Impact of Hypertensive Disorders of Pregnancy and Gestational Diabetes Mellitus on Offspring Cardiovascular Health in Early Adolescence.

BACKGROUND: Adverse pregnancy outcomes, including hypertensive disorders of pregnancy (HDP) and gestational diabetes mellitus (GDM), influence maternal cardiovascular heath (CVH) long after pregnancy, but their relationship to offspring CVH following in utero exposure remains uncertain. OBJECTIVE: To examine associations of HDP or GDM with offspring CVH in early adolescence. STUDY DESIGN: This analysis used data from the prospective Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study from 2000 to 2006 and the HAPO Follow-Up Study from 2013 to 2016. This analysis included 3,317 mother-child dyads from 10 field centers, comprising 70.8% of HAPO Follow-Up Study participants. Those with pregestational diabetes and chronic hypertension were excluded. The exposures were having any HDP or GDM compared with not having HDP or GDM, respectively (reference). The outcome was offspring CVH at ages 10 to 14 years, based on four metrics: body mass index, blood pressure, total cholesterol level, and glucose level. Each metric was categorized as ideal, intermediate, or poor using a framework provided by the American Heart Association. The outcome was primarily defined as having at least one CVH metric that was non-ideal versus all ideal (reference), and secondarily as the number of non-ideal CVH metrics: at least one intermediate metric, one poor metric, or at least two poor metrics versus all ideal (reference). Modified Poisson regression with robust error variance was used and adjusted for covariates at pregnancy enrollment, including field center, parity, age, gestational age, alcohol or tobacco use, child's assigned sex at birth, and child's age at follow-up. RESULTS: Among 3,317 maternal-child dyads, the median (IQR) ages were 30.4 (25.6, 33.9) years for pregnant individuals and 11.6 (10.9, 12.3) years for children. During pregnancy, 10.4% of individuals developed HDP and 14.6% developed GDM. At follow-up, 55.5% of offspring had at least one non-ideal CVH metric. In adjusted models, having HDP (aRR 1.14; 95% CI 1.04, 1.25) or having GDM (aRR 1.10; 95% CI 1.02, 1.19) was associated with greater risk that offspring developed less-than-ideal CVH at ages 10 to 14 years. The above associations strengthened in magnitude as the severity of adverse CVH metrics increased (i.e., with the outcome measured as >1 intermediate, 1 poor, and >2 poor adverse metrics), albeit the only statistically significant association was with the "1-poor-metric" exposure. CONCLUSONS: In this multi-national prospective cohort, pregnant individuals who experienced either HDP and GDM were at significantly increased risk of having offspring with worse CVH in early adolescence. Reducing adverse pregnancy outcomes and increasing surveillance with targeted interventions after an adverse pregnancy outcome should be studied as potential avenues to enhance long-term cardiovascular health in the offspring exposed in utero.

Effective interventions in preventing gestational diabetes mellitus: A systematic review and meta-analysis.

BACKGROUND: Lifestyle choices, metformin, and dietary supplements may prevent GDM, but the effect of intervention characteristics has not been identified. This review evaluated intervention characteristics to inform the implementation of GDM prevention interventions. METHODS: Ovid, MEDLINE/PubMed, and EMBASE databases were searched. The Template for Intervention Description and Replication (TIDieR) framework was used to examine intervention characteristics (who, what, when, where, and how). Subgroup analysis was performed by intervention characteristics. RESULTS: 116 studies involving 40,940 participants are included. Group-based physical activity interventions (RR 0.66; 95% CI 0.46, 0.95) reduce the incidence of GDM compared with individual or mixed (individual and group) delivery format (subgroup p-value = 0.04). Physical activity interventions delivered at healthcare facilities reduce the risk of GDM (RR 0.59; 95% CI 0.49, 0.72) compared with home-based interventions (subgroup p-value = 0.03). No other intervention characteristics impact the effectiveness of all other interventions. CONCLUSIONS: Dietary, physical activity, diet plus physical activity, metformin, and myoinositol interventions reduce the incidence of GDM compared with control interventions. Group and healthcare facility-based physical activity interventions show better effectiveness in preventing GDM than individual and community-based interventions. Other intervention characteristics (e.g. utilization of e-health) don't impact the effectiveness of lifestyle interventions, and thus, interventions may require consideration of the local context.

