Menopause and its impact on the effectiveness of fremanezumab for migraine prophylaxis: post-hoc analysis of a prospective, real-world Greek registry.

OBJECTIVE: This post-hoc analysis of data extracted from a prospective study aimed to explore for the first time if the efficacy of fremanezumab in preventing difficult-to-treat migraine, according to ICHD-III, would differ between pre-menopausal and post-menopausal women. METHODS: A total of 171 (aged 18-70 years) fremanezumab-treated female migraine patients for six consecutive months were classified to those at pre-menopausal (n = 82) or post-menopausal (n = 89). Monthly headache days (MHD), disability, and quality of life (QOL) outcomes were assessed at baseline and at week 24 post-fremanezumab within subgroups and were then compared between them. Safety and tolerability were also assessed. RESULTS: In both groups, fremanezumab demonstrated significant reductions in MHDs, reduced disability, and higher QOL scores at week 24 post-treatment, compared to baseline. However, the between-subgroup comparison documented that pre-menopausal women and those at post-menopausal comparably benefited with significant reductions in overall MHDs (p = 0.883). Less disability, according to MIDAS (p = 0.696) and HIT-6 scores (p = 0.912), as well as higher QOL scores at week 24 post-fremanezumab, were also comparably evident in both groups. Safety was excellent across both subgroups. CONCLUSION: Fremanezumab can be considered a very effective treatment option for preventing migraines in difficult-to-treat women, aged 18-70 years, regardless of their menopausal status.

Intact FGF23 and Markers of Iron Homeostasis, Inflammation, and Bone Mineral Metabolism in Acute Pediatric Infections.

We intend to evaluate the association of intact Fibroblast Growth Factor 23 (i-FGF23), a phosphaturic hormone that contributes to anemia of inflammation, with markers of iron homeostasis, inflammation, and bone mineral metabolism in acute pediatric infections. Seventy-nine children, aged 1 month-13 years, out of which forty-two were males and thirty-seven females, participated in this study. Children with diseases and nutrient deficiencies causing anemia were excluded. Twenty-six patients had bacterial infections, twenty-six had viral infections, and twenty-seven children served as healthy controls. Complete blood count, markers of inflammation, iron and mineral metabolism, serum hepcidin, and i-FGF23 were compared between the groups. Thirty-nine percent of patients with bacterial infection and twelve percent of patients with viral infection presented characteristics of anemia of inflammation (p < 0.001). Ninety-two percent of patients with bacterial infection and eighty-one percent of patients with viral infection had functional iron deficiency (p < 0.001). Hepcidin was significantly positively correlated with the duration of fever, markers of inflammation, and negatively with iron, mineral metabolism parameters, and i-FGF23. i-FGF23 was positively correlated with iron metabolism parameters and negatively with the duration of fever, markers of inflammation, and hepcidin. Hepcidin levels increase, whereas i-FGF23 levels decrease in acute pediatric infections. Further research is required to understand the role of FGF23 in the hepcidin-ferroportin axis and for hepcidin in the diagnosis of bacterial infections and mineral metabolism.

Bioinformatics in Neonatal/Pediatric Medicine-A Literature Review.

Bioinformatics is a scientific field that uses computer technology to gather, store, analyze, and share biological data and information. DNA sequences of genes or entire genomes, protein amino acid sequences, nucleic acid, and protein-nucleic acid complex structures are examples of traditional bioinformatics data. Moreover, proteomics, the distribution of proteins in cells, interactomics, the patterns of interactions between proteins and nucleic acids, and metabolomics, the types and patterns of small-molecule transformations by the biochemical pathways in cells, are further data streams. Currently, the objectives of bioinformatics are integrative, focusing on how various data combinations might be utilized to comprehend organisms and diseases. Bioinformatic techniques have become popular as novel instruments for examining the fundamental mechanisms behind neonatal diseases. In the first few weeks of newborn life, these methods can be utilized in conjunction with clinical data to identify the most vulnerable neonates and to gain a better understanding of certain mortalities, including respiratory distress, bronchopulmonary dysplasia, sepsis, or inborn errors of metabolism. In the current study, we performed a literature review to summarize the current application of bioinformatics in neonatal medicine. Our aim was to provide evidence that could supply novel insights into the underlying mechanism of neonatal pathophysiology and could be used as an early diagnostic tool in neonatal care.

