T cell help induces Myc transcriptional bursts in germinal center B cells during positive selection.

Antibody affinity maturation occurs in secondary lymphoid organs within germinal centers (GCs). At these sites, B cells mutate their antibody-encoding genes in the dark zone, followed by preferential selection of the high-affinity variants in the light zone by T cells. The strength of the T cell-derived selection signals is proportional to the B cell receptor affinity and to the magnitude of subsequent Myc expression. However, because the lifetime of Myc mRNA and its corresponding protein is very short, it remains unclear how T cells induce sustained Myc levels in positively selected B cells. Here, by direct visualization of mRNA and active transcription sites in situ, we found that an increase in transcriptional bursts promotes Myc expression during B cell positive selection in GCs. Elevated T cell help signals predominantly enhance the percentage of cells expressing Myc in GCs as opposed to augmenting the quantity of Myc transcripts per individual cell. Visualization of transcription start sites in situ revealed that T cell help promotes an increase in the frequency of transcriptional bursts at the Myc locus in GC B cells located primarily in the LZ apical rim. Thus, the rise in Myc, which governs positive selection of B cells in GCs, reflects an integration of transcriptional activity over time rather than an accumulation of transcripts at a specific time point.

Clinical and immunological characteristics of children diagnosed with-Type 1 diabetes during the COVID-19 pandemic.

AIMS: To find clinical and immunological signatures of the SARS-CoV-2 and the COVID-19 pandemic on children newly diagnosed with type 1 diabetes (T1D). METHODS: A single-centre, retrospective, observational study comparing the clinical and immunological characteristics of children diagnosed with T1D the year before and during the first 2 years of the COVID-19 pandemic. Data extracted from the medical records included clinical and demographic parameters, COVID-19 PCR results and the presence of anti-islet, thyroid and celiac-related antibodies. Also obtained from the medical records was a family history of T1D, celiac disease and autoimmune thyroid disease in a first-degree family member. RESULTS: A total of 376 children were diagnosed with T1D during the study period. A total of 132 in the pre-COVID era and 246 in the first 2 years of the pandemic. At diagnosis, the pH in children with DKA was lower, and HbA1c tended to be higher in the COVID-19 group compared to the pre-COVID-19 group (7.30 [7.18, 7.35] vs 7.33 [7.19, 7.36], p = 0.046) and (110.9 [86.9, 129.5] vs 100 [80.3, 129.5], p = 0.067]) respectively. Multiple islet antibodies (IA) were significantly more common among patients in the pre-COVID-19 group compared to the COVID-19 group (72% vs 61%, p = 0.032). Tissue transglutaminase antibodies were more common among children diagnosed in the COVID-19 compared to the pre-COVID group (16.6% vs 7.9%, p = 0.022). CONCLUSIONS: Our findings suggest that SARS-CoV-2 and the environmental alterations caused by the pandemic affected the clinical characteristics and the immunological profile of children diagnosed with T1D. It is, therefore, plausible that the virus plays a role in the autoimmune process causing T1D.

Linear growth of children with X-linked hypophosphatemia treated with burosumab: a real-life observational study.

