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Journal: Pediatric research


Background:In preterm infants, low levels of insulin-like growth factor-I (IGF-I) and IGF binding protein 3 (IGFBP-3) are associated with impaired brain growth and retinopathy of prematurity (ROP). Treatment with IGF-I/IGFBP-3 may be beneficial for brain development and may decrease the prevalence of ROP.Methods:In a phase II pharmacokinetics and safety study, five infants (three girls) with a median (range) gestational age (GA) of 26 wk + 6 d (26 wk + 0 d to 27 wk + 2 d) and birth weight of 990 (900-1,212) g received continuous intravenous infusion of recombinant human (rh)IGF-I/rhIGFBP-3. Treatment was initiated during the first postnatal day and continued for a median (range) duration of 168 (47-168) h in dosages between 21 and 111 µg/kg/24 h.Results:Treatment with rhIGF-I/rhIGFBP-3 was associated with higher serum IGF-I and IGFBP-3 concentrations (P < 0.001) than model-predicted endogenous levels. Of 74 IGF-I samples measured during study drug infusion, 37 (50%) were within the target range, 4 (5%) were above, and 33 (45%) were below. The predicted dose of rhIGF-I/rhIGFBP-3 required to establish circulating levels of IGF-I within the intrauterine range in a 1,000 g infant was 75-100 µg/kg/24 h. No hypoglycemia or other adverse effects were recorded.Conclusion:In this study, continuous intravenous infusion of rhIGF-I/rhIGFBP-3 was effective in increasing serum concentrations of IGF-I and IGFBP-3, and was found to be safe.

Concepts: Pregnancy, Childbirth, Embryo, Fetus, Obstetrics, Insulin-like growth factor 1, Growth hormone, IGFBP3


Background:Fetal intrauterine growth restriction (IUGR) results in increased placental resistance to blood flow, fetal hypertension and increased pulsatility stresses shown to lead to vascular remodeling. We tested our hypothesis that IUGR causes decreased compliance in the carotid and umbilical arteries due to altered extracellular matrix (ECM) composition and structure.Methods:A sheep model of placental insufficiency-induced IUGR (PI-IUGR) was created by exposure of the pregnant ewe to elevated ambient temperatures. Umbilical and carotid arteries from near-term fetuses were tested with pressure-diameter measurements to compare passive compliance in control and PI-IUGR tissues. ECM composition was measured via biochemical assay, and the organization was determined by using histology and second-harmonic generation imaging.Results:We found that PI-IUGR increased arterial stiffness with increased collagen engagement, or transition stretch. PI-IUGR carotid arteries exhibited increased collagen and elastin quantity and PI-IUGR umbilical arteries exhibited increased sulfated glycosaminoglycans. Histomorphology showed altered collagen to elastin ratios with altered cellular proliferation. Increased stiffness indicates altered collagen to elastin ratios with less elastin contribution leading to increased collagen engagement.Conclusion:Because vessel stiffness is a significant predictor in the development of hypertension, disrupted ECM deposition in IUGR provides a potential link between IUGR and adult hypertension.Pediatric Research (2012); doi:10.1038/pr.2012.156.

Concepts: Pregnancy, Blood, Myocardial infarction, Embryo, Fetus, Obstetrics, Umbilical vein, Placenta


BackgroundChronic rhinosinusitis (CRS) is characterized by mucous overproduction and submucosal gland hyperplasia. The global protein profile of sinonasal secretions in pediatric CRS has not been studied. We hypothesized that MUC5B, a glandular mucin, would be relatively increased in CRS secretions compared to other mucins.MethodsSecretions were collected at Children’s National Health System (Children’s National) from CRS patients undergoing sinus surgery and from control patients without CRS undergoing craniofacial procedures. Proteins were extracted, digested to peptides, and analyzed by mass spectometry. Fold change significance was calculated using the QSpec algorithm. Western blot analysis was performed to validate proteomic findings.ResultsIn total, 294 proteins were identified. Although both MUC5B and MUC5AC were identified in a majority of samples, the relative abundance of MUC5B was found to be significantly higher (p < 0.05). Western blot data validated these findings. Other proteins with the highest significant positive-fold change in CRS samples were BP1 fold-containing family A member 1, chitinase-3-like protein 1, plastin-2, serpin 10, and BP1 fold-containing family B member 1.ConclusionOverall our data demonstrates an increase of MUC5B abundance in the sinus secretions of pediatric patients with CRS.Pediatric Research (2014); doi:10.1038/pr.2014.187.

Concepts: Proteins, Protein, Molecular biology, Secretion, Western blot, Gel electrophoresis, Proteomics, Gland


Heavy parent digital technology use has been associated with suboptimal parent-child interactions and internalizing/externalizing child behavior, but directionality of associations is unclear. This study aims to investigate longitudinal bidirectional associations between parent technology use and child behavior, and understand whether this is mediated by parenting stress.


