Should neonatal-perinatal medicine move to two-year fellowships?

The duration of the majority of fellowships in pediatrics has been three-years. With increasing shortages of some outpatient-based pediatric subspecialists, shorter two-year fellowships are being considered for clinically oriented trainees not interested in a career based on research. Shortening the duration of fellowship may have some financial merits such as achieving a higher salary earlier after shorter training. However, we feel that continuing with a three-year duration for neonatology is more pragmatic at this time due to reductions in intensive care rotations during residency, time required to  achieve procedural excellence, the need for exposure to quality assurance methodology, proficiency in novel techniques such as bedside ultrasound, and to maintain the physician-scientist pipeline. The demand for neonatal fellowship continues to be high. Ongoing evaluation of the job market, training needs and fellowship curriculum is needed to determine if the duration of fellowship should be altered in the future.

Child and Adolescent Health in the United States: The Role of Adverse and Positive Childhood Experiences.

Background: Adverse childhood experiences (ACEs) have been associated with poorer health from childhood into adulthood. There has been limited prior research examining the associations between positive childhood experiences (PCEs) and health among children. Objective: The present study examines the association between PCES and child health, controlling for ACE counts, using a nationally representative sample. Participants and Setting: : The data for this study came from the 2019-2020 National Survey of Children's Health and were limited to children six years of age or older with complete demographic information and information on ACEs, PCEs, and child health (n = 46,913). Methods: Bivariate analyses between PCEs, ACEs, child/adolescent characteristics, or caregiver's characteristics and child/adolescent health were examined using Pearson's Chi-square tests, weighted to produce nationally representative distributions. Multivariable regression models were used to examine the association between selected PCEs and good health, controlling for whether a child had two or more ACEs. Results: In adjusted analyses, children who experienced any of the following PCEs had a higher odds of good health, compared to children who did not experience each type of these PCEs: after school activities (aOR 1.85; 95% CI 1.11-3.09), resilient family (aOR 2.22; 95% CI 1.45-3.41), supportive neighborhood (aOR 1.56; 95% CI 1.01-2.41), and connected caregiver (aOR 1.84; 95% CI 1.22-2.77). Conclusions: Examining and understanding PCEs and how they are associated with child health is a unique opportunity to guide more targeted policies and intervention efforts. Efforts to provide PCEs in schools, homes, and communities may help to reduce health inequities early in childhood.

Brief Report: Rural-Urban Differences in Disability Prevalence, Healthcare Services Utilization, and Participation in Special Education.

Previous research has found that rural children are more likely to be disabled but are less likely to receive care. Both rural and disabled children were significantly impacted by the pandemic, particularly in terms of service utilization. Therefore, this study seeks to identify rural-urban differences in the prevalence of various disability indicators and in the receipt of educational and healthcare services. Data from 12,828 children aged 2-17 who participated in the 2021-2022 National Health Interview Survey (NHIS) was used to examine rural-urban differences in three different disability indicators and in education and health services utilization. Disability indicators included the Washington Group Short Set Composite Disability Indicator, a developmental disability indicator, and a neurodivergence indicator. Bivariate analysis, via Rao-Scott chi-square tests, was used to examine rural-urban disparities. Compared to their urban counterparts, rural children were more likely to have a positive Washington Group Short Set Composite Disability Indicator (14.3% vs. 10.6%) and neurodivergence indicator (17Ð.3% vs. 14.1%). Rural children with disabilities were more likely to have received prescription medication for behavioral, mental, or emotional health or concentration in the past year than urban children (34.2% vs. 25.9%). There was no rural-urban difference in the prevalence of developmental disabilities or other forms of health care use and special education participation. This report highlights the need for further investigation into underlying causes of rural-urban disparities in the prevalence of disabilities, as well as the need for continued support for programs and policies designed to support rural children with disabilities.

Health care access barriers among metropolitan and nonmetropolitan populations of eight geographically diverse states, 2018.

