Frank Brus

Local Interferon‐γ Levels during Respiratory Syncytial Virus Lower Respiratory Tract Infection Are Associated with Disease Severity

To investigate the role of cell-mediated immunity during respiratory syncytial virus (RSV) infection, interferon (IFN)-gamma and interleukin (IL)-10 levels in nasopharyngeal secretions were measured in infants with lower respiratory tract infection (LRTI) caused by RSV. A novel technique was used to measure in vivo cytokine levels in nasopharyngeal aspirates (NPAs). Cytokine levels in the NPAs of 17 mechanically ventilated infants and 43 nonventilated hospitalized infants were compared. As expected, mechanically ventilated infants were significantly younger than nonventilated infants (7 vs. 14 weeks). IFN-gamma levels were above the limit of detection in the NPAs of 3 (18%) mechanically ventilated infants and in the NPAs of 26 (60%) nonventilated infants. IL-10 levels in the NPAs of mechanically ventilated and nonventilated infants were comparable. It is hypothesized that maturation-related mechanisms have a key role in the development of RSV LRTI that results in mechanical ventilation.

Seasonality of long term wheezing following respiratory syncytial virus lower respiratory tract infection

Background: It is well known that respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) is associated with subsequent wheezing episodes, but the precise natural course of wheezing following RSV LRTI is not known. This study aimed to determine the continuous development of wheezing following RSV LRTI in children up to the age of 3 years. Methods: A prospective cohort study was performed in 140 hospitalised infants with RSV LRTI. Continuous follow up data were obtained with a unique log in which parents noted daily respiratory symptoms. Results: A marked decrease in wheezing was seen during the first year of follow up. The burden of wheezing following RSV LRTI was observed during the winter season. Signs of airflow limitation during RSV LRTI were strongly associated with wheezing during the follow up period. Total and specific serum immunoglobulin E levels, patient eczema, and parental history of atopy were not associated with wheezing. Conclusions: Airway morbidity following RSV LRTI has a seasonal pattern, which suggests that viral upper respiratory tract infections are the predominant trigger for wheezing following RSV LRTI. There is a significant decrease in airway symptoms during the first 12 months after admission to hospital. Simple clinical variables, but not allergic risk factors, can predict the development of wheezing following RSV LRTI.

Iron intake and status of children aged 6-36 months in Europe: a systematic review.

Background: Iron deficiency is the most common nutritional disorder in the world. Young children are particularly vulnerable to the consequences of iron deficiency because of their rapidly developing brain. This review evaluates the prevalence of inadequate iron intake and iron deficiency (anaemia) in European children aged 6-36 months. Summary: Computerized searches for relevant articles were performed in November 2013. A total of 7,297 citations were screened and 44 studies conducted in 19 European countries were included in this review. In both infants (6-12 months) and young children (12-36 months), the mean value of iron intakes in most countries was close to the RDA. Nevertheless, proportions of inadequate intakes were considerable, ranging from about 10% in the Netherlands up to 50% in Austria, Finland and the United Kingdom. The prevalence of iron deficiency varied between studies and was influenced by childrens characteristics. Two to 25% of infants aged 6-12 months were found to be iron deficient, with a higher prevalence in those who were socially vulnerable and those who were drinking cows milk as a main type of drink in their first year of life. In children aged 12-36 months, prevalence rates of iron deficiency varied between 3 and 48%. Prevalence of iron deficiency anaemia in both age groups was high in Eastern Europe, as high as 50%, whereas the prevalence in Western Europe was generally below 5%. Key Messages: In most European countries, mean iron intakes of infants and children aged 6 to 36 months were found to be close to the RDA. Nevertheless, high proportions of inadequate intakes and high prevalence rates of iron deficiency were observed. Health programs should (keep) focus(ing) on iron malnutrition by educating parents on food choices for their children with iron-rich and iron-fortified foods, and encourage iron supplementation programmes where iron intakes are the lowest.

The validity of biochemical markers in metabolic bone disease in preterm infants: a systematic review

To establish the validity of biochemical markers of metabolic bone disease (MBD) in preterm infants.

Airflow limitation during respiratory syncytial virus lower respiratory tract infection predicts recurrent wheezing.

