Ventilatory Support, Extubation, and Cerebral Perfusion Changes in Pre-Term Neonates: A Near Infrared Spectroscopy Study.

Early extubation is considered to be beneficial for pre-term neonates. On the other hand, premature extubation can cause lung derecruitment, compromised gas exchange, and need for reintubation, which may be associated with severe brain injury caused by sudden cerebral blood flow changes. We used near infrared spectroscopy (NIRS) to investigate changes in cerebral oxygenation (rScO2) and fractional tissue oxygen extraction (+) after extubation in pre-term infants. This is a single-center retrospective study of NIRS data at extubation time of all consecutive pre-term neonates born at our institution over a 1-year period. Comparison between subgroups was performed. Nineteen patients were included; average gestational age (GA) was 29.4 weeks. No significant change was noted in rScO2 and cFTOE after extubation in the whole population. GA and germinal matrix hemorrhage (GMH)-intraventricular hemorrhage (IVH) showed a significant change in rScO2 and cFTOE after extubation. A significant increase in cFTOE was noted in patients with previous GMH-IVH (+0.040; p = 0.05). To conclude, extubation per se was not associated with significant change in cerebral oxygenation and perfusion. Patients with a diagnosed GMH-IVH showed an increase in cFTOE, suggesting perturbation in cerebral perfusion suggesting further understanding during this challenging phenomenon. Larger studies are required to corroborate our findings.

Severe cellulitis from methicillin-resistant Staphylococcus aureus (MRSA) in a couple of preterm twins: a case report.

BACKGROUND: Preterms are at risk of systemic infections as the barrier function of their immature skin is insufficient. The long period of hospitalization and the huge number of invasive procedures represent a risk factor for complications. Among the nosocomial infections of the skin, methicillin-resistant Staphylococcus aureus (MRSA) is associated with significant morbidity and mortality. We report a clinical case of cellulitis and abscess in two preterm twins caused by MRSA in a tertiary level Neonatal Intensive Care Unit (NICU). CASE PRESENTATION: Two preterm female babies developed cellulitis from MRSA within the first month of extrauterine life. The first one (BW 990 g) showed signs of clinical instability 4 days before the detection of a hyperaemic and painful mass on the thorax. The second one (BW 1240 g) showed signs of clinical instability contextually to the detection of an erythematous, oedematous and painful area in the right submandibular space. In both cases the diagnosis of cellulitis was confirmed by ultrasound. A broad spectrum, multidrug antimicrobial therapy was administered till complete resolution. CONCLUSIONS: Due to the characteristic antibiotic resistance of MRSA and the potential complications of those infections in such delicate patients, basic prevention measures still represent the key to avoid the spreading of neonatal MRSA infections in NICUs, which include hand hygiene and strict precautions, as well as screening of patients for MRSA on admission and during hospital stay, routine prophylactic topical antibiotic of patients, enhanced environmental cleaning, cohorting and isolation of positive patients, barrier precautions, avoidance of ward crowding, and, in some units, surveillance, education and decolonization of healthcare workers and visiting parents.

Disruption of Cerebellar Granular Layer as a Consequence of Germinal Matrix Intraventricular Hemorrhage in Extreme Prematurity: An Acute Direct Mechanism Too?

Cerebellum is an important brain structure for the future development of motor, cognitive, and behavioral abilities in children. This structure undergoes its most significant growth during the third trimester of pregnancy. Prematurity gathers several risk factors for cerebellar impairment and underdevelopment, and among them is ventricular dilatation following germinal matrix intraventricular hemorrhage (GMH-IVH). In this report, we illustrate how this prevalent complication associated with prematurity may induce secondary cerebellar cortical damage. A premature male born by an emergency Caesarean section displayed massive GMH-IVH at brain ultrasound performed after three hours of extrauterine life and died after 18 hours of life, despite maximized vital support. We report a postmortem histopathological specimen of the cerebellar cortex showing the disruption of the external granular layer (EGL) by hemorrhagic content flowing from the supratentorial ventricles into the fourth ventricle and cisterna magna. The expansion of the ventricular system and the presence of blood in the lateral ventricles can cause inflammation and damage to the cerebellar gyri. Experimental models have shown a thinning of the EGL, suggesting that blood surrounding the cerebellum has a harmful action. Additionally, a sudden influx of cerebrospinal fluid from the lateral ventricles may directly contribute to cerebellar damage, indicating that this may be another way in which the cerebellar gyri are impaired during acute severe GMH-IVH. This is the first histopathologically confirmed case of acute disruption in the cerebellar cortex during a GMH-IVH in a premature baby.

