Child Health and the Neonatal-Perinatal Medicine Workforce: 2020-2040.

In 2022, 3.7 million children were born in the United States, of whom ∼600 000 received care from a neonatologist. The dramatic growth of the neonatal-perinatal medicine (NPM) workforce from 375 in 1975 to 5250 in 2022 has paralleled exploding clinical demand. As newborn medicine continues to push the limits of gestational viability and medical complexity, the NPM workforce must advance in numbers, clinical capability, scientific discovery, and leadership. This article, as part of an American Board of Pediatrics Foundation-sponsored supplement that is designed to project the future of the pediatric subspecialty workforce, features a discussion of the NPM workforce's history and current status, factors that have shaped its current profile, and some plausible scenarios of the workforce's needs and configuration in the future. In the article, we use an analytical model that forecasts the growth trajectory of the neonatologist workforce from 2020 through 2040. The model uses recent data on the number of neonatologists and clinical work equivalents per 100 000 children and projects future workforce supply under several theoretical scenarios created by modifying key baseline parameters. The predictions of this model confirm the need for a greater sustainable clinical capacity of the NPM workforce. Several future trends indicate that there may be geographic shortages of neonatologists, similar to expected shortages in other pediatric subspecialties. We do not address what an appropriate target for workforce size should be with the model or this article because the current and projected geographic variability in the NPM workforce and risk-appropriate care suggest that a uniform answer is unlikely.

Parents' Perspectives on the Utility of Genomic Sequencing in the Neonatal Intensive Care Unit.

BACKGROUND: It is critical to understand the wide-ranging clinical and non-clinical effects of genome sequencing (GS) for parents in the NICU context. We assessed parents' experiences with GS as a first-line diagnostic tool for infants with suspected genetic conditions in the NICU. METHODS: Parents of newborns (N = 62) suspected of having a genetic condition were recruited across five hospitals in the southeast United States as part of the SouthSeq study. Semi-structured interviews (N = 78) were conducted after parents received their child's sequencing result (positive, negative, or variants of unknown significance). Thematic analysis was performed on all interviews. RESULTS: Key themes included that (1) GS in infancy is important for reproductive decision making, preparing for the child's future care, ending the diagnostic odyssey, and sharing results with care providers; (2) the timing of disclosure was acceptable for most parents, although many reported the NICU environment was overwhelming; and (3) parents deny that receiving GS results during infancy exacerbated parent-infant bonding, and reported variable impact on their feelings of guilt. CONCLUSION: Parents reported that GS during the neonatal period was useful because it provided a "backbone" for their child's care. Parents did not consistently endorse negative impacts like interference with parent-infant bonding.

Gender analysis of Journal of Perinatology authorship during COVID-19.

OBJECTIVE: To examine authorship gender distributions before and during COVID-19 in the Journal of Perinatology. STUDY DESIGN: We collected data from the Journal of Perinatology website. The author gender was determined using Genderize.io or a systematic internet search. Our primary outcome was the difference between the number of published articles authored by women during the pandemic period (March 2020-May 2021, period two), compared with the preceding 15-month period (period one). We analyzed the data using chi-square tests. RESULTS: Publications increased from period one to two by 8.9%. There were slightly more female than male first (62%) and overall (53%) authors, but fewer last authors (43%) for the combined time periods. Female authorship distribution was not different between periods. CONCLUSIONS: Though publications increased overall, authorship gender distribution did not change significantly during the COVID-19 pandemic. Women authors remain underrepresented overall and specifically as last author, considering the majority of neonatologists are women.

Cost-effectiveness frameworks for comparing genome and exome sequencing versus conventional diagnostic pathways: A scoping review and recommended methods.

