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Based on a survey sent to seven Dutch hospitals, we observed an substantial increase in invasive group A streptococcal infections in children in the Netherlands, comparing the pre-COVID-19 pandemic cohort of 2018-2019 to 2021-2022. The most affected age group were children between 0-5 years. Main diagnosis was pneumonia with empyema. Necrotizing fasciitis and streptococcal toxic shock syndrome were also reported in 11% and 7% respectively. A significant number was admitted to the Paediatric Intensive Care Unit. Vigilance is needed.

The coronavirus disease 2019 pandemic has enormous impact on society and healthcare. Countries imposed lockdowns, which were followed by a reduction in care utilization. The aims of this study were to quantify the effects of lockdown on pediatric care in the Netherlands, to elucidate the cause of the observed reduction in pediatric emergency department (ED) visits and hospital admissions, and to summarize the literature regarding the effects of lockdown on pediatric care worldwide. ED visits and hospital admission data of 8 general hospitals in the Netherlands between January 2016 and June 2020 were summarized per diagnosis group (communicable infections, noncommunicable infections, (probable) infection-related, and noninfectious). The effects of lockdown were quantified with a linear mixed effects model. A literature review regarding the effect of lockdowns on pediatric clinical care was performed. In total, 126,198 ED visits and 47,648 admissions were registered in the study period. The estimated reduction in general pediatric care was 59% and 56% for ED visits and admissions, respectively. The largest reduction was observed for communicable infections (ED visits: 76%; admissions: 77%), whereas the reduction in noninfectious diagnoses was smaller (ED visits 36%; admissions: 37%). Similar reductions were reported worldwide, with decreases of 30–89% for ED visits and 19–73% for admissions.Conclusion: Pediatric ED utilization and hospitalization during lockdown were decreased in the Netherlands and other countries, which can largely be attributed to a decrease in communicable infectious diseases. Care utilization for other conditions was decreased as well, which may indicate that care avoidance during a pandemic is significant. What is Known:• The COVID-19 pandemic had enormous impact on society.• Countries imposed lockdowns to curb transmission rates, which were followed by a reduction in care utilization worldwide. What is New:• The Dutch lockdown caused a significant decrease in pediatric ED utilization and hospitalization, especially in ED visits and hospital admissions because of infections that were not caused by SARS-CoV-2.• Care utilization for noninfectious diagnoses was decreased as well, which may indicate that pediatric care avoidance during a pandemic is significant.

Background: Current strategies for risk stratification and prediction of neonatal early-onset sepsis (EOS) are inefficient and lack diagnostic performance. The aim of this study was to use machine learning to analyze the diagnostic accuracy of risk factors (RFs), clinical signs and biomarkers and to develop a prediction model for culture-proven EOS. We hypothesized that the contribution to diagnostic accuracy of biomarkers is higher than of RFs or clinical signs.Study Design: Secondary analysis of the prospective international multicenter NeoPInS study. Neonates born after completed 34 weeks of gestation with antibiotic therapy due to suspected EOS within the first 72 hours of life participated. Primary outcome was defined as predictive performance for culture-proven EOS with variables known at the start of antibiotic therapy. Machine learning was used in form of a random forest classifier.Results: One thousand six hundred eighty-five neonates treated for suspected infection were analyzed. Biomarkers were superior to clinical signs and RFs for prediction of culture-proven EOS. C-reactive protein and white blood cells were most important for the prediction of the culture result. Our full model achieved an area-under-the-receiver-operating-characteristic-curve of 83.41% (±8.8%) and an area-under-the-precision-recall-curve of 28.42% (±11.5%). The predictive performance of the model with RFs alone was comparable with random.Conclusions: Biomarkers have to be considered in algorithms for the management of neonates suspected of EOS. A 2-step approach with a screening tool for all neonates in combination with our model in the preselected population with an increased risk for EOS may have the potential to reduce the start of unnecessary antibiotics.

Backgrounds The large, international, randomized controlled NeoPInS trial showed that procalcitonin (PCT)-guided decision making was superior to standard care in reducing the duration of antibiotic therapy and hospitalization in neonates suspected of early-onset sepsis (EOS), without increased adverse events. This study aimed to perform a cost-minimization study of the NeoPInS trial, comparing health care costs of standard care and PCT-guided decision making based on the NeoPInS algorithm, and to analyze subgroups based on country, risk category and gestational age. Methods Data from the NeoPInS trial in neonates born after 34 weeks of gestational age with suspected EOS in the first 72 h of life requiring antibiotic therapy were used. We performed a cost-minimization study of health care costs, comparing standard care to PCT-guided decision making. Results In total, 1489 neonates were included in the study, of which 754 were treated according to PCT-guided decision making and 735 received standard care. Mean health care costs of PCT-guided decision making were not significantly different from costs of standard care (€3649 vs. €3616). Considering subgroups, we found a significant reduction in health care costs of PCT-guided decision making for risk category ‘infection unlikely’ and for gestational age ≥ 37 weeks in the Netherlands, Switzerland and the Czech Republic, and for gestational age Conclusions Health care costs of PCT-guided decision making of term and late-preterm neonates with suspected EOS are not significantly different from costs of standard care. Significant cost reduction was found for risk category ‘infection unlikely,’ and is affected by both the price of PCT-testing and (prolonged) hospitalization due to SAEs.

