Creo, Ana L.

Background: Pregnancy in teenagers and emerging adults is associated with an increased risk of adverse outcomes. Similarly, pregnancies complicated by pregestational and gestational diabetes mellitus (GDM) carry a higher risk of complications. However, limited data exist on the intersection of these two high-risk conditions. Our objective was to establish the prevalence of teenage and emerging adult pregnancies complicated by diabetes in a population-based cohort and compare outcomes to pregnancies uncomplicated by diabetes, noting a background prevalence of GDM of 8.1% and pregestational diabetes of 1.2% across all age groups in the United States. Methods: This is a retrospective cohort study conducted in Olmsted County, Minnesota, USA. It includes female residents aged ≤21 years with a pregnancy ICD-10 code between January 1, 2013, and December 31, 2022. The main outcome measures assessed include maternal characteristics and maternal and fetal pregnancy outcomes. Results: A total of 1491 pregnancies in 1379 individuals were identified and included. In total, 68 (4.6%) pregnancies were complicated by diabetes: 51 (3.4%) with GDM and 17 (1.1%) with pregestational diabetes. In this study, pregnancies with diabetes had higher rates of adverse outcomes including cesarean delivery (GDM 29.4% vs. pregestational 60.0% vs. no diabetes 17.0%, P < 0.001), preeclampsia (GDM 15.7% vs. pregestational 40.0% vs. no diabetes 7.3%, P < 0.001), large-for-gestational-age neonates (GDM 13.7% vs. pre-existing 50.0% vs. no diabetes 5.8%, P < 0.001), and neonatal hypoglycemia (GDM 42.6% vs. pregestational 60.0% vs. no diabetes 13.3%, P < 0.001). Conclusions: The prevalence of pregestational diabetes in our teenage and emerging adult population is similar to that of the general pregnancy population; however, the prevalence of GDM is significantly lower. Overall, diabetes in teenage pregnancy is associated with an elevated risk of adverse maternal and neonatal outcomes. Future research should evaluate interventions aimed at reducing adverse pregnancy outcomes in this vulnerable population.

We assessed associations of pediatrician demographic characteristics with patient satisfaction (PS) scores. We performed a retrospective analysis of PS scores among pediatricians at a single academic institution and their associations with individual demographic features including gender, race, and geographic location of medical school education. We analyzed PS survey results for 153 pediatricians, 48.4% of whom were female. Males received higher scores in 4 out of 10 questions including “Likelihood of your recommending this care provider to others” ( P = .007). We observed similar findings for white pediatricians compared to Black, Indigenous, and People of Color (BIPOC) ( P = .033) and US medical school graduates compared to international school graduates ( P = .044). Overall, we observed that pediatricians who are female, BIPOC, or international medical school graduates receive lower PS scores than their counterparts. The impact of potential survey responder bias should be acknowledged when interpreting PS scores for pediatricians.

Abstract Context Pituitary adenomas and cysts are rare in pediatric patients and improved understanding can guide management recommendations. Objective To report incidence, presentation, management, and outcomes in a pediatric population-based cohort with pituitary adenomas and cysts, and to explore the relationship between these lesions and brain magnetic resonance imaging (MRI) rates, as well as lesion size and headaches with disease progression. Methods In this retrospective cohort study of pediatric patients (≤18 years) with incident pituitary adenomas and cysts in Olmsted County, MN, from 1976 to 2021, 234 unique patients were identified using diagnostic codes through the Rochester Epidemiology Project, with 37 confirmed cases of pituitary adenoma or cyst included. Incidence rates were calculated using census data. Descriptive statistics were used for extracted clinical data. Results Incidence of pediatric adenomas and cysts was 2.29 cases per 100 000 person-years. Of the 37 cases, 68% were nonfunctioning adenomas or cysts, 27% were prolactinomas, and there was 1 each of growth hormone (GH)– and thyrotropin (TSH)-secreting adenomas. Median lesion diameter was 5.5 mm (IQR, 4.0-8.0). Median follow-up was 7.4 years (IQR, 4.5-15.4). Four patients had disease progression which stabilized with second-line therapy. Brain MRI rates did not correlate with lesion incidence. No clinically meaningful relationship was found between lesion size or headache and disease progression. Conclusion Pituitary adenomas and cysts are rare in pediatric patients. Most are small, nonfunctioning, and stable on long-term follow-up. Larger studies on small nonfunctioning pituitary lesions are needed to enhance understanding of their natural history and develop long-term management recommendations.