To assess the long-term efficacy of burosumab for pediatric patients with X-linked hypophosphatemia, focusing on linear growth. This multi-center retrospective study included 35 pediatric patients who began treatment with burosumab between January 2018 and January 2021. We collected clinical data, anthropometric measurements, laboratory results, and Rickets Severity Score (RSS), from 2 years prior to treatment initiation and up to 4 years after. Burosumab was initiated at a mean age of 7.5 ± 4.4 years (range 0.6-15.9), with a mean initial dose of 0.8 ± 0.3 mg/kg, which was subsequently increased to 1.1 ± 0.4 mg/kg. The patients were followed for 2.9 ± 1.4 years (range 1-4) after initiating burosumab. Serum phosphorus levels increased from 2.7 ± 0.8 mg/dl at burosumab initiation to 3.4 ± 0.6 mg/dl after 3 months and remained stable (p < 0.001). Total reabsorption of phosphorus increased from 82.0 ± 6.8 to 90.1 ± 5.3% after 12 months of treatment (p = 0.041). The RSS improved from 1.7 ± 1.0 at burosumab initiation to 0.5 ± 0.6 and 0.3 ± 0.6 after 12 and 24 months, respectively (p < 0.001). Both height z-score and weight z-score improved from burosumab initiation to the end of the study: from - 2.07 ± 1.05 to - 1.72 ± 1.04 (p < 0.001) and from - 0.51 ± 1.12 to - 0.11 ± 1.29 (p < 0.001), respectively. Eight children received growth hormone combined with burosumab treatment. Height z-score improved among those who received growth hormone (from - 2.33 ± 1.12 to - 1.94 ± 1.24, p = 0.042) and among those who did not (from - 2.01 ± 1.01 to - 1.66 ± 1.01, p = 0.001). CONCLUSION:  Burosumab treatment in a real-life setting improved phosphate homeostasis and rickets severity and enhanced linear growth. WHAT IS KNOWN: • Compared to conventional therapy, burosumab treatment has been shown to increase serum phosphate levels and reduce the severity of rickets. • The effect of burosumab on growth is still being study. WHAT IS NEW: • Height z-score improved between the start of burosumab treatment and the end of the study (-2.07 ± 1.05 vs. -1.72 ± 1.04, p < 0.001). • Eight children received burosumab combined with growth hormone treatment without side effects during the concomitant treatments.

Post-operative anterior diaphragmatic hernias in children with Trisomy 21 after cardiac surgery.

Morgagni hernias account for less than 5% of congenital diaphragmatic hernias. They are characteristically retrosternal and bilateral, with right-sided predominance. An association between Trisomy 21 and diaphragmatic hernias resembling Morgagni hernia has been reported, but the effect of cardiac surgery on its formation has not been investigated. The purpose of this study was to determine whether there is a higher incidence of anterior diaphragmatic hernias in children with Trisomy 21 after cardiac surgery. We compared the prevalence of anterior diaphragmatic hernias in 92 patients with Trisomy 21 who underwent cardiac surgery with its prevalence in 100 children without Trisomy 21 who underwent cardiac surgery. All available CXRs of all children underwent revision for the presence of an anterior diaphragmatic hernia by a pediatric radiologist. Within the study group, four cases of an anterior diaphragmatic hernia were detected, all upon presentation to the emergency room due to breathing difficulties. No cases of an anterior diaphragmatic hernia were found in the control group (P = 0.0094). CONCLUSIONS: A high index of suspicion for an anterior diaphragmatic hernia should be maintained in children with Trisomy 21 who have undergone cardiac surgery and present with breathing difficulty. If CXR findings are uncertain, UGI series and\or CT should be performed. In light of our findings, the surgical technique has been modified in patients with DS in our medical center. WHAT IS KNOWN: • Several studies reported an association between Trisomy 21 and diaphragmatic hernia resembling Morgagni hernia, but the effect of cardiac surgery on its formation has not been investigated. WHAT IS NEW: • There is a higher incidence of anterior diaphragmatic hernia resembling a Morgagni hernia in children with Trisomy 21 after cardiac surgery. • A high index of suspicion for an anterior diaphragmatic hernia should be maintained in children with Trisomy 21 who have undergone cardiac surgery and present with breathing difficulty. If CXR findings are uncertain, UGI series and\or CT should be performed.

Challenging and Facilitating Factors When Coping with the News of a Newborn's Down Syndrome Diagnosis: Perceptions of Activist Israeli Mothers.

Studies have shown that healthcare professionals (HP) play a significant role in parents' experience when informed of the birth of a child with Down Syndrome (DS). Past studies have focused on faith dilemmas of religious mothers that were informed that their child was born with DS and on understanding how faith was a source of emotional support for them. Studies that focus on religious activist mothers are scarce. We utilized a qualitative methodology to explore the experiences of Jewish mothers who are religious and activists. Semistructured interviews and focus groups were conducted with 17 religious Jewish mothers of children with DS, who participated in an activist, self-support group. The data were analyzed using interpretative phenomenological analysis (IPA). Most mothers felt unsupported by the HP although a few mentioned being congratulated on the birth and empowered by a physician who focused on their child's potential to develop. The mothers appreciated when HPs considered their opinions and values. They shared the common goal of changing the existing pathological, statistics-based discourse concerning children with DS. The study reinforces the important role of HP and policymakers' in collaborating with parents and their support groups early in the diagnostic stage.

