Intrafamilial phenotypic heterogeneity in siblings with pseudohypoparathyroidism 1B due to maternal STX16 deletion.

OBJECTIVES: Pseudohypoparathyroidism (PHP1B) is most commonly caused by epigenetic defects resulting in loss of methylation at the GNAS locus, although deletions of STX16 leading to GNAS methylation abnormalities have been previously reported. The phenotype of this disorder is variable and can include hormonal resistances and severe infantile obesity with hyperphagia. A possible time relationship between the onset of obesity and endocrinopathies has been previously reported but remains unclear. Understanding of the condition's natural history is limited, partly due to a scarcity of literature, especially in children. CASE PRESENTATION: We report three siblings with autosomal dominant PHP1B caused by a deletion in STX16 who presented with early childhood onset PTH-resistance with normocalcemia with a progressive nature, accompanied by TSH-resistance and severe infantile obesity with hyperphagia in some, not all of the affected individuals. CONCLUSIONS: PHP1B from a STX16 deletion displays intrafamilial phenotypic variation. It is a novel cause of severe infantile obesity, which is not typically included in commercially available gene panels but must be considered in the genetic work-up. Finally, it does not seem to have a clear time relationship between the onset of obesity and hormonal resistance.

Leuprolide Protects Ovarian Reserve in Adolescents Undergoing Gonadotoxic Therapy.

Purpose: Treatment sequelae compromising reproductive health are highly prevalent in childhood cancer survivors, and a main determinant of health and quality of life. Follicular reserve determines ovarian function life span; thus, its preservation is important in the care of female survivors. Anti-Müllerian hormone (AMH) is a biomarker to measure functional ovarian reserve. We aimed to evaluate the effect of leuprolide during gonadotoxic therapy on pubertal females' post-treatment functional ovarian reserve using AMH levels. Methods: We conducted a single-center retrospective study including all pubertal females who had undergone gonadotoxic treatments between January 2010 and April 2020, and had an AMH level after completion of therapy. We used multivariable linear regressions to compare AMH-level beta coefficients in patients stratified by gonadotoxic risk, adjusting for leuprolide use. Results: Fifty-two females meeting study eligibility were included, of which 35 received leuprolide. The use of leuprolide was associated with higher post-treatment AMH levels in the lower gonadotoxic risk group (beta 2.74, 95% CI 0.97-4.51; p = 0.004). This association was lost in the higher gonadotoxic risk groups. Conclusions: Leuprolide may have a protective effect on the functional ovarian reserve. However, this is limited by increasing treatment gonadotoxicity. Larger, prospective studies are needed to elucidate the potential benefits of gonadotropin-releasing hormone agonist on preservation of ovarian reserve among children receiving gonadotoxic therapies, as cancer survivors.

A View from the past into our collective future: the oncofertility consortium vision statement.

PURPOSE: Today, male and female adult and pediatric cancer patients, individuals transitioning between gender identities, and other individuals facing health extending but fertility limiting treatments can look forward to a fertile future. This is, in part, due to the work of members associated with the Oncofertility Consortium. METHODS: The Oncofertility Consortium is an international, interdisciplinary initiative originally designed to explore the urgent unmet need associated with the reproductive future of cancer survivors. As the strategies for fertility management were invented, developed or applied, the individuals for who the program offered hope, similarly expanded. As a community of practice, Consortium participants share information in an open and rapid manner to addresses the complex health care and quality-of-life issues of cancer, transgender and other patients. To ensure that the organization remains contemporary to the needs of the community, the field designed a fully inclusive mechanism for strategic planning and here present the findings of this process. RESULTS: This interprofessional network of medical specialists, scientists, and scholars in the law, medical ethics, religious studies and other disciplines associated with human interventions, explore the relationships between health, disease, survivorship, treatment, gender and reproductive longevity. CONCLUSION: The goals are to continually integrate the best science in the service of the needs of patients and build a community of care that is ready for the challenges of the field in the future.

Prevalence of Adrenal Insufficiency and Glucocorticoid Use in Pediatric Pseudotumor Cerebri Syndrome.

