Serum calcium normal range in 1000 term newborns.

INTRODUCTION: Serum calcium rapidly declines at birth because of the sudden interruption of the maternal-fetal calcium influx. Several factors are known to influence serum calcium in the first days of life, including circulating concentrations of maternal vitamin D. Objective was to establish the normal range variations of neonatal serum calcium according to the French current vitamin D supplementation during pregnancy, i.e. 100,000 IU of cholecalciferol during the third trimester. METHODS: We included in our prospective cohort study 1002 mother-newborn dyads from, with recruitments from April 2012 to July 2014 in France, in two recruiting centers located in Paris neighborhoods. RESULTS: Total serum calcium at 3 days of life in neonates varied from 2.06 to 2.73 mmol/L [2.5 and 97.5 percentiles], with a mean of 2.45 mmol/L. Serum calcium was similar between babies born from vitamin D supplemented mothers and those born from the non-supplemented ones. Univariate and multivariable analyses demonstrated the importance of maternal and cord blood 25(OH)D concentrations for newborn serum calcium maintenance. CONCLUSION: We established that the expected serum calcium in neonates ranges between 2.06 and 2.73 mmol/L which is significantly wider than the adult range. This finding should help physicians in the diagnosis of hypo- or hypercalcemia. In addition, our study supports the importance of vitamin D supplementation and 25(OH)D status for neonatal serum calcium maintenance.

Reference values for serum calcium in neonates should be established in a population of vitamin D-replete subjects.

INTRODUCTION: Serum calcium is frequently measured during the neonatal period, and is known to be influenced by the vitamin D status. We hypothesized that the 25OHD concentration may influence the lower limit of the serum calcium normal range in neonates. METHODS: We included in our prospective cohort study 1002 mother-newborn pair recruited from April 2012 to July 2014, in two centers located in the neighborhoods of Paris, France, whose serum calcium was measured at 3 days of life. We established, after exclusion of outliers, a 95% confidence interval (CI) for serum calcium 1) in our whole population of 1002 neonates, 2) in neonates with a cord blood 25OHD concentration ≥ 30 nmol/L, and 3) in those with a 25OHD ≥ 50 nmol/L. RESULTS: The mean serum total calcium was 2.46 ± 0.13 nmol/L [95% CI: 2.19-2.72 mmol/L], 2.47 ± 0.25 mmol/L [95% CI: 2.22-2.72 mmol/L], and 2.50 ± 0.25 mmol/L [95% CI: 2.25-2.75 mmol/L] in the whole group, in the 514 neonates with 25OHD ≥ 30 nmol/L, and in the 202 neonates with 25OHD ≥ 50 nmol/L respectively. The lower limit of the 95% range was significantly higher in neonates with 25 OHD ≥ 30 nmol/L (p<0.05) and ≥ 50 nmol/L (p<0.001) than in the entire cohort. CONCLUSION: We show that the lower limit of the normal serum calcium range is higher in groups with a higher 25OHD than in unselected subjects. We propose that the reference range for serum calcium in neonates is 2.25 to 2.75 mmol/L.

Antimicrobial treatment of lower respiratory tract infections in children.

Lower respiratory tract infections (LRTI) encompass a wide range of clinical syndromes, prominently including bronchiolitis, bronchitis and pneumonia. LRTIs are the second leading cause of antibiotic prescriptions. The vast majority of these infections are due to (or triggered by) viruses and are self-limited diseases. Pneumonia in children is responsible for significant morbidity and mortality worldwide. For clinicians, one of the main difficulties consists in diagnosing pneumonia in febrile children with (or without) cough. The diagnosis is given on the basis of anamnesis, clinical examination and (if necessary) complementary examinations, with chest X-ray or thoracic ultrasound; biological markers are particularly important. Over recent years, since the implementation of PCV13, the bacterial epidemiology of pneumonia and empyema has evolved; involvement in these diseases of pneumococcus has been reduced, and resistance to penicillin has lessened - and remained extremely low. In 2021, according to the National Pneumococcal Reference Center, only 6% of the strains isolated from blood cultures in children are resistant to amoxicillin. The therapeutic choices proposed in this article are in full compliance with the previously published official French recommendations.