Optimizing haemoglobin measurements in VLBW newborns: Insights from a comparative retrospective study.

INTRODUCTION: Haemoglobin levels assessment is a crucial part of neonatal intensive care practice, the painful experience of repeated heel pricks and venepunctures blood sampling may negatively affect neonatal clinical course. To date the reliability of haemoglobin levels obtained by point-of-care testing (POCT) analysis if compared to standard blood cell count remains controversial. MATERIALS AND METHODS: Retrospective study conducted on all inborn premature infants (gestational age < 32 weeks) admitted to NICU of the IRCCS Giannina Gaslini Institute during the period May 2021-April 2023. We considered blood samplings occurred within the first 28 days of life recording the laboratory haemoglobin levels (Hblab) (reference method), the point-of-care haemoglobin levels (HbPOCT) (alternative method) and the type of puncture (arterial, venous and capillary). A Bland-Altman analysis was performed to evaluate the Hb agreement, it determines the bias (mean difference between the reference and alternative methods) and limits of agreement (LOA; lower, l-LOA; upper, u-LOA) of measures. An acceptable limit of agreement was 1 g/dl according to the existing literature. RESULTS: We considered 845 blood samplings from 189 enrolled patients. The comparison between the reference and the alternative method showed a good agreement for the capillary sampling technique with l-LOA of -0.717 (-0.776; -0.659) and u-LOA of 0.549 (0.490; 0.607), these results were not achievable with the other techniques, with LOAs over ±1 g/dl threshold (venous

The Transport of Respiratory Distress Syndrome Twin Newborns: The 27-Year-Long Experience of Gaslini Neonatal Emergency Transport Service Using Both Single and Double Ventilators.

OBJECTIVE: Twin pregnancy rates have increased in the past 30 years. We describe the experience of the Neonatal Emergency Transport Service of the Gaslini Hospital, Genoa, Italy, in the transport of twin newborns. METHODS: This was a retrospective study (1996-2021); 7,852 medical charts from the Neonatal Emergency Transport Service were reviewed. We included all twin newborns who were transported with respiratory distress syndrome in the study. We split the included patients into 2 groups (group A and group B) based on if they were simultaneously ventilated by a single ventilator or by 2 different ventilators, and then each group was split by the different types of ventilation (nasal continuous positive airway pressure or intermittent positive pressure ventilation). The pH level, base excess, O2 saturation, Pco2, body temperature, plasma glucose, and Transport Risk Index of Physiologic Stability score were recorded at departure and arrival. RESULTS: One hundred thirty-six patients were included (68 pairs of twins); group A consisted of 92 newborns and group B 44 newborns. Although some significant differences were observed (statistic), none of these had real clinical significance. CONCLUSION: Transporting respiratory distress syndrome twin newborns is challenging. Our study provided a 27-year experience in the field. Transporting twins by a single ventilator is possible, but, in our opinion, using 2 ventilators mounted on the same transport module is the best possible choice in terms of clinical performance, logistics, and cost.

Continuous Glucose Monitoring in Preterm Infants: The Role of Nutritional Management in Minimizing Glycemic Variability.

Glycemic variability (GV) is common in preterm infants. In the premature population, GV is a risk factor for morbidity and mortality. Both hypo- and hyperglycemia can impair neurodevelopment. We investigated the impact of continuous versus intermittent tube enteral feeding on GV. In our prospective observational study, 20 preterm infants with a gestational age ≤ 34 weeks at either continuous or intermittent bolus full enteral feeding. For five days, continuous glucose monitoring (CGM) was utilized, which was achieved through the subcutaneous insertion of a sensor. A total of 27,532 measurements of blood glucose were taken. The mean amplitude of glycemic excursions did not differ between the two cohorts statistically. Continuous feeding resulted in higher positive values, increasing the risk of hypo- and hyperglycemia. Subjects who were small for their gestational age had a higher standard deviation during continuous feeding (p = 0.001). Data suggest that intermittent bolus nutrition is better for glycemic control than continuous nutrition. Nutritional management optimization of preterm infants appears to be critical for long-term health. In the future, CGM may provide a better understanding of the optimal glucose targets for various clinical conditions, allowing for a more personalized approach to management.