PURPOSE: Methodological challenges have limited economic evaluations of genome sequencing (GS) and exome sequencing (ES). Our objective was to develop conceptual frameworks for model-based cost-effectiveness analyses (CEAs) of diagnostic GS/ES. METHODS: We conducted a scoping review of economic analyses to develop and iterate with experts a set of conceptual CEA frameworks for GS/ES for prenatal testing, early diagnosis in pediatrics, diagnosis of delayed-onset disorders in pediatrics, genetic testing in cancer, screening of newborns, and general population screening. RESULTS: Reflecting on 57 studies meeting inclusion criteria, we recommend the following considerations for each clinical scenario. For prenatal testing, performing comparative analyses of costs of ES strategies and postpartum care, as well as genetic diagnoses and pregnancy outcomes. For early diagnosis in pediatrics, modeling quality-adjusted life years (QALYs) and costs over ≥20 years for rapid turnaround GS/ES. For hereditary cancer syndrome testing, modeling cumulative costs and QALYs for the individual tested and first/second/third-degree relatives. For tumor profiling, not restricting to treatment uptake or response and including QALYs and costs of downstream outcomes. For screening, modeling lifetime costs and QALYs and considering consequences of low penetrance and GS/ES reanalysis. CONCLUSION: Our frameworks can guide the design of model-based CEAs and ultimately foster robust evidence for the economic value of GS/ES.

Genome sequencing as a first-line diagnostic test for hospitalized infants.

PURPOSE: SouthSeq is a translational research study that undertook genome sequencing (GS) for infants with symptoms suggestive of a genetic disorder. Recruitment targeted racial/ethnic minorities and rural, medically underserved areas in the Southeastern United States, which are historically underrepresented in genomic medicine research. METHODS: GS and analysis were performed for 367 infants to detect disease-causal variation concurrent with standard of care evaluation and testing. RESULTS: Definitive diagnostic (DD) or likely diagnostic (LD) genetic findings were identified in 30% of infants, and 14% of infants harbored an uncertain result. Only 43% of DD/LD findings were identified via concurrent clinical genetic testing, suggesting that GS testing is better for obtaining early genetic diagnosis. We also identified phenotypes that correlate with the likelihood of receiving a DD/LD finding, such as craniofacial, ophthalmologic, auditory, skin, and hair abnormalities. We did not observe any differences in diagnostic rates between racial/ethnic groups. CONCLUSION: We describe one of the largest-to-date GS cohorts of ill infants, enriched for African American and rural patients. Our results show the utility of GS because it provides early-in-life detection of clinically relevant genetic variations not detected by current clinical genetic testing, particularly for infants exhibiting certain phenotypic features.

Seeking racial and ethnic equity among neonatologists.

OBJECTIVE: Racial and ethnic inequities in leadership achievement, compensation, scholarly productivity, and grant funding exists among physicians. This study explores whether similar inequities exist among neonatologists within the United States. STUDY DESIGN: A voluntary anonymous survey was distributed to members of the American Academy of Pediatrics Section on Neonatal-Perinatal Medicine with 560 respondents. Logistic regression and ordinary least squares were used to assess whether racial and ethnic identity is associated with clinical time, leadership, compensation, publication, grant funding, or academic rank. RESULTS: As compared to non-Hispanic White neonatologists, statistical differences were found for underrepresented minorities in medicine in: regions of the country where they worked, total cash compensation received, being awarded an NIH grant, and location of graduate medical education. Fewer differences were found for Asian neonatologists and included location of graduate medicine education. CONCLUSION: Racial and ethnic identity remains a significant independent factor influencing professional achievement and compensation.

Equity for women in medicine-neonatologists identify issues.

OBJECTIVE: Inequity between genders with regards to leadership achievement, compensation, scholarly productivity, and grant funding exist among physicians. This study explores whether similar inequities exist among board certified neonatologists within the USA. STUDY DESIGN: A voluntary anonymous survey was distributed to 3575 members of the American Academy of Pediatrics Section on Neonatal-Perinatal Medicine with 560 respondents (15.7% response rate). The survey contained questions assessing clinician characteristics, work environment, compensation, professional productivity, and social factors. Statistical analysis was done using JMP Pro 15.0.0 by SAS. RESULTS: Female neonatologists, compared to male peers, were less likely to hold leadership positions (OR 0.36, p = 0.005), received lower compensation by an average of $34,916 or 12.47% (p < 0.001), and had 6.71 fewer primary authored publications (p = 0.025) after adjusting for several confounding factors. CONCLUSION: Gender remains a significant independent factor influencing leadership attainment, compensation, and academic productivity in this cohort of neonatologists.

