Showing papers in "Pediatric Research in 2016"
TL;DR: Childhood adversity and traumatic toxic stress is reviewed, epidemiologic data on the prevalence of ACEs and their physical and mental health impacts are presented, and intervention modalities for prevention are discussed.
Abstract: Adverse childhood experiences (ACEs) are related to short- and long-term negative physical and mental health consequences among children and adults. Studies of the last three decades on ACEs and traumatic stress have emphasized their impact and the importance of preventing and addressing trauma across all service systems utilizing universal systemic approaches. Current developments on the implementation of trauma informed care (TIC) in a variety of service systems call for the surveillance of trauma, resiliency, functional capacity, and health impact of ACEs. Despite such efforts in adult medical care, early identification of childhood trauma in children still remains a significant public health need. This article reviews childhood adversity and traumatic toxic stress, presents epidemiologic data on the prevalence of ACEs and their physical and mental health impacts, and discusses intervention modalities for prevention.
301 citations
TL;DR: Models of care that use telemedicine have the potential to address pediatric specialists’ geographic misdistribution and address disparities in the quality of care delivered to children in underserved communities.
Abstract: The regionalization of pediatric services has resulted in differential access to care, sometimes creating barriers to those living in underserved, rural communities. These disparities in access contribute to inferior healthcare outcomes among infants and children. We review the medical literature on telemedicine and its use to improve access and the quality of care provided to pediatric patients with otherwise limited access to pediatric subspecialty care. We review the use of telemedicine for the provision of pediatric subspecialty consultations in the settings of ambulatory care, acute and inpatient care, and perinatal and newborn care. Studies demonstrate the feasibility and efficiencies gained with models of care that use telemedicine. By providing pediatric subspecialty care in more convenient settings such as local primary care offices and community hospitals, pediatric patients are more likely to receive care that adheres to evidence-based guidelines. In many cases, telemedicine can significantly improve provider, patient, and family satisfaction, increase measures of quality of care and patient safety, and reduce overall costs of care. Models of care that use telemedicine have the potential to address pediatric specialists' geographic misdistribution and address disparities in the quality of care delivered to children in underserved communities.
219 citations
TL;DR: rScO2 and cFTOE reference curves are provided for the first 72 h of life in preterm infants, which might support the broader implementation of NIRS in neonatal intensive care.
Abstract: Currently, reliable reference values of regional cerebral oxygen saturation (rScO2) for different gestational age (GA) groups are lacking, which hampers the implementation of near-infrared spectroscopy (NIRS) alongside monitoring arterial oxygen saturation (SaO2) and blood pressure in neonatal intensive care. The aim of this study was to provide reference values for rScO2 and cerebral fractional tissue oxygen extraction (cFTOE; (SaO2 − rScO2)/SaO2) for small adult and neonatal NIRS sensors. In this study, 999 infants born preterm (GA <32 wk) were monitored with NIRS during the first 72 h of life. Mixed modeling was used to generate reference curves grouped per 2 wk of GA. In addition, the influence of a hemodynamically significant patent ductus arteriosus, gender, and birth weight were explored. Average rScO2 was ~65% at admission, increased with GA (1% per week) and followed a parabolic curve in relation to postnatal age with a peak at ~36 h. The cFTOE showed similar but inverse effects. On average, the neonatal sensor measured 10% higher than the adult sensor. rScO2 and cFTOE reference curves are provided for the first 72 h of life in preterm infants, which might support the broader implementation of NIRS in neonatal intensive care.
152 citations
TL;DR: The molecular mechanisms and clinical manifestations of hyperbilirubinemia andotor syndrome are described, as well as current approaches to diagnosis and therapy.
Abstract: Inherited disorders of hyperbilirubinemia may be caused by increased bilirubin production or decreased bilirubin clearance. Reduced hepatic bilirubin clearance can be due to defective (i) unconjugated bilirubin uptake and intrahepatic storage, (ii) conjugation of glucuronic acid to bilirubin (e.g., Gilbert syndrome, Crigler-Najjar syndrome, Lucey-Driscoll syndrome, breast milk jaundice), (iii) bilirubin excretion into bile (Dubin-Johnson syndrome), or (iv) conjugated bilirubin re-uptake (Rotor syndrome). In this review, the molecular mechanisms and clinical manifestations of these conditions are described, as well as current approaches to diagnosis and therapy.
115 citations
TL;DR: The evidence that determinants of childhood obesity act at many levels and at different stages of childhood is of policy relevance to those planning early health promotion and primary prevention programs as it suggests the need to address the individual, the family, the physical environment, the social environment, and social policy.