Preferences and perceptions of 617 migraine patients on acute and preventive migraine treatment attributes and clinical trial endpoints.

BACKGROUND: To identify the preferences and perceptions of migraine patients for acute and preventive treatment options and to investigate which treatment outcomes are the most important. DESIGN AND METHODS: The authors performed a choice-format survey in a cohort of migraine patients from Greece and Cyprus. A self-administered questionnaire developed in collaboration with the Greek Society of Migraine Patients was used. RESULTS: Questionnaires were collected from 617 migraine patients. Efficacy was preferred over safety as the single most important parameter, both in acute and preventive treatment. When analyzing single outcomes, patients prioritized a complete pain remission at 1-hour post-dose for acute therapies. Regarding migraine prevention, a 75% reduction in frequency, intensity of pain, accompanying symptoms and acute medication intake were considered as most important. Conversely, outcomes routinely used in clinical trials, namely complete or partial pain remission at 2-hours post-dose for acute treatment and 50% or 30% reduction in migraine frequency for prevention, were not deemed particularly relevant. Tablet formulation was mostly preferred, both in acute and preventive treatment. Conclusion: Listening to patients' needs may add a piece of the puzzle that is generally missing in clinical practice and often explains the lack of adherence in both acute and preventative anti-migraine therapies.

Reporting Quality and Risk of Bias Analysis of Published RCTs Assessing Anti-CGRP Monoclonal Antibodies in Migraine Prophylaxis: A Systematic Review.

Objective: Phase II/III randomized clinical trials (RCTs) are vulnerable to many types of bias beyond randomization. Insights into the reporting quality of RCTs involving migraine patients treated with monoclonal antibodies targeting the calcitonin gene-related peptide system (anti-CGRP MAbs) are currently lacking. Our aim was to analyze the reporting quality of phase II/III RCTs involving migraine patients treated with anti-CGRP MAbs. Methods: A systematic search was performed on the PubMed and EMBASE databases, according to PRISMA guidelines, for relevant RCTs in either episodic or chronic migraine prevention. Additionally, an adapted version of the 2010 CONSORT statement checklist was utilized. The ROBvis online tool was used to document the risk of bias. Results: From the initially identified 179 articles, we finally found 31 RCTs that were eligible for evaluation. The average CONSORT compliance was 88.7% (69.7-100%), while 93.5% (N = 29) of the articles had a compliance greater than 75%. Twenty-eight CONSORT items were reported in more than 75% of the articles. The average compliance of the analyzed RCTs was 93.9% for Galcanezumab, 91.3% for Fremanezumab, followed by 85.4% for Erenumab and Eptinezumab studies. Implementation of the ROB2 tool showed some concerning "missing information" arising from the inadequate reporting. Specifically, 50% of the studies (N = 16) were categorized as having inadequate information regarding the randomization process. Conclusions: Adequate reporting quality was disclosed in the evaluated RCTs with anti-CGRP MAbs in migraine prevention. However, some methodological issues need to be highlighted to be addressed in future studies assessing the efficacy of new molecules targeting CGRP or other candidate pathways implicated in migraine pathophysiology.

Maternal Obesity Modulates Cord Blood Concentrations of Proprotein Convertase Subtilisin/Kexin-type 9 Levels.

Context: In utero exposure to maternal obesity or diabetes is considered a pro-inflammatory state. Objective: To evaluate whether cord blood proprotein convertase subtilisin/kexin-type 9 (PCSK9), which is regulated by inflammation and metabolic derangements, is elevated in neonates born to overweight, obese, or diabetic mothers. Methods: A retrospective study in full-term neonates born between 2010 and 2023, at Brigham and Women's Hospital. There were 116 neonates included in our study, of which 74 (64%) were born to overweight/obese mothers and 42 (36%) were born to nonoverweight/nonobese mothers. Results: Neonates born to overweight/obese mothers had significantly higher cord blood concentrations of PCSK9 compared with neonates born to nonoverweight/nonobese group (323 [253-442] ng/mL compared with 270 [244-382] ng/mL, P = .041). We found no significant difference in cord blood concentrations of PCSK9 between neonates of diabetic mothers compared with neonates of nondiabetic mothers. In multivariate linear regression analysis, higher cord plasma PCSK9 concentration was significantly associated with maternal overweight/obesity status (b = 50.12; 95% CI, 4.02-96.22; P = .033), after adjusting for gestational age, birth weight, male sex, and intrauterine growth restriction. Conclusion: Neonates born to mothers with overweight/obesity have higher cord blood PCSK9 concentrations compared with the nonoverweight/nonobese group, and higher cord blood PCSK9 concentrations were significantly associated with maternal overweight/obesity status, after adjusting for perinatal factors. Larger longitudinal studies are needed to examine the role of PCSK9 in the development of metabolic syndrome in high-risk neonates born to overweight, obese, or diabetic mothers.

