Clinical Prediction of Iron Deficiency at Age 2 Years: A National Cross-sectional Study in France.

OBJECTIVE: To assess the diagnostic accuracy of existing clinical criteria and to develop prediction tools for iron deficiency in 2-year-old children. STUDY DESIGN: In a national cross-sectional study conducted in primary care pediatricians' practices throughout France, 2-year-old children were consecutively included (2016-2017). Multivariable logistic regression modeling and bootstrapping were used to develop several clinical models to predict iron deficiency (serum ferritin <12 µg/L). These models used the best criteria and combinations among the American Academy of Pediatrics' (AAP) criteria adapted to the European context (n = 10), then all potential predictors (n = 19). One model was then simplified into a simple prediction tool. RESULTS: Among 568 included infants, 38 had iron deficiency (6.7%). In univariable analyses, no significant association with iron deficiency was observed for 8 of the 10 adapted AAP criteria. Three criteria (both parents born outside the European Union, low weight at 1 year old, and weaning to cow's milk without supplemental iron) were retained in the AAP model, which area under the receiver operating characteristic curve, sensitivity, and specificity were 0.62 (95% CI, 0.58-0.67), 30% (95% CI, 22%-39%), and 95% (95% CI, 92%-97%), respectively. Four criteria were retained in a newly derived simple prediction tool (≥1 criterion among the 3 previous plus duration of iron-rich formula consumption <12 months), which area under the receiver operating characteristic curve, sensitivity, and specificity were 0.72 (95% CI, 0.65-0.79), 63% (95% CI, 47%-80%), and 81% (95% CI, 70%-91%), respectively. CONCLUSIONS: All prediction tools achieved acceptable diagnostic accuracy. The newly derived simple prediction tool offered potential ease of use. TRIAL REGISTRATION: ClinicalTrials.gov NCT02484274.

Iron-fortified formula use in young children and association with socioeconomic factors in the French nationwide ELFE cohort.

AIM: To study the rate of iron-fortified infant formula (IFF) use in young children in France and its association with socioeconomic factors. METHODS: The ELFE national birth cohort included, in 2011, 18 329 living births in 349 hospitals randomly selected. The present analyses were restricted to children with follow-up at age two years. Milk consumption was evaluated by parental telephone interview, and its association with socioeconomic factors was studied. RESULTS: The 12 341 analysed children had a mean age of 26 months; 50% were girls. Rate of IFF use before two years old and at two years old was 65% and 43%, respectively. At age two years, use of IFF was lower with young age of the mother (adjusted OR [aOR] = 0.4, 95% CI: 0.3-0.5), low educational level (aOR = 0.7, 95% CI: 0.6-0.9), high parity (aOR = 0.3, 95% CI 0.2-0.4), and mother smoking (aOR = 0.8, 95% CI: 0.7-0.9) as well as low household income (aOR = 0.5, 95% CI: 0.4-0.7), and parents' unemployment (aOR = 0.7, 95% CI: 0.5-0.9). CONCLUSION: In this national population-based study, the rate of implementation of the ID prevention strategy was much lower at two years old than before two years old, and significantly lower in disadvantaged populations.

Very low prevalence of iron deficiency among young French children: A national cross-sectional hospital-based survey.

Although iron deficiency (ID) is considered the most frequent micronutrient deficiency in industrialized countries and is associated with impaired neurodevelopment when occurring in early years, accurate recent estimations of its prevalence are lacking. Our objective was to estimate ID prevalence and associated sociodemographic markers in young children in France. The Saturn-Inf national cross-sectional hospital-based survey recruited 3,831 French children <6 years old between 2008 and 2009 to assess lead poisoning prevalence and to establish a biobank. This secondary analysis measured serum ferritinemia (SF) in sera kept frozen at -80 °C for children with sufficient serum aliquots and C-reactive protein <10 mg/L. For the 657 participating children (17% of the Saturn-Inf study), the median age was 3.9 years (interquartile range: 2.2-5.1); 52% were boys. The median SF was 44 µg/L (interquartile range: 28-71). ID prevalence was 2.8% (95% confidence interval [1.7, 4.7]) and 3.2% (95% confidence interval [2.0, 5.1]) with an SF threshold of 10 and 12 µg/L, respectively. Low SF was significantly associated (p < .05) with mother being a migrant (32 vs. 45 µg/L for a mother born in France) or unemployed (37 vs. 50 µg/L for a mother employed). In this first national cross-sectional hospital-based study in France, ID prevalence was much lower than that in other French and European studies performed in underprivileged populations but close to the lowest values observed in other population-based studies in Europe.

