Weeks Of Postnatal Life Research Articles

Metabolic bone disease in premature infants receiving parenteral nutrition: Incidence, clinical, laboratory and nutritional profile

BackgroundMetabolic bone disease (MBD) of newborns (NB) is characterized by tissue reduction and inadequate postnatal bone mineralization with clinical, laboratory, and/or radiologic repercussions between the third and twelfth weeks of postnatal life, which, in its most severe forms, can lead to a growth deficit and fractures. The aim of our study is to evaluate the incidence of MBD in premature patients receiving parenteral nutrition for >15 days in the neonatal intensive care unit (NICU) and assess their clinical and laboratory characteristics. MethodsSingle-center retrospective cohort study. From 2015 to 2020, patients <33 weeks of gestational age or <1500 g birth weight receiving parenteral nutrition for >15 days who met the metabolic bone disease criteria (alkaline phosphatase >800 U/L and phosphorus <3.5 mg/dL and/or compatible radiological alterations) were evaluated. Exclusion criteria: skeletal dysplasia, orthopedic surgeries, intraventricular hemorrhage grades III and IV, periventricular leukomalacia and chronic renal failure or severe liver disease. Clinical, laboratory and radiological data were collected during the first 90 days of life and/or discharge/death. ResultsThe MBD incidence was 17.7 % over a five-year period. The gestational age at birth was 26 ± 1.41 weeks; birth weight was 745 (592–858) grams; maximum alkaline phosphatase level was 1091 ± 243.87 U/L and phosphorus nadir was 2.45 ± 0.48 md/dL. Among the 14 patients with metabolic bone disease, twelve had laboratory diagnosis, six had radiological and four had both; two patients had fractures; 42 % of patients received enteral calcium and phosphorus supplementation, and 50 % received intravenous calcium replacement. ConclusionsMetabolic bone disease incidence was in accordance with international literature. The metabolic bone disease diagnosis was, in most cases, based on surveillance of laboratory tests. However, treatment for metabolic bone disease requires more active and preventive measures in risk groups.

Early and late postnatal lung distribution of collagen type VI in preterm and term infants

Collagen type VI (COL6) is an important component of the extracellular matrix (EM) and may have a major role in lung development and disease. Studies on COL6 expression during lung development are mainly based on animal models. The aim of the study was to define COL6 expression pattern in lung parenchyma in infants with different lung maturational stages.COL6 expression in 115 lung samples from deceased newborn infants (21–41 weeks’ gestational age; 0–228 days’ postnatal age) was studied by immunohistochemistry combined with digital image analysis.The distribution of COL6 expression was generally heterogeneous in the lung parenchyma of preterm and term infants. The size of the high-density and low-density areas appeared with logarithmic correlation and COL6 defined the basement membrane (BM) with a prominent expression around the air spaces in the canalicular stage during the first postnatal week. Infants at the alveolar stage showed linear correlation and a fine filamentous appearance during the first week of postnatal life, similarly to adults.COL6 is condensed to areas corresponding to the BM during the first postnatal week of the canalicular stage of lung development. After the first postnatal week COL6 expression changes to a microfibrillar appearance in the ECM, similar to the pattern that characterizes the later alveolar stage and adults. The localization of COL6 during the canalicular and saccular stages might have a higher impact on lung development than the amount of COL6.

Late maternal separation provides resilience to chronic variable stress-induced anxiety- and depressive-like behaviours in male but not female mice

Maternal separation can have long-lasting effects on an individual’s susceptibility to stress later in life. Maternal separation during the postnatal period is a commonly used paradigm in rodents to investigate the effects of early life stress on neurobehavioural changes and stress responsiveness. However, maternal separation during stress hyporesponsive and responsive periods of postnatal development may differ in its effects on stress resilience. Therefore, we hypothesised that late maternal separation (LMS) from postnatal day 10 to 21 in mice may have different effect on resilience than early maternal separation during the first week of postnatal life. Our results suggested that male LMS mice are more resilient to chronic variable stress (CVS)-induced anxiety and depressive-like behaviour as confirmed by the open field, light-dark field, elevated plus maze, sucrose preference and tail suspension tests. In contrast, female LMS mice were equally resilient as non-LMS female mice. We found increased expression of NPY, NPY1R, NPY2R, NPFFR1, and NPFFR2 in the hypothalamus of male LMS mice whereas the opposite effect was observed in the hippocampus. LMS in male and female mice did not affect circulating corticosterone levels in response to psychological or physiological stressors. Thus, LMS renders male mice resilient to CVS-induced neurobehavioural disorders in adulthood.