BACKGROUND: The pathophysiology underlying pseudotumor cerebri syndrome (PTCS) is complex and not well understood. There are clear differences between PTCS in adults and pediatrics. Few and isolated case reports have suggested that adrenal function may be involved, yet no large cohort study has examined this relationship. METHODS: We conducted a retrospective single-center study of children who presented with a diagnosis of PTCS and had cortisol testing measured between January 2010 and September 2019. We included all subjects meeting the revised PTCS diagnostic criteria after the chart review. Based on morning, random or 1-µg cosyntropin stimulated cortisol levels, adrenal functioning was classified as: (1) insufficient (peak cortisol <16 µg/dL and AM cortisol <5 µg/dL), (2) at risk (peak cortisol 16-20 µg/dL, AM cortisol 5-13 µg/dL, or random <13 µg/dL), or (3) sufficient (peak cortisol >20 µg/dL and AM or random cortisol >13 µg/dL). RESULTS: A total of 398 individuals were reviewed, and 64 were included for analysis. Of these, 40.6% were men, of mixed race and ethnicity with a mean age of 10.5 (SD 4.7) years. Of these, 23% and 52% had insufficient or at-risk cortisol levels. The majority of those in the insufficient (70%) or at-risk (80%) groups were exposed to topical, nasal, or inhaled glucocorticoids but not systemic. Only 60% and 12% of those with PTCS with insufficient or at-risk cortisol testing, respectively, underwent definitive testing with a stimulation test. CONCLUSIONS: Glucocorticoid use and hypocortisolism are prevalent in PTCS and need consideration as a potential underlying cause. Most children had insufficient or at-risk cortisol levels, and many did not undergo further testing/workup. Children who present with PTCS, particularly young, males should be evaluated for adrenal insufficiency and its risk factors, including nonsystemic steroids. Prospective studies are necessary to further evaluate the effect of cortisol in relation to pediatric PTCS.

Availability of Fertility Preservation Information on the Websites of U.S. News and World Report Top-Ranked Pediatric Cancer Programs.

Purpose: To evaluate the availability of fertility preservation (FP) services and educational resources on the websites of top-ranked U.S. pediatric cancer programs. Methods: Cross-sectional survey of information and resources related to FP on websites from top-ranked pediatric cancer programs according to the 2018-2019 U.S.-News & World Report (USNWR) ranking. Factors that predicted the website availability of FP information or a fertility team were analyzed, as was availability in Spanish and for specific groups by sex and puberty status. As a surrogate marker of comprehensive oncological services, the availability of resources for psychological support was compared to FP. Results: A fertility team was referenced on the website of 36% of programs, but only 32% provided FP educational resources for patients. Among them, 100%, 93.8%, 93.8%, and 68.8% provided specific information for postpubertal females, prepubertal females, postpubertal males, and prepubertal males, respectively. The majority (93.8%) did not provide information in Spanish. The ranking on USNWR (p < 0.05) and patient volume (p < 0.05) positively correlated with the availability of FP information and fertility team on the program's website. Information regarding psychological support was provided more often than information regarding FP (96% vs. 32%, p < 0.05). Conclusion: The majority of the top-ranked pediatric cancer programs in the United States do not list FP resources or a fertility team on their website. The lack of resources is particularly concerning for the Spanish-speaking population, as well as for prepubertal males. This may be potentially hindering access to FP and contributing to health care disparities.

Association of Adrenal Insufficiency With Pediatric Pseudotumor Cerebri Syndrome.

