DH and NHS England policies and practice frameworks. It is now everybody's business.

Could peripartum antibiotics have delayed health consequences for the infant?

Antibiotics are increasingly prescribed in the peripartum period, for both maternal and fetal indications. Their effective use undoubtedly reduces the incidence of specific invasive infections in the newborn, such as group B streptococcal septicaemia. However, the total burden of infectious neonatal disease may not be reduced, particularly if broad-spectrum agents are used, as the pattern of infections has been shown to alter to allow dominance of previously uncommon organisms. This area has been relatively understudied, and there are almost no studies of long-term outcome. Recent findings suggest that such long-term data should be sought. First, there is evidence that organisms initially colonising the gut at birth may establish chronic persistence in many children, in contrast to prompt clearance if first encountered in later infancy, childhood or adulthood. Second, there is a rapidly advancing basic scientific data showing that individual members of the gut flora specifically induce gene activation within the host, modulating mucosal and systemic immune function and having an additional impact on metabolic programming. We thus review the published data on the impact of perinatal antibiotic regimens upon composition of the flora and later health outcomes in young children and summarise the recent scientific findings on the potential importance of gut flora composition on immune tolerance and metabolism.

New modalities for treating neonatal infection.

While the overall incidence of infection has remained constant at approximately 7/1000 livebirths, the last decade has witnessed a reduction in early onset infections and a relative increase in nosocomial sepsis, chiefly with coagulase-negative staphylococci. Immaturity of host defence mechanisms contributes to an increasing susceptibility to infection with decreasing gestational age and birth weight. In the past, efforts to enhance host defence have included the use of granulocyte infusions, fresh frozen plasma, exchange blood transfusions and immunoglobulin therapy. Current trials are investigating the use of agents which enhance endogenous defence mechanisms, such as, recombinant human granulocyte colony-stimulating factant and recombinant human granulocyte-macrophage colony-stimulating factor and of pentoxifylline. In the meantime strict attention to handwashing and aseptic technique remain the best methods of preventing nosocomial sepsis.

Hospitalisation for RSV infection in ex-preterm infants-implications for use of RSV immune globulin.

BACKGROUND: Respiratory syncytial virus (RSV) specific immune globulin is now being marketed for prevention of RSV infection in ex-preterm infants. However, there are no published UK data on the morbidity or mortality from RSV in these infants. AIMS: To determine the morbidity and mortality from RSV infection in a cohort of infants previously treated at a regional neonatal unit, and compare the cost of hospitalisation for RSV with the potential cost of administering RSV immune globulin (RSV-IG) prophylaxis. METHODS: Infants born at a gestation of less than 32 weeks were studied. Details of admissions for respiratory illness in the first two years of life were collected from hospital records, referring hospitals, and general practitioners. RESULTS: Data on 82 infants were collected. Up to three RSV seasons were encountered. The hospitalisation rate for confirmed RSV infection for the first season encountered was 4%. Rates of ward and paediatric intensive care unit admission were higher for infants with chronic lung disease. There were no deaths from RSV. RSV-IG would not have been cost effective for most infants. CONCLUSION: The morbidity and mortality rates from RSV observed in this group do not support the widespread introduction of RSV-IG prophylaxis for ex-preterm infants.

The development of anti-HLA antibodies in multiply transfused preterm infants.

The development of antihuman leucocyte antigen antibodies (aHLAA) in response to multiple transfusions in preterm infants was studied prospectively. Fifty seven infants requiring a minimum of two blood transfusions were recruited after obtaining informed written parental consent. They were randomised to receive either whole blood or blood that had been passed through a leucocyte filter. Anti-HLAA were sought in maternal and cord blood so as to ensure that any aHLAA detected after transfusion had not been passively transferred antenatally, and in 1 ml samples drawn monthly from the baby, at least 10 days from a previous transfusion, until discharge from hospital. Anti-HLAA were detected by microlymphocytotoxicity assay. Results were obtained in 42 babies, 19 in the filter and 23 in the no filter group. Fifteen babies had to be excluded because of protocol violation or because they died. None of the babies receiving filtered blood developed aHLAA, but seven babies in the no filter group developed aHLAA. In conclusion, multiply transfused preterm infants have the ability to elaborate antibodies to HLA and leucocyte filters may prevent this.

Accidental ingestion of 'Ecstasy' (3,4-methylenedioxymethylamphetamine).

There is no report of the effects of 'Ecstasy' (3,4-methylenedioxymethylamphetamine) poisoning in childhood. The case of a 13 month old boy who ingested one capsule of Ecstasy is reported. Neurological and cardiovascular side effects predominated, which responded well to treatment with a chlormethiazole infusion.

The in vitro effects of granulocyte and granulocyte-macrophage colony-stimulating factor on interleukin-3-dependent proliferation of human neonatal circulating progenitor cells.

Recombinant human granulocyte (rhG) colony-stimulating factor (CSF) and recombinant human granulocyte-macrophage (rhGM) CSF have been used to enhance neonatal neutrophil host defense. We aimed to determine the comparative efficacy of rhG-CSF and rhGM-CSF in increasing numbers of granulocyte colony-forming unit (CFU-G) and granulocyte-macrophage colony-forming unit (CFU-GM) in recombinant human (rh) IL-3-dependent cultures of human neonatal circulating hematopoietic progenitor cells, including cells from infants born to hypertensive mothers. We also investigated the relationship between fractional increase in CFU-G and endogenous plasma concentration of G-CSF. Circulating mononuclear cells were harvested from 25 neonates, and standard short-term assays in semisolid agar were established in the presence of rhIL-3 alone, rhIL-3 with rhG-CSF and rhGM-CSF, and both rhG-CSF and rhGM-CSF. CFU-G and CFU-GM were counted on d 14. Total colony number and CFU-G were significantly greater in cultures supplemented with rhG-CSF, with or without rhGM-CSF (p < 0.001 and p < 0.0005 for total colony number and CFU-G, respectively), when compared with cultures with rhIL-3 alone. Progenitor cells from three infants born to hypertensive mothers responded similarly. Total colony numbers and CFU-G were not increased by rhGM-CSF alone or by addition of rhGM-CSF to rhG-CSF; however, the proportions of CFU-GM were (p < 0.05 and p < 0.001, respectively, compared with rhIL-3 alone).(ABSTRACT TRUNCATED AT 250 WORDS)