Nutrition of Newborns with Hypoxic-Ischaemic Encephalopathy during Therapeutic Hypothermia - A Survey of Practice in Polish Neonatal Care Units.

BACKGROUND: The nutritional practice for newborns with hypoxic-ischaemic encephalopathy during therapeutic hypothermia differs among Polish neonatal care units, as no guidelines are provided. We assessed the prevailing procedures. MATERIAL AND METHODS: Data was collected through an anonymous, web-based questionnaire. We surveyed aspects of the current nutritional practices and the reasoning behind the choice of the feeding strategy. RESULTS: Thirty-one responses were obtained (31/33, 94%). Based on participants' estimations, 342 newborns are diagnosed with hypoxic-ischaemic encephalopathy and qualified for therapeutic hypothermia annually. Among them, almost ⅓ is fed exclusively parenterally, while 71% both ways-parenterally and enterally. In the vast majority of units, the introduction of enteral nutrition takes place during the first 48 hours of therapeutic hypothermia, and breast milk is primarily provided, although with substantial first feeding volume differentiation (an average of 2,9 ml/kg (0,3 - 10ml/kg)). Adverse events, such as necrotising enterocolitis, sepsis, and glycemia level disturbances that derive from the initiation of enteral nutrition, are difficult to estimate as no official statistics are provided. CONCLUSIONS: The majority of newborns after hypoxic-ischaemic encephalopathy treated with therapeutic hypothermia are fed both parenterally and enterally during the procedure, predominantly with expressed or donor breast milk. However, due to the lack of nutritional guidelines, significant variability of nutritional strategies concerning initiation time, type and volume of enteral feeds given is noted. Therefore, further studies are required to clarify feeding recommendations.

Paternal uniparental disomy of chromosome 2 resulting in a concurrent presentation of Crigler-Najjar syndrome type I and long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency.

This is the first report of the concurrent development of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) and Crigler-Najjar syndrome type 1 (CNs1) inherited via uniparental disomy of chromosome 2, which are both autosomal recessive pathologies. Through an expanded newborn metabolic panel, a male infant was identified as having an acylcarnitine pattern typical for LCHADD, later confirmed to be caused by a well-characterized pathogenic variant in the HADHA gene located at 2p23. Prolonged non-hematologic jaundice requiring repetitive phototherapy prompted further genetic analysis, leading to the identification of another genetic abnormality consistent with CNs1, which was caused by a novel pathogenic variant in the UGT1A1 gene located at 2q37. The two identified point mutations in chromosome 2 were homozygous and present on separate arms, which indicated potential uniparental disomy. Microarray analysis of the genetic material from the patient and his parents confirmed paternal isodisomy of chromosome 2. Further studies are needed to identify other possible pathogenic variants located on the same defective chromosome, evaluate the combined effect of the two metabolic abnormalities, and plan the best possible treatment and care.

Plasma Free Fatty Acids and their Binding Proteins in Preterm Infants.

BACKGROUND/AIMS: The objective of the study was to evaluate the circulating concentrations of plasma free fatty acids (FFA), fatty acid binding proteins: FABP-1 and FABP-4 in preterm infants depending on different feeding protocol. METHODS: A total of 43 premature infants (≤34 weeks) were enrolled in the study, and divided into 3 subgroups: nursed while staying in the department (53%), breast-fed only during the first 24 h (16%), and formulafed from the beginning (31%). The control group consisted of 12 healthy, full-term, breast-fed newborns. Blood samples were collected after delivery and 1 month later. We measured plasma concentrations of FFA, FABP-1, and FABP-4. RESULTS: FFA plasma concentrations were significantly lower in preterm babies when compared to control group (p = 0.003) in the prenatal period. After 1 month, a significant decrease in FFA concentration was noted in all groups of preterm babies independently from feeding protocol. After a month, breast-fed preterm infants and controls had significantly lower FABP-1 levels than preterm formula-fed infants (all p < 0.05), while the highest concentrations of FABP-4 were noted in formula-fed preterm infants when compared to breast-fed preterm infants and the control group (all p < 0.05). CONCLUSIONS: Prematurity is connected with disturbances in plasma FFA concentrations. FABP-1, as well as FABP-4, plasma levels in preterm infants depend on feeding protocol.

Relationship between Proton Magnetic Resonance Spectroscopy of Frontoinsular Gray Matter and Neurodevelopmental Outcomes in Very Low Birth Weight Children at the Age of 4.

Very low birth weight is associated with long term neurodevelopmental complications. Macroscopic brain abnormalities in prematurity survivors have been investigated in several studies. However, there is limited data regarding local cerebral metabolic status and neurodevelopmental outcomes. The purpose of this study was to characterize the relationship between proton magnetic resonance spectra in basal ganglia, frontal white matter and frontoinsular gray matter, neurodevelopmental outcomes assessed with the Leiter scale and the Developmental Test of Visual Perception and selected socioeconomic variables in a cohort of very low birth weight children at the age of four. Children were divided in three groups based on the severity of neurodevelopmental impairment. There were no differences in spectroscopy in basal ganglia and frontal white matter between the groups. Lower concentrations of N-acetylaspartate (NAA), choline (Cho) and myoinositol (mI) were observed in the frontoinsular cortex of the left hemisphere in children with neurodevelopmental impairment compared to children with normal neurodevelopmental outcomes. Higher parental education, daycare attendance and breastfeeding after birth were associated with more favorable neurodevelopmental prognosis, whereas rural residence was more prevalent in children with moderate and severe impairment. Our study demonstrates the role of long term neurometabolic disruption in the left frontoinsular cortex and selected socioeconomic variables in determination of neurodevelopmental prognosis in prematurity survivors.

Hypoxia-reoxygenation affects whole-genome expression in the newborn eye.

PURPOSE: Resuscitation of newborns is one of the most frequent procedures in neonatal medicine. The use of supplementary oxygen during resuscitation of the asphyxiated newborn has been shown to be detrimental to vulnerable tissues. We wanted to assess transcriptional changes in ocular tissue after the acute use of oxygen in the delivery room in a hypoxia-reoxygenation model of the newborn mouse. METHODS: C57BL/6 mice (n = 57), postnatal day 7, were randomized to receive either 120 minutes of hypoxia, at 8% O2, followed by 30 minutes of reoxygenation with 21, 40, 60, or 100% O2 or to normoxia followed by 30 minutes of 21% or 100% O2. Whole ocular homogenates were analyzed by Affymetrix 750k expression array, and RT-PCR was performed for validation. Bayesian analysis of variance for microarray data (BAMarray) was used to identify single significant genes, and Gene Set Enrichment Analysis (GSEA) was applied to reveal significant pathway systems. RESULTS: In total, ∼ 92% of the gene expression changes were altered in response to reoxygenation with 60% or 100% O2 compared to expression at the lower percentages of 21% and 40%. After 100% O2 treatment, genes involved in inflammation (Ccl12), angiogenesis (Igfr1, Stat3), and metabolism (Hk2) were upregulated. Pathway analyses after hypoxia-reoxygenation revealed significant alterations of six pathways which included apoptosis, TGF-beta signaling, oxidative phosphorylation, voltage-gated calcium channel complex, mitochondrion, and regulation of RAS protein signal transduction. CONCLUSIONS: Hypoxia-reoxygenation can induce immediate transcriptional responses in ocular tissue involving inflammation, angiogenesis, energy failure, and Ras signaling.