Sudden Unexpected Death in Infancy: Current Practices in Virological Investigations and Documentation in the French Registry.

OBJECTIVE: To describe pre-COVID-19 pandemic current practices in virological investigations, including type, frequency of samplings, and documented viruses, in sudden unexpected death in infancy (SUDI) and to compare results according to the cause of death. STUDY DESIGN: Between May 2015 and December 2019, infants under 2 years of age included in the French SUDI registry were classified in one of 4 groups by causes of death according to the classification by Goldstein et al. : unexplained (SIDS), infectious, explained but noninfectious, and undetermined. Sampling sites and viruses detected were described, and then SIDS and explained deaths (control group) were compared. RESULTS: Among 639 infants, 3.6% died of an established viral infection. From 23 sampling sites and 2238 samples, 19 virus species were detected. Overall, 43.3% of infants carried a virus, with no significant difference between SIDS infants and the control group (P = .06). We found wide variations in frequencies of samples by site (550 for nasopharynx to one for saliva). The highest positivity rate was from the nasopharynx (195/2238; 8.7%). Rhinovirus was the predominant virus detected (135/504; 26.8%), mostly in SIDS (83/254; 32.7%). We found no significant difference between positivity rates and distribution of viruses between the SIDS and control groups. At-autopsy virological analysis never contributed to determining the cause of death. CONCLUSION: Current practices in virological investigations in SUDI are heterogeneous, with wide variability despite published guidelines. Investigations should be limited to the most relevant sites, and systematic at-autopsy sampling should be reconsidered. We found no association between virus detection and SIDS.

Determinants of incomplete vaccination in children at age two in France: results from the nationwide ELFE birth cohort.

Incomplete vaccination in the pediatric population is a growing public health issue in high-income countries, but its determinants are poorly understood. Their identification is necessary to design target actions that can improve vaccination uptake. Our aim was to assess the determinants of incomplete vaccination in two-year-old children in France. Among the 18,329 children included in the 2011 ELFE French nationwide population-based birth cohort, we selected those for whom vaccination status was available at age two years. Incomplete vaccination was defined as ≥ 1 missing dose of recommended vaccines. Potential determinants of incomplete vaccination were identified by using logistic regression, taking into account attrition and missing data. Of the 5,740 (31.3%) children analyzed, 46.5% (95% confidence interval [CI] 44.7-48.0) were incompletely vaccinated. Factors independently associated with incomplete vaccination were having older siblings (adjusted odds ratio 1.18, 95% CI [1.03-1.34] and 1.28 [1.06-1.54] for one and ≥ 2 siblings, respectively, vs. 0), residing in an isolated area (1.92 [1.36-2.75] vs. an urban area), parents not following health recommendations or using alternative medicines (1.81 [1.41-2.34] and 1.23 [1.04-1.46], respectively, vs. parents confident in institutions and following heath recommendations), not being visited by a maternal and child protection service nurse during the child's first two months (1.19 [1.03-1.38] vs. ≥ 1 visit), and being followed by a general practitioner (2.87 [2.52-3.26] vs. a pediatrician). CONCLUSIONS: Incomplete vaccination was highly prevalent in the studied pediatric population and was associated with several socio-demographic, parental, and healthcare service characteristics. These findings may help in designing targeted corrective actions. WHAT IS KNOWN: • Incomplete vaccination in the pediatric population is a growing public health issue in high-income countries. • The partial understanding of the determinants of incomplete vaccination precludes the design of effective targeted corrective actions. WHAT IS NEW: • High prevalence of incomplete vaccination at age two years in France. • Incomplete vaccination was independently associated with several socio-demographic, parental, and healthcare service characteristics.

Taste and smell alterations affect nutritional status in children under chemotherapy.

AIM: This study aimed to evaluate the incidence of self-reported taste and smell alterations (TSA) in cancer paediatric patients and evaluate the impact of TSA on nutritional status in this population. We also developed and validated a composite score to detect TSA in children undergoing chemotherapy. METHODS: Paediatric patients who were undergoing chemotherapy in a paediatric oncology unit were included. TSA were assessed from the Gustonco questionnaire from which a composite score was developed and internally validated, eating behaviour was assessed using Child Eating Behaviour Questionnaire, and major weight loss was defined from nutritional status. All data were calculated at 1, 3 and 6 months after chemotherapy start. Associations between nutritional status and scores were studied by using logistic models. RESULTS: Among 49 patients included, TSA occurred in 71.7% of patients at 1 month after chemotherapy start and persisted at 3 and 6 months. TSA led to altered appetite since 1 month after chemotherapy start. The occurrence of a major weight loss at 6 months seemed to be associated with a high Gustonco score. CONCLUSION: Taste and smell alterations often occurred in paediatric cancer patients after chemotherapy start and seemed to be associated with impaired nutrition at 6 months after chemotherapy.