Dissecting signal transduction pathways that regulate cardiomyocyte proliferation

Abstract Funding Acknowledgements None. Introduction During cardiac development, the Notch, Hippo, and Wnt/β-catenin signalling pathways play a crucial role in the tuning of cardiomyocyte proliferation. The individual engagement of each of these pathways during the early postnatal life, however, is still unclear. Purpose We wanted to develop a method to visualize over time, both in vitro and in vivo, the topography of activation of the Notch, Wnt/β-catenin, and Hippo pathways and their crosstalk upon cardiomyocyte treatment with a series of pro-proliferative stimuli. Methods We obtained Adeno-Associated Virus (AAV) constructs expressing distinct fluorescent proteins (ECFP, GFP, mCherry, DsRed) under the control of promoters that are specifically activated downstream of the signalling cascades of interest (a synthetic promoter consisting of 12 CSL binding sites for Notch1, a synthetic promoter consisting of 8 TEAD binding sites for YAP, and a synthetic promoter containing 7 TCF/LEF1 binding sites for β-catenin). Results First, by high content microscopy we followed the time of the activation of the AAV vectors coding for fluorescent reporters, either alone or in combination. We observed that a crosstalk exists between Yap and Notch signalling in proliferating cardiomyocytes, as detected by the activation of their respective fluorescent reporters. We confirmed our data by gene expression analysis and co-immunoprecipitation using specific antibodies in fractionated cardiomyocyte extracts. Next, we observe that miR-1825, miR-199a-3p, and miR-590-3p – three pro-regenerative miRNAs in cardiomyocytes– specifically activate both Yap and Notch signalling. Finally we characterized the reporter systems in vivo, to dissect the intracellular signalling pathways that are active in the first week of postnatal life. Beta-catenin signalling was quite undetectable in any of the conditions tested. In contrast, both Notch and Yap showed significant activation, consistent with their role in regulating early postnatal cardiomyocyte proliferation. Conclusions The developed AAV-fluorescent reporters allow to efficiently and specifically visualize the pro-proliferative activation of Notch and Yap signalling both in vitro and in vivo. The results obtained are supportive of a crosstalk existing between Notch and Yap pathways in proliferating cardiomyocytes.

Neonatal brain dynamic functional connectivity in term and preterm infants and its association with early childhood neurodevelopment

Brain dynamic functional connectivity characterises transient connections between brain regions. Features of brain dynamics have been linked to emotion and cognition in adult individuals, and atypical patterns have been associated with neurodevelopmental conditions such as autism. Although reliable functional brain networks have been consistently identified in neonates, little is known about the early development of dynamic functional connectivity. In this study we characterise dynamic functional connectivity with functional magnetic resonance imaging (fMRI) in the first few weeks of postnatal life in term-born (n = 324) and preterm-born (n = 66) individuals. We show that a dynamic landscape of brain connectivity is already established by the time of birth in the human brain, characterised by six transient states of neonatal functional connectivity with changing dynamics through the neonatal period. The pattern of dynamic connectivity is atypical in preterm-born infants, and associated with atypical social, sensory, and repetitive behaviours measured by the Quantitative Checklist for Autism in Toddlers (Q-CHAT) scores at 18 months of age.

Tmem263 deletion disrupts the GH/IGF-1 axis and causes dwarfism and impairs skeletal acquisition