Complementary Feeding Practices: Recommendations of Pediatricians for Infants with and without Allergy Risk.

AIM: To investigate the routine guidance provided by pediatricians concerning the timing of complementary feeding (CF) for both healthy infants and those at a heightened risk of allergies. METHODS: A total of 233 pediatricians participated in an anonymous online survey that included questions about demographics and recommendations for CF. Specifically, they provided guidance on the types of foods, preparation methods, supplements, time intervals for introducing new foods to infants at low and high allergy risk, and delayed food introductions for high-risk cases. RESULTS: The respondents advised introducing certain foods at specific ages: fruits, starchy non-gluten grains, vegetables, olive oil, and meat were appropriate at 6 months; gluten-rich grains at 7 months; yogurt, hard-boiled eggs, and legumes at 8 months; fish at 8.5 months; and nuts at 9 months. Pediatricians, especially those with less than 15 years of practice, often introduced egg, seafood, gluten-rich grains, legumes, and nuts earlier for high-risk infants. Parenthood and male gender were associated with the earlier introduction of eggs and grains. CONCLUSIONS: Greek pediatricians follow a structured food introduction schedule for CF in infants. Interestingly, they tend to delay the introduction of common food allergens and recommend longer intervals between introducing new foods, particularly for high-risk infants. Key Notes: Despite recent evidence-based indications on healthy complementary feeding strategies for infants, discrepancies persist among pediatricians regarding food choices and the order and timing of food introduction, both for healthy infants and those at risk of allergy. Guidance on complementary feeding by pediatricians is influenced by their individual characteristics. Pediatricians tend to delay the introduction of common food allergens and recommend longer intervals between introducing new foods, particularly for high-risk infants.

Nine-Month Continuous Fremanezumab Prophylaxis on the Response to Triptans and Also on the Incidence of Triggers, Hypersensitivity and Prodromal Symptoms of Patients with High-Frequency Episodic Migraine.

Objective: To investigate whether the incidence of triggers, prodromal symptoms, hypersensitivity symptoms accompanying headache and responses to triptans were modified during a continuous 9-month fremanezumab therapy for migraine prophylaxis. Patients and methods: We studied 63 patients with high-frequency episodic migraine (HFEM). Enrolled patients received fremanezumab for nine consecutive months before defining the response rates and being stratified into treatment responders (≥50-74% reduction in monthly headache days (MHDs)), super responders (≥75%), partial non-responders (<50%) and super non-responders (<30%). Through headache diaries, patients provided data in order to document the impact of fremanezumab on the incidence of triggers, associated symptoms followed by headache and response to triptans (the use of the migraine treatment optimization questionnaire-4 (mTOQ-4)) during the 9-month treatment period. Results: Fremanezumab had early (after 3 monthly cycles) beneficial effects on the response to triptans in the majority of responders with relevant increases in mTOQ-4 scoring, but also in half of partial non-responders. A significant reduction in median days with migraine-associated symptoms was seen in responders after 6 months of therapy with fremanezumab, mostly for osmophobia, photophobia, phonophobia and nausea/vomiting, but partial non-responders also benefited. Likewise, the incidence of self-reported prodromal symptoms was significantly reduced in responders and was modestly diminished in partial non-responders. Triggers remained unaffected in both responders and non-responders. Conclusions: Fremanezumab given for at least 6-9 months may exert neuromodulatory effects in the migraine brain. These effects could result both in the inhibition of migraine chronification, but also in the diminishing of the magnitude of migraine-associated symptoms, mostly in responders and in partial non-responders.

