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..

Efficacy and safety of fremanezumab for migraine prophylaxis in patients with at least three previous preventive failures: Prospective, multicenter, real-world data from a Greek registry.

OBJECTIVE: To prospectively assess the efficacy and safety of fremanezumab for migraine prophylaxis in patients with failure of at least three previous preventive treatments. Changes in disability as quality-of-life outcomes after fremanezumab treatment were also examined. METHODS: Two hundred and four patients with either high-frequency EM (HFEM) or chronic migraine (CM), who attained at least three consecutive monthly sessions with fremanezumab 225 mg and otherwise met the inclusion criteria, were included in the study. The crude response (at least 50% reduction in monthly headache days [MHD]) rates to fremanezumab were assessed. Scores in the following efficacy outcomes were then compared from baseline to the last efficacy evaluation follow-up: (i) MHD, (ii) monthly days with moderate/severe peak headache intensity, and (iii) monthly days with intake of abortive medication. The disability was evaluated with the Migraine Disability Assessment; the quality of life (QOL) status was assessed with the Headache Impact-6 Test, and the EQ-5D questionnaire. RESULTS: In the majority of HFEM cases (n = 81/97; 83.5%) and CM patients (n = 67/107; 62.6%), fremanezumab proved effective in reducing the MHDs by at least 50% and was associated with clinically meaningful improvement in all other efficacy variables. The migraine-related disability experienced by our patients decreased and their QOL increased. We recorded just 36 cases reporting mild adverse events, including pain, rash or pruritus (n = 26), flu-like symptoms (n = 8), and hair loss (n = 2). CONCLUSION: With our prospective results, we provide further real-world data to support the favorable benefit/risk profile of fremanezumab in the prophylaxis of both HFEM and CM.

The role of serum vitamin 25(OH)D concentration in the Covid-19 pandemic in children.

The ongoing Coronavirus disease 19 (Covid-19) pandemic and associated mortality in children led to an effort to address risk factors and develop protective measures. Observational studies in adults showed that vitamin D deficiency is associated with Covid-19 severity. The aim of this review was to summarise data regarding the role of serum vitamin 25(OH)D concentration in the severity of Covid-19 and the associated multisystem inflammatory syndrome in children (MIS-C). Many studies noted lower concentrations of vitamin 25(OH)D in children with Covid-19 compared with healthy controls; however, studies that assessed vitamin 25(OH)D suboptimal concentrations as a risk factor for Covid-19 severity were scarce. There was no high-quality evidence that vitamin 25(OH)D concentrations are associated with Covid-19 severity. Similarly, for MIS-C, a few studies with a small number of patients found that vitamin D deficiency was associated with more severe MIS-C. Vitamin D has many immunomodulatory actions and is consumed in the immunomodulatory cells, especially in infections such as the Covid-19 which is associated with increased inflammation and cytokine storm. Therefore, decreased concentrations of plasma vitamin 25(OH)D have been proposed to be the result of vitamin use by immunomodulatory cells in severe Covid-19, rather than a predisposing factor. In conclusion, the available data cannot prove that vitamin D deficiency is a risk factor for severe Covid-19 disease. More studies, of prospective design, are needed to investigate the role of this marker independently of other risk factors.

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.

Gaucher Disease Type 2 Manifested as Hemophagocytic Lymphohistiocytosis in a Neonate in the COVID-19 Era.

BACKGROUND: A term neonate presented with persistent severe thrombocytopenia, elevated liver enzymes, conjugated hyperbilirubinemia, hepatosplenomegaly, and mild hypotonia. OBSERVATIONS: A thorough workup for infections, congenital thrombocytopenias, and neonatal malignancies was negative. Because of increased anti-SARS-CoV-2 IgG antibodies after maternal COVID-19, multisystem inflammatory syndrome of neonates was considered and intravenous immunoglobulin was administered. The clinical condition of the neonate deteriorated and due to laboratory evidence of hyperinflammation, hemophagocytic lymphohistiocytosis was suspected, and treatment with etoposide and dexamethasone was initiated with temporary stabilization. Gaucher disease type 2 was eventually diagnosed. CONCLUSION: Gaucher disease can rarely present in neonates as hemophagocytic lymphohistiocytosis.