Abstract: The prevalence of childhood obesity has increased globally over the past three decades, with evidence of recent leveling off in developed countries. Reduction in the, currently high, prevalence of obesity will require a full understanding of the biological and social pathways to obesity in order to develop appropriately targeted prevention strategies in early life. Determinants of childhood obesity include individual level factors, including biological, social, and behavioral risks, acting within the influence of the child's family environment, which is, in turn, imbedded in the context of the community environment. These influences act across childhood, with suggestions of early critical periods of biological and behavioral plasticity. There is evidence of sex and gender differences in the responses of boys and girls to their environments. The evidence that determinants of childhood obesity act at many levels and at different stages of childhood is of policy relevance to those planning early health promotion and primary prevention programs as it suggests the need to address the individual, the family, the physical environment, the social environment, and social policy. The purpose of this narrative review is to summarize current, and emerging, literature in a multilevel, life course framework.
112 citations
TL;DR: Increased exposure to several PFAS was associated with lower levels to mumps and rubella antibody concentrations, especially among seropositive individuals, which may indicate a less robust response to vaccination or greater waning of vaccine-derived immunity over time.
Abstract: Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are immunotoxic in laboratory studies. Human studies of immune effects are inconsistent. Using the US National Health and Nutrition Examination Survey (NHANES), we examined PFAS serum concentration and indicators of prevalent immune function among 12–19-y-old children. In this cross-sectional study, we examined PFAS serum concentration in relation to measles, mumps, and rubella antibody concentrations in NHANES 1999–2000 and 2003–2004 (n = 1,191) and to allergic conditions and allergic sensitization in NHANES 2005–2006 (n = 640). In adjusted, survey-weighted models, a doubling of perfluorooctane sulfonate (PFOS) concentration among seropositive children was associated with a 13.3% (95% confidence interval (CI): −19.9, −6.2) decrease in rubella antibody concentration and a 5.9% decrease in mumps antibody concentration (95% CI: −9.9, −1.6). We observed no adverse association between exposure and current allergic conditions, including asthma. Children with higher PFOS concentration were less likely to be sensitized to any allergen (odds ratio (OR): 0.74; 95% CI: 0.58, 0.95). Increased exposure to several PFAS was associated with lower levels to mumps and rubella antibody concentrations, especially among seropositive individuals. These lower antibody concentrations may indicate a less robust response to vaccination or greater waning of vaccine-derived immunity over time.
110 citations
Radboud University Nijmegen1, Cambridge University Hospitals NHS Foundation Trust2, University Hospital of North Tees3, Karolinska University Hospital4, University College Cork5, Cornell University6, John Radcliffe Hospital7, University of Oslo8, Oslo University Hospital9, Royal Women's Hospital10, Karolinska Institutet11, Boston Children's Hospital12, Rotunda Hospital13, Royal College of Surgeons in Ireland14
TL;DR: Recommendations for neonatologist performed echocardiography in Europe: Consensus Statement endorsed by European Society for Paediatric Research and European Society For Neonatology (ESN)
Abstract: Recommendations for neonatologist performed echocardiography in Europe: Consensus Statement endorsed by European Society for Paediatric Research (ESPR) and European Society for Neonatology (ESN)
108 citations
TL;DR: In this article, the authors focus on studies conducted in high adolescent HIV-burden countries targeted by the "All In to End Adolescent AIDS" initiative, and describe barriers to adolescent HIV uptake and coverage.
Abstract: More than 80% of the HIV-infected adolescents live in sub-Saharan Africa. Acquired immune deficiency syndrome (AIDS)-related mortality has increased among adolescents 10-19 y old. The impact is highest in sub-Saharan Africa, where >80% of HIV-infected adolescents live. The World Health Organization has cited inadequate access to HIV testing and counseling (HTC) as a contributing factor to AIDS-related adolescent deaths, most of which occur in sub-Saharan Africa. This review focuses on studies conducted in high adolescent HIV-burden countries targeted by the "All In to End Adolescent AIDS" initiative, and describes barriers to adolescent HTC uptake and coverage. Fear of stigma and family reaction, fear of the impact of a positive diagnosis, perceived risk with respect to sexual exposure, poor attitudes of healthcare providers, and parental consent requirements are identified as major impediments. Most-at-risk adolescents for HIV infection and missed opportunities for testing include, those perinatally infected, those with early sexual debut, high mobility and multiple/older partners, and pregnant and nonpregnant females. Regional analyses show relatively low adolescent testing rates and more restrictive consent requirements for HTC in West and Central Africa as compared to East and southern Africa. Actionable recommendations for widening adolescent access to HTC and therefore timely care include minimizing legal consent barriers, healthcare provider training, parental education and involvement, and expanding testing beyond healthcare facilities.
