Nutrient Status and Intakes of Adults with Phenylketonuria.

A phenylalanine-restricted diet, supplemented with protein substitutes (PSs), remains the cornerstone of phenylketonuria (PKU) management. However, adherence is challenging in adulthood, and data on the nutritional status of early and continuously treated adults with PKU (ETAwPKU) are scarce. A total of 34 ETAwPKU (16 females; mean ± SD, age: 28 ± 9 years, phenylalanine concentration: 847 ± 285 µmol/L) and 34 age- and sex-matched control subjects were compared regarding their blood nutrient status, self-reported dietary intake, and cognitive wellbeing. Though diet adherence varied, all ETAwPKU were taking a PS. No significant differences were found for blood DHA, calcium, ferritin, transferrin, and zinc concentrations. However, selenium and ubiquinone concentrations were 16% and 29% lower in ETAwPKU, respectively (p < 0.01 and <0.0001). Vitamin concentrations (D, B12, B6, and folic acid) were significantly higher in ETAwPKU except for alpha-tocopherol. Amino acid (AA) concentrations differed between ETAwPKU and controls: they were significantly lower for 12 AAs and higher for phenylalanine and glycine. ETAwPKU had a significantly higher intake of most minerals and vitamins, except for niacin and phosphorus (no difference). Depending on the nutrient, PSs represented 52-100% of patients' daily intake and 19% of total daily energy intake. Compared with controls, ETAwPKU scored significantly lower in three of the four subscales of the cognitive wellbeing questionnaire. Overall, the blood DHA and micronutrient status of ETAwPKU was adequate, except for selenium, with higher intakes than controls for most micronutrients. Patients relied heavily on PSs to meet the recommended intakes for protein, DHA, and micronutrients. The potential clinical impact of differences found in AA status should be further studied.

Pain and heart rate variability in neonates receiving dexmedetomidine.

INTRODUCTION: Neonates in a NICU experience pain. Based on the cardiovascular and nociceptive systems link, a Newborn Infant Parasympathetic Evaluation (NIPE) monitor was designed to assess pain. The use of α2-agonists as analgesic-sedative drugs has increased in neonates. Given their effect on the autonomic system, we hypothesized that their use may alter NIPE's measurement capacity. METHODS: Data were prospectively collected. The included patients were evaluated using combined pain assessment systems. RESULTS: Sixteen newborns requiring sedoanalgesia underwent a total of 84 pain assessments. A good correlation was found between the NIPE-index and the COMFORT-neo and the crSO2 (cerebral regional oxygen saturation). No correlation was found in premature infants. By sedation group, the correlation remained in those receiving α2-agonist. CONCLUSION: NIPE is a reliable tool for pain assessment. Further studies in premature infants are needed. The use of α2-agonist does not alter the measuring capacity of NIPE. The correlation between NIPE-index and crSO2 was also demonstrated.

Age- and Sex-Dynamic Fluctuations and Reference Intervals for Alkaline Phosphatase Among the Spanish Population.

CONTEXT.­: Interpretation of alkaline phosphatase (ALP) activity is essential for the diagnosis of certain diseases. ALP changes during life and may vary between different populations. OBJECTIVE.­: To establish reference intervals (RIs) and percentile charts for ALP activity in the Spanish population through a multicentric observational study and to compare the RIs to those defined in other countries. DESIGN.­: A total of 662 350 ALP measurements from individuals ages 0 to 99 years from 9 Spanish tertiary care centers collected between 2020 and 2022 were analyzed. This study is the largest published in the literature to date. RESULTS.­: Continuous percentile charts for ALP according to sex and age were established which can be used as RIs. Higher levels are reached during the first weeks of life. In puberty, a differential evolution is observed in both sexes, reaching a peak at 10 to 13 years of age in boys and remaining stable in girls at this age. Significant differences were also observed in adults, higher in men between ages 20 and 49 years and between ages 50 and 79 years in women, as reported in some countries. CONCLUSIONS.­: ALP activity follows an age- and sex-dependent fluctuation with geographic differences. It is important to have appropriate reference values for each population in order to allow for a correct diagnostic interpretation and early diagnosis of diseases related to ALP abnormalities.