Saliva for molecular detection of SARS-CoV-2 in pre-school and school-age children.

SARS-CoV-2 diagnosis is a cornerstone for the management of coronavirus disease 2019 (COVID-19). Numerous studies have assessed saliva performance over nasopharyngeal sampling (NPS), but data in young children are still rare. We explored saliva performance for SARS-CoV-2 detection by RT-PCR according to the time interval from initial symptoms or patient serological status. We collected 509 NPS and saliva paired samples at initial diagnosis from 166 children under 12 years of age (including 57 children under 6), 106 between 12 and 17, and 237 adults. In children under 12, overall detection rate for SARS-CoV-2 was comparable in saliva and NPS, with an overall agreement of 89.8%. Saliva sensitivity was significantly lower than that of NPS (77.1% compared to 95.8%) in pre-school and school-age children but regained 96% when considering seronegative children only. This pattern was also observed to a lesser degree in adolescents but not in adults. Sensitivity of saliva was independent of symptoms, in contrary to NPS, whose sensitivity decreased significantly in asymptomatic subjects. Performance of saliva is excellent in children under 12 at early stages of infection. This reinforces saliva as a collection method for early and unbiased SARS-CoV-2 detection and a less invasive alternative for young children.

Neuroinflammatory Disease following Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Children.

OBJECTIVE: To describe neurologic, radiologic and laboratory features in children with central nervous system (CNS) inflammatory disease complicating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. STUDY DESIGN: We focused on CNS inflammatory diseases in children referred from 12 hospitals in the Paris area to Necker-Sick Children Reference Centre. RESULTS: We identified 19 children who had a history of SARS-CoV-2 infection and manifest a variety of CNS inflammatory diseases: encephalopathy, cerebellar ataxia, acute disseminated encephalomyelitis, neuromyelitis optica spectrum disorder, or optic neuritis. All patients had a history of SARS-CoV-2 exposure, and all tested positive for circulating antibodies against SARS-CoV-2. At the onset of the neurologic disease, SARS-CoV-2 PCR results (nasopharyngeal swabs) were positive in 8 children. Cerebrospinal fluid was abnormal in 58% (11/19) and magnetic resonance imaging was abnormal in 74% (14/19). We identified an autoantibody co-trigger in 4 children (myelin-oligodendrocyte and aquaporin 4 antibodies), representing 21% of the cases. No autoantibody was found in the 6 children whose CNS inflammation was accompanied by a multisystem inflammatory syndrome in children. Overall, 89% of patients (17/19) received anti-inflammatory treatment, primarily high-pulse methylprednisolone. All patients had a complete long-term recovery and, to date, no patient with autoantibodies presented with a relapse. CONCLUSIONS: SARS2-CoV-2 represents a new trigger of postinfectious CNS inflammatory diseases in children.

Agreement between a regional pharmacovigilance centre and an adjudication committee regarding adverse drug reactions on a cohort of hospitalised children.

BACKGROUND AND PURPOSE: The EREMI project was set up to collect data on adverse drug reactions (ADRs) occurring due to off-label and/or unlicensed drugs prescribed to hospitalised children in France. These events were evaluated by a regional pharmacovigilance centre (RPC) and an adjudication committee (AC). The aim of this study was to assess the agreement between these two different entities on their evaluation of ADRs. EXPERIMENTAL APPROACH: The RPC first validated the ADRs and assessed their causality using the Naranjo scale. The AC assessed then ADRs using all available information, including the RPC evaluation. The agreement on severity and nature of ADRs, role of treatment (suspect or concomitant) and drug causality was calculated using Cohen's nonparametric kappa coefficient (k). KEY RESULTS: Three hundred and eighty-six events were reported in 219 children. The RPC excluded 65 events and validated 321 ADRs. Agreement was very good on nature of ADRs (k=0.85) and role of treatment (k=0.81), moderate on severity of ADRs (k=0.60) and very poor on drug causality (k=0.05). CONCLUSION AND IMPLICATIONS: Agreement between the RPC and the AC was not constant throughout this evaluation. They troubled to agree on severe ADRs and on drug causality.

