Early-onset group B streptococcal infections in five Nordic countries with different prevention policies, 1995 to 2019.

BackgroundNeonatal early-onset disease caused by group B Streptococcus (GBS) is a leading cause of infant morbidity. Intrapartum antibiotic prophylaxis (IAP) is effective in preventing early-onset GBS disease, but there is no agreement on the optimal strategy for identifying the pregnant women requiring this treatment, and both risk-based prophylaxis (RBP) and GBS screening-based prophylaxis (SBP) are used.AimThe aim of this study was to evaluate the effect of SBP as a public health intervention on the epidemiology of early-onset GBS infections.MethodsIn 2012, Finland started the universal SBP, while Denmark, Iceland, Norway and Sweden continued with RBP. We conducted an interrupted time series analysis taking 2012 as the intervention point to evaluate the impact of this intervention. The incidences of early- and late-onset GBS infections during Period I (1995-2011) and Period II (2012-2019) were collected from each national register, covering 6,605,564 live births.ResultsIn Finland, a reduction of 58% in the incidence of early-onset GBS disease, corresponding to an incidence rate ratio (IRR) of 0.42 (95% CI: 0.34-0.52), was observed after 2012. At the same time, the pooled IRR of other Nordic countries was 0.89 (95% CI: 0.80-1.0), specifically 0.89 (95% CI: 0.70-1.5) in Denmark, 0.34 (95% CI: 0.15-0.81) in Iceland, 0.72 (95% CI: 0.59-0.88) in Norway and 0.97 (95% CI: 0.85-1.1) in Sweden.ConclusionsIn this ecological study of five Nordic countries, early-onset GBS infections were approximately halved following introduction of the SBP approach as compared with RBP.

Adequate immune responses to vaccines after chemotherapy for leukaemia diagnosed in childhood.

AIM: The survival rate after treatment for childhood leukaemia has greatly improved, but could result in protracted immune deficiency. This study examined the immune status of children after chemotherapy and evaluated their responses to immunisation. METHODS: Subjects who had completed their treatment for acute lymphoblastic leukaemia at The Children's Hospital Reykjavík, Iceland, during 2011-2020 had blood drawn and were then immunised for influenza in October 2021. Blood was drawn again 4 weeks later and their humoral and cellular responses were measured with a haemagglutination inhibition assay and lymphocyte stimulation test. Antibodies to other immunisations were also evaluated. RESULTS: We studied 18 patients (10 male) who had completed their treatment at 3.7-20.3 years of age (mean 9.1), 11-84 months (mean 36.9) before enrolment. Conventional immunological evaluation did not reveal notable abnormalities. The responses to several childhood vaccinations, including the pneumococcal conjugate vaccination, were adequate in most patients. Humoral responses to the influenza vaccine confirmed adequate reactions in all but one patient. Considerable variations were observed in the lymphocyte stimulations tests. CONCLUSION: Most patients reacted adequately to immunisation, especially against annual influenza and Streptococcus pneumoniae, reiterating the usefulness of vaccinations. The most appropriate timing for vaccination after treatment still needs to be determined.

Decreasing death rates and causes of death in Icelandic children-A longitudinal analysis.

BACKGROUND: Global death rate in children has been declining during the last decades worldwide, especially in high income countries. This has been attributed to several factors, including improved prenatal and perinatal care, immunisations, infection management as well as progress in diagnosis and treatment of most diseases. However, there is certainly room for further progress. The aim of the current study was to describe the changes in death rates and causes of death in Iceland, a high-income country during almost half a century. METHODS: The Causes of Death Register at The Directorate of Health was used to identify all children under the age of 18 years in Iceland that died during the study period from January 1st, 1971 until December 31st, 2018. Using Icelandic national identification numbers, individuals could be identified for further information. Hospital records, laboratory results and post-mortem diagnosis could be accessed if cause of death was unclear. FINDINGS: Results showed a distinct decrease in death rates in children during the study period that was continuous over the whole period. This was established for almost all causes of death and in all age groups. This reduction was primarily attributed to a decrease in fatal accidents and fewer deaths due to infections, perinatal or congenital disease as well as malignancies, the reduction in death rates from other causes was less distinct. Childhood suicide rates remained constant. INTERPRETATION: Our results are encouraging for further prevention of childhood deaths. In addition, our results emphasise the need to improve measures to detect and treat mental and behavioural disorders leading to childhood suicide.