Optic pathway glioma and endocrine disorders in patients with and without NF1.

BACKGROUND: Optic pathway gliomas (OPGs) are classified by anatomic location and the association with neurofibromatosis type 1 (NF1). Children with OPGs face sequelae related to tumor location and treatment modalities. We assessed the prevalence of endocrine dysfunction in children with OPGs and compared outcomes between those with and without NF1. METHODS: We performed a retrospective medical record review of medical history, and clinical and laboratory data, of children diagnosed with OPGs (n = 59, 61% with NF1) during 1990-2020, followed at a tertiary endocrine clinic. Growth and puberty parameters and occurrence of endocrine dysfunction were evaluated. RESULTS: Isolated optic nerve involvement was higher among patients with than without NF1. Patients without NF1 were younger at OPG diagnosis and more often treated with debulking surgery or chemotherapy. At the last endocrine evaluation, patients without NF1 had comparable height SDS, higher BMI SDS, and a higher rate of endocrine complications (78.3% vs. 41.7%, p = 0.006). Younger age at diagnosis, older age at last evaluation, and certain OPG locations were associated with increased endocrine disorder incidence. CONCLUSIONS: Endocrine dysfunction was more common in patients without NF1; this may be related to younger age at presentation, tumor locations, a greater progressive rate, and more aggressive treatments. IMPACT: The literature is sparse regarding sporadic OPGs, and the mean duration of follow-up is shorter than at our study. Our data show a higher rate of endocrine dysfunction in patients with OPGs than previously described. We also found a higher prevalence of endocrine dysfunctions among patients without compared to those with NF-1. A better understanding of the true prevalence of endocrine disabilities that may evolve along time can help in guiding physicians in the surveillance needed in patients with OPG.

Youth-onset type 2 diabetes in Israel: A national cohort.

BACKGROUND: Prevalence of youth-onset type 2 diabetes (T2D) has increased worldwide, paralleling the rise in pediatric obesity. Occurrence and clinical manifestations vary regionally and demographically. OBJECTIVES: We assessed the incidence, and clinical and demographic manifestations of youth-onset T2D in Israel. METHODS: In a national observational study, demographic, clinical, and laboratory data were collected from the medical records of children and adolescents, aged 10-18 years, diagnosed with T2D between the years 2008 and 2019. RESULTS: The incidence of youth-onset T2D in Israel increased significantly from 0.63/100,000 in 2008 to 3.41/100,000 in 2019. The study cohort comprised 379 individuals (228 girls [59.7%], 221 Jews [58.3%], mean age 14.7 ± 1.9 years); 73.1% had a positive family history of T2D. Mean body mass index (BMI) z-score was 1.96 ± 0.7, higher in Jews than Arabs. High systolic (≥ 130 mmHg) and diastolic blood pressure (≥ 85 mmHg) were observed in 33.7% and 7.8% of patients, respectively; mean glycosylated hemoglobin (A1c) level at diagnosis was 8.8 ± 2.5%. Dyslipidemia, with high triglyceride (>150 mg/dl) and low HDL-c (<40 mg/dl) levels, was found in 45.6% and 56.5%, respectively. Microalbuminuria and retinopathy were documented at diagnosis, 15.2% and 1.9%, respectively) and increased (36.7% and 4.6%, respectively) at follow-up of 2.9 ± 2.1 years. Criteria of metabolic syndrome were met by 224 (62.2%) patients, and fatty liver documented in 65%, mainly Jews. Psychosocial comorbidity was found in 31%. Treatment with metformin (45.6%), insulin (20.6%), and lifestyle modification (18%) improved glycemic control. CONCLUSION: Youth-onset T2D in Israel has increased significantly and presents a unique profile.

