Seizure burden and neurodevelopmental outcome in newborns with hypoxic-ischemic encephalopathy treated with therapeutic hypothermia: A single center observational study.

OBJECTIVE: To examine the relationship between electrographic seizures and developmental outcome at 18 and 24 months in neonates with moderate and severe hypoxic-ischemic encephalopathy [HIE] treated with therapeutic hypothermia [TH]. STUDY DESIGN: 30 term infants with moderate-severe HIE treated with TH were enrolled prospectively from June 2012 to May 2018. All had continuous single channel amplitude integrated EEG (aEEG) monitoring for a minimum of 72 h and brain MR within 4 weeks. The aEEG was classified by severity of background and seizure burden. MR images were graded by the severity of injury. Outcome (defined abnormal in case of death, dyskinetic or spastic quadriplegic cerebral palsy, epilepsy, or Bayley III score < 85 in all three subscales or < 70 in any individual subscale) was assessed at 18 and 24 months. RESULTS: Seizures were recorded in 24 out of 30 [80 %] neonates and an abnormal outcome was observed in 7 [23 %] of infants. Patients with poor outcome had a statistically significant correlation with: high seizure burden (p = 0.0004), need for more than one antiepileptic drugs (p = 0.006), a persistent abnormal aEEG trace at 48 h (p = 0.0001) and moderate-severe brain injury at MRI (p = 0.0001). Moreover, infants with status epilepticus or frequent seizures reported a significantly association with abnormal MR imaging and poor outcome than patients with sporadic seizures (p = 0.0009). CONCLUSION: The role of seizures in the pathogenesis of brain injury remains controversial. In our cohort the presence of seizures, per se, was not associated with abnormal outcome; however a high seizure burden as well as a persistent abnormal aEEG background pattern and MR lesions resulted significantly associated with poor prognosis.

Early Protein Intake Influences Neonatal Brain Measurements in Preterms: An Observational Study.

Introduction: To limit extrauterine growth restriction, recent guidelines on nutrition of preterm neonates recommended high protein intake since the first day of life (DOL). The impact of this nutritional strategy on the brain is still controversial. We aimed to evaluate the effects of protein intake on early cerebral growth in very low birth weight newborns. Materials and Methods: We performed serial cranial ultrasound (cUS) scans at 3-7 DOL and at 28 DOL in very low birth weight newborns consecutively observed in the neonatal intensive care unit. We analyzed the relation between protein intake and cerebral measurements at 28 DOL performed by cUS. Results: We enrolled 100 newborns (gestational age 29 ± 2 weeks, birth weight 1,274 ± 363 g). A significant (p < 0.05) positive correlation between enteral protein intake and biparietal diameter (r = 0.490**), occipital-frontal diameter (r = 0.608**), corpus callosum (length r = 0.293*, genu r = 0.301*), caudate head (right r = 0.528**, left r = 0.364**), and cerebellum (transverse diameter r = 0.440**, vermis height r = 0.356**, vermis width r = 0.377**) was observed at 28 DOL. Conversely, we found a significant negative correlation of protein intake given by parenteral nutrition (PN) with biparietal diameter (r = -0.524**), occipital-frontal diameter (r = -0.568**), body of corpus callosum (r = -0.276*), caudate head (right r = -0.613**, left r = -0.444**), and cerebellum (transverse diameter r = -0.403**, vermis height r = -0.274*, vermis width r = -0.462**) at 28 DOL. Multivariate regression analysis showed that measurements of occipital-frontal diameter, caudate head, and cerebellar vermis at 28 DOL depend positively on protein enteral intake (r = 0.402*, r = 0.305*, and r = 0.271*) and negatively by protein parenteral intake (r = -0.278*, r = -0.488*, and r = -0.342*). Conclusion: Brain development in neonatal life depends on early protein intake. High protein intake affects cerebral structures' measurements of preterm newborn when administered by PN. Positive impact on brain development encourages the administration of recommended protein intake mainly by enteral nutrition.

Trace elements, oxidative status and antioxidant capacity as biomarkers in very low birth weight infants.