Impact of routine S100B protein assay on CT scan use in children with mild traumatic brain injury.

OBJECTIVES: To evaluate the impact of implementing a modified Pediatric Emergency Care Applied Research Network (PECARN) rule including the S100B protein assay for managing mild traumatic brain injury (mTBI) in children. METHODS: A before-and-after study was conducted in a paediatric emergency department of a French University Hospital from 2013 to 2015. We retrospectively included all consecutive children aged 4 months to 15 years who presented mTBI and were at intermediate risk for clinically important traumatic brain injury (ciTBI). We compared the proportions of CT scans performed and of in-hospital observations before (2013-2014) and after (2014-2015) implementation of a modified PECARN rule including the S100B protein assay. RESULTS: We included 1,062 children with mTBI (median age 4.5 years, sex ratio [F/M] 0.73) who were at intermediate risk for ciTBI: 494 (46.5%) during 2013-2014 and 568 (53.5%) during 2014-2015. During 2014-2015, S100B protein was measured in 451 (79.4%) children within 6 h after mTBI. The proportion of CT scans and in-hospital observations significantly decreased between the two periods, from 14.4 to 9.5% (p=0.02) and 73.9-40.5% (p<0.01), respectively. The number of CT scans performed to identify a single ciTBI was reduced by two-thirds, from 18 to 6 CT scans, between 2013-2014 and 2014-2015. All children with ciTBI were identified by the rules. CONCLUSIONS: The implementation of a modified PECARN rule including the S100B protein assay significantly decreased the proportion of CT scans and in-hospital observations for children with mTBI who were at intermediate risk for ciTBI.

Serum (1 → 3)-ß-D-glucan could be useful to rule out invasive candidiasis in neonates with an adapted cut-off.

AIM: We assessed the diagnostic accuracy of serum (1 â†’ 3)-ß-D-glucan (BDG) for neonatal invasive candidiasis (NIC) using the recommended cut-off usually used in adults for detecting invasive candidiasis and searched for an optimal cut-off for ruling out NIC. METHODS: We conducted a prospective cross-sectional study at Nantes University medical centre from January 2017 to July 2018. All consecutive newborn infants of less than 28 days of corrected age, with clinically suspected NIC, who underwent BDG assay, were included. Sensitivity and specificity were calculated by using the recommended cut-off of 80 pg/mL. Receiver operating characteristic curve analysis was used to identify an optimal cut-off value. RESULTS: We included 55 newborn infants with 61 episodes of suspected NIC. Their median gestational and chronological ages were 28.0 weeks (interquartile range [IQR] 26.4-34.1) and 10.0 days (IQR 6.0-22.0), respectively. Of 61 episodes, seven revealed NIC. Sensitivity and specificity were 85.7% (95% confidence interval [CI] 42.1%-99.6%) and 51.9% (37.8%-65.7%) with the recommended cut-off, respectively. An optimal cut-off of 174 pg/mL offered the same sensitivity but higher specificity 77.8% (64.4%-88.0%). CONCLUSION: The recommended cut-off of 80 pg/mL was probably too low for ruling out NIC. A higher cut-off might have been more appropriate.

Evaluation of a Temporal Association between Vaccination and Subdural Hematoma in Infants.

