BACKGROUND: Biliary atresia (BA) is a severe immune-related disease that is characterized by biliary obstruction and cholestasis. The etiology of BA is unclear, our aim was to explore the relationship between biliary tract inflammation and immune-related genes. METHODS: We selected 14 SNPs in 13 immune-related genes and investigated their associations with BA by using a large case‒control cohort with a total of 503 cases and 1473 controls from southern China. RESULTS: SNP rs1518111 in interleukin10 (IL10) was identified as associated with BA (P = 5.79E-03; OR: 0.80; 95% CI: 0.68-0.94). The epistatic effects of the following pairwise interactions among these SNPs were associated with BA: signal transducer and activator of transcription 4 (STAT4) and chemokine (C-X-C motif) ligand 3 (CXCL3); STAT4 and damage-regulated autophagy modulator1 (DRAM1); CXCL3 and RAD51 paralog B (RAD51B); and interferon gamma (IFNG) and interleukin26 (IL26). Furthermore, we explored the potential role of IL-10 in the pathogenesis of the neonatal mouse model of BA. IL-10 effectively prevented biliary epithelial cell injury and biliary obstruction in murine BA as well as inhibit the activation of BA-related immune cells. CONCLUSIONS: In conclusion, this study provided strong evidence implicating IL10 as a susceptibility gene for BA in the southern Chinese population. IMPACT: This study provided strong evidence implicating IL10 as a susceptibility gene for BA in the southern Chinese population. This study could infer that IL-10 may play a protective role in BA mouse model. We found that four SNPs (rs7574865, rs352038, rs4622329, and rs4902562) have genetic interactions.

BACKGROUND: We investigated the role of postnatal steroids on the severity of retinopathy of prematurity (ROP) and its impact on peripheral avascular retina (PAR). METHODS: A retrospective cohort study of infants born at ≤32 weeks gestation and/or birth weight ≤1500 g. Demographics, the dose and duration of steroid treatment, and age when full retinal vascularization occurred were collected. The primary outcomes were the severity of ROP and time to full vascularization of the retina. RESULTS: A total of 1695 patients were enrolled, 67% of whom received steroid therapy. Their birth weight was 1142 ± 396 g and gestational age was 28.6 ± 2.7 weeks. The total hydrocortisone-equivalent dose prescribed was 28.5 ± 74.3 mg/kg. The total days of steroid treatment were 8.9 ± 35.1 days. After correction for major demographic differences, infants who received a higher cumulative dose of steroids for a longer duration had a significantly increased incidence of severe ROP and PAR (P < 0.001). For each day of steroid treatment, there was a 3.2% increase in the hazard of the severe form of ROP (95% CI: 1.022-1.043) along with 5.7% delay in achieving full retinal vascularization (95% CI: 1.04-1.08) (P < 0.001). CONCLUSION: Cumulative dose and duration of postnatal steroid use were independently associated with the severity of ROP and PAR. Thus, postnatal steroids should be used very prudently. IMPACT: We report ROP outcomes in a large cohort of infants from two major healthcare systems where we have studied the impact of postnatal steroids on the severity of ROP, growth, and development of retinal vessels. After correcting our data for three major outcome measures, we show that high-dose postnatal steroids used for a prolonged duration of time are independently associated with severe ROP and delay in retinal vascularization. Postnatal steroids impact the visual outcomes of VLBW infants significantly, so their clinical use needs to be moderated.

BACKGROUND: This study provides reference values for cardiovascular modulation at rest, during maximal exercise test and recovery after exercise in Caucasian children according to weight status and cardiorespiratory fitness (CRF) level. Additionally, the current study analyzed several correlations between autonomic cardiovascular modulation, cardiorespiratory performance and cardiometabolic risk. The principal goal of this study was to analyze cardiac function at rest, during maximum exercise, and during the recovery phase in children grouped according to weight status and CRF level. METHODS: One hundred and fifty-two healthy children (78 girls) 10-16 years of age were divided into three groups: soccer and basketball players (SBG), endurance group (EG), and sedentary people with overweight and obesity (OOG). A cardiac RR interval monitor recorded the cardiac data and specific software analyzed the cardiac autonomic response through heart rate (HR) and HR variability. The study analyzed resting HR (RHR), HRpeak, and HR recovery (HRR). RESULTS: OOG showed significant poorer performance in the Léger test lower V̇O2 max and higher values of blood pressure at rest and post-exercise than sport groups. The EG presented the best results in CRF and cardiometabolic risk (CMR) in relation to SBG and OOG. The OOG showed higher percentage of HR values, compatible with an unhealthy cardiovascular autonomic modulation than the sport groups, with significant differences in bradycardia, HR reserve, and HRR 5 min. CONCLUSIONS: Aerobic performance, vagal activity, blood pressure, chronotropic competence, and HRR have significant associations with CMR parameters. IMPACT: The current study presents reference values of autonomic cardiac function in Caucasian children according to weight status and cardiorespiratory fitness level. Aerobic performance, vagal activity, blood pressure, chronotropic competence, and heart rate during the recovery period after exercise have significant associations with cardiometabolic risk parameters. Children with overweight and obesity show signs of autonomic dysfunction reflected as low cardiac vagal activity and poor chronotropic competence.