Fall of Community-Acquired Pneumonia in Children following COVID-19 Non-Pharmaceutical Interventions: A Time Series Analysis.

Non-pharmaceutical interventions (NPIs) were implemented to reduce the spread of coronavirus disease 2019 (COVID-19). A first national lockdown was decided in France on the 17 March 2020. These measures had an impact on other viral and non-viral infectious diseases. We aimed to assess this impact on community-acquired pneumonia (CAP) in children. We performed a quasi-experimental interrupted time series analysis. We used data from a French prospective surveillance system of six pediatric emergency departments (PEDs). All visits from 1 January 2017 to 31 December 2020 were included. Pre-intervention period was before 17 March 2020 and post-intervention period was after 18 March 2020. We estimated the impact on the weekly number of visits for CAP and CAP admission using quasi-Poisson regression modeling. A total of 981,782 PEDs visits were analyzed; among them, 8318 visits were associated with CAP, and 1774 of these were followed by a hospital admission. A major decrease was observed for CAP visits (-79.7% 95% CI [-84.3; -73.8]; p < 0.0001), and CAP admission (-71.3% 95 CI [-78.8; -61.1]; p < 0.0001). We observed a dramatic decrease of CAP in children following NPIs implementation. Further studies are required to assess the long-term impact of these measures.

Relay oral therapy in febrile urinary tract infections caused by extended spectrum beta-lactamase-producing Enterobacteriaceae in children: A French multicenter study.

OBJECTIVES: We need studies assessing therapeutic options for oral relay in febrile urinary tract infection (FUTI) due to ESBL-producing Enterobacteriaceae (ESBL-E) in children. Amoxicillin-clavulanate/cefixime (AC-cefixime) combination seems to be a suitable option. We sought to describe the risk of recurrence at 1 month after the end of treatment for FUTI due to ESBL-E according to the oral relay therapy used. MATERIALS AND METHODS: We retrospectively identified children <18 years who were included in a previous prospective observational multicentric study on managing FUTI due to ESBL-E between 2014 and 2017 in France. We collected whether children who received cotrimoxazole, ciprofloxacin or the AC-cefixime combination as the oral relay therapy reported a recurrence within the first month after the end of treatment. Then, we analyzed the susceptibility drug-testing of the strains involved. RESULTS: We included 199 children who received an oral relay therapy with cotrimoxazole (n = 72, 36.2%), ciprofloxacin (n = 38, 19.1%) or the AC-cefixime combination (n = 89, 44.7%). Nine (4.5%) patients had a recurrence within the first month after the end of treatment, with no difference between the 3 groups of oral relay (p = 0.8): 4 (5.6%) cotrimoxazole, 2 (5.3%) ciprofloxacin and 3 (3.4%) AC-cefixime combination. Phenotype characterization of 249 strains responsible for FUTI due to ESBL-E showed that 97.6% were susceptible to the AC-cefixime combination. CONCLUSIONS: The AC-cefixime combination represents an interesting therapeutic option for oral relay treatment of FUTI due to ESBL-E as the recurrence rate at 1 month after the end of treatment was the same when compared to cotrimoxazole and ciprofloxacin.

Clinical course and cost assessment of infants with a first episode of acute bronchiolitis presenting to the emergency department: Data from the GUERANDE clinical trial.