OBJECTIVE: To investigate a temporal association between vaccination and subdural hematoma, the main feature of abusive head trauma. STUDY DESIGN: From a prospective population-based survey carried out in 1 administrative district in France between January 2015 and April 2017, including all infants between 11 and 52 weeks old who underwent a first cerebral imaging (computerized tomography scan or magnetic resonance imaging), we conducted a nested case-control study. Vaccine exposure was compared between cases (infants with subdural hematoma) and 2-3 paired controls, without subdural hematoma or any other imaging findings compatible with abusive head trauma. Cases and controls were matched on chronological (±7 days) and gestational (≤33 vs >33 weeks) ages, respectively. Vaccination status was collected in the personal national pediatric health booklet. RESULTS: Among the 228 prospectively surveyed infants, 28 had subdural hematoma including 22 with abusive head trauma. The mean chronological age at imaging was 5.3 months among the 28 cases and the 62 controls, who did not differ significantly in median time since last vaccination (1.4 vs 1.3 months, P = .62) or frequency of at least 1 vaccination since birth (86% vs 89%; matched-pairs OR 0.77, 95% CI 0.17-3.86) or within 7 days (0.94, 0.08-6.96), 14 days (0.70, 0.12-2.92), or 21 days (0.48, 0.08-1.98) before cerebral imaging. CONCLUSIONS: We found no significant temporal association between vaccination and subdural hematoma diagnosis, which must continue to be considered a red flag for abusive head trauma and child abuse.

Are selection criteria for healthy pregnancies responsible for the gap between fetal growth in the French national Elfe birth cohort and the Intergrowth-21st fetal growth standards?

BACKGROUND: The Intergrowth-21st (IG) project proposed prescriptive fetal growth standards for global use based on ultrasound measurements from a multicounty study of low-risk pregnancies selected using strict criteria. We examined whether the IG standards are appropriate for fetal growth monitoring in France and whether potential differences could be due to IG criteria for "healthy" pregnancies. METHOD: We analysed data on femur length and abdominal circumference at the second and/or the third recommended ultrasound examination from 14 607 singleton pregnancies from the Elfe national birth cohort. We compared concordance of centile thresholds using the IG standards and current French references and used restricted cubic splines to plot z-scores by gestational age. A "healthy pregnancy" sub-sample was created based on maternal and pregnancy selection criteria, as specified by IG. RESULTS: Mean gestational age-specific z-scores for femur length and abdominal circumference using French references fluctuated around 0 (-0.2 to 0.1), while those based on IG standards were higher (0.3-0.8). Using IG standards, 2.5% and 5.2% of fetuses at the third ultrasound were <10th centile for femur length and abdominal circumference, respectively, and 31.5% and 16.7% were >90th. Only 34% of pregnancies fulfilled IG low-risk criteria, but sub-analyses yielded very similar results. CONCLUSION: Intergrowth standards differed from fetal biometric measures in France, including among low-risk pregnancies selected to replicate IG's healthy pregnancy sample. These results challenge the project's assumption that careful constitution of a low-risk population makes it possible to describe normative fetal growth across populations.

Survey highlights important discrepancies between definitions of paediatric abnormal growth taught to medical students in 23 European countries.

AIM: This study compared the definitions of abnormal growth that are taught across Europe to explain previously reported variations in growth-monitoring practices. METHODS: We developed two online surveys in 2016 to obtain the definitions of abnormal growth in European countries and approached the national chairs of the European Confederation of Primary Care Paediatricians in 18 countries and the International Federation of Medical Students' Associations in 33 countries. RESULTS: We obtained definitions from 10 of 18 paediatricians and 18 of 33 students, covering 23 of the 33 European countries surveyed. Abnormal faltering growth was always defined, either by a single parameter (24%) or combined parameters (76%). Four static parameters were used: standardised height (100%), standardised weight (60%), standardised body mass index (12%) and distance to target height (20%). Two dynamic parameters were used: growth deflection (28%) and growth velocity (32%). The thresholds used to define abnormal faltering growth varied slightly in some cases and widely in others. Abnormal accelerated growth appeared in 52% of the definitions, with important variations in parameters and thresholds. CONCLUSION: There were important between-country discrepancies in the definitions of paediatric abnormal growth that were taught in 23 European countries. Standardisation is vital.

Postnatal weight and height growth modeling and prediction of body mass index as a function of time for the study of growth determinants.