HSCT in two brothers with CGD arising from mutations in CYBC1 corrects the defect in neutrophil function.

Homozygous mutations in cytochrome b-245 chaperone 1 (CYBC1) have been recently described as causing recurrent infections and inflammatory disease in an Icelandic cohort and a patient from Saudi Arabia, by destabilising the dimerisation of gp91phox with p22phox, manifesting as phenotypic chronic granulomatous disease (CGD). Haematopoietic stem cell transplantation is the treatment of choice in CGD, though experience of transplantation in this subtype of CGD is limited to a brief description in one patient. We provide clinical and transplant data for two Icelandic brothers with CGD due to homozygous p.Tyr2Ter mutations in CYBC1, demonstrating maintained cure of the immune defect 11 years post-transplant in one brother, and death in the peri-transplant period for the other.

Children may need higher vancomycin doses to achieve therapeutic levels.

AIM: Vancomycin is frequently used in paediatric hospitals. Data suggest trough levels of 10-20 mg/L are needed to achieve bacterial killing. This study aimed to evaluate if commonly used dosing regimens are efficient in reaching these levels and if therapeutic drug monitoring (TDM) was appropriately used. METHODS: All children receiving intravenous vancomycin at the Children´s Hospital Iceland between 2012 and 2016 were included. Vancomycin trough levels were registered. Student t test, Wilcoxon test and regression models were used for statistical analysis. RESULTS: A total of 105 children received 163 vancomycin treatments (55/105 neonates). Average daily dose in neonates was 23.4 mg/kg/day and 38.4 mg/kg/day for older children. No TDM was done in 58 treatments (35.6%). First trough levels were <10mg/L in 52.4% and <15mg/L in 92% of cases. Therapeutic levels were less likely achieved in children with malignancy (11.8%) compared with others (36.8%, p = 0.09). CONCLUSIONS: In more than half of the cases, trough drug levels were <10 mg/L and malignancy was associated with the lowest probability of reaching therapeutic levels. This study suggests that starting doses of vancomycin in children should be higher, especially in relation to malignant diseases and supports the importance of antibiotic stewardship to ensure optimal antibiotic use.

Low Risk of Central Line-associated Bloodstream Infections in Pediatric Hematology/Oncology Patients.

BACKGROUND: Central venous lines (CVLs) are essential for standard care of pediatric hematology/oncology patients providing safe administration of cytotoxic drugs and pain-free blood sampling. Central line-associated bloodstream infections (CLABSIs) cause significant morbidity. This study describes the epidemiology, microbiology, and risk factors for CLABSI in all children with malignancies in Iceland. METHODS: All children that were diagnosed with malignancy in Iceland and received a CVL during 2008-2017 were included in the study. Characteristics of CVLs and patients were registered, information on risk factors, and microbiology was collected. International standards were used for CLABSI definition. RESULTS: One hundred forty-three CVLs were placed in 94 children. Acute lymphoblastic leukemia was the most common underlying disease (31/94). Median age was 7 years. Implantable ports were the most commonly placed CVLs (82/143, 57%), tunneled lines were 39 (27%). Overall CLABSI rate was 0.24 infections/1000 line-days (14 episodes in 58,830 line-days), with little fluctuations. No CLABSI episodes occurred for 4 consecutive years (2012-2015). Staphylococci (of which 7 Staphylococcus aureus) were the cause of 10/14 episodes. Nine CLABSI episodes led to line removal, but no deaths were linked to CLABSIs. CONCLUSION: We report very low CLABSI rates over a 9-year period at our hospital, with 4 consecutive CLABSI-free years. Even with the addition of episodes of possible CLABSI, rates were still very low and lower than most published reports.

Hematopoietic Stem Cell Transplantation Resolves the Immune Deficit Associated with STAT3-Dominant-Negative Hyper-IgE Syndrome.