Importance: Pediatric pseudotumor cerebri syndrome pathophysiology is complex and not well delineated. Therefore, it is important to identify potential contributors or targets underlying the primary pathogenesis for its development. Objective: To report cases highlighting the association of pediatric pseudotumor cerebri syndrome with adrenal insufficiency. Design, Setting, and Participants: This noncontrolled, observational case series included pediatric patients diagnosed with pseudotumor cerebri syndrome and adrenal insufficiency at an urban academic children's hospital in Houston, Texas, from June 2015 to October 2019. Main Outcomes and Measures: Monitoring optic nerve edema by clinical examination, fundus photography, and optical coherence topography images of the optic nerve. Results: Data were collected from 5 pediatric patients (age range, 5-10 years) diagnosed with pseudotumor cerebri syndrome and adrenal insufficiency. One was a girl; all were White and prepubertal. Three patients had unrecognized glucocorticoid exposure. All patients had bilateral optic nerve edema that was initially treated with acetazolamide or topiramate, but cortisol functional testing by either 8 am cortisol or cosyntropin stimulation tests revealed a diagnosis of central adrenal insufficiency. Treatment with physiological doses of hydrocortisone resulted in resolution of optic nerve edema and clinical symptoms of pseudotumor cerebri syndrome, as well as a shorter time receiving medical therapy. Conclusions and Relevance: In this case series, adrenal insufficiency was associated with both primary and secondary prepubertal pediatric pseudotumor cerebri syndrome. As a potential target specific to causative mechanism, physiologic hydrocortisone therapy resolved the condition. To date, there remains a global unawareness among clinicians about the suppressive outcome that glucocorticoids may have on the developing hypothalamic-pituitary-adrenal axis, resulting in adrenal insufficiency and so-called episodic pseudotumor cerebri syndrome in young children. Ophthalmologists and pediatric subspecialists should implement cortisol testing via either 8 am cortisol or cosyntropin stimulation tests at initial evaluation of all children with pseudotumor cerebri syndrome and risk factors for adrenal insufficiency, no predisposing causes, or nonresponse to conventional treatment. Further management and treatment should be in combination with ophthalmology and endocrine services.

Primary ovarian insufficiency in an adolescent population: clinical phenotype and diagnostic approach.

Background Primary ovarian insufficiency (POI) can be seen in adolescents secondary to genetic or autoimmune conditions, or gonadotoxic therapies. Often times, its underlying cause is not identified. It is a rare condition in pediatrics, but a thorough evaluation is required for a timely diagnosis and optimizing outcomes. Objectives We aim to describe the clinical phenotype of idiopathic POI in an adolescent population seen in a referral center, and evaluate its diagnostic approach. Methods All patients evaluated between 2012 and 2018 were identified using the diagnostic codes for POI. Medical records were manually reviewed and clinical information was extracted. Cases were excluded from the final sample if they were found to have incomplete diagnostic information, Turner syndrome, eating disorders, gonadal surgeries and/or a history of oncological conditions or treatments. Results Forty-eight patients with POI were identified, and only seven met the established criteria. Anti-ovarian and anti-thyroid antibodies were evaluated in 100% and 86%, respectively, while only 29% were tested for anti-adrenal autoimmunity. The karyotype was obtained consistently, while the fragile X mental retardation 1 (FMR1) gene expansion was only assessed in approximately a third of the patients. Finally, only 29% of patients received reproductive counseling or referral to a fertility specialist. Conclusions Diagnostic evaluation for POI appears to be challenging to pediatric providers. Anti-ovarian antibodies are frequently obtained despite the lack of their clinical significance in POI, while anti-adrenal antibodies, which are the preferred diagnostic test, are not commonly obtained. Reproductive orientation or referral is seldom provided to the adolescent population.

Association of nutritional support programs with zinc deficiency in Colombian children: a cross-sectional study.