Weight, height and body mass index (BMI) growth trajectories have been associated with several chronic diseases in later life. Our aim was to describe a method to model individual weight and height growth curves during infancy and to show how it can be used to study their determinants and relationships with later health outcomes as well as to predict BMI trajectories. In the EDEN mother-child cohort, we collected 17 measurements of weight and 16 of length/height per child between birth and 3 years of age in 1,900 infants from their health care booklet and during the study clinical examinations at 1 and 3 years; 1,436 (76%) had at least 1 measurement between 2 and 3 years. We fitted individual weight and height growth trajectories using the Jenss nonlinear model including random effects using the 'SAEMIX' package (R software). We studied whether individual growth model parameters were associated with gender in one- and two-step approaches. We indirectly calculated BMI increase against time from both weight and height growth models combined and compared the fit with a direct multilevel spline model. By modeling observed growth data, we homogenized the data in terms of number and age of measurements and were able to calculate other specific parameters as growth velocities.

Birth weight and head circumference discordance and outcome in preterms: results from the EPIPAGE-2 cohort.

OBJECTIVE: To determine whether the relative measurement of birth weight (BW) and head circumference (HC) in preterm infants is associated with neurological outcomes. METHODS: The EPIPAGE-2 Study included 3473 infants born before 32 weeks' gestation, classified based on their Z-score of BW and HC on the Fenton curves as concordant (≤1 SD apart) or discordant (>1 SD difference). We defined four mutually exclusive categories: discordant smaller BW (sBW) with BW-1SD and concordant small measurement (CsM) with BW and HC concordant and both ≤-1SD. Neurological outcomes at 5.5 years were evaluated with standard tests. RESULTS: 2592 (74.8%) preterm neonates were categorised as CM, 258 (7.4%) CsM, 378 (10.9%) sHC and 239 (6.9%) sBW. Compared with the CM children, those born with CsM had significantly higher risks of cognitive deficiency (adjusted OR (aOR) 1.3, 95% CI (1.0 to 2.0)), developmental coordination disorders (aOR 2.6 (1.5 to 4.4)) and need for special school services (aOR 2.3 (1.5 to 3.7)). Those born with sBW had significantly lower risk of cognitive deficiency (aOR 0.6 (0.4 to 0.9)) and the sHC group significantly higher risk of developmental coordination disorders (aOR 1.8 (1.0 to 3.2)). CONCLUSIONS: The relative discordance of these preterm infants' BW and HC was associated with their neurological outcomes. It merits further exploration as an indirect indicator of development. TRIAL REGISTRATION NUMBER: NCT03078439.

Performance of glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) biomarkers in predicting CT scan results and neurological outcomes in children with traumatic brain injury (BRAINI-2 paediatric study): protocol of a European prospective multicentre study.

INTRODUCTION: In light of the burden of traumatic brain injury (TBI) in children and the excessive number of unnecessary CT scans still being performed, new strategies are needed to limit their use while minimising the risk of delayed diagnosis of intracranial lesions (ICLs). Identifying children at higher risk of poor outcomes would enable them to be better monitored. The use of the blood-based brain biomarkers glial fibrillar acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase-L1 (UCH-L1) could help clinicians in this decision. The overall aim of this study is to provide new knowledge regarding GFAP and UCH-L1 in order to improve TBI management in the paediatric population. METHODS AND ANALYSIS: We will conduct a European, prospective, multicentre study, the BRAINI-2 paediatric study, in 20 centres in France, Spain and Switzerland with an inclusion period of 30 months for a total of 2880 children and adolescents included. To assess the performance of GFAP and UCH-L1 used separately and in combination to predict ICLs on CT scans (primary objective), 630 children less than 18 years of age with mild TBI, defined by a Glasgow Coma Scale score of 13-15 and with a CT scan will be recruited. To evaluate the potential of GFAP and UCH-L1 in predicting the prognosis after TBI (secondary objective), a further 1720 children with mild TBI but no CT scan as well as 130 children with moderate or severe TBI will be recruited. Finally, to establish age-specific reference values for GFAP and UCH-L1 (secondary objective), we will include 400 children and adolescents with no history of TBI. ETHICS AND DISSEMINATION: This study has received ethics approval in all participating countries. Results from our study will be disseminated in international peer-reviewed journals. All procedures were developed in order to assure data protection and confidentiality. TRIAL REGISTRATION NUMBER: NCT05413499.

Associations of childhood adiposity with adult intima-media thickness and inflammation: a 20-year longitudinal population-based cohort.

