Effects of COVID-19 pandemic on pediatric endocrinology practice, childhood obesity, pubertal progression and diabetes

In the COVID-19 pandemic, millions of people have had to stay in isolation for months. Children did not go to school for a long time, they spent much more time at home and were sedentary. They also spent much more time on screen-related activities (personal computer (PC), mobile phone, music player, tablet, game console, and television (TV). These situations have had various effects on children and adolescents. Undoubtedly, long-term restrictions and lifestyle changes have had effects on individuals with childhood obesity, pubertal progression, and type 1 diabetes (T1D). In this review, articles investigating the effect of COVID-19 quarantine/pandemic on adolescence, childhood obesity and diabetes were compiled and the effect of the COVID pandemic on these frequently encountered situations in pediatric endocrine practice was tried to be revealed. © 2022, Pamukkale University. All rights reserved.

Analysis of disease spectrum of hospitalized children during outbreak of coronavirus disease 2019 in pediatric department of a tertiary general hospital in Shanghai.

Objective To analyze the changes of disease spectrum in pediatric inpatients before and after the outbreak of coronavirus disease 2019 (COVID-19). Methods The data of gender, age, habitual residence, diagnosis and other relevant information of 1 931 hospitalized children in Department of Pediatrics, The First Affiliated Hospital of Naval Medical University (Second Military Medical University) from Feb. 2019 to Jan. 2020 (1 year before the COVID-19 epidemic) and 618 hospitalized children from Feb. 2020 to Jan. 2021 (1 year after the COVID-19 epidemic) were collected. The total number, habitual residence, gender and disease spectrum of hospitalized children 1 year before and 1 year after the COVID-19 epidemic were statistically analyzed. Results The number of hospitalized children decreased by 68.00% (1 313/1 931) 1 year after the COVID-19 epidemic. The number of hospitalized children from other provinces and cities was decreased (17.80%110/618vs 29.00%560/1 931) and there was significantly difference in the distribution of habitual residence of hospitalized children between 1 year before and 1 year after the COVID-19 epidemic (P<0.01). One year after the COVID-19 epidemic, the number of children with respiratory diseases decreased by 92.04% (971/1 055), and the proportion was also decreased (13.59%84/618vs 54.63%1 055/1 931);the number of children with endocrine system diseases increased by 20.71% (29/140), and the proportion was increased (27.35%169/618vs 7.25%140/1 931);the number of children with neonatal diseases decreased by 43.01% (166/386), but the proportion was increased (35.60%220/618 vs 19.99%386/1 931). Compared with 1 year before the COVID-19 epidemic, there were significant differences in the proportions of respiratory diseases, endocrine system diseases and neonatal diseases in hospitalized children 1 year after the COVID-19 epidemic (all P<0.01). The age distribution of hospitalized children 1 year before and 1 year after the epidemic of COVID-19 was different (P<0.01), and the number of hospitalized children was also different in different seasons (P<0.05). One year after the epidemic of COVID-19, the number of hospitalized children with respiratory diseases was decreased most significantly, and the number of children with pneumonia decreased by 93.71% (655/699), with a significant difference found in the proportions of pneumonia between 1 year before and 1 year after the COVID-19 epidemic (52.38%44/84vs 66.26% 699/1 055, P<0.05). Compared with 1 year before the COVID-19 epidemic, the proportion of endocrine system diseases such as short stature/growth retardation was decreased and the proportion of precocious puberty/early puberty development was increased 1 year after the COVID-19 epidemic (P<0.05). Conclusion The COVID-19 epidemic has led to a significant decrease in hospitalized children in department of pediatric, especially in the proportion of respiratory diseases, but it has led to an increase in hospitalized children with endocrine system diseases, suggesting that epidemic prevention and control measures can effectively reduce respiratory diseases requiring hospitalization, but may increase precocious puberty and early puberty development. These changes should be considered by department of pediatrics in general hospitals.Copyright © 2022, Second Military Medical University Press. All rights reserved.

Myocardial infarction at night . . . and other stories

Body weight and fat content are known to influence the timing of puberty but the association remained after adjustment for pre-pubertal body mass index. [...]a large retrospective study from the US finds that patients who underwent plasma exchange spent a week longer in hospital and were two to three times more likely to die than those who received immunoglobulin (Muscle Nerve doi:10.1002/mus.26831). A case study in NEJM Catalyst identifies early testing (particularly of people arriving from places where the disease was prevalent), rapid mobilisation of microbiological laboratories, and a coherent and consistent national strategy as crucial interventions.