BACKGROUND: Aromatic L-amino acid decarboxylase (AADC) deficiency is an autosomal recessive neurotransmitter metabolism disorder and is clinically characterized by infancy hypotonia, ophthalmic crisis, and developmental delay. With the emergence of gene therapy for AADC deficiency, accurate prediction of AADC deficiency is required. This study aimed to analyze the carrier frequency and expected incidence of AADC deficiency using exome data from the Genome Aggregation Database (gnomAD). METHODS: We analyzed 125,748 exomes from gnomAD, including 9197 East Asian exomes, for the DDC gene. All identified variants were classified according to the 2015 American College of Medical Genetics and Genomics and the Association for Molecular Pathology guidelines. RESULTS: The worldwide carrier frequency of AADC deficiency was 0.17%; the highest frequency was observed in East Asians at 0.78%, and the lowest was in Latinos at 0.07%. The estimated incidence of AADC deficiency was 1 in 1,374,129 worldwide and 1 in 65,266 in East Asians. CONCLUSION: The results demonstrated that East Asians have a higher carrier frequency of AADC deficiency than other ethnic groups. The variant spectrum of DDC genes in East Asian populations differed greatly from those of other ethnic groups. Our data will serve as a reference for further investigation of AADC deficiency. IMPACT: This study analyzed exome data from the Genome Aggregation Database (gnomAD) to estimate the carrier frequency and expected incidence of aromatic L-amino acid decarboxylase (AADC) deficiency. The article provides updated carrier frequency and incidence estimates for AADC deficiency, particularly in East Asian populations, and emphasizes the significant differences in the variant spectrum of DDC genes in this population compared to other ethnic groups. The study provides important information for accurate prediction and early diagnosis of AADC deficiency, particularly in high-risk populations, and may aid in the development of more effective targeted screening programs and gene therapies for this disorder.

BACKGROUND: Paediatric inflammatory multisystem syndrome (PIMS) is a rare condition temporally associated with SARS-CoV-2 infection. Using national surveillance data, we compare presenting features and outcomes among children hospitalized with PIMS by SARS-CoV-2 linkage, and identify risk factors for intensive care (ICU). METHODS: Cases were reported to the Canadian Paediatric Surveillance Program by a network of >2800 pediatricians between March 2020 and May 2021. Patients with positive versus negative SARS-CoV-2 linkages were compared, with positive linkage defined as any positive molecular or serologic test or close contact with confirmed COVID-19. ICU risk factors were identified with multivariable modified Poisson regression. RESULTS: We identified 406 children hospitalized with PIMS, including 49.8% with positive SARS-CoV-2 linkages, 26.1% with negative linkages, and 24.1% with unknown linkages. The median age was 5.4 years (IQR 2.5-9.8), 60% were male, and 83% had no comorbidities. Compared to cases with negative linkages, children with positive linkages experienced more cardiac involvement (58.8% vs. 37.4%; p < 0.001), gastrointestinal symptoms (88.6% vs. 63.2%; p < 0.001), and shock (60.9% vs. 16.0%; p < 0.001). Children aged ≥6 years and those with positive linkages were more likely to require ICU. CONCLUSIONS: Although rare, 30% of PIMS hospitalizations required ICU or respiratory/hemodynamic support, particularly those with positive SARS-CoV-2 linkages. IMPACT: We describe 406 children hospitalized with paediatric inflammatory multisystem syndrome (PIMS) using nationwide surveillance data, the largest study of PIMS in Canada to date. Our surveillance case definition of PIMS did not require a history of SARS-CoV-2 exposure, and we therefore describe associations of SARS-CoV-2 linkages on clinical features and outcomes of children with PIMS. Children with positive SARS-CoV-2 linkages were older, had more gastrointestinal and cardiac involvement, and hyperinflammatory laboratory picture. Although PIMS is rare, one-third required admission to intensive care, with the greatest risk amongst those aged ≥6 years and those with a SARS-CoV-2 linkage.