INTRODUCTION: Nonmetropolitan populations face frequent health care access barriers compared to their metropolitan counterparts, but differences in the number of these barriers across groups are not known. Our objective was to examine the differences in health care access barriers across metropolitan, micropolitan, and noncore populations. METHODS: We used Behavioral Risk Factor Surveillance System data from the optional "Health Care Access" module to perform a cross-sectional analysis examining access barriers across levels of rurality using bivariate analyses and Poisson models. Access barriers were operationalized as a count ranging from 0 to 5, reflective of the number of financial barriers and nonfinancial barriers. RESULTS: Micropolitan and noncore respondents had lower educational attainment, were older, and were less racially/ethnically diverse than metropolitan respondents. They also reported more barriers, including lacking health insurance, medical debt, and foregoing care or medication due to cost. These barriers were most pronounced in non-Hispanic Black, Hispanic, and American Indian/Alaska Native nonmetropolitan populations, compared to their White counterparts. In adjusted analysis, micropolitan respondents reported more barriers compared to metropolitan (prevalence rate ratio = 1.06; 95% confidence interval: 1.02-1.10) as did women, racial/ethnic minority populations, and those with less education. CONCLUSIONS: Micropolitan populations experience more barriers to health care, and nonmetropolitan respondents report more cost-related barriers than their metropolitan counterparts, raising concerns on health care disparities and financial burdens for these underserved populations. This underscores the need to mitigate these barriers, particularly among those in micropolitan areas and minorized populations.

Perivascular NOTCH3+ stem cells drive meningioma tumorigenesis and resistance to radiotherapy.

Meningiomas are the most common primary intracranial tumors. Treatments for patients with meningiomas are limited to surgery and radiotherapy, and systemic therapies remain ineffective or experimental. Resistance to radiotherapy is common in high-grade meningiomas and the cell types and signaling mechanisms that drive meningioma tumorigenesis and resistance to radiotherapy are incompletely understood. Here we report NOTCH3 drives meningioma tumorigenesis and resistance to radiotherapy and find that perivascular NOTCH3+ stem cells are conserved across meningiomas from humans, dogs, and mice. Integrating single-cell transcriptomics with lineage tracing and imaging approaches in genetically engineered mouse models and xenografts, we show NOTCH3 drives tumor initiating capacity, cell proliferation, angiogenesis, and resistance to radiotherapy to increase meningioma growth and reduce survival. To translate these findings to patients, we show that an antibody stabilizing the extracellular negative regulatory region of NOTCH3 blocks meningioma tumorigenesis and sensitizes meningiomas to radiotherapy, reducing tumor growth and improving survival.

A Vascular-Centric Approach to Autism Spectrum Disorders.

Brain development and function are highly reliant on adequate establishment and maintenance of vascular networks. Early impairments in vascular health can impact brain maturation and energy metabolism, which may lead to neurodevelopmental anomalies. Our recent work not only provides novel insights into the development of cerebrovascular networks but also emphasizes the importance of their well-being for proper brain maturation. In particular, we have demonstrated that endothelial dysfunction in autism spectrum disorders (ASD) mouse models is causally related to altered behavior and brain metabolism. In the prenatal human brain, vascular cells change metabolic states in the second trimester. Such findings highlight the need to identify new cellular and molecular players in neurodevelopmental disorders, raising awareness about the importance of a healthy vasculature for brain development. It is thus essential to shift the mostly neuronal point of view in research on ASD and other neurodevelopmental disorders to also include vascular and metabolic features.

Availability and Quality of Dialysis Care in Rural versus Urban US Counties.