Symptoms and Glycemic Control in Young People With Type 1 Diabetes Following SARS-CoV-2 Infection: An Observational Study.

CONTEXT: Data is needed regarding the effect of SARS-CoV-19 infection on young people with established type 1 diabetes. Identifying the disease outcomes, short and long-term sequelae may help to establish an evidence-based prevention and education policy for sick days management and DKA prevention. OBJECTIVE: This work aims to describe clinical manifestations of SARS-CoV-2 infection in children, adolescents, and young adults with established type 1 diabetes (T1D) and explore the effects of COVID-19 on glycemic control and disease course. METHODS: An observational study was conducted at 3 pediatric diabetes clinics in Israel between mid-March 2020 and mid-March 2021. Included were young people with established T1D, age younger than 30 years, who tested positive for SARS-CoV-2 (quantitative real-time polymerase chain reaction). Data were collected from medical files, diabetes devices, and COVID-19 questionnaire. Outcome measures were analyzed by the presence/absence of clinical symptoms (symptomatic/asymptomatic) and by age group (pediatric, < 19 years/young adults, 19-30 years). RESULTS: Of 132 patients, mean age 16.9 ±â€…5.3years, with COVID-19-confirmed infection, 103 (78%) had related symptoms; the most common were headaches, fatigue, fever, and loss of sense of smell. All had a mild disease course, but 4 required hospitalization and 2 cases were directly related to COVID-19 infection (pleuropneumonia in a patient with immunodeficiency syndrome, 1 case of diabetic ketoacidosis). Logistic regression analysis showed that age (odds ratio [OR] = 1.11; 95% CI, 1.01-1.23; P = .033), elevated glucose levels (OR = 5.23; 95% CI, 1.12-24.41; P = .035), and comorbidities (OR = 8.21; 95% CI, 1.00-67.51; P = .050) were positively associated with symptomatic infection. Persistent symptoms occurred in 16.5% of the cohort over a median of 6.7 months; age (OR = 1.14; 95% CI, 1.01-1.29; P = .030) and elevated glucose levels (OR = 3.42; 95% CI, 1.12-10.40; P = .031) were positively associated with persistent symptoms. Usually, no change was reported in glucose levels (64%) except for a temporary deterioration in glycemic control during the short infection period. CONCLUSION: Young people with established T1D experience mild COVID-19 infection. Elevated glucose levels during COVID-19 infection and older age were associated with prolonged disease course.

Diagnosing Growth Hormone Deficiency: Can a Combined Arginine and Clonidine Stimulation Test Replace 2 Separate Tests?

OBJECTIVE: Given the large number of false-positive growth hormone deficiency (GHD) diagnoses from a single growth hormone (GH) stimulation test in children, 2 different pharmacologic tests, performed on separate days or sequentially, are required. This study aimed to assess the reliability and safety of a combined arginine-clonidine stimulation test (CACST). METHODS: This was a retrospective, single-center, observational study. During 2017-2019, 515 children aged >8 years underwent GH stimulation tests (CACST: n = 362 or clonidine stimulation test [CST]: n = 153). The main outcome measures used to compare the tests were GH response (sufficiency/deficiency) and amplitude and timing of peak GH and safety parameters. RESULTS: Population characteristics were as follows: median age of 12.2 years (interquartile range [IQR]: 10.7, 13.4), 331 boys (64%), and 282 prepubertal children (54.8%). The GHD rate was comparable with 12.7% for CACST and 14.4% for CST followed by a confirmatory test (glucagon or arginine) (P = .609). Peak GH was higher and occurred later in response to CACST compared with CST (14.6 ng/mL [IQR: 10.6, 19.4] vs 11.4 ng/mL [IQR: 7.0, 15.8], respectively, P < .001; 90 minutes [IQR: 60, 90] vs 60 minutes [IQR: 60, 90], respectively, P < .001). No serious adverse events occurred following CACST. CONCLUSION: Our findings demonstrate the reliability and safety of CACST in detecting GHD in late childhood and adolescence, suggesting that it may replace separate or sequential GH stimulation tests. By diminishing the need for the second GH stimulation test, CACST saves time, is more cost-effective, and reduces discomfort for children, caregivers, and medical staff.