The effect of any given intervention to prevent gestational diabetes (high blood sugar levels that arise during pregnancy) may depend on the way it is delivered (how, when, what, etc). This study reviewed published literature to investigate if the effects of interventions (diet, exercise, metformin, probiotics, myoinositol) to prevent gestational diabetes differ according to the way it is being delivered (e.g., online vs in-person, by health professionals or others, etc.). Exercise delivered to group settings, or those delivered at a healthcare facility worked better to prevent gestational diabetes. Although we did not observe any differences with other delivery characteristics (e.g., online vs in-person), it does not mean they are always equally effective, it is important to consider individual situations when prescribing or developing interventions.

Leptin and adiposity measures from birth to later childhood: Findings from the Hyperglycemia and Adverse Pregnancy Outcomes Follow-Up Study.

BACKGROUND: Cord blood (CB) leptin is positively associated with adiposity at birth, but the association with child adiposity is unclear. OBJECTIVES: We hypothesized that CB leptin is positively associated with adiposity in peripubertal children and with childhood leptin. METHODS: Leptin was measured in 986 CB and 931 childhood stored samples from a prospective birth cohort. Adiposity measures were collected at birth and mean age 11.5 years. Linear and logistic regression analyses were used to evaluate associations between log-transformed CB leptin and neonatal and childhood adiposity measures as continuous and categorical variables, respectively. RESULTS: CB leptin was positively associated with neonatal and childhood adiposity. Childhood associations were attenuated when adjusted for maternal body mass index (BMI) and glucose, but remained statistically significant for childhood body fat percentage (ß = 1.15%, confidence interval [CI] = 0.46-1.84), body fat mass (ß = 0.69 kg, 95% CI = 0.16-1.23), sum of skin-folds (ß = 1.77 mm, 95% CI = 0.31-3.24), log-transformed child serum leptin (ß = 0.13, 95% CI = 0.06-0.20), overweight/obesity (OR = 1.21, 95% CI = 1.03-1.42), obesity (OR = 1.31, 95% CI = 1.04-1.66) and body fat percentage >85th percentile (OR = 1.38, 95% CI = 1.12-1.73). Positive associations between newborn adiposity measures and CB leptin confirmed previous reports. CONCLUSION: CB leptin is positively associated with neonatal and childhood adiposity and child leptin levels, independent of maternal BMI and maternal hyperglycemia. CB leptin may be a biomarker of future adiposity risk.

One children's hospital planning and development process to adhere to the FDA recommendation that babies and young children undergo thyroid function testing after receiving an injection of iodine-containing contrast media for medical imaging.

The United States (US) Food and Drug Administration (FDA) has issued multiple statements and guidelines since 2015 on the topic of thyroid function testing in babies and children through 3 years old after receiving iodinated contrast media for medical imaging exams. In April 2023, the FDA adjusted this recommendation to target babies and young children younger than 4 years of age who have a history of prematurity, very low birth weight, or underlying conditions which affect thyroid gland function, largely in response to solid arguments from expert statements from the American College of Radiology (ACR) which is endorsed by the Society for Pediatric Radiology (SPR), Pediatric Endocrinology Society (PES), and the Society for Cardiovascular Angiography & Intervention (SCAI). Herein we describe our approach and development of a clinical care guideline along with the steps necessary for implementation of the plan including alterations in ordering exams requiring iodinated contrast media, automatic triggering of lab orders, reporting, and follow-up, to address the 2022 FDA guidance statement to monitor thyroid function in children after receiving iodinated contrast media. The newly implemented clinical care guideline at Ann and Robert H. Lurie Children's Hospital of Chicago remains applicable following the 2023 updated recommendation from the FDA. We will track patients less than 3 months of age who undergo thyroid function testing following computed tomography (CT), interventional radiology, and cardiac catheterization exams for which an iodinated contrast media is administered as a clinical care quality initiative.

Participant characteristics in the prevention of gestational diabetes as evidence for precision medicine: a systematic review and meta-analysis.