In this retrospective cohort study, the response to routinely administered Haemophilus influenzae type B vaccine, pneumococcal and pertussis vaccinations in 27 children exposed to antitumor necrosis factor alpha (anti-TNF alpha) during pregnancy was measured. The overall vaccination response seems comparable for children exposed to anti-TNF alpha and healthy infants. After primary vaccination series, inadequate response was present in some patients and might be related to exposure to anti-TNF alpha.

BACKGROUND Neonatal early-onset sepsis (EOS) is one of the main causes of global neonatal mortality and morbidity, and initiation of early antibiotic treatment is key. However, antibiotics may be harmful. METHODS We performed a secondary analysis of results from the Neonatal Procalcitonin Intervention Study, a prospective, multicenter, randomized, controlled intervention study. The primary outcome was the diagnostic accuracy of serial measurements of C-reactive protein (CRP), procalcitonin (PCT), and white blood count (WBC) within different time windows to rule out culture-positive EOS (proven sepsis). RESULTS We analyzed 1678 neonates with 10 899 biomarker measurements (4654 CRP, 2047 PCT, and 4198 WBC) obtained within the first 48 hours after the start of antibiotic therapy due to suspected EOS. The areas under the curve (AUC) comparing no sepsis vs proven sepsis for maximum values of CRP, PCT, and WBC within 36 hours were 0.986, 0.921, and 0.360, respectively. The AUCs for CRP and PCT increased with extended time frames up to 36 hours, but there was no further difference between start to 36 hours vs start to 48 hours. Cutoff values at 16 mg/L for CRP and 2.8 ng/L for PCT provided a sensitivity of 100% for discriminating no sepsis vs proven sepsis. CONCLUSIONS Normal serial CRP and PCT measurements within 36 hours after the start of empiric antibiotic therapy can exclude the presence of neonatal EOS with a high probability. The negative predictive values of CRP and PCT do not increase after 36 hours., + ID der Publikation: unilu_51625 + Sprache: Englisch + Letzte Aktualisierung: 2021-04-26 13:29:30

Current guidelines advise to maintain immunomodulators and biologicals in pregnant patients because relapse of inflammatory bowel is associated with unfavourable pregnancy outcome. With the exception of Methotrexate, IBD therapy seems not to be related to an increase of congenital malformations or infections requiring hospitalisation of the babies, although the effect the on the developing immune system of the exposed infants remains unknown. In this review we will focus on the effect of IBD drugs on health-related outcomes in children taking into account possible long-term effects of biologicals and immunomodulators, which are transferred across the placenta.

Objective Inflammatory bowel disease (IBD) is often diagnosed in women in their reproductive years of life and therefore children are born to mothers with IBD. Health outcomes of children born to mothers with IBD seem favorable. However, little is known about the quality of life related to their health compared to children born to healthy mothers. Therefore, our first objective was to investigate the effect of having IBD during pregnancy on the health-related quality of life (HRQoL) of children born to mothers with IBD in the first 5 years of age compared to children born to healthy mothers. Secondly, we studied the effect of the different IBD related factors on the HRQoL. Methods We prospectively followed 264 women with IBD, who visited the preconception outpatient clinic at our tertiary health center in the Netherlands from April 2013 through November 2016. Women of children aged 1–5 years were approached to fill in a 43-item validated TNO-AZL Preschool Children Quality of Life questionnaire (TAPQOL) to assess HRQoL (Fekkes et al., 2000; Bunge et al., 2005 [ 1 , 2 ]). Outcomes were compared to children of mothers without IBD. Results One-hundred-eighty-two women completed the TAPQOL questionnaire. In total 182 children of mothers with IBD were included [median age 3.0 years (IQR 2–4)]. From 70 healthy mothers, 70 children were included as controls. There was no significant difference in the HRQoL between children who were and were not born to mothers with IBD (P = .18). Also, no effect of the different IBD related factors was found. Conclusion In this study, we found no effect of having IBD during pregnancy on the health-related quality of life of children in the first 5 years of life.

Relapse of inflammatory bowel disease (IBD) during conception and pregnancy has been associated with a negative pregnancy outcome. Therefore, it is advised to maintain drugs in order to prevent relapse. The effect of drugs, which cross the placenta, on children who have been exposed during pregnancy will be discussed in this review. Areas covered: A literature search was performed using the following search terms: inflammatory bowel disease, pregnancy, infant, antitumor necrosis factor alpha, infliximab, adalimumab, golimumab, certolizumab, anti-integrins, vedolizumab, anti-interleukin (IL)-12/23 ustekinumab, placenta, vaccination. Other studies were identified by using references from articles identified through our original literature search. The occurrence of unfavorable pregnancy outcome and congenital malformations does not seem to be increased after exposure to anti-TNFα, but the effects on the developing immune system are largely unknown. For anti-integrins and anti IL-12/23, the numbers of exposed pregnancies are too small to draw any conclusions. Expert commentary: Follow-up of the developing immune system in children exposed to these drugs seems warranted, preferably in a prospective study design.