Autosomal dominant hyper-IgE syndrome caused by dominant-negative loss-of-function mutations in signal transducer and activator of transcription factor 3 (STAT3) (STAT3-HIES) is a rare primary immunodeficiency with multisystem pathology. The quality of life in patients with STAT3-HIES is determined by not only the progressive, life-limiting pulmonary disease, but also significant skin disease including recurrent infections and abscesses requiring surgery. Our early report indicated that hematopoietic stem cell transplantation might not be effective in patients with STAT3-HIES, although a few subsequent reports have reported successful outcomes. We update on progress of our patient now with over 18 years of follow-up and report on an additional seven cases, all of whom have survived despite demonstrating significant disease-related pathology prior to transplant. We conclude that effective cure of the immunological aspects of the disease and stabilization of even severe lung involvement may be achieved by allogeneic hematopoietic stem cell transplantation. Recurrent skin infections and abscesses may be abolished. Donor TH17 cells may produce comparable levels of IL17A to healthy controls. The future challenge will be to determine which patients should best be offered this treatment and at what point in their disease history.

A homozygous loss-of-function mutation leading to CYBC1 deficiency causes chronic granulomatous disease.

Mutations in genes encoding subunits of the phagocyte NADPH oxidase complex are recognized to cause chronic granulomatous disease (CGD), a severe primary immunodeficiency. Here we describe how deficiency of CYBC1, a previously uncharacterized protein in humans (C17orf62), leads to reduced expression of NADPH oxidase's main subunit (gp91phox) and results in CGD. Analyzing two brothers diagnosed with CGD we identify a homozygous loss-of-function mutation, p.Tyr2Ter, in CYBC1. Imputation of p.Tyr2Ter into 155K chip-genotyped Icelanders reveals six additional homozygotes, all with signs of CGD, manifesting as colitis, rare infections, or a severely impaired PMA-induced neutrophil oxidative burst. Homozygosity for p.Tyr2Ter consequently associates with inflammatory bowel disease (IBD) in Iceland (P = 8.3 × 10-8; OR = 67.6), as well as reduced height (P = 3.3 × 10-4; -8.5 cm). Overall, we find that CYBC1 deficiency results in CGD characterized by colitis and a distinct profile of infections indicative of macrophage dysfunction.

Ataxia-telangiectasia: Immunodeficiency and survival.

Ataxia-telangiectasia (AT) is a neurodegenerative disorder characterized by ataxia, telangiectasia, and immunodeficiency. An increased risk of malignancies and respiratory diseases dramatically reduce life expectancy. To better counsel families, develop individual follow-up programs, and select patients for therapeutic trials, more knowledge is needed on factors influencing survival. This retrospective cohort study of 61 AT patients shows that classical AT patients had a shorter survival than variant patients (HR 5.9, 95%CI 2.0-17.7), especially once a malignancy was diagnosed (HR 2.5, 95%CI 1.1-5.5, compared to classical AT patients without malignancy). Patients with the hyper IgM phenotype with hypogammaglobulinemia (AT-HIGM) and patients with an IgG2 deficiency showed decreased survival compared to patients with normal IgG (HR 9.2, 95%CI 3.2-26.5) and patients with normal IgG2 levels (HR 7.8, 95%CI 1.7-36.2), respectively. If high risk treatment trials will become available for AT, those patients with factors indicating the poorest prognosis might be considered for inclusion first.

Nationwide Incidence of Acquired Central Nervous System Demyelination in Icelandic Children.

INTRODUCTION: Recognizing acquired demyelinating syndromes and multiple sclerosis is important to commence early treatment. The objective of this study was to describe the incidence of acquired demyelinating syndromes and multiple sclerosis among the entire Icelandic pediatric population according to recently promoted criteria. PATIENTS AND METHODS: The study included all children in Iceland (<18 years) with acquired demyelinating syndromes and multiple sclerosis from 1990 to 2009 with a minimum of 5-year follow-up. Clinical data were gathered and radiological images reviewed. The cohort included all patients with acquired demyelinating syndromes and multiple sclerosis in the Icelandic pediatric population. RESULTS: Eighteen patients with acquired demyelinating syndromes and multiple sclerosis were included, the total annual incidence being 1.15/100,000 (acquired demyelinating syndromes 1.02 and multiple sclerosis 0.45/100,000). The median age at diagnosis was 14.25 years (range 1.25-17.5 years). Thirteen patients were initially diagnosed with clinically isolated syndrome, two had acute disseminated encephalomyelitis, two had multiple sclerosis, and one had neuromyelitis optica. Seven children were diagnosed with multiple sclerosis; three patients with clinically isolated syndrome developed multiple sclerosis after the age of 18 and were not included in the multiple sclerosis group. The gender ratio was equal. Of the nine girls, seven were diagnosed with clinically isolated syndrome. Most patients (11 of 18) were diagnosed during the period January through March. Oligoclonal bands in cerebrospinal fluid were exclusively found in patients with multiple sclerosis and clinically isolated syndrome and 13 of 14 available magnetic resonance images revealed clear abnormalities. CONCLUSION: The annual incidence of acquired demyelinating syndromes and multiple sclerosis in Iceland was 1.15/100,000 children. The risk of progression from clinically isolated syndrome to multiple sclerosis was high. There was no female preponderance.