Analysis of disease spectrum of hospitalized children during outbreak of coronavirus disease 2019 in pediatric department of a tertiary general hospital in Shanghai

Objective To analyze the changes of disease spectrum in pediatric inpatients before and after the outbreak of coronavirus disease 2019 (COVID-19). Methods The data of gender, age, habitual residence, diagnosis and other relevant information of 1 931 hospitalized children in Department of Pediatrics, The First Affiliated Hospital of Naval Medical University (Second Military Medical University) from Feb. 2019 to Jan. 2020 (1 year before the COVID-19 epidemic) and 618 hospitalized children from Feb. 2020 to Jan. 2021 (1 year after the COVID-19 epidemic) were collected. The total number, habitual residence, gender and disease spectrum of hospitalized children 1 year before and 1 year after the COVID-19 epidemic were statistically analyzed. Results The number of hospitalized children decreased by 68.00% (1 313/1 931) 1 year after the COVID-19 epidemic. The number of hospitalized children from other provinces and cities was decreased (17.80%[110/618]vs 29.00%[560/1 931]) and there was significantly difference in the distribution of habitual residence of hospitalized children between 1 year before and 1 year after the COVID-19 epidemic (P<0.01). One year after the COVID-19 epidemic, the number of children with respiratory diseases decreased by 92.04% (971/1 055), and the proportion was also decreased (13.59%[84/618]vs 54.63%[1 055/1 931]);the number of children with endocrine system diseases increased by 20.71% (29/140), and the proportion was increased (27.35%[169/618]vs 7.25%[140/1 931]);the number of children with neonatal diseases decreased by 43.01% (166/386), but the proportion was increased (35.60%[220/618] vs 19.99%[386/1 931]). Compared with 1 year before the COVID-19 epidemic, there were significant differences in the proportions of respiratory diseases, endocrine system diseases and neonatal diseases in hospitalized children 1 year after the COVID-19 epidemic (all P<0.01). The age distribution of hospitalized children 1 year before and 1 year after the epidemic of COVID-19 was different (P<0.01), and the number of hospitalized children was also different in different seasons (P<0.05). One year after the epidemic of COVID-19, the number of hospitalized children with respiratory diseases was decreased most significantly, and the number of children with pneumonia decreased by 93.71% (655/699), with a significant difference found in the proportions of pneumonia between 1 year before and 1 year after the COVID-19 epidemic (52.38%[44/84]vs 66.26% [699/1 055], P<0.05). Compared with 1 year before the COVID-19 epidemic, the proportion of endocrine system diseases such as short stature/growth retardation was decreased and the proportion of precocious puberty/early puberty development was increased 1 year after the COVID-19 epidemic (P<0.05). Conclusion The COVID-19 epidemic has led to a significant decrease in hospitalized children in department of pediatric, especially in the proportion of respiratory diseases, but it has led to an increase in hospitalized children with endocrine system diseases, suggesting that epidemic prevention and control measures can effectively reduce respiratory diseases requiring hospitalization, but may increase precocious puberty and early puberty development. These changes should be considered by department of pediatrics in general hospitals.Copyright © 2022, Second Military Medical University Press. All rights reserved.

The effect of environmental factors on precocious puberty in children: a case-control study.

BACKGROUND: Recently the prevalence of precocious puberty development is increasing among Chinese children. Proper understanding of the risk factors for precocious puberty in children is pivotal as could help to improve children's health. This study aims to evaluate the effect of environmental factors on precocious puberty in children. METHODS: We matched the cases and controls by age at the ratio of 1:1 (201 cases and 201 controls) for girls and 1:4 (24 cases and 96 controls) for boys. We used conditional logistic regression to explore the effect of environmental factors on precocious puberty, and a random forest model to identify the most important risk factor. RESULTS: In the multivariate regression, cesarean section (OR = 1.99, 95% CI: 1.05, 3.76), child body mass index [BMI] (OR = 1.25, 95% CI: 1.10, 1.43), maternal BMI (OR = 1.13, 95%CI: 1.01, 1.26), and exposure to secondhand smoke several times a month but less than once a week (OR = 4.09, 95%CI: 1.79,9.35), and almost every day (OR = 6.48, 95% CI: 2.14, 19.56) were risk factors for precocious puberty in girls. While maternal height (OR = 0.82, 95% CI: 0.75, 0.88), paternal height (OR = 0.91, 95% CI: 0.85, 0.98), bedtime at night (OR = 0.30, 95% CI: 0.17, 0.51), and night sleep (OR = 0.43, 95% CI: 0.21, 0.86) were protective factors. In boys, only exposure to secondhand smoke several times a month but less than once a week (OR = 7.94, 95% CI: 1.25, 50.33) was a risk factor for precocious puberty. In the random forest model, Child BMI was the most important risk factor for precocious puberty in girls. CONCLUSIONS: Our findings suggest that environmental factors were associated with precocious puberty in children, particularly in girls.

Precocious puberty under stressful conditions: new understanding and insights from the lessons learnt from international adoptions and the COVID-19 pandemic.

