Emotional and behavioural outcomes at 8 years of age in preterm-born children: A longitudinal study.

AIM: To evaluate the predictive value of perinatal factors and neurodevelopmental evaluation in the emotional and behavioural outcomes in preterm-born children at 7-9 years of age. METHODS: We evaluated the Strengths and Difficulties Questionnaire (SDQ) extended score at 8.2 ± 0.2 years, among 70 preterm-born children (32 early and 38 moderately preterms) with a previous Bayley-III neurodevelopmental evaluation. RESULTS: Early compared to moderately preterms had a higher total SDQ (12 compared to 8, p = 0.031), and emotional symptoms score (4 compared to 3, p = 0.022); no significant differences were recorded in abnormal/borderline-scored children between the two groups. The total SDQ and emotional symptoms scores were significantly correlated with gestational age, birth weight, perinatal factors and the cognitive and motor Bayley-III scores. Early prematurity was associated with the total SDQ score (beta 2.09, 95% CI 1.32, 3.87), and the score of emotional symptoms (beta 1.70, 95% CI 1.38, 2.19), after adjusting for sex, neonatal sepsis and the existence of an older sibling. CONCLUSION: Prematurity, birth weight, perinatal factors and the cognitive and motor Bayley-III scores were significantly associated with the total SDQ and the emotional symptoms score, in preterm-born children.

Osteomyelitis and Thrombosis in a Newborn with Group A Streptococcus Infection.

Neonatal osteomyelitis (OM), although exceptionally rare, has been linked to detrimental sequel, as diagnosis in the early stages is challenging and any delay in treatment can lead to disturbance in skeletal growth. In pediatric OM the most commonly grown bacteria is Staphylococcus aureus followed by group A Streptococcus (GAS). Notwithstanding, sepsis-induced coagulopathy is a well-known entity in children and adults, still sepsis-associated thrombosis is sparsely observed. we present a case of a newborn with GAS associated OM and thrombosis. A term neonate on the 11th day of life was referred to our NICU due to right (R) lower limb edema, cyanosis and core temperature up to 39 °C. Late onset sepsis was suspected and started on vancomycin and amikacin. A colour Doppler scan showed thrombosis of the R common femoral vein. The neonate started on iv unfractionated heparin. Ampicillin was added given positive for GAS blood culture. An MRI on the 5th day of admission, showed evidence of thrombosis resolution. On the 14th day of admission, a bone Tc99 scan showed evidence of OM of R femur. Antibiotic treatment switched to amoxicillin per os. The management was restricted to anticoagulant therapy with low molecular weight heparin for 3 months and antibiotic therapy for 6 months without surgery intervention and the patient recovered and discharged at 42 days of age. Early diagnosis and treatment of neonatal osteomyelitis can prevent bone destruction. Sepsis-associated thrombosis is barely observed during osteomyelitis, yet it should be considered as an emerged case requiring prompt treatment.

Urine neutrophil gelatinase-associated lipocalin to predict acute kidney injury in preterm neonates. A pilot study.

BACKGROUND: The efficacy of urine neutrophil gelatinase-associated lipocalin (uNGAL) as an early acute kidney injury (AKI) biomarker in preterm neonates was evaluated. METHODS: Thirty-five preterm neonates were prospectively evaluated for serum creatinine (sCre)-documented AKI during the first 14 days of life. Urine samples were collected daily throughout the study period. Of the neonates evaluated, we analyzed 11 who developed AKI (cases) and an equal number of neonates without AKI (controls) matched for gestational and postnatal age (case-control study). uNGAL was measured on the day of AKI occurrence (day 0) and on the 2 days preceding the event (day -1 and day -2, respectively) using an enzyme-linked immunosorbent assay. RESULTS: Cases had significantly higher sCre levels than controls on day 0 (1.21 ± 0.48 vs. 0.83 ± 0.16 mg/dL, p =0.031) but not on days -1 and -2. Similarly, uNGAL levels (ng/mL) were significantly higher in cases than in controls only on day 0 (19.1 ± 3.5 vs. 13.3 ± 7.3, p=0.017) and not on days -1 (18.8 ± 3.4 vs. 16.3 ± 5.9, p=0.118) and -2 (19.3 ± 1.8 vs. 19.4 ± 0.8, p =0.979). The receiver operating characteristic curve analysis showed no significant ability of uNGAL to predict AKI on days -2 and -1. CONCLUSIONS: In this pilot study in preterm neonates, although uNGAL detected sCre-based AKI upon its documentation, it failed to predict its development 1-2 days earlier.