108 citations
TL;DR: Given the known differences between various bifidobacterial species and subspecies in metabolic capacity and colonization abilities, the prevalence of misidentified bifids in these products is cause for concern for those involved in clinical trials and consumers of probiotic products.
Abstract: The ingestion of probiotics to attempt to improve health is increasingly common; however, quality control of some commercial products can be limited. Clinical practice is shifting toward the routine use of probiotics to aid in prevention of necrotizing enterocolitis in premature infants, and probiotic administration to term infants is increasingly common to treat colic and/or prevent atopic disease. Since bifidobacteria dominate the feces of healthy breast-fed infants, they are often included in infant-targeted probiotics. We evaluated 16 probiotic products to determine how well their label claims describe the species of detectable bifidobacteria in the product. Recently developed DNA-based methods were used as a primary means of identification, and were confirmed using culture-based techniques. We found that the contents of many bifidobacterial probiotic products differ from the ingredient list, sometimes at a subspecies level. Only 1 of the 16 probiotics perfectly matched its bifidobacterial label claims in all samples tested, and both pill-to-pill and lot-to-lot variation were observed. Given the known differences between various bifidobacterial species and subspecies in metabolic capacity and colonization abilities, the prevalence of misidentified bifidobacteria in these products is cause for concern for those involved in clinical trials and consumers of probiotic products.
108 citations
TL;DR: The objective of this review will be to examine this recent research on the association of each of these sets of social determinants on racial/ethnic disparities PTB, infant mortality, and fetal mortality to highlight potential areas for targeted intervention to reduce these differences.
Abstract: In the United States, there continue to be significant racial/ethnic disparities in preterm birth (PTB) rates, infant mortality, and fetal mortality rates. One potential mediator of these disparities is social determinants of health, including individual socioeconomic factors; community factors such as crime, poverty, housing, and the racial/ethnic makeup of the community; and the physical environment. Previous work has identified statistically significant associations between each of these factors and adverse pregnancy outcomes. However, there are recent studies that provide new, innovative insights into this subject, including adding social determinant data to population-based datasets; exploring multiple constructs in their analysis; and examining environmental factors. The objective of this review will be to examine this recent research on the association of each of these sets of social determinants on racial/ethnic disparities PTB, infant mortality, and fetal mortality to highlight potential areas for targeted intervention to reduce these differences.
107 citations
TL;DR: There was substantial variation in methods used to estimate and calculate nutritional intakes and in the approaches used in reporting these intakes and measures of infant growth, which makes comparisons amongst studies difficult and meta-analysis unreliable.
Abstract: The ultimate goal of neonatal nutrition care is optimal growth, neurodevelopment, and long-term health for preterm babies. International consensus is that increased energy and protein intakes in the neonatal period improve growth and neurodevelopment, but after more than 100 y of research the optimum intakes of energy and protein remain unknown. We suggest an important factor contributing to the lack of progress is the lack of a standardized approach to reporting nutritional intake data and growth in the neonatal literature. We reviewed randomized controlled trials and observational studies documented in MEDLINE and the Web of Science from 2008 to 2015 that compared approximately 3 vs. 4 g.kg(-1).d(-1) protein for preterm babies in the first month after birth. Consistency might be expected in the calculation of nutritional intake and assessment of growth outcomes in this relatively narrow scope of neonatal nutrition research. Twenty-two studies were reviewed. There was substantial variation in methods used to estimate and calculate nutritional intakes and in the approaches used in reporting these intakes and measures of infant growth. Such variability makes comparisons amongst studies difficult and meta-analysis unreliable. We propose the StRONNG Checklist-Standardized Reporting Of Neonatal Nutrition and Growth to address these issues.
TL;DR: This study provides a robust estimate for physiological growth trajectories of infants after undisturbed postnatal adaptation and provides the concept of a target postnatal trajectory during NICU care may be useful.