BACKGROUND: Precision prevention involves using the unique characteristics of a particular group to determine their responses to preventive interventions. This study aimed to systematically evaluate the participant characteristics associated with responses to interventions in gestational diabetes mellitus (GDM) prevention. METHODS: We searched MEDLINE, EMBASE, and Pubmed to identify lifestyle (diet, physical activity, or both), metformin, myoinositol/inositol and probiotics interventions of GDM prevention published up to May 24, 2022. RESULTS: From 10347 studies, 116 studies (n = 40940 women) are included. Physical activity results in greater GDM reduction in participants with a normal body mass index (BMI) at baseline compared to obese BMI (risk ratio, 95% confidence interval: 0.06 [0.03, 0.14] vs 0.68 [0.26, 1.60]). Combined diet and physical activity interventions result in greater GDM reduction in participants without polycystic ovary syndrome (PCOS) than those with PCOS (0.62 [0.47, 0.82] vs 1.12 [0.78-1.61]) and in those without a history of GDM than those with unspecified GDM history (0.62 [0.47, 0.81] vs 0.85 [0.76, 0.95]). Metformin interventions are more effective in participants with PCOS than those with unspecified status (0.38 [0.19, 0.74] vs 0.59 [0.25, 1.43]), or when commenced preconception than during pregnancy (0.21 [0.11, 0.40] vs 1.15 [0.86-1.55]). Parity, history of having a large-for-gestational-age infant or family history of diabetes have no effect on intervention responses. CONCLUSIONS: GDM prevention through metformin or lifestyle differs according to some individual characteristics. Future research should include trials commencing preconception and provide results disaggregated by a priori defined participant characteristics including social and environmental factors, clinical traits, and other novel risk factors to predict GDM prevention through interventions.

An individual's characteristics, such as medical, biochemical, social, and behavioural may affect their response to interventions aimed at preventing gestational diabetes, which occurs during pregnancy. Here, we evaluated the published literature on interventions such as diet, lifestyle, drug treatment and nutritional supplement and looked at which individual participant characteristics were associated with response to these interventions. Certain participant characteristics were associated with greater prevention of gestational diabetes through particular treatments. Some interventions were more effective when started prior to conception. Future studies should consider individual characteristics when assessing the effects of preventative measures.

Maternal and Cord Blood Serum Metabolite Associations with Childhood Adiposity and Body Composition Outcomes.

Maternal metabolites influence the size of newborns independently of maternal body mass index (BMI) and glycemia, highlighting the importance of maternal metabolism on offspring outcomes. This study examined associations of maternal metabolites during pregnancy with childhood adiposity, and cord blood metabolites with childhood adiposity using phenotype and metabolomic data from the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study and the HAPO Follow-Up Study. The maternal metabolites analyses included 2324 mother-offspring pairs, while the cord blood metabolites analyses included 937 offspring. Multiple logistic and linear regression were used to examine associations between primary predictors, maternal or cord blood metabolites, and childhood adiposity outcomes. Multiple maternal fasting and 1 hr metabolites were significantly associated with childhood adiposity outcomes in Model 1 but were no longer significant after adjusting for maternal BMI and/or maternal glycemia. In the fully adjusted model, fasting lactose levels were negatively associated with child BMI z-scores and waist circumference, while fasting urea levels were positively associated with waist circumference. One-hour methionine was positively associated with fat-free mass. There were no significant associations between cord blood metabolites and childhood adiposity outcomes. Few metabolites were associated with childhood adiposity outcomes after adjusting for maternal BMI and glucose, suggesting that maternal BMI accounts for the association between maternal metabolites and childhood adiposity.

A systematic review and meta-analysis of participant characteristics in the prevention of gestational diabetes: a summary of evidence for precision medicine.