Reference data on trace elements, oxidative status and antioxidants in very low birth weight infants (VLBW) are limited and need to be updated for use in clinical settings. Serum and urine of 30 VLBW infants (mean weight, 1167g) at mean age of 23.8 (t0) and 37.8 (t1) days were analyzed. Cadmium (Cd), copper (Cu), iron (Fe), mercury (Hg), manganese (Mn), selenium (Se) and zinc (Zn), nitrate/nitrite (NOx), catalase (CAT), CuZnFeMn-superoxide dismutases (CuZnFeMn-SODs), total antioxidant capacity (SAC: sum of thiols, proteins, bilirubin, uric acid, ß-beta-carotene, ascorbic acid, vitamin E) and total oxidative status (SOS: sum of lipo- and hydroperoxides) were determined. A higher urinary excretion of Cu and Zn was observed at t0 than at t1; while an increase in urine Cd was found at t1 respect to t0. A deficiency in serum levels of Cu and Zn was also found. A lower CAT activity, a higher total oxidants level (SOS) and a reduction of total antioxidant barriers (SAC) were observed in some infants. No Fe and Mn deficiency or Hg overload was found; also CuZnFeMn-SODs and NOx levels did not change. The findings showed that losses of trace elements and incomplete mineral body stores were more pronounced in the earlier life stage (at 23.8th day) than later on; moreover, antioxidant defenses were poor and lipo- and hydroperoxides were higher still at 5 weeks of infants' life.

(1)H NMR-based urine metabolic profile of IUGR, LGA, and AGA newborns in the first week of life.

Under conditions of non-optimal supply of nutrients, maternal diet during gestation can alter the balance between anabolic and catabolic pathways of fetus and triggers an effect of programming to the metabolic syndrome. Metabolomics is an analytical technique that has been recently attracting increasing interest for the identification of biomarkers of dietary exposure. In this study, a NMR-based metabolomic approach was employed for an explorative analysis of the time-related urinary metabolic profiles of three groups of newborns receiving a different fetal nutrition: adequate for gestational age (AGA), with intrauterine growth retardation (IUGR), and large for gestational age (LGA). Urine samples were collected over the first week of life. Application of Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA) evidenced similar time-related modifications in the metabolic profiles of the three classes of infants, consisting mainly of changes in levels of taurine, creatinine, betaine, and glycine. Furthermore, alterations in the content of citrate and myo-inositol were found to be characteristic of IUGR and LGA, whole levels were higher with respect to controls, while higher contents of betaine and succinate were noted in AGA. Our results positively support the application of the metabolomic approach in the study of the metabolic pathways associated to fetal malnutrition.

Investigation of the ¹H-NMR based urine metabolomic profiles of IUGR, LGA and AGA newborns on the first day of life.

(1)H-NMR spectroscopy coupled with multivariate statistical analysis was used for the first time to compare the urinary NMR metabolic profiles of neonates with intrauterine growth retardation (IUGR) and large for gestational age (LGA). For the sake of comparison, infants who were adequate for gestational age (AGA) were also analyzed. Pattern recognition methods, including Principal Component Analyses (PCA), Partial Least Squares Discriminant Analysis (PLS-DA) and Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA), were used to analyze NMR data. Clear differences among the metabolic profiles of AGA, IUGR and LGA were observed. The main metabolites responsible for these differentiations were identified as myo-inositol, creatinine, creatine, citrate, urea and glycine. In particular, among these, myo-inositol may be a potential biomarker of an altered glucose metabolism during fetal development both in IUGR and LGA. This study highlights the applicability of NMR-based metabolomics for improving the understanding of the relations among nutrition, integrated metabolism and health in neonatology.

Management strategies in the treatment of neonatal and pediatric gastroenteritis.

Acute gastroenteritis, characterized by the onset of diarrhea with or without vomiting, continues to be a major cause of morbidity and mortality in children in mostly resource-constrained nations. Although generally a mild and self-limiting disease, gastroenteritis is one of the most common causes of hospitalization and is associated with a substantial disease burden. Worldwide, up to 40% of children aged less than 5 years with diarrhea are hospitalized with rotavirus. Also, some microorganisms have been found predominantly in resource-constrained nations, including Shigella spp, Vibrio cholerae, and the protozoan infections. Prevention remains essential, and the rotavirus vaccines have demonstrated good safety and efficacy profiles in large clinical trials. Because dehydration is the major complication associated with gastroenteritis, appropriate fluid management (oral or intravenous) is an effective and safe strategy for rehydration. Continuation of breastfeeding is strongly recommended. New treatments such as antiemetics (ondansetron), some antidiarrheal agents (racecadotril), and chemotherapeutic agents are often proposed, but not yet universally recommended. Probiotics, also known as "food supplement," seem to improve intestinal microbial balance, reducing the duration and the severity of acute infectious diarrhea. The European Society for Paediatric Gastroenterology, Hepatology and Nutrition and the European Society of Paediatric Infectious Diseases guidelines make a stronger recommendation for the use of probiotics for the management of acute gastroenteritis, particularly those with documented efficacy such as Lactobacillus rhamnosus GG, Lactobacillus reuteri, and Saccharomyces boulardii. To date, the management of acute gastroenteritis has been based on the option of "doing the least": oral rehydration-solution administration, early refeeding, no testing, no unnecessary drugs.