Genome-wide association studies (GWAS) have identified a large number of candidate genes believed to affect longitudinal bone growth and bone mass. One of these candidate genes, TMEM263, encodes a poorly characterized plasma membrane protein. Single nucleotide polymorphisms in TMEM263 are associated with bone mineral density in humans and mutations are associated with dwarfism in chicken and severe skeletal dysplasia in at least one human fetus. Whether this genotype-phenotype relationship is causal, however, remains unclear. Here, we determine whether and how TMEM263 is required for postnatal growth. Deletion of the Tmem263 gene in mice causes severe postnatal growth failure, proportional dwarfism, and impaired skeletal acquisition. Mice lacking Tmem263 show no differences in body weight within the first 2 weeks of postnatal life. However, by P21 there is a dramatic growth deficit due to a disrupted growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis, which is critical for longitudinal bone growth. Tmem263-null mice have low circulating IGF-1 levels and pronounced reductions in bone mass and growth plate length. The low serum IGF-1 in Tmem263-null mice is associated with reduced hepatic GH receptor (GHR) expression and GH-induced JAK2/STAT5 signaling. A deficit in GH signaling dramatically alters GH-regulated genes and feminizes the liver transcriptome of Tmem263-null male mice, with their expression profile resembling wild-type female, hypophysectomized male, and Stat5b-null male mice. Collectively, our data validates the causal role for Tmem263 in regulating postnatal growth and raises the possibility that rare mutations or variants of TMEM263 may potentially cause GH insensitivity and impair linear growth.

Tmem263 deletion disrupts the GH/IGF-1 axis and causes dwarfism and impairs skeletal acquisition.

Genome-wide association studies (GWAS) have identified a large number of candidate genes believed to affect longitudinal bone growth and bone mass. One of these candidate genes, TMEM263, encodes a poorly characterized plasma membrane protein. Single nucleotide polymorphisms in TMEM263 are associated with bone mineral density in humans and mutations are associated with dwarfism in chicken and severe skeletal dysplasia in at least one human fetus. Whether this genotype-phenotype relationship is causal, however, remains unclear. Here, we determine whether and how TMEM263 is required for postnatal growth. Deletion of the Tmem263 gene in mice causes severe postnatal growth failure, proportional dwarfism, and impaired skeletal acquisition. Mice lacking Tmem263 show no differences in body weight within the first 2 weeks of postnatal life. However, by P21 there is a dramatic growth deficit due to a disrupted growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis, which is critical for longitudinal bone growth. Tmem263-null mice have low circulating IGF-1 levels and pronounced reductions in bone mass and growth plate length. The low serum IGF-1 in Tmem263-null mice is associated with reduced hepatic GH receptor (GHR) expression and GH-induced JAK2/STAT5 signaling. A deficit in GH signaling dramatically alters GH-regulated genes and feminizes the liver transcriptome of Tmem263-null male mice, with their expression profile resembling wild-type female, hypophysectomized male, and Stat5b-null male mice. Collectively, our data validates the causal role for Tmem263 in regulating postnatal growth and raises the possibility that rare mutations or variants of TMEM263 may potentially cause GH insensitivity and impair linear growth.

Breast-feeding as protective factor against bronchopulmonary dysplasia in preterm infants.

Breast-feeding is associated with fewer comorbidities in very-low-birth-weight (VLBW) preterm infants. Bronchopulmonary dysplasia (BPD) of VLBW infants is a multifactorial pathology in which nutritional aspects may be of special importance. The aim of this study is to determine, in a cohort of VLBW infants, whether breast milk nutrition is associated with a reduced prevalence and severity of BPD. A retrospective study was conducted to record the intake of mother's own milk (MOM), pasteurised donor human milk or preterm formula milk in the first 2 weeks of postnatal life of 566 VLBW newborns at our hospital during the period January 2008-December 2021. After applying the relevant exclusion criteria, data for 489 VLBW infants were analysed; 195 developed some degree of BPD. Moderate or severe BPD is associated with less weight gain. Moreover, the preferential ingestion of breast milk in the first and second postnatal weeks had effects associated with lower OR for BPD, which were statistically demonstrable for mild (OR 0·16; 95 % CI 0·03, 0·71) and severe (OR 0·08; 95 % CI 0·009, 0·91) BPD. Breast-feeding during the first weeks of postnatal life is associated with a reduced prevalence of BPD, which is frequently associated with less weight gain as a result of greater respiratory effort with greater energy expenditure.