Neuro-biological variations in the timing of sexual maturation within a species are part of an evolved strategy that depend on internal and external environmental conditions. An increased incidence of central precocious puberty (CPP) has been described in both adopted and "covid-19 pandemic" children. Until recently, it was hypothesised that the triggers for CPP in internationally adopted children were likely to be better nutrition, greater environmental stability, and improved psychological wellbeing. However, following data collected during and after the coronavirus (COVID-19) global pandemic, other possibilities must be considered. In a society with high levels of child wellbeing, the threat to life presented by an unknown and potentially serious disease and the stressful environment created by lockdowns and other public health measures could trigger earlier pubertal maturation as an evolutionary response to favour early reproduction. The main driver for increased rates of precocious and rapidly progressive puberty during the pandemic could have been the environment of "fear and stress" in schools and households. In many children, CPP may have been triggered by the psychological effects of living without normal social contact, using PPE, being near adults concerned about financial and other issues and the fear of getting ill. The features and time of progression of CPP in children during the pandemic are similar to those observed in adopted children. This review considers the mechanisms regulating puberty with a focus on neurobiological and evolutionary mechanisms, and analyses precocious puberty both during the pandemic and in internationally adopted children searching for common yet unconsidered factors in an attempt to identify the factors which may have acted as triggers. In particular, we focus on stress as a potential factor in the early activation of the hypothalamic-pituitary-gonadal axis and its correlation with rapid sexual maturation.

Increased frequency of central precocious puberty during the coronavirus disease (COVID-19) pandemic at a single center in the Osaka Metropolitan Area of Japan

As environmental factors are known to affect the timing of puberty, self-isolation during the coronavirus disease (COVID-19) pandemic may affect the incidence of central precocious puberty (CPP). This study aimed to evaluate the frequency of CPP during the COVID-19 pandemic at a single center in the Osaka metropolitan area of Japan. We retrospectively analyzed the annual frequency of CPP occurrence before and after the first declaration of COVID-19 state of emergency in Japan at our hospital. We performed an interrupted time-series analysis to investigate the frequency of patients with CPP at our hospital from 2016 to 2021. There was a significant increase in the frequency of patients with CPP before and after the state of emergency declaration, both overall and among females. However, there was no significant increase in the number of males. There were no significant differences in the clinical, auxological, and endocrinological features between those diagnosed before and after the state of emergency. Overall, the frequency of CPP significantly increased during the COVID-19 pandemic at a single center in the Osaka metropolitan area of Japan.

Analysis of the incidence of central precocious puberty treated with gonadotropin-releasing hormone analogs. Impact of the COVID-19 pandemic / Análisis de la incidencia de pubertad precoz central tratada con análogos de hormona liberadora de gonadotrofina. Impacto de la pandemia por COVID-19

Introducción. Desde inicios de la pandemia por coronavirus 2019 (COVID-19), fue comunicado en varios países un incremento de las consultas de niñas con pubertad precoz central idiopática (PPCI), sin que contáramos con datos argentinos. Este aumento estaría vinculado con los cambios en el estilo de vida y los niveles de estrés resultantes del aislamiento que afectó particularmente a la población infantil. Objetivos. 1) Describir la evolución de la incidencia de PPCI con requerimiento de inhibición del eje hipotálamo-hipófiso-gonadal (EHHG) en niñas entre 2010 y 2021 en una cohorte del Área Metropolitana de Buenos Aires. 2) Comparar las características de las niñas, con dicho diagnóstico realizado durante la pandemia, con las de un grupo control. Métodos. Serie de tiempo interrumpida y estudio de casos y controles. Resultados. La incidencia anual fue estable entre 2010 y 2017. Desde 2017 hubo un ascenso anual que promedió el 59,9 % (IC95 % 18,6-115,5) y pareciera haberse acelerado durante la pandemia. Constatamos asociación entre haber desarrollado PPCI y haber requerido tratamiento inhibitorio entre el 01 de junio de 2020 y el 31 de mayo de 2021, y dos variables: edad de menarca materna (OR 0,46; IC95 % 0,28-0,77) y antecedente familiar de PPCI (OR 4,42; IC95 % 1,16-16,86). Conclusión. Evidenciamos desde 2017 un aumento significativo en la incidencia de PPCI con requerimiento de inhibición del EHHG. El incremento en la exposición a diversos desencadenantes ambientales durante la pandemia por COVID-19 podría haber ejercido mayor influencia en las niñas con alguna predisposición genética.