Loss-of-function variants in ATM confer risk of gastric cancer.

Gastric cancer is a serious health problem worldwide, with particularly high prevalence in eastern Asia. Genome-wide association studies (GWAS) in Asian populations have identified several loci that associate with gastric cancer risk. Here we report a GWAS of gastric cancer in a European population, using information on 2,500 population-based gastric cancer cases and 205,652 controls. We found a new gastric cancer association with loss-of-function mutations in ATM (gene test, P = 8.0 × 10(-12); odds ratio (OR) = 4.74). The combination of the loss-of-function variants p.Gln852*, p.Ser644* and p.Tyr103* (combined minor allele frequency (MAF) = 0.3%) also associates with pancreatic and prostate cancers (OR = 3.81 and 2.18, respectively) and gives an indication of risk of breast and colorectal cancers (OR = 1.82 and 1.97, respectively). Cancers in those carrying loss-of-function ATM mutations are diagnosed at a significantly earlier age than in non-carriers. Our results confirm an association between gastric cancer in Europeans and three loci previously reported in Asians, MUC1, PRKAA1 and PSCA, refine the association signal at PRKAA1 and support a pathogenic role for the tandem repeat identified in MUC1.

Antibody deficiency in patients with ataxia telangiectasia is caused by disturbed B- and T-cell homeostasis and reduced immune repertoire diversity.

BACKGROUND: Ataxia telangiectasia (AT) is a multisystem DNA-repair disorder caused by mutations in the ataxia telangiectasia mutated (ATM) gene. Patients with AT have reduced B- and T-cell numbers and a highly variable immunodeficiency. ATM is important for V(D)J recombination and immunoglobulin class-switch recombination (CSR); however, little is known about the mechanisms resulting in antibody deficiency severity. OBJECTIVE: We sought to examine the immunologic mechanisms responsible for antibody deficiency heterogeneity in patients with AT. METHODS: In this study we included patients with classical AT plus early-onset hypogammaglobulinemia (n = 3), classical AT (n = 8), and variant AT (late onset, n = 4). We studied peripheral B- and T-cell subsets, B-cell subset replication history, somatic hypermutation frequencies, CSR patterns, B-cell repertoire, and ATM kinase activity. RESULTS: Patients with classical AT lacked ATM kinase activity, whereas patients with variant AT showed residual function. Most patients had disturbed naive B-cell and T-cell homeostasis, as evidenced by low cell numbers, increased proliferation, a large proportion CD21(low)CD38(low) anergic B cells, and decreased antigen receptor repertoire diversity. Impaired formation of T cell-dependent memory B cells was predominantly found in patients with AT plus hypogammaglobulinemia. These patients had extremely low naive CD4(+) T-cell counts, which were more severely reduced compared with those seen in patients with classical AT without hypogammaglobulinemia. Finally, AT deficiency resulted in defective CSR to distal constant regions that might reflect an impaired ability of B cells to undergo multiple germinal center reactions. CONCLUSION: The severity of the antibody deficiency in patients with AT correlates with disturbances in B- and T-cell homeostasis resulting in reduced immune repertoire diversity, which consequently affects the chance of successful antigen-dependent cognate B-T interaction.

[Survival and causes of death in children diagnosed with cancer in Iceland 1981-2006]. / Lifun og dánarorsakir barna sem greindust með krabbamein á Íslandi 1981-2006.