Association between intermittent hypoxemia and neurodevelopmental outcomes in extremely premature infants: A single-center experience

ObjectiveTo describe the association between intermittent hypoxemic events (IHEs) and severe neurodevelopmental impairment (SNDI) or death in extremely premature infants. Study designRetrospective study of extremely premature infants 230/7–276/7 weeks gestational age (GA) and birthweight (BW) ≤1250 g (g) admitted to a level IV neonatal intensive care unit (NICU) from 2013 to 2017. IHEs, defined as events with SpO2 ≤ 80 % lasting 10 s to 5 min, were algorithmically identified using data extracted from bedside monitors at 2 s intervals (0.5 Hz). The primary outcome was SNDI at 18–24 months corrected age (CA), defined as a Bayley-III motor, language or cognitive composite score ≤69, or death before discharge while the secondary outcome was SNDI alone. We used mixed-effects regression models to evaluate the relationship between mean daily IHE rate per postnatal week of life for the first 12 weeks and the outcomes, and logistic regression models to assess the association between outcomes and summary measures of hypoxic burden for the entire NICU hospitalization. ResultsThe mortality rate was 7 % (18/249) during NICU hospitalization. Of 249 infants born during this time period, IHE and neurodevelopmental outcome data were fully available for 65 infants (mean GA 26 ± 1.4 weeks, mean birth weight (BW) 738 ± 199 g). The outcome of SNDI alone occurred in 34 % (22/65) with a majority demonstrating motor or language delay on the Bayley-III. Although mean daily IHE rate/week was not associated with SNDI or death, total IHE duration was associated with increased odds of SNDI (OR (95 % CI) 1.03 (1.01, 1.05), p = 0.008) in models adjusted for GA. ConclusionsIn a cohort of extremely premature infants 23–27 weeks GA, each hour of total IHE duration (SpO2 ≤ 80 %) was associated with a 2.7 % (0.7 %, 4.8 %) increase in the odds of SNDI at 18–24 months CA.

Early social isolation differentially affects the glucocorticoid receptor system and alcohol-seeking behavior in male and female Marchigian Sardinian alcohol-preferring rats

Adverse early life experiences during postnatal development can evoke long-lasting neurobiological changes in stress systems, thereby affecting subsequent behaviors including propensity to develop alcohol use disorder. Here, we exposed genetically selected male and female Marchigian Sardinian alcohol-preferring (msP) and Wistar rats to mild, repeated social deprivation from postnatal day 14 (PND14) to PND21 and investigated the effect of the early social isolation (ESI) on the glucocorticoid receptor (GR) system and on the propensity to drink and seek alcohol in adulthood. We found that ESI resulted in higher levels of GR gene and protein expression in the prefrontal cortex (PFC) in male but not female msP rats. In female Wistars, ESI resulted in significant downregulation of Nr3c1 mRNA levels and lower GR protein levels. In male and female msP rats, plasma corticosterone levels on PND35 were similar and unaffected by ESI. Wistar females exhibited higher levels of corticosterone compared with males, independently from ESI. In alcohol self-administration experiments we found that the pharmacological stressor yohimbine (0.0, 0.312, 0.625, and 1.25 mg/kg) increased alcohol self-administration in both rat lines, regardless of ESI. After extinction, 0.625 mg/kg yohimbine significantly reinstated alcohol seeking in female rats only. ESI enhanced reinstatement in female msP rats. Overall, the present results indicate that repeated social deprivation during the third week of postnatal life affects GR expression in a strain- and sex-dependent manner: such effect may contribute, at least partially, to the heightened sensitivity of female msP rats to the effects of yohimbine-induced alcohol seeking.

Postnatal Development of the Amygdala of Rat Offspring after Prenatal Exposure to Valproic Acid: A Histological and Morphometric Study