Predictors of successful extubation from volume-targeted ventilation in extremely preterm neonates.

OBJECTIVE: To identify variables associated with extubation success in extremely preterm neonates extubated from invasive volume-targeted ventilation. STUDY DESIGN: We retrospectively evaluated 84 neonates ≤28 weeks' gestational age, on their first elective extubation. The primary outcome of successful extubation was defined as non-reintubation within seven days. We used multivariate logistic regression analysis. RESULTS: We identified 58 (69%) neonates (mean gestational age of 26.5 ± 1.4 weeks, birthweight 921 ± 217 g) who met the primary outcome. Female sex (OR 1.15, 95% CI 1.01-9.10), higher pre-extubation weight (OR 1.29, 95% CI 1.05-1.59), and pH (OR 2.54, 95% CI 1.54-4.19), and lower pre-extubation mean airway pressure (MAP) (OR 0.49, 95% CI 0.33-0.73) were associated with successful extubation. CONCLUSIONS: In preterm neonates, female sex, higher pre-extubation weight and pH, and lower pre-extubation MAP were predictors of successful extubation from volume-targeted ventilation. Evaluation of these variables will likely assist clinicians in selecting the optimal time for extubation in such vulnerable neonates.

Pneumoprotein CC16 in the Umbilical Cord Blood of Preterm Neonates.

OBJECTIVE: We examined the impact of perinatal factors on cord serum club cell protein (CC16) and the association of CC16 with mechanical ventilation and bronchopulmonary dysplasia (BPD) in preterm neonates. STUDY DESIGN: A retrospective cohort study including 60 neonates born with gestational age (GA) < 34 weeks. The impact of categorical perinatal factors on cord blood levels of CC16 was examined with univariate and multivariate regression analyses. RESULTS: In neonates with GA < 32 weeks, cord blood CC16 concentrations were significantly lower compared to neonates with GA between 320/7 and 336/7 weeks (5.4 ± 2.5 compared to 7.6 ± 2.9 ng/mL, p = 0.039). Neonates with prolonged rupture of membranes had significantly lower CC16 compared to those without prolonged rupture of membranes (4.0 ± 1.9 compared to 7.2 ± 2.2, p < 0.001). Finally, neonates with BPD had significantly lower CC16, compared to neonates without BPD (4.2 ± 2.1 compared to 7.0 ± 2.2 ng/mL, p = 0.004).Prolonged rupture of membranes was significantly negatively associated with CC16 (b = -2.67, 95% confidence interval [CI] -0.49 to -4.85, p = 0.017), after adjusting for GA (b = 0.23, 95% CI 0.03-0.42, p = 0.022), mode of conception, and mode of delivery. Finally, higher CC16 levels were significantly inversely associated with BPD (odds ratio = 0.33, 95% CI 0.12-0.88, p = 0.028), after adjusting for GA (b = 0.27, 95% CI 0.09-0.78, p = 0.015), and birth weight. CONCLUSION: Prolonged rupture of membranes was significantly negatively associated with cord serum CC16, after adjusting for GA, conception, and delivery mode, and CC16 was significantly inversely associated with BPD, after adjusting for GA and birth weight. KEY POINTS: · Neonates with prolonged rupture of membranes had lower CC16 levels.. · CC16 was significantly negatively associated with BPD.. · CC16 could be a biomarker of lung injury and BPD..

Effects of Fremanezumab on Psychiatric Comorbidities in Difficult-to-Treat Patients with Chronic Migraine: Post Hoc Analysis of a Prospective, Multicenter, Real-World Greek Registry.