Development and Impact of Helping Babies Breathe Educational Methodology.

The educational pedagogy surrounding Helping Babies Breathe (HBB) has been transformative in going beyond a curriculum focused only on basic neonatal resuscitation; indeed, it created the framework for an educational program that has served as a model for replication for other impactful programs, such as the Helping Mothers Survive and other Helping Babies Survive curricula. The tenets of HBB include incorporation of innovative learning strategies such as small group discussion, skills-based learning, simulation and debriefing, and peer-to-peer learning, all of which begin the hard work of changing behaviors that may eventually affect health care systems. Allowing for adaptation for local resources and culture, HBB has catalyzed innovation in the development of simplified, pictorial educational materials, in addition to low-tech yet realistic simulators and adjunct devices that have played an important role in empowering health care professionals in their care of newborns, thereby improving outcomes. In this review, we describe the development of HBB as an educational program, the importance of field testing and input from multiple stakeholders including frontline workers, the strategies behind the components of educational materials, and the impact of its pedagogy on learning.

Helping Babies Survive: Lessons Learned From Global Trainers.

BACKGROUND: The Helping Babies Survive (HBS) suite of programs was launched in 2010 as an evidence-based educational package to train health care workers in low- and middle-income countries in neonatal resuscitation, immediate newborn care, and complications of prematurity. To date, there has been no purposeful examination of lessons learned from HBS trainers. Our intent with this study is to gather that data from the field. METHODS: To estimate the total global reach of the HBS program, we obtained equipment distribution data from Laerdal and HBS material download data from the HBS Web site as of March 2020. To understand the lessons learned from HBS trainers, we examined comments from trainers who recorded their trainings on the HBS Web site, and other first-hand accounts. RESULTS: More than 1 million pieces of equipment (simulators, flip charts, provider guides, and action plans) have been distributed worldwide. HBS materials have been downloaded from the Web site >130 000 times and have now been translated into 27 languages. HBS equipment and training has reached an estimated 850 000 providers in 158 countries. Qualitative analysis revealed 3 major themes critical to building successful and sustainable HBS programs: support, planning and local context, and subthemes for each. CONCLUSIONS: Lessons learned from experienced trainers represent a vital distillation of first-hand experience into widely applicable knowledge to be used to reduce potential failures and achieve desired outcomes. Findings from this study offer further guidance on best practices for implementing and sustaining HBS programs and provide insight into challenges and successes experienced by HBS trainers.

Willingness of women to participate in obstetrical and pediatric research involving biobanks.

Use of biobanks for future genetic/genomic testing has increased. Biospecimens are increasingly being collected from infants/children; however, little is known about attitudes towards collection of biospecimens from postpartum women and their child. Using a hypothetical consent, this study investigated willingness to participate and attitudes, beliefs, and concerns related to consent materials requesting the biobanking genetic samples. A cross-sectional mixed methods design included women who reviewed a hypothetical consent related to biobanking genetic samples. Women were asked about their willingness to participate, followed by a focus group about biobanks and genetic/genomic testing. Post-focus group questionnaires assessed willingness to participate, the influence of study characteristics, and attitudes about genetic testing. Women (N = 37) were 29.0± 7.3 years of age (range 19-44); 51% had children and 28% were currently pregnant. A total of 46% were Hispanic (H), 38% were White non-Hispanic (WNH), and 16% were Native American (NA). Seventy-six percent (28/37) initially indicated that they would participate in the hypothetical study. Race and ethnicity impacted whether women would participate. Fewer NA women indicated that they would participate compared with H women and with WNH women (p < 0.02). Age, pregnancy status, having children, education level, insurance status, and income had no impact on participation decision and willingness to biobank specimens. NA and H women indicated that they were less likely than WNH women to agree to participate in a long-term biobank study. Given the importance of determining the genetic influence of health and disease, it is critical to attend to the questions and concerns of minority women regarding genetic studies.

A case report of embolized umbilical venous catheter retrieval from the heart via femoral access in 660 g premature neonate.