BACKGROUND: The associations between childhood adiposity and adult increased carotid intima-media thickness (cIMT) have been well established, which might be corroborated by the association between adiposity in children and inflammation in adults. However, longitudinal data regarding biological pathways associated with childhood adiposity are lacking. METHODS: The current study included participants from the STANISLAS cohort who had adiposity measurements at age 5-18 years [ N  = 519, mean (SD) age, 13.0 (2.9) years; 46.4% male], and who were measured with cIMT, vascular-related and metabolic-related proteins at a median follow-up of 19 ±â€Š2 years. BMI, waist-to-height ratio and waist circumference were converted to age-specific and sex-specific z -scores. RESULTS: A minority of children were overweight/obese (16.2% overweight-BMI z -score >1; 1.3% obesity- z -score >2). Higher BMI, waist-height ratio and waist circumference in children were significantly associated with greater adult cIMT in univariable analysis, although not after adjusting for C-reactive protein. These associations were more pronounced in those with consistently high adiposity status from childhood to middle adulthood. Participants with higher adiposity during childhood (BMI or waist-height ratio) had higher levels of insulin-like growth factor-binding protein-1, protein-2, matrix metalloproteinase-3, osteopontin, hemoglobin and C-reactive protein in adulthood. Network analysis showed that IL-6, insulin-like growth factor-1 and fibronectin were the key proteins associated with childhood adiposity. CONCLUSION: In a population-based cohort followed for 20 years, higher BMI or waist-to-height ratio in childhood was significantly associated with greater cIMT and enhanced levels of proteins reflective of inflammation, supporting the importance of inflammation as progressive atherosclerosis in childhood adiposity.

Non-immunization associated with increased risk of sudden unexpected death in infancy: A national case-control study.

OBJECTIVE: In the context of vaccine scepticism, our study aimed to analyse the association between immunization status and the occurrence of sudden unexpected death in infancy (SUDI). STUDY DESIGN: A multi-centre case-control study was conducted between May 2015 and June 2017 with data from the French national SUDI registry (OMIN) for 35 French regional SUDI centres. Cases were infants under age 1 year who died from SUDI and who were registered in OMIN. Controls, matched to cases by age and sex at a 2:1 ratio, were infants admitted to Nantes University Hospital. All immunization data for diphtheria (D), tetanus (T), acellular pertussis (aP), inactivated poliovirus (IPV), Haemophilus influenzae b (Hib), hepatitis B (HB) and 13-valent pneumococcal conjugate vaccine (PCV13) were collected by a physician. Cases and controls were considered immunized if at least one dose of vaccine was administered. RESULTS: A total of 91 cases and 182 controls were included. The median age was 131 days (interquartile range 98-200.0) and the sex ratio (M/F) was about 1.1. For all vaccines combined (D-T-aP-IPV-Hib and PCV13), 22 % of SUDI cases versus 12 % of controls were non-immunized, which was significantly associated with SUDI after adjustment for potential adjustment factors (adjusted odds ratio 2.01 [95 % confidence interval 1.01-3.98, p = 0,047]). CONCLUSIONS: Non-immunization for D-T-aP-IPV-Hib-HB and PCV13 was associated with increased risk of SUDI. This result can be used to inform the general public and health professionals about this risk of SUDI in case of vaccine hesitancy.

Extent of the protection afforded by histo-blood group polymorphism against rotavirus gastroenteritis in metropolitan France and French Guiana.

Human rotaviruses attach to histo-blood group antigens glycans and null alleles of the ABO, FUT2 and FUT3 genes seem to confer diminished risk of gastroenteritis. Yet, the true extent of this protection remains poorly quantified. Here, we conducted a prospective study to evaluate the risk of consulting at the hospital in non-vaccinated pediatric patients according to the ABO, FUT2 (secretor) and FUT3 (Lewis) polymorphisms, in Metropolitan France and French Guiana. At both locations, P genotypes were largely dominated by P [8]-3, with P [6] cases exclusively found in French Guiana. The FUT2 null (nonsecretor) and FUT3 null (Lewis negative) phenotypes conferred near full protection against severe gastroenteritis due to P [8]-3 strains (OR 0.03, 95% CI [0.00-0.21] and 0.1, 95% CI [0.01-0.43], respectively in Metropolitan France; OR 0.08, 95% CI [0.01-0.52] and 0.14, 95%CI [0.01-0.99], respectively in French Guiana). Blood group O also appeared protective in Metropolitan France (OR 0.38, 95% CI [0.23-0.62]), but not in French Guiana. The discrepancy between the two locations was explained by a recruitment at the hospital of less severe cases in French Guiana than in Metropolitan France. Considering the frequencies of the null ABO, Secretor and Lewis phenotypes, the data indicate that in a Western European population, 34% (95% CI [29%; 39%]) of infants are genetically protected against rotavirus gastroenteritis of sufficient severity to lead to hospital visit.