Abstract Background The amygdala has a major role in emotion regulation, social behavior development and reward learning. Being subject to several factors makes it vulnerable to numerous neurodevelopmental disorders. Aim of the Work The aim of the current work was to study the structural and morphometric changes of the amygdala of rat's offspring following maternal exposure to valproic acid during pregnancy and to compare it with the control. Material and methods 20 adult female and 10 adult male Sprague dawley albino rats weighing 150-200 g body weight were used in the current study. After induction of pregnancy, pregnant rats were divided into two groups 6 in each group; control group (I) and valproic acid treated group (II). Pregnant rats received one ml of saline in group (I) or 500 mg/kg BW valproic acid dissolved in one ml saline in group (II) by oral gavage on day 11-13 of pregnancy. Pregnant rats were observed till end of pregnancy and four male newborn rats were sacrificed at each time point of the experiment from the two groups (week1, 2, &amp;3). Brains were extracted and processed for paraffin blocks and sectioned then stained with H&amp;E, cresyl violet stains and immunohistochemically stained for GFAP antibody. Image analysis &amp;morphometry were performed on stained sections for; number of neurons, number of oligodendrocytes, surface area of basal nucleus of amygdala and density of GFAP staining. Results On examination of H&amp;E-stained sections of control groups during the first three weeks postnatally, the amygdala contained mainly three types of cells: pyramidal cells, oligodendrocytes, and astrocytes. Pyramidal cells had basophilic cytoplasm with large rounded open face nuclei and prominent nucleoli. Some pyramidal cells showed apical dendrites. The oligodendrocytes were seen to have rounded nuclei with condensed chromatin surrounded by thin cytoplasmic ring. Astrocytes possessed nuclei with pale vesicular chromatin pattern less dense than that of oligodendrocytes and showed relatively small indistinct nucleoli. Morphometric studies using image analysis had recorded statistically non-significant changes in the number of neurons during development, however concerning oligodendrocytes there was a statistically significant increase in their number in week 2 and 3 when compared to week 1. Using Nissl staining (cresyl violet) it demonstrated negative or very weak staining in the first week postnatally, the staining becomes more obvious in the next 2 weeks postnatally. GFAP immune stained sections of the amygdala of the 3 weeks revealed mild positive immune reaction. There was no statistically significant difference regarding density of staining across the three weeks. The surface area of the basal nucleus of amygdala of the control groups showed statistically significant increase during development across the three weeks. On examination of H&amp;E-stained sections of VPA treated groups during the first three weeks postnatally, numerous cells with pyknotic deeply basophilic stained nuclei were seen. Morphometric studies on the same groups using image analysis recorded statistically significant decrease in neurons and oligodendrocytes number when compared to control. On examination of the cresyl violet stained sections, there were numerous darkly stained degenerating cells that did not reveal the presence of Nissl granules denoting chromatolysis. On examining GFAP immune stained sections of the amygdala, week 2 and 3 postnatally showed strong positive immune reaction. The surface area of the basal nucleus of amygdala of VPA treated groups of weeks 1 showed a highly significant decrease when compared to week 1 of control groups, however the surface area of the amygdala of week 2 and 3 showed an increase more than the increase recorded in the control groups. The increase in the surface area was non-significant in week 2 but highly significant in week 3. Conclusion Results of the present experimental study demonstrated the developmental structural changes of the rat amygdala across the first three weeks of postnatal life. The study also explored the devastating effect of the prenatal exposure to VPA on the structure of the amygdala leading to neuronal death and gliosis particularly in the third week of age postnatally.

Maternal developmental history alters transfer of circadian clock genes to offspring in Japanese quail (Coturnix japonica)

Maternal signals shape embryonic development, and in turn post-natal phenotypes. RNA deposition is one such method of maternal signalling and circadian rhythms are one trait thought to be maternally inherited, through this mechanism. These maternal circadian gene transcripts aid development of a functioning circadian system. There is increasing evidence that maternal signals can be modified, depending on prevailing environmental conditions to optimise offspring fitness. However, currently, it is unknown if maternal circadian gene transcripts, and consequently early embryonic gene transcription, are altered by maternal developmental conditions. Here, using avian mothers who experienced either pre-natal corticosterone exposure, and/or post-natal stress as juveniles we were able to determine the effects of the timing of stress on downstream circadian RNA deposition in offspring. We demonstrated that maternal developmental history does indeed affect transfer of offspring circadian genes, but the timing of stress was important. Avian mothers who experienced stress during the first 2 weeks of post-natal life increased maternally deposited transcript levels of two core circadian clock genes, BMAL1 and PER2. These differences in transcript levels were transient and disappeared at the point of embryonic genome transcription. Pre-natal maternal stress alone was found to elicit delayed changes in circadian gene expression. After activation of the embryonic genome, both BMAL1 and PER2 expression were significantly decreased. If both pre-natal and post-natal stress occurred, then initial maternal transcript levels of BMAL1 were significantly increased. Taken together, these results suggest that developmental stress differentially produces persistent transgenerational effects on offspring circadian genes.