Pregnant women's alcohol consumption and knowledge about its risks: An Israeli survey.

BACKGROUND: Alcohol consumption is found in a significant proportion of women during their pregnancies. The only study on the prevalence of alcohol consumption during pregnancy in Israel was conducted over a decade ago. Thus, our study aimed to assess alcohol consumption before and during pregnancy, associations with demographic characteristics, knowledge of possible risks of prenatal alcohol exposure, and relations among such knowledge, sociodemographic characteristics, and drinking habits. METHODS: A convenience sample of 802 pregnant Israeli women completed an anonymous online questionnaire regarding their alcohol consumption during pregnancy, recommendations received, and knowledge of possible risks. RESULTS: Of the sample, 539 (67.2 %) women self-reported drinking alcohol in the 2 months prior to learning they were pregnant, and 96 (12 %) during their pregnancy. Twice as many (28.1 %) reported knowing other women who had consumed alcohol during pregnancy. Women with higher education, in their first pregnancies, ethnically Jewish, and secular reported the highest pre-pregnancy rates of alcohol consumption. About 40 % reported receiving no education about the dangers of alcohol consumption during pregnancy. CONCLUSIONS: A concerning percentage of pregnant women in Israel acknowledge drinking alcohol near and after conception. Although most participants reported discontinuing use after realizing they were pregnant, a worrying percentage continued consumption with little knowledge of the dangers. Actual rates may be higher. Information about risks of prenatal alcohol exposure is not widely disseminated, emphasizing the need to increase public awareness.

Growth assessment of children during the COVID-19 pandemic-Can we rely on parental measurements?

AIM: The COVID-19 pandemic prompted the rapid development of remote medical services. During lockdown periods, children's growth data were obtained from parents' home assessments. This study aimed to assess the accuracy of home height and weight measurements and analyse their utility in clinical decision-making. METHODS: A retrospective, single-centre observational study. Children aged 3-18 years were measured for weight and height at home using guidance provided to parents on proper measurements techniques before subsequent professional re-evaluation at our endocrine institution clinic. The two sets of measurements were compared and analysed according to various clinical parameters. RESULTS: Height measurements at home and in the clinic were comparable (diff = 0.1 ± 1.3cm, p = 0.42) amongst the 107 children (mean age 10.2 ± 3.7, 56.1% males) participating in the study, except in overweight and obese children where they were significantly higher in the clinic (diff = 0.86 ± 1.48cm, p = 0.018). Weight and BMI were significantly higher in the clinic (diff = 0.45 ± 0.8kg and diff = 0.3 ± 0.6kg/m2 , p<0.001 and p<0.001, respectively). CONCLUSIONS: Height measurements of children by their parents were accurate except in obese and overweight children, whereas weight measurements tended to be lower than in the clinic. With proper guidance, parents' home measurements of height and weight are accurate and suitable for clinical decision-making.

Dyslipidemia and cardiovascular disease risk factors in patients with type 1 diabetes: A single-center experience.

