Using metabolic abnormalities of carriers in the neonatal period to evaluate the pathogenicity of variants of uncertain significance in methylmalonic acidemia.

Objective: To accurately verify the pathogenicity of variants of uncertain significance (VUS) in MUT and MMACHC genes through mass spectrometry and silico analysis. Methods: This multicenter retrospective study included 35 participating units (ClinicalTrials.gov ID: NCT06183138). A total of 3,071 newborns (within 7 days of birth) were sorted into carrying pathogenic/likely pathogenic (P/LP) variants and carrying VUS, non-variant groups. Differences in metabolites among the groups were calculated using statistical analyses. Changes in conservatism, free energy, and interaction force of MMUT and MMACHC variants were analyzed using silico analysis. Results: The percentage of those carrying VUS cases was 68.15% (659/967). In the MMUT gene variant, we found that C3, C3/C2, and C3/C0 levels in those carrying the P/LP variant group were higher than those in the non-variant group (p < 0.000). The conservative scores of those carrying the P/LP variant group were >7. C3, C3/C0, and C3/C2 values of newborns carrying VUS (c.1159A>C and c.1286A>G) were significantly higher than those of the non-variant group and the remaining VUS newborns (p < 0.005). The conservative scores of c.1159A>C and c.1286A>G calculated by ConSurf analysis were 9 and 7, respectively. Unfortunately, three MMA patients with c.1159A>C died during the neonatal period; their C3, C3/C0, C3/C2, and MMA levels were significantly higher than those of the controls. Conclusion: Common variants of methylmalonic acidemia in the study population were categorized as VUS. In the neonatal period, the metabolic biomarkers of those carrying the P/LP variant group of the MUT gene were significantly higher than those in the non-variant group. If the metabolic biomarkers of those carrying VUS are also significantly increased, combined with silico analysis the VUS may be elevated to a likely pathogenic variant. The results also suggest that mass spectrometry and silico analysis may be feasible screening methods for verifying the pathogenicity of VUS in other inherited metabolic diseases.

Iron administered in the neonatal period changed memory, brain monoamine levels, and BDNF mRNA expression in adult Sprague-Dawley rats.

BACKGROUND: Iron is one of the key microelements in the mammalian body and is the most abundant metal in the brain. Iron, a very important chemical element in the body of mammals, is the most abundant metal in the brain. It participates in many chemical reactions taking place in the central nervous system acting as a cofactor in key enzymatic reactions involved in neurotransmitter synthesis and degradation, dendritic arborization, and myelination. Moreover, iron accumulation in the brain has been implicated in the pathogenesis of neurogenerative disorders. MATERIAL AND METHODS: The aim of our study was to assess the influence of iron administered orally (30 mg/kg) to rats in the neonatal period (p12-p14) by testing the performance of rats in the open field and social interaction tests, and by evaluating the recognition memory, monoamine levels in some brain structures, and BDNF mRNA expression. The behavioral and biochemical tests were performed in adult p88-p92 rats. RESULTS: Iron administered to rats in the neonatal period induced long-term deficits in behavioral tests in adult rats. It reduced the exploratory activity in the open field test. In the social interaction test, it induced deficits in the parameters studied, and decreased memory retention. Moreover, iron changed the brain monoamine levels in some studied brain structures and decreased the expression of BDNF mRNA in the hippocampus. CONCLUSIONS: All earlier and our present results indicated that iron administered to rats in the neonatal period induced an increase in oxidative stress which resulted in a change in the brain monoamine levels and decreased BDNF mRNA expression which may play a role in iron-induced memory impairment in adult rats.

Neonatal dysregulation of 2-arachidonoylglycerol induces impaired brain function in adult mice.

The endocannabinoid system (ECS) regulates neurotransmission linked to synaptic plasticity, cognition, and emotion. While it has been demonstrated that dysregulation of the ECS in adulthood is relevant not only to central nervous system (CNS) disorders such as autism spectrum disorder, cognitive dysfunction, and depression but also to brain function, there are few studies on how dysregulation of the ECS in the neonatal period affects the manifestation and pathophysiology of CNS disorders later in life. In this study, DO34, a diacylglycerol lipase alpha (DAGLα) inhibitor affecting endocannabinoid 2-AG production, was injected into C57BL/6N male mice from postnatal day (PND) 7 to PND 10, inducing dysregulation of the ECS in the neonatal period. Subsequently, we examined whether it affects neuronal function in adulthood through electrophysiological and behavioral evaluation. DO34-injected mice showed significantly decreased cognitive functions, attributed to impairment of hippocampal synaptic plasticity. The findings suggest that regulation of ECS activity in the neonatal period may induce enduring effects on adult brain function.

