Early Postnatal Period Research Articles

Essential Coaching for Every Mother Tanzania (ECEM-TZ): Protocol for a Type 1 Hybrid Effectiveness-Implementation Randomized Controlled Trial.

Despite global goals to improve maternal, newborn, and child health outcomes, mortality and morbidity continue to be a concern, particularly during the postnatal period in low- and middle-income countries. While mothers have the responsibility of providing ongoing care for newborns at home, they often receive insufficient newborn care education in Tanzania. Mobile health via text messaging is an ever-growing approach that may address this gap and provide timely education. We aim to evaluate a text message intervention called Essential Coaching for Every Mother Tanzania (ECEM-TZ) to improve maternal access to essential newborn care education during the immediate 6-week postnatal period. ECEM-TZ consists of standardized text messages from birth to 6 weeks post partum that provide evidence-based information on caring for their newborn and recognizing danger signs. Messages were developed and then reviewed by Tanzanian mothers and nurse midwives before implementation. A hybrid type 1 randomized controlled trial will compare ECEM-TZ to standard care among mothers (n=124) recruited from 2 hospitals in Dar es Salaam. The effectiveness outcomes include newborn care knowledge, maternal self-efficacy, breastfeeding self-efficacy, maternal mental health, attendance at the 6-week postnatal checkup, and newborn morbidity and mortality. The implementation outcomes include the reach and quality of implementation of the ECEM-TZ intervention. Recruitment for this study occurred between June 13, 2024, and July 22, 2024. A total of 143 participants were recruited, 71 in the control and 72 in the intervention. The 6-week follow-up data collection began on July 30, 2024, and was completed on September 21, 2024. This study will generate evidence about the effectiveness of implementing text messaging during the early postnatal period and the feasibility of doing so in 2 hospitals in Dar es Salaam. The intervention has been designed in collaboration with mothers and nurse midwives in Tanzania. ClinicalTrials.gov NCT05362305; https://clinicaltrials.gov/study/NCT05362305. DERR1-10.2196/63454.

Characteristics of gut microbiota of premature infants in the early postnatal period and their relationship with intraventricular hemorrhage

BackgroundStudies have shown correlations between gut microbiota and neurocognitive function, but little was known about the early postnatal gut microbiota and intraventricular hemorrhage (IVH). We aimed to explore the characteristics of gut microbiota in premature infants and their relationship with IVH, further exploring potential therapeutic targets.MethodsPremature infants delivered at Peking University First Hospital from February 2023 to August 2023 were recruited as a cohort. Feces samples were collected on postnatal days 1, 3, and 5. Premature infants were divided into normal, mild IVH, and severe IVH groups based on cranial ultrasound. 16S rRNA amplicon sequencing technology was used to determine the fecal microbiota, and the results were analyzed.ResultsThirty-eight premature infants were enrolled. There was a significant difference in alpha and beta diversity among the three groups. The relative abundance of E. coli and A. muciniphila was different among the three groups. Further random forest analysis indicated that S. lutetiensis, L. mirabilis, and N. macacae can effectively distinguish premature infants with IVH. Finally, the phylogenetic investigation of communities by reconstruction of unobserved states2 (PICRUSt2) functional gene analysis predicted significant differences in energy metabolism, carbohydrate metabolism, metabolism of cofactors and vitamins, and membrane transport between normal and severe IVH groups.ConclusionsThe gut microbiota in the early postnatal period of premature infants is closely associated with the IVH status. As age increases, the differences in gut microbiota of premature infants with different degrees of IVH continue to increase, and the trend of changes with severity of IVH becomes more and more obvious. E. coli, A. muciniphila, S. lutetiensis, L. mirabilis, N. macacae, G. haemolysans, and S. oralis can effectively distinguish between IVH infants and normal premature infants. The results indicate that gut microbiota is expected to provide effective therapeutic targets for the diagnosis and treatment of IVH.

Association of early life exposure to PM2.5 and its components with offspring neurodevelopment: a prospective birth cohort study