Mydriasis for retinopathy of prematurity screening in Europe: A cross-sectional online survey.

PURPOSE: To compile real-time data on the preferred mydriasis practice patterns for retinopathy of prematurity (ROP) screening in Europe. METHODS: A cross-sectional online survey was conducted from December 2022 to January 2023, using a self-report online questionnaire which was distributed via email to the members of the European Pediatric Ophthalmological Society and the Greek National ROP Task Force. A six-week period of recruitment was determined, and a reminder email was sent after two weeks. Descriptive statistics were used to explore the data, which was summarized with frequencies and percentages. RESULTS: Sixty-six responses were recorded (response rate: 29.5%), representing practices in 55 Neonatal Intensive Care Units from 21 European countries. In 94.5%, the applied mydriatic regimen consists of phenylephrine with at least one muscarinic antagonist, either tropicamide or cyclopentolate. The concentration of phenylephrine ranges from 0.5% to 5%, of tropicamide from 0.25% to 1%, and of cyclopentolate from 0.2% to 1%. The most commonly used regimen (43.6%) contains phenylephrine 2.5% and tropicamide 0.5%, administered either combined or separately. About 54.5% of the reported mydriatic solutions are non-commercial, in-house preparations. Systemic adverse events, including oxygen desaturation, bradycardia and cardiopulmonary arrest were reported in 14.5%. CONCLUSION: There is considerable heterogeneity in the applied mydriatic regimens for ROP screening in Europe, reflecting the absence of universal guidelines. The wide use of in-house preparations underlines the gap in the pharmaceutical industry. Concern should be raised against the wide use of undiluted commercial drugs, that reach adult dose, in the fragile population of preterm infants.

The Effect of Breastfeeding on Food Allergies in Newborns and Infants.

Breastfeeding is the preferred method of infant feeding and its establishment is one of the primary goals for the infant. Allergic diseases are common in childhood, with increased morbidity. Food allergies are also associated with a strong negative impact on health-related quality of life and is a major public health problem. In addition, maternal exclusion of common allergens during pregnancy and/or lactation suggests that supplementation with regular cow's milk formula during the first week of life should be avoided. Breast milk contains many active immune factors, such as cytokines, inflammatory mediators, signaling molecules and soluble receptors, which may also reduce the risk of allergic disease. The prophylactic effects of breastfeeding have been the subject of many studies, some with weak evidence. In this narrative review, we aim to provide an up-to-date account of the effects of prophylactic breastfeeding on food allergy and other common allergies in infants and children up to 5 years of age. Colostrum in particular has been shown to be prophylactic against food allergy. The American Academy of Pediatrics cautions that the relationship between duration of breastfeeding and incidence of food allergy in early childhood is unclear. The protective role of breastfeeding has a positive effect on allergy prevention, which is opposed by the early introduction of solid foods, but larger studies are needed to confirm the evidence. There is evidence that breastfeeding is effective in providing partial protection to infants.

Is thrombocytopenia and postnatal weight gain associated with treatment-requiring retinopathy of prematurity? A matched case-control study.

PURPOSE: The purpose of the study was to investigate the association of platelet parameters and postnatal weight gain with treatment-requiring ROP (TR-ROP). METHODS: In this retrospective matched case-control study, infants with TR-ROP were individually matched, according to gestational age and birth weight, with one or two untreated infants who developed no or spontaneously regressed ROP. Longitudinal data on platelet count (PLT), mean platelet volume (MPV), daily weight and platelet transfusions were collected. Platelet mass index (PMI) and weight standard deviation score (WSDS) were also calculated. Conditional logistic regression analysis was performed to adjust for matching. RESULTS: Fourteen cases, presenting type I ROP, and 25 matched controls were included. The odds of developing TR-ROP decreased as PLT increased during 31st week of postmenstrual age (PMA) or during 1st and 2nd week of postnatal age (PNA). The odds of developing TR-ROP were 16.7 times higher in infants receiving at least one platelet transfusion compared with those who were not transfused. The odds of developing TR-ROP increased by 31.2% as the mean volume of platelet transfusion per infant increased by 1 ml. The odds of developing TR-ROP decreased as PMI increased during 1st week PNA, and as weight and WSDS increased during 4th -6th week PNA. Analysis of MPV, number of thrombopenic episodes per infant, number of platelet transfusions per infant and days with WSDS < -2 showed no association with TR-ROP. CONCLUSION: To our knowledge, this is the first study ascertaining an association of platelet transfusions with type I ROP. Prospective cohort studies are required to confirm our findings.