INTRODUCTION: Bronchiolitis is the leading cause of hospitalization for infants but its economic burden is not well documented. Our objective was to describe the clinical evolution and to assess the 1-month cost of a first episode of acute bronchiolitis presenting to the emergency department (ED). METHODS: Our study was an epidemiologic analysis and a cost study of the cohort drawn from the clinical trial GUERANDE, conducted in 24 French pediatric EDs. Infants of 6 weeks to 12 months of age presenting at pediatric EDs with a first episode of bronchiolitis were eligible. The costs considered were collected from a societal viewpoint, according to the recommendations of the French National Health Authority. RESULTS: A total of 777 infants were included with a median age of 4 months. A total of 57% were hospitalized during the month following the first consultation in the ED, including 28 (3.6%) in an intensive care unit. The mean length of stay was 4.2 days (SD = 3.7). The average time to relief of all symptoms was 13 days (SD = 7). Average total cost per patient was €1919 (95% confidence interval: 1756-2138) from a societal perspective, mostly due to hospitalization cost. The estimated annual cost of bronchiolitis in infants was evaluated to be between €160 and €273 million in France. DISCUSSION: Bronchiolitis represent a high cost for the health care system and broadly for society, with hospitalizations costs being the main cost driver. Thus significant investments should be made to develop innovative therapies, to reduce the number of hospitalizations and length of stay.

Clavulanate combinations with mecillinam, cefixime or cefpodoxime against ESBL-producing Enterobacterales frequently associated with blaOXA-1 in a paediatric population with febrile urinary tract infections.

OBJECTIVES: Oral treatment of febrile urinary tract infections (FUTIs) can be impaired by MDR Enterobacterales often combining ESBL and inhibitor-resistant genes. We studied the impact of ß-lactamases and Enterobacterales' genotypes on the cefixime, cefpodoxime and mecillinam ± amoxicillin/clavulanate MICs. MATERIALS AND METHODS: In this multicentric study, we included 251 previously whole-genome-sequenced ESBL-producing Enterobacterales, isolated in French children with FUTIs. The MICs of cefixime, cefpodoxime, mecillinam alone and combined with amoxicillin/clavulanate were determined and analysed with respect to genomic data. We focused especially on the isolates' ST and their type of ß-lactamases. Clinical outcomes of patients who received cefixime + amoxicillin/clavulanate were also analysed. RESULTS: All isolates were cefixime and cefpodoxime resistant. Disparities depending on blaCTX-M variants were observed for cefixime. The addition of amoxicillin/clavulanate restored susceptibility for cefixime and cefpodoxime in 97.2% (MIC50/90 of 0.38/0.75 mg/L) and 55.4% (MIC50/90 of 1/2 mg/L) of isolates, respectively, whatever the ST, the blaCTX-M variants or the association with inhibitor-resistant ß-lactamases (34.2%). All isolates were susceptible to mecillinam + amoxicillin/clavulanate with MIC50/90 of 0.19/0.25 mg/L, respectively. Neither therapeutic failure nor any subsequent positive control urine culture were reported for patients who received cefixime + amoxicillin/clavulanate as an oral relay therapy (n = 54). CONCLUSIONS: Despite the frequent association of ESBL genes with inhibitor-resistant ß-lactamases, the cefixime + amoxicillin/clavulanate MICs remain low. The in vivo efficacy of this combination was satisfying even when first-line treatment was ineffective. Considering the MIC distributions and pharmacokinetic parameters, mecillinam + amoxicillin/clavulanate should also be an alternative to consider when treating FUTIs in children.

High Frequency of Viral Co-Detections in Acute Bronchiolitis.

Over two years (2012-2014), 719 nasopharyngeal samples were collected from 6-week- to 12-month-old infants presenting at the emergency department with moderate to severe acute bronchiolitis. Viral testing was performed, and we found that 98% of samples were positive, including 90% for respiratory syncytial virus, 34% for human rhino virus, and 55% for viral co-detections, with a predominance of RSV/HRV co-infections (30%). Interestingly, we found that the risk of being infected by HRV is higher in the absence of RSV, suggesting interferences or exclusion mechanisms between these two viruses. Conversely, coronavirus infection had no impact on the likelihood of co-infection involving HRV and RSV. Bronchiolitis is the leading cause of hospitalizations in infants before 12 months of age, and many questions about its role in later chronic respiratory diseases (asthma and chronic obstructive pulmonary disease) exist. The role of virus detection and the burden of viral codetections need to be further explored, in order to understand the physiopathology of chronic respiratory diseases, a major public health issue.