BACKGROUND: Type 1 diabetes (T1D) contributes to altered lipid profiles and increases the risk of cardiovascular disease (CVD). Youth with T1D may have additional CVD risk factors within the first decade of diagnosis. AIM: To examine risk factors for dyslipidemia in young subjects with T1D. METHODS: Longitudinal and cross-sectional retrospective study of 170 young subjects with T1D (86 males; baseline mean age 12.2 ± 5.6 years and hemoglobin A1c 8.4% ± 1.4%) were followed in a single tertiary diabetes center for a median duration of 15 years. Predictors for outcomes of lipid profiles at last visit (total cholesterol [TC], triglycerides [TGs], low-density lipoprotein-cholesterol [LDL-c], and high-density lipoprotein-cholesterol [HDL-c]) were analyzed by stepwise linear regression models. RESULTS: At baseline, 79.5% of the patients had at least one additional CVD risk factor (borderline dyslipidemia/dyslipidemia [37.5%], pre-hypertension/hypertension [27.6%], and overweight/obesity [16.5%]) and 41.6% had multiple (≥ 2) CVD risk factors. A positive family history of at least one CVD risk factor in a first-degree relative was reported in 54.1% of the cohort. Predictors of elevated TC: family history of CVD (ß[SE] = 23.1[8.3], P = 0.006); of elevated LDL-c: baseline diastolic blood pressure (DBP) (ß[SE] = 11.4[4.7], P = 0.003) and family history of CVD (ß[SE] = 20.7[6.8], P = 0.017); of elevated TGs: baseline DBP (ß[SE] = 23.8[9.1], P = 0.010) and family history of CVD (ß[SE] = 31.0[13.1], P = 0.020); and of low HDL-c levels: baseline DBP (ß[SE] = 4.8[2.1], P = 0.022]). CONCLUSION: Our findings suggest that elevated lipid profiles are associated with DBP and a positive family history of CVD. It is of utmost importance to prevent and control modifiable risk factors such as these, as early as childhood, given that inadequate glycemic control and elevation in blood pressure intensify the risk of dyslipidemia.

Coronavirus and People with Intellectual Disabilities: A Special Perspective.

BACKGROUND: The attention of the world is focused on the coronavirus disease-2019 (COVID-19) pandemic. There is s general awareness that certain population groups are at greater risk. However, some other populations may be transparent and may not be receiving the attention they warrant. We focused on those with intellectual disability explaining why they are vulnerable during the current pandemic and require special attention.

Hydrocarbon Intoxication in Children: Clinical and Sociodemographic Characteristics.

OBJECTIVES: Hydrocarbon intoxication in children still occurs, although it is preventable. It may cause a variety of clinical manifestations, involving the respiratory system and the nervous system. Our goal was to investigate all cases of hydrocarbon poisoning in children hospitalized in the Hadassah-Hebrew university hospitals in Jerusalem due to exposure to hydrocarbon in 2 decades. METHODS: We retrieved the clinical and sociodemographic characteristics of all children who were admitted to our hospitals because of hydrocarbon intoxication in 2 decades. RESULTS: One hundred seventy-two children were hospitalized, primarily because of ingestion of kerosene. In most cases, the poisons were stored in a bottle or other easily accessible container. Boys were more likely than girls to be hospitalized. Most of the children were of Arab origin in families with more than 3 children. Coughing, vomiting, and a decrease in conscious state were common at presentation, followed by fever and dyspnea. The clinical course was usually mild to moderate and self-resolving. Some children were treated with oxygen, fluids, and antibiotics. The main result of hydrocarbon poisoning was chemical pneumonitis, and many had pathological chest x-rays. Only one severe case resulted in death. CONCLUSIONS: Hydrocarbon intoxication results in a variety of clinical manifestations and can be life-threatening. Most cases of poisoning could have been easily prevented if the substances were kept out of the reach of children.

Pediatricians as Case Managers Reduce the Exposure to Computerized Tomography in Children Experiencing Minor Head Trauma.