OBJECTIVE: Of children diagnosed with cancer, approximately one fourth die of the disease or disease related complications. The aim of this study was to investigate survival and causes of death in children with cancer in Iceland. METHODS: This study is retrospective; population based and includes all children, less than 18 years of age, diagnosed with cancer in Iceland from 1981 to 2006. Information was extracted from the Icelandic Cancer Registry, patients hospital records and data from Statistics Iceland. RESULTS: Of 279 children diagnosed with cancer in the research period 215 were alive at the end of 2008. The overall 5-year survival was 81.2% and 10-year survival was 76.7%. There was not a significant survival difference with respect to age at diagnosis, year of diagnosis, gender or geographical residence. The small cohort size could be the explanation. Eleven individuals developed secondary neoplasm, eight of whom died. Sixteen of the 64 nonsurvivors were treated with curative intent until death, 12 of them died of therapy related complications. CONCLUSIONS: Survival rate in childhood cancer in Iceland is comparable to other Western countries. As previously reported, prognosis of patients with secondary neoplasm is unfavorable. Therapy related complications are the most common cause of death in patients treated with curative intent.

[Childhood cancer in Iceland 1981-2006]. / Krabbamein hjá börnum á lslandi árin 1981-2006.

BACKGROUND: Childhood cancer is the second most common cause of death in children. The aim of this study was to gather epidemiological information on childhood cancer in Iceland. METHODS: The study was population based and included all children younger than 18 years of age, diagnosed with cancer in Iceland from 1981 to 2006. Information was extracted from the Icelandic Cancer Registry and patient hospital records. RESULTS: During the study period 288 cancer cases were diagnosed in 279 children, 10 cases were secondary neoplasms. Age standardized incidence was 16.1 per 100.000 (95% CI 13,6-18,6) for boys and 12.8 per 100.000 (95% CI 10,5-15,0) for girls. There was no significant difference in the incidence rate between the first and second half of the study period. For children aged 0-14 years, the age standardized incidence was 13.6 per 100.000. The incidence was highest in the 0-4 year age group (17.3 per 100.000) and in the 15-17 year age group (19.6 per 100.000). Brain tumors (27.1%) and leukemia (25.0%) were the most common cancer groups diagnosed. Lymphoid leukemia was the most common cancer type (17.9%) and astrocytoma (13.1%) came second. CONCLUSIONS: The incidence of childhood cancer in Iceland is similar to other Western countries. Long-term follow-up is very important in childhood cancer survivors.

Suspected infections in children treated for ALL.

AIM: The aim of our study was to get epidemiological information on bacterial infections in children treated for ALL and to analyse which patients have an enhanced infection risk. METHODS: Episodes of suspected or confirmed infections were evaluated during the first 12 months of treatment for childhood acute lymphoblastic leukaemia (ALL). RESULTS: The number of patients was 73 (43 boys). The median age was 4.6 years. A total of 179 episodes occurred, varying from none in six patients to eight in one. Bacteria were cultured in 57 episodes (31.8%), the most common being coagulase-negative staphylococci. The number of episodes fell significantly with increasing age for suspected and confirmed infections (p < 0.001 and p = 0.03). The proportion of confirmed infections was significantly higher (p < 0.001) in the first episodes. The average number of suspected infections was higher in girls than in boys (p = 0.03), but confirmed infections were not. CONCLUSION: Most of the serious infections occur early in the treatment and the number of suspected and confirmed infections falls with age. Suspicion of infection is more likely in girls, but the number of confirmed infections is equal in both sexes. Coagulase-negative staphylococcus was most commonly isolated, highlighting the importance of careful handling of central venous devices.

[Appendicitis and appendectomy in children in Reykjavik Hospitals in 1996 and 2006]. / Botnlangabólga og botnlangataka hjá börnum á sjúkrahúsum í Reykjavík 1996 og 2006.

