Henry A. Feldman

Boston Children's Hospital · Institutional Centers for Clinical and Translational Research

Introduction: The Chiari II is a relatively common birth defect that is associated with open spinal abnormalities and is characterized by caudal migration of the posterior fossa contents through the foramen magnum. The pathophysiology of Chiari II is not entirely known, and the neurobiological substrate beyond posterior fossa findings remains unex...

The hematopoietic niche is a supportive microenvironment composed of distinct cell types, including specialized vascular endothelial cells that directly interact with hematopoietic stem and progenitor cells (HSPCs). The molecular factors that specify niche endothelial cells and orchestrate HSPC homeostasis remain largely unknown. Using multi-dimens...

Background: Moyamoya is a disease with progressive cerebral arterial stenosis leading to stroke and silent infarct. Diffusion-weighted magnetic resonance imaging (dMRI) studies show that adults with moyamoya have significantly lower fractional anisotropy (FA) and higher mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) com...

Tethered cord syndrome (TCS) is characterized by leg pain and weakness, bladder and bowel dysfunction, orthopedic malformations such as scoliosis, and motor deficits caused by the fixation of the spinal cord to surrounding tissues. TCS is surgically treatable and often found in conjunction with other syndromic conditions. KBG syndrome is caused by...

Introduction: Moyamoya is a progressive cerebrovascular disease leading to stenosis of arteries located in the circle of Willis which increases risk of hypoperfusion in specific areas of the brain called watershed regions. Using diffusion weighted magnetic resonance imaging (dMRI), adults with moyamoya have significantly lower fractional anisotropy...

Objective Roux-en-Y gastric bypass surgery (RYGB) is among the most effective therapies for obesity and type 2 diabetes, and intestinal adaptation is a proposed mechanism for these effects. It was hypothesized that intestinal adaptation precedes and relates to metabolic improvement in humans after RYGB. Methods This was a prospective, longitudinal...

Early variations of fetal movements are the hallmark of a healthy developing central nervous system. However, there are no automatic methods to quantify the complex 3D motion of the developing fetus in-utero. The aim of this prospective study was to use machine learning (ML) on in-utero MRI to perform quantitative kinematic analysis of fetal limb m...

Human fetal brains show regionally different temporal patterns of sulcal emergence following a regular timeline, which may be associated with spatiotemporal patterns of gene expression among cortical regions. This study aims to quantify the timing of sulcal emergence and its temporal variability across typically developing fetuses by fitting a logi...

Introduction: Children with self-limited delayed puberty (constitutional delay) enter puberty after variable waiting times, and the factors associated with their eventual pubertal timing are not well understood. Methods: We conducted a retrospective study of 99 girls and 228 boys with self-limited delayed puberty (DP) at an academic medical cent...

Maternal-placental perfusion can be temporarily compromised by Braxton Hicks (BH) uterine contractions. Although prior studies have employed T2* changes to investigate the effect of BH contractions on placental oxygen, the effect of these contractions on the fetus has not been fully characterized. We investigated the effect of BH contractions on qu...

Breastmilk provides key nutrients and bio-active factors that contribute to infant neurodevelopment. Optimizing maternal nutrition could provide further benefit to psychomotor outcomes. Our observational cohort pilot study aims to determine if breastfeeding extent and breastmilk nutrients correlate with psychomotor outcomes at school age. The breas...

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder which can result from a range of observed symptoms pertaining to social, emotional, and cognitive processing difficulties especially regarding communication of their own feelings, opinions, and thoughts with others. Although a diagnosis received by 1 in 68 children in the Unite...

Background: Platelet transfusions (PTxs) are often given to septic preterm neonates at high platelet count thresholds in an attempt to reduce bleeding risk. However, the largest randomized controlled trial (RCT) of neonatal transfusion thresholds found higher mortality and/or major bleeding in infants transfused at higher thresholds. Using a murin...

The purpose of this study was to develop and regionally pilot a digitally innovative curriculum in ethics and professionalism in neonatology and study the effects on trainee knowledge and confidence. We developed 13 modules in ethics for neonatology fellows and piloted them at three academic institutions utilizing a flipped-classroom approach. Base...