Intubation Rate Evaluation of Inborn Versus Outborn Premature Newborns Affected by Respiratory Distress Syndrome: Impact of Neonatal Transport.

OBJECTIVE: The aim of this study was to compare the management of preterm newborns with respiratory distress both in the delivery room and during transportation. METHODS: We retrospectively evaluated the intubation rate in preterm newborns (inborn vs. outborn), gestational age (GA) < 34 weeks, admitted to the Gaslini neonatal intensive care unit, Genoa, Italy (January 2019-December 2020). RESULTS: A total of 251 newborns were included (202 inborn and 49 outborn). The intubation rate was significantly higher in outborn newborns (69.4% vs. 42.1%, P = .001) in the GA 30- to 34- week subgroup (63.2% vs 20.6%, P = .001) but not in the GA < 30-week subgroup (90.9% vs. 81.7%, P = .68). CONCLUSION: Although the medical staff members involved in neonatal transport were the same who work both in the neonatal intensive care unit and the delivery room, we found a significantly higher intubation rate in outborn newborns, probably due to the transport itself. It is fundamental to encourage in utero transportation to reduce the risk linked to invasive ventilation due to neonatal transportation.

Early and Late Onset Neonatal Sepsis: Epidemiology and Effectiveness of Empirical Antibacterial Therapy in a III Level Neonatal Intensive Care Unit.

Bloodstream infections play an important role in neonatal morbidity and mortality. In this study, we retrospectively analyzed etiology and antibiotic resistance profiles of bacteria isolated from blood or Cerebro Spinal Fluid (CSF) cultures to evaluate the appropriateness of initial empirical therapy of neonatal sepsis. METHODS: microbiological data from patients admitted to Neonatal Intensive Care Unit (NICU), from January 2005 to October 2018, were anonymously extracted from the Laboratory of Microbiology database. According to the neonatal sepsis definition for patients admitted to NICU, positive cultures obtained within the first 72 h of life were labeled as Early Onset Sepsis (EOS); and Late Onset Sepsis (LOS) for those obtained later. RESULTS: 859 bacterial strains, 846 from blood and 13 from CSF, were detected in 611 neonates. In EOS, 75 blood cultures were found: 61 yielded Gram-positives and 14 Gram-negatives. Coagulase Negative Staphylococci (CoNS) represented the majority (52% n = 39). Streptococcus agalactiae and Escherichia coli were both isolated in 8% (n = 6) of cases. 784 strains were isolated in LOS: 686 (87%) Gram-positives and 98 (13%) Gram-negatives. CoNS represented most pathogens (n = 560, 71.4%) followed by Staphylococcus aureus (n = 57, 7.3%) and Enterococcus faecalis (n = 33, 4.2%). Ampicillin/gentamicin therapy resulted effective in 15/20 (75%) of EOS isolates. Internal protocol for LOS initial empirical therapy, calling for piperacillin/tazobactam and vancomycin resulted effective in 98.5% (734/745) of LOS strains. CONCLUSIONS: knowledge of local epidemiology of resistant pathogens, both in EOS and LOS, is fundamental to set up an effective empirical therapy in NICU. Aminoglycosides were fundamental in EOS. On the other side, LOS empirical therapy with vancomycin is sustained by the observation of 38% of methicillin resistance among S. aureus and about 95% in CoNS.

External ventricular drainage for posthemorrhagic ventricular dilatation in preterm infants: insights on efficacy and failure.