Early growth according to protein content of infant formula: Results from the EDEN and ELFE birth cohorts.

BACKGROUND: In several systematic reviews, rapid weight gain in early life has been related to increased risk of later obesity. In line with this finding, the "early protein hypothesis" suggests that reducing early protein intake is a potential lever for obesity prevention. OBJECTIVE: To determine whether the variability of protein content of infant formula used in France over the period 2003-2012 is significantly associated with early growth in children. METHODS: A pooled sample of infants from the EDEN (Etude des Déterminants pré et postnatals de la santé et du développement de l'Enfant) mother-child cohort (born in 2003-2006) and the ELFE (Etude Longitudinale Française depuis l'Enfance) birth cohort (born in 2011) (ntotal  = 5846) was used. Protein content of the infant formula received at 4 months was classified into five groups. Associations between protein content (or breastfed status) at 4 months and weight-, length- and BMI-for-age z-scores at 6, 12 and 18 months were analysed by multivariable linear regression. RESULTS: This analysis showed a positive association between protein content and weight-, length- and BMI-for-age z-scores at 6 months and only for weight-for-age at 12 months. At 6 months, as compared with the intermediate protein-content group (2.1-2.5 g/100 kcal), infants receiving very-high protein content (>2.8 g/100 kcal) had higher BMI-for-age z-score and those from the very-low protein-content group (<2.0 g/100 kcal) had lower BMI-for-age z-score. Exclusively breastfed infants had lower length and weight z-scores than formula-fed infants at any age. CONCLUSIONS: Our findings show a positive association, under real conditions of use, between protein contents in infant formula still on the market and weight-, length- and BMI-for-age z-scores from 6 to 18 months.

Head circumference from birth to five years in France: New national reference charts and comparison to WHO standards.

BACKGROUND: The monitoring of head circumference (HC) is essential to early detect any conditions affecting its growth in early childhood. A positive secular trend and regional specificities in HC suggested the need to provide updated national HC reference growth charts. METHODS: We extracted all growth data collected from 42 primary-care physicians from across the French metropolitan territory who used the same electronic medical-records software. We selected HC measurements up to age five years for all children who were born after 1990 with birth weight > 2500 g. We derived new HC growth charts by using Generalized Additive Models for Location, Scale and Shape, then externally validated them until 30 months of age by comparison with the national population-based Étude Longitudinale Française depuis l'Enfance (ELFE) birth cohort and compared them to previous French and WHO growth charts. FINDINGS: With 973,869 HC measurements from 157,762 children, new calibrated HC growth charts from birth to age five years were generated. The new HC growth charts showed good external fit by comparison with the ELFE birth cohort. As compared with the new HC growth charts, the previous French and WHO growth charts mean HC z-scores were, respectively, -0.4 and -0.6 SD for girls and -0.2 and -0.6 SD for boys. INTERPRETATION: We produced and validated national calibrated HC growth charts by using a novel big-data approach applied to data routinely collected in clinical practice. Comparison with previous French and WHO growth charts confirmed a positive secular trend since the 1960s and regional specificities. FUNDING: The French Ministry of Health; Laboratoires Guigoz-General Pediatrics section of the French Society of Pediatrics-Paediatric Epidemiological Research Group; the French Association of Ambulatory Pediatrics; and educational grant from the Regional Health Agency of Ile-de-France.

Earlier diagnosis in anorexia nervosa: better watch growth charts!