Mild isolated fetal ventriculomegaly (iFVM) is the most common abnormality of the fetal central nervous system. It is characterized by enlargement of one or both of the lateral ventricles (defined as ventricular width greater than 10 mm, but less than 12 mm). Despite its high prevalence, the pathophysiology of iFVM during fetal brain development an...

Introduction: Moyamoya is a progressive cerebrovascular disease leading to arterial stenosis of the circle of Willis. Using diffusion tensor imaging (DTI), adults with moyamoya have significantly decreased white matter fractional anisotropy (FA) compared to controls even when conventional imaging is normal. This raises concern for under recognized...

Eltrombopag (ELT) is a thrombopoietic agent approved for immune thrombocytopenia and also a potent iron chelator. Here we found that ELT exhibited dose-dependent opposing effects on in vitro megakaryopoiesis: low concentrations (≤6 µM, ELT6) stimulated megakaryopoiesis, but high concentrations (30 µM, ELT30) suppressed megakaryocyte (MK) differenti...

OBJECTIVE To assess sex-specific differences in early brain structure and function of preterm infants after red blood cell (RBC) transfusions. STUDY design A single-center subset of infants with a birth weight <1000 g and gestational age 22-29 weeks were enrolled from the NICHD Neonatal Research Network Transfusion of Prematures (TOP) Trial. Hemog...

Thrombocytopenia affects 18-35% of all neonates in the Neonatal Intensive Care Unit and ~70% of those born extremely prematurely, with sepsis being a frequent cause. Platelet transfusions (PTx) are frequently given to septic preterm neonates at higher platelet count (PC) thresholds than those used in adults, in an attempt to reduce their bleeding r...

Background Platelet and packed red blood cell (pRBC) transfusion practices for preterm infants vary significantly worldwide. Recent randomized trials of preterm infants receiving platelet or pRBC transfusions have not shown any benefit with higher compared to lower transfusion thresholds. In the recent PlaNeT2 study published in January 2019, infan...

Platelet transfusions (PTx) are frequently given to thrombocytopenic preterm neonates at higher platelet count (PC) thresholds than those used in adults, in an attempt to reduce their bleeding risk. However, in the largest randomized trial of neonatal PTx thresholds, infants transfused at a higher PC threshold had a significantly higher mortality a...

The hematopoietic niche is a supportive microenvironment comprised of distinct cell types, including specialized vascular endothelial cells that directly interact with hematopoietic stem and progenitor cells (HSPCs). The molecular factors that specify niche endothelial cells and orchestrate HSPC homeostasis remain largely unknown. Using multi-dimen...

Phlebotomy-induced anemia (PIA) is universal and variable in degree among preterm infants and may contribute to neurodevelopmental risk. In mice, PIA causes brain tissue hypoxia, iron deficiency, and long-term sex-dependent neurobehavioral abnormalities. The neuroregulatory molecular pathways disrupted by PIA underlying these effects are unknown. M...

Introduction MR relaxometry has been used to assess placental exchange function, but methods to date are not sufficiently fast to be robust to placental motion. Magnetic resonance fingerprinting (MRF) permits rapid, voxel-wise, intrinsically co-registered T1 and T2 mapping. After characterizing measurement error, we scanned pregnant women during ai...

The immature platelet fraction (IPF) is a measure of newly released platelets, which has been used as a marker of platelet production in multiple human studies but is not widely available in multispecies analyzers. We developed gates to measure the IPF in diluted and undiluted murine blood samples on the Sysmex XN-1000V multispecies hematology anal...

Variation exists in neonatal platelet transfusion practices. Recent studies found potential harm in liberal platelet transfusion practices, supporting the use of lower transfusion thresholds. Our aim was to reduce non-indicated platelet transfusions through implementation of a restrictive platelet transfusion guideline. Platelet transfusions from J...