Abstract: International guidelines suggest that growth of preterm infants should match intrauterine rates. However, the trajectory for extrauterine growth may deviate from the birth percentile due to an irreversible, physiological loss of extracellular fluid during postnatal adaptation to extrauterine conditions. To which “new” physiological growth trajectory preterm infants should adjust to after completed postnatal adaptation is unknown. This study analyzes the postnatal growth trajectories of healthy preterm infants using prospective criteria defining minimal support, as a model for physiological adaptation. International, multi-center, longitudinal, observational study at five neonatal intensive care units (NICUs). Daily weights until day of life (DoL) 21 of infants with undisturbed postnatal adaptation were analyzed (gestational ages: (i) 25–29 wk, (ii) 30–34 wk). 981 out of 3,703 admitted infants included. Maximum weight loss was 11% (i) and 7% (ii) by DoL 5, birth weight regained by DoL 15 (i) and 13 (ii). Infants transitioned to growth trajectories parallel to Fenton chart percentiles, 0.8 z-scores below their birth percentiles. The new trajectory after completed postnatal adaptation could be predicted for DoL 21 with R2 = 0.96. This study provides a robust estimate for physiological growth trajectories of infants after undisturbed postnatal adaptation. In the future, the concept of a target postnatal trajectory during NICU care may be useful.
TL;DR: GDM could constitute a state of placental microbiota-driven altered immunologic tolerance, making placental microbiome a new target for therapy in GDM, and a distinct microbiota profile and microbiome is present.
Abstract: The human microbiota is a modulator of the immune system. Variations in the placental microbiota could be related with pregnancy disorders. We profiled the placental microbiota and microbiome in women with gestational diabetes (GDM) and studied its relation to maternal metabolism and placental expression of anti-inflammatory cytokines. Placental microbiota and microbiome and expression of anti-inflammatory cytokines (IL10, TIMP3, ITGAX, and MRC1MR) were analyzed in placentas from women with GDM and from control women. Fasting insulin, glucose, O’Sullivan glucose, lipids, and blood cell counts were assessed at second and third trimester of pregnancy. Bacteria belonging to the Pseudomonadales order and Acinetobacter genus showed lower relative abundance in women with GDM compared to control (P < 0.05). In GDM, lower abundance of placental Acinetobacter associated with a more adverse metabolic (higher O’Sullivan glucose) and inflammatory phenotype (lower blood eosinophil count and lower placental expression of IL10 and TIMP3) (P < 0.05 to P = 0.001). Calcium signaling pathway was increased in GDM placental microbiome. A distinct microbiota profile and microbiome is present in GDM. Acinetobacter has been recently shown to induce IL-10 in mice. GDM could constitute a state of placental microbiota-driven altered immunologic tolerance, making placental microbiota a new target for therapy in GDM.
TL;DR: This is an integrated mechanism review of animal and human literature related to the hypothesis that maternal obesity causes maternal and fetal inflammation, and that this inflammation adversely affects the neurodevelopment of children.
Abstract: Children of obese mothers are at increased risk of developmental adversities. Maternal obesity is linked to an inflammatory in utero environment, which, in turn, is associated with neurodevelopmental impairments in the offspring. This is an integrated mechanism review of animal and human literature related to the hypothesis that maternal obesity causes maternal and fetal inflammation, and that this inflammation adversely affects the neurodevelopment of children. We propose integrative models in which several aspects of inflammation are considered along the causative pathway linking maternal obesity with neurodevelopmental limitations.
TL;DR: A review of the literature on early-life effects on epigenetic patterns, with special emphasis on social environmental influences, and a discussion of the current state of the area’s research, its future direction, and its potential use in pediatric health.
Abstract: Epigenetics, and especially DNA methylation, have recently become provocative biological explanations for early-life environmental effects on later health. Despite the large increase in papers on the topic over the last few years, many questions remain with regards to the biological feasibility of this mechanism and the strength of the evidence to date. In this review, we examine the literature on early-life effects on epigenetic patterns, with special emphasis on social environmental influences. First, we review the basic biology of epigenetic modification of DNA and debate the role of early-life stressful, protective, and positive environments on gene-specific, system-specific, and whole-genome epigenetic patterns later in life. Second, we compare the epigenetic literatures of both humans and other animals and review the research linking epigenetic patterns to health in order to complete the mechanistic pathway. Third, we discuss physical environmental and social environmental effects, which have to date, generally not been jointly considered. Finally, we close with a discussion of the current state of the area’s research, its future direction, and its potential use in pediatric health.
TL;DR: The alterations to cardiovascular structure, function, and control that have been observed in growth-restricted fetuses, neonates, and infants following uteroplacental vascular insufficiency are discussed.