OBJECTIVE: this post hoc analysis aimed to evaluate the efficacy of fremanezumab in difficult-to-treat chronic migraine (CM) patients with and without psychiatric comorbidities (PCs), mainly anxiety and/or depression. METHODS: We assessed data from CM patients with and without PCs who failed at least 3 preventives and eventually received at least 3 consecutive monthly doses of fremanezumab 225 mg. Outcomes included the crude response (≥50% reduction in monthly headache days (MHDs)) rates to fremanezumab from the baseline to the last clinical follow-up. The changes in MHDs; MHDs of moderate/greater severity; monthly days with intake of abortive medication; and the proportion of patients' changing status from with PCs to decreased/without PCs were also compared. Disability and quality of life (QOL) outcomes were also assessed. RESULTS: Of 107 patients enrolled, 65 (60.7%) had baseline PCs. The percentage of patients with (n = 38/65; 58.5%) and without (n = 28/42; 66.6%) PCs that achieved a ≥50% reduction in MHDs with fremanezumab was comparable (p = 0.41), whereas MHDs were significantly reduced (difference vs. baseline) in both patients with PCs (mean -8.9 (standard error: 6.8); p < 0.001) and without PCs (-9.8 (7.5); p < 0.001). Both groups experienced significant improvements in all other efficacy, disability, and QOL outcomes at comparable rates, including in MHD reduction. A significant proportion of fremanezumab-treated patients with baseline PCs de-escalated in corresponding severities or even reverted to no PCs (28/65; 43.1%) post-fremanezumab. CONCLUSIONS: fremanezumab appears to be effective as a preventive treatment in difficult-to-treat CM patients with and without PCs while also being beneficial in reducing the severity of comorbid anxiety and/or depression.

A systematic review and meta-analysis of the role of Doppler ultrasonography of the superior mesenteric artery in detecting neonates at risk of necrotizing enterocolitis.

The role of postnatal Doppler measurements of the superior mesenteric artery (SMA) in detecting neonates at risk of necrotizing enterocolitis (NEC) remains uncertain; therefore, we systematically reviewed and meta-analyzed the existing evidence regarding the usefulness of SMA Doppler measurements in detecting neonates at risk for NEC. We used the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines, and we included studies which reported the following Doppler ultrasonography indices: peak systolic velocity, end-diastolic velocity, time average mean velocity, differential velocity, pulsatility index (PI) and resistive index. Eight studies were eligible for inclusion in the meta-analysis. Evidence suggested that, during the first postnatal day, neonates who developed NEC had a significantly higher peak systolic velocity (mean difference of 2.65 cm/s (95% confidence interval [CI] 1.23, 4.06, overall effect Z=3.66, P<0.001)), higher PI (mean difference of 1.52 (95% CI 0.00, 3.04, Z=1.96, P=0.05)) and higher resistive index (mean difference of 1.09 (95% CI 0.59, 1.60, Z=4.24, P<0.001)), compared to neonates who did not develop NEC. However, our findings do not support a strong association between the Doppler ultrasound indices and development of NEC at the time of disease onset. This meta-analysis suggests that first postnatal day SMA Doppler parameters, namely peak systolic velocity, PI and resistive index, are higher in neonates who develop NEC. On the other hand, the aforementioned indices are of uncertain significance once the diagnosis of NEC has been established.

Classification and Special Nutritional Needs of SGA Infants and Neonates of Multiple Pregnancies.

Data regarding the nutritional management of preterm small for gestational age (SGA) infants are scarce. In the recent report of ESPGHAN, the recommended energy for very preterm infants during hospitalization has been increased, yet this may not fit the needs of all preterm infants. It is important to distinguish fetal growth-restricted (FGR) infants from constitutional SGA infants, as well as preterm SGA from preterm AGA infants, since they may have different nutritional needs. Preterm FGR infants, and specifically infants < 29 weeks' gestation, accumulate nutrient deficits due to intrauterine malnutrition, prematurity, morbidities, delayed initiation of feeding, and feeding intolerance. Therefore, these infants may need more aggressive nutrition for optimal catch-up growth and neurologic development. However, a balance should be kept between optimal and excessive catch-up growth, since the combination of intrauterine malnutrition and excessive postnatal growth has been linked with later adverse metabolic consequences. Furthermore, multiple gestation is often complicated by FGR and prematurity. There is controversy in the definition of FGR in multiple gestations, and it should be noted that FGR in multiple gestation usually differs etiologically from FGR in singletons. The aim of this review is to summarize existing knowledge regarding the nutritional needs of preterm FGR and FGR infants of multiple gestation.

Growth trajectories during infancy have a significant impact on body composition in childhood.