BACKGROUND: Head trauma is one of the most common reasons for pediatric emergency medicine department (PED) visits. Computerized tomography (CT) scan is considered the criterion standard for the diagnosis of traumatic brain injury but was shown to increases the risk of malignancies. METHODS: We retrospectively analyzed collected data of all children (ages 0-16 years) experiencing mild head trauma who were admitted to a single center, from January 1, 2010, to December 31, 2015. Comparison between patients treated by pediatricians/pediatric emergency medicine physicians (PEMP) with those treated by surgeons regarding CT rates and prognosis was done. RESULTS: During the previously mentioned period, 4232 children presented to the PED after minor head trauma, the average age was 5.4 (±4) years and 67.1% were male. Head CT was done in 7.7%, of which 30.7% had positive findings. Younger children tended to have higher percentage of positive findings on CT scan (60%, 43.8%, 26.6%, P = 0.003, for children up to 5 months, 5-24 months, and older than 24 months, respectively). Pediatricians ordered less CT scans when compared with surgeons (5.4% vs 8.5%, P < 0.001). Moreover, they had higher rates of positive findings on CT scan (52.5% vs 25.8%, P < 0.001). When all other characteristics were similar, if the case manager was a pediatrician, the patient's chances to undergo a CT scan were 4.3 times lower than if the case manager was a surgeon (odds ratio, 4.277; confidence interval, 2.274-7.104). No difference in readmissions or other complications were found between the 2 groups. DISCUSSION: This study highlights that when the case manager of children with minor head trauma is a pediatrician/PEMP, CT scan rates and thus exposure to radiation are diminished without a failure to detect clinically important traumatic brain injury.In conclusion, our findings suggest that when possible, all children experiencing minor head trauma should be treated by a pediatrician/PEMP in the PED.

Pediatric reference values of TSH should be personalized according to BMI and ethnicity.

OBJECTIVE: The need for personalization of the reference values of thyroid function tests has been previously suggested. We aimed at determining TSH reference values in a large cohort of children according to age, sex, BMI, and ethnicity. DESIGN: A population-based cohort study. METHODS: The study cohort included 75 549 healthy children aged 5-18 years. Data analyzed included age, gender, TSH, FT4 levels, BMI and ethnicity. Multivariate logistic regression analysis examined the associations between the study parameters. RESULTS: TSH in the Jewish population is lower than in the non-Jewish population (median: 2.1 IU/L (IQR: 1.5) vs 2.2 IU/L (IQR: 1.5), P < 0.0001). TSH is significantly affected by BMI for children defined as underweight, normal weight, overweight or obese, levels increased as weight diverged from the normal range (median levels: 2.1 IU/L (IQR: 1.4), 2.0 IU/L (IQR: 1.3), 2.1 IU/L (IQR: 1.4), 2.4 (IQR: 1.5), respectively, P < 0.001). The 2.5 percentile is affected by gender and BMI (P < 0.02 and P < 0.001, respectively), while the 97.5 percentile is affected by ethnic origin and BMI (P < 0.001 for both). New TSH reference intervals (RI) adjusted according to BMI and ethnicity are suggested. Comparison of the old and new RI demonstrate the significance of RI personalization: 25.1% of the children with TSH levels above the old RI are within the new RI, while 2.3% of the children who were in the old RI are below the new RI. CONCLUSIONS: TSH reference values in children are affected by BMI and ethnicity. Reference values should be individualized accordingly to improve future clinical decision-making and treatment.

Fetal alcohol spectrum disorder among pre-adopted and foster children.

BACKGROUND: Fetal alcohol spectrum disorder (FASD) is a leading cause of neurodevelopmental disorders. Children in foster care or domestically adopted are at greater risk for FASD. The aim of this study was to determine the prevalence or risk for FASD in a selected population of foster and adopted children. METHODS: Children between 2 and 12 years who were candidates for adoption in foster care were evaluated for clinical manifestations and historical features of fetal alcohol spectrum disorder based on established criteria for FASD. RESULTS: Of the 89 children evaluated, 18 had mothers with a confirmed history of alcohol consumption during pregnancy. Two children had fetal alcohol syndrome and one had partial fetal alcohol syndrome. In addition, five had alcohol-related neurodevelopmental disorder, one had alcohol-related birth defects, and a single child had manifestations of both. Of the 71 children in which fetal alcohol exposure could not be confirmed, many had manifestations that would have established a diagnosis of FASD were a history of maternal alcohol consumption obtained. CONCLUSIONS: In a population of high-risk children seen in an adoption clinic, many had manifestations associated with FASD especially where prenatal alcohol exposure was established. The reported prevalence in this study is higher than that reported in our previous study of younger children. This is most likely due to the higher number of children diagnosed with alcohol-related neurodevelopmental disorders that typically manifest at an older age.