Sepsis-induced coagulopathy in preterm neonates with Gram-positive sepsis presents with hypercoagulation and reduced platelet activation compared with healthy preterm neonates.

Background: Neonatal sepsis is frequently accompanied by coagulopathy and thrombocytopenia attributed to the cross-link between inflammation and coagulation. However, sepsis-induced coagulopathy and platelet function in septic preterm neonates remain to be elucidated. In addition, there is no robust evidence for a causal relationship between thrombocytopenia and bleeding in preterm neonates with sepsis. Objective: This single-center prospective cohort study aimed to assess sepsis-induced coagulopathy and platelet function in preterm neonates during sepsis. Methods: We included 25 preterm neonates with Gram-positive sepsis born at gestational age 24 + 1 to 34 + 3 and studied in comparison to 30 healthy counterparts. Coagulation was assessed using conventional coagulation tests (CCTs) and rotational thromboelastometry (ROTEM). Platelet function was evaluated by flow cytometry. The study was conducted at 3-time points, at 1st, at 2nd to 3rd, and at 5th to 7th day of sepsis, respectively. Results: Compared with healthy controls, neonates with Gram-positive sepsis present in ROTEM a hypercoagulable state; a higher maximum clot firmness (MCF) and higher amplitudes of intrinsic rotational thromboelastometry (INTEM) (INTEM MCF: median, 71; P .004 and INTEM A10: median, 67; P .005, respectively), extrinsic rotational thromboelastometry (EXTEM) (EXTEM MCF: median, 70; P .02 and EXTEM A10: median, 67; P .02, respectively), and rotational thromboelastometry assay for fibrin formation (FIBTEM) (FIBTEM MCF: median, 25; P < .001 and FIBTEM A10: median, 23; P .002, respectively). Conversely, CCTs exhibited hypocoagulation. Thrombocytopenia in preterm neonates with Gram-positive sepsis is not associated with an increased bleeding risk. In Gram-positive sepsis, platelets display increased glycoprotein (GP) surface receptors' expression (GPIb: median, 2.8; P .03, GPIIb: median, 3.1; P .004, and GPIIIa: median, 3.9; P .008, respectively) and reduced activation (P-selectin: median, 1; P < .001). A higher expression of platelets GP and improved degranulation capacity were recorded in patients in higher gestational age groups of >32 weeks of gestation. Platelet GPIb expression is age-dependent in healthy neonates. Conclusion: Neonatal Gram-positive sepsis is characterized by a progressive hypercoagulation along with increased GP expression, reduced platelet activation, and thrombocytopenia without bleeding. Platelet GP expression and degranulation capacity are age-dependent among neonates with sepsis. Platelet GP expression is age-dependent among healthy counterparts.

Serum and urine acute kidney injury biomarkers in asphyxiated neonates.

