Effects of Pharmacologic Treatment for Neonatal Abstinence Syndrome on DNA Methylation and Neurobehavior

Pharmacologic treatment of NAS is associated with decreased DNAm of the OPRM1 gene and improved neonatal neurobehavior.

source: J Pediatr.

Summary

A Prospective Cohort Study

[Posted 4/May/2022]

AUDIENCE: Pediatric

KEY FINDINGS: Pharmacologic treatment of NAS is associated with decreased DNAm of the OPRM1 gene and improved neonatal neurobehavior. Epigenetic changes may play a role in these changes in neonatal neurobehavior.

BACKGROUND: Aim of this study is to determine whether pharmacologic treatment for neonatal abstinence syndrome (NAS) is associated with changes in DNA methylation (DNAm) of the mu-opioid receptor gene (OPRM1) and improvements in neonatal neurobehavior.

DETAILS: Buccal swabs were collected from 37 neonates before and after morphine treatment for NAS. Genomic DNA was extracted, and DNAm was examined at 4 cytosine-phosphate-guanine (CpG) sites within the OPRM1 gene. Assessment with the NICU Network Neurobehavioral Scales (NNNS) was also performed before and after NAS treatment. Changes in DNAm (DNAmpost-tx – DNAmpre-tx) and NNNS summary scores (NNNSpost-tx – NNNSpre-tx) were then calculated. Path analysis was used to examine associations among pharmacologic treatment (length of treatment [LOT] and total dose of morphine), changes in DNAm, and changes in NNNS summary scores. DNAm was significantly decreased from pretreatment to post-treatment at 1 of 4 CpG sites within the OPRM1 gene. Neonates also demonstrated decreased excitability, hypertonia, lethargy, signs of stress and abstinence, and increased quality of movement and regulation from pretreatment to post-treatment. Longer LOT and higher morphine dose were associated with greater decreases in DNAm; greater decreases in DNAm were associated with greater decreases in excitability and hypertonia on the NNNS.

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Copyright © Elsevier Inc. All rights reserved.

Source: Camerota, M., Davis, J. M., Dansereau, L. M., et al. (2022). Effects of Pharmacologic Treatment for Neonatal Abstinence Syndrome on DNA Methylation and Neurobehavior: A Prospective Cohort Study. J Pediatr.. 2022; 243: 21-26. Published: April, 2022. DOI: 10.1016/j.jpeds.2021.12.057.



Diagnostic Accuracy of Point-Of-Care Ultrasound for Paediatric Testicular Torsion

The present systematic review and meta-analysis showed that POCUS had high sensitivity and specificity for identifying testicular torsion in paediatric patients although the risk of bias was high in the studies analysed.

source: Emerg Med J.

Summary

A Systematic Review And Meta-Analysis

[Posted 17/May/2022]

AUDIENCE: Emergency Medicine, Pediatric

KEY FINDINGS: The present systematic review and meta-analysis showed that POCUS had high sensitivity and specificity for identifying testicular torsion in paediatric patients although the risk of bias was high in the studies analysed.

BACKGROUND: Previous studies have examined the utility of ultrasonography performed by radiologists for diagnosing paediatric testicular torsion. While point-of-care ultrasound (POCUS) is used in paediatric emergency medicine, its diagnostic accuracy is still unknown. The present systematic review and meta-analysis aimed to clarify the accuracy of POCUS in diagnosing testicular torsion in children.

DETAILS: Following the Preferred Reporting Items for Systematic Review and Meta-analysis of Diagnostic Test Accuracy guidelines, a systematic review was performed. Any study investigating the diagnostic accuracy of POCUS for paediatric testicular torsion was extracted. The primary outcome was the assessment of the diagnostic accuracy of POCUS for paediatric testicular torsion. The pooled sensitivity and specificity were calculated. Quality analysis was conducted using Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). Four studies enrolling 784 patients in total were included. The pooled sensitivity, specificity, and positive and negative likelihood ratios of POCUS were 98.4% (95% CI: 88.5% to 99.8%), 97.2% (95% CI: 87.2% to 99.4%), 34.7 (95% CI: 7.4 to 164.4) and 0.017 (95% CI: 0.002 to 0.12), respectively. Risk-of-bias assessment using QUADAS-2 revealed that two of the studies had a high risk of bias in patient selection.

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Copyright © BMJ Publishing Group Ltd and the College of Emergency Medicine. All rights reserved.

Source: Mori, T., Ihara, T., Nomura, O. (2022). Diagnostic Accuracy Of Point-Of-Care Ultrasound For Paediatric Testicular Torsion: A Systematic Review And Meta-Analysis. Emergency Medicine Journal . 2022; e212281. Published: May 6, 2022. DOI: 10.1136/emermed-2021-212281.