BackgroundSurgical treatment for gastroschisis and congenital diaphragmatic hernia (CDH) commonly leads to abdominal compartment syndrome (ACS) associated with hypoxic renal injury. We hypothesized that measurement of urinary and serum concentrations of VEGF, π-GST, and MCP-1 may serve for non-invasive detection of hypoxic renal injury in such patients.MethodsIntra-abdominal pressure (IAP), renal excretory function, and the biomarker levels were analyzed before, 4 and 10 day after surgery. Association between the biomarker levels and renal histology was investigated using an original model of ACS in newborn rats.ResultsFour days after surgery, IAP increased, renal excretory function decreased, and the levels of VEGF, π-GST, and MCP-1 increased, indicating renal injury. Ten days after surgery, IAP partially decreased, renal excretory function completely restored, but the biomarker levels remained elevated, suggesting the ongoing kidney injury. In the model of ACS, increase in the biomarker levels was associated with progressing kidney morphological alteration.ConclusionSurgical treatment for gastroschisis and CDH is associated with prolonged hypoxic kidney injury despite complete restoration of renal excretory function. Follow-up measurement of VEGF, π-GST, and MCP-1 levels may provide a better tool for non-invasive assessment of renal parenchyma in newborns with ACS.Pediatric Research accepted article preview online, 20 October 2017. doi:10.1038/pr.2017.263.

Concepts: Kidney, Surgery, Urinary system, Ureter, Hernia, Renal cortex, Congenital disorders, Congenital diaphragmatic hernia


This study aimed to investigate the effect of nutrition and growth during the first 4 weeks after birth on cerebral volumes and white matter maturation at term equivalent age(TEA) and on neurodevelopmental outcome at 2 years corrected age(CA), in preterm infants.

Concepts: Childbirth


At birth, some organs in premature infants are not developed enough to meet challenges of the extra-uterine life. Although growth and maturation continues after premature birth, postnatal organ development may become sluggish or even arrested, leading to organ dysfunction. There is no clear mechanistic concept of this postnatal organ developmental failure in premature neonates. This review introduces a concept-forming hypothesis: Mitochondrial bioenergetic dysfunction is a fundamental mechanism of organs maturation failure in premature infants. Data collected in support of this hypothesis are relevant to two major diseases of prematurity: white matter injury and broncho-pulmonary dysplasia. In these diseases, totally different clinical manifestations are defined by the same biological process, developmental failure of the main functional units-alveoli in the lungs and axonal myelination in the brain. Although molecular pathways regulating alveolar and white matter maturation differ, proper bioenergetic support of growth and maturation remains critical biological requirement for any actively developing organ. Literature analysis suggests that successful postnatal pulmonary and white matter development highly depends on mitochondrial function which can be inhibited by sublethal postnatal stress. In premature infants, sublethal stress results mostly in organ maturation failure without excessive cellular demise.Pediatric Research (2016); doi:10.1038/pr.2016.216.

Concepts: Childbirth, Biology, Mitochondrion, Heart, Myelin, Mechanism, Organs, Functionalism


The impact of secondhand marijuana smoke exposure on children is unknown. New methods allow detection of secondhand marijuana smoke in children.

Concepts: Detection theory, Smoke


Human biology follows recurring daily rhythms that are governed by circadian cues in the environment. Here we show that human milk is a powerful form of “chrononutrition,” formulated to communicate time-of-day information to infants. However, 85% of breastfed infants in the US consume some milk that does not come directly from the breast but is pumped and stored in advance of feeding. Expressed milk is not necessarily circadian-matched (e.g., an infant might drink breastmilk pumped in the evening on the following morning). Ingesting mistimed milk may disrupt infants' development of circadian rhythms, potentially contributing to sleep problems and decreased physiological attunement with their mothers and environments. Dysregulated circadian biology may compromise infant health and development. Despite wide-ranging public health implications, the timing of milk delivery has received little empirical study, and no major pediatric or public health organization has issued recommendations regarding the circadian-matching of milk. However, potential adverse developmental and health consequences could be ameliorated by simple, low-cost interventions to label and circadian-match stored milk. The current paper reviews evidence for human milk as chrononutrition and makes recommendations for future research, practice, and policy.


BackgroundTuberculosis (TB) diagnosis in children is a challenge with up to 94% of children with TB treated empirically in TB high-burden countries. Therefore, new diagnostic tests are needed for TB diagnosis. We determined the performance of trained rats in the diagnosis of pediatric TB and whether they can improve detection rate compared to the standard of care.MethodsPresumptive TB patients in 24 TB clinics in Tanzania were tested. Samples indicated as TB-positive by rats underwent confirmation by concentrated smear microscopy. TB yield of bacteriologically confirmed pediatric TB patients (≤5 years) was compared with yield of standard of care.ResultsSputum samples from 55,148 presumptive TB patients were tested. Nine hundred eighty-two (1.8%) were the children between 1 and 5 years. Clinics detected 34 bacteriologically positive children, whereas rats detected additional 23 children yielding 57 bacteriologically TB-positive children. Rats increased pediatric TB detection by 67.6%. Among 1-14-year-old children, clinics detected 331 bacteriologically positive TB whereas rats found the additional 208 children with TB that were missed by clinics. Relative increase in TB case detection by rats decreased with the increase in age (P<0.0001).ConclusionTrained rats increase pediatric TB detection significantly and could help address the pediatric TB diagnosis challenges. Further determination of accuracy of rats involving other sample types is still needed.Pediatric Research advance online publication, 4 April 2018; doi:10.1038/pr.2018.40.

Concepts: Hospital, Physician, Tuberculosis, Yield, Confirmation, United Methodist Church, Tuberculosis diagnosis