The trends for the "trend toward significance" in the pediatric literature.

Purpose This study is to examine whether the term "trend toward statistical significance" is used to describe statistically nonsignificant results in biomedical literature. We examined articles published in five high-impact pediatric journals, including The Lancet Child & Adolescent Health, The Journal of Pediatrics, Early Human Development, Frontiers in Pediatrics, and BMC Pediatrics to identify manuscripts where a "trend" was used to describe a statistically nonsignificant result, from January 2020 to December 2021, and, furthermore, for The Journal of Pediatrics, Early Human Development, and BMC Pediatrics from January 2010 to December 2011. We detected that a "trend toward significance" was used to describe a statistically nonsignificant result at least once in 146 articles (2.7%) during the period between 2020 and 2021 and in 97 articles (4.0%) during the period between 2010 and 2011. We found no significant difference in the proportion of published articles with inappropriate use of "trend" across journals belonging to the first quartile of impact compared to the second quartile or across journals publishing under the subscription model or open access policy compared to journals publishing solely under the open access policy, in any period. The overall proportion of the inappropriate use of "trend" declined significantly between 2010 and 2011 to 2020 and 2021 (p = 0.002, RR 0.66 95% CI 0.51-0.86). CONCLUSION: "Trend" statements were sporadically used to describe statistically nonsignificant results across pediatric literature. The inappropriate use of "trend" to describe almost significant differences could be misleading, and "trend" should be reserved only when a specific statistical test for trend has been performed, or in relation to appropriate scientific definitions. WHAT IS KNOWN: •Previously, researchers have reported inappropriate use of "trend" in articles across anaesthesia or major oncology journals. •In many cases, hypothesized results that are close but not lower than the statistical significance threshold are emphasized as "almost" significant. WHAT IS NEW: •"Trend" statements were sporadically used to describe statistically nonsignificant results across pediatric literature. •Inappropriate use of  "trend" was similar in journals with a subscription model compared to those having an open access policy and decreased within a 10-year period.

Is small for gestational age status independently correlated with body composition during childhood?

This study aims to examine if small for gestation age (SGA) status is correlated with alterations in body composition at prepuberty, independently of other factors, comparing SGA-born children with appropriate for gestational age (AGA)-born children. We examined anthropometrics, waist circumference, body mass index (BMI), six skinfold thickness, and body composition using the method of bioelectrical impedance in 636 children aged 7 to 10 years. We also considered age, gender, birth mode, mother's age, prepregnancy weight, weight gain during pregnancy, social status, parental BMI, type of feeding, and daily exercise. We examined 636 children at a mean age of 9 years: 106 SGA-born and 530 AGA-born children. SGA as compared to AGA-born children had a lower BMI z-score (0.26 ± 0.89 kg/cm2 vs 0.46 ± 0.84 kg/cm2, p < 0.050) and a lower lean mass, although that was not statistically significant (24.0 ± 6.6 kg vs 25.6 ± 6.4 kg, p < 0.100). SGA-born children presented no difference in waist circumference or fat mass in comparison to children born AGA. Logistic regression analysis revealed a strong independent negative association between SGA status and BMI (beta = - 2.33, OR = 0.70 p = 0.019) and SGA status and lean mass (beta = - 2.43, OR = 0.95 p = 0.010).  Conclusion: Our findings suggest that SGA-born children had a lower BMI as compared to AGA-born subjects, whereas SGA status was negatively associated with BMI and lean mass. What is Known: • Deviant birth weight for gestation has been associated with an increased risk of childhood adiposity. • Evidence remains scarce on whether small for gestational age status affects body composition and obesity later in childhood. What is New: • Among school-aged children, small for gestational age subjects had a lower body mass index as compared to appropriate for gestational age counterparts, whereas small for gestational age status was negatively associated with body mass index and lean mass. • A meticulous observation is needed during childhood in children born with deviant birth weight.

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.

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.

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.

A systematic review indicates an association between birth weight and body fat in childhood.