Emerging data have explored early life fine particulate (PM2.5) exposure and its relationship with offspring neurodevelopment. However, the findings remain inconsistent, and the roles of specific PM2.5 components are unclear. We investigated these associations and explored the potential interactive role of children’s physical activity (PA). A total of 1547 mother-child pairs from the Shenzhen Birth Cohort were included. Neurodevelopment was assessed at seven time points (1, 3, 6, 8, 12, 18, and 24 months) using the Ages and Stages Questionnaire. An established spatiotemporal model was used to estimate early life exposure to PM2.5 and five components [sulfate (SO42), nitrate (NO3-), ammonium (NH4+), organic matter (OM), and black carbon (BC)]. Associations of individual and joint exposure to components with neurodevelopment were analyzed using generalized estimating equation and quantile-based g-computation models with a binomial distribution. Most mothers (79.1%) were under 35 at delivery, and 43.6% of the children were boys. During the early postnatal period, a 5μg/m3 increase in PM2.5 was associated with higher adjusted odds ratios (aORs) for developmental delays in gross motor (1.24, 95%CI:1.12, 1.37), fine motor (1.11, 95%CI:1.04, 1.20), and problem-solving (1.12, 95%CI:1.03, 1.22) domains. Similar associations were observed for individual PM2.5 components. Each quintile increase in early postnatal exposure to PM2.5 mixtures was correlated with higher aORs for these domains, with NO3- constituting the largest weight. No significant associations were found for the prenatal period. The children’s PA showed no interaction. These findings underscore the need to reduce PM2.5 exposure, particularly its toxic components, to minimize developmental risks.

Age-related features of the intestinal microbiota changes in Wistar rat pups after application of antibiotics and prebiotic 2′-fucosyllactose

The gut microbiota plays an important role in the formation of the body’s regulatory systems (nervous, endocrine, immune), which is especially important at an early age. Hence, gut dysbiosis can lead to an impaired development of both the intestinal microbiota and these regulatory systems. Prebiotics can have a positive effect on the development of the intestinal microbiome, which can correct negative changes.The aim of this study is to investigate the features of development of antibiotic-associated dysbiosis in the early postnatal period in rats and to evaluate the effect of 2′-fucosyllactose in health and during dysbiosis.The study was conducted on Wistar rats aged 12–26 days. To develop dysbiosis at an early age, the following mixtures were used: a mixture of ampicillin trihydrate 75 mg/kg and metronidazole 50 mg/kg and a mixture of amoxicillin 30 mg/kg and cephalexin 20 mg/kg for three days, starting on the 12th day of life. As a prebiotic 2′-fucosyllactose at a dose of 1 g/kg was used, starting on the 12th day and to the last experiment day.In healthy animals, there is a decrease in the gut content of Bifidobacterium spp. and Enterococcus spp. at the age of 26 days. A mixture of ampicillin trihydrate 75 mg/kg and metronidazole 50 mg/kg leads to gut dysbiosis – growth suppression of bifidobacteria, lactobacilli and enterococci. After the end of antibiotics application and continued lactation, the titer of the described bacteria is restored. 2′-fucosyllactose has an effect on the preservation of the titer of Bifidobacterium spp. and Enterococcus spp., both in healthy animals and after early dysbiosis.Our results indicate that antibiotic-associated dysbiosis at an early age is characterized by a temporary but powerful effect. At the same time, the use of 2′-fucosyllactose leads to preserving important probiotic groups of intestinal bacteria, both in health and after dysbiosis.

Gestational hypoxia elicits long-term cardiovascular dysfunction in female guinea pigs

BackgroundGestational hypoxia (GH) has been implicated in the developmental programming of cardiovascular diseases (CVDs) in the offspring, with most studies focusing on males, conversely, the effects on female cardiovascular health remain understudied. We aimed to investigate the impact of GH on the cardiovascular system of female guinea pig offspring from the early postnatal period to adulthood. MethodsPregnant guinea pigs were subjected to normoxic or hypoxic conditions from gestational day 30 until delivery (∼70 days). Female offspring were monitored with biometric parameters and peripheral vascular function (ultrasound) from birth to one year old. In addition, we assessed cardiovascular structure, oxidative stress, inflammatory state (IHC, qPCR, and immunoblot assays), and thoracic aorta reactivity (wire-myography) at one year of age. Key findingsGH increased heart rate and peripheral pulsatility index. At one year old, GH-exposed females exhibited cardiac remodeling, characterized by increased left ventricular luminal area and coronary artery muscle occupation. Furthermore, GH increased aortic vascular wall, intima-media thickness and contractile capacity. This was accompanied by reduced endothelium-dependent vasodilation and enhanced oxidative stress. Additionally, GH increased collagen deposition and oxidative stress in the right ventricle, accompanied by reduced antioxidant enzymes expression and reduced inflammatory mediator levels. SignificanceGH exerts long-lasting effects on the cardiovascular health of female guinea pig offspring, contributing to cardiac remodeling, vascular dysfunction, oxidative stress, and inflammatory changes. These findings highlight the importance of GH as a risk factor for developing CVDs in female offspring and emphasize the need for sex-specific interventions to mitigate adverse long-term gestational effects.