Abstract: Intrauterine growth restriction (IUGR) refers to the situation where a fetus does not grow according to its genetic growth potential. One of the main causes of IUGR is uteroplacental vascular insufficiency. Under these circumstances of chronic oxygen and nutrient deprivation, the growth-restricted fetus often displays typical circulatory changes, which in part represent adaptations to the suboptimal intrauterine environment. These fetal adaptations aim to preserve oxygen and nutrient supply to vital organs such as the brain, the heart, and the adrenals. These prenatal circulatory adaptations are thought to lead to an altered development of the cardiovascular system and "program" the fetus for life long cardiovascular morbidities. In this review, we discuss the alterations to cardiovascular structure, function, and control that have been observed in growth-restricted fetuses, neonates, and infants following uteroplacental vascular insufficiency. We also discuss the current knowledge on early life surveillance and interventions to prevent progression into chronic disease.
TL;DR: US-guided CVC placement is associated with significantly higher success rates and decreased mean number of attempts required for cannulation, and should be utilized in pediatric patients.
Abstract: Ultrasound-guided central venous catheter placement increases success rates in pediatric patients: a meta-analysis
TL;DR: Use of cyclooxygenase inhibitors and ligation for PDA in VLBW infants decreased over a 10-y period at the studied hospitals, and there was no detectable correlation between hospital-specific changes in PDA management and hospital- specific changes in outcomes of preterm birth during the study period.
Abstract: We examined recent trends and interhospital variation in use of indomethacin, ibuprofen, and surgical ligation for patent ductus arteriosus (PDA) in very-low-birth-weight (VLBW) infants. Included in this retrospective study of the Pediatric Hospital Information System database were 13,853 VLBW infants from 19 US children’s hospitals, admitted at age < 3 d between 1 January 2005 and 31 December 2014. PDA management and in-hospital outcomes were examined for trends and variation. PDA was diagnosed in 5,719 (42%) VLBW infants. Cyclooxygenase inhibitors and/or ligation were used in 74% of infants with PDA overall, however studied hospitals varied greatly in PDA management. Odds of any cyclooxygenase inhibitor or surgical treatment for PDA decreased 11% per year during the study period. This was temporally associated with improved survival but also with increasing bronchopulmonary dysplasia, periventricular leukomalacia, retinopathy of prematurity, and acute renal failure in unadjusted analyses. There was no detectable correlation between hospital-specific changes in PDA management and hospital-specific changes in outcomes of preterm birth during the study period. Use of cyclooxygenase inhibitors and ligation for PDA in VLBW infants decreased over a 10-y period at the studied hospitals. Further evidence is needed to assess the impact of this change in PDA management.
TL;DR: Higher DHA and lower LA levels in the first few weeks of life are associated with decreased intraventricular haemorrhage, improved microstructural brain development, and improved outcomes in preterm born children.
Abstract: Preterm birth has a dramatic impact on polyunsaturated fatty acid exposures for the developing brain. This study examined the association between postnatal fatty acid levels and measures of brain injury and development, as well as outcomes. A cohort of 60 preterm newborns (24–32 wk gestational age) was assessed using early and near-term magnetic resonance imaging (MRI) studies. Red blood cell fatty acid composition was analyzed coordinated with each scan. Outcome at a mean of 33 mo corrected age was assessed using the Bayley Scales of Infant Development, 3rd edition. Adjusting for confounders, a 1% increase in postnatal docosahexaenoic acid (DHA) levels at early MRI was associated with 4.3-fold decreased odds of intraventricular hemorrhage, but was not associated with white matter injury or cerebellar haemorrhage. Higher DHA and lower linoleic acid (LA) levels at early MRI were associated with lower diffusivity in white matter tracts and corresponding improved developmental scores in follow-up. Higher DHA and lower LA levels in the first few weeks of life are associated with decreased intraventricular haemorrhage, improved microstructural brain development, and improved outcomes in preterm born children. Early and possibly antenatal interventions in high-risk pregnancies need to be studied for potential benefits in preterm developmental outcomes.
TL;DR: The findings suggest that while both factors predict temperament status at 6 mo, they do so primarily in an independent manner, and pathways through which maternal stress and illness during pregnancy influence temperament status differ.
Abstract: To determine whether disaster-related prenatal maternal stress and maternal illness during pregnancy predict maternal-rated temperament status in 6-mo-old infants. The temperamental status of 121 infants (60 boys and 61 girls) exposed in utero to varying degrees of maternal stress and/or illness during either first (n = 40), second (n = 43), or third (n = 38) trimester of pregnancy was assessed using the Infant Characteristics Questionnaire. Higher levels of maternal subjective distress and illness were primarily independently associated with poorer temperamental status in the infants. Maternal subjective distress explained 3.4, 3.1, and 9.8% and early pregnancy illness explained 4.3, 5.8, and 2.9% of the variance of the infants’ fussy/difficult, dullness, and needs attention temperament dimensions, respectively. This is the first study to assess whether temperament status is influenced by disaster-related prenatal maternal stress. Moreover, this is the first study to assess whether maternal stress and illness during pregnancy interact to determine infant temperament status. The findings suggest that while both factors predict temperament status at 6 mo, they do so primarily in an independent manner. These results suggest that pathways through which maternal stress and illness during pregnancy influence temperament status differ.