Background and aims: Precision prevention involves using the unique characteristics of a particular group to determine their responses to preventive interventions. This study aimed to systematically evaluate the participant characteristics associated with interventions in gestational diabetes mellitus (GDM) prevention. Methods: We searched MEDLINE, EMBASE, and Pubmed to identify lifestyle (diet, physical activity, or both), metformin, myoinositol/inositol and probiotics interventions of GDM prevention published up to May 24, 2022. Results: From 10347 studies, 116 studies (n=40940 women) were included. Physical activity resulted in greater GDM reduction in participants with a normal body mass index (BMI) at baseline compared to obese BMI (risk ratio, 95% confidence interval: 0.06 [0.03, 0.14] vs 0.68 [0.26, 1.60]). Diet and physical activity interventions resulted in greater GDM reduction in participants without polycystic ovary syndrome (PCOS) than those with PCOS (0.62 [0.47, 0.82] vs 1.12 [0.78-1.61]) and in those without a history of GDM than those with unspecified history (0.62 [0.47, 0.81] vs 0.85 [0.76, 0.95]). Metformin interventions were more effective in participants with PCOS than those with unspecified status (0.38 [0.19, 0.74] vs 0.59 [0.25, 1.43]), or when commenced preconception than during pregnancy (0.22 [0.11, 0.45] vs 1.15 [0.86-1.55]). Parity, history of having a large-for-gestational-age infant or family history of diabetes had no effect. Conclusions: GDM prevention through metformin or lifestyle differs according to some individual characteristics. Future research should include trials commencing preconception and provide results stratified by participant characteristics including social and environmental factors, clinical traits, and other novel risk factors to predict GDM prevention through interventions. Plain language summary: Precision prevention involves using a group’s unique context to determine their responses to preventive interventions. This study aimed to evaluate the participant characteristics associated with interventions in GDM prevention. We searched medical literature databases to identify lifestyle (diet, physical activity), metformin, myoinositol/inositol and probiotics interventions. A total of 116 studies (n=40903 women) were included. Diet and physical activity interventions resulted in greater GDM reduction in participants without polycystic ovary syndrome (PCOS) and those without a history of GDM. Metformin interventions resulted in greater GDM reduction in participants with PCOS or when started during the preconception period. Future research should include trials starting in the preconception period, and provide results stratified by participant characteristics to predict GDM prevention through interventions.

Perioperative outcomes in children with Hashimoto's thyroiditis undergoing total thyroidectomy.

BACKGROUND: Hashimoto's thyroiditis (HT) affects 1-2 % of the pediatric population. In adults with HT, thyroidectomy is considered challenging and prone to postoperative complications due to the chronic inflammatory process. However, the complications of thyroidectomy among children with HT have not been established. The objective of our study was to evaluate whether children with HT undergoing total thyroidectomy for presumed thyroid cancer have higher complication rates than children without HT. METHODS: A retrospective cohort study of children who underwent total thyroidectomy by high-volume pediatric otolaryngologists between 2014 and 2021. RESULTS: 111 patients met inclusion criteria, 15 of these were diagnosed with HT preoperatively. Operative time and length of admission were similar among the groups. Postoperatively, patients with HT were more likely to have low levels of parathyroid hormone (60 % vs 26 %, p = 0.014) and transient hypocalcemia compared to non-HT patients, present with symptomatic hypocalcemia (67 % vs 27 %, p = 0.006), demonstrate EKG changes (20 % vs 6.3 %, p = 0.035) within 24 h of surgery, and to require both oral and intravenous calcium supplements (80 % vs 35 %, p = 0.001 and 60 % vs 22 % p = 0.004 respectively). Persistent hypocalcemia at 6 months follow-up, and recurrent laryngeal nerve paralysis rates were similar between groups. Parathyroid tissue was found in the thyroid specimen of 9 (60 %) HT patients vs 34 (35 %) non-HT patients (p = 0.069). CONCLUSIONS: The risk of permanent complications among children with HT following thyroidectomy is low. However, patients with HT are more likely to develop symptomatic transient hypocalcemia and to require oral and intravenous calcium supplements in the immediate post-operative period compared to non-HT patients. Tailoring a perioperative treatment protocol to optimize calcium levels may be considered for children with HT.

Total Thyroidectomy and Subsequent Weight Gain in Pediatric Populations.

OBJECTIVE: To evaluate weight gain in children post-thyroidectomy and identify predictors. METHODS: Charts from patients at a tertiary health care facility who underwent total thyroidectomy from 2014 to 2020 were reviewed for Body Mass Index z-scores (BMIz) at the time of thyroidectomy and at 1 and 2-year post-operation intervals. Patient demographic information, comorbidities, pre- and postoperative thyroid stimulating hormone, and postoperative free T4 levels were also extracted. Patients with other known endocrine abnormalities, chronic kidney disease, or without sufficient follow-up were excluded. RESULTS: A total of 56 patients (ages 3-17 years old) met the inclusion criteria (n = 17 Graves' disease; n = 39 presumed cancer). Over the first year, average BMIz significantly increased in patients with Graves' disease (∆BMIz = 0.45 ± 0.77, p = 0.03), Hispanic ethnicity (∆BMIz = 0.43 ± 0.68, p = 0.004), Medicaid/no insurance coverage (∆BMIz = 0.33 ± 0.74, p = 0.038), age <13 years at thyroidectomy (∆BMIz = 0.35 ± 0.68, p = 0.016), and persistent postoperative hypothyroidism (∆BMIz = 0.41 ± 0.41, p = 0.012). These changes remained significant after the second year. Age at thyroidectomy correlated negatively with ∆BMIz only after the first year (r = -0.40, p = 0.002). Regression analysis, controlling for Graves' status, persistent postoperative hypothyroidism, and insurance coverage, identified age at thyroidectomy as a significant predictor of ∆BMIz after the first year (b = -0.06, p = 0.004) and Hispanic ethnicity as a significant predictor after the second year (b = 0.60, p = 0.003). CONCLUSION: A small increase in BMIz post-thyroidectomy was observed across several patient subgroups. Younger age at thyroidectomy and Hispanic ethnicity were associated with increased BMIz in the first 2 years post-thyroidectomy. LEVEL OF EVIDENCE: Level 4 - Historically controlled cohort Laryngoscope, 133:1518-1523, 2023.