An extremely premature infant born at a gestational age 24 5/7 and birth weight of 637 g was found to have retained a distal segment of an umbilical venous catheter (UVC) on chest radiograph after removal of the UVC. The catheter was retrieved by interventional radiology on day 10 of life when the baby weighed 660 g. To our knowledge, this is the smallest baby reported to have successfully retrieved catheter percutaneously via femoral access.

Neonatologist salary: factors, equity and gender.

OBJECTIVE: Physician compensation has been found to be influenced by gender, academic affiliation, specialty, productivity, and time in practice. This study explores their impact in the field of neonatology to inform institutional strategic planning and decisions by current and future practitioners. STUDY DESIGN: A voluntary anonymous survey was distributed to members of the American Academy of Pediatrics Section on Neonatal-Perinatal Medicine with a 15% response rate. The survey contained questions assessing clinician characteristics, work environment, and professional productivity. Statistical analysis was done using JMP Pro 14.0.0 by SAS. RESULTS: Median salary was $256,000 (interquartile range, $213,608-315,000). Generalized linear model found that years post fellowship, academic affiliation, gender, practice location, professional duties, and clinical team member types independently influenced expected salary. CONCLUSION: Several factors influence the expected compensation of this cohort of neonatologists, even after adjustments for differences in clinician characteristics, work environment, and productivity.

Neuron/Oligodendrocyte Myelination Coculture.

Myelination cell culture systems are useful tools for studying myelin biology and myelin-related disorders. Compared to a number of established protocols for dissociated pure oligodendrocyte (OL) culture, methods for myelination culture are limited. We recently developed a mixed neuron-glia coculture system that generates robust and efficient myelination. By optimizing cell culture conditions, dissociated neural progenitor cells from embryonic rat spinal cords develop into neurons and glial cells including profiles of oligodendrocyte (OL) lineage. Within 4 weeks, OL progenitor cells (OPC) proliferate, differentiate into mature OLs, and myelinate axons. The formation of compact myelin sheath is confirmed by electron microscopy. For morphological analysis by light microscopy, cells grown on glass coverslips are fixed and immunostained for various myelin-related proteins, including those embedded within the myelin sheath and those clustered at the node of Ranvier. Myelinated axons can be quantified readily by either manual counting or ImageJ software. The culture system may also be used for electron microscopic analysis by slightly modifying the cell culture procedure.

Neuroprotective Effects of Intranasal IGF-1 against Neonatal Lipopolysaccharide-Induced Neurobehavioral Deficits and Neuronal Inflammation in the Substantia Nigra and Locus Coeruleus of Juvenile Rats.

Neonatal lipopolysaccharide (LPS) exposure-induced brain inflammation resulted in motor dysfunction and brain dopaminergic neuronal injury, and increased the risks of neurodegenerative disorders in adult rats. Our previous studies showed that intranasal administration of insulin-like growth factor-1 (IGF-1) protects against LPS-induced white matter injury in the developing rat brain. To further examine whether IGF-1 protects against LPS-induced brain neuronal injury and neurobehavioral dysfunction, recombinant human IGF-1 (rhIGF-1) at a dose of 50 µg/pup was administered intranasally 1 h following intracerebral injection of LPS (1 mg/kg) in postnatal day 5 (P5) Sprague-Dawley rat pups. Neurobehavioral tests were carried out from P7 to P21, and brain neuronal injury was examined at P21. Our results showed that LPS exposure resulted in disturbances of motor behaviors in juvenile rats. Moreover, LPS exposure caused injury to central catecholaminergic neurons, as indicated by a reduction of tyrosine hydroxylase (TH) immunoreactivity in the substantia nigra (SN), ventral tegmental area (VTA) and olfactory bulb (OB), and brain noradrenergic neurons, as indicated by a reduction of TH immunoreactivity in the locus coeruleus (LC) of the P21 rat brain. The LPS-induced reduction of TH+ cells was observed at a greater degree in the SN and LC of the P21 rat brain. Intranasal rhIGF-1 treatment attenuated LPS-induced central catecholaminergic neuronal injury and motor behavioral disturbances, including locomotion, beam walking test and gait analysis. Intranasal rhIGF-1 administration also attenuated LPS-induced elevation of IL-1ß levels and numbers of activated microglia, and cyclooxygenase-2+ cells, which were double labeled with TH+ cells in the SN, VTA, OB and LC of the P21 rat brain. These results suggest that IGF-1 may provide protection against neonatal LPS exposure-induced central catecholaminergic neuronal injury and motor behavioral disturbances, and that the protective effects are associated with the inhibition of microglia activation and the reduction of neuronal oxidative stress by the suppression of the neuronal cyclooxygenase-2 expression.