Introduction. Since the onset of the coronavirus disease 2019 (COVID-19) pandemic, consultations of girls with idiopathic central precocious puberty (ICPP) increased in several countries, but there were no data from Argentina. This increase may be related to changes in lifestyle and stress levels resulting from the lockdown, which particularly affected the child population. Objectives. 1) To describe the progression of the incidence of ICPP requiring inhibition of the hypothalamic- pituitary-gonadal (HPG) axis in girls between 2010 and 2021 in a cohort from the Metropolitan Area of Buenos Aires. 2) To compare the characteristics of girls diagnosed with ICPP during the pandemic with those of a control group. Methods. Interrupted time-series and case-control study. Results. The annual incidence remained stable between 2010 and 2017. Since 2017, it increased to an average of 59.9% (95% CI: 18.6­115.5) and appears to have accelerated during the pandemic. We found an association between ICPP and requiring inhibitory treatment between June 1 st, 2020 andMay 31 st, 2021 and 2 variables: maternal age at menarche (OR: 0.46, 95% CI: 0.28­0.77) and family history of ICPP (OR: 4.42, 95% CI: 1.16­16.86). Conclusion. We evidenced a significant increase in the incidence of ICPP with requirement of HPG axis inhibition since 2017. Increased exposure to various environmental triggers during the COVID-19 pandemic may have had a greater influence in girls with some genetic predisposition.

The Role of Estradiol in Modifying Circadian Rhythms, Sleep Regularity and Risk for Depression During the Pubertal Transition

Background: The pubertal transition (PT) is characterized by dramatic reproductive hormone fluctuations, a developmental circadian delay, and significant changes in sleep and wake patterns. The PT also marks an abrupt divergence between the sexes in risk for depression and sleep disorders that remains elevated for females across the reproductive lifespan, implicating ovarian hormones (i.e., estradiol (E2)) as a common pathway of risk. Notably, inconsistent schedules during the COVID-19 pandemic have contributed to greater sleep irregularity (especially for adolescents), which is associated with affective impairment and inferior clinical outcomes. The objective of this research is to characterize the pathophysiological impact of E2 on sleep disturbances, endocrine rhythm dysregulation and depressive symptoms in peripubertal females. Method(s): 44 peripubertal females (ages 11-14, within 1-year post-menarche) provided daily hormone (E1G-urinary metabolite of E2) and mood assessments for one menstrual cycle and completed an 8-day sleep assessment (actigraphy, daily sleep diaries), with cortisol and melatonin circadian measurement (over four days) starting at day 7 of the following menstrual cycle. Minute-to-minute consistency in sleep/wake state over 24-hrs was calculated to index sleep regularity (SRI). Result(s): A multiple regression model predicted depressive symptoms (CES-DC) from follicular menstrual cycle phase E1G-AUC, sleep regularity index (SRI), cortisol and melatonin AUCs (F(4,18) = 3.833, p=.020, R2=.46). E1G, cortisol-AUC (p<.05) and SRI (marginally, p=.08) contributed to the prediction. Conclusion(s): Results suggest that greater sleep irregularity, greater follicular estradiol and blunted cortisol may contribute to increased depressive symptoms in peripubertal females, providing mechanistic insight into the estradiol-related sleep and affect disruptions experienced during the pubertal transition. Funding Source: K01MH121575;Foundation of Hope for Research and Treatment of Mental Illness (NC) Keywords: Puberty, Sleep Disturbances, Estradiol, Circadian Rhythms, Depressive SymptomsCopyright © 2023

When it doesn't run in the blood(vessels) - events involved in vascular disorders.

In the current issue of the Biomedical Journal the underlying pathology of hemodynamic compromise in acute small subcortical infarction are elucidated. A follow-up study in patients with childhood Kawasaki disease is presented, as well as an insight into the gradually decreasing antigen expression in cases of acute myeloid leukemia. Furthermore this issue provides an exciting update concerning COVID-19 and the use of CRISPR-Cas, a review about computational approaches in the research of kidney stone formation, factors connected to central precocious puberty, and why a rock star of paleogenetics recently received a Nobel Prize. Additionally, this issue contains an article proposing the repurposing of the lung cancer drug Capmatinib, a study of how the gut microbiome develops in neonates, an impulse about the role of the transmembrane protein TMED3 in esophageal carcinoma, and the revelation about how competing endogenous RNA influences ischemic stroke. Lastly, genetic reasons for male infertility are discussed, as well as the relation between non-alcoholic fatty liver disease and chronic kidney disease.

Differential diagnosis of precocious puberty in girls during the COVID-19 pandemic: a pilot study.