Evidence supports that growth trajectory during infancy has a major impact on body composition. We aimed to examine body composition in children born small for gestational age (SGA) or appropriate for gestational age (AGA) adjusted for postnatal growth velocity. We enrolled 365 children, 75 SGA and 290 AGA, aged 7 to 10 years, examining anthropometrics, skinfold thickness, and body composition using bioelectrical impedance analysis. Growth velocity was defined as rapid or slow (weight gain > or <0.67 z-scores, respectively). Gestational age, sex, delivery mode, gestational diabetes, hypertension, nutrition, exercise, parental body mass index (BMI), and socioeconomic status were considered. At a mean of 9 years of age, SGA compared with AGA-born children, had significantly lower lean mass. BMI was negatively associated with SGA status (beta = 0.80, P = .046), after adjusting for birth weight, delivery mode, and breastfeeding. The lean mass index was negatively associated with SGA status (beta = 0.39, P = .018), after adjusting for the same factors. SGA-born participants with slow growth velocity had significantly lower lean mass in comparison to AGA-born counterparts. SGA-born children with rapid compared with those with slow growth velocity had significantly higher absolute fat mass. BMI was negatively associated with a slow postnatal growth pattern (beta = 0.59, P = .023), and the lean mass index was negatively associated with a slow postnatal growth pattern (beta = 0.78, P = .006), after adjusting for the same factors. In conclusion, SGA-born children presented a lower lean mass in comparison to AGA-born counterparts, whereas BMI and lean mass index were negatively associated with slow postnatal growth velocity.

Predictors of Response to Fremanezumab in Migraine Patients with at Least Three Previous Preventive Failures: Post Hoc Analysis of a Prospective, Multicenter, Real-World Greek Registry.

OBJECTIVE: To define, in a real-world population of patients with high-frequency episodic (HFEM) or chronic migraine (CM), the predictive role of socio-demographic or phenotypic profiling of responders to fremanezumab. PATIENTS AND METHODS: Two-hundred and four adult fremanezumab-treated patients with either HFEM or CM, who failed to at least three preventive treatments, provided data at baseline on several individual socio-demographic and phenotypic variables. These variables were analyzed for their ability to independently predict the response (50-74% response rates) or super-response (≥ 75% response rates) to fremanezumab. Patients were followed from 3-18 months of fremanezumab exposure. RESULTS: The main finding to emerge from univariate analyses was that three baseline socio-demographic/clinical variables, i.e., age group 41-70 years (p = 0.02); female gender (p = 0.03); patients with HFEM (p = 0.001), and three clinical phenotypic variables, i.e., strict unilateral pain (p = 0.05); pain in the ophthalmic trigeminal branch (p = 0.04); and the "imploding" quality of pain (p = 0.05), were significantly related to fremanezumab response. However, in multivariate analysis, only HFEM (p = 0.02), the presence of strict unilateral (p = 0.03), and pain location in the ophthalmic trigeminal branch (p = 0.036) were independently associated with good fremanezumab response. Allodynia (p = 0.04) was the only clinical predictive variable of super-responsiveness to fremanezumab. CONCLUSIONS: A precise phenotypic profiling with identification of pain characteristics consistent with peripheral and/or central sensitization might reliably predict the responsiveness to fremanezumab in migraine prophylaxis.

Serum PCSK9 levels in infants with deviant birth weight: a biomarker of the lipoprotein metabolism.