BACKGROUND: We evaluated serum (s) cystatin C (CysC) and neutrophil gelatinase-associated lipocalin (NGAL) and urine (u) CysC, NGAL and kidney injury molecule-1 (KIM-1) as markers of acute kidney injury (AKI) in asphyxiated neonates. METHODS: AKI biomarkers were measured in 13 asphyxiated neonates born at ≥ 36 weeks gestational age (eight with AKI and five without AKI) and 22 controls. AKI was defined as serum creatinine ≥ 1.5 mg/dl for >24 h or rising values >0.3 mg/dl from day of life (DOL) 1. Biomarkers were measured on DOL 1, 3, and 10. RESULTS: Asphyxiated neonates had significantly higher sCysC on DOL 1 as well as sNGAL and uCysC and uNGAL (standardized to urine creatinine and absolute values) than controls at all time points. Compared to controls, significantly higher sNGAL, uCysC, and uNGAL values were observed in the asphyxia-AKI and asphyxia-no AKI subgroups. Regarding uKIM-1, only the absolute values were significantly higher in asphyxiated neonates (DOL 10). sNGAL, uCyst, and uNGAL had a significant diagnostic performance as predictors AKI on DOL 1. CONCLUSIONS: sNGAL, uCysC, and uNGAL are sensitive, early AKI biomarkers, increasing significantly in asphyxiated neonates even in those not fulfilling AKI criteria. Their measurement on DOL 1 is predictive of post-asphyxia-AKI.

Is there an association between necrotizing enterocolitis in premature neonates and functional gastrointestinal disorders later in childhood?

BACKGROUND: Stressful events during infancy may predispose to the development of functional gastrointestinal disorders (FGIDs) in childhood. AIMS: To evaluate the association of necrotizing enterocolitis (NEC) with childhood FGIDs. METHODS: We conducted a study, comparing 29 children of eight to ten years with a history of NEC with 58 children with no history of NEC. Subjects were assessed for FGIDs, based on Rome-III criteria. RESULTS: Among 29 subjects with NEC, 17 had surgical and 12 conservative NEC. Subjects with surgically, or conservatively managed NEC developed FGIDs at a significantly higher proportion, as compared to children with no history of NEC, later in childhood (41%, 33%, and 13% respectively, p = 0.033). Functional constipation was the most frequently identified disorder (35%, 33%, and 7% respectively). A significant association was detected between FGIDs and the history of perinatal stress (p = 0.049), NEC (p = 0.011), and the surgical management of NEC (p = 0.015). CONCLUSIONS: Our study suggests that there is a potential association between NEC and FGIDs later in childhood with functional constipation being the most frequently identified disorder.

Efficacy and safety of mydriatic microdrops for retinopathy of prematurity screening: an external pilot crossover randomized controlled trial.

OBJECTIVE: To study the efficacy and safety of mydriatic microdrops compared with standard drops for retinopathy of prematurity (ROP) screening. STUDY DESIGN: Preterm infants undergoing ROP screening received microdrops and standard drops of phenylephrine 1.67% and tropicamide 0.33% in a random allocation sequence at two consecutive weekly examinations. Primary outcome was pupil diameter measured by two masked observers at 45 (T45) and 90 (T90) minutes after instillation. RESULTS: Twenty-five infants were randomized. No differences observed in mean pupil diameter after either administration technique at all time points (T45 Mean Difference: -0.14; 95% Confidence Interval: -0.38, 0.09; p = 0.23). Heart rate values at T120 were lower after microdrop instillation (p = 0.046). Otherwise, adverse events did not differ after either administration technique. CONCLUSION: This pilot study provides evidence of microdrops mydriasis efficacy, while justifying a full-scale trial to confirm their non-inferiority compared with standard drops and provide more data about safety. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04623684.

Avoiding use of lid speculum and indentation reduced infantile stress during retinopathy of prematurity examinations.

PURPOSE: To study the safety and efficacy of indirect ophthalmoscopy with (Sp) or without (speculum free, SpF) the use of lid speculum and scleral indentation for retinopathy of prematurity (ROP) screening. METHODS: In this crossover randomized controlled trial, preterm infants received either the Sp on their first and the SpF technique on their second examination a week later or vice versa. Video recordings of the infants' reactions were assessed by two observers, using Premature Infant Pain Profile-Revised score and the crying score of the Bernese Pain Scale for Neonates. Fundoscopy adequacy, its duration and adverse events within the first 24 hr postscreening were also recorded. RESULTS: Thirty-seven infants with median (interquartile range) gestational age of 28.7 (28.0, 30.2) weeks and mean (standard deviation, SD) birth weight 1225 (377) grams were enrolled. The mydriasis-induced stress was similar between the Sp and SpF exam (mean difference [MD]: 0.78, 95% confidence interval [CI]: -0.83, 2.38; p = 0.33). The stress induced by fundoscopy (MD: 4.98, 95% CI: 3.58, 6.37; p < 0.001) and examination overall (MD: 2.32, 95% CI: 0.96, 3.67; p = 0.001) were higher in the Sp than in the SpF exam, and so was the crying score during fundoscopy (MD: 1.31, 95% CI: 1.06, 1.56; p < 0.001). Adverse events in the two groups were similar (p = 0.13). Fundoscopy was adequate in identifying the absence of treatment-requiring ROP in all cases, and lasted longer in the Sp than in the SpF exam (p < 0.001). CONCLUSION: Our study suggests that the use of speculum and indentation should be reserved for the few cases where fundus visualization is insufficient for excluding the presence of severe ROP.