TL;DR: Frequency of apnea events is a function of GA and PMA in infants born preterm, and increased apnea is associated with acute but not with chronic pathologic conditions.
Abstract: Apnea of prematurity (AOP) is nearly universal among very preterm infants, but neither the apnea burden nor its clinical associations have been systematically studied in a large consecutive cohort. We analyzed continuous bedside monitor chest impedance and electrocardiographic waveforms and oxygen saturation data collected on all neonatal intensive care unit (NICU) patients 50 infant-years of data). Apneas, with bradycardia and desaturation (ABDs), defined as central apnea ≥10 s associated with both bradycardia <100 bpm and oxygen desaturation <80%, were identified using a validated automated algorithm. Number and duration of apnea events decreased with increasing gestational age (GA) and postmenstrual age (PMA). ABDs were more frequent in infants <31 wk GA at birth but were not more frequent in those with severe retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD), or severe intraventricular hemorrhage (IVH) after accounting for GA. In the day before diagnosis of late-onset septicemia and necrotizing enterocolitis, ABD events were increased in some infants. Many infants continued to experience short ABD events in the week prior to discharge home. Frequency of apnea events is a function of GA and PMA in infants born preterm, and increased apnea is associated with acute but not with chronic pathologic conditions.
TL;DR: The results suggest a primary growth abnormality in AT, rather than secondary to nutritional impairment or disease severity, should be considered for female patients.
Abstract: BACKGROUND Ataxia telangiectasia (AT) is a genetic multisystem disorder, presenting with progressive ataxia, immune deficiency, and propensity toward malignancy. Endocrine abnormalities (growth retardation, reproductive dysfunction, and diabetes) have been described, however detailed information regarding this aspect is lacking. We aimed to characterize endocrine anomalies and growth patterns in a large cohort of AT patients. METHODS Retrospective study comprising all 52 patients (aged 2-26.2 y) followed at a national AT Clinic. Anthropometric and laboratory measurements were extracted from the charts. RESULTS Median height-SDS was already subnormal during infancy, remaining negative throughout follow up to adulthood. Height-SDS was more impaired than weight-SDS up to age 4 y, thereafter weight-SDS steadily decreased, resulting in progressively lower BMI-SDS. IGF-I-SDS was low (-1.53 ± 1.54), but did not correlate with height-SDS. Gonadal failure was present in all 13 females older than 10 y but only in one male. Two patients had diabetes and 10 had dyslipidemia. Vitamin D deficiency was observed in 52.2% of the evaluated patients. CONCLUSION Our results suggest a primary growth abnormality in AT, rather than secondary to nutritional impairment or disease severity. Sex hormone replacement should be considered for female patients. Vitamin D levels should be followed and supplementation given if needed.
Copenhagen University Hospital1, Utrecht University2, Cambridge University Hospitals NHS Foundation Trust3, University College Cork4, University of Tübingen5, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico6, University of Zurich7, Hospital Universitario La Paz8, Medical University of Graz9
TL;DR: Treatment guided by NIRS reduced the cerebral burden of hypoxia without affecting EEG or the selected blood biomarkers.
Abstract: The SafeBoosC II randomized trial: treatment guided by near-infrared spectroscopy reduces cerebral hypoxia without changing early biomarkers of brain injury
TL;DR: Low Rsat < 66% was associated with the presence of an hsPDA in the preterm infant, suggesting that Csat may be preserved if cerebral autoregulation is largely intact and Bedside NIRS monitoring may reasonably increase suspicion for a significant PDA.