Supplementation for Performance and Health in Patients with Phenylketonuria: An Exercise-Based Approach to Improving Dietary Adherence.

Supplementation is crucial for improving performance and health in phenylketonuria (PKU) patients, who face dietary challenges. Proteins are vital for athletes, supporting muscle growth, minimizing catabolism, and aiding muscle repair and glycogen replenishment post-exercise. However, PKU individuals must limit phenylalanine (Phe) intake, requiring supplementation with Phe-free amino acids or glycomacropeptides. Tailored to meet nutritional needs, these substitutes lack Phe but fulfill protein requirements. Due to limited supplement availability, athletes with PKU may need higher protein intake. Various factors affect tolerated Phe levels, including supplement quantity and age. Adhering to supplement regimens optimizes performance and addresses PKU challenges. Strategically-timed protein substitutes can safely enhance muscle synthesis and sports performance. Individualized intake is essential for optimal outcomes, recognizing proteins' multifaceted role. Here, we explore protein substitute supplementation in PKU patients within the context of physical activity, considering limited evidence.

Health care-associated infections in neonatology.

Health care-associated infections are common in neonatology, but there is no consensus on their definitions. This makes it difficult to compare their incidence or assess the effectiveness of prevention bundles. This is why we think it is very important to achieve a consensus on the definitions and diagnostic criteria for one of the most frequent causes of morbidity in hospitalised neonates. This document aims to standardise the definitions for the most frequent health care-associated infections, such as catheter-associated bloodstream infection, ventilator-associated pneumonia and surgical wound infection, as well as the approach to their diagnosis and treatment.

Non-invasive biomonitoring of infant exposure to environmental organic pollutants in north-western Spain based on hair analysis. Identification of potential sources.

Recent years have seen growing interest in hair sample analysis to detect organic pollutants (OPs). This biological matrix can be analysed non-invasively for biomonitoring of OPs over a wide exposure window. Obtaining hair sample amounts that meet the needs of the analytical methodology required for the determination of the POs of interest can be challenging, especially in infants. As a result, studies assessing organic pollutants in infant hair have been very scarce. We quantified levels of about 60 OPs, including persistent organic pollutants (POPs), in 110 hair samples from a patient cohort (60 mothers and 50 infants) from Santiago de Compostela (north-western Spain). For each participant we examined relationship between OP levels and corresponding epidemiological parameters using correlations, principal component analysis (PCA), hierarchical cluster analysis, and Multivariate analysis of variance (MANOVA). For many OPs we observed significant correlations with place of residence, parity, and maternal age, as well as pet ownership. Evaluation of dietary habits showed significant associations between levels some OPs and the consumption of fish, molluscs, and cereal. There were significant associations between chlorpyrifos and deltamethrin levels and infant birth characteristics such as birthweight and head circumference. Relations between OP levels in the hair of mothers and their infants were also examined, revealing common sources of exposure for dioxin-like polychlorinated biphenyls (DLPCBs), non-dioxin-like polychlorinated biphenyls (NDLPCBs), polybrominated diphenyl ethers (PBDEs), and polycyclic aromatic hydrocarbons (PAHs). Levels of fluoranthene (F), pyrene (P), endrin, and some PBDEs in maternal hair were significantly correlated with those in infant hair. Our findings identified common sources of exposure to OPs of distinct chemical classes.

Breastfeeding and Inborn Errors of Amino Acid and Protein Metabolism: A Spreadsheet to Calculate Optimal Intake of Human Milk and Disease-Specific Formulas.