Laparoscopic pyeloplasty for newborns with severe hydronephrosis.

Aim: We aimed to investigate the short-term efficacy and safety of laparoscopic pyeloplasty for treating newborns with severe hydronephrosis due to ureteropelvic junction obstruction (UPJO). Methods: A retrospective analysis was performed on 16 newborn patients with severe neonatal hydronephrosis who underwent laparoscopic pyeloplasty at our hospital from January 2021 to November 2022. All patients were regularly followed up. Laparoscopic pyeloplasty with double J stent placement was performed after the presence of severe hydronephrosis was confirmed. Results: Among the 16 pediatric patients (13 males, 3 females), the left side was affected in 13 cases and the right side in 3. The average age at surgery was 9.50 (8.50-12.00) days, with an average weight of 3.30 ± 0.95 kg. Laparoscopic pyeloplasty was performed in all cases without the need for open conversion. The mean surgery duration was 292.06 ± 73.60 min, with minimal blood loss (2.50, 2.00-5.00 ml). Postoperative hospital stays averaged 13.44 ± 4.70 days. No anastomotic leakage occurred, and follow-ups at 1, 3, 6, and 12 months showed no stent displacement, except for one case where the stent was removed at 1 month, and the others at 3 months. There were no cases of worsened hydronephrosis, except for one with renal atrophy at the 6-month follow-up. Changes in renal pelvis anteroposterior diameter exhibited a time effect (F = 49.281, P < 0.001), with significant differences at 1, 3, 6, and 12 months postoperatively compared to preoperative values (P < 0.05). Notably, differences were observed between 6 and 3 months, as well as between 12 and 3 months postoperatively (P < 0.05). Similarly, renal parenchymal thickness changes showed a time effect Pediatric urology, Guangdong Women and Children Hospital, Guangzhou, China (F = 49.281, P < 0.001), with significant differences at 1, 3, 6, and 12 months postoperatively compared to preoperative values (P < 0.05). Significant differences were also noted between 6 and 1 month, as well as between 12 and 1 month postoperatively (P < 0.05). There was one case of urinary tract infection after surgery, and no case of recurrence was observed. Conclusion: Severe neonatal hydronephrosis must be treated promptly. Laparoscopic pyeloplasty is a safe and feasible treatment with minimal complications for newborn patients with severe hydronephrosis due to UPJO.

Neurodevelopment outcomes in the first 5 years of the life of children with transposition of the great arteries surgically corrected in the neonatal period: systematic review and meta-analysis.

OBJECTIVES: In patients with transposition of the great arteries, surgical correction may achieve definitive treatment, so a thorough knowledge of the long-term outcomes, particularly neurodevelopment outcomes, is essential. Therefore, we conducted a systematic review and meta-analysis to study the neurodevelopment outcomes in the first 5 years of the life of children submitted to corrective surgery for transposition of the great arteries in the neonatal period. METHODS: A total of 17 studies from 18 reports were included, assessing 809 individuals with surgically corrected transposition of the great arteries. The neurodevelopmental outcomes were assessed with the Bayley Scales of Infant and Toddler Development (BSID) and the Wechsler Intelligence Scale for Children (WISC). RESULTS: Mean Mental Development Index (MDI) and Psychomotor Development Index (PDI) were within the average values from 1 to 3 years of age, although the proportion of children scoring more than 1 standard deviation below the mean in PDI, MDI, motor, and language composite scores was significantly higher than in the general population. From 4 to 5 years, mean full-scale global intelligence quotient (IQ), verbal IQ, and performance IQ scores did not differ significantly from the general population. CONCLUSION: This study revealed neurodevelopment scores within the normal range at 5 years of age in children submitted to corrective surgery for transposition of the great arteries in the neonatal period. However, these early outcomes may not adequately predict long-term outcomes. Further studies are needed to identify specific risk factors and early markers of later impairment to guide the establishment of early interventions.