AIM: To summarise the existing evidence regarding the body fat of small or large for gestation subjects, evaluated from birth up to 18 years of age. METHODS: The PRISMA guidelines were adopted for the current systematic review, including studies having evaluated body fat with bioelectrical impedance analysis, air displacement plethysmography, dual-energy X-ray absorptiometry or magnetic resonance imaging. RESULTS: A total of 31 studies was included. The balance of evidence suggests that small for gestation infants have decreased fat mass at birth; postnatally they experience increased adiposity. In the long term, however, the evidence is inconclusive, since some studies suggest that foetal-restricted children with increased catch-up growth are at increased risk of fat accumulation, whereas other studies suggest a neutral or even negative association. Large for gestation infants have increased fat mass at birth, but in the long term, they have a lower body fat ratio, especially when they develop a catch-down growth. CONCLUSION: Some studies suggested that foetal-restricted children with increased catch-up growth are at increased risk of later adiposity, while other studies suggested a neutral or negative association. Given that the evidence is inconclusive, further studies are warranted. Large for gestation subjects have lower body fat when they develop catch-down growth.

Evaluation of cerebral oxygenation and perfusion in small for gestational age neonates and neurodevelopmental outcome at 24-36 months of age.

Objective To examine cerebral oxygenation and perfusion in small for gestational age (SGA) compared with appropriate for gestational age (AGA) neonates during the first postnatal week, and to investigate any association with neurodevelopmental outcomes at 24-36 months of age. Methods A prospective matched case-control study was conducted evaluating cerebral oxygenation and perfusion, using near-infrared spectroscopy (NIRS), between SGA and AGA neonates, during the first postnatal week. A neurodevelopmental assessment with Bayley-III was performed at 24-36 months of age. Results Forty-eight SGA and 48 AGA neonates of similar gestation (32.8 ± 2.1 vs. 32.5 ± 1.9) were enrolled. On the first postnatal day, the cerebral oxygenation was equal between SGA and AGA neonates (71 ± 7% vs. 72 ± 8%); however, in the subgroup analysis, males had higher oxygenation compared to female SGA neonates (73 ± 7% vs. 69 ± 7%, P = 0.04). Cerebral perfusion was significantly higher in SGA neonates on the first postnatal day (1.4 ± 0.6 vs. 1.1 ± 0.5, P = 0.04), but this difference was diminished on subsequent measurements. There were no significant differences between the SGA and AGA infants regarding the composite cognitive, communication and motor index scores. The length of mechanical ventilation and late-onset sepsis were significant risk factors affecting the cognitive and communication composite index scores, respectively. Conclusion Cerebral oxygenation was equal between SGA and AGA neonates, while cerebral perfusion was transiently increased in SGA neonates during the first postnatal day. There was no significant association of cerebral oxygenation and perfusion with neurodevelopmental outcomes.

Evaluation of Cerebral Oxygenation in Neonates with Sepsis with Near-Infrared Spectroscopy.

Objective Neonates with sepsis have increased risk of cerebral injury. Our aim was to evaluate cerebral oxygenation in septic neonates using near-infrared spectroscopy. Study Design A prospective study was designed enrolling neonates with sepsis, as defined by the International Consensus Conference of Pediatric Sepsis criteria and matched controls. Three cerebral half-hourly measurements were performed during the first, third, and seventh day of the episode and the values of tissue oxygenation index (TOI) and fractional tissue oxygen extraction (FTOE) were compared between the two groups. Result The study population consisted of 50 septic and 44 control neonates with similar characteristics. No differences on TOI and FTOE were recorded in the first and third day. However, on the seventh day, septic neonates had significantly decreased oxygenation (62.7 ± 7 vs. 71.4 ± 4.4%, p < 0.001) and increased oxygen extraction (0.35 ± 0.07 vs. 0.27 ± 0.05, p < 0.001), irrespectively of the severity of the infection. Conclusion Although septic neonates have normal cerebral oxygenation in the first and third day of the sepsis, they present decreased cerebral oxygenation in the seventh day independently of the infection severity.

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.

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.

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.

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.