Context: The decision whether to treat a child with delayed puberty with sex steroids is primarily based on patient, family, and provider preference. Knowing when children with constitutional delay eventually enter puberty would inform this decision. Objective, design, setting, participants, and outcome measures: To estimate and compare rates of...

Background: Neonatal hypothermia is a common source of morbidity and mortality in low resource settings. We developed the Dream Warmer, a low cost, re-usable non-electric infant warmer to prevent and treat hypothermia. Methods: We conducted a cluster-randomized stepped-wedge trial. The primary aim was to assess the effect on overall euthermia ra...

The objective of this study was to determine sex-specific differences in inflammatory cytokine responses to red blood cell (RBC) transfusion in preterm infants in the neonatal period and their relationship to later neurocognitive status. Infants with a birth weight <1000 g and gestational age 22–29 weeks were enrolled in the Transfusion of Prematur...

Down syndrome (DS) is the most common genetic cause of developmental disabilities. Advanced analysis of brain magnetic resonance imaging (MRI) has been used to find brain abnormalities and their relationship to neurocognitive impairments in children and adolescents with DS. Because genetic factors affect brain development in early fetal life, there...

Context Children with brain tumors may have pubertal onset at an inappropriately young chronologic age. Hypothalamic-pituitary irradiation ≥18 Gy has been found to be a risk factor; age at irradiation is associated with pubertal timing. However, the underlying mechanisms are unknown. Objective To determine the impact of body mass index (BMI) and c...

Background A 2018 American Heart Association science advisory indicated that, pending further research, artificially sweetened beverages (ASBs) may be an appropriate initial replacement for sugar‐sweetened beverages (SSBs) during transition to unsweetened beverages (USBs). Methods and Results We randomly assigned 203 adults (121 males, 82 females;...

Objectives: To determine if a home oxygen therapy (HOT) management strategy that includes analysis of recorded home oximetry (RHO) data, compared with standard monthly clinic visit assessments, reduces duration of HOT without harm in premature infants. Methods: The RHO trial was an unmasked randomized clinical trial conducted in 9 US medical cen...

Background Nucleated red blood cells (nRBCs) are associated with adverse outcomes for pediatric and adult intensive care patients. Methods The association between nRBC count and mortality was examined in an observational cohort of patients admitted to the neonatal intensive care unit from December 2015 – December 2018. Results Among the 1059 pati...

Background: Psychological and behavioral correlates are considered important in the development and persistence of obesity in both adults and youth. This study aimed to identify such features in youth with severe obesity (BMI ≥ 120% of 95thpercentile of sex-specific BMI-for-age) compared to those with overweight or non-severe obesity. Methods: Y...

Context According to the carbohydrate-insulin model of obesity, an elevated insulin-to-glucagon ratio in response to a high-carbohydrate diet directs metabolic fuels toward storage, resulting in lower circulating energy. Objective To determine differences in total circulating energy post-meal related to dietary carbohydrate. Design Ancillary stud...

This cohort study analyzes the association of closure time in response to adenosine diphosphate (CT-ADP) with bleeding score and the associations of platelet transfusions with change in platelet count, CT-ADP, and bleeding scores in preterm neonates with thrombocytopenia.

Hypogenesis (hCC) and dysgenesis (dCC) of the corpus callosum (CC) are characterized by its smaller size or absence. The outcomes of these patients vary considerably and are unrelated to the size of the CC abnormality. The aim of the current study was to characterize the sulcal pattern in children with hCC and dCC and to explore its relation to cli...

Background While Roux-en-Y gastric bypass (RYGB) is one of the most effective and durable treatment options for obesity and its comorbidities, it is complicated by long-term weight regain in over 20% of patients. Aims We sought to determine the metabolite signatures of serum samples of patients with weight regain (RYGB-WR) after RYGB and features...

Introduction Before using blood-oxygen-level-dependent magnetic resonance imaging (BOLD MRI) during maternal hyperoxia as a method to detect individual placental dysfunction, it is necessary to understand spatiotemporal variations that represent normal placental function. We investigated the effect of maternal position and Braxton-Hicks contraction...