Perception of medical education by learners and teachers during the COVID-19 pandemic: a cross-sectional survey of online teaching.

COVID-19 lockdowns have deeply impacted teaching programs. Online teaching has suddenly become the main form of medical education, a form that may be used as long as the pandemic continues. We aimed at analyzing how online teaching was perceived by both teachers and learners to help determine how to adapt curricula in the next few years. An anonymous cross-sectional survey of medical students, pediatric residents, neonatal fellows, and their respective teachers was conducted between June and August 2020 to assess feelings about quality, attendance, equivalence, and sustainability of online teaching programs. 146 Students and 26 teachers completed the survey. 89% of students agreed that the offered online teaching was an appropriate way of teaching during the pandemic. Less than half of learners and teachers felt they have received or provided a training of an equivalent level and quality as in usual courses. About one-third thought that this online teaching should continue after the crisis ends. Medical school students had significantly more mixed opinions on online teaching than residents and fellows did. Attendance of learners significantly improved with synchronous online classes (p < 0.001), and among more advanced learners (p < 0.002). Our study is the first of this kind to assess simultaneously the feelings of learners at different levels (medical students, residents, and fellows) and their respective teachers of pediatric on programs taught online. It showed that online programs were perceived as appropriate ways of teaching during the COVID pandemic. Further studies are, however, needed to assess the efficacy of such teaching methods on medical skills and communication capabilities.

Prior infection by seasonal coronaviruses, as assessed by serology, does not prevent SARS-CoV-2 infection and disease in children, France, April to June 2020.

BackgroundChildren have a low rate of COVID-19 and secondary severe multisystem inflammatory syndrome (MIS) but present a high prevalence of symptomatic seasonal coronavirus infections.AimWe tested if prior infections by seasonal coronaviruses (HCoV) NL63, HKU1, 229E or OC43 as assessed by serology, provide cross-protective immunity against SARS-CoV-2 infection.MethodsWe set a cross-sectional observational multicentric study in pauci- or asymptomatic children hospitalised in Paris during the first wave for reasons other than COVID (hospitalised children (HOS), n = 739) plus children presenting with MIS (n = 36). SARS-CoV-2 antibodies directed against the nucleoprotein (N) and S1 and S2 domains of the spike (S) proteins were monitored by an in-house luciferase immunoprecipitation system assay. We randomly selected 69 SARS-CoV-2-seropositive patients (including 15 with MIS) and 115 matched SARS-CoV-2-seronegative patients (controls (CTL)). We measured antibodies against SARS-CoV-2 and HCoV as evidence for prior corresponding infections and assessed if SARS-CoV-2 prevalence of infection and levels of antibody responses were shaped by prior seasonal coronavirus infections.ResultsPrevalence of HCoV infections were similar in HOS, MIS and CTL groups. Antibody levels against HCoV were not significantly different in the three groups and were not related to the level of SARS-CoV-2 antibodies in the HOS and MIS groups. SARS-CoV-2 antibody profiles were different between HOS and MIS children.ConclusionPrior infection by seasonal coronaviruses, as assessed by serology, does not interfere with SARS-CoV-2 infection and related MIS in children.

SARS-CoV-2 transmission among children and staff in daycare centres during a nationwide lockdown in France: a cross-sectional, multicentre, seroprevalence study.