INTRODUCTION: Rural areas face significant disparities in dialysis care compared to urban areas due to limited access to dialysis facilities, longer travel distances, and a shortage of healthcare professionals. The objective of this study was to conduct a national examination of rural-urban differences in quality of dialysis care offered across counties in the USA. METHODS: Data were gathered from Medicare-certified dialysis facilities in 2020 from the Centers for Medicare and Medicaid Services website. To identify high-need counties, county-level estimated crude prevalence of diabetes in adults was obtained from the 2022 CDC PLACES data portal. Our analysis reviewed 3,141 counties in the USA. The primary outcome measured was whether the county had a dialysis facility. Among those counties that had a dialysis facility, additional outcomes were the average star rating, whether peritoneal dialysis was offered, and whether home dialysis was offered. RESULTS: The type of services offered by dialysis facilities varied significantly, with peritoneal dialysis being the most commonly offered service (50.8%), followed by home hemodialysis (28.5%) and late-shift services (16.0%). These service availabilities are more prevalent in urban facilities than in rural facilities. The Centers for Medicare and Medicaid Services Five Star Quality ratings were quite different between urban and rural facilities, with 40.4% of rural facilities having a ranking of five, compared to 27.1% in urban. CONCLUSION: The majority of rural counties lack a single dialysis facility. Counties with high rates of chronic kidney disease, diabetes, and blood pressure, deemed high need, were less likely to have a highly rated dialysis facility. The findings can be used to further inform targeted efforts to increase diabetes educational programming and design appropriate interventions to those residing in rural communities and high-need counties who may need it the most.

Rural-urban differences in access to care among children and adolescents in the United States.

PURPOSE: Rural children and adolescents face disproportionate challenges in access to health care services than their urban counterparts. Yet, recent evidence on disparities in access to health care between rural and urban children and adolescents has been limited. This study examines the associations of residence location with receipt of preventive care, foregone medical care, and continuity of insurance coverage among US children and adolescents. METHODS: This study used cross-sectional data from the 2019 to 2020 National Survey of Children's Health, with a final sample size of 44,679 children. Descriptive statistics, bivariate analyses, and multivariable logistic regression models were used to examine the differences in preventive care, foregone care, and continuity of insurance coverage between rural and urban children and adolescents. FINDINGS: Rural children had lower odds of receiving preventive care (aOR 0.64; 95% CI 0.56-0.74) and having continuous health insurance coverage (aOR 0.68; 95% CI 0.56-0.83) compared to urban children. The odds of foregone care were similar between rural and urban children. Children at every federal poverty level (FPL) less than 400% were less likely to receive preventive care, and more likely to forego care than children residing at 400% or above FPL. CONCLUSIONS: Rural disparities in child preventive care and insurance continuity warrant ongoing surveillance and local access to care initiatives, especially for children in low-income households. Without updated public health surveillance, policymakers and program developers may not be aware of current disparities. School-based health centers are 1 avenue for meeting the unmet health care needs of rural children.

Changes in Positive Childhood Experiences During the COVID-19 Pandemic.

OBJECTIVE: Changes in family life associated with COVID-19 precautions may have reduced children's access to positive childhood experiences (PCEs). The purpose of this study is to examine the prevalence of PCEs before and during the COVID-19 pandemic among school-age children. METHODS: This cross-sectional study used data from the 2018-19 National Survey of Children's Health (NSCH, n = 42,464) and the 2020-21 NSCH (n = 54,256) to examine the pre-pandemic period (June 2018-January 2020) and compared results to information obtained during the early pandemic period (June 2020-January 2022) using bivariate analyses and Z-tests. RESULTS: PCEs declined in four of the seven PCEs measured, from 2018 to 2019-2020-2021: after-school activities, community volunteerism, guiding mentor, and resilient family, with all differences significant by P < .0001. After-school activities decreased from 79.8% to 72.2%, community volunteering decreased from 43.9% to 35.1%, guiding mentor decreased from 88.8% to 86.3%, and resilient family decreased from 92.7% to 84.6%. PCEs increased for safe neighborhood (64.7-67.2%), supportive neighborhood (55.8-57.5%), and connected caregiver (65.3-94.7%). CONCLUSIONS: As children have experienced higher levels of parental stress and disruption during their lives during the COVID-19 pandemic, policymakers and program makers must find ways to increase exposure to PCEs following the pandemic. The quantification of these PCEs is a great start, with further research needed to describe ways that schools and community organizations have found to expose children to PCEs in safe ways.

Identifying the Need for and Availability of Evidence-Based Care for Sexually Transmitted Infections in Rural Primary Care Clinics.