OBJECTIVE: The objective of this study was to describe the clinical and neuroradiological characteristics of a cohort of preterm infants who had undergone external ventricular drain insertion as a temporary measure to treat posthemorrhagic ventricular dilatation. In addition, the authors investigated the factors predicting permanent shunt dependency. METHODS: The authors retrospectively reviewed the medical records of a cohort of preterm infants who had undergone external ventricular drain insertion at Gaslini Children's Hospital (Genoa, Italy) between March 2012 and February 2018. They also analyzed clinical characteristics and magnetic resonance imaging data, including diffusion- and susceptibility-weighted imaging studies, which were obtained before both catheter insertion and removal. RESULTS: Twenty-eight infants were included in the study. The mean gestational age was 28.2 ± 2.7 weeks, and the mean birth weight was 1209 ± 476 g. A permanent ventriculoperitoneal shunt was inserted in 15/28 (53.6%) infants because of the failure of external ventricular drainage as a temporary treatment option. Compared with the shunt-free group, the shunt-dependent group had a significantly lower gestational age (29.3 ± 2.3 vs 27.2 ± 2.7 weeks, p = 0.035) and tended toward a lower birth weight (p = 0.056). None of the clinical and neuroradiological characteristics significantly differed between the shunt-free and shunt-dependent groups at the time of catheter insertion. As expected, ventricular parameters as well as the intraventricular extension of intracerebral hemorrhage, as assessed using the intraventricular hemorrhage score, were reportedly higher in the shunt-dependent group than in the shunt-free group before catheter removal. CONCLUSIONS: External ventricular drainage is a reliable first-line treatment for posthemorrhagic hydrocephalus. However, predicting its efficacy as a unique treatment remains challenging. A lower gestational age is associated with a higher risk of posthemorrhagic hydrocephalus progression, suggesting that the more undeveloped the mechanisms for the clearance of blood degradation products, the greater the risk of requiring permanent cerebrospinal fluid diversion, although sophisticated MRI investigations are currently unable to corroborate this hypothesis.

Neonatal Air Medical Transportation Practices in Italy: A Nationwide Survey.

The present article shows the current neonatal air transport organization and activity in Italy. The results were obtained on the basis of a recent 2019 survey (year of activity 2018) performed by the Neonatal Transport Study Group of the Italian Society of Neonatology. The total number of newborn transports during the year 2018 was 6,464. The air-suitable transports were 512 of 5,852 (8.74%), and among them, 101 of 512 (19.72%) were performed by helicopter and 34 by airplane. Besides the availability of air transport, the interfacility distance, weather and traffic conditions, and rural mountainous roads were the main factors in determining the vehicle choice. Neonatal air transport in Italy is not homogeneously distributed and needs organizational corrections. The high density of neonatal emergency transport services on the national territory indicates the need to overcome the limits imposed by regional administrative borders, thus expanding the geographic area of competence.

Nosological Differences in the Nature of Punctate White Matter Lesions in Preterm Infants.

Background: The pathogenesis of punctuate white matter lesions (PWMLs), a mild form of white matter damage observed in preterm infants, is still a matter of debate. Susceptibility-weighted imaging (SWI) allows to differentiate PWMLs based on the presence (SWI+) or absence (SWI-) of hemosiderin, but little is known about the significance of this distinction. This retrospective study aimed to compare neuroradiological and clinical characteristics of SWI+ and SWI- PWMLs. Materials and Methods: MR images of all VLBW infants scanned consecutively at term-equivalent age between April 2012 and May 2018 were retrospectively reviewed, and infants with PWMLs defined as small areas of high T1 and/or low T2 signal in the periventricular white matter were selected and included in the study. Each lesion was analyzed separately and characterized by localization, organization pattern, and distance from the lateral ventricle. Clinical data were retrieved from the department database. Results: A total of 517 PWMLs were registered in 81 patients, with 93 lesions (18%) visible on SWI (SWI+), revealing the presence of hemosiderin deposits. On univariate analysis, compared to SWI- PWML, SWI+ lesions were closer to the ventricle wall, more frequently organized in linear pattern and associated with lower birth weight, lower gestational age, lower admission temperature, need for intubation, bronchopulmonary dysplasia, retinopathy of prematurity, and presence of GMH-IVH. On multivariate analysis, closer distance to the ventricle wall on axial scan and lower birth weight were associated with visibility of PMWLs on SWI (p = 0.003 and p = 0.0001, respectively). Conclusions: Our results suggest a nosological difference between SWI+ and SWI- PWMLs. Other prospective studies are warranted to corroborate these observations.

Neonatal Hypoglycemia and Brain Vulnerability.

Neonatal hypoglycemia is a common condition. A transient reduction in blood glucose values is part of a transitional metabolic adaptation following birth, which resolves within the first 48 to 72 h of life. In addition, several factors may interfere with glucose homeostasis, especially in case of limited metabolic stores or increased energy expenditure. Although the effect of mild transient asymptomatic hypoglycemia on brain development remains unclear, a correlation between severe and prolonged hypoglycemia and cerebral damage has been proven. A selective vulnerability of some brain regions to hypoglycemia including the second and the third superficial layers of the cerebral cortex, the dentate gyrus, the subiculum, the CA1 regions in the hippocampus, and the caudate-putamen nuclei has been observed. Several mechanisms contribute to neuronal damage during hypoglycemia. Neuronal depolarization induced by hypoglycemia leads to an elevated release of glutamate and aspartate, thus promoting excitotoxicity, and to an increased release of zinc to the extracellular space, causing the extensive activation of poly ADP-ribose polymerase-1 which promotes neuronal death. In this review we discuss the cerebral glucose homeostasis, the mechanisms of brain injury following neonatal hypoglycemia and the possible treatment strategies to reduce its occurrence.