Improving Safe and Effective Use of Drugs in Pregnancy and Lactation: Workshop Summary.

In February 2015, given high rates of use of medications by pregnant women and the relative lack of data on safety and efficacy of many drugs utilized in pregnancy, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the Society for Maternal-Fetal Medicine (SMFM), the American College of Obstetricians and Gynecologists (ACOG), and the American Academy of Pediatrics (AAP) convened a group of experts to review the "current" state of the clinical care and science regarding medication use during the perinatal period. The expert panel chose select medications to demonstrate what existing safety and efficacy data may be available for clinicians and patients when making decisions about use in pregnancy or lactation. Furthermore, these example medications also provided opportunities to highlight where data are lacking, thus forming a list of research gaps. Last, after reviewing the existing vaccine safety surveillance system as well as the legislative history surrounding the use of drugs for pediatric diseases, the expert panel made specific recommendations concerning policy efforts to stimulate more research and regulatory attention on drugs for pregnant and lactating women.

Association between theta power in 6-month old infants at rest and maternal PTSD severity: A pilot study.

Compared to infants born to mothers without PTSD, infants born to mothers with active PTSD develop poorer behavioral reactivity and emotional regulation. However, the association between perinatal maternal PTSD and infant neural activation remains largely unknown. This pilot study (N=14) examined the association between perinatal PTSD severity and infant frontal neural activity, as measured by MEG theta power during rest. Results indicated that resting left anterior temporal/frontal theta power was correlated with perinatal PTSD severity (p=0.004). These findings suggest delayed cortical maturation in infants whose mothers had higher perinatal PTSD severity and generate questions regarding perinatal PTSD severity and infant neurophysiological consequences.

Erythropoietin Ameliorates Neonatal Hypoxia-Ischemia-Induced Neurobehavioral Deficits, Neuroinflammation, and Hippocampal Injury in the Juvenile Rat.

The hematopoietic growth factor erythropoietin (EPO) has been shown to be neuroprotective against hypoxia-ischemia (HI) in Postnatal Day 7 (P7)-P10 or adult animal models. The current study was aimed to determine whether EPO also provides long-lasting neuroprotection against HI in P5 rats, which is relevant to immature human infants. Sprague-Dawley rats at P5 were subjected to right common carotid artery ligation followed by an exposure to 6% oxygen with balanced nitrogen for 1.5 h. Human recombinant EPO (rEPO, at a dose of 5 units/g) was administered intraperitoneally one hour before or immediately after insult, followed by additional injections at 24 and 48 h post-insult. The control rats were injected with normal saline following HI. Neurobehavioral tests were performed on P8 and P20, and brain injury was examined on P21. HI insult significantly impaired neurobehavioral performance including sensorimotor, locomotor activity and cognitive ability on the P8 and P20 rats. HI insult also resulted in brain inflammation (as indicated by microglia activation) and neuronal death (as indicated by Jade B positive staining) in the white matter, striatum, cortex, and hippocampal areas of the P21 rat. Both pre- and post-treatment with rEPO significantly improved neurobehavioral performance and protected against the HI-induced neuronal death, microglia activation (OX42+) as well as loss of mature oligodendrocytes (APC-CC1+) and hippocampal neurons (Nissl+). The long-lasting protective effects of rEPO in the neonatal rat HI model suggest that to exert neurotrophic activity in the brain might be an effective approach for therapeutic treatment of neonatal brain injury induced by hypoxia-ischemia.