BACKGROUND: Increasing rates of bacterial sexually transmitted infections (STIs) may lead to increased HIV rates, as the STI and HIV epidemics are syndemic. Centers for Disease Control and Prevention guidelines recommend including extragenital (i.e., rectal and/or pharyngeal) STI screenings for certain populations at increased risk of STIs and concurrent infections with HIV. METHODS: A descriptive study was conducted by interviewing staff members from 4 rural primary care clinics in areas of high need for STI and HIV services in South Carolina. Qualitative data about their clinical practices in 2021 were obtained. The primary outcome was to determine the awareness and availability of health care services associated with STI and HIV care in these locations. RESULTS: Clinics in target counties provided limited STI and HIV testing and treatment services, especially for populations at risk of infection, indicating the need for additional clinical training and professional development for all clinic staff. Specifically, only 1 of 4 clinics provided extragenital STI testing, and no clinics reported prescribing preexposure prophylaxis. CONCLUSIONS: Rural primary care clinics can fill important gaps in the availability of STI and HIV services with appropriate support and incentives. Findings from this study may aid in facilitating policy (state Medicaid agency) and program (state health department) decisions related to STI and HIV testing and treatment.

Evaluating the Impact of CenteringPregnancy Program Versus Individual Prenatal Care on Gestational Weight Gain.

Introduction: The CenteringPregnancy (CP) program-proven to reduce preterm births-was modified to achieve more optimal gestational weight gain (GWG) by an intentional incorporation of nutrition education. We compared the effect of the modified CP program versus individual prenatal care (IPNC) on GWG. Methods: This observational study used linked birth certificate data and hospital discharge records of women who received prenatal care (PNC) in South Carolina Midlands' obstetric clinics between 2015 and 2019. Linear and multinomial logistic regressions were used to compare participants in CP (n = 568) versus IPNC on weight gain, measured by total GWG (delivery weight minus prepregnancy weight), weekly rate of weight gain, and meeting the Institute of Medicine's recommendations (inadequate, adequate, and excessive GWG). Nonrandom assignment to program was controlled by propensity scoring. Results: CP participants differed from IPNC participants in race, nulliparous, education, and type of health insurance, but not in parity or month PNC began (p-Value <0.05). CP and IPNC participants had a similar GWG experience: total GWG (coef(ß) = -0.054; 95% confidence interval [CI] -0.78 to 0.6), total weekly weight gain (coef(ß) = -0.004; 95% CI -0.03 to 0.03), total GWG category (inadequate GWG: RRR = 0.85, 95% CI 0.64-1.21, and excessive GWG: relative risk ratio (RRR) = 0.92, 95% CI 0.71-1.20 vs. adequate), and weekly weight gain category (inadequate GWG: RRR = 0.73, 95% CI 0.53-1.01, and excessive GWG: RRR = 0.83, 95% CI 0.61-1.13 vs. adequate). Conclusion: The CP program with an enhanced nutritional knowledge component was not associated with achieving recommended GWG. Further investigation is needed to explain the lack of impact.

Profiling human brain vascular cells using single-cell transcriptomics and organoids.

Angiogenesis and neurogenesis are functionally interconnected during brain development. However, the study of the vasculature has trailed other brain cell types because they are delicate and of low abundance. Here we describe a protocol extension to purify prenatal human brain endothelial and mural cells with FACS and utilize them in downstream applications, including transcriptomics, culture and organoid transplantation. This approach is simple, efficient and generates high yields from small amounts of tissue. When the experiment is completed within a 24 h postmortem interval, these healthy cells produce high-quality data in single-cell transcriptomics experiments. These vascular cells can be cultured, passaged and expanded for many in vitro assays, including Matrigel vascular tube formation, microfluidic chambers and metabolic measurements. Under these culture conditions, primary vascular cells maintain expression of cell-type markers for at least 3 weeks. Finally, we describe how to use primary vascular cells for transplantation into cortical organoids, which captures key features of neurovascular interactions in prenatal human brain development. In terms of timing, tissue processing and staining requires ~3 h, followed by an additional 3 h of FACS. The transplant procedure of primary, FACS-purified vascular cells into cortical organoids requires an additional 2 h. The time required for different transcriptomic and epigenomic protocols can vary based on the specific application, and we offer strategies to mitigate batch effects and optimize data quality. In sum, this vasculo-centric approach offers an integrated platform to interrogate neurovascular interactions and human brain vascular development.