BACKGROUND Respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) is frequently followed by recurrent wheezing. Thus far no clinical risk factors have been identified to predict which infants will have wheezing episodes subsequent to RSV LRTI. OBJECTIVE To determine clinical predictors for airway morbidity after RSV LRTI. METHODS In a 1-year follow-up study we investigated the predictive value of auscultatory findings characteristic of airflow limitation (wheezing) during RSV LRTI for subsequent airway morbidity. Clinical characteristics, including the presence or absence of signs of airflow limitation, of hospitalized infants with RSV LRTI were prospectively recorded during 2 winter epidemics. During a 1-year follow-up period parents of 130 infants recorded daily airway symptoms. OUTCOME MEASURE Recurrent wheezing defined as > or = 2 episodes of wheezing. RESULTS Signs of airflow limitation during RSV LRTI were absent in 47 (36%) infants and present in 83 (64%) infants. Recurrent wheezing was recorded in 10 (21%) infants without signs of airflow limitation and in 51 (61%) with signs of airflow limitation during initial RSV LRTI (relative risk, 0.29, P < 0.001). In a multiple logistic regression model, airflow limitation during initial RSV LRTI proved independent from other clinical parameters, including age, parental history of asthma and smoke exposure. CONCLUSIONS A sign of airflow limitation during RSV LRTI is the first useful clinical predictor for subsequent recurrent wheezing.

Prevalence and risk factors of iron deficiency in healthy young children in the southwestern Netherlands.

Objectives: Iron deficiency (ID) and iron deficiency anemia (IDA), during the first years of life, are associated with delayed motor and neurological development. Many studies evaluated iron status without an assessment of an acute-phase protein to identify infection. Because most indicators of iron status are influenced by infection, these data may underestimate the ID prevalence. A food consumption survey in the Netherlands showed that the mean iron intake of children ages 2 to 3 years was below the advised adequate intake of 7 mg/day. The aim of the study was to investigate iron status in a well-defined, healthy population of young children in the southwestern region of the Netherlands and to identify risk factors for ID. Methods: We conducted a multicenter, observational study in healthy children ages 0.5 to 3 years. We defined ID as ferritin <12 &mgr;g/L and IDA when, in addition, hemoglobin was <110 g/L. Children with elevated C-reactive protein levels (>5 mg/L) or underlying causes for anemia were excluded. Parents filled in a questionnaire to identify risk factors for ID. Results: We included 400 children in the study. ID and IDA were detected in 18.8% and 8.5% of the children, respectively. The present use of formula and the visit of preschool/day care were associated with a lower prevalence of ID, and a high intake of cows milk was associated with a higher prevalence of ID, after adjustment for age. Conclusions: ID is present in 18.8% of healthy children ages 0.5 to 3 years and living in the southwestern region of the Netherlands. The present visit of preschool/day care and the use of formula are associated with a reduced risk of ID, whereas a high intake of cows milk is associated with an increased risk of ID.

Iron and Vitamin D Deficiency in Healthy Young Children in Western Europe Despite Current Nutritional Recommendations.

Background and aim: Iron deficiency (ID) and vitamin D deficiency (VDD) are the 2 most common micronutrient deficiencies in young children worldwide and may lead to impaired neurodevelopment and rickets, respectively. Risk factors for ID and VDD differ between populations. The objective of this study was to determine the prevalence of and risk factors for ID and VDD in 12- to 36-month-old children in Western Europe. Methods: This study took place in Germany, the Netherlands, and the United Kingdom from 2012 to 2014. A venous blood sample was taken to establish iron and vitamin D status. ID was defined as serum ferritin <12 &mgr;g/L in the absence of infection (high sensitivity C-reactive protein <10 mg/L). VDD was defined as serum 25-hydroxyvitamin D <50 nmol/L (20 ng/mL). Furthermore, parents were asked to fill out a questionnaire regarding their childs demographic- and socioeconomic characteristics, food intake, sun exposure, and medical history. Results: In 325 children (white race 95%, boys 56%, mean age 20.7 months) the overall prevalence of ID and VDD was 11.8% and 22.8%, respectively. The use of primarily cows milk as major type of milk was associated with ID (odds ratio [OR] 3.20, 95% confidence interval [CI] 1.12–8.53) and VDD (OR 7.17, 95% CI 3.10–16.57). The use of vitamin D supplements (OR 0.20, 95% CI 0.07–0.56) was associated with a lower prevalence of VDD. Conclusion: Despite current nutritional recommendations, ID and VDD are common in healthy young white children. Health programs focusing on adequate iron and vitamin D intake at an early age should be implemented to prevent deficiencies.