BACKGROUND: The majority of neonatal NIRS literature recommends target ranges for cerebral saturation (rScO2) based on data using adult sensors. Neonatal sensors are now commonly used in the neonatal intensive care unit (NICU). However, there is limited clinical data correlating these two measurements of cerebral oxygenation. METHODS: A prospective observational study was conducted in two NICUs between November 2019 and May 2021. An adult sensor was placed on infants undergoing routine cerebral NIRS monitoring with a neonatal sensor. Time-synchronized rScO2 measurements from both sensors, heart rate, and systemic oxygen saturation values were collected over 6 h under varying clinical conditions and compared. RESULTS: Time-series data from 44 infants demonstrated higher rScO2 measurements with neonatal sensors than with adult sensors; however, the magnitude of the difference varied depending on the absolute value of rScO2 (Adult = 0.63 × Neonatal + 18.2). While there was an approximately 10% difference when adult sensors read 85%, readings were similar when adult sensors read 55%. CONCLUSION: rScO2 measured by neonatal sensors is typically higher than measured by adult sensors, but the difference is not fixed and is less at the threshold indicative of cerebral hypoxia. Assuming fixed differences between adult and neonatal sensors may lead to overdiagnosis of cerebral hypoxia. IMPACT: In comparison to adult sensors, neonatal sensors rScO2 readings are consistently higher, but the magnitude of the difference varies depending on the absolute value of rScO2. Marked variability during high and low rScO2 readings was noted, with approximately 10% difference when adult sensors read 85%, but nearly similar (58.8%) readings when adult sensors read 55%. Estimating fixed differences of approximately 10% between adult and neonatal probes may lead to an inaccurate diagnosis of cerebral hypoxia and result in subsequent unnecessary interventions.

Despite considerable advances, there is a need to improve the outcomes of newborn infants, especially related to prematurity, encephalopathy and other conditions. In principle, cell therapies have the potential to protect, repair, or sometimes regenerate vital tissues; and improve or sustain organ function. In this review, we present highlights from the First Neonatal Cell Therapies Symposium (2022). Cells tested in preclinical and clinical studies include mesenchymal stromal cells from various sources, umbilical cord blood and cord tissue derived cells, and placental tissue and membrane derived cells. Overall, most preclinical studies suggest potential for benefit, but many of the cells tested were not adequately defined, and the optimal cell type, timing, frequency, cell dose or the most effective protocols for the targeted conditions is not known. There is as yet no clinical evidence for benefit, but several early phase clinical trials are now assessing safety in newborn babies. We discuss parental perspectives on their involvement in these trials, and lessons learnt from previous translational work of promising neonatal therapies. Finally, we make a call to the many research groups around the world working in this exciting yet complex field, to work together to make substantial and timely progress to address the knowledge gaps and move the field forward. IMPACT: Survival of preterm and sick newborn infants is improving, but they continue to be at high risk of many systemic and organ-specific complications. Cell therapies show promising results in preclinical models of various neonatal conditions and early phase clinical trials have been completed or underway. Progress on the potential utility of cell therapies for neonatal conditions, parental perspectives and translational aspects are discussed in this paper.

Finding and respecting the human facets of the patient-parent-physician relationship will enable us to return to where we come from and to offer what is worthy of the appellation "care". The poem adds a piece to the mosaic of humanist pediatrics. Hopefully, the message will add a silver lining to the clouds of professional responsibility and burnout hovering over large parts of the pediatric workforce.

BACKGROUND: Systemic inflammation plays a key role in the development of bronchopulmonary dysplasia (BPD). Cortisol is known to dampen inflammation. However, adrenal function following preterm birth is characterized by insufficient cortisol levels for the degree of inflammation, and a relative abundancy of cortisol precursors. We investigated whether this pattern could contribute to the development of BPD in preterm infants born <30 weeks of gestation. METHODS: Cortisol, cortisone, 17-OH progesterone (17-OHP) and 11-deoxycortisol were measured in serum obtained at postnatal days 1, 3, 7, 14 and 28, using liquid-chromatography-tandem-mass-spectrometry. The presence of BPD was ascertained at 36 weeks postmenstrual age. RESULTS: Sixty-five infants were included for analysis, of whom 32 (49%) developed BPD. Preterm infants developing BPD, as compared to those without BPD, had higher levels of 17-OHP, 11-deoxycortisol and cortisone relative to cortisol in their first week of life, but not at birth or beyond day 7. CONCLUSION: Preterm infants developing BPD had higher levels of cortisol precursors and cortisone relative to cortisol in their first week of life than infants without BPD. These findings suggest that BPD is preceded by an activated hypothalamus-pituitary-adrenal axis that could not meet the high cortisol demands, which may predispose to inflammation and BPD. IMPACT: Relative adrenal insufficiency is common in the first weeks after preterm birth, resulting in insufficient cortisol production for the degree of inflammation and a relative abundance of cortisol precursors; Whether this pattern contributes to the development of bronchopulmonary dysplasia (BPD) is not fully elucidated, since most studies focused on cortisol levels; Preterm infants developing BPD had higher levels of cortisol precursors and cortisone relative to cortisol in the first week of life, suggestive of a hypothalamus-pituitary-adrenal-axis activation during BPD development which cannot meet the high cortisol demands in tissues; This glucocorticoid pattern is likely to dispose to inflammation and BPD.