Efficacy and safety of Mydriatic Microdrops for Retinopathy Of Prematurity Screening (MyMiROPS): study protocol for a non-inferiority crossover randomized controlled trial.

BACKGROUND: Retinopathy of prematurity (ROP) eye examination screening presupposes adequate mydriasis for an informative fundoscopy of preterm infants at risk, on a weekly basis. Systemic absorption of the instilled mydriatic regimens has been associated with various adverse events in this fragile population. This report aims to present the fully developed protocol of a full-scale trial for testing the hypothesis that the reduced mydriatic drop volume achieves adequate mydriasis while minimizing systemic adverse events. METHODS: A non-inferiority crossover randomized controlled trial will be performed to study the efficacy and safety of combined phenylephrine 1.67% and tropicamide 0.33% microdrops compared with standard drops in a total of 93 preterm infants requiring ROP screening. Primary outcome will be the pupil diameter at 45 (T45) min after instillation. Pupil diameter at T90 and T120 will constitute secondary efficacy endpoints. Mixed-effects linear regression models will be developed, and the 95% confidence interval approach will be used for assessing non-inferiority. Whole blood samples will be analyzed using hydrophilic liquid chromatography-tandem mass spectrometry method (HILIC-MS/MS), for gathering pharmacokinetic (PK) data on the instilled phenylephrine, at nine specific time points within 3 h from mydriasis. Pooled PK data will be used due to ethical restrictions on having a full PK profile per infant. Heart rate, oxygen saturation, blood pressure measurements, and 48-h adverse events will also be recorded. DISCUSSION: This protocol is designed for a study powered to assess non-inferiority of microdrops compared with standard dilating drops. If our hypothesis is confirmed, microdrops may become a useful tool in ROP screening. TRIAL REGISTRATION: ClinicalTrials.gov NCT05043077 . Registered on 2 September 2021.

The Mediterranean diet adherence by pregnant women delivering prematurely: association with size at birth and complications of prematurity.

Background: The Mediterranean diet (MD) is associated with decreased risk of metabolic syndrome and gestational diabetes due to the anti-inflammatory and antioxidative properties of its components. The aim was to investigate the potential association of MD adherence (MDA) during pregnancy by mothers delivering prematurely, with intrauterine growth as expressed by neonates' anthropometry at birth and complications of prematurity. Participants and methods: This is a single-center, prospective, observational cohort study of 82 women who delivered preterm singletons at post conceptional age (PCA) ≤ 34 weeks and their live-born neonates. Maternal and neonatal demographic and clinical data were recorded. All mothers filled in a food frequency questionnaire, and the MDA score was calculated. Based on 50th centile of MD score, participants were classified into high-MDA and low-MDA groups. Results: The low-MDA mothers had significantly higher pregestational BMI and rates of overweight/obesity (odd ratios (OR) 3.5) and gestational hypertension/preeclampsia (OR 3.8). Neonates in the low-MDA group had significantly higher incidence of intrauterine growth restriction (IUGR) (OR 3.3) and lower z-scores of birth weight and BMI. Regarding prematurity-related complications, the low MDA-group was more likely to develop necrotizing enterocolitis, bronchopulmonary dysplasia, and retinopathy of prematurity (OR 3.2, 1.3, and 1.6, respectively), while they were less likely to develop respiratory distress syndrome (OR 0.49), although the differences were not statistically significant. However, adjustment for confounders revealed MDA as a significant independent predictor of hypertension/preeclampsia, IUGR, birth weight z-score, necrotizing enterocolitis, and bronchopulmonary dysplasia. Conclusions: High MDA during pregnancy may favorably affect intrauterine growth and certain acute and chronic complications of prematurity as well as maternal hypertension/preeclampsia.

