Safety of mRNA-based COVID-19 vaccination in paediatric patients with a PEG-asparaginase allergy.

Background: Children treated for a malignancy are at risk to develop serious illness from a COVID-19 infection. Pegylated E. coli asparaginase (PEG-asparaginase) is used in the treatment of acute lymphoblastic leukemia. Allergy to this drug is common and both asparaginase and polyethylene glycol (PEG) are identified as possible antigens. The mRNA-based vaccines against COVID-19 contain PEG as a stabilizing component. Methods: We developed a protocol to be able to safely vaccinate children with a PEG-asparaginase allergy. All patients with a history of allergy to PEG-asparaginase have been included and skin prick testing for various PEGs was performed before vaccination with the mRNA Pfizer-BioNTech COVID-19 vaccine. Results: Twelve children between six and 16 years old were vaccinated, without allergic reaction. None of them got a positive skin prick test for PEG. Ten patients had pre-existing IgG or IgM antibodies against PEG. Conclusion: Children with a PEG-asparaginase allergy can be safely vaccinated against COVID-19 with mRNA vaccines containing PEG irrespective of IgG/IgM antibodies to PEG-asparaginase. Routine skin prick testing in patients with PEG-asparaginase allergy does not seem to be of added value.

Vitamin A intake and serum retinol levels in children and adolescents with cystic fibrosis.

BACKGROUND: Pancreatic insufficient cystic fibrosis (CF) patients receive vitamin A supplementation according to CF-specific recommendations to prevent deficiencies. Whether current recommendations are optimal for preventing both deficiency and toxicity is a subject of debate. We assessed the longitudinal relation between serum retinol levels and appropriate variables. METHODS: We studied vitamin A intake, and the long-term effects of vitamin A intake, coefficient of fat absorption (CFA) and immunoglobulin G (IgG) on serum retinol levels in 221 paediatrics CF patients during a seven-year follow up period. RESULTS: Total vitamin A intake, derived from 862 dietary assessments, exceeded the tolerable upper intake level in 30% of the assessments, mainly up to age six. Although CF patients failed to meet the CF-specific recommendations, serum retinol deficiency was found in only 17/862 (2%) of the measurements. Longitudinally, we observed no association to serum retinol levels for total vitamin A intake, CFA, gender or age but serum retinol levels were associated with serum IgG levels. Each g/L increase in serum IgG level would result in a 2.49% (95% CI -3.60 to -1.36%) reduction in serum retinol levels. CONCLUSION: In this large sample of children and adolescents with CF, serum retinol deficiency was rare despite lower than the CF-specific recommendations. However, the TUL was commonly exceeded. A reduction in CF-specific vitamin A supplementation recommendations should therefore be considered. Moreover, serum retinol levels were not associated with vitamin A intake, CFA, gender or age, although a decreased serum retinol was associated with an increased serum IgG.

Vitamin E intake, α-tocopherol levels and pulmonary function in children and adolescents with cystic fibrosis.

Pancreatic insufficiency cystic fibrosis (CF) patients receive vitamin E supplementation according to CF-specific recommendations in order to prevent deficiencies. It has been suggested that higher serum α-tocopherol levels could have protective effects on pulmonary function (PF) in patients with CF. Whether current recommendations are indeed optimal for preventing deficiency and whether vitamin E has therapeutic benefits are subjects of debate. Therefore, we studied vitamin E intake as well as the long-term effects of vitamin E intake, the coefficient of fat absorption (CFA) and IgG on α-tocopherol levels. We also examined the long-term effects of serum α-tocopherol and serum IgG on forced expiratory volume in 1 s expressed as percentage of predicted (FEV1% pred.) in paediatric CF patients during a 7-year follow-up period. We found that CF patients failed to meet the CF-specific vitamin E recommendations, but serum α-tocopherol below the 2·5th percentile was found in only twenty-three of the 1022 measurements (2 %). Furthermore, no clear effect of vitamin E intake or the CFA on serum α-tocopherol was found (both P≥ 0·103). FEV1% pred. was longitudinally inversely associated with age (P< 0·001) and serum IgG (P= 0·003), but it was not related to serum α-tocopherol levels. We concluded that in the present large sample of children and adolescents with CF, vitamin E intake was lower than recommended, but serum α-tocopherol deficiency was rare. We found no evidence that higher serum α-tocopherol levels had protective effects on PF. Adjustment of the recommendations to the real-life intake of these patients may be considered.

[Inhaled corticosteroids and behavioural changes in children]. / Inhalatieglucocorticoïden en gedragsveranderingen bij kinderen.

Behavioural changes, such as hyperactivity, aggression, mood swings and agitation may occur during the use of inhaled corticosteroids. Children are particularly vulnerable to this possible adverse drug reaction. As this side effect is reversible, timely recognition is important in order to prevent unnecessary diagnostic investigations and problems at home or at school. In this article we present two patients, a seven-year-old boy and a nine-year-old girl, who illustrate the importance of awareness of this unwanted effect of inhaled corticosteroids.

Fever following immunization with influenza A (H1N1) vaccine in children: a survey-based study in the Netherlands.