BACKGROUND: Despite treatment with therapeutic hypothermia, hypoxic-ischemic encephalopathy (HIE) is associated with adverse developmental outcomes, suggesting the involvement of subcortical structures including the thalamus and basal ganglia, which may be vulnerable to perinatal asphyxia, particularly during the acute period. The aims were: (1) to examine subcortical macrostructure in neonates with HIE compared to age- and sex-matched healthy neonates within the first week of life; (2) to determine whether subcortical brain volumes are associated with HIE severity. METHODS: Neonates (n = 56; HIE: n = 28; Healthy newborns from the Developing Human Connectome Project: n = 28) were scanned with MRI within the first week of life. Subcortical volumes were automatically extracted from T1-weighted images. General linear models assessed between-group differences in subcortical volumes, adjusting for sex, gestational age, postmenstrual age, and total cerebral volumes. Within-group analyses evaluated the association between subcortical volumes and HIE severity. RESULTS: Neonates with HIE had smaller bilateral thalamic, basal ganglia and right hippocampal and cerebellar volumes compared to controls (all, p < 0.02). Within the HIE group, mild HIE severity was associated with smaller volumes of the left and right basal ganglia (both, p < 0.007) and the left hippocampus and thalamus (both, p < 0.04). CONCLUSIONS: Findings suggest that, despite advances in neonatal care, HIE is associated with significant alterations in subcortical brain macrostructure. IMPACT: Compared to their healthy counterparts, infants with HIE demonstrate significant alterations in subcortical brain macrostructure on MRI acquired as early as 4 days after birth. Smaller subcortical volumes impacting sensory and motor regions, including the thalamus, basal ganglia, and cerebellum, were seen in infants with HIE. Mild and moderate HIE were associated with smaller subcortical volumes.

BACKGROUND: Sociodemographic disparities in adolescent physical activity have been documented but mostly rely on self-reported data. Our objective was to examine differences in device-based step metrics, including daily step count (steps d-1), by sociodemographic factors among a diverse sample of 10-to-14-year-old adolescents in the US. METHODS: We analyzed prospective cohort data from Year 2 (2018-2020) of the Adolescent Brain Cognitive Development (ABCD) Study (N = 6460). Mixed-effects models were conducted to estimate associations of sociodemographic factors (sex, sexual orientation, race/ethnicity, household income, parental education, and parental marital status) with repeated measures of steps d-1 over the course of 21 days. RESULTS: Participants (49.6% female, 39.0% racial/ethnic minority) accumulated an average of 9095.8 steps d-1. In mixed-effects models, 1543.6 more steps d-1 were recorded for male versus female sex, Black versus White race (328.8 more steps d-1), heterosexual versus sexual minority sexual orientation (676.4 more steps d-1), >$200,000 versus <$25,000 household income (1003.3 more steps d-1), and having married/partnered parents versus unmarried/unpartnered parents (326.3 more steps d-1). We found effect modification by household income for Black adolescents and by sex for Asian adolescents. CONCLUSIONS: Given sociodemographic differences in adolescent steps d-1, physical activity guidelines should focus on key populations and adopt strategies optimized for adolescents from diverse backgrounds. IMPACT: Sociodemographic disparities in physical activity have been documented but mostly rely on self-reported data, which can be limited by reporting and prevarication bias. In this demographically diverse sample of 10-14-year-old early adolescents in the U.S., we found notable and nuanced sociodemographic disparities in Fitbit steps per day. More daily steps were recorded for male versus female sex, Black versus White race, heterosexual versus sexual minority, >$100,000 versus <$25,000 household income, and having married/partnered versus unmarried/unpartnered parents. We found effect modification by household income for Black adolescents and by sex for Asian adolescents.

BACKGROUND: Prenatal or postnatal lung inflammation and oxidative stress disrupt alveolo-vascular development leading to bronchopulmonary dysplasia (BPD) with and without pulmonary hypertension. L-citrulline (L-CIT), a nonessential amino acid, alleviates inflammatory and hyperoxic lung injury in preclinical models of BPD. L-CIT modulates signaling pathways mediating inflammation, oxidative stress, and mitochondrial biogenesis-processes operative in the development of BPD. We hypothesize that L-CIT will attenuate lipopolysaccharide (LPS)-induced inflammation and oxidative stress in our rat model of neonatal lung injury. METHODS: Newborn rats during the saccular stage of lung development were used to investigate the effect of L-CIT on LPS-induced lung histopathology and pathways involved in inflammatory, antioxidative processes, and mitochondrial biogenesis in lungs in vivo, and in primary culture of pulmonary artery smooth muscle cells, in vitro. RESULTS: L-CIT protected the newborn rat lung from LPS-induced: lung histopathology, ROS production, NFκB nuclear translocation, and upregulation of gene and protein expression of inflammatory cytokines (IL-1β, IL-8, MCP-1α, and TNF-α). L-CIT maintained mitochondrial morphology, increased protein levels of PGC-1α, NRF1, and TFAM (transcription factors involved in mitochondrial biogenesis), and induced SIRT1, SIRT3, and superoxide dismutases protein expression. CONCLUSION: L-CIT may be efficacious in decreasing early lung inflammation and oxidative stress mitigating progression to BPD. IMPACT: The nonessential amino acid L-citrulline (L-CIT) mitigated lipopolysaccharide (LPS)-induced lung injury in the early stage of lung development in the newborn rat. This is the first study describing the effect of L-CIT on the signaling pathways operative in bronchopulmonary dysplasia (BPD) in a preclinical inflammatory model of newborn lung injury. If our findings translate to premature infants, L-CIT could decrease inflammation, oxidative stress and preserve mitochondrial health in the lung of premature infants at risk for BPD.