Abnormal TSH Prior to Surgery in Children with Graves' Disease Predicts Abnormal TSH Following Thyroidectomy.

OBJECTIVE: To identify variables that are associated with poor compliance to thyroid hormone replacement therapy in children after total thyroidectomy. METHOD: A retrospective cohort study of children who underwent total thyroidectomy by high-volume pediatric otolaryngologists between 1/2014 and 9/2021. Postoperative poor compliance was characterized by at least three separate measurements of high TSH levels not associated with radioactive iodine treatment. RESULTS: There were 100 patients, ages 3-20 years old who met inclusion criteria; 44 patients underwent thyroidectomy for cancer diagnosis, and 56 for Graves' disease. The mean follow-up time was 36.5 months (range 3.0-95.6 months). Overall, 42 patients (42%) were found to have at least three measurements of high TSH during follow-up, and 29 patients (29%) were diagnosed with clinical hypothyroidism. Sex, race, income, insurance type, and benign versus malignant etiology for thyroidectomy were not associated with adherence to therapy. Multivariate regression analysis identified patients with Graves' disease and hyperthyroidism at the time of surgery and Hispanic ethnicity to be associated with postoperative clinical hypothyroidism (OR 9.38, 95% CI 2.16-49.2, p = 0.004 and OR 6.15, 95% CI 1.21-36.0, p = 0.033, respectively). CONCLUSIONS: Preoperative hyperthyroidism in patients with Graves' disease and Hispanic ethnicity were predictors of postoperative TSH abnormalities. Preoperative counseling for patients and their families on the implications of total thyroidectomy and the need for life-long medications postoperatively is necessary. Efforts should be made to evaluate and improve adherence to therapy pre-and postoperatively in patients with Graves' disease. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:2402-2406, 2023.

Short-Term Complications After Total Thyroidectomy in Children.

INTRODUCTION: Total thyroidectomy for benign disease is becoming more common among children. The purpose of this study was to evaluate 30-day outcomes in children undergoing total thyroidectomy and determine if the short-term outcomes are different in those with a malignant versus benign indication for surgery. METHODS: This retrospective cohort study used the American College of Surgeons National Surgical Quality Improvement Program-Pediatric (NSQIP-Pediatric) to identify all children who underwent total thyroidectomy from 2015 to 2019. Fisher's exact test was used to compare postoperative outcomes between benign and malignant indications for thyroidectomy. RESULTS: Among 1595 total thyroidectomy patients, 1091 (68.4%) had a benign indication and 504 (31.6%) had a malignant indication. There were 1234 (77.4%) females, and the median age was 14.9 y (interquartile range [IQR] 12.5, 16.6). Average length of stay (LOS) was similar between cohorts (1.7 d for benign and 1.9 d for malignant, P = 0.30). Parathyroid auto-transplantation was performed in 71 (6.5%) patients in the benign cohort and 43 (8.6%) in the malignant cohort (P = 0.15). The most common complications were readmissions (23 [2.1%] benign and 15 [3.0%] malignant, P = 0.29) and reoperations (7 [0.6%] benign and 5 [1.0%] malignant, P = 0.54). Complication profiles were similar between benign and malignant cohorts (2.8% and 4.6%, respectively [P = 0.10]). CONCLUSIONS: Children undergoing total thyroidectomy for benign and malignant indications have low rates of 30-d postoperative complications, suggesting that total thyroidectomy is a safe option for children with benign disease. Evaluation of long-term outcomes is needed.