Long-Term Effect of Moderate Hypoxia and Chronic Administration of Fluoxetine during the Neonatal Period on Cognitive and Stress-Hormonal Functions in Adult Male Rats.

We studied the effect of moderate neonatal normobaric hypoxia on the indicators of spatial learning, memory, and reactivity of the hypothalamic-pituitary-adrenocortical system in adult male Wistar rats. The pharmacological effect of chronic injections of the serotonin reuptake inhibitor fluoxetine during the neonatal period on the studied behavioral and the physiological indices was evaluated. Hypoxia impaired spatial training, increased the short-term memory performance, but did not change long-term memory and stress indicator in response to its testing. The use of fluoxetine normalized learning, but did not change memory indicators and the stress-induced level of corticosterone in blood plasma in the hypoxic rats and control animals. New results indicate a protective effect of fluoxetine in the neonatal period under conditions of moderate normobaric hypoxia.

Fibroblast growth factor 23 levels in cord and peripheral blood during early neonatal period as possible predictors of affected offspring of X-linked hypophosphatemic rickets: report of three female cases from two pedigrees.

OBJECTIVES: The role of serum fibroblast growth factor 23 (FGF23) level in early neonatal period on the diagnosis of X-linked hypophosphatemic rickets (XLH) remains unclear. CASE PRESENTATION: Two female patients from the first pedigree had an affected mother, and the other female from the second pedigree had an affected father. In all three cases, FGF23 levels were high in cord blood and peripheral blood at day 4-5. Additionally, the FGF23 levels considerably increased from birth to day 4-5. We identified a PHEX pathogenic variant and initiated treatment during infancy in each case. CONCLUSIONS: In neonates with a parent diagnosed as PHEX-associated XLH, FGF23 in cord blood and peripheral blood at day 4-5 may be useful markers for predicting the presence of XLH.

EFFICACY OF PRIMARY REHABILITATION MEASURES ASSOCIATED WITH THE DEVELOPMENT OF RECURRENT BRONCHIAL OBSTRUCTION SYNDROME IN YOUNG CHILDREN WITH RESPIRATORY DISORDERS IN NEONATAL PERIOD.

OBJECTIVE: The aim: To improve primary prophylactic measures associated with the development and progression of recurrent bronchial obstruction syndrome in young children, who had suffered respiratory disorders in neonatal period. PATIENTS AND METHODS: Materials and methods: Algorithm of primary prophylactic measures implied adequate balanced nutrition, sanation of living conditions, restriction of contact with infectious agents, sanation of chronic foci of infection, systematic training and general fitness. The investigation included 160 young children (1 day - 3 years of age). The basic group (n=80) involved children, who had experienced respiratory disorders in neonatal period and received appropriate respiratory therapy (artificial ventilation and / or spontaneous breathing with continuous positive airway pressure and supply of free oxygen), control group - children, who did not have respiratory disorders and respiratory therapy (n=80). RESULTS: Results: Conducted investigation throughout 12-month monitoring enabled to record the development of recurrent bronchial obstruction syndrome in 43 children (respectively, 30 - 37.50% patients of the basic group versus 13 - 16.25% of control group; p 0.05), could not be obtained. CONCLUSION: Conclusions: Comparative analysis within groups did not show a reliable difference in the development of recurrent bronchial obstruction syndrome in children (р>0.05), which can be explained by partial following of doctor's recommendations. There is the need in further study of the issue involving more patients for a longer period of monitoring.

Clinical study on prevention of atopic dermatitis by oral administration of probiotics in infants.

Introduction: This study aimed to investigate the preventive effects of oral administration of probiotics on the incidence and severity of atopic dermatitis (AD) in infants. Material and methods: A total of 396 full-term infants were enrolled in this study. Of these, 132 newborns without a family history of AD were assigned to group A, and the other 264 newborns were randomly divided into groups B and C. Infants in groups A and B were solely breastfed, while probiotics were administered to those in group C as well as breastfeeding. The information of all subjects was recorded, and the incidence of AD was followed up. The levels of serum IgE and IL-4 were measured at the age of 3 years. Results: The incidence of AD in infants in group B was higher than that in group A at 3 months, 4-6 months, and 7-36 months after birth, together with increased symptom scores. For infants in group C, the incidence of AD at 4-6 months and 7-36 months after birth and the SCORAD scores at 0-3 months and 4-6 months after birth were lower than those in group B. The levels of IgE and IL-4 in group B were higher than those in groups A and C at 36 months old. Conclusions: Adding probiotics could favor the establishment of the intestinal microecological balance in the neonatal period, thereby reducing the incidence of AD, decreasing the levels of serum immune indexes and alleviating the severity of the disease.