BACKGROUND: A better understanding of the healthcare pathway of children and adolescents with anorexia nervosa (AN) may contribute to earlier detection and better disease management. Here we measured and compared the symptomatic time to diagnosis (TTD) (time between the first symptoms, as reported by parents, and the diagnosis) and the auxological TTD (time between the deviation in the weight growth curve and the diagnosis). METHODS: We performed a monocentric retrospective study including all patients age 9 years to 16 years who were hospitalized in Nantes University Hospital for AN between 2013 and 2016. We analysed the two TTDs by medical record review and growth curve investigation. TTDs were described by medians and Kaplan-Meier curves. Two profiles of patients were compared according to the kinetics of growth deviation and the occurrence of symptoms. RESULTS: Among the 137 patients included, the median symptomatic and auxological TTDs was 7.0 months (IQR: 4.0-12.0) and 7.2 months (IQR: 2.0-18.0). TTDs were significantly different but clinically similar. For 48% of the patients, a deviation in the growth curve could have been noted at a median of 9.7 months (IQR: 3.0-18.0) before the first symptoms were reported by parents. Those patients showed significantly slower weight loss than did patients with first symptoms reported before growth deviation (weight loss rate 0.41% vs 1.90% per month, p < 0.0001). CONCLUSIONS: Careful study of growth curves remains an essential step in detecting eating disorders, possibly allowing for earlier detection of the disease in nearly half of these patients.

Algorithms to Define Abnormal Growth in Children: External Validation and Head-To-Head Comparison.

Background: Growth monitoring of apparently healthy children aims at early detection of serious conditions by use of both clinical expertise and algorithms that define abnormal growth. The seven existing algorithms provide contradictory definitions of growth abnormality and have a low level of validation. Objective: An external validation study with head-to-head comparison of the seven algorithms combined with study of the impact of use of the World Health Organization (WHO) vs national growth charts on algorithm performance. Design: With a case-referent approach, we retrospectively applied all algorithms to growth data for children with Turner syndrome, GH deficiency, or celiac disease (n = 341) as well as apparently healthy children (n = 3406). Sensitivity, specificity, and theoretical reduction in time to diagnosis for each algorithm were calculated for each condition by using the WHO or national growth charts. Results: Among the two algorithms with high specificity (>98%), the Grote clinical decision rule had higher sensitivity than the Coventry consensus (4.6% to 54% vs 0% to 8.9%, P < 0.05) and offered better theoretical reduction in time to diagnosis (median: 0.0 to 0.9 years vs 0 years, P < 0.05). Sensitivity values were significantly higher with the WHO than national growth charts at the expense of specificity. Conclusion: The Grote clinical decision rule had the best performance for early detection of the three studied diseases, but its limited potential for reducing time to diagnosis suggests the need for better-performing algorithms based on appropriate growth charts.

A big-data approach to producing descriptive anthropometric references: a feasibility and validation study of paediatric growth charts.

BACKGROUND: Both national and WHO growth charts have been found to be poorly calibrated with the physical growth of children in many countries. We aimed to generate new national growth charts for French children in the context of huge datasets of physical growth measurements routinely collected by office-based health practitioners. METHODS: We recruited 32 randomly sampled primary care paediatricians and ten volunteer general practitioners from across the French metropolitan territory who used the same electronic medical records software, from which we extracted all physical growth data for the paediatric patients, with anonymisation. We included measurements from all children born from Jan 1, 1990, and aged 1 month to 18 years by Feb 8, 2018, with birthweight greater than 2500 g, to which an automated process of data cleaning developed to detect and delete measurement or transcription errors was applied. Growth charts for weight and height were derived by using generalised additive models for location, scale, and shape with the Box-Cox power exponential distribution. We compared the new charts to WHO growth charts and existing French national growth charts, and validated our charts using growth data from recent national cross-sectional surveys. FINDINGS: After data cleaning, we included 1 458 468 height and 1 690 340 weight measurements from 238 102 children. When compared with the existing French national and WHO growth charts, all height SD and weight percentile curves for the new growth charts were distinctly above those for the existing French national growth charts, as early as age 1 month, with an average difference of -0·75 SD for height and -0·50 SD for weight for both sexes. Comparison with national cross-sectional surveys showed satisfactory calibration, with generally good fit for children aged 5-6 years and 10-11 years in height and weight and small differences at age 14-15 years. INTERPRETATION: We successfully produced calibrated paediatric growth charts by using a novel big-data approach applied to data routinely collected in clinical practice that could be used in many fields other than anthropometry. FUNDING: The French Ministry of Health; Laboratoires Guigoz-General Pediatrics section of the French Society of Pediatrics-Pediatric Epidemiological Research Group; and the French Association for Ambulatory Pediatrics.