The effect of hyperthyroidism at thyroidectomy on complication rates in children with Graves' disease.

BACKGROUND: Graves' disease (GD) is the most common cause of childhood hyperthyroidism. Surgery is often chosen as a treatment modality given the high relapse rates and side effects of antithyroid drugs and has shown to be safe and efficacious. The goal of our study was to evaluate whether hyperthyroidism at time of thyroidectomy is associated with higher intra and postoperative complication rates. METHODS: A retrospective cohort study of children who underwent thyroidectomy for GD by high-volume pediatric otolaryngologists between 2014 and 2021. RESULTS: 64 patients met inclusion criteria. Patients with hyperthyroidism (defined as free T4≥1.63 ng/dL) were more likely to be treated with beta-blocker preoperatively compared to the euthyroid group (20/24 patients (83%) vs 23/40 patients (58%) respectively, p = 0.035). Twenty (83%) patients with hyperthyroidism and 39 euthyroid patients (98%) were treated with methimazole prior to surgery. Intraoperative tachycardia was noted in 5% of euthyroid patients and 20.8% of patients with hyperthyroidism. The mean peak heart rate intra-operatively and the number of patients with heart rate ≥120bmp were significantly higher for patients with hyperthyroidism (96.5 ± 16.2 vs 87.6 ± 22.1bpm, p = 0.02). Two patients required administration of esmolol during surgery for heart rate control, both with hyperthyroidism. Intra-operative peak systolic blood pressure, operative time, estimated blood loss, persistent hypocalcemia, length of admission and recurrent laryngeal nerve paralysis rates were similar among groups. CONCLUSIONS: Hyperthyroidism at surgery is associated with increased heart rate intraoperatively, with no increased risk for other complications. While optimizing thyroid hormone levels before surgery should be pursued in all children, our data suggest that hyperthyroidism should not delay the surgery.

The 2015 American Thyroid Association guidelines and trends in hemithyroidectomy utilization for pediatric thyroid cancer.

BACKGROUND: In 2015, the American Thyroid Association (ATA) released its inaugural recommendations for the management of thyroid cancer in children. We aim to evaluate whether there has been a change in hemithyroidectomy utilization for pediatric differentiated thyroid cancer, and the association between those changes and the release of the ATA guidelines. METHODS: The National Cancer Database was queried and identified 4776 patients ≤18 years old with differentiated thyroid cancer. Causal impact time-series analysis and logistic analysis were utilized to assess factors associated with use of hemithyroidectomy. RESULTS: Post-2015 hemithyroidectomy rate was greater than predicted based on preguideline trends (predicted: 8.4%, actual: 12.6%, p = 0.001). In logistic analysis of factors associated with hemithyroidectomy use, we find that Papillary histology, tumor size >1 cm, nodal examination, and positive nodes were associated with lower rate of hemithyroidectomy (OR: 0.23, 0.51, 0.62, and 0.18, respectively). CONCLUSION: There has been a significant increase in hemithyroidectomy utilization for pediatric differentiated thyroid cancer.

Neurofibromatosis Type 1 Has a Wide Spectrum of Growth Hormone Excess.

Overgrowth due to growth hormone (GH) excess affects approximately 10% of patients with neurofibromatosis type 1 (NF1) and optic pathway glioma (OPG). Our aim is to describe the clinical, biochemical, pathological, and genetic features of GH excess in a retrospective case series of 10 children and adults with NF1 referred to a tertiary care clinical research center. Six children (median age = 4 years, range of 3−5 years), one 14-year-old adolescent, and three adults (median age = 42 years, range of 29−52 years) were diagnosed with NF1 and GH excess. GH excess was confirmed by the failure to suppress GH (<1 ng/mL) on oral glucose tolerance test (OGTT, n = 9) and frequent overnight sampling of GH levels (n = 6). Genetic testing was ascertained through targeted or whole-exome sequencing (n = 9). Five patients (all children) had an OPG without any pituitary abnormality, three patients (one adolescent and two adults) had a pituitary lesion (two tumors, one suggestive hyperplasia) without an OPG, and two patients (one child and one adult) had a pituitary lesion (a pituitary tumor and suggestive hyperplasia, respectively) with a concomitant OPG. The serial overnight sampling of GH levels in six patients revealed abnormal overnight GH profiling. Two adult patients had a voluminous pituitary gland on pituitary imaging. One pituitary tumor from an adolescent patient who harbored a germline heterozygous p.Gln514Pro NF1 variant stained positive for GH and prolactin. One child who harbored a heterozygous truncating variant in exon 46 of NF1 had an OPG that, when compared to normal optic nerves, stained strongly for GPR101, an orphan G protein-coupled receptor causing GH excess in X-linked acrogigantism. We describe a series of patients with GH excess and NF1. Our findings show the variability in patterns of serial overnight GH secretion, somatotroph tumor or hyperplasia in some cases of NF1 and GH excess. Further studies are required to ascertain the link between NF1, GH excess and GPR101, which may aid in the characterization of the molecular underpinning of GH excess in NF1.