Comparison of calf morbidity, mortality, and future performance across categories of passive immunity: A retrospective cohort study in a dairy herd.

Four categories of transfer of passive immunity (TPI) were recently proposed in response to the widespread high preweaning morbidity and mortality risks in calves with adequate TPI when a dichotomous classification was used. Hitherto, however, the risks of preweaning morbidity and mortality and future performance among these TPI categories have not been compared. Thus, the objective of this retrospective cohort study was to compare dairy calf morbidity, mortality, growth until weaning, and reproductive efficiency until first calving among the categories of poor (<5.1 g/dL total protein), fair (5.1-5.7 g/dL), good (5.8-6.1 g/dL), and excellent (>6.2 g/dL) TPI. For this, the records from 4,336 dairy calves (2,272 female, 2,064 male) born January 2014 to April 2017 on a commercial dairy farm in Michigan were analyzed. These calves had been randomly selected for weekly serum total protein determination on calves 2 to 7 d old. Data from both sexes were used to evaluate preweaning health and mortality, whereas only the female's data were used to investigate average daily gain (ADG), reproductive performance, and first-lactation milk yield. For each calf, data regarding disease status, growth, and reproductive parameters were obtained from the farm's software database. Associations of TPI categories with disease events (diarrhea or pneumonia), reproduction indices (age at first insemination, successful insemination, and calving, and number of inseminations), first-lactation milk yield and ADG at weaning were evaluated by survival analysis and mixed models. Compared with calves with excellent TPI, calves in the inferior TPI categories showed increased risk of diarrhea: poor [hazard ratio (HR) = 1.49; 95% CI: 1.22-1.82], fair (HR = 1.32; 95% CI: 1.16-1.51), good (HR = 1.14; 95% CI: 1.02-1.29). However, the risk of pneumonia differed only between the calves in the poor and excellent TPI groups (HR = 1.39; 95% CI: 1.05-1.84). The preweaning mortality risk was also higher in calves with poor TPI (HR = 4.29; 95% CI: 1.98-9.27) compared with excellent TPI. However, mortality risks were not statistically different between calves with fair or good TPI and those with excellent TPI. Similarly, calves with poor TPI had a 64, 55, and 24% lower risk of reaching first insemination, successful insemination, or first calving, respectively. However, there were no differences in ADG, number of inseminations, or first-lactation 305-d mature equivalent milk production across TPI groups. Our results confirm the positive effects of optimal TPI in calf preweaning health and postweaning reproductive efficiency. The 4 proposed categories of TPI can assist in decreasing the incidence of diseases that occur in the first weeks of life (i.e., diarrhea), but their effect on other diseases or future performance might be more limited. Although conducted in one herd, this study can be used to illustrate the effect of TPI on future calf performance.

Biliary Atresia Remnants Revisited: Myogenesis, Hepatic Duct-Like Structures, and Fate of Peribiliary Glands.

PURPOSE AND CONTEXT: Proximal levels of excised remnants from youngest infants may reveal early features of biliary atresia (BA). METHOD: A targeted IHC survey was applied to 34 most proximal 2 levels in 17 BA remnants excised at age 10-74 days including 7 = <30 days old and 6 control hepatic ducts (HD). KEY RESULTS: Severity of inflammation and extent of active fibroplasia do not distinguish proximal remnants in younger (n = 7) and older (n = 10) infants. In 27/34 levels of 14/17 remnants, reactive stroma is focally SM-MHC-2 (+), marking smooth muscle myosin, termed reactive myogenesis (RM), that is absent in controls. RM facilitates identification of 3 novel hepatic duct remnants (HDR): an HD-like collagen collar lined by degenerating cholangiocytes (n = 5); erosion defects in loose reactive stroma (n = 14); solitary foci of hyperplastic squamoid epithelium (n = 4). Peribiliary glands are either hyperplastic or atretic and typically lack RM. CONCLUSION: Minimally inflammed end-stage lesions in BA remnants occur at youngest ages favoring prenatal onset. Three novel HDR are defined. RM, a useful surrogate for HDR, is a prevalent inappropriate stromal reaction in proximal remnants of uncertain biological significance. RM is the source of mature smooth muscle in BA remnants.