Abstract: Near-infrared spectroscopy (NIRS) may assist with characterization of a hemodynamically significant patent ductus arteriosus (hsPDA) by measuring cerebral and renal saturation (Csat and Rsat) levels. We hypothesized that Csat and Rsat in preterm infants with an hsPDA would be decreased compared to those with no PDA or nonsignificant PDA. This non a-priori designed study retrospectively investigated clinical and ECHO characteristics of preterm infants <29 wk gestation who underwent routine NIRS monitoring. Logistic regression assessed association between NIRS measures and an hsPDA by ECHO. Of 47 infants, 21 had a confirmed hsPDA by ECHO, 14 had a nonsignificant PDA, and 12 had no ECHO performed due to low clinical suspicion for PDA. Logistic regression adjusted for gestational age found that lower Rsat was associated with an hsPDA by ECHO (OR 0.9, 95% CI 0.83–0.98, P = 0.01). Using ROC curves, Rsat < 66% identified an hsPDA with a sensitivity of 81% and specificity of 77%, while Csat was not significant. Low Rsat < 66% was associated with the presence of an hsPDA in the preterm infant. Csat may be preserved if cerebral autoregulation is largely intact. Bedside NIRS monitoring may reasonably increase suspicion for a significant PDA in the preterm infant.
TL;DR: Smad7 expression in NEC macrophages interrupts TGF-β signaling and promotes NF-κB-mediated inflammatory signaling in these cells through increased expression of IKK-β.
Abstract: Necrotizing enterocolitis (NEC) is an inflammatory bowel necrosis of premature infants. Based on our recent findings of increased Smad7 expression in surgically resected bowel affected by NEC, we hypothesized that NEC macrophages undergo inflammatory activation because increased Smad7 expression renders these cells resistant to normal, gut-specific, transforming growth factor (TGF)-β-mediated suppression of inflammatory pathways. We used surgically resected human NEC tissue, murine models of NEC-like injury, bone marrow-derived and intestinal macrophages, and RAW264.7 cells. Smad7 and IκB kinase-beta (IKK-β) were measured by quantitative PCR, western blots, and immunohistochemistry. Promoter activation was confirmed in luciferase reporter and chromatin immunoprecipitation assays. NEC macrophages showed increased Smad7 expression, particularly in areas with severe tissue damage and high bacterial load. Lipopolysaccharide-induced Smad7 expression suppressed TGF-β signaling and augmented nuclear factor-kappa B (NF-κB) activation and cytokine production in macrophages. Smad7-mediated NF-κB activation was likely mediated via increased expression of IKK-β, which, further increased Smad7 expression in a feed-forward loop. We show that Smad7 induced IKK-β expression through direct binding to the IKK-β promoter and its transcriptional activation. Smad7 expression in NEC macrophages interrupts TGF-β signaling and promotes NF-κB-mediated inflammatory signaling in these cells through increased expression of IKK-β.
TL;DR: Phlebotomy-induced negative iron balance limits iron availability to the developing brain in neonatal twin lamb pairs and in animals with negativeIron balance, total RBC iron was maintained while brain iron concentration decreased as a percentage of the iron present in RBCs.
Abstract: Critically ill preterm and term neonates are at high risk for negative iron balance due to phlebotomy that occurs with frequent laboratory monitoring, and the high iron demand of rapid growth. Understanding the prioritization of iron between red blood cells (RBCs) and brain is important given iron’s role in neurodevelopment. Ten neonatal twin lamb pairs (n = 20) underwent regular phlebotomy for 11 d. Lambs were randomized to receive no iron or i.v. daily iron supplementation from 1 to 5 mg/kg. Serum hemoglobin concentration and reticulocyte count were assayed, iron balance calculated, and iron content of RBCs, liver, brain, muscle, and heart measured at autopsy. Among phlebotomized lambs: (i) liver iron concentration was directly related to net iron balance (r = 0.87; P < 0.001) and (ii) brain iron concentration was reduced as a function of net iron balance (r = 0.63) only after liver iron was depleted. In animals with negative iron balance, total RBC iron was maintained while brain iron concentration decreased as a percentage of the iron present in RBCs (r = −0.70; P < 0.01) and as a function of reticulocyte count (r = −0.63; P < 0.05). Phlebotomy-induced negative iron balance limits iron availability to the developing brain.
TL;DR: These findings contribute to the currently limited state of knowledge regarding the breast milk and salivary microbiomes in mother–child pairs and may inform future studies seeking to elucidate the relationship between early-life microbial exposures and pediatric health.
Abstract: The childhood salivary microbiome, which plays an important role in healthy development, may be influenced by breast milk consumption. The composition of the milk microbiome and the role it plays in the establishment of the infant microbiome are not well understood. Here, we sequenced the bacterial 16S rRNA gene to characterize microbial communities in breast milk and 5-year-old child saliva from 10 low-income, Mexican-American mother–child pairs with a high prevalence of obesity. Members of the genus Streptococcus dominated both milk and salivary microbial communities in most subjects. Staphylococcus was observed predominately in milk samples while Prevotella was more prevalent in child saliva. No statistically significant relationships were observed between maternal and child microbiomes or between child microbiome and BMI. However, prepregnancy BMI was correlated with both lower Streptococcus abundance (r = −0.67) and higher microbial diversity (r = 0.77) in breast milk (P < 0.05 for both). Diversity estimates were notably similar to data from other low-income cohorts or children. These findings contribute to the currently limited state of knowledge regarding the breast milk and salivary microbiomes in mother–child pairs and may inform future studies seeking to elucidate the relationship between early-life microbial exposures and pediatric health.