Parents' Views on Autopsy, Organ Donation, and Research Donation After Neonatal Death.

Importance: Parents who experience neonatal loss have the option to participate in autopsy, organ donation, and research donation. However, clinicians are uncomfortable discussing autopsy and may not be aware of research and organ donation opportunities. Objective: To capture the perspectives of parents who had experienced neonatal loss about autopsy, organ donation, and research donation. Design, Setting, and Participants: This qualitative study used virtual focus groups with parents who attended a local bereavement support group in the US. Participants were recruited from Helping After Neonatal Death, a support group with a local chapter. Participants self-selected from an email request if they met the following criteria: aged 18 years or older, English speaking, at least 6 months elapsed since neonatal death, and access to a video conference device with internet. Focus groups took place between April and September 2021. The recorded sessions were analyzed using a grounded theory-informed approach by the research team that included parents with experience of neonatal loss. Data were analyzed from December 2021 through December 2022. Results: A total of 14 mothers engaged in the focus group; 9 (75%) were aged 30 to 39 years, and 8 (66%) were White. The mothers were overall well educated. The first main theme grew from the lived experience of neonatal loss, specifically the importance of offering all parents the option to donate, rather than prejudging who would or would not be interested. Parents of neonates who die have few opportunities to parent that child and make loving decisions for them. Participants emphasized that the conversation about autopsy, organ donation, and research donation, albeit difficult, can offer a meaningful parenting experience. A second main theme that emerged related to how organ or tissue donation could provide additional meaning to a child's life. These choices contributed to building a legacy to honor their child's memory, which also helped with grief and coping with their loss. A third theme included recommendations to clinicians and health systems for improving communication, including written information for parents and communication training for health care professionals. Conclusions and Relevance: In this qualitative study, parents who experienced neonatal loss endorsed the importance of offering parents the choice of autopsy, organ donation, or research donation with skillful and empathetic communication. They provided practical recommendations to improve communication and empower families.

Adverse Childhood Experiences and Positive Childhood Experiences Among United States Military Children.

INTRODUCTION: Many facets of military life are contributors to child health including frequent mobility, family separation, and increased risk to parental physical and mental health, as well as strong social networks and military support systems; yet, there has not been an examination of adverse childhood experiences (ACEs) and positive childhood experiences (PCEs) among military children. MATERIALS AND METHODS: This study used the 2020-2021 National Survey of Children's Health, limited to children aged 6 to 17 years of age, to examine the association between a child who has ever had a caregiver on active duty and their exposure to ACEs and PCEs (n = 54,256 children). Bivariate analyses used Pearson's chi-squared tests and were weighted to be nationally representative. Multivariable regression models were used to examine the association between military status and selected ACEs. RESULTS: There were no statistically significant differences in PCEs between military and civilian children. Compared to children with a civilian caregiver, children who had a caregiver who had ever served on active duty had a higher odds of experiencing domestic violence (adjusted Odds Ratio (aOR), 1.61; 95% CI 1.23-2.11), mental health issues or depression in the household (aOR 1.28; 95% CI 1.07-1.52), and substance use (aOR 1.28; 95% CI 1.06-1.55). CONCLUSIONS: This study complements and extends previous research that has taken a deficit approach and focused exclusively on the hardships faced by children in military families. The findings from this study may be instructive for child welfare advocates and policymakers as they intervene in communities with programming that promotes PCEs among children and adolescents.

Rural-Urban Differences in Overweight and Obesity, Physical Activity, and Food Security Among Children and Adolescents.