[About the term «newborn¼ in forensic medicine]. / K ponyatiyu «novorozhdennyi¼ v sudebnoi meditsine.

The aim of this work is to prove necessity of using the term «newborn¼ as common both in forensic medicine and general medicine (from the moment of birth till 28th day), to show legality of using the term «signs of recent birth¼, to demonstrate the importance of understanding not only the higher border in definition of neonatal period but its initial moment that is necessary to solve some investigative questions and determine legal capacity of people and provide criminal justice defense of citizens' life and health.

A Case of Congenital Glucose Galactose Malabsorption with a New Mutation in the SLC5A1 Gene.

Congenital glucose-galactose malabsorption (CGGM) is an autosomal recessive disorder originating from an abnormal transporter mechanism in the intestines. It was sourced from a mutation in the SLC5A1 gene, which encodes a sodium-dependent glucose transporter. Here we report a 2-day-old girl with CGGM who presented with severe hypernatremic dehydration due to diarrhea beginning in the first hours of life. Mutation analysis revealed a novel homozygous mutation NM_000343.3 c.127G > A (p.Gly43Arg) in the SLC5A1 gene. Since CGGM can cause fatal diarrhea in the early neonatal period, timely diagnosis of the disease seems to be essential.

Neonatal near miss and associated factors among neonates admitted to neonatal intensive care unit of hospitals in East Wollega, Western Ethiopia, 2019.

Background: Neonatal near miss is an infant who nearly died but survived from birth to 28 days. Neonatal period is the most vulnerable time for child's healthiness and continued existence. Globally, about 2.5 million children died in their first month of life and 7000 die/day. Objective: To assess neonatal near miss and associated factors among neonates admitted to intensive care unit at hospitals in East Wollega, West Ethiopia, 2019. Methods: Quantitative, facility-based cross-sectional study was conducted from 15 July to 30 August 2019 on 403 neonates admitted to neonatal intensive care unit of hospitals. After ethical clearance, five recruited and trained nurses collected the data with pretested structured questionnaire. Neonates sampled were selected using systematic random sampling. Data entered into Epi-info version 7.1 and exported to SPSS Version 24. Binary logistic regression was performed, and adjusted odds ratio with P-value ⩽ 0.05 at 95% confidence interval was used as statistically significant. Results: All, 403, study participants were included in this study, yielding 100% response rate. From these, 196 (48.60%) neonates were near miss. In multivariable logistic regression, mother who lived in rural area (adjusted odds ratio = 3.84, 95% confidence interval = (1.78, 8.31)), cesarean section (adjusted odds ratio = 10.68, 95% confidence interval = (2.95, 38.71)), and neonates referred to hospitals (adjusted odds ratio = 3.32, 95% confidence interval = (3.27, 12.01)). Also, female neonates (adjusted odds ratio = 2.99, 95% confidence interval = (1.45, 6.14)) and multiple birth (adjusted odds ratio = 3.07, 95% confidence interval = (1.32, 7.16)) were significantly associated with neonatal near miss. Conclusion: Neonatal near miss found to be high compared to previously existing research in Brazil. Health institutions, health professionals, and concerned bodies on plan and implementation of neonatal care need to consider these factors during pregnancy, delivery, and for neonates immediate after birth and in neonatal intensive care unit.

Impact of prelacteal feeds and neonatal introduction of breast milk substitutes on breastfeeding outcomes: A systematic review and meta-analysis.