BACKGROUND: The extent to which very young children contribute to the transmission of SARS-CoV-2 is unclear. We aimed to estimate the seroprevalence of antibodies against SARS-CoV-2 in daycare centres that remained open for key workers' children during a nationwide lockdown in France. METHODS: Children and staff who attended one of 22 daycare centres during a nationwide lockdown in France (between March 15 and May 9, 2020) were included in this cross-sectional, multicentre, seroprevalence study. Hospital staff not occupationally exposed to patients with COVID-19, or to children, were enrolled in a comparator group. The primary outcome was SARS-CoV-2 seroprevalence in children, daycare centre staff, and the comparator group. The presence of antibodies against SARS-CoV-2 in capillary whole blood was measured with a rapid chromatographic immunoassay. We computed raw prevalence as the percentage of individuals with a positive IgG or IgM test, and used Bayesian smoothing to account for imperfect sensitivity and specificity of the assay. This study is registered with ClinicalTrials.gov, NCT04413968. FINDINGS: Between June 4 and July 3, 2020, we enrolled 327 children (mean age 1·9 [SD 0·9] years; range 5 months to 4·4 years), 197 daycare centre staff (mean age 40 [12] years), and 164 adults in the comparator group (42 [12] years). Positive serological tests were observed for 14 children (raw seroprevalence 4·3%; 95% CI 2·6-7·1) and 14 daycare centre staff (7·7%; 4·2-11·6). After accounting for imperfect sensitivity and specificity of the assay, we estimated that 3·7% (95% credible interval [95% CrI] 1·3-6·8) of the children and 6·8% (3·2-11·5) of daycare centre staff had SARS-CoV-2 infection. The comparator group fared similarly to the daycare centre staff; nine participants had a positive serological test (raw seroprevalence 5·5%; 95% CI 2·9-10·1), leading to a seroprevalence of 5·0% (95% CrI 1·6-9·8) after accounting for assay characteristics. An exploratory analysis suggested that seropositive children were more likely than seronegative children to have been exposed to an adult household member with laboratory-confirmed COVID-19 (six [43%] of 14 vs 19 [6%] of 307; relative risk 7·1 [95% CI 2·2-22·4]). INTERPRETATION: According to serological test results, the proportion of young children in our sample with SARS-CoV-2 infection was low. Intrafamily transmission seemed more plausible than transmission within daycare centres. Further epidemiological studies are needed to confirm this exploratory hypothesis. FUNDING: Assistance Publique-Hôpitaux de Paris; Mairie de Paris, Conseil Départemental de Seine Saint Denis. TRANSLATIONS: For the French translation of the abstract see Supplementary Materials section.

Coronavirus Disease 2019 Pandemic: Impact Caused by School Closure and National Lockdown on Pediatric Visits and Admissions for Viral and Nonviral Infections-a Time Series Analysis.

A time series analysis of 871 543 pediatric emergency visits revealed that the coronavirus disease 2019 (COVID-19) lockdown and school closures were associated with a significant decrease in infectious diseases disseminated through airborne or fecal-oral transmission: common cold, gastroenteritis, bronchiolitis, and acute otitis. No change was found for urinary tract infections.

Factors Associated With Severe SARS-CoV-2 Infection.

BACKGROUND: Initial reports on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in children suggested that very young age and comorbidities may increase risk of severe evolution, but these findings remained to be confirmed. We aimed to analyze the clinical spectrum of hospitalized pediatric SARS-CoV-2 infection and predictors of severe disease evolution. METHODS: We conducted a French national prospective surveillance of children hospitalized with SARS-CoV-2 infection. We included all children with confirmed SARS-CoV-2 infection in 60 hospitals during February 15 to June 1, 2020. The main outcome was the proportion of children with severe disease, defined by hemodynamic or ventilatory (invasive or not) support requirement. RESULTS: We included 397 hospitalized children with SARS-CoV-2 infection. We identified several clinical patterns, ranging from paucisymptomatic children, admitted for surveillance, to lower respiratory tract infection or multisystem inflammatory syndrome in children. Children <90 days old accounted for 37% of cases (145 of 397), but only 4 (3%) had severe disease. Excluding children with multisystem inflammatory syndrome in children (n = 29) and hospitalized for a diagnosis not related to SARS-CoV-2 (n = 62), 23 of 306 (11%) children had severe disease, including 6 deaths. Factors independently associated with severity were age ≥10 years (odds ratio [OR] = 3.4, 95% confidence interval: 1.1-10.3), hypoxemia (OR = 8.9 [2.6-29.7]), C-reactive protein level ≥80 mg/L (OR = 6.6 [1.4-27.5]). CONCLUSIONS: In contrast with preliminary reports, young age was not an independent factor associated with severe SARS-CoV-2 infection, and children <90 days old were at the lowest risk of severe disease evolution. This may help physicians to better identify risk of severe disease progression in children.