Impact of duration of kangaroo mother care on growth in preterm and low birth weight neonates: a prospective cohort study

Background: Care of low-birth-weight infants is one of the most important challenges faced globally. Kangaroo mother care (KMC) is a simple and powerful, yet most cost-effective means to provide warmth, nutrition, protection from infections, caring environment and bonding, thus promoting growth. Aim was to study the impact of duration of KMC on growth in preterm low birth weight (LBW) infants. Methods: This prospective cohort study was done in the NICU and postnatal ward in a teaching institute in Karnataka. All preterm neonates weighing 1500-2000 gm with stable hemodynamics were included in this study and allotted into two groups based on average duration of KMC per day-group I (KMC 4 hours), and group II (KMC 8 hours). All these neonates were monitored daily during their stay in the hospital and advised follow up till 6 weeks of life. The impact of KMC on growth was measured in terms of anthropometric parameters every two weeks, till 6 weeks of post-natal life. Results: With increase in duration of KMC there was significant improvement in the anthropometric parameters (p=0.001). Those infants in group I had mean weight gain of 10.5 gm/day, length 0.80 cm/week, head circumference 0.62 cm/week, and chest circumference 0.73 cm/week. Those in group II had a mean weight gain of 15.07 gm/day, length 0.85 cm/week, head circumference 0.71 cm/week and chest circumference of 0.81 cm/week. Conclusions: There were significant increments in anthropometric parameters when the duration of KMC per day increased. KMC can be implemented in all the healthcare centres especially in resource poor settings.

Time-resolved transcriptomic profiling of the developing rabbit’s lungs: impact of premature birth and implications for modelling bronchopulmonary dysplasia

BackgroundPremature birth, perinatal inflammation, and life-saving therapies such as postnatal oxygen and mechanical ventilation are strongly associated with the development of bronchopulmonary dysplasia (BPD); these risk factors, alone or combined, cause lung inflammation and alter programmed molecular patterns of normal lung development. The current knowledge on the molecular regulation of lung development mainly derives from mechanistic studies conducted in newborn rodents exposed to postnatal hyperoxia, which have been proven useful but have some limitations.MethodsHere, we used the rabbit model of BPD as a cost-effective alternative model that mirrors human lung development and, in addition, enables investigating the impact of premature birth per se on the pathophysiology of BPD without further perinatal insults (e.g., hyperoxia, LPS-induced inflammation). First, we characterized the rabbit’s normal lung development along the distinct stages (i.e., pseudoglandular, canalicular, saccular, and alveolar phases) using histological, transcriptomic and proteomic analyses. Then, the impact of premature birth was investigated, comparing the sequential transcriptomic profiles of preterm rabbits obtained at different time intervals during their first week of postnatal life with those from age-matched term pups.ResultsHistological findings showed stage-specific morphological features of the developing rabbit’s lung and validated the selected time intervals for the transcriptomic profiling. Cell cycle and embryo development, oxidative phosphorylation, and WNT signaling, among others, showed high gene expression in the pseudoglandular phase. Autophagy, epithelial morphogenesis, response to transforming growth factor β, angiogenesis, epithelium/endothelial cells development, and epithelium/endothelial cells migration pathways appeared upregulated from the 28th day of gestation (early saccular phase), which represents the starting point of the premature rabbit model. Premature birth caused a significant dysregulation of the inflammatory response. TNF-responsive, NF-κB regulated genes were significantly upregulated at premature delivery and triggered downstream inflammatory pathways such as leukocyte activation and cytokine signaling, which persisted upregulated during the first week of life. Preterm birth also dysregulated relevant pathways for normal lung development, such as blood vessel morphogenesis and epithelial-mesenchymal transition.ConclusionThese findings establish the 28-day gestation premature rabbit as a suitable model for mechanistic and pharmacological studies in the context of BPD.