Iron deficiency occurs frequently in children with cystic fibrosis

In adult CF patients iron deficiency (ID) is common and primarily functional due to chronic inflammation. No recent data are available on the cause of ID and iron deficiency anemia (IDA) in children with CF. Over the last decades onset of inflammation and pulmonary disease in children with CF is delayed by improved nutritional status. We questioned whether ID occurs in the same extent among children with CF as in adult CF patients. We therefore conducted a study to investigate the iron status of children with CF and to determine whether ID and IDA are associated with dietary iron intake, lung disease severity and Pseudomonas aeruginosa (PA) infection.

Serum hepcidin measured by immunochemical and mass-spectrometric methods and their correlation with iron status indicators in healthy children aged 0.5-3 y.

Background:The diagnostic use of hepcidin is limited by the absence of standardization and lack of age-specific reference ranges in children in particular. The aim of this study was to determine reference ranges of serum hepcidin in healthy children aged 0.5–3 y using mass spectometry (MS) and a commercial immunochemical (IC) assay, and to investigate its association with other indicators of iron status and inflammation.Methods:We included 400 healthy children aged 0.5–3 y. We constructed reference ranges for MS-hepcidin and IC-hepcidin concentrations using the median, P2.5, and P97.5 in a normative population of 219 children with no anemia, no infection and/or inflammation, and no iron deficiency.Results:Median concentrations (P2.5–P97.5) of MS-hepcidin and IC-hepcidin were 3.6 nmol/l (0.6–13.9 nmol/l) and 7.9 nmol/l (1.9–28.6 nmol/l), respectively. We found a good correlation between both methods. However, MS-hepcidin was consistently lower than IC-hepcidin. Hepcidin correlated with ferritin and C-reactive protein.Conclusion:We provide reference ranges for hepcidin for an MS and commercial IC method. Absolute values between assays differed significantly, but hepcidin concentrations obtained by MS and IC methods correlate with each other, and both correlate with ferritin and CRP.

A micronutrient-fortified young-child formula improves the iron and vitamin D status of healthy young European children: a randomized, double-blind controlled trial

BACKGROUND Iron deficiency (ID) and vitamin D deficiency (VDD) are common among young European children because of low dietary intakes and low compliance to vitamin D supplementation policies. Milk is a common drink for young European children. Studies evaluating the effect of milk fortification on iron and vitamin D status in these children are scarce. OBJECTIVE We aimed to investigate the effect of a micronutrient-fortified young-child formula (YCF) on the iron and vitamin D status of young European children. DESIGN In this randomized, double-blind controlled trial, healthy German, Dutch, and English children aged 1-3 y were allocated to receive either YCF (1.2 mg Fe/100 mL; 1.7 μg vitamin D/100 mL) or nonfortified cow milk (CM) (0.02 mg Fe/100 mL; no vitamin D) for 20 wk. Blood samples were taken before and after the intervention. The primary and secondary outcomes were change from baseline in serum ferritin (SF) and 25-hydroxyvitamin D [25(OH)D], respectively. ID was defined as SF <12 μg/L in the absence of infection (high-sensitivity C-reactive protein <10 mg/L) and VDD as 25(OH)D <50 nmol/L. Statistical adjustments were made in intention-to-treat analyses for sex, country, age, baseline micronutrient status, and micronutrient intake from food and supplements (and sun exposure in the case of vitamin D outcomes). RESULTS The study sample consisted of 318 predominantly Caucasian (∼95%) children. The difference in the SF and 25(OH)D change between the treatment groups was 6.6 μg/L (95% CI: 1.4, 11.7 μg/L; P = 0.013) and 16.4 nmol/L (95% CI: 9.5, 21.4 nmol/L; P < 0.001), respectively. The probability of ID (OR 0.42; 95% CI:0.18, 0.95; P = 0.036) and VDD (OR 0.22; 95% CI: 0.01, 0.51; P < 0.001) after the intervention was lower in the YCF group than in the CM group. CONCLUSION Micronutrient-fortified YCF use for 20 wk preserves iron status and improves vitamin D status in healthy young children in Western Europe. This trial was registered at www.trialregister.nl as NTR3609.