Abstract Context Variants in melanocortin 4 receptor (MC4R) pathway-related genes have been associated with obesity. The association of these variants with cardiometabolic parameters are not fully known. Objective We compared the severity of obesity and cardiometabolic risk markers in children with MC4R pathway-related clinically reported genetic variants relative to children without these variants. Methods A retrospective chart review was performed in children with obesity who underwent multigene panel testing for monogenic obesity. Results Data on a total of 104 children were examined, with 93 (89%) identified as White. Thirty-nine (37.5%) patients had clinically reported variants in the MC4R pathway, and the remaining 65 patients did not have reported MC4R pathway-related variants. Among the MC4R-related variants, PCSK1 risk alleles were most common, reported in 15 children (14%). The maximum body mass index percent of the 95th percentile was not different between groups (P = .116). Low-density lipoprotein cholesterol (LDL-C) was not different between groups (P = .132). However, subgroup analysis demonstrated higher LDL cholesterol in children with the PCSK1 c.661A&gt;G risk allele relative to those with MC4R-related variant of uncertain significance (P = .047), negative genetic testing (P = .012), and those with non-MC4R related variants (P = .048). The blood pressure, fasting glucose, hemoglobin A1C, total cholesterol, alanine transaminase, and high-density lipoprotein cholesterol were not different between groups. Conclusion Variants in the MC4R pathway-related genes were not associated with severity of obesity and cardiometabolic risk markers except for the c.661A&gt;G PCSK1 risk allele, which was associated with higher LDL-C levels.

A 13-year-old male undergoing maintenance chemotherapy with methotrexate and 6-mercaptopurine (6MP), for very high-risk B-cell acute lymphoblastic leukemia (ALL), presented with vomiting due to severe hypoglycemia with metabolic acidosis. While his laboratory values were concerning for a critically ill child, the patient was relatively well appearing. Hypoglycemia is a rare but serious side effect of 6MP with an unexpectedly variable presentation; therefore, a high index of suspicion is needed for its prompt detection and treatment. This patient also had severe metabolic acidosis, likely secondary to hypoglycemia, creating a serious clinical picture despite a well-appearing child. This example of incongruity between laboratory tests and clinical appearance adds nuance to the existing literature. Moreover, although 6MP-associated hypoglycemia is rare, it may be more prevalent than the literature suggests, as symptoms of hypoglycemia—nausea, vomiting, and somnolence—mirror common chemotherapy side effects. 6MP-induced hypoglycemia can be ameliorated with the addition of allopurinol to shunt metabolism in favor of the production of therapeutic metabolites over hepatotoxic metabolites. Additionally, a morning administration of 6MP and frequent snacks may also help to prevent hypoglycemia. Overall, this case adds to the literature of unusual reactions to 6MP including hypoglycemia in an older child without traditional risk factors.

Purpose of review Hyponatremia and hypernatremia are commonly encountered electrolyte abnormalities that require timely and careful intervention, as they can be associated with significant morbidity and mortality. Recent findings This review article addresses the etiology, presentation, diagnosis, and management of both hyponatremia and hypernatremia, emphasizing the latest advancements and emerging trends in pediatric care. Summary A methodical approach is needed to accurately assess and treat hyponatremia and hypernatremia. Both conditions continue to rely on serum and urine testing, however newer tests such as copeptin and stimulated testing may hold promise to further refine testing in the future.