BACKGROUND: Zinc is an essential trace element that plays a key role in the immune, gastrointestinal, respiratory and nervous systems. In Colombia, a vast percentage of children live in low-income households with food insecurity and nutritional deficiencies, including zinc. In an effort to improve children's well-being, public health measures such as nutritional support programs that provide meals have targeted the poorest populations. The aim of the present study was to assess the role of nutritional support programs on zinc deficiency in Colombian children, while considering their wealth and food security. METHODS: Cross-sectional study using data from the 2010 Colombian National Nutrition Survey, a population-based study representative of Colombia. A total of 4275 children between 12 and 59 months of age were included in the study. Stepwise logistic regressions were modelled with SPSS, first for zinc deficiency on wealth and food security, then adding enrolment in a nutritional support program, and finally, adjusting for socio-demographic variables. RESULTS: A zinc deficiency prevalence of 49% was found. The adjusted models showed an association of wealth quintiles: very poor (OR = 1.48) and poor (OR = 1.39), food security (OR = 0.75) and enrolment in a nutritional support program (OR = 0.76) with zinc deficiency. Enrolment in nutritional programs did not modify the relationship of wealth and food security to zinc deficiency. CONCLUSION: Zinc deficiency is associated with wealth, food security and enrolment in nutritional support programs. Nutritional programs may be a good alternative against zinc deficiency, if they focus appropriately on the needs of children according to their wealth and food security.

In utero virilization secondary to a maternal Krukenberg tumor: case report and review of literature.

BACKGROUND: Krukenberg tumors are ovarian metastatic adenocarcinomas with a primary origin usually located in the stomach, colon, gallbladder, pancreas, or breast. Occasionally, these tumors produce virilization in the affected individual due to androgen production by luteinization of the tumoral stroma. It is believed that during pregnancy these tumors are more likely to increase androgen production due to the elevated levels of human chorionic gonadotropin (hCG). High maternal androgens can cross the placenta producing virilization of the female fetus. CASE PRESENTATION: A 46,XX newborn female, whose mother was diagnosed with a metastatic ovarian tumor during her second trimester of gestation associated with worsening hirsutism and acne, was found to have ambiguous genitalia at birth. Testosterone levels in both the mother and infant were elevated. Follow-up laboratory tests showed progressive normalization of circulating androgens after delivery. CONCLUSIONS: Krukenberg tumors are rare and may produce virilization of the mother and the female fetus when present during pregnancy.

Acute respiratory infection in children from developing nations: a multi-level study.

BACKGROUND: Worldwide, acute respiratory infections (ARI) are the leading cause of death of children under 5 years of age. AIM: To assess the accomplishment of the Millennium Development Goal on under-5 mortality particularly related to ARI in developing countries, and to explore the associations between country characteristics and ARI in children under 5 taking into account child, mother and household attributes. METHODS: The study included a representative sample of 354,633 children under 5 years from 40 developing nations. A multilevel analysis of data from the Demographic and Health Surveys and the World Bank was conducted. RESULTS: The prevalence of ARI was 13%. Country inequalities were associated with the disease - GINI index (95% CI 1.01-1.04). The country's per capita gross domestic product (GDP) (95% CI 1.00-1.01) and health expenditure (95% CI 1.01-1.01) affected the relationship between immunization and ARI, while inequalities influenced the relationship between household wealth (95% CI 0.99-0.99) and the disease. Other factors positively associated with ARI were male gender, low birthweight, working mothers and a high-risk indoor environment. Factors associated with ARI reduction were older children, immunization, breastfeeding for more than 6 months, older maternal age, maternal education and planned pregnancy. CONCLUSIONS: In developing countries, public health campaigns to target ARI should consider the country's macro characteristics. At country level, inequalities but not health expenditure or GDP were associated with the disease and were independent of child, family and household characteristics. The effect of immunization on reducing ARI is greater in countries with a higher GDP and health expenditure. The effect of household wealth on ARI is less in countries with fewer inequalities. Reduction of inequalities is an important measure to decrease ARI in developing countries.

Country characteristics and acute diarrhea in children from developing nations: a multilevel study.