Human milk (HM) offers important nutritional benefits. However, except for phenylketonuria (PKU), there are little data on optimal levels of consumption of HM and a special formula free of disease-related amino acids (SF-AA) in infants with inborn errors of metabolism of amino acids and proteins (IEM-AA-P). We designed a spreadsheet to calculate the amounts of SF-AA and HM required to cover amino acid, protein, and energy needs in patients with the nine main IEM-AA-P in infants aged under 6 months. Upon entering the infant's weight and the essential amino acid or intact protein requirements for the specific IEM, the spreadsheet calculates the corresponding required volume of HM based on the amino acid concentration in HM. Next, the theoretical daily fluid intake (typical range, 120-200 mL/kg/day) is entered, and the estimated daily fluid intake is calculated. The required daily volume of SF-AA is calculated as the difference between the total fluid intake value and the calculated volume of HM. The spreadsheet allows for the introduction of a range of requirements based on the patient's metabolic status, and includes the option to calculate the required volume of expressed HM, which may be necessary in certain conditions such as MMA/PA and UCD. In cases in which breastfeeding on demand is feasible, the spreadsheet determines the daily amount of SF-AA divided over 6-8 feeds, assuming that SF-AA is administered first, followed by HM as needed. Intake data calculated by the spreadsheet should be evaluated in conjunction with data from clinical and nutritional analyses, which provide a comprehensive understanding of the patient's nutritional status and help guide individualized dietary management for the specific IEM.

A phase I/II study on intracerebroventricular tralesinidase alfa in patients with Sanfilippo syndrome type B.

BackgroundSanfilippo type B is a mucopolysaccharidosis (MPS) with a major neuronopathic component characterized by heparan sulfate (HS) accumulation due to mutations in the NAGLU gene encoding alfa-N-acetyl-glucosaminidase. Enzyme replacement therapy for neuronopathic MPS requires efficient enzyme delivery throughout the brain in order to normalize HS levels, prevent brain atrophy, and potentially delay cognitive decline.MethodsIn this phase I/II open-label study, patients with MPS type IIIB (n = 22) were treated with tralesinidase alfa administered i.c.v. The patients were monitored for drug exposure; total HS and HS nonreducing end (HS-NRE) levels in both cerebrospinal fluid (CSF) and plasma; anti-drug antibody response; brain, spleen, and liver volumes as measured by MRI; and cognitive development as measured by age-equivalent (AEq) scores.ResultsIn the Part 1 dose escalation (30, 100, and 300 mg) phase, a 300 mg dose of tralesinidase alfa was necessary to achieve normalization of HS and HS-NRE levels in the CSF and plasma. In Part 2, 300 mg tralesinidase alfa sustained HS and HS-NRE normalization in the CSF and stabilized cortical gray matter volume (CGMV) over 48 weeks of treatment. Resolution of hepatomegaly and a reduction in spleen volume were observed in most patients. Significant correlations were also established between the change in cognitive AEq score and plasma drug exposure, plasma HS-NRE levels, and CGMV.ConclusionAdministration of tralesinidase alfa i.c.v. effectively normalized HS and HS-NRE levels as a prerequisite for clinical efficacy. Peripheral drug exposure data suggest a role for the glymphatic system in altering tralesinidase alfa efficacy.Trial registrationClinicaltrials.gov NCT02754076.FUNDINGBioMarin Pharmaceutical Inc. and Allievex Corporation.

Postnatal exposure to organic pollutants in maternal milk in north-western Spain.

Evaluation of postnatal exposure to organic pollutants is especially important for suckling infants during breastfeeding, a crucial perinatal growth period when organs and hormonal systems develop. We determined levels of 60 pollutants, including organochlorine pesticides (OCPs), organophosphorus pesticides (OPPs), pyrethroids (PYRs), polychlorinated biphenyls (PCBs), polycyclic aromatic hydrocarbons (PAHs), and polybrominated diphenyl ethers (PBDEs), in 81 breast milk samples from breastfeeding mothers from Santiago de Compostela (north-western Spain). For most detected organic pollutants, levels were correlated with the season of milk sampling, maternal age at delivery, and place of residence. Dietary consumption habits (eggs, molluscs, and vegetable oils) were also correlated with OCP, OPP, PCB, PBDE and PYR levels. We also assessed the risk to infant health of exposure to organic pollutants in breast milk. PAHs, OCPs, OPPs, and PYRs accounted for almost 95% of the targeted organic pollutants in the samples analysed.