BACKGROUND: Despite multifactorial pathogenesis, dysregulation of inflammatory immune response may play a crucial role in necrotizing enterocolitis (NEC). Regulatory T cells (Tregs) are involved in immune tolerance early in life. We aimed to investigate the predicting role of Tregs in developing NEC in neonates at high risk. METHODS: We studied six newborns with a diagnosis of NEC (cases) in comparison with 52 controls (without NEC). We further classified controls as neonates with feeding intolerance (FI) and neonates without it (FeedTol). The rate of female and male neonates (sex defined as a biological attribute) was similar. We analyzed the blood frequency of Tregs (not overall numbers) at three time points: 0-3 (T0), 7-10 (T1), and 27-30 (T2) days after birth by flow cytometry. Neonates' sex was defined based on the inspection of external genitalia at birth. RESULTS: We observed, at T0, a significantly lower frequency of Tregs in NEC cases (p < 0.001) compared with both FI (p < 0.01) and FeedTol controls (p < 0.01). Multivariate analysis reported that the occurrence of NEC was independently influenced by Treg frequency at birth (ß 2.98; p = 0.039). CONCLUSION: Tregs frequency and features in the peripheral blood of preterm neonates, early in life, may contribute to identifying neonates at high risk of developing NEC. IMPACT: Regulatory T cells may play a pivotal role in regulating the immune response in early life. Reduction of Tregs in early life could predispose preterm newborns to necrotizing enterocolitis. Early markers of necrotizing enterocolitis are still lacking. We demonstrated a predicting role of assessment of regulatory T cells in the diagnosis of this gastrointestinal emergency. Early identification of newborns at high risk of necrotizing enterocolitis through measurement of regulatory T cells may guide clinicians in the management of preterm newborns in order to reduce the development of this severe condition.

While pregnancy post-bariatric surgery has become increasingly common, little is known about whether and how maternal bariatric surgery affects the next generation. This scoping review aimed to collate available evidence about the long-term health of offspring following maternal bariatric surgery. A literature search was conducted using three databases (PubMed, PsycINFO, EMBASE) to obtain relevant human and animal studies. A total of 26 studies were included: 17 were ancillary reports from five "primary" studies (three human, two animal studies) and the remaining nine were "independent" studies (eight human, one animal studies). The human studies adopted sibling-comparison, case-control, and single-group descriptive designs. Despite limited data and inconsistent results across studies, findings suggested that maternal bariatric surgery appeared to (1) modify epigenetics (especially genes involved in immune, glucose, and obesity regulation); (2) alter weight status (unclear direction of alteration); (3) impair cardiometabolic, immune, inflammatory, and appetite regulation markers (primarily based on animal studies); and (4) not affect the neurodevelopment in offspring. In conclusion, this review supports that maternal bariatric surgery has an effect on the health of offspring. However, the scarcity of studies and heterogenous findings highlight that more research is required to determine the scope and degree of such effects. IMPACT: There is evidence that bariatric surgery modifies epigenetics in offspring, especially genes involved in immune, glucose, and obesity regulation. Bariatric surgery appears to alter weight status in offspring, although the direction of alteration is unclear. There is preliminary evidence that bariatric surgery impairs offspring's cardiometabolic, immune, inflammatory, and appetite regulation markers. Therefore, extra care may be needed to ensure optimal growth in children born to mothers with previous bariatric surgery.

BACKGROUND: Baby-led weaning (BLW) is an alternative method to spoon-feeding to introduce solid foods. This study aimed to describe and understand the experiences and opinions of pediatricians and pediatric nurse specialists of the implementation of the BLW approach. METHODS: An interpretive descriptive qualitative research was carried out. A focus group with 7 participants and 13 face-to-face interviews were conducted between February and May 2022 (17 females and 3 males). All were audio-recorded, transcribed, and analyzed with the supported by Atlas.Ti qualitative data analysis software. RESULTS: From the data, two themes developed: (1) BLW as an ideal method of introducing solid food, with the subthemes: "a natural method of introducing complementary feeding" and "BLW is a safe method"; (2) Perceived barriers to the uptake of the BLW method, with the subthemes: "a lack of BLW training prevents the best practice" and "the influence of family and social context on parents." CONCLUSIONS: Healthcare professionals perceive BLW to be a safe and natural weaning approach. The lack of training of healthcare professionals and the influence of family social context on parents may limit the implementation of BLW. IMPACT: Baby-led weaning is perceived by healthcare professionals as a safe complementary feeding method that promotes chewing, improves growth, and the development of fine motor skills. However, lack of training of healthcare professionals and the family social context of the parents hinders the uptake of baby-led weaning. The views of the family and parents' social context about baby-led weaning may restrict their willingness to use the method. Family education delivered by healthcare professionals may avoid risks and allay parental anxieties about safety.