A Mini-Review of Pediatric Anthropometrics as Predictors of Future Insulin Resistance.

The impact of rising rates of childhood obesity is far reaching. Metabolic syndrome in children is increasing, yet for most children the consequences of excess adiposity will manifest in adulthood. Excess early fat accrual is a risk factor for future insulin resistance. However, certain types of fat and patterns of fat distribution are more relevant than others to metabolic risk. Therefore, adiposity measures are important. The link between childhood obesity and future insulin resistance was initially established with body mass index (BMI), but BMI is an in imperfect measure of adiposity. It is worthwhile to evaluate other anthropometrics as they may more accurately capture metabolic risk. While measures such as waist to height ratio are established as superior screening measures in adulthood - the findings are not as robust in pediatrics. Emerging evidence suggests that alternative anthropometrics may be slightly superior to BMI in identifying those youth most at risk of developing insulin resistance, but the clinical significance of that superiority appears limited. Increasing study is needed in longitudinal and varied cohorts to identify which pediatric anthropometric best predicts adult insulin resistance. We review alternative anthropometrics as predictors of future insulin resistance and identify current gaps in knowledge and potential future directions of inquiry.

Effect of surgeon volume on pediatric thyroid surgery outcomes: A systematic review.

BACKGROUND: Pediatric thyroidectomy has been identified as a surgical procedure that may benefit from concentrating cases to high-volume surgeons. This systematic review aimed to address the definition of "high-volume surgeon" for pediatric thyroidectomy and to examine the relationship between surgeon volume and outcomes. METHODS: PubMed, Embase, Cochrane Library, Scopus, Web of Science, ClinicalTrials.gov, and OpenGrey databases were searched for through February 2020 for studies which reported on pediatric thyroidectomy and specified surgeon volume and surgical outcomes. RESULTS: Ten studies, encompassing 6430 patients, were included in the review. Five single-center retrospective studies reported only on high-volume surgeons, one single center retrospective study reported on only low-volume surgeons, and four national database studies (2 cross sectional, 2 retrospective reviews) reported outcomes for both high-volume and low-volume surgeons. Majority of patients underwent total thyroidectomy (54.9%); common indications for surgery were malignancy (41.7%) and hyperthyroidism/thyroiditis (40.5%). Rates of transient hypocalcemia (11.4% - 74.2%), transient recurrent laryngeal nerve injury (0% - 9.7%), and bleeding (0.5% - 4.3%) varied across studies. Definitions for high-volume pediatric thyroid surgeons ranged from ≥9 annual pediatric thyroid operations to >200 annual thyroid operations (with >30 pediatric cases). Four studies reported significantly better outcomes, including lower post-operative complications and shorter length of hospital stay, for patients treated by high-volume surgeons. CONCLUSIONS: Despite significant variation in caseloads to define volume, pediatric thyroid patients have generally better outcomes when operated on by higher volume surgeons. Concentration thyroidectomy cases to a smaller cohort of surgeons within pediatric practices may confer improved outcomes. LEVEL OF EVIDENCE: Systematic Reviews and Meta-Analyses; Level IV.

Surgeon perceptions of volume threshold and essential practices for pediatric thyroidectomy✰.