Association Between RAI Treatment for Pediatric and Young Adulthood DTC and Risk of Second Primary Malignancies

In addition to leukemia, RAI treatment for childhood and young-adulthood DTC was associated with increased risks of several solid cancers, particularly more than 20 years after exposure, supporting the need for long-term surveillance of these patients.

source: J Clinical Oncology

Summary

[Posted 6/May/2022]

AUDIENCE: Oncology, Pediatric, Internal Medicine

KEY FINDINGS: In addition to leukemia, RAI treatment for childhood and young-adulthood DTC was associated with increased risks of several solid cancers, particularly more than 20 years after exposure, supporting the need for long-term surveillance of these patients.

BACKGROUND: Since the 1980s, both the incidence of differentiated thyroid cancer (DTC) and use of radioactive iodine (RAI) treatment increased markedly. RAI has been associated with an increased risk of leukemia, but risks of second solid malignancies remain unclear. We aimed to quantify risks of second malignancies associated with RAI treatment for DTC in children and young adults, who are more susceptible than older adults to the late effects of radiation.

DETAILS: Using nine US SEER cancer registries (1975-2017), estimated relative risks (RRs) for solid and hematologic malignancies associated with RAI (yes v no or unknown) using Poisson regression among >= 5- and >= 2-year survivors of nonmetastatic DTC diagnosed before age 45 years, respectively. Among 27,050 >= 5-year survivors (median follow-up = 15 years), RAI treatment (45%) was associated with increased risk of solid malignancies (RR = 1.23; 95% CI, 1.11 to 1.37). Risks were increased for uterine cancer (RR = 1.55; 95% CI, 1.03 to 2.32) and nonsignificantly for cancers of the salivary gland (RR = 2.15; 95% CI, 0.91 to 5.08), stomach (RR = 1.61; 95% CI, 0.70 to 3.69), lung (RR = 1.42; 95% CI, 0.97 to 2.08), and female breast (RR = 1.18; 95% CI, 0.99 to 1.40). Risks of total solid and female breast cancer, the most common cancer type, were highest among >= 20-year DTC survivors (RRsolid = 1.47; 95% CI, 1.24 to 1.74; RRbreast = 1.46; 95% CI, 1.10 to 1.95). Among 32,171 >= 2-year survivors, RAI was associated with increased risk of hematologic malignancies (RR = 1.51; 95% CI, 1.08 to 2.01), including leukemia (RR = 1.92; 95% CI, 1.04 to 3.56). We estimated that 6% of solid and 14% of hematologic malignancies in pediatric and young adult DTC survivors may be attributable to RAI.

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Copyright © American Society of Clinical Oncology

Source: Pasqual, E., Schonfeld, S., Morton, L. M., et al. (2022). Association Between Radioactive Iodine Treatment for Pediatric and Young Adulthood Differentiated Thyroid Cancer and Risk of Second Primary Malignancies. ournal of Clinical Oncology . 2022; 40(13): 1439-1449. Published: May 1, 2022. DOI: 10.1200/JCO.21.01841.



Fetal Brain Volume Predicts Neurodevelopment in Congenital Heart Disease

Small fetal brain volume is a strong independent predictor of 2-year neurodevelopmental outcomes and may be an important imaging biomarker of future neurodevelopmental risk in CHD.

source: Circulation

Summary

[Posted 21/Apr/2022]

AUDIENCE: Cardiology, Emergency Medicine

KEY FINDINGS: Small fetal brain volume is a strong independent predictor of 2-year neurodevelopmental outcomes and may be an important imaging biomarker of future neurodevelopmental risk in CHD. Future studies are needed to support this hypothesis. Our findings support inclusion of fetal brain volume in risk stratification models and as a possible outcome in fetal neuroprotective intervention studies.

BACKGROUND: Neurodevelopmental impairment is common in children with congenital heart disease (CHD), but postnatal variables explain only 30% of the variance in outcomes. To explore whether the antecedents for neurodevelopmental disabilities might begin in utero, we analyzed whether fetal brain volume predicted subsequent neurodevelopmental outcome in children with CHD.

DETAILS: Fetuses with isolated CHD and sociodemographically comparable healthy control fetuses underwent fetal brain magnetic resonance imaging and 2-year neurodevelopmental evaluation with the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) and the Adaptive Behavior Assessment System, Third Edition (ABAS-3). Hierarchical regression evaluated potential predictors of Bayley-III and ABAS-3 outcomes in the CHD group, including fetal total brain volume adjusted for gestational age and sex, sociodemographic characteristics, birth measures, and medical history. The CHD group (n=52) had lower Bayley-III cognitive, language, and motor scores than the control group (n=26), but fetal brain volumes were similar. Within the CHD group, larger fetal total brain volume correlated with higher Bayley-III cognitive, language, and motor scores and ABAS-3 adaptive functioning scores (r=0.32–0.47; all P0.05), but this was not noted in the control group. Fetal brain volume predicted 10% to 21% of the variance in neurodevelopmental outcome measures in univariate analyses. Multivariable models that also included social class and postnatal factors explained 18% to 45% of the variance in outcome, depending on developmental domain. Moreover, in final multivariable models, fetal brain volume was the most consistent predictor of neurodevelopmental outcome across domains.