Perinatal iron deficiency alters the cardiac proteome and mitochondrial function in neonatal offspring.

Aims: Iron deficiency (ID) is common during gestation and early infancy and can alter developmental trajectories with lasting consequences on cardiovascular health. Iron plays a critical role in systemic oxygen transport (via hemoglobin) and aerobic respiration (as a component of mitochondrial complexes). Perinatal ID has been shown to cause cardiac dysfunction in neonates, but the mechanisms underlying these changes have not been characterized. Here, we examined the effects of perinatal ID on cardiac mitochondrial function in the early postnatal period in rats. Methods and Results: Female rats were fed an iron-restricted or iron-replete diet before and during pregnancy. Offspring hearts were collected postmortem for quantitative shotgun proteomic analysis (postnatal days [PD]0 and 28) and mitochondrial function was assessed by high-resolution respirometry (at PD0, 14 and 28). Markers of oxidative stress were measured by fluorescence microscopy and assessment of antioxidant gene expression profiles. Both male and female ID pups had reduced body weight and increased relative heart weights at all time points assessed, despite recovering from anemia by PD28. Proteomics analysis revealed dysregulation of mitochondrial proteins by ID, and these differences were most pronounced in males. In male hearts, ID increased mitochondrial content and decreased normalized mitochondrial respiration through the NADH-pathway, succinate-pathway, and FAO-pathway. Conclusions: ID causes changes in cardiac mitochondrial function in neonates, which may reflect an inadequate or maladaptive compensation during the transition from intrauterine to extrauterine life. Further, the results presented herein, which were stratified by offspring sex, underscore the need for follow-up studies to directly assess differences in the way male and female offspring cope with ID as a perinatal stressor.

SMN Deficiency Induces an Early Non-Atrophic Myopathy with Alterations in the Contractile and Excitatory Coupling Machinery of Skeletal Myofibers in the SMN∆7 Mouse Model of Spinal Muscular Atrophy.

Spinal muscular atrophy (SMA) is caused by a deficiency of the ubiquitously expressed survival motor neuron (SMN) protein. The main pathological hallmark of SMA is the degeneration of lower motor neurons (MNs) with subsequent denervation and atrophy of skeletal muscle. However, increasing evidence indicates that low SMN levels not only are detrimental to the central nervous system (CNS) but also directly affect other peripheral tissues and organs, including skeletal muscle. To better understand the potential primary impact of SMN deficiency in muscle, we explored the cellular, ultrastructural, and molecular basis of SMA myopathy in the SMNΔ7 mouse model of severe SMA at an early postnatal period (P0-7) prior to muscle denervation and MN loss (preneurodegenerative [PND] stage). This period contrasts with the neurodegenerative (ND) stage (P8-14), in which MN loss and muscle atrophy occur. At the PND stage, we found that SMN∆7 mice displayed early signs of motor dysfunction with overt myofiber alterations in the absence of atrophy. We provide essential new ultrastructural data on focal and segmental lesions in the myofibrillar contractile apparatus. These lesions were observed in association with specific myonuclear domains and included abnormal accumulations of actin-thin myofilaments, sarcomere disruption, and the formation of minisarcomeres. The sarcoplasmic reticulum and triads also exhibited ultrastructural alterations, suggesting decoupling during the excitation-contraction process. Finally, changes in intermyofibrillar mitochondrial organization and dynamics, indicative of mitochondrial biogenesis overactivation, were also found. Overall, our results demonstrated that SMN deficiency induces early and MN loss-independent alterations in myofibers that essentially contribute to SMA myopathy. This strongly supports the growing body of evidence indicating the existence of intrinsic alterations in the skeletal muscle in SMA and further reinforces the relevance of this peripheral tissue as a key therapeutic target for the disease.

Analysis of ultrasonographic measurements of inferior vena cava and abdominal aorta diameters in neonates