Background Roughly half of all extremely preterm infants will be diagnosed with bronchopulmonary dysplasia (BPD), and a third will be discharged on home oxygen therapy (HOT). To date, there have been no studies that have examined the relationship between respiratory medication utilization in infants with BPD on HOT. Methods The recorded home oxime...

The regional specification of the cerebral cortex can be described by protomap and protocortex hypotheses. The protomap hypothesis suggests that the regional destiny of cortical neurons and the relative size of the cortical area are genetically determined early during embryonic development. The protocortex hypothesis suggests that the regional grow...

Introduction: To increase the rate of iron sufficiency among neonatal intensive care unit (NICU) patients from 16% to >35% within 12 months of implementing standardized assessment of reticulocyte hemoglobin (retHE). Methods: We implemented a quality improvement (QI) study to improve iron sufficiency in our out-born level III/IV NICU. We screened...

Objective: Delayed puberty is a common condition, and typical management includes “watchful waiting” and/or sex-steroid therapy. We sought to characterize treatment practices and to assess provider comfort with the management of delayed puberty in girls and boys. Methods: A national survey of pediatric endocrine providers assessed definitions of de...

The diffuse nature of mild traumatic brain injury (mTBI) impacts brain white-matter pathways with potentially long-term consequences, even after initial symptoms have resolved. To understand post-mTBI recovery in adolescents, longitudinal studies are needed to determine the interplay between highly individualised recovery trajectories and ongoing d...

Eltrombopag (ELT), a small molecular thrombopoietin (TPO) mimetic approved for children and adults, could offer a therapeutic alternative to selected neonates and young children with chronic thrombocytopenias. ELT has also been proposed as a potential anti-cancer drug due to its anti-proliferative effects in tumor cells, which are mediated by its s...

Background: Little evidence supports use of chlorhexidine gluconate (CHG) baths to reduce health care-associated infections, including central catheter-associated bloodstream infections in infants less than 2 months old. Objective: To describe the safety of biweekly CHG baths in infants less than 2 months old by measuring blood levels of CHG, li...

Background. Neonatal hypothermia remains a challenge in resource-limited settings. Methods. We conducted a prospective mixed-methods cohort study in rural Rwandan health centers to assess the performance of an infant warmer we designed for low-resource settings. All hypothermic infants were eligible for enrollment. Outcomes. Safety: incidence of ad...

Structural asymmetries and sexual dimorphism of the human cerebral cortex have been identified in newborns, infants, children, adolescents, and adults. Some of these findings were linked with cognitive and neuropsychiatric disorders, which have roots in altered prenatal brain development. However, little is known about structural asymmetries or sex...

Enhancing LRP5 signaling and inhibiting TGFβ signaling have each been reported to increase bone mass and improve bone strength in wild-type mice. Monotherapy targeting LRP5 signaling, or TGFβ signaling, also improved bone properties in mouse models of Osteogenesis Imperfecta (OI). We investigated whether additive or synergistic increases in bone pr...

The diffused nature of mild traumatic brain injury (mTBI) impacts brain white-matter pathways with potentially long-term consequences, even after initial symptoms have resolved. To understand post-mTBI recovery in adolescents, longitudinal studies are needed to determine the interplay between highly individualised recovery trajectories and ongoing...

Background Psychological and behavioral correlates are considered important in the development and persistence of obesity in both adults and youth. This study aimed to identify such features in youth with severe obesity (BMI ≥ 120% of 95th percentile of sex-specific BMI-for-age) compared to those with overweight or non-severe obesity. Methods Youth...

Background: Psychological and behavioral correlates are considered important in the development and persistence of obesity in both adults and youth. This study aimed to identify such features in youth with severe obesity (BMI ³ 120% of 95th percentile of sex-specific BMI-for-age) compared to those with overweight or non-severe obesity. Methods: You...

Purpose: Adolescents with anorexia nervosa (AN) have decreased dehydroepiandrosterone (DHEA) and estrogen concentrations that may contribute to skeletal deficits. We sought to determine whether DHEA + estrogen replacement (ERT) prevented bone loss in young adolescents with AN. Methods: We recruited females with AN (n = 70, ages 11-18 years) into...