BACKGROUND: To investigate the differential diagnosis of girls aged 6 to 8 years with idiopathic premature thelarche (IPT) and central precocious puberty (CPP) during the COVID-19 pandemic. We explored predicted adult height (PAH) discrepancy to guide appropriate diagnosis and treatment. METHODS: From January 2020 to December 2021, Chinese girls aged 6 to 8 years with precocious puberty were recruited. They were divided into IPT and CPP groups. Clinical characteristics, including height, weight, body mass index (BMI), basal luteinizing hormone (LH), oestradiol, uterine length and volume, follicle numbers (d > 4 mm) and bone age (BA) were recorded. We analysed differential diagnosis and PAH discrepancy in both groups. Binary logistic regression analysis was used to explore risk factors for CPP, and receiver operating characteristic (ROC) curves were generated to evaluate the diagnostic value of related indexes. RESULTS: Sixty patients, including 40 girls with IPT and 20 girls with CPP, were recruited. The prevalence of overweight and obesity in the entire cohort was 25% (15/60) and was significantly higher in IPT than CPP, 32.5% (13/40) vs. 10% (2/20), respectively (P=0.045). There were significant differences in LH, uterine volume, follicle numbers and BA (P<0.05). The impaired PAH of IPT and CPP was 0.01 ± 1.19 SD and 0.62 ± 0.94 SD with significant differences (P=0.047). Logistic regression analysis showed that LH and follicle numbers were independent risk factors for CPP. The ROC curve showed that the area under the curve (AUC) of LH and follicle numbers were 0.823 and 0.697. The sensitivity and specificity of LH with a cut off of 0.285 IU/L were 78.9% and 77.8%. The sensitivity and specificity of follicle numbers with a cut off of 3.5 were 89.5% and 52.8%. CONCLUSION: The prevalence of overweight and obesity in 6- to 8-year-old girls with precocious puberty was high. Auxological data should not be used in the differential diagnosis of IPT and CPP. Basal LH above 0.285 IU/L and follicle numbers greater than 4 were important features suggestive of CPP. PAH was impaired in individuals with CPP, but it was not impaired in individuals with IPT.

COVID-19 and early puberty-An unintended consequence of COVID-19 lockdown?

The novel coronavirus (SARS-CoV-2) causes the disease COVID-19, also termed as acute atypical pneumonia leading to respiratory failure. Children were more likely to spend time at home due to the lockdown mandated by governments as a preventive measure, which led to alterations in dietary habits and sleeping patterns which could have had a substantial influence on their sexual development, including but not limited to faster onset of puberty. Existing data suggested a plausible relationship between COVID-19 and early puberty. Obesity, physical activity, mental health, and birth weight are major risk factors that have further contributed to the early onset of puberty. In order to address such health crises affecting children, comprehensive solutions are urgently required. As COVID-19 continues to have multiple unpredictable health consequences, spreading awareness regarding this specific problem is of paramount importance.

Impacts of the COVID-19 pandemic on the diagnosis of idiopathic central precocious puberty in pediatric females in New York City.

OBJECTIVES: The COVID-19 pandemic had profound effect on physical and mental health. Stress was due physical inactivity, increased screen time, social isolation, fear of illness/death, as well as relative lack of resources including healthy food and finances. These stressors may be associated with an increase in idiopathic central precocious puberty (ICPP). The aim of the study was to assess the incidence of ICPP in females during the COVID-19 pandemic and compare biochemical and radiological parameters of females diagnosed in the previous two years, looking at associations among BMI, screen time, isolation, and stress in relation to the development of early puberty. METHODS: A retrospective chart review was performed of females diagnosed with ICPP. We divided subjects into a pandemic group and pre-pandemic group based on time of diagnosis. We compared anthropometric, serologic and radiologic data between the two groups. To assess psychosocial stress, we reviewed a COVID-19 impact survey which was administered to families at our endocrine clinic. RESULTS: There were a total of 56 subjects in the study; 23 subjects in the pre-pandemic group and 33 in the pandemic group. The pandemic cohort had significantly higher estradiol and LH levels and larger ovarian volumes. Survey results showed parental report of stress was moderate in 38 % of subjects and severe in 25 % of parents. In children, reported stress was moderate in 46 % of subjects. CONCLUSIONS: As puberty is influenced by exogenous factors including weight gain and psychosocial stress, we suspect that the environmental stress surrounding the pandemic influenced the increase in ICPP.

The importance of vaginoscopy in premenarchal girls with vaginal bleeding- call for more PAG practioners

Introduction: Prepubertal vaginal bleeding outside the neonatal period is always abnormal and is very alarming to both parents and physicians. The variable etiologies of vulvovaginitis are the most common causes of vaginal bleeding during the prepubertal period. We report a series of three cases observed during covid" period of 2020-2022. Case report: two patients 8 and 9 year -old girls, were refered to pediatric secondary center due to of external vaginal bleeding. Hormonal levels were pre-pubertal and bone age was not advanced. Both girls were hospitalized and sellar X-ray and pelvic MRI were done during further course, not revealing the etiology of bleeding. Six months after the first bleeding, they were reffered to a pediatric gynecologist where foreign bodies (grass seed) were found during vaginoscopy. Third patient, a 3-year- old girl, was examined by her pediatrician because of heavy bleeding. Hormonal analysis and bone age were not suggestive of precocious puberty. Additional analyses revealed elevated alpha fetoprotein level (>5000 IJ,), which led to the diagnosis of yolk sac tumor in vagina wall, which was then confirmed by vagionoscopy and biopsy. It is important to perform vaginoscopy in premenarchal girls with repeated vaginal bleeding because in patients older than five years, a common reason for vaginal bleeding is foreign body but in younger patients, the primary goal is to exclude a malignant tumor.Copyright © 2023