INTRODUCTION: Appendicitis is a common disease and can be life-threatening if not adequately treated. Studies have shown that if less than 20% of appendices removed are normal it indicates missing or delaying the diagnosis of appendicitis, resulting in an increased incidence of perforation. The purpose of this study was to analyze appendicitis in children during two separate time periods in the pediatric wards of the hospitals in Reykjavík and to increase our knowledge of appendicitis in children in the country. MATERIALS AND METHODS: Patients entering this study are two groups of 100 children (< or =16 years) consecutively undergoing appendectomy in the Reykjavik hospitals, one group in 1996 and the other in 2006. Data on sex, age, clinical symptoms and treatment was obtained from patients records. The impression of the surgeon at time of operation on the inflammation of the removed appendix was compared with results of histopathology analysis. All histopathology slides from appendices from 2006 were re-evaluated. The parameters in open appendectomies were compared to those in laparoscopic appendectomies. The two study periods were compared. RESULTS: The proportion of normal appendices was similar in both periods of the study, 18% in 2006 and 20% in 1996. The appendices were more often normal in female patients (p<0.05) and the large majority of those were removed by laparoscopic surgery. Perforation was present in 17% of inflamed appendices in both study groups. The time from patients arrival to hospital until surgery surpassed 10 hours in only one case in each study group. A discrepancy between the surgeon's assessment and the pathology result was noted only once in 2006 and in one additional case was the histopathological diagnosis altered following re-evaluation of the pathology slides. DISCUSSION: The proportion of non-inflamed appendices in appendectomies in children in Reykjavik is in accordance with that reported elsewhere and perforation is not common. There is a good concordance between surgical and pathological assessment with regard to inflammation of the appendices.

High prevalence of allergic diseases and sensitization in a low allergen country.

BACKGROUND: The prevalence of adult atopic diseases in Iceland is lower than in other West European countries, despite an affluent lifestyle, but limited data are available on children. The main aim of this study was to investigate the prevalence of atopic diseases and sensitivity to common allergens in 10- to 11-year-old Icelandic schoolchildren as part of phase II of the International Study of Asthma and Allergies in Children (ISAAC). METHODS: Nine hundred and forty-six children and their parents answered a questionnaire about atopic diseases. Skin prick tests with six allergens were performed on 773 children and they were examined for signs of atopic dermatitis (AD). RESULTS: The 12-month prevalence of allergic rhinoconjunctivitis and asthma was 11.5% and 8.9% respectively. The reported prevalence of AD was 27%, but only 9.2% had signs when inspected. A positive skin prick test (SPT) was found in 24.4% of the children, that is 18.8% to grass, 12.9% to cat, 3.6% to trees, 3.0% to Dermatophagoides pteronyssinus, 1.4% to D. farinae and 0.5% to Alternaria. CONCLUSION: The high prevalence of atopic diseases in children at 10-11 years is surprising, as the prevalence in adults is low in Iceland. The findings resemble those in developing countries. Iceland has had an affluent lifestyle for a considerable time, but the absence of dust mites, low pet ownership and relatively low pollen counts in the country raise doubts about the role of exposure levels in the development of sensitization and atopic diseases.

[Bacteremia in children with tumors or malignant diseases 1991-2000]. / Blódsýkingar barna med aexli og illkynja sjúkdóma 1991-2000.

INTRODUCTION: Ten to twelve children with tumors or malignant diseases are diagnosed annually in Iceland. Cancer treatment can cause severe immune suppression, which makes the patients susceptible to serious infections. The aim of the current study was to evaluate sepsis in children with tumors or haematological malignancies, describe the types of bacteria cultured and their antibiotic susceptibilities, and collect information on associated risk factors. MATERIALS AND METHODS: This was a retrospective study on all children 0-15 years of age in Iceland who were diagnosed with a tumor or malignant disease between 1991 and 2000. Information was gathered on diagnosis, treatment, blood cultures, blood tests, antibiotic use, presence of foreign bodies (such as CVC) and survival. RESULTS: Hundred-and-eighteen children were diagnosed with cancer or benign central nervous system (CNS) tumors in Iceland during the period 1991-2000. Central nervous system tumors were most common (N=28, 23.7%), leukemia (N=21, 17.8%) and lymphoma (N=17, 14%) were the second and third. The mean age at diagnosis was 5.9 years. Sufficient data was found in the hospital records on 99 children who were included in the study. Five hundred and twenty two blood cultures were drawn from 51 of the 99 children during the period. The mean number of blood cultures per patient was 14.8 for children with leukemia, but 2.6 for children with solid tumors. Of all blood cultures, 63.6% were from a central venous catheter or a Port-A Catheter , 5% from a peripheral site, but 30% were undisclosed. Of the 522 blood cultures, 90 grew bacteria (17.2%). Coagulase-negative staphylococci were isolated from 53 blood cultures (60%) and Staphylococcus aureus from 12 (13%). Positive cultures were regarded as a definite or possible infection in 47 blood cultures (52%), contamination in 17 (18.9% ), but uncertain in 26 (27.7%). Over 60 percent of the blood cultures (N=302) were drawn when a child was neutropenic (ANC < or =1.0 *109/L). The mean length of neutropenic episodes was 9.0 days. The mean CRP level was 63.9 mg/L. The mean temperature was 38.8 degrees C. In 138 instances the child was receiving antibiotics at the time of culture (35.1%). Children with positive blood cultures had similar clinical and laboratory tests results as children with negative cultures. CONCLUSION: Gram-positive bacteria, especially coagulase-negative staphylococci, are much more common in children undergoing cancer therapy than Gram-negative bacteria. Results of blood tests appear to have low predictive values for blood culture results. No child died of a proven bacterial sepsis during the study period. Empiric antibiotic treatment at the Children s Hospital Iceland for children with malignant diseases is still effective.