BACKGROUND: Extremely low birth weight (ELBW) infants comprise a fragile population at risk for neurodevelopmental disabilities (NDD). Systemic steroids were previously associated with NDD, but more recent studies suggest hydrocortisone (HCT) may improve survival without increasing NDD. However, the effects of HCT on head growth adjusted for illness severity during NICU hospitalization are unknown. Thus, we hypothesize that HCT will protect head growth, accounting for illness severity using a modified neonatal Sequential Organ Failure Assessment (M-nSOFA) score. METHODS: We conducted a retrospective study that included infants born at 23-29 weeks gestational age (GA) and < 1000 g. Our study included 73 infants, 41% of whom received HCT. RESULTS: We found negative correlations between growth parameters and age, similar between HCT and control patients. HCT-exposed infants had lower GA but similar normalized birth weights; HCT-exposed infants also had higher illness severity and longer lengths of hospital stay. We found an interaction between HCT exposure and illness severity on head growth, such that infants exposed to HCT had better head growth compared to those not exposed to HCT when adjusted for illness severity. CONCLUSION: These findings emphasize the importance of considering patient illness severity and suggest that HCT use may offer additional benefits not previously considered. IMPACT: This is the first study to assess the relationship between head growth and illness severity in extremely preterm infants with extremely low birth weights during their initial NICU hospitalization. Infants exposed to hydrocortisone (HCT) were overall more ill than those not exposed, yet HCT exposed infants had better preserved head growth relative to illness severity. Better understanding of the effects of HCT exposure on this vulnerable population will help guide more informed decisions on the relative risks and benefits for HCT use.

BACKGROUND: We assessed (a) the effects of postpartum depression (PPD) trajectories until 6 months postpartum on infants' socioemotional development (SED) at age 12 months, and (b) the mediating role of maternal self-efficacy (MSE), and the additional effect of postpartum anxiety at age 12 months. METHODS: We used data from POST-UP trial (n = 1843). PPD was assessed using the Edinburgh Postnatal Depression Scale (EPDS) at 1, 3, and 6 months. Infants' SED was assessed at 12 months using the Ages and Stages Questionnaire-Social-Emotional (ASQ-SE). Structural equations were applied to estimate the effect of PPD trajectories on infants' SED and mediation by MSE. The additional effects of postpartum anxiety were assessed with conditional regression. RESULTS: Higher levels of PPD over time were associated with a lower SED (coefficient for log-EPDS 3.5, 95% confidence interval 2.8; 4.2, e.g., an increase in the EPDS score from 9 to 13 worsens the ASQ-SE by 1.3 points). About half of this relationship was mediated by MSE. Postpartum anxiety had an independent adverse effect on SED. CONCLUSIONS: PPD and postpartum anxiety have a negative impact on infants' SED. MSE as a mediator may be a potential target for preventive interventions to alleviate the negative effects of maternal psychopathology on infants' SED. IMPACT: The trajectories of postpartum depression (PPD) from 1 month to 6 months were negatively related to infants' socioemotional development (SED) at age 12 months, underlining the importance of repeated assessment of PPD. Maternal self-efficacy (MSE) mediated the association between PPD and SED, implying MSE could be a potential target for preventive interventions. An additional independent negative effect of postpartum anxiety was identified, implying the assessment of postpartum anxiety also has a surplus value to identify mothers at risk.

BACKGROUND: Advances in surgical and neonatal care have led to improved survival of patients with œsophageal atresia (OA) over time. Morbidity remains significant, with one-third of patients being affected by a postoperative complication. Several aspects of management are not consensual, such as the use of œsophagogram before starting oral feeding. METHODS: We conducted a multicenter retrospective study, including all children with OA that underwent a primary anastomosis in the first days of life, between 2012 and 2018 in five French centers, to determine the usefulness of postoperative œsophagogram during the 10 days after early primary repair of OA to diagnose the anastomotic leak and congenital œsophageal stenosis. RESULTS: Among 225 included children, 90 (40%) had a routine œsophagogram and 25 (11%) had an anastomotic leak, clinically diagnosed before the scheduled œsophagogram in 24/25 (96%) children at median postoperative day 4. Ten patients had associated congenital œsophageal stenosis diagnosed on the œsophagogram in only 30% of cases. CONCLUSION: Early œsophagogram is rarely useful in the diagnosis of an anastomotic leak, which is clinically diagnosed before performing an œsophagogram in the majority of cases. The need for a postoperative œsophagogram should be evaluated on a case-by-case basis. IMPACT: Early œsophagogram is not helpful in the diagnosis of an anastomotic leak in the majority of cases. An anastomotic leak is most often diagnosed clinically before performing an œsophagogram. Early postoperative œsophagogram could be helpful for the diagnosis of congenital œsophageal stenosis. However, dysphagia occurs later and early diagnosis of congenital œsophageal stenosis has no impact on the management and outcome of asymptomatic children. Indication of postoperative œsophagogram has to be evaluated on a case-by-case basis.