In French Children

A cohort of 120 pre-pubertal French children, aged 6-12 years, 45%F/55%M, with Type 1 diabetes since 5.1+/-2.2 years treated by continuous subcutaneous insulin infusion since 4.4+/-2.4 years, with HbA1c of 7.8+/-0.6%, were included in a 18-week randomized control study to assess 24/7 vs. evening and night Automated Insulin Delivery (AID) using Control-IQ algorithm and were further followed-up with free-life 24/7 AID for up to 83 to 101 weeks. Under 24/7 AID with a mean of 94.1% of time in closed-loop, the time in 70-180 mg/dl target range (TIR) reached 67.5+/-5.6% after 18 weeks (+12.5% vs. baseline), while time below 70 mg/dl (TBR) was 2.6% (95%CI 1.9-3.6) (reduction by 41% from baseline) and mean HbA1c was reduced by 0.5%. TIR at night-time was 77.2 +/-7.7% and TBR 2.2% (95%CI 1.0-3.7). During the follow-up after 36 and 83-101 weeks, similar glucose metrics were sustained with no occurrence of severe hypoglycemia or ketoacidosis. Meanwhile, 45% of children entered in puberty with no impact on glucose control. During a 13-week period of closed-loop interruption, TIR and TBR went back to baseline levels, whereas a later 13-week confinement due to the COVID-19 pandemic while Control-IQ was active had no impact on TIR and TBR levels. Our data shows that AID using active Control-IQ in free-life provides sustained improvement of glucose control with no safety concern in children, including during the pubertal period.

Bring the life stages into the domain of basic and clinical pharmacology.

Completely distinct physiological conditions and immune responses exist among different human life stages. Age is not always consistent with the life stage. We proposed to incorporate the concept of the life stages into basic and clinical pharmacology, including clinical trials, drug labels, and drug usage in clinical practice. Life-stage-based medical treatment is the application of medicine according to life stages such as prepuberty, reproductive, and aging. A large number of diseases are life-stage-dependent. Many medications and therapy have shown various age effects but not been recognized as life-stage-dependent. The same dosage and drug applications used in different life stages lead to divergent outcomes. Incorporating life stages in medicine and drug usage will enhance the efficacy and precision of the medication in disease treatment.

Rapidly progressive precocious puberty during the COVID-19 lockdown. / Pubertad precoz y pubertad rápidamente progresiva durante el confinamiento por la pandemia por COVID-19.

Introduction. During the COVID-19 pandemic, an increase in consultations for precocious puberty (PP) was observed. Our objective was to determine the frequency of PP and its progression before and during the pandemic. Methods. Retrospective, observational, analytical study. The medical records of patients who consulted with the Department of Pediatric Endocrinology between April 2018 and March 2021 were assessed. Consultations for suspected PP during the pandemic (period 3) were analyzed and compared to the 2 previous years (periods 1 and 2). Clinical data and ancillary tests done in the initial assessment and PP progression information were collected. Results. Data from 5151 consultations were analyzed. An increase in consultations for suspected PP was observed during period 3 (21% versus 10% and 11%, p < 0.001). Patients who consulted for suspected PP during period 3 increased 2.3-fold (80 versus 29 and 31, p < 0.001). In total, 95% were female; this was the population analyzed. We included 132 patients with similar age, weight, height, bone age, and hormonal characteristics in the 3 periods. During period 3, a lower body mass index, a higher percentage of Tanner breast stage 3-4, and a greater uterine length were observed. Treatment was indicated upon diagnosis in 26% of the cases. In the rest, their evolution was monitored. During follow-up, a rapidly progressive course was observed more frequently in period 3 (47% versus 8% versus 13%, p: 0.02). Conclusions. We observed an increase in PP and a rapidly progressive evolution in girls during the pandemic.