The effects of smoking in pregnancy on factors influencing fetal growth.

AIM: To evaluate the influence of maternal smoking during pregnancy on factors influencing fetal growth. METHODS: Thirty newborns of smoking mothers were prospectively compared with 60 newborns of non-smoking mothers. Pre-albumin, albumin, triglycerides, glucose, insulin, insulin-like growth factor I, IGF binding protein 3, pH, lactic acid, erythropoietin and hemoglobin concentrations were measured in umbilical cord blood. RESULTS: Infants of smoking mothers had a significantly lower birth weight (3418 +/- 533 vs. 3863 +/- 503 g; p < 0.001), length (50.5 +/- 2,6 vs. 52.3 +/- 1.9 cm; p < 0.001) and head circumference (34.6 +/- 1.8 vs. 35.8 +/- 1.1 cm; p < 0.001) than controls. They also had significantly lower insulin (3.2 (2.0-4.9) vs. 5.8 (4.6-7.1) mU/L; p = 0.008), insulin-like growth factor I (54.4 +/- 32.5 vs. 93.8 +/- 54.5 microg/L; p = 0.001) and IGF binding protein 3 (1664 +/- 432 vs. 1943 +/- 421 microg/L; p = 0.01) concentrations, than controls. Infants of smoking mothers also had significantly higher hemoglobin (167 +/- 14 vs. 157 +/- 13 g/L; p = 0.002) and erythropoietin (42.3 (25.1-72.4) vs. 26.3 (21.9-30.9) U/L; p = 0.03) than controls, but not pH or lactate concentrations. There was no significant difference in pre-albumin, albumin, triglycerides and glucose concentrations. CONCLUSIONS: Smoking during pregnancy causes symmetrical fetal growth impairment, possibly due to decreased oxygen transport to the fetus and decreased concentrations of fetal insulin, insulin-like growth factor I and IGF binding protein 3.

The effect of dietary fish oil on survival after infection with Klebsiella pneumoniae or Streptococcus pneumoniae.

Dietary fish oil is believed to have a beneficial effect in various infections and in autoimmune disorders. This effect may correspond to an altered immune response. In order to discover whether the effect of dietary fish oil is different in various infections, we studied the survival of mice fed fish oil or corn oil supplemented diets and infected in the lungs with either Klebsiella pneumoniae or Streptococcus pneumoniae. 120 NMRI mice were divided into 4 groups, of which 2 groups were fed a fish oil supplemented diet and 2 a corn oil supplemented diet. After 6 weeks the mice were infected in the lungs with Klebsiella pneumoniae (fish oil groups and corn oil groups) or with Streptococcus pneumoniae serotype 3 (both groups). The survival rate was monitored. The experiment was performed twice. The survival of the mice fed fish oil enriched diet and infected with Klebsiella pneumoniae was significantly better compared with the mice fed corn oil enriched diet (p = 0.0001 and p = 0.0013). No difference was found between the mice fed corn oil enriched diet or fish oil enriched diet and infected with Streptococcus pneumoniae serotype 3 (p = 0.74 and p = 0.15). Our results indicate that dietary fish oil has a beneficial effect on survival of mice after experimental pneumoniae when infected with Klebsiella pneumoniae, but not after infection with Streptococcus pneumoniae serotype 3.