BACKGROUND: Each year 2.5 billion cases of diarrheal disease are reported in children under five years, and over 1,000 die. Country characteristics could play a role on this situation. We explored associations between country characteristics and diarrheal disease in children under 5 years of age, adjusting by child, mother and household attributes in developing countries. METHODS: This study included 348,706 children from 40 nations. We conducted a multilevel analysis of data from the Demographic and Health Surveys and the World Bank. RESULTS: The prevalence of acute diarrhea was 14 %. Country inequalities (OR = 1.335; 95 % CI 1.117-1.663) and country's low income (OR = 1.488; 95 % CI 1.024-2.163) were associated with diarrhea, and these country characteristics changed the associations of well-known determinants of diarrhea. Specifically, living in poor countries strengthens the association of poor household wealth and mother's lack of education with the disease. Other factors associated with diarrhea were female sex of the child (OR = 0.922; 95 % CI 0.900-0.944), age of the child (OR = 0.978; 95 % CI 0.978-0.979), immunization status (OR = 0.821; 95 % CI 0.799-0.843), normal birthweight (OR = 0.879; 95 % CI 0.834-0.926), maternal age (OR = 0.987; 95 % CI 0.985-0.989), lack of maternal education (OR = 1.416; 95 % CI 1.283-1.564), working status of the mother (OR = 1.136; 95 % CI 1.106-1.167), planned pregnancy (OR = 0.774; 95 % CI 0.753-0.795), a nuclear family structure (OR = 0.949; 95 % CI 0.923-0.975), and household wealth (OR = 0.948; 95 % CI 0.921-0.977). CONCLUSIONS: Inequalities and lack of resources at the country level in developing countries -but not health expenditure- were associated with acute diarrhea, independently of child, family and household features. The broad environment considerably modifies well-known social determinants of acute diarrhea and public health campaigns designed to target diarrhea should consider macro characteristics of the country.

Low birth weight and prenatal care in Colombia: a cross-sectional study.

BACKGROUND: Low birth weight (LBW) is one of the most important factors affecting child morbidity and mortality worldwide; approximately one third of neonatal deaths are attributable to it. Most research and public health policy on LBW arise from developed nations, despite that most cases (96.5%) take place in developing countries. The specific features of prenatal care that prevent LBW in developing countries are unclear. This study aims to identify the characteristics of prenatal care associated with LBW in a developing country as Colombia. METHODS: Observational cross-sectional study using data from the Colombian Demographic and Health Survey 2010. A total of 10,692 children were included. Descriptive statistics were calculated, followed by bivariate regressions of LBW with all other study variables. Finally, stepwise logistic binomial regression analyses were done. RESULTS: A LBW prevalence of 8.7% was found. Quality of prenatal care (95%CI: 0.33, 0.92; OR = 0.55), number of prenatal visits (95%CI: 0.92, 0.93; OR = 0.92), and first prenatal visits during pregnancy (95%CI: 1.02, 1.07; OR = 1.08) were associated with LBW even after controlling for all the studied variables. The health care provider conducting prenatal checkup, and insurance coverage, were not associated with LBW. CONCLUSION: This research provides information on the characteristics of prenatal care (quality, number of visits, and gestational age at first prenatal visit) which may strengthen LBW prevention in Colombia and possibly in countries with similar socioeconomic characteristics.

Percretismo placentario asociado con placenta previa y abruptio: reporte de un caso / Placenta percreta associated with placenta previa and abruptio: a case report

El número de partos por cesárea ha aumentado durante los últimos años. Esto se ha relacionado con un incremento en las anormalidades de la inserción placentaria para embarazos futuros, así como de otras complicaciones feto-placentarias. Las patologías placentarias y el manejo quirúrgico que suelen requerir ensombrecen drásticamente el pronóstico materno-fetal. Reportamos un caso de una mujer multípara quien cursa con un caso de percretismo placentario, placenta previa y abruptio de placenta, que ingresó en el servicio de ginecoobstetricia en un hospital universitario siendo sometida a manejo quirúrgico multidisciplinario de urgencia obteniendo resultados materno-fetales satisfactorios (AU)

The number of cesarean sections has risen during the recent years, leading to an increase in abnormal placentation in future pregnancies, as well as other materno-fetal complications. Placental abnormalities and the surgical management they usually required, drastically obscure maternal and fetal outcomes. We report the case of a multiparous woman admitted to labor and delivery service of a university hospital presenting with placenta percreta, placenta previa and abruptio placentae. She received opportune emergency multidisciplinary management, obtaining satisfactory (AU)