TL;DR: Inflammatory cytokines are elevated in HIE newborns with brain injury by MRI, and cytokine response may identify infants in need of additional neuroprotective interventions.
Abstract: Cytokines have been proposed as mediators of neonatal brain injury via neuroinflammatory pathways triggered by hypoxia-ischemia. Limited data are available on cytokine profiles in larger cohorts of newborns with hypoxic-ischemic encephalopathy (HIE) undergoing therapeutic hypothermia (TH). Serum cytokines interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-13, tumor necrosis factor-α, and interferon-γ were measured in newborns with HIE at 24 and 72 h of TH. Differences between infants with favorable (survivors with mild/no magnetic resonance imaging (MRI) injury) vs. adverse outcome (death or moderate/severe MRI injury) were compared using mixed models to adjust for covariates. Data from 36 term newborns with HIE (favorable outcome: n = 20, adverse outcome: n = 16) were evaluated. Cytokines IL-1β, IL-2, IL-6, IL-8, IL-10, and IL-13 were elevated in the adverse relative to favorable outcome group at 24 h. IL-6 remained significantly elevated in the adverse outcome group at 72 h. IL-6 and IL-10 remained significantly associated with outcome group after controlling for covariates. Inflammatory cytokines are elevated in HIE newborns with brain injury by MRI. In particular, IL-6 and IL-10 were associated with adverse outcomes after controlling for baseline characteristics and severity of presentation. These data suggest that cytokine response may identify infants in need of additional neuroprotective interventions.
TL;DR: Postnatal nutrition ameliorates cardiovascular remodeling induced by FGR while increased BMI worsened cardiovascular endpoints, which opens opportunities for targeted postnatal interventions from early life.
Abstract: Our aim was to determine the influence of breastfeeding and postnatal nutrition on cardiovascular remodeling induced by fetal growth restriction (FGR). A cohort study including 81 children with birthweight 6 mo (coefficient: 0.0982) and healthy-fat dietary intake (coefficient: −0.0128) showed an independent beneficial effect on LVSI and cIMT, respectively. Overweight/obesity induced an additional increment of 1 SD on cIMT in FGR children (interaction coefficient: 0.0307) when compared with its effect in AGA. BMI increased systolic BP (coefficient: 0.7830) while weight catch-up increased diastolic BP (coefficient: 4.8929). Postnatal nutrition ameliorates cardiovascular remodeling induced by FGR. Breastfeeding and healthy-fat dietary intake improved while increased BMI worsened cardiovascular endpoints, which opens opportunities for targeted postnatal interventions from early life.
TL;DR: Regional variability in the susceptibility/sensitivity of WM maturation to perinatal factors and relationships between altered diffusion measures and developmental outcomes in preterm neonates is demonstrated.
Abstract: BACKGROUND Preterm infants are at risk for white matter (WM) injury and adverse neurodevelopmental outcomes. METHODS Serial diffusion tensor magnetic resonance imaging data were obtained from very preterm infants (N = 78) born <30 wk gestation imaged up to four times from 26-42 wk postmenstrual age. Slopes were calculated for fractional anisotropy (FA) and mean diffusivity (MD) within regions of interest for infants with ≥2 scans (N = 50). Sixty-five children underwent neurodevelopmental testing at 2 y of age. RESULTS FA slope for the posterior limb of the internal capsule was greater than other regions. The anterior limb of the internal capsule (ALIC), corpus callosum, and optic radiations demonstrated greater FA slope with increasing gestational age. Infants with patent ductus arteriosus had lower FA slope in the ALIC. MD slope was lower with prolonged ventilation or lack of antenatal steroids. At 2 y of age, lower motor scores were associated with lower FA in the left but higher FA in the right inferior temporal lobe at term-equivalent age. Better social-emotional competence was related to lower FA in the left cingulum bundle. CONCLUSION This study demonstrates regional variability in the susceptibility/sensitivity of WM maturation to perinatal factors and relationships between altered diffusion measures and developmental outcomes in preterm neonates.