Functional state of the kidneys in the neonatal period in children with very low and extremely low body weight

BACKGROUND. Preterm birth is still associated with an increased risk of neonatal morbidity and mortality in the early neonatal period. There is strong evidence demonstrating an association between a decrease in the number of nephrons in preterm infants and an increase in blood pressure, the risk of developing chronic kidney disease, which undoubtedly negatively affects the quality of life. THE AIM: to assess the functional state of the kidneys in children with very low (VLBW) and extremely low body weight (ELBW) in the first 8 weeks of postnatal life. PATIENTS AND METHODS. The study involved 134 newborns less than 37 weeks of gestation, who were divided into three groups depending on birth weight. The levels of protein and fluid intake, serum creatinine concentration, GFR according to Schwartz were taken into account as evaluation parameters. The Python programming language, t-tests, ShapiroWilk and d'Agostino tests were used as statistical methods. A threshold level of 0.05 was chosen to interpret the value of p tests for normality testing. RESULTS. There were no differences in the amount of protein received by preterm infants in the study groups both in the first week and subsequent 2–8 weeks of life. The average level of incoming fluid in the first week of postnatal life increased from 1 to 7 days in all study groups. There was a trend towards a more significant decrease in serum creatinine in children born with a larger birth weight. Analyzing the level of glomerular filtration rate in the studied groups, there is a clear picture of a progressive increase in the rate with age. CONCLUSION. The values of diuresis, creatinine level and GFR in premature babies with birth weight less than 1500 grams in the first 2 months of life have been established, which can be used in practice for comparison in the study of various pathologies.

Fetal echocardiography and early neonatal balloon valvuloplasty improved overall survival in prenatally detected aortic stenosis over 25 years of tertiary center experience.

This article aimed to present the factors determining survival and prognosis in fetuses and newborns with critical prenatal aortic stenosis (AS) and to present 26 years of tertiary center experience. Study included 87 fetuses with critical AS requiring surgical intervention during neonatal period. All results were expressed as means ± SD, in numbers and percentages. The statistically significant results were those with p < 0.05. An increase in the number of cases of AS was observed in our center along with a decrease in gestational age of our patients during the first echocardiographic exam. The survival rate of newborns was considerably higher when born in due time (p < 0.05) with body weight > 2500 g (p < 0.05). Balloon valvuloplasty performed in the first days after birth occurred to be an optimal solution in these cases. Fetal echocardiography and special perinatal care with transplacental maternal pharmacotherapy in selected cases and an early neonatal aortic balloon valvuloplasty have shown improvement in survival rate. The most dangerous for the newborn with AS was the first week of postnatal life. It is vital to refer the fetuses with AS to the reference centers which offer the possibility of invasive cardiac intervention on the first day after birth, and it might be an optimal solution.

Formation of N-acyl-phosphatidylethanolamines by cytosolic phospholipase A2ε in an ex vivo murine model of brain ischemia

N-Acyl-phosphatidylethanolamines (NAPEs), a minor class of membrane glycerophospholipids, accumulate along with their bioactive metabolites, N-acylethanolamines (NAEs) during ischemia. NAPEs can be formed through N-acylation of phosphatidylethanolamine by cytosolic phospholipase A2ε (cPLA2ε, also known as PLA2G4E) or members of the phospholipase A and acyltransferase (PLAAT) family. However, the enzyme responsible for the NAPE production in brain ischemia has not yet been clarified. Here, we investigated a possible role of cPLA2ε using cPLA2ε-deficient (Pla2g4e−/−) mice. As analyzed with brain homogenates of wild-type mice, the age dependency of Ca2+-dependent NAPE-forming activity showed a bell-shape pattern being the highest at the first week of postnatal life, and the activity was completely abolished in Pla2g4e−/− mice. However, liquid chromatography-tandem mass spectrometry revealed that the NAPE levels of normal brain were similar between wild-type and Pla2g4e−/− mice. In contrast, post-mortal accumulations of NAPEs and most species of NAEs were only observed in decapitated brains of wild-type mice. These results suggested that cPLA2ε is responsible for Ca2+-dependent formation of NAPEs in the brain as well as the accumulation of NAPEs and NAEs during ischemia, while other enzyme(s) appeared to be involved in the maintenance of basal NAPE levels.

Surface and Structural Studies of Age-Related Changes in Dental Enamel: An Animal Model.