Introduction: Oral glucose tolerance testing is recommended for all children with CF older than 9 years, yet compliance remains poor across centers. Methods: We performed a small pilot study assessing the glycemic curves and participant satisfaction in seven children and adolescents. Results: We chose a dextrose-based candy (Nerds®) free of any fat, fiber, gelatin, or corn syrup and performed the candy OGTT 1–4 days following the standard oral dextrose solution OGTT. Glucose values at 120 min were similar between the candy and oral dextrose solution (p = 0.8986). Conclusions: Our small pilot suggests that a carefully selected candy alternative may result in similar glycemic OGTT when compared to the standard oral dextrose solution. However, some participants preferred the oral dextrose solution to candy due to having to consume a large volume in a short period of time. This may have significant implications as centers consider candy alternatives to increase OGTT adherence rates.

Abstract Objectives There have been recent advances assessing copeptin levels in adults with suspected disorders of vasopressin release. Very limited data exits on copeptin levels in children and infants, especially in a critically-ill hospitalized population where hyper- and hypo-natremia are very common. Our objective is to describe the institutional experience assessing copeptin levels in hospitalized infants and children with hyper- or hypo-natremia. Methods We performed a single-center retrospective case series of all infants, children, and adolescents who had an ultrasensitive plasma copeptin level obtained between 2019-2021. Results A total of 29 critically ill patients (6 infants) were identified with 38 % of patients having copeptin levels after neurosurgical procedures for tumors or trauma. Approximately 13/17 children with hypernatremia had central diabetes insipidus (central diabetes insipidus) to diagnose CDI, A copeptin level ≤ 4.9 pmol/L resulted in an 88 % sensitivity (95 % CI 47–99 %), and 66 % specificity (95 % CI 30–93 %). Amongst those with hyponatremia levels were more variable, 8/12 children had syndrome of inappropriate antidiuresis (SIAD) with copeptin levels ranging 4.7–72.6 pmol/L. Conclusions While difficult to conclude due to multiple limitations, this case series highlights that typical copeptin cutoffs used to diagnose DI in adults in an ambulatory setting may also translate to a critically-ill pediatric population. Large prospective studies are needed to confirm this observation. In addition, postoperative copeptin levels could potentially be utilized as an additional marker to predict permanent from transient DI, but much larger studies are needed. Further work is needed to establish normative copeptin levels in infants and patients with SIAD.

Abstract Background In the United States, rare disease (RD) is defined as a condition that affects fewer than 200,000 individuals. Collectively, RD affects an estimated 30 million Americans. A significant portion of RD has an underlying genetic cause; however, this may go undiagnosed. To better serve these patients, the Mayo Clinic Program for Rare and Undiagnosed Diseases (PRaUD) was created under the auspices of the Center for Individualized Medicine (CIM) aiming to integrate genomics into subspecialty practice including targeted genetic testing, research, and education. Methods Patients were identified by subspecialty healthcare providers from 11 clinical divisions/departments. Targeted multi-gene panels or custom exome/genome-based panels were utilized. To support the goals of PRaUD, a new clinical service model, the Genetic Testing and Counseling (GTAC) unit, was established to improve access and increase efficiency for genetic test facilitation. The GTAC unit includes genetic counselors, genetic counseling assistants, genetic nurses, and a medical geneticist. Patients receive abbreviated point-of-care genetic counseling and testing through a partnership with subspecialty providers. Results Implementation of PRaUD began in 2018 and GTAC unit launched in 2020 to support program expansion. Currently, 29 RD clinical indications are included in 11 specialty divisions/departments with over 142 referring providers. To date, 1,152 patients have been evaluated with an overall solve rate of 14.1% and as high as 66.7% depending on the phenotype. Noteworthy, 42.7% of the solved or likely solved patients underwent changes in medical management and outcome based on genetic test results. Conclusion Implementation of PRaUD and GTAC have enabled subspecialty practices advance expertise in RD where genetic counselors have not historically been embedded in practice. Democratizing access to genetic testing and counseling can broaden the reach of patients with RD and increase the diagnostic yield of such indications leading to better medical management as well as expanding research opportunities.