pCLIF-SOFA is a reliable outcome prognostication score of critically ill children with cirrhosis: an ESPNIC multicentre study.

BACKGROUND AND AIMS: Data on outcome of critically ill children with cirrhosis are scarce. We aimed to evaluate the prognostic accuracy of sequential organs scoring systems in children with cirrhosis admitted to Paediatric Intensive Care Units (PICU). METHODS: We performed a multicentre retrospective analysis of children with cirrhosis admitted into four European PICUs between 2011 and 2016. Investigators were members of the ESPNIC liver failure and support working group. Paediatric End-Stage Liver Disease (PELD) and paediatric chronic liver failure sequential organ failure assessment score (pCLIF-SOFA) diagnostic accuracy for 28- and 60-day liver transplantation, 28-day mortality and 60-day composite outcome (ie. death or liver transplantation) were tested. RESULTS: One-hundred-and-thirty children were included. The main causes for PICU admission were acute-on-chronic liver failure (ACLF), gastrointestinal bleeding and sepsis. Twenty-nine percent died and 22.3% were transplanted by day-60 after PICU admission. On multivariable analysis, pCLIF-SOFA was the only predictor of mortality at day-28 and of composite outcome. Both pCLIF-SOFA and ACLF were independently associated with emergent liver transplantation. The pCLIF-SOFA score higher than 9 well predicted a 28-day mortality with a sensitivity of 87.8% and a specificity of 77.3%. A pCLIF-SOFA score higher than 7 was independently associated with liver transplantation on day-60. Stage 3 AKI assessed with KDIGO classification was significantly associated with 28-day mortality. CONCLUSIONS: Half of critically ill cirrhotic children admitted to PICU either died or were transplanted within the initial 28-day period. On admission pCLIF-SOFA score accurately identify patients transplanted at day-28 and day-60 to those alive without LT and is associated with 28-day mortality and composite outcome at day-60.

Appropriate thresholds for accurate screening for ß-thalassemias in the newborn period: results from a French center for newborn screening.

Objectives: Newborn screening (NBS) for ß-thalassemia is based on measuring the expression of the hemoglobin A (HbA) fraction. An absence or very low level of HbA at birth may indicate ß-thalassemia. The difficulty is that the HbA fraction at birth is correlated with gestational age (GA) and highly variable between individuals. We used HbA expressed in multiples of the normal (MoM) to evaluate relevant thresholds for NBS of ß-thalassemia. Methods: The chosen threshold (HbA≤0.25 MoM) was prospectively applied for 32 months in our regional NBS program for sickle cell disease, for all tests performed, to identify patients at risk of ß-thalassemia. Reliability of this threshold was evaluated at the end of the study. Results: In all, 343,036 newborns were tested, and 84 suspected cases of ß-thalassemia were detected by applying the threshold of HbA≤0.25 MoM. Among the n=64 cases with confirmatory tests, 14 were confirmed using molecular analysis as ß-thalassemia diseases, 37 were confirmed as ß-thalassemia trait and 13 were false-positive. Determination of the optimum threshold for ß-thalassemia screening showed that HbA≤0.16 MoM had a sensitivity of 100% and a specificity of 95.3%, whatever the GA. Conclusions: NBS for ß-thalassemia diseases is effective, regardless of the birth term, using the single robust threshold of HbA≤0.16 MoM. A higher threshold would also allow screening for carriers, which could be interesting when ß-thalassemia constitutes a public health problem.