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Copyright © American Heart Association, Inc. All rights reserved.

Source: Sadhwani, A., Wypij, D., Rofeberg, V., et al. (2022). Fetal Brain Volume Predicts Neurodevelopment in Congenital Heart Disease. Circulation. 2022; 145(15): 1108–1119. Published: April 12, 2022. DOI: 10.1161/CIRCULATIONAHA.121.056305.



Influence of Placental and Peripheral Malaria Exposure In Fetal Life

The subtle elevations of plasma glucose might represent an early risk marker for later development of type 2 diabetes if combined with aging and a more obesogenic living environment.

source: BMJ DRC

Summary

Influence of Placental and Peripheral Malaria Exposure In Fetal Life On Cardiometabolic Traits In Adult Offspring

[Posted 12/Apr/2022]

AUDIENCE: Endocrinology, Pediatric, Ob/Gyn

KEY FINDINGS: Using the state-of-the-art euglycemic clamp technique, we were unable to prove our a priori primary hypothesis of peripheral insulin resistance in young adult offspring of pregnancies affected by malaria. However, the subtle elevations of plasma glucose might represent an early risk marker for later development of type 2 diabetes if combined with aging and a more obesogenic living environment.

BACKGROUND: Fetal malaria exposure may lead to intrauterine growth restriction and increase the risk of developing diabetes and cardiovascular diseases in adulthood. We investigated the extent to which fetal peripheral and placental malaria exposure impacts insulin sensitivity and secretion, body composition and cardiometabolic health 20 years after in utero malaria exposure.

DETAILS: During the study, traced 101 men and women in Muheza district, Tanga region whose mothers participated in a malaria chemosuppression during a pregnancy study in 1989-1992. All potential participants were screened for malaria, hepatitis B and HIV to ascertain study eligibility. Seventy-six individuals (44 men, 32 women) were included in this cohort study. The participants underwent a thorough clinical examination including anthropometric measurements, ultrasound scanning for abdominal fat distribution, blood pressure, 75 g oral glucose tolerance test, an intravenous glucose tolerance test followed by a hyperinsulinemic euglycemic clamp and a submaximal exercise test. Offspring exposed to placental malaria during pregnancy had significantly higher 30-minute plasma post-glucose load levels, but no significant difference in peripheral insulin resistance, insulin secretion or other cardiometabolic traits compared with non-exposed individuals.

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Source: Grunnet, L. G., Bygbjerg, I. C., Mutabingwa, T. K., et al. (2022). Influence of Placental and Peripheral Malaria Exposure In Fetal Life On Cardiometabolic Traits In Adult Offspring. BMJ Open Diabetes Research and Care. 2022; 10(2): e002639. Published: April 4, 2022. DOI: 10.1136/bmjdrc-2021-002639.



The Use of Monoclonal Antibody Therapy in Pediatric Patients with COVID-19

The administration of MCA therapy in high-risk pediatric patients in the pediatric ED was well-tolerated with subjective improvement noted in COVID-19 symptoms post-therapy.

source: Int J Emerg Med

Summary

A Retrospective Case Series.

[Posted 11/Apr/2022]

AUDIENCE: Emergency Medicine, Pediatric, Infectious Disease

KEY FINDINGS: The administration of MCA therapy in high-risk pediatric patients in the pediatric ED was well-tolerated with subjective improvement noted in COVID-19 symptoms post-therapy. Further studies are necessary to determine the role MCA therapy may play in reducing morbidity from COVID-19 infection in high-risk pediatric patients.

BACKGROUND: Monoclonal antibody (MCA) therapies have been utilized under emergency use authorization (EUA) for high-risk pediatric patients with mild to moderate coronavirus disease 2019 (COVID-19) in the outpatient setting since late 2019. The purpose of this study was to describe the use of MCA therapy in pediatric patients in the pediatric emergency department (ED) at a large community hospital.

DETAILS: This was a retrospective case series of high-risk pediatric patients 12 to 17 years of age who received MCA therapy in the pediatric ED between December 8, 2020 and June 3, 2021. The primary outcome was to describe the patient characteristics, clinical presentation, and safety profile of the pediatric population that received MCA therapy. The secondary outcome was to describe the incidence of hospitalizations or ED visits up to 28 days following therapy. A total of 44 patients were included in the analysis. The median number of days of symptoms was 4 with 41% of patients having symptoms between 0 and 3 days at time of MCA administration. Only one patient experienced a mild adverse event that did not require epinephrine administration. Two patients returned to the ED for reevaluation during the study follow-up period. No patients required admission within 28 days post-therapy.

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Copyright © BioMed Central Ltd unless otherwise stated. All rights reserved.

Source: Santos, J.D.L., Bhisitkul, D., Carman, M., et al. (2022). The Use of Monoclonal Antibody Therapy in Pediatric Patients with COVID-19: A Retrospective Case Series. Int J Emerg Med. 2022; 15(9). Published: March 3, 2022. DOI: 10.1186/s12245-022-00414-8.



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