Childhood-onset autoimmune cytopenia as the presenting feature of biallelic ACP5 mutations.

Childhood-onset chronic and refractory cytopenias are rare and may be genetic in etiology. We report three pediatric cases of severe autoimmune thrombocytopenia or anemia associated with growth retardation and spastic diplegia with intracranial calcification. The identification of platyspondyly and metaphyseal lesions suggested a potential diagnosis of spondyloenchondrodysplasia (SPENCD), which was confirmed with the identification of biallelic ACP5 mutations. Two patients demonstrated elevated serum interferon alpha levels. Our report highlights ACP5-associated disease as a cause of childhood-onset autoimmune cytopenia, particularly combined with growth retardation and/or spasticity. Furthermore, a role for type I interferon in the pathogenesis of autoimmune cytopenias is supported.

Clinical characteristics and outcomes of childhood-onset ANCA-associated vasculitis: a French nationwide study.

BACKGROUND: Data on anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis are scarce in children. The current study is aimed at describing the clinical features and outcomes of childhood-onset ANCA-associated vasculitis (AAV). METHODS: We conducted a retrospective French multicentre study involving patients in whom AAV was diagnosed before the age of 18 years. Inclusion criteria were (i) granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) according to classification criteria of the European League Against Rheumatism/Paediatric Rheumatology European Society, and (ii) ANCA positivity. Patient and renal survival were analysed. RESULTS: Among 66 children included, 80% were female, 42% had GPA and 58% MPA including renal-limited vasculitis, 67% were pANCA+ and 33% cANCA+. The mean incidence of reported cases increased to 0.45 per million children/year in the period 2006-10. Median age at diagnosis was 11.5 years, and median time to diagnosis was 1 month. Initial symptoms included fever and fatigue (79%), skin lesions (41%), arthritis (42%), pulmonary (45%) and renal involvement (88%). Clinical features were similar between GPA and MPA with the exception of upper airway impairment (28%) specific of GPA. Ninety percent of the patients achieved remission after induction treatment. After a median follow-up of 5.2 years, 4 patients (6%) died, corresponding to a mortality rate of 1.2 per 100 person-years, and 22 patients (34%) developed end-stage renal disease (ESRD). Renal survival was 74, 70 and 59% at 1, 5 and 10 years, respectively. In a multivariable Cox regression model, baseline glomerular filtration rate, ethnic origin, histopathological classification and era of treatment were associated with the occurrence of ESRD. Relapse-free survival was 57% at 5 years and 34% at 10 years of follow-up. Patient and renal outcome did not significantly differ between GPA and MPA. CONCLUSION: Childhood-onset AAV is a rare disease characterized by female predominance, delayed diagnosis, frequent renal impairment and a high remission rate. Baseline GFR and new histopathological classification system are strong predictors of ESRD. Renal survival in childhood AAV has improved over time.

Young children formula consumption and iron deficiency at 24 months in the general population: A national-level study.

BACKGROUND & AIMS: Iron deficiency (ID) is considered the most frequent micronutrient deficiency in industrialized countries where strategies for its primary prevention vary widely and are insufficiently evaluated. We aimed to study the effectiveness for iron status of a national iron deficiency prevention strategy based on recommendations for young-child formula (YCF) use after age 12 months, taking into consideration other sources of iron and the family's socio-economic status. METHODS: In a cross-sectional observational study conducted in primary care pediatrician offices throughout France from 2016 to 2017, infants aged 24 months were consecutively included for a food survey and blood sampling. Associations between YCF consumption and serum ferritin (SF) level were studied by multivariable regression after adjustment on sociodemographic, perinatal and dietary characteristics, notably other intakes of iron. RESULTS: Among the 561 infants analyzed, the ID prevalence was 6.6% (37/561; 95% confidence interval [CI] 4.7-9.0). Daily iron intake excluding YCF and total daily iron intake including YCF were below the 5-mg/day recommended average requirements for 63% and 18% of children, respectively. ID frequency was significantly decreased (or SF level was independently higher) with any YCF consumption after age 10 months (odds ratio 0.15, 95% CI 0.07-0.31), current YCF consumption at age 24 months (median SF level 29 vs 21 µg/L if none), prolonged YCF consumption (28 µg/L if >12 months vs 17 µg/L if none), and increasing daily volume of YCF consumed at age 24 months from a small volume (e.g., 29 µg/L if <100 mL/day vs 21 µg/L if none). CONCLUSIONS: Current or past YCF use was independently associated with a better iron status at age 24 months than non-use. The strategy recommending YCF use at weaning after age 12 months seems effective in the general population. CLINICALTRIALS. GOV IDENTIFIER: NCT02484274.