Introducción. Durante la pandemia por COVID-19, observamos un aumento de consultas por pubertad precoz (PP). Nuestro objetivo fue determinar la frecuencia de PP y su progresión antes y durante la pandemia. Métodos. Estudio retrospectivo, observacional y analítico. Se evaluaron las historias clínicas de los pacientes que consultaron en Endocrinología Infantil entre abril de 2018 y marzo de 2021. Se analizaron las consultas por sospecha de PP durante la pandemia (período 3) y se compararon con 2 años previos (períodos 1 y 2). Se recolectaron datos clínicos y estudios complementarios de la evaluación inicial y su progresión. Resultados. Se analizaron 5151 consultas. Se observó un aumento de consultas por sospecha de PP durante el período 3 (21 % vs.10 % y 11 %, p <0,001). Los pacientes que consultaron por sospecha de PP durante el período 3 aumentaron 2,3 veces (80 vs. 29 y 31, p <0,001). El 95 % fueron niñas; esa población fue analizada. Se incluyeron 132 pacientes que fueron similares en edad, peso, talla, edad ósea y determinaciones hormonales en los 3 períodos. En el período 3, se observó un menor índice de masa corporal, mayor porcentaje de estadio mamario Tanner 3-4 y mayor longitud uterina. Se indicó tratamiento al diagnóstico en el 26 % de los casos. En el resto, se controló su evolución. Durante el seguimiento, se observó una evolución rápidamente progresiva con mayor frecuencia durante el período 3 (47 % vs. 8 % vs. 13 %; p: 0,02). Conclusiones. Evidenciamos un aumento de la PP y una evolución rápidamente progresiva en niñas durante la pandemia.

COVID-19 pandemic phases and female precocious puberty: The experience of the past 4 years (2019 through 2022) in an Italian tertiary center.

Objective: Since the outbreak of COVID-19 pandemic, several centers of pediatric endocrinology worldwide have observed a significant increase in the number of girls presenting with precocious or early puberty. We aimed to compare the incidence rates of female precocious puberty before and during the different phases of COVID-19 pandemic. Methods: We have retrospectively analyzed all the consultations recorded in the outpatient clinic database of the Endocrinology Unit of Bambino Gesù Children's Hospital, Rome, Italy, from the lockdown start in March 2020 up to September 2020, in comparison with the consultations recorded in the same months of 2019, 2021 and 2022. Age, height, weight, body mass index, Tanner's pubertal stage and bone age at presentation, birth weight, ethnicity, family history of central precocious puberty (CPP), maternal age at menarche, history of adoption were retrieved from clinical records. Serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH) both at baseline and after gonadotropin-releasing hormone (GnRH) stimulation, and basal estradiol levels were collected. Results: In 2019, 78 girls with suspected precocious puberty were referred for endocrinological consultation, compared to 202 girls in 2020, 158 girls in 2021 and 112 girls in 2022. A significant increase in the proportion of girls diagnosed with rapidly progressive CPP was observed in 2020, compared to 2019 (86/202 vs. 18/78, p<0.01). In the following periods of 2021 and 2022, a gradual decrease in the number of cases of progressive CPP was evident, so much that the number of cases was not significantly different from that observed in 2019 (56/158 in 2021 and 35/112 in 2022, p=0.054 and p=0.216 respectively, compared to 2019). Conclusions: Our research suggests that drastic lifestyle changes, such as those imposed by COVID-19 lockdown, and the consequent stress may affect the regulation of pubertal timing. The remarkable increase in CPP cases observed during the 2020 first pandemic wave seems to be reduced in 2021 and 2022, concurrently with the progressive resumption of daily activities. These data seem to support the hypothesis of a direct relationship between profound life-style changes related to the pandemic and the rise in precocious puberty cases.

Analysis of the incidence of central precocious puberty treated with gonadotropin-releasing hormone analogs. Impact of the COVID-19 pandemic. / Análisis de la incidencia de pubertad precoz central tratada con análogos de hormona liberadora de gonadotrofina. Impacto de la pandemia por COVID-19.

Introduction. Since the onset of the coronavirus disease 2019 (COVID-19) pandemic, consultations of girls with idiopathic central precocious puberty (ICPP) increased in several countries, but there were no data from Argentina. This increase may be related to changes in lifestyle and stress levels resulting from the lockdown, which particularly affected the child population. Objectives. 1) To describe the progression of the incidence of ICPP requiring inhibition of the hypothalamic-pituitary-gonadal (HPG) axis in girls between 2010 and 2021 in a cohort from the Metropolitan Area of Buenos Aires. 2) To compare the characteristics of girls diagnosed with ICPP during the pandemic with those of a control group. Methods. Interrupted time-series and case-control study. Results. The annual incidence remained stable between 2010 and 2017. Since 2017, it increased to an average of 59.9% (95% CI: 18.6-115.5) and appears to have accelerated during the pandemic. We found an association between ICPP and requiring inhibitory treatment between June 1st, 2020 and May 31st, 2021 and 2 variables: maternal age at menarche (OR: 0.46, 95% CI: 0.28-0.77) and family history of ICPP (OR: 4.42, 95% CI: 1.16-16.86). Conclusion. We evidenced a significant increase in the incidence of ICPP with requirement of HPG axis inhibition since 2017. Increased exposure to various environmental triggers during the COVID-19 pandemic may have had a greater influence in girls with some genetic predisposition.