Modifications of Own Mothers' Milk Fortification Protocol Affect Early Plasma IGF-I and Ghrelin Levels in Preterm Infants. A Randomized Clinical Trial.

The aim was to investigate the effect of two own mother's milk (OMM) fortification protocols on (a) IGF-I and ghrelin plasma levels at 35 post-conceptional weeks (PCW, T2) and whether this effect is maintained after elimination of the differences in OMM fortification, and (b) growth until 12 months corrected age. Forty-eight OMM-fed preterm infants (GA 24-32 weeks) were randomly allocated to the fixed-fortification (FF) group (n = 23) and the protein-targeting fortification (PTF) group (n = 25) targeting the recommended daily protein intake (PI). Plasma IGF-I and ghrelin were assessed at 35 (T2) and 40 (T3) PCW while growth was longitudinally assessed until 12 months corrected age. PTF group had lower IGF-I and higher ghrelin than FF group at T2, while receiving lower daily protein and energy amounts. PI correlated positively to T2-IGF-I and inversely to T3-ghrelin while energy intake (EI) correlated inversely to T2- and T3-ghrelin. Group and PI were independent predictors of adjusted T2-IGF-I, while group and EI were predictors of adjusted and T2-ghrelin. Growth parameter z-scores were comparable between groups up to 12 months corrected age. Modifications of OMM fortification have a transient effect on early plasma IGF-I and ghrelin levels in preterm infants in a way consistent with the previously recognized protein-energy/endocrine balance, indicating a potential programming effect.

Clara cell secretory protein (CC16) as a peripheral blood biomarker of lung injury in ventilated preterm neonates.

The aim of this study was to assess the serum concentrations of Clara cell secretory protein (CC16) in association with acute and chronic lung injury in mechanically ventilated preterm neonates. Thirty-five preterm neonates (gestational age [GA]

Use of Tigecycline in Pediatric Patients With Infections Predominantly Due to Extensively Drug-Resistant Gram-Negative Bacteria.

BACKGROUND.: Emergence of extensively drug-resistant (XDR) bacteria has forced clinicians to use off-label antimicrobial agents such as tigecycline. We present our experience on salvage use of tigecycline for the treatment of infections caused by XDR Gram-negative bacteria in critically ill children and review published cases. METHODS.: We conducted a retrospective chart review in pediatric departments of a tertiary level hospital from January 2009 to May 2014. Patients were identified using pharmacy database. For the literature review, relevant articles were identified from PubMed. RESULTS.: In our case series, 13 children (7 males) with a median age of 8 years (range, 2.5 months-14 years) received tigecycline for ≥2 days as treatment for healthcare-associated infections including 5 bacteremias, 6 lower respiratory tract infections, and 3 other infections. Isolated pathogens were XDR Gram-negative bacteria except 1. A loading dose (range, 1.8-6.5 mg/kg) was given in all except 2 cases. Maintenance dose was given at 1-3.2 mg/kg q12 h. Other antimicrobials including colistin and aminoglycosides (85% and 62%, respectively) were coadministered to all patients. No serious adverse events were detected in these very ill children. Twenty cases of children treated with tigecycline were previously published, mostly for multidrug-resistant/XDR bacteria. An episode of acute pancreatitis and neutrophil engraftment delay in 2 cases were reported during tigecycline treatment. Analyzing reported and all our cases together, mortality in bloodstream infections was 86%, whereas in nonbacteremic cases it was 24% (P = .009). CONCLUSIONS.: Tigecycline, given at the range of administered doses as salvage therapy and in combination with other antimicrobial agents, seemed to be well tolerated in a series of mainly critically ill pediatric patients and demonstrated relatively good clinical response in nonbacteremic patients.

Urine metabolomics in neonates with late-onset sepsis in a case-control study.