OBJECTIVE: Proprotein Convertase Subtilisin/Kexin-Type 9 (PCSK9), a modulator of low-density lipoprotein (LDL) cholesterol metabolism, has been reported to be a promising biomarker for evaluating lipoprotein metabolism; however, evidence in infants is limited. In the current study, we sought to investigate potential differences in serum PCSK9 levels between infants with deviant birth weight and controls. METHODS: We enrolled 82 infants, classified into 33 small (SGA), 32 appropriate (AGA), and 17 large for gestation (LGA) infants. Serum PCSK9 was measured on routine blood analysis within the first postnatal 48 h. RESULTS: PCSK9 was significantly higher in SGA as compared to AGA and LGA infants [322 (236-431) as compared to 263 (217-302) and 218 (194-291) ng/ml respectively, p = .011]. In comparison to term AGA infants, PCSK9 was significantly elevated in preterm AGA and SGA infants. We also found a significantly higher level of PCSK9 in term female SGA infants as compared to term male SGA infants [325 (293-377) as compared to 174 (163-216) ng/ml, p = .011]. PCSK9 was significantly correlated with gestational age (R = -0.404, p < .001), birth weight (R = -0.419, p < .001), total cholesterol (R = 0.248, p = .028) and LDL cholesterol (R = 0.370, p = .001). SGA status (OR 2.56, p = .004, 95% CI 1.83-4.28) and prematurity (OR 3.10, p = .001, 95% CI 1.39-4.82) were strongly related to serum PCSK9 levels. CONCLUSION: PCSK9 levels were significantly associated with total and LDL cholesterol. Moreover, PCSK9 levels were higher in preterm and SGA infants, suggesting that PCSK9 might be a promising biomarker for evaluating infants with increased later cardiovascular risk.HighlightsWhat's already known? Proprotein Convertase Subtilisin/Kexin-Type 9 (PCSK9) is a promising biomarker for evaluating lipoprotein metabolism; however, evidence in infants is limited. Infants that were born with a deviant birth weight have a unique lipoprotein metabolism profile.What this study adds? Serum PCSK9 levels were significantly associated with total and LDL cholesterol. PCSK9 levels were higher in preterm and small for gestation infants, suggesting that PCSK9 might be a promising biomarker for evaluating infants with increased later cardiovascular risk.

Fighting Antimicrobial Resistance in Neonatal Intensive Care Units: Rational Use of Antibiotics in Neonatal Sepsis.

Antibiotics are the most frequently prescribed drugs in neonatal intensive care units (NICUs) due to the severity of complications accompanying neonatal sepsis. However, antimicrobial drugs are often used inappropriately due to the difficulties in diagnosing sepsis in the neonatal population. The reckless use of antibiotics leads to the development of resistant strains, rendering multidrug-resistant pathogens a serious problem in NICUs and a global threat to public health. The aim of this narrative review is to provide a brief overview of neonatal sepsis and an update on the data regarding indications for antimicrobial therapy initiation, current guidance in the empirical antimicrobial selection and duration of therapy, and indications for early discontinuation.

Are the current feeding volumes adequate for the growth of very preterm neonates?

Postnatal growth failure, a common problem in very preterm neonates associated with adverse neurodevelopmental outcome, has recently been shown not to be inevitable. There is a wide discussion regarding feeding practices of very preterm neonates, specifically regarding feeding volumes and nutrients supply to avoid postnatal growth failure. Current guidelines recommend an energy intake of 115­140 kcal /kg per d with a considerably higher upper limit of 160 kcal/kg per d. The feeding volume corresponding to this energy supply is not higher than 200 ml/kg in most cases. From the other side, randomised and observational studies used higher feeding volumes, and these were associated with better weight gain and growth, while no complications were noted. Taking into account the above, nutritional practices should be individualised in each very and extremely preterm infant trying to reduce postnatal growth failure, pointing out that available data are inconclusive regarding the effect of high-volume feeds on growth. Large clinical trials are necessary to conclude in the best feeding practices of very preterm neonates.

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.

Wolfram Syndrome 1: A Pediatrician's and Pediatric Endocrinologist's Perspective.

Wolfram syndrome 1 (WS1) is a rare autosomal recessive neurodegenerative disease caused by mutations in WFS1 and WFS2 genes that produce wolframin, a protein involved in endoplasmic reticulum calcium homeostasis and cellular apoptosis. Its main clinical features are diabetes insipidus (DI), early-onset non-autoimmune insulin-dependent diabetes mellitus (DM), gradual loss of vision due to optic atrophy (OA) and deafness (D), hence the acronym DIDMOAD. Several other features from different systems have been reported such as urinary tract, neurological, and psychiatric abnormalities. In addition, endocrine disorders that can appear during childhood and adolescence include primary gonadal atrophy and hypergonadotropic hypogonadism in males and menstrual cycle abnormalities in females. Further, anterior pituitary dysfunction with deficient GH and/or ACTH production have been described. Despite the lack of specific treatment for the disease and its poor life expectancy, early diagnosis and supportive care is important for timely identifying and adequately managing its progressive symptoms. The current narrative review focuses on the pathophysiology and the clinical features of the disease, with a special emphasis on its endocrine abnormalities that appear during childhood and adolescence. Further, therapeutic interventions that have been proven to be effective in the management of WS1 endocrine complications are discussed.