BACKGROUND: Perfluoroalkyl substances (PFASs) are transferred through human milk and may cause elevated exposure during infancy. Given the lack of early postnatal blood samples, PFAS concentrations can be estimated to serve as predictors of subsequent metabolic toxicity. METHODS: A total of 298 children from a prospective birth cohort were followed up through to age 9 years. Serum-PFAS was measured at birth and 18 months of age, while exposures during infancy were estimated by structural equations. Adiponectin, resistin, leptin, and the leptin receptor were measured in serum at age 9. Adjusted regression coefficients for estimated serum-PFAS concentrations were calculated, with additional consideration of the duration of breastfeeding and potential effect modification by sex. RESULTS: A doubling in estimated serum-PFAS concentrations, particularly at ages 6 and 12 months, was associated with a loss of about 10-15% in age 9 resistin concentrations, while other associations were much weaker. Sex dependence of the associations was not observed, and neither did the duration of breastfeeding affect outcomes at age 9. CONCLUSION: Lowered serum-resistin concentrations at age 9 years were most strongly associated with early postnatal PFAS exposures. These findings suggest that infancy may represent a vulnerable time window for some aspects of metabolic programming that may be affected by PFAS exposure. IMPACT: Serum-PFAS concentrations during infancy can be estimated in the absence of blood samples. Adipokine concentrations were measured at age 9 years as metabolic biomarkers. Resistin was significantly lower in children with elevated PFAS exposures in infancy. The findings suggest that early postnatal PFAS exposures may affect subsequent metabolic health. Assessment of infancy vulnerability to PFAS can be explored using estimated serum-PFAS concentrations.

BACKGROUND: Opportunities for adjunct therapies with cooling in neonatal encephalopathy are imminent; however, robust biomarkers of early assessment are lacking. Using an optical platform of broadband near-infrared spectroscopy and diffuse correlation spectroscopy to directly measure mitochondrial metabolism (oxCCO), oxygenation (HbD), cerebral blood flow (CBF), we hypothesised optical indices early (1-h post insult) after hypoxia-ischaemia (HI) predicts insult severity and outcome. METHODS: Nineteen newborn large white piglets underwent continuous neuromonitoring as controls or following moderate or severe HI. Optical indices were expressed as mean semblance (phase difference) and coherence (spectral similarity) between signals using wavelet analysis. Outcome markers included the lactate/N-acetyl aspartate (Lac/NAA) ratio at 6 h on proton MRS and TUNEL cell count. RESULTS: CBF-HbD semblance (cerebrovascular dysfunction) correlated with BGT and white matter (WM) Lac/NAA (r2 = 0.46, p = 0.004, r2 = 0.45, p = 0.004, respectively), TUNEL cell count (r2 = 0.34, p = 0.02) and predicted both initial insult (r2 = 0.62, p = 0.002) and outcome group (r2 = 0.65 p = 0.003). oxCCO-HbD semblance (cerebral metabolic dysfunction) correlated with BGT and WM Lac/NAA (r2 = 0.34, p = 0.01 and r2 = 0.46, p = 0.002, respectively) and differentiated between outcome groups (r2 = 0.43, p = 0.01). CONCLUSION: Optical markers of both cerebral metabolic and vascular dysfunction 1 h after HI predicted injury severity and subsequent outcome in a pre-clinical model. IMPACT: This study highlights the possibility of using non-invasive optical biomarkers for early assessment of injury severity following neonatal encephalopathy, relating to the outcome. Continuous cot-side monitoring of these optical markers can be useful for disease stratification in the clinical population and for identifying infants who might benefit from future adjunct neuroprotective therapies beyond cooling.