BACKGROUND: In November 2009, all children in the Netherlands from 6 months up to 4 years of age were indicated to receive the Influenza A (H1N1) vaccine. Fever is a common adverse event following immunization in children. Pandemrix®, an inactivated, split-virus influenza A (H1N1) vaccine, was used for this age group. A clinical study mentioned in the Summary of Product Characteristics of Pandemrix® found an increased reactogenicity after the second dose in comparison with the first dose, particularly in the rate of fever. In the Netherlands, this adverse reaction was a point of concern for the parents or caregivers of these children. OBJECTIVE: To investigate the course and height of fever following the first and second dose of Pandemrix® in children aged from 6 months up to 4 years. The secondary aim was to evaluate the use of an online survey during a vaccination campaign. DESIGN: Survey-based descriptive study. SETTING: Adverse drug reaction reporting database of the Netherlands Pharmacovigilance Centre (Lareb). PARTICIPANTS: Parents or caregivers (n = 839) of vaccinated children who reported fever to Lareb following the first immunization with Pandemrix®. Questionnaires were sent by email to parents or caregivers of eligible children following the first and second doses of Pandremix®. MAIN OUTCOME MEASURES: Time between vaccination and the occurrence of fever, the maximum measured temperature, the occurrence of other adverse events after first and second vaccination, the decision to get the second vaccination and the social implication of the fever in terms of absence from work, nursery or school, and hospitalization. RESULTS: Following the first vaccination against Influenza A (H1N1), the height of the fever was between 39.0 and 40.0°C in 359/639 (56.2%) of the children. In most of these children (235/639 [36.8%]), the onset of fever was between 6 and 12 hours following vaccination. 450/639 (70.4%) children recovered within 2 days. Of the 539 responders to the second questionnaire, 380 (70.5%) received the second vaccination against Influenza A (H1N1) and 213 (56.1%) of these children experienced fever again. The height of the fever was significantly lower (t-test; p = 0.001) and the duration was significantly shorter (Pearson's Chi-square; p = 0.002) in comparison with the first vaccination. The height of the fever after the first vaccination was associated with the decision to receive the second vaccination (t-test; p = 0.000). In the studied group, 342 (53.5%) parents or caregivers needed to stay home from work and 405 (63.4%) children stayed home from nursery or school due to fever following the first vaccination. CONCLUSIONS: The results of this study can be used in future vaccination campaigns to be able to inform people in an evidence-based manner about the risks and benefits of the vaccine and to avoid unnecessary concern and negative media attention. This could contribute to improved immunization levels. A web-based survey is demonstrated to be a useful tool to quickly gather information about a current safety concern and consequently inform the public to support an ongoing vaccination campaign.

Monitoring adverse events of the vaccination campaign against influenza A (H1N1) in the Netherlands.

BACKGROUND: In November 2009, a vaccination campaign against Influenza A (H1N1) was started in the Netherlands. The accelerated registration procedure of the vaccines used in this campaign and the use of these vaccines on a large scale indicated a need for real-time safety monitoring. OBJECTIVE: To describe the processing, analysing and performing of signal detection by the Netherlands Pharmacovigilance Centre (Lareb) on reports of adverse events following immunization (AEFI) with respect to the two pandemic influenza vaccines, Focetria® and Pandemrix®, used in the Netherlands. The secondary aim is to provide a summary of the results of the safety monitoring of both vaccines. STUDY DESIGN: Description of the process of collecting information and analysis of the safety monitoring of the pandemic vaccines during the vaccination campaign against H1N1 in the Netherlands. An observational study on adverse events following immunization (AEFIs) associated with vaccines used in this campaign was conducted. RESULTS: The use of a dedicated web form with predefined AEFIs enabled an efficient way of processing and analysing the reports, resulting in a close to real-time monitoring of the safety of the vaccines. From 1 November 2009 until 1 March 2010, 7534 reports concerning one or more AEFIs possibly related to the administration of both vaccines were received. 2788 of the reports related to Focetria® and 4746 of the reports related to Pandemrix®. The total time between receiving the reports and completion was longer for the serious reports (average 2.8 days) compared with the non-serious reports (average 0.8 days). The profile of the reported adverse events is comparable with the information provided in the Summary of Product Characteristics (SPC). Differences in reported AEFIs between both vaccines may be caused by bias and confounding due to the different populations for which these vaccines have been used. No signals of possible batch-related problems were detected for either vaccine. CONCLUSIONS: The method applied allowed for real-time monitoring for AEFIs during the mass vaccination campaign. The use of web-based forms, preferably with information on venue and used batch numbers, enabled an efficient monitoring of possible batch-related problems. No major safety issues occurred with respect to the type of reported AEFIs, or with the batches of either vaccine.

[Omeprazole of limited value in crying babies]. / Waarde omeprazol bij huilende zuigelingen beperkt.

OBJECTIVE: To determine the role of omeprazole treatment in crying infants under the age of 1 year in whom acid gastroesophageal reflux is suspected and to study the evidence for efficacy, prescribing behaviour and side effects of this medicine, which is not registered for use in infants. DESIGN: Literature study. METHOD: To assess efficacy we conducted a study of the literature using PubMed with the search terms 'gastro-esophageal reflux disease', 'crying', 'adverse drug reactions' and 'omeprazole', in the age category 'all infants 0-23 months' We used the medicine prescription database Interactie DataBase to assess prescribing data and studied reports of suspected side effects of omeprazole in children younger than 1 year to the Lareb Netherlands pharmacovigilance centre. RESULTS: We found 139 articles including 32 clinical trials. In only 3 of these was the efficacy of omeprazole studied in children under the age of 1 year. These studies showed that there was an effect on the acidity of the stomach, but not on symptoms. Although many side effects may occur during the use of omeprazole, few suspected side effects were reported to the Lareb Netherlands pharmacovigilance centre. Omeprazole is supplied in 10 mg amounts and it is therefore difficult to adjust dose to weight. Pharmacoepidemiological data show therefore that nearly all children receive 10 mg or multiples thereof. Given the age and corresponding weights we expected doses of 4-20 mg/day to be prescribed. CONCLUSION: It is uncertain whether acid reflux is the cause of crying in babies and, if reflux is suspected, whether omeprazole is the preferred treatment.