INTRODUCTION: The topics of sub-specialization and regionalization of care have garnered increased attention among pediatric surgeons. Thyroid surgeries are one such sub-specialty and are commonly concentrated within practices. A national survey was conducted examining current surgeon practices and beliefs surrounding pediatric thyroid surgery. METHODS: Non-resident members of the American Pediatric Surgical Association (APSA) were surveyed in October 2020. Respondents were stratified based on self-reported thyroid surgical experience. Those who performed thyroid surgery were asked about surgical technique and operative practices; those who did not were asked about referral patterns. All respondents were asked about perceptions surrounding the volume-outcome relationship for pediatric thyroid surgery. RESULTS: Among 1015 APSA members, 405 (40%) responded, with 79% (317/400) practicing at academic hospitals, 58% (232/401) practicing in major metropolitan area, and 41% (161/392) with over 10 years of attending pediatric surgery experience. Most respondents (88%, n = 356) agreed that thyroid surgery volume affects outcome, though wide variation was reported in the annual case threshold for "high volume" surgery. Eighty-four respondents (21%) reported performing ≥ 1 pediatric thyroid surgery in the past year. Of these, 82% routinely use recurrent laryngeal nerve monitoring, 32% routinely send hemithyroidectomy patients home the same day, and there was little consensus surrounding postoperative hypocalcemia management. The majority of respondents endorse performing thyroid procedures with a colleague. CONCLUSIONS: Pediatric thyroid surgery appears to be performed by a subset of active pediatric surgeons, most of whom endorse the use of a dual operating team. More evidence is needed to build consensus around additional perioperative practices.

Early Growth and Cognitive Development in Children Born Preterm: Relevance of Maternal Body Mass Index.

OBJECTIVE: Maternal prepregnancy body mass index (BMI) represents a surrogate marker of fetal exposures to the maternal metabolism during pregnancy. Yet, it remains poorly understood whether this marker indicates risk of altered trajectories in postnatal growth and development in children born preterm. This study aimed to determine whether maternal prepregnancy BMI is associated with altered growth and development in children born preterm. STUDY DESIGN: A retrospective cohort study evaluated prepregnancy BMI as the exposure for childhood outcomes using linear regression and mixed effects models. The 38 children included in this follow-up evaluation originally participated in a prospective, observational cohort study to determine longitudinal levels of lipid species in preterm human milk expressed by women who delivered prior to 32 weeks. Childhood outcomes in this study were anthropometric measures during hospitalization (n = 38), after discharge through 36 months (n = 34) and Bayley-III developmental scores through 18 months corrected age (n = 26). RESULTS: In 38 children born prior to 32 weeks, higher maternal prepregnancy BMI was independently associated with higher preterm infant growth velocity during hospitalization, but not associated with in-hospital change in length or head circumference and/or postdischarge growth. In univariate linear regression models, higher maternal BMI was associated with lower cognitive scores at 18 months corrected age. This significant association remained in an adjusted model accounting for relevant influences on early childhood development. CONCLUSION: Increasing maternal prepregnancy BMI may reflect risk of altered growth and cognitive development in children born preterm. KEY POINTS: · Maternal BMI was associated with early preterm infant weight gain.. · Maternal BMI was not associated with postdischarge growth.. · Increased maternal BMI may be associated with lower cognitive function scores in offspring..

Long-term follow-up of children with in utero exposure to sulfonylurea medications.

BACKGROUND: Offspring born to mothers with gestational diabetes mellitus (GDM) are more likely to have negative neurodevelopmental health outcomes, early obesity, type 2 diabetes, and metabolic syndrome in childhood, adolescence, and adulthood. Standard of care management for GDM and type 2 diabetes mellitus during pregnancy is insulin, but oral sulfonylurea use is increasing, and these medications cross the placenta. Literature on treatment with sulfonylureas for maternal GDM has focused on maternal glycemic control and neonatal outcomes. Studies that have evaluated the long-term outcomes of children exposed to sulfonylureas in utero are limited. OBJECTIVE: This study evaluated anthropometric and neurodevelopmental outcomes of 55 children (ages 5-10) born to mothers with diabetes during pregnancy treated with sulfonylurea or insulin. METHODS AND RESULTS: A group of 25 sulfonylurea-exposed and 30 insulin-exposed participants were age- and sex-matched between groups. No significant differences were identified in z-scores for body mass index (BMI), waist circumference, skinfold measurements, and body fat or rates of overweight/obese BMI between groups. On performance-based cognitive assessment, the sulfonylurea-exposed group had significantly lower scores on inhibition (p = 0.043). CONCLUSION: In summary, children with in utero sulfonylurea exposure had similar physical measurements compared to children with insulin exposure and lower performance on a measure of executive function (inhibition), which is associated with adverse health outcomes.