In the animal kingdom, continuously erupting incisors provided an attractive model for studying the enamel matrix and mineral composition of teeth during development. Enamel, the hardest mineral tissue in the vertebrates, is a tissue sensitive to external conditions, reflecting various disturbances in its structure. The developing dental enamel was monitored in a series of incisor samples extending the first four weeks of postnatal life in the spiny mouse. The age-dependent changes in enamel surface morphology in the micrometre and nanometre-scale and a qualitative assessment of its mechanical features were examined by applying scanning electron microscopy (SEM) and atomic force microscopy (AFM). At the same time, structural studies using XRD and vibrational spectroscopy made it possible to assess crystallinity and carbonate content in enamel mineral composition. Finally, a model for predicting the maturation based on chemical composition and structural factors was constructed using artificial neural networks (ANNs). The research presented here can extend the existing knowledge by proposing a pattern of enamel development that could be used as a comparative material in environmental, nutritional, and pharmaceutical research.

Intrauterine inflammation exacerbates maladaptive remodeling of the immature myocardium after preterm birth in lambs

BackgroundAntenatal conditions that are linked with preterm birth, such as intrauterine inflammation, can influence fetal cardiac development thereby rendering the heart more vulnerable to the effects of prematurity. We aimed to investigate the effect of intrauterine inflammation, consequent to lipopolysaccharide exposure, on postnatal cardiac growth and maturation in preterm lambs.MethodsPreterm lambs (~129 days gestational age) exposed antenatally to lipopolysaccharide or saline were managed according to contemporary neonatal care and studied at postnatal day 7. Age-matched fetal controls were studied at ~136 days gestational age. Cardiac tissue was sampled for molecular analyses and assessment of cardiac structure and cardiomyocyte maturation.ResultsLambs delivered preterm showed distinct ventricular differences in cardiomyocyte growth and maturation trajectories as well as remodeling of the left ventricular myocardium compared to fetal controls. Antenatal exposure to lipopolysaccharide resulted in further collagen deposition in the left ventricle and a greater presence of immune cells in the preterm heart.ConclusionsAdverse impacts of preterm birth on cardiac structure and cardiomyocyte growth kinetics within the first week of postnatal life are exacerbated by intrauterine inflammation. The maladaptive remodeling of the cardiac structure and perturbed cardiomyocyte growth likely contribute to the increased vulnerability to cardiac dysfunction following preterm birth.ImpactPreterm birth induces maladaptive cardiac remodeling and adversely impacts cardiomyocyte growth kinetics within the first week of life in sheep.These effects of prematurity on the heart are exacerbated when preterm birth is preceded by exposure to intrauterine inflammation, a common antecedent of preterm birth.Inflammatory injury to the fetal heart coupled with preterm birth consequently alters neonatal cardiac growth and maturation and thus, may potentially influence long-term cardiac function and health.

PECULIARITIES OF ELECTRON MICROSCOPIC HIPPOCAMPAL FORMATION DEVELOPMENT CHARACTERISTICS IN POSTERITY OF RATS AFTER PGE2 INJECTION FOR LABOR INDUCTION

The aim: To determine the peculiarities of electron microscopic hippocampal formation development characteristics in postetry of rats during two first weeks of postnatal life after intravaginal injection of prostaglandin E2 for labor induction. Materials and methods: The ultrastructural changes of hippocampal formation in posterity of white syngenic rats at the 1st, 7th and 14th days of postnatal life were examined. In this study we used electron-microscopic method. Brain tissue from experimental animals underwent standart stages necessary for electron microscopy and poured into pure Epon. Epon polymerization was carried out in two stages at 36 ° C (12 h) and 56 ° C (24 h). Ultrathin (50-60 nm) sections were obtained on a PowerTome RMC Boeckeler ultratome and then contrasted according to the E. Reynolds method. Ultrathin sections were studied in a PEM-100 electron microscope with an accelerating voltage 60 kV. Results: Based on the obtained data in the study of the hippocampal formation in postery of rats after induction of labor, analysis of the literature devoted to the electron microscopic study of the brain after ischemic injuries, it can be concluded that on the background of stimulation of labor by PgE2, changes corresponding to ischemic damage take place in the rat brain. Conclusions: In posterity of rats after receiving PgE2 for labour induction it was revealed microcirculatory changes; edema of the presynaptic endings, synaptic vesicles aggregation in the center of the presynaptic processes, swelling and destruction of mitochondria; oligodendroglia changes; ultrastructural changes in neurons like edema and vacuolization of mitochondria.