Anemia in children: prevalence, causes, diagnostic work-up, and long-term consequences.

INTRODUCTION: Anemia in children is a major public health problem throughout the world. It is often multifactorial, iron deficiency being the most frequent etiology. Consequences are diverse and largely under evaluated. Areas covered: This paper briefly reviews the main causes and focus on the potential consequences of acute and chronic anemia in children. Expert commentary: Anemia in children should never be trivialized. Even if iron deficiency is frequently involved, other potentially life-threatening causes are possible and should be looked for. The exact contribution of anemia to child mortality and morbidity is difficult to assess because of overlapping comorbidities. Chronic anemia may impair growth, cardiac function and cognitive development in infants but other consequences are rather poorly described and should be explored more thoroughly.

Stability of serum ferritin measured by immunoturbidimetric assay after storage at -80°C for several years.

BACKGROUND: Iron deficiency (ID) may impair long-term neurological development when it occurs in young infants. In cohort studies, it is sometimes necessary to evaluate ID with sera kept frozen for several years. To assess ID, learned societies recommend measuring serum ferritin (SF) level combined with C-reactive protein level. The long-term stability of C-reactive protein in frozen samples is well established but not ferritin. METHODS: We measured SF level (immunoturbidimetric assay; in micrograms per liter) immediately after collection from 53 young adults recruited and followed-up in Porto, Portugal, from 2011 to 2013 (SF1), and then, in 2016 in two aliquots kept frozen at- 80°C for 3 to 5 years: one without (SF2A) and one with (SF2B) intermediate thawing in 2014. We compared SF1 to SF2A then SF2B; statistical agreement was evaluated by the Bland and Altman method and the effect of intermediate thawing by regression modelling. RESULTS: Mean SF2A-SF1 and SF2B-SF1 differences were -2.1 (SD 7.0) and 48.9 (SD 66.9). Values for Bland and Altman 95% limits of agreement were higher for the comparison of SF2B and SF1 than SF2A and SF1: -82.2 to 179.9 and -15.8 to 11.8, respectively; the effect of thawing was highly significant (p <0.001). CONCLUSIONS: Agreement between SF values before and after 3 to 5 years of constant freezing at -80°C was in a generally accepted range, which supports the hypothesis of ferritin's stability at this temperature for a long period. In long-term storage by freezing, intermediate thawing induced a major increase in values.

Transmission of acute gastroenteritis and respiratory illness from children to parents.

BACKGROUND: Acute respiratory illness (ARI) and acute gastroenteritis (AGE) are the most common infections in children; the risk of such illness increases with daycare attendance. We estimated the risk of transmission of ARI and AGE from daycare attendees to their parents and describe measures used by families to prevent that transmission. METHODS: We performed a retrospective cohort study of parents and children 12-60 months of age attending childcare centers attended by ≥60 children in the greater Québec City area, Canada. Participants were contacted at home by phone to answer a standardized questionnaire on infections that occurred in children and parents during the winter period. RESULTS: Overall, 374 households and 608 participants were included. AGE and ARI occurred at an incidence of 8.7 and 19 episodes per 100 child-months, respectively. Transmission to parents occurred about once in every 3 episodes for both types of infections. AGE in parents caused more frequent work absenteeism than ARI (62% vs. 34%, P < 0.005) with slightly longer duration (23% vs. 15% missing ≥2 days). Hand hygiene with soap was the primary household preventive measure. The 2009 pandemic may have positively influenced home hand hygiene practices overall but alcohol-based disinfection was infrequently applied. CONCLUSIONS: Parental risk and impact of AGE and ARI acquisition from their children are substantial. ARI occur more frequently overall among children, but parental work loss appears greater with AGE transmission. Our findings suggest that preventive practices to reduce the risk of secondary ARI and AGE transmission to parents warrants greater emphasis, evaluation and education.