INTRODUCTION: Childhood obesity has been associated with numerous poor health conditions, with geographic disparities demonstrated. Limited research has examined the association between rurality and food security, physical activity, and overweight or obesity among children. We examined rates of food security, physical inactivity, and overweight or obesity among rural and urban children and adolescents, and associations between rurality and these 3 outcomes. METHODS: We used cross-sectional data from a nationally representative sample of children and adolescents aged 10 to 17 years from the 2019-2020 National Survey of Children's Health (N = 23,199). We calculated frequencies, proportions, and unadjusted associations for each variable by using descriptive statistics and bivariate analyses. We used multivariable logistic regression models to examine the association between rurality and food security, physical activity, and overweight or obesity. RESULTS: After adjusting for sociodemographic factors, rural children and adolescents had higher odds than urban children and adolescents of being overweight or obese (adjusted odds ratio = 1.30; 95% CI, 1.11-1.52); associations between rurality and physical inactivity and food insecurity were not significant. CONCLUSION: The information from this study is timely for policy makers and community partners to make informed decisions on the allocation of healthy weight and obesity prevention programs for children and adolescents in rural settings. Our study provides information for public health programming and the designing of appropriate dietary and physical activity interventions needed to reduce disparities in obesity prevention among children and adolescents.

LIF signaling regulates outer radial glial to interneuron fate during human cortical development.

Radial glial (RG) development is essential for cerebral cortex growth and organization. In humans, the outer radial glia (oRG) subtype is expanded and gives rise to diverse neurons and glia. However, the mechanisms regulating oRG differentiation are unclear. oRG cells express leukemia-inhibitory factor (LIF) receptors during neurogenesis, and consistent with a role in stem cell self-renewal, LIF perturbation impacts oRG proliferation in cortical tissue and organoids. Surprisingly, LIF treatment also increases the production of inhibitory interneurons (INs) in cortical cultures. Comparative transcriptomic analysis identifies that the enhanced IN population resembles INs produced in the caudal ganglionic eminence. To evaluate whether INs could arise from oRGs, we isolated primary oRG cells and cultured them with LIF. We observed the production of INs from oRG cells and an increase in IN abundance following LIF treatment. Our observations suggest that LIF signaling regulates the capacity of oRG cells to generate INs.

Meningeal solitary fibrous tumor cell states phenocopy cerebral vascular development and homeostasis.

Meningeal solitary fibrous tumors (SFTs) are rare mesenchymal neoplasms that are associated with hematogenous metastasis, and the cell states and spatial transcriptomic architecture of SFTs are unknown. Here we use single-cell and spatial RNA sequencing to show SFTs are comprised of regionally distinct gene expression programs that resemble cerebral vascular development and homeostasis. Our results shed light on pathways underlying SFT biology in comparison to other central nervous system tumors and provide a framework for integrating single-cell and spatial transcriptomic data from human cancers and normal tissues.

NOTCH3 drives meningioma tumorigenesis and resistance to radiotherapy.

Meningiomas are the most common primary intracranial tumors1-3. Treatments for patients with meningiomas are limited to surgery and radiotherapy, and systemic therapies remain ineffective or experimental4,5. Resistance to radiotherapy is common in high-grade meningiomas6, and the cell types and signaling mechanisms driving meningioma tumorigenesis or resistance to radiotherapy are incompletely understood. Here we report NOTCH3 drives meningioma tumorigenesis and resistance to radiotherapy and find NOTCH3+ meningioma mural cells are conserved across meningiomas from humans, dogs, and mice. NOTCH3+ cells are restricted to the perivascular niche during meningeal development and homeostasis and in low-grade meningiomas but are expressed throughout high-grade meningiomas that are resistant to radiotherapy. Integrating single-cell transcriptomics with lineage tracing and imaging approaches across mouse genetic and xenograft models, we show NOTCH3 drives tumor initiating capacity, cell proliferation, angiogenesis, and resistance to radiotherapy to increase meningioma growth and reduce survival. An antibody stabilizing the extracellular negative regulatory region of NOTCH37,8 blocks meningioma tumorigenesis and sensitizes meningiomas to radiotherapy, reducing tumor growth and improving survival in preclinical models. In summary, our results identify a conserved cell type and signaling mechanism that underlie meningioma tumorigenesis and resistance to radiotherapy, revealing a new therapeutic vulnerability to treat meningiomas that are resistant to standard interventions.