Background Up to 7% of term and late-preterm neonates in high-income countries receive antibiotics during the first 3 days of life because of suspected early-onset sepsis. The prevalence of culture-proven early-onset sepsis is 0·1% or less in high-income countries, suggesting substantial overtreatment. We assess whether procalcitonin-guided decision making for suspected early-onset sepsis can safely reduce the duration of antibiotic treatment. Methods We did this randomised controlled intervention trial in Dutch (n=11), Swiss (n=4), Canadian (n=2), and Czech (n=1) hospitals. Neonates of gestational age 34 weeks or older, with suspected early-onset sepsis requiring antibiotic treatment were stratified into four risk categories by their treating physicians and randomly assigned [1:1] using a computer-generated list stratified per centre to procalcitonin-guided decision making or standard care-based antibiotic treatment. Neonates who underwent surgery within the first week of life or had major congenital malformations that would have required hospital admission were excluded. Only principal investigators were masked for group assignment. Co-primary outcomes were non-inferiority for re-infection or death in the first month of life (margin 2·0%) and superiority for duration of antibiotic therapy. Intention-to-treat and per-protocol analyses were done. This trial was registered with ClinicalTrials.gov, number NCT00854932. Findings Between May 21, 2009, and Feb 14, 2015, we screened 2440 neonates with suspected early-onset sepsis. 622 infants were excluded due to lack of parental consent, 93 were ineligible for reasons unknown (68), congenital malformation (22), or surgery in the first week of life (3). 14 neonates were excluded as 100% data monitoring or retrieval was not feasible, and one neonate was excluded because their procalcitonin measurements could not be taken. 1710 neonates were enrolled and randomly assigned to either procalcitonin-guided therapy (n=866) or standard therapy (n=844). 1408 neonates underwent per-protocol analysis (745 in the procalcitonin group and 663 standard group). For the procalcitonin group, the duration of antibiotic therapy was reduced (intention to treat: 55·1 vs 65·0 h, p

Purpose Complete interferon-γ receptor 1 (IFN-γR1) deficiency is a primary immunodeficiency causing predisposition to severe infection due to intracellular pathogens. Only 36 cases have been reported worldwide. The purpose of this article is to describe a large novel deletion found in 3 related cases, which resulted in the complete removal of the IFNGR1 gene. Methods Whole blood from three patients was stimulated with lipopolysaccharide (LPS) and IFN-γ to determine production of tumor necrosis factor (TNF), interleukin-12 p40 (IL-12p40) and IL-10. Expression of IFN-γR1 on the cell membrane of patients’ monocytes was assessed using flow cytometry. IFNGR1 transcript was analyzed in RNA and the gene and adjacent regions were analyzed in DNA. Finally, IL22RA2 transcript levels were analyzed in whole blood cells and dendritic cells. Results There was no expression of the IFN-γR1 on the monocytes. Consistent with this finding, there was no IFN-γ response in the whole blood assay as measured by effect on LPS-induced IL-12p40, TNF and IL-10 production. A 119.227 nt homozygous deletion on chromosome 6q23.3 was identified, removing the IFNGR1 gene completely and ending 117 nt upstream of the transcription start of the IL22RA2 gene. Transcript levels of IL22RA2 were similar in patient and control. Conclusions We identified the first large genomic deletion of IFNGR1 causing complete IFN-γR1 deficiency. Despite the deletion ending very close to the IL22RA2 gene, it does not appear to affect IL22RA2 transcription and, therefore, may not have any additional clinical consequence. Electronic supplementary material The online version of this article (doi:10.1007/s10875-016-0244-y) contains supplementary material, which is available to authorized users.

Only 10-15% of neonates with congenital cytomegalovirus infection have symptoms at birth. The most common symptoms are intrauterine growth retardation, microcephaly, petechiae, jaundice, hepatosplenomegaly, intracranial abnormalities, ophthalmological abnormalities and hearing loss. Symptomatic and asymptomatic CMV infections can both have long-term effects. CMV infection during pregnancy is diagnosed using a blood test and possible testing of the amniotic fluid for viral DNA. Infection of the fetus may be prevented by treating the mother with CMV hyperimmune globulin. In the neonate a diagnosis can be made by viral culture or PCR in urine. PCR in saliva could be an alternative. Blood testing is of limited value. If symptoms of CMV infection occur in the neonate, such as petechiae, microcephaly, central nervous system abnormalities, sensorineural hearing loss or chorioretinitis, antiviral treatment should be considered. Long-term follow-up is advisable because of the possibility of delayed-onset hearing loss and chorioretinitis.