BACKGROUND While very low birth weight (VLBW) infants often require multiple red blood cell transfusions, efforts to minimize transfusion‐associated risks have resulted in more restrictive neonatal transfusion practices. However, whether restrictive transfusion strategies limit transfusions without increasing morbidity and mortality in this populat...

Introduction: Given the adverse health effects of added sugars, particularly in liquid form, dietary guidelines recommend replacing sugar-sweetened beverages (SSB) with non-caloric options. However, data are limited regarding the effects of artificially sweetened (ASB) compared to unsweetened (USB) beverages. Hypothesis: We tested the hypothesis th...

Platelet transfusions are frequently given to neonates with platelet counts (PCs) below an arbitrary trigger,¹,2 but studies have shown a poor correlation between low PC and bleeding,²,3 highlighting the need for better tests to identify infants at risk.

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...

Setting: Rural Rwandan hospitals, where thermoregulation is critical yet a challenge for pre-term, low-birth-weight (LBW) or sick newborns. Objective: To assess the safety, effectiveness, and feasibility of an inexpensive, reusable, non-electric warmer to complement kangaroo mother care (KMC). Methods: Prospective single-arm, non-randomized interve...

Despite extensive literature showing damages in the sensorimotor projection fibers of children with hemiplegic cerebral palsy (HCP), little is known about how these damages affect the global brain network. In this study, we assess the relationship between the structural integrity of sensorimotor projection fibers and the integrity of intergyral ass...

Objective To determine the effects of diets varying in carbohydrate to fat ratio on total energy expenditure. Design Randomized trial. Setting Multicenter collaboration at US two sites, August 2014 to May 2017. Participants 164 adults aged 18-65 years with a body mass index of 25 or more. Interventions After 12% (within 2%) weight loss on a run...

Improved survival among preterm infants has led to an increase in diagnosis of chronic lung disease and infants discharged home from the NICU on supplemental oxygen. Despite this increased prevalence, no clearly defined guidelines for the management of home oxygen therapy (HOT) exist. This lack of consensus leads to significant variability in the d...

Context Most pediatric thyroid nodules are cytologically benign, but few data exist to guide management of these nodules. Objective To describe the natural history and outcomes of cytologically benign pediatric thyroid nodules. Design Cohort study Setting Multidisciplinary thyroid clinic at an academic pediatric and adult center Patients Consec...

Objective: To develop and validate the Test of Ethics Knowledge in Neonatology (TEK-Neo) with good internal consistency reliability, item performance, and construct validity that reliably assesses interprofessional staff and trainee knowledge of neonatal ethics. Study design: We adapted a published test of ethics knowledge for use in neonatology...

Despite the remarkable, early remission of T2D after RYGB, the surgery’s key mechanisms have yet to be defined in a way that can be translated to less invasive therapies. Recently, we demonstrated that improved glucose homeostasis after RYGB in rodents is associated with intestinal metabolic reprogramming: the Roux Limb (RL) exhibits dramatic morph...

Objective: Reduce chronic lung disease by 10% among very-low birth weight infants by implementing a consistent respiratory care bundle. Study design: Prospective quality improvement study of infants below 32 weeks gestation in a small neonatal intensive care unit. A respiratory care bundle to eliminate inter-provider variability and minimize use...

Objectives: To assess the validity of body mass index (BMI) and age- and sex-standardized BMI z-score (BMIZ) as surrogates for adiposity (body fat percentage [BF%], fat mass, and fat mass index [kg/m2]) at 3 time points in infancy (1, 4, and 7 months) and to assess the extent to which the change in BMIZ represents change in adiposity. Study desig...

Introduction: Children undergoing lung transplant are at risk for low bone mineral density (BMD) and fractures. The effect of lung transplantation on bone health in pediatric patients is unknown. Materials and methods: We performed a retrospective chart review of all patients ages 2-21 years who underwent lung transplantation at our hospital fro...