Introducción. Desde inicios de la pandemia por coronavirus 2019 (COVID-19), fue comunicado en varios países un incremento de las consultas de niñas con pubertad precoz central idiopática (PPCI), sin que contáramos con datos argentinos. Este aumento estaría vinculado con los cambios en el estilo de vida y los niveles de estrés resultantes del aislamiento que afectó particularmente a la población infantil. Objetivos. 1) Describir la evolución de la incidencia de PPCI con requerimiento de inhibición del eje hipotálamo-hipófiso-gonadal (EHHG) en niñas entre 2010 y 2021 en una cohorte del Área Metropolitana de Buenos Aires. 2) Comparar las características de las niñas, con dicho diagnóstico realizado durante la pandemia, con las de un grupo control. Métodos. Serie de tiempo interrumpida y estudio de casos y controles. Resultados. La incidencia anual fue estable entre 2010 y 2017. Desde 2017 hubo un ascenso anual que promedió el 59,9 % (IC95 % 18,6-115,5) y pareciera haberse acelerado durante la pandemia. Constatamos asociación entre haber desarrollado PPCI y haber requerido tratamiento inhibitorio entre el 01 de junio de 2020 y el 31 de mayo de 2021, y dos variables: edad de menarca materna (OR 0,46; IC95 % 0,28-0,77) y antecedente familiar de PPCI (OR 4,42; IC95 % 1,16-16,86). Conclusión. Evidenciamos desde 2017 un aumento significativo en la incidencia de PPCI con requerimiento de inhibición del EHHG. El incremento en la exposición a diversos desencadenantes ambientales durante la pandemia por COVID-19 podría haber ejercido mayor influencia en las niñas con alguna predisposición genética.

Precocious puberty in relation to the COVID-19 pandemic. A survey among Argentine pediatric endocrinologists. / Pubertad precoz relacionada con la pandemia por COVID-19. Encuesta a endocrinólogos pediátricos argentinos.

Introduction. Puberty is manifested initially by the onset of secondary sexual characteristics as a result of hormonal changes that progressively lead to complete sexual maturity. In Argentina and worldwide, the lockdown resulting from the SARS-CoV-2 pandemic may have interfered in the onset and timing of pubertal development. Objective. To describe the perception of pediatric endocrinologists in Argentina regarding consultations for suspected precocious and/or rapidly progressive puberty during the pandemic. Materials and methods. Descriptive, observational, cross-sectional study. Anonymous survey among pediatric endocrinologists members of the Sociedad Argentina de Pediatría and/or the Asociación de Endocrinología Pediátrica Argentina administered in December 2021. Results. Out of 144 pediatric endocrinologists, 83 completed the survey (rate of response: 58%). All of them considered that consultation for precocious or early puberty increased, either in terms of early thelarche (84%), early pubarche (26%), and/or precocious puberty (95%). Ninety-nine percent agreed that this has occurred to a greater extent in girls. All survey respondents also consider that the diagnosis of central precocious puberty has increased. In total, 96.4% of respondents consider that the number of patients treated with GnRH analogs has increased. Conclusion. Our results about the perception of pediatric endocrinologists are consistent with data published in other regions on the increase in the diagnosis of precocious puberty during the COVID-19 pandemic. We underscore the need to develop national registries of central precocious puberty, and to disseminate the evidence for a timely detection and management.

Introducción. La pubertad se manifiesta inicialmente por la aparición de los caracteres sexuales secundarios, como consecuencia de cambios hormonales que progresivamente conducen a la madurez sexual completa. En Argentina y el mundo, la pandemia ocasionada por el coronavirus SARS-CoV-2 generó un confinamiento que pudo haber interferido en el inicio y tempo del desarrollo puberal. Objetivo. Describir la percepción de los endocrinólogos pediatras del país sobre las consultas por sospecha de pubertad precoz y/o pubertad de rápida progresión durante la pandemia. Materiales y métodos. Estudio descriptivo, observacional, transversal. Encuesta anónima a endocrinólogos pediatras pertenecientes a la Sociedad Argentina de Pediatría y/o a la Asociación de Endocrinología Pediátrica Argentina, en diciembre de 2021. Resultados. Respondieron la encuesta 83 de 144 endocrinólogos pediátricos (tasa de respuesta 58 %). Todos consideraron que aumentó la consulta por desarrollo precoz o temprano, ya sea en sus variantes telarca precoz (84 %), pubarca precoz (26 %) y/o pubertad precoz (95 %). El 99 % acuerda con que se ha dado en mayor medida en niñas. La totalidad de los encuestados también considera que aumentó el diagnóstico de pubertad precoz central. El 96,4 % considera que ha aumentado el número de pacientes tratados con análogos de GnRH. Conclusión. Nuestros resultados sobre la percepción de endocrinólogos pediatras coinciden con datos publicados en otras regiones sobre el aumento del diagnóstico de pubertad precoz durante la pandemia por COVID-19. Se reafirma la necesidad de generar registros nacionales de pubertad precoz central, difundir las evidencias para su detección y abordaje oportuno.