Autonomic Function in Obese Children and Adolescents: Systematic Review and Meta-Analysis.

Background: Obesity is invariably accompanied by autonomic dysfunction, although data in pediatric populations are conflicting. Methods: We conducted a systematic review and meta-analysis of 12 studies (totaling 1102 participants) comparing obese and normal-weight subjects (5-18 years of age), defined as body mass index >95th or <85th percentile, respectively. Using a random-effects model, we report the standardized mean differences (SMD) of sympathetic and vagal indices of heart rate variability. Results: Autonomic dysfunction was present in the obesity group, based on the average SMD in the standard deviation of sinus intervals (at -0.5340), and on the ratio of low (LF)- to high (HF)-frequency spectra (at 0.5735). There was no difference in sympathetic activity, but the heterogeneity among the relevant studies weakens this result. SMD in HF (at 0.5876), in the root mean square of successive differences between intervals (at -0.6333), and in the number of times successive intervals exceeded 50 ms divided by the total number of intervals (at -0.5867) indicated lower vagal activity in the obesity group. Conclusions: Autonomic dysfunction is present in obese children and adolescents, attributed to lower vagal activity. Further studies are needed in various pediatric cohorts, placing emphasis on sympathetic activity.

Reintroduction of Legacy Antibiotics in Neonatal Sepsis: The Special Role of Fosfomycin and Colistin.

Neonatal sepsis is a leading cause of morbidity and mortality in neonates, particularly in low- and middle-income countries. The emergence of antimicrobial resistance is a rapidly growing global problem. A significant proportion of the pathogens that commonly cause neonatal sepsis are resistant to multiple antibiotics. Therefore, for the empirical treatment of neonatal sepsis, the repurposing of older antibiotics that are effective against multidrug-resistant pathogens is being investigated. This review aims to provide an overview of current research and experience using the repurposed antibiotics colistin and fosfomycin for the empirical treatment of neonatal sepsis. Based on current knowledge, colistin and fosfomycin may be potentially helpful for the empirical treatment of sepsis in neonates due to their efficacy against a wide range of pathogens and acceptable safety profile.

A literature review on the redundancy of additional thyroid function tests in neonates of mothers with hypothyroidism.

AIM: Newborn thyroid screening tests are carried out during the first days after birth in many parts of the world. The aim of this review was to assess whether additional thyroid function tests of neonates born to mothers with hypothyroidism are necessary to diagnose newborns with congenital hypothyroidism (CH) missed by the usual screening test. METHODS: A search in PubMed and Google Scholar databases was conducted for pertinent studies, using relevant keywords. All studies that were published in any language from 1 January 2000 to 30 June 2023 were included. Observational cohort studies were included in the analysis, while case reports and studies not referring to neonates were excluded. RESULTS: Thirteen studies were identified comprising more than 4400 infants with CH. Studies with the larger study populations recommended against additional testing in healthy infants of hypothyroid mothers. Similar were the results of some smaller retrospective studies. Few studies identified in total 16 infants with CH that were missed on neonatal screening without, though, a definite causative link between the mother's and the infant's thyroid dysfunction. CONCLUSION: Based on available data, additional thyroid function tests seem redundant in identifying undiagnosed cases of CH. Larger studies are needed to reach a definite conclusion.

Beta Cell Dysfunction in Youth- and Adult-Onset Type 2 Diabetes: An Extensive Narrative Review with a Special Focus on the Role of Nutrients.

Traditionally a disease of adults, type 2 diabetes (T2D) has been increasingly diagnosed in youth, particularly among adolescents and young adults of minority ethnic groups. Especially, during the recent COVID-19 pandemic, obesity and prediabetes have surged not only in minority ethnic groups but also in the general population, further raising T2D risk. Regarding its pathogenesis, a gradually increasing insulin resistance due to central adiposity combined with a progressively defective ß-cell function are the main culprits. Especially in youth-onset T2D, a rapid ß-cell activity decline has been observed, leading to higher treatment failure rates, and early complications. In addition, it is well established that both the quantity and quality of food ingested by individuals play a key role in T2D pathogenesis. A chronic imbalance between caloric intake and expenditure together with impaired micronutrient intake can lead to obesity and insulin resistance on one hand, and ß-cell failure and defective insulin production on the other. This review summarizes our evolving understanding of the pathophysiological mechanisms involved in defective insulin secretion by the pancreatic islets in youth- and adult-onset T2D and, further, of the role various micronutrients play in these pathomechanisms. This knowledge is essential if we are to curtail the serious long-term complications of T2D both in pediatric and adult populations.

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.

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.

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.

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.

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.

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.

C-reactive protein in infants with no evidence of early-onset sepsis.