BACKGROUND: A variable percentage of children and adolescents with obesity do not have cardiometabolic comorbidities. A phenotype called metabolically healthy obese (MHO) has emerged to describe this population subgroup. Early identification of this condition may prevent the progression to metabolically unhealthy obesity (MUO). MATERIAL AND METHODS: A cross-sectional descriptive study of 265 children and adolescents from Cordoba (Spain) conducted in 2018. The outcome variables were MHO, established based on three criteria: International Criterion, HOMA-IR, and a combination of the previous two. RESULTS: The prevalence of MHO ranged from 9.4% to 12.8% of the study population, between 41% and 55.7% of the sample with obesity. The highest agreement was reached between the HOMA-IR definitions and the combined criteria. The waist-to-height ratio (WHtR) was the indicator with the highest discriminant capacity for MHO in 2 of the three criteria, with its best cut-off point at 0.47 for both. CONCLUSION: The prevalence of MHO in children and adolescents differed according to the criteria used for diagnosis. The anthropometric variable with the most remarkable discriminating capacity for MHO was WHtR, with the same cut-off point in the three criteria analysed. IMPACT STATEMENT: This research work defines the existence of metabolically healthy obesity through anthropometric indicators in children and adolescents. Definitions that combine cardiometabolic criteria and insulin resistance are used to identify metabolically healthy obesity, as well as the prediction of this phenomenon through anthropometric variables. The present investigation helps to identify metabolically healthy obesity before metabolic abnormalities begin.

BACKGROUND: COVID-19 pandemic introduced significant challenges that may have exacerbated healthcare worker (HCW) burnout. To date, assessments of burnout during COVID-19 pandemic have been cross-sectional, limiting our understanding of changes in burnout. This longitudinal study assessed change across time in pediatric HCW burnout during the COVID-19 pandemic and whether demographic and psychological factors were associated with changes in burnout. METHODS: This longitudinal study included 162 physicians, physician assistants, nurses, and medical technicians within the emergency department (ED), intensive care, perioperative, and inter-hospital transport services in a children's hospital. HCW demographics, anxiety and personality traits were reported via validated measures. HCWs completed the Maslach Burnout Inventory in April 2020 and March 2021. Data were analyzed using generalized estimating equations. RESULTS: The percentage of HCWs reporting high emotional exhaustion and/or depersonalization burnout increased significantly across time (18.5% to 28.4%, P = 0.010). Factors associated with increased emotional exhaustion included working in the ED (P = 0.011) or perioperative department (P < 0.001), being a nurse or medical technician (P's < 0.001), not having children (P < 0.001), and low conscientiousness (P < 0.001). CONCLUSIONS: Pediatric HCW burnout significantly increased over 11-months of the COVID-19 pandemic. Results suggest that certain demographic and psychological factors may represent potential area to target for intervention for future pandemics. IMPACT: This longitudinal study revealed that the COVID-19 pandemic has had a significant impact on pediatric healthcare worker burnout. The percentage of healthcare workers reporting high levels of emotional exhaustion and depersonalization burnout increased significantly over 11-months of the COVID-19 pandemic. Results suggest that certain demographic and psychological factors may represent potential targets for future interventions.

BACKGROUND: Phthalates exposure might affect children's intelligence development. This study aimed to determine (1) whether sex and age affect cognitive function and (2) whether sex differences in cognitive performance are wider with higher phthalate concentrations. METHODS: Data were collected from PubMed (1998-2022), PROQUEST (1997-2022), and SpringerLink (1995-2022). The study followed the PRISMA process. The included articles were followed by PECO framework. The GRADE applied to assess the certainty of evidence. Of 2422 articles obtained, nine were selected using inclusion criteria. The random-effects model was used to estimate the pooled effects. RESULTS: Our meta-regression indicated a significant difference between sex differences with age at phthalate concentration assessment (β = -0.25; 95% CI = -0.47, -0.03) and MEHP concentration (β = -0.20; 95% CI = -0.37, -0.03). CONCLUSIONS: The limitation of the current article is it only provides information on intelligence level rather than other aspects of cognitive function. Thus, the sequelae of phthalate exposure on attention and executive function are still unclear. Our analysis shows significant difference between sex differences in cognitive function scores associated with age at phthalate concentration assessment. Girls might be more resilient in cognitive function at a younger age or during lower concentrations of phthalates metabolites. IMPACT: This is the first meta-analysis to evaluate the pooled estimates of sex differences in objective cognitive functions among children with phthalate exposure. The female might be a protective factor when exposed to toxic plasticizers while the concentration is low. This study captures the possible role of sex in cognitive functioning and plasticizer exposure through a meta-analysis of children's sex, cognitive scores, and plasticizer exposure.

Author information: (1)University Hospitals Bristol NHS Foundation Trust, Bristol, UK. avramanan@hotmail.com. (2)Translational Health Sciences, University of Bristol, Bristol, UK. avramanan@hotmail.com. (3)Section of Neonatal Medicine, Department of Public Health and Primary Care, Imperial College London, London, UK. (4)Chelsea and Westminster NHS Foundation Trust, London, UK. (5)Department of Pharmacology and Toxicology, Radboud Institute for Health Sciences, Radboudumc, Nijmegen, The Netherlands. (6)Intensive Care and Department of Paediatric Surgery, Erasmus MC Sophia Children's Hospital, Rotterdam, The Netherlands.