New Formula for Nasal Endotracheal Intubation in Extremely Low-Birth Weight Infants in the Emergency Transport Setting: The "Genoa Formula".

OBJECTIVE: The purpose of this study was to find a predictive equation for estimating the optimal nasal endotracheal tube insertion depth in extremely low-birth weight infants (ELBWs) requiring invasive ventilation in the critical care interfacility transport setting. METHODS: We retrospectively calculated the optimal tube insertion depth in a cohort of neonates ≤ 1,000 g born at our neonatal intensive care unit and nasally intubated within the first 24 hours of life from January 2019 to May 2020. RESULTS: A total of 75 ELBW infants were included, with a median gestational age of 26.6 weeks (range, 22.1-32.6 weeks) and a median birth weight of 780 g (range, 410-990 g). The linear regression of the estimated optimal endotracheal tube insertion depth showed a good correlation when plotted against weight (R2 = 0.491); thus, a new weight-based formula was obtained. CONCLUSION: The proposed weight-based formula (the "Genoa formula") may help in predicting optimal insertion depths for nasal intubation in ELBW neonates, especially when a prompt radiologic confirmation of the tube position is not available, as during neonatal critical care transport.

Intravenous paracetamol in comparison with ibuprofen for the treatment of patent ductus arteriosus in preterm infants: a randomized controlled trial.

Our aim was to assess the efficacy and safety of intravenous (i.v.) paracetamol vs. i.v. ibuprofen for the treatment of hemodynamically significant patent ductus arteriosus (hsPDA) in preterm infants. This is a multicenter randomized controlled study. Infants with a gestational age of 25+0-31+6 weeks were randomized to receive i.v. paracetamol (15 mg/kg/6 h for 3 days) or i.v. ibuprofen (10-5-5 mg/kg/day). The primary outcome was the closure rate of hsPDA after the first treatment course with paracetamol or ibuprofen. Secondary outcomes included the constriction rate of hsPDA, the re-opening rate, and the need for surgical closure. Fifty-two and 49 infants received paracetamol or ibuprofen, respectively. Paracetamol was less effective in closing hsPDA than ibuprofen (52 vs. 78%; P = 0.026), but the constriction rate of the ductus was similar (81 vs. 90%; P = 0.202), as confirmed by logistic regression analysis. The re-opening rate, the need for surgical closure, and the occurrence of adverse effects were also similar.Conclusions: Intravenous paracetamol was less effective in closing hsPDA than ibuprofen, but due to a similar constriction effect, its use was associated with the same hsPDA outcome. These results can support the use of i.v. paracetamol as a first-choice drug for the treatment of hsPDA.Trial registration: Clinicaltrials.gov : NCT02422966, Date of registration: 04/09/2015; EudraCT no: 2013-003883-30. What is Known: • The successful closure of patent ductus arteriosus with oral paracetamol has been recently reported in several preterm infants, but only one randomized controlled study investigated the efficacy of intravenous paracetamol. What is New: • Intravenous paracetamol is less effective in closing hsPDA than ibuprofen, but have a similar constriction effect. • These results can support the use of i.v. paracetamol as a first-choice drug for the treatment of hsPDA.

Early Pain Exposure Influences Functional Brain Connectivity in Very Preterm Neonates.