The introduction of fluids other than breast milk during the first few days of life or later neonatal period has been identified as a risk factor for suboptimal breastfeeding (BF) outcomes in numerous studies using varying study designs. However, the relationship between early introduction of fluids other than breast milk and BF outcomes has not been systematically assessed using only prospective studies that can establish temporality, which is critical for determining whether observed associations are causal. We conducted a systematic review and meta-analysis of prospective studies to assess if there is a difference in BF outcomes as a result of the introduction of: (a) milk-based prelacteals, (b) water-based prelacteals and (c) breast milk substitutes (BMS) between 4 days and 4 weeks postpartum. We searched PubMed, Lilacs, Web of Science and other repositories for original research investigating the relationship between early introduction of prelacteals and/or BMS and BF outcomes. Forty-eight studies met the inclusion criteria for the systematic review. Of the 39 prelacteal feeding studies, 27 had the prerequisite statistical information for inclusion in the meta-analysis. Findings from the meta-analysis showed a relationship between prelacteals and exclusive BF cessation (RR 1.44; 1.29-1.60) and any BF cessation (2.23; 1.63-3.06) among infants under 6 months old. Nine studies focusing on the introduction of BMS during the neonatal period identified this practice as a statistically significant risk factor for a shorter BF duration. Effective interventions are needed to prevent the introduction of unnecessary milk-based prelacteals and BMS during the perinatal and neonatal periods to improve BF outcomes.

Effect of Maternal Docosahexaenoic Acid Supplementation on Very Preterm Infant Growth: Secondary Outcome of a Randomized Clinical Trial.

INTRODUCTION: The aim of the study was to determine the effect of a maternal docosahexaenoic acid (DHA) supplementation during lactation, compared with a placebo, on the neonatal growth profile of breastfed very preterm infants. METHODS: Preterm infants' growth profile, growth velocity from birth to 36 weeks' postmenstrual age (PMA), and growth at 36 weeks' PMA were pre-specified secondary outcomes of a randomized placebo-controlled trial conducted in 16 Canadian neonatal intensive care units (2015-2018). Lactating mothers who delivered before 29 weeks' gestation were given 1.2 g of DHA daily or a placebo within 72 h of delivery and up to 36 weeks' PMA. Analyses were performed using a linear regression model with generalized estimating equations. RESULTS: 461 mothers and their 528 infants (DHA, N = 273; placebo, N = 255) were included with mean gestational age of 26.5 weeks (standard deviation [SD] = 1.6); 275 (52.1%) were males; mean birth weight was 895 g (SD = 240). DHA interaction with sex was significant on weight profile (interaction p < 0.001), weight velocity (interaction p = 0.05), and weight at 36 weeks' PMA (interaction p = 0.02). Females in the DHA group gained more weight compared to the placebo group (mean difference [MD], 52.6 g [95% confidence interval [CI]: 24.5-80.8], p < 0.001). Weight velocity was significantly higher in females of the DHA group (MD, 3.4 g/kg/day [95% CI: 0.6-6.2], p = 0.02). At 36 weeks' PMA, the weight of males in the DHA group was significantly smaller (MD, -88.9 g [95% CI: -166.2 to -11.6], p = 0.02). CONCLUSION: DHA positively affected female infants' neonatal weight profile and velocity and negatively affected male infants' weight at 36 weeks' PMA.

[Chest X-rays in children and adolescents : Indications and limitations]. / Röntgenuntersuchungen des Thorax bei Kindern und Jugendlichen : Indikationen und Limitationen.

CLINICAL ISSUE: Chest X­ray is the most commonly performed X­ray examination in children and adolescents. The aim of this review is to present the benefit of this radiologic modality, but also its limitations. METHODS: Compared with older children, most X­ray examinations of the chest were performed in newborns. After the neonatal period, this review focusses on the diagnosis of inflammatory pulmonary changes, foreign body aspiration, detection of pulmonary nodules, and cystic fibrosis. METHODOLOGICAL INNOVATIONS: The radiation exposure of X­ray examinations is continuously decreasing due to technical innovations. However, other imaging modalities were also continuously being optimized; therefore, alternatives without radiation exposure, i.e., magnetic resonance imaging [MRI] and ultrasound, should be considered in case of specific clinical indications. PRACTICAL RECOMMENDATION: Even if the diagnostic performance of chest X­ray examinations is often minor compared to computed tomography or MRI, chest X­ray still has a high value in children and adolescents, due to its ubiquitous availability and the relatively simple acquisition.

An Unusual Case of Infantile Hepatic Steatosis Caused by Coconut-Based Infant Formula.

We report a 5-month-old African American male with hepatic steatosis secondary to chronic and exclusive homemade coconut milk formula ingestion. Findings resolved with discontinuation.