Although late-onset sepsis (LOS) is a major cause of neonatal morbidity and mortality, biomarkers evaluated in LOS lack high diagnostic accuracy. In this prospective, case-control, pilot study, we aimed to determine the metabolic profile of neonates with LOS. Urine samples were collected at the day of initial LOS evaluation, the 3rd and 10th day, thereafter, from 16 septic neonates (9 confirmed and 7 possible LOS cases) and 16 non-septic ones (controls) at respective time points. Urine metabolic profiles were assessed using non-targeted nuclear magnetic resonance spectroscopy and targeted liquid chromatography-tandem mass spectrometry analysis. Multivariate statistical models with data from either analytical approach showed clear separation between the metabolic profiles of septic neonates (both possible and confirmed) and the controls. Metabolic changes appeared to be related to disease progression. Overall, neonates with confirmed or possible LOS exhibited comparable metabolic profiles indicating similar metabolic alternations upon the onset of clinical manifestations. This methodology therefore enabled the discrimination of neonates with LOS from non-septic individuals, providing potential for further research toward the discovery of LOS-related biomarkers.

Plasma citrulline levels in preterm neonates with necrotizing enterocolitis.

BACKGROUND AND AIM: Citrulline is a non-protein amino acid synthesized in the small intestine. In children with short-bowel syndrome, citrulline has served as a reliable marker of the residual bowel length and parenteral nutrition (PN) independence. In the present study we aim to assess the value of citrulline measurement in preterm neonates developing necrotizing enterocolitis (NEC). METHODS: Plasma citrulline levels were measured prospectively in 17 preterm neonates with NEC stage II during the entire course of the disease. Serial citrulline determinations in 24 healthy preterm neonates on 2, 7, 14, 21 and 28 days of life (DOL), served as reference values. RESULTS: In healthy preterm neonates plasma citrulline levels showed a progressive increase in relation to age. In neonates presenting with NEC, mean citrulline levels were significantly lower as compared to controls' citrulline levels of the most approximate day of life (DOL 7: 16.85±4.2 vs 20.5±4.5 µmol/L, p<0.05; DOL 14: 18±4.2 vs 23.5±4.3 µmol/L, p<0.01; DOL 21: 17±2.5 vs 30±5.7 µmol/L, p<0.01). The optimal citrulline cut-off distinguishing NEC patient from controls was 17.75 µmol/L (sensitivity 76%, specificity 87%). Plasma citrulline at presentation correlated inversely with the duration of parenteral nutrition (r=-0.49, p<0.05). Consecutive citrulline determinations revealed that plasma citrulline increased during reintroduction and gradual increase of enteral nutrition. CONCLUSIONS: Our findings provide preliminary evidence that citrulline levels that are reduced in preterm neonates with NEC in comparison to age-matched controls and serial citrulline determinations could help to monitor improvement of functional enterocyte mass during the course and resolution of NEC.

Diagnostic utility of elevated serum soluble triggering receptor expressed on myeloid cells (sTREM)-1 in infected neonates.

OBJECTIVE: To assess the value of serum levels of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) for early diagnosis of late-onset sepsis (LOS) in neonates, compared with interleukin-6 (IL-6). DESIGN AND SETTING: Prospective, observational study in a single, level III neonatal intensive care unit of a university hospital. PATIENTS: Fifty-two preterm and term neonates evaluated for suspected LOS were studied. Neonates were classified into two groups: infected [confirmed sepsis (n = 22) and possible sepsis (n = 9)] and noninfected neonates (n = 21). MEASUREMENTS AND RESULTS: Serum sTREM-1 and IL-6 were measured (enzyme-linked immunosorbent assays) when signs suggestive of sepsis emerged. Infected neonates had significantly higher sTREM-1 (p = 0.004) and IL-6 (p < 0.0001) than noninfected neonates. Receiver operating characteristic (ROC) curve analysis resulted in significant areas under the curve (AUC) for both sTREM-1 (AUC = 0.733, p = 0.005) and IL-6 (AUC = 0.892, p = 0.001) for identification of infected neonates, with the difference between the two AUC not being significant. Further analysis documented acceptable diagnostic performance of sTREM-1 and IL-6, which was not improved, however, when the two markers were combined. CONCLUSIONS: Serum sTREM-1 increases in infected neonates. Diagnostic accuracy of sTREM-1 either alone or in combination with IL-6 is not better than that of IL-6.