OBJECTIVE: C-reactive protein (CRP) is one of the most extensively used biomarkers in the investigation of early-onset sepsis (EOS). Current evidence suggests the normal kinetics of serum CRP should be considered when evaluating infants for presumable EOS. The current study aimed to evaluate the CRP kinetics, and to establish percentiles in a cohort of term and near-term infants with no evidence of confirmed or clinical EOS. METHODS: We retrospectively reviewed the medical records of all neonates ≥34 weeks' gestation screened for presumable EOS, from January until December 2019. We also recorded the clinical management, the blood culture, serial CRP, and white blood cell count analysis of each infant. All infants that received antibiotics for confirmed or presumed EOS were excluded from the analysis. RESULTS: During the study period, 145 infants were detected; 109 (75%) term and 36 (25%) preterm. Term infants had significantly higher median values of CRP at all time points in comparison to preterm infants. Term infants presented a significant rise of CRP at 24 and 36 h, with a peak at 24 h (median 4 (range 1-12) mg/L). Preterm infants had a significant rise of CRP at 24 but not at 36 h, with a peak at 24 h (median 3 (range 1-9) mg/L). In term infants, the 90th percentile of CRP at 24 h was 10.80 mg/L and the 97th percentile was 12.00 mg/L. In preterm infants, the 90th percentile of CRP at 24 h was 7.60 mg/L and the 97th percentile was 8.00 mg/L. CONCLUSIONS: Term and near-term asymptomatic infants had a rise in CRP during the first days of life. Term infants had a more pronounced CRP response in comparison to preterm infants.

Association of fluid overload with patent ductus arteriosus during the first postnatal day.

BACKGROUND: Evidence examining the association of over-hydration during early life with haemodynamically significant patent ductus arteriosus (hsPDA) and other morbidities is limited. Our aim was to evaluate the association of fluid overload during the first postnatal day with hsPDA and common neonatal morbidities such as bronchopulmonary dysplasia in preterm infants. METHODS: A retrospective cohort study was conducted enrolling infants ≤30 weeks' gestation and ≤1500 grams' birth weight, admitted to a tertiary Neonatal Unit. We calculated the fluid balance and we estimated the incidence of infants with fluid overload ≥5% during the first postnatal day, evaluating any possible correlation with hsPDA. RESULTS: 103 infants of 27.3±1.6 weeks' gestation and 1009±225 grams' birth weight were enrolled; of whom 32 (31%) were diagnosed with HsPDA. Fluid overload during the first postnatal day was recorded in 42 infants (41%). Infants with fluid overload were diagnosed with hsPDA in 48%, compared to 20% of infants without fluid overload (p=0.004). No differences were recorded in the development of bronchopulmonary dysplasia or survival. Fluid overload of ≥5% was significantly correlated with hsPDA (r=0.37, p=0.003) and had an independent contribution to the risk of hsPDA (OR 1.17, 95% CI 1.05-1.58), irrespective of other perinatal factors. CONCLUSIONS: In preterm infants, fluid overload ≥5% is significantly associated with hsPDA, therefore, fluid management during the first postnatal day should be closely regulated.

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.

A comparison between risk-factor guidance for neonatal early-onset sepsis and Kaiser Permanente sepsis risk calculator in a Greek cohort.

BACKGROUND: The management of neonates with early-onset sepsis (EOS) is based on maternal risk factors and infant clinical indications. An online sepsis risk calculator (SRC) has been established taking into consideration how clinical appearance modifies the initial risk for EOS. AIMS: To compare our clinical practice based on risk-factor guidance with that projected through the application of the SRC. STUDY DESIGN: Retrospective cohort study. METHODS: All neonates ≥34 weeks' gestation, during 01/2019-8/2020. The SRC was applied retrospectively to determine the recommendation. EOS was defined based on a positive blood or cerebrospinal fluid culture-proven infection within 72 h of age. Clinical sepsis was defined according to the European Medicine Agency criteria. OUTCOME MEASURES: Differences on antibiotic administration and management. RESULTS: Overall, 2084 infants were identified, of whom 150 (7%) received antibiotics. Of them, 34 infants were diagnosed with clinical sepsis, while one was diagnosed with culture positive-proven EOS. Applying SRC, 87 (4%) infants would have received antibiotics. Clinical sepsis was diagnosed in 29 infants, while one infant had culture positive-proven EOS. Sixty-seven of 150 (45%) infants that received antibiotics would not have been treated based on SRC; five infants that developed clinical sepsis would have been missed with SRC. A 99.7% agreement between both guidance was found regarding infants not indicated for antibiotics. SRC application led to an absolute reduction of antibiotic administration by 2.93% (95% CI 2.19-3.75), p < 0.0001. CONCLUSIONS: The adoption of SRC would have significantly reduced antibiotic usage; however, a significant portion of cases with clinical EOS would have been missed.

Are thyroid function tests in neonates born to mothers with hypothyroidism clinically useful?

Thyroid function tests from all babies born to mothers with hypothyroidism (381 neonates) during a 6-year period, were collected and examined against findings of the universal screening test. No difference was found between the results of bloodspot test and later blood test. Additional blood tests for thyroid function in this population of neonates seem to be without clinical value and may be discontinued.