BACKGROUND: Early exposure to nociceptive events may cause brain structural alterations in preterm neonates, with long-lasting consequences on neurodevelopmental outcome. Little is known on the extent to which early pain may affect brain connectivity. We aim to evaluate brain functional connectivity changes in preterm neonate that underwent multiple invasive procedures during the postnatal period, and to correlate them with the neurodevelopmental outcome at 24 months. METHODS: In this prospective case-control study, we collected information about exposure to painful events during the early postnatal period and resting-state BOLD-fMRI data at term equivalent age from two groups of preterm neonate: 33 subjected to painful procedures during the neonatal intensive care (mean gestational age 27.9 ± 1.8 weeks) and 13 who did not require invasive procedures (average gestational age 31.2 ± 2.1 weeks). A data-driven principal-component-based multivariate pattern analysis (MVPA) was used to investigate the effect of early pain exposure on brain functional connectivity, and the relationship between connectivity changes and neurodevelopmental outcome at 24 months, assessed with Griffiths, Developmental Scale-Revised: 0-2. RESULTS: Early pain was associated with decreased functional connectivity between thalami and bilateral somatosensory cortex, and between the right insular cortex and ipsilateral amygdala and hippocampal regions, with a more evident effect in preterm neonate undergoing more invasive procedures. Functional connectivity of the right thalamocortical pathway was related to neuromotor outcome at 24 months (P = 0.003). CONCLUSION: Early exposure to pain is associated with abnormal functional connectivity of developing networks involved in the modulation of noxious stimuli in preterm neonate, contributing to the neurodevelopmental consequence of preterm birth.

Rethinking the neonatal transport ground ambulance.

OBJECTIVES: This article describes the detailed project aimed to realize a dedicated ground ambulance for neonatal emergency transport service (NETS). To date, the European Community rules specify requirements for the design, testing, performance, and equipping of road ambulance used for transport and care of adult injured or ill patients, completely ignoring neonatal transport. METHODS: The project consisted of electric and gas supply planning, interior design taking into account ergonomic and occupant protection principles, both during travel and during medical care performances. RESULTS: A detailed project is presented. Main differences between European Type C ambulance and the new proposed Type D neonatal ground ambulance are the presence on board of air compressed cylinder, iNO cylinders and delivery system, phototheraphy, shock adsorbing stretcher support, cooling device, patient's placenta (refrigeration box), and transcutaneous gas analyzer. CONCLUSION: The European Community rules specify requirements for road ambulance used for transport and care of adult injured or ill patients, completely ignoring neonatal transport. This study describes the detailed project aimed to realize a dedicated ground ambulance for neonatal emergency transport service. This study demonstrated that it is not possible simply to adapt the currently dedicated ambulance for mobile intensive care and resuscitation services (actual type C European Community) in a modern dedicated NETS ambulance; it is of paramount importance suggesting to European Community to introduce a further ambulance type, to be identified type D, strictly reserved to neonatal transport activities.

Group B Streptococcus late onset sepsis in very low birth weight newborns: 10 years experience.

PURPOSE: The incidence of late-onset neonatal infection (LONS) group B streptococcus (GBS) in very low birth weight (VLBW) is still matter of debate. In the present 10-years retrospective study we investigated the epidemiology of GBS LONS in VLBW neonates. MATERIALS AND METHODS: From January 2006 to July 2015 we conducted a retrospective study in all preterm infants admitted at our third level referral center for neonatal intensive care (NICU). From our database we were able to retrieve all cases of bloodstream infections/meningitis GBS positive. Perinatal data were also collected Results: On a total of 13 747 infants 975 (7%) were VLBW and in seven cases of GBS LONS was observed with a incidence of 7.2/1000 live births. CONCLUSIONS: The higher rate of LONS GBS in our series offer additional support to further investigations in wider population in order to better define GBS screening and therapeutic management in a such specific population.

Long-chain polyunsaturated fatty acids profile in plasma phospholipids of hyperphenylalaninemic children on unrestricted diet.

INTRODUCTION: The aim of the present study was to examine whether hyperphenylalaninemic children on unrestricted diet (MHP) may exhibit a different LCPUFA profile from PKU or healthy children in plasma phospholipids. PATIENTS AND METHODS: Forty-five MHP children (age 9-14 years) were age and sex matched with 45 PKU and 45 healthy children. Fatty acids were determined and expressed as % of total fatty acids. RESULTS: MHP children showed docosahexaenoic acid (DHA) levels higher than PKU children (mean difference, 0.2%; 95% confidence interval, 0.02%-0.38%), although difference was not significant after correction for multiple comparisons, and lower levels than healthy children (-0.8%; -1.01% to -0.59%). Concentration of n-3 PUFA was higher in MHP than PKU children (0.6%; 0.4% to 0.8%), CONCLUSIONS: The results suggest that low DHA levels in plasma phospholipids not only are evident in PKU but also may occur in MHP children, who are on unrestricted diet, as compared to healthy children.