Objective: To analyze the ultrasonographic measurements of inferior vena cava (IVC) and abdominal aorta in healthy full-term neonates throughout the early postnatal period. Methods: Prospective observational study was conducted. A total of 132 healthy full-term neonates, who were born in the Department of Obstetrics of Kunshan First People's Hospital between May 1st and August 30th, 2023, were enrolled as the study subjects. Two-dimensional and M-mode ultrasonography were used to measure the maximum and minimum diameters of the IVC and abdominal aorta in the early postnatal period. The IVC collapsibility index, the ratio of maximum IVC diameter to abdominal aorta diameter, and the ratio of minimum IVC diameter to abdominal aorta diameter were calculated. These neonates were stratified by gender, birth mode, gestational age and birth weight (<3 000 or≥3 000 g), and independent sample t-test or Kruskal-Wallis test was used to compare the ultrasonography measurements by different groups. Results: Among the 132 neonates, 81 were males, with a gestational age of (39.2±1.0) weeks, and a birth weight of (3 326±409) g. There were no significant statistical differences in the the maximum and minimum diameters of the IVC and abdominal aorta assessed by both two-dimensional and M-modes between the first and second days (all P>0.05). Additionally, no statistical differences were observed in the ultrasonographic measurements among neonates of different sexes, birth modes, and gestational ages (all P>0.05); but there were statistically differences between the group with birth weight of <3 000 g and the group with birth weight of ≥3 000 g (all P<0.05). There were no statistically differences in IVC collapsibility index, the ratio of the maximum diameter of IVC to the diameter of abdominal aorta, and the ratio of the minimum diameter of IVC to the diameter of abdominal aorta between the group with birth weight of <3 000 g and the group with birth weight of≥3 000 g (all P>0.05). Conclusion: The diameters of the IVC and abdominal aorta in healthy full-term neonates during the early postnatal period are correlated with birth weight. The IVC collapsibility index and the ratio of IVC diameter to abdominal aorta diameter are unrelated to birth weight and can be used to assess newborn blood volume or right cardiac preload.

The association between maternal stress and human milk concentrations of cortisol and prolactin

Psychosocial stress affects the relationship between prolactin (PRL) and cortisol (CORT). The dynamics of PRL and CORT changes under stress in human milk (HM) are largely unknown. We investigated how maternal stress related to recent life changes affects milk CORT and PRL concentrations. The study involved 116 mothers exclusively breastfeeding 5-month-old infants. Maternal psychological stress was evaluated using the Recent Life Changes Questionnaire (RLCQ). Stress response was determined by administering the cold pressor test and measuring CORT in saliva taken during and in milk collected after the test. Hormones concentrations were assayed using the ELISA method. The hierarchical regression models were run to test the association between maternal RLCQ, salivary CORT, and PRL, and CORT in milk. Maternal RLCQ correlated positively with the CORT in saliva, however, no direct association was found between RLCQ and PRL. After controlling for covariates, a positive association was found between salivary and milk CORT. A negative relationship was observed between salivary CORT and milk PRL. The results of the present study indicate that maternal psychological stress may affect the relationship between CORT and PRL in HM. In response to psychological stress, both hormones transported via milk can program infant development in the early postnatal period.

Study of the biochemical status of calves in the early postnatal period in connection with dyspepsia

Purpose: to study changes in the most important metabolic parameters in case of dyspepsia in calves.Materials and methods. Two groups of calves of 8 heads each, aged from 6 to 14 days, were formed. The first group included calves with signs of dyspepsia, who, in addition to diarrhea syndrome, had decreased appetite, weakness, and signs of abdominal pain. At the time of the study, the duration of the illness was 2-4 days. The second (control) group included clinically healthy animals of the same age. Blood was taken from the calves from the jugular vein in the morning before feeding. Blood serum was examined in a clinical biochemical laboratory using standard test systems to determine biochemical parameters.Results. In calves with dyspepsia, a significant decrease in the concentration of triglycerides by 1,8 times, cholesterol by 1,57 times, total protein by 5,5 % and albumin by 12,3 % was revealed. They also revealed a significant increase in the activity of transamination enzymes — ALT (2,6 times) and AST (1,6 times), which may indicate both damage to hepatocytes and the induction of enzymes to accelerate transamination reactions in order to meet energy needs calf body. The studies did not reveal significant changes in the concentrations of urea, creatinine and bilirubin.Conclusion. Studies have revealed metabolic changes that occur due to decreased absorption of nutrients in the intestines. Damage to the intestinal mucosa leads not only to a deterioration in the absorption of nutrients, but also to the penetration of proteins, primarily albumins, into the intestinal lumen and their removal from the body into the external environment. Redistribution of metabolic pathways to ensure homeostasis plays an adaptive role, but subsequently can have a negative role in the processes of growth and development of the calf’s body.

Remodeling of adult rat heart subjected to pressure overload from the neonatal period is dependent on the sex

Abstract Background Congenital heart diseases (CHD) represents the most common birth defect. Despite progress in their treatment improving acute survival, there is a paucity of data concerning the long-term consequences of CHD in adults. Purpose Here, we investigate the remodeling in adult rat hearts subjected to pressure overload from the early postnatal period. Methods We used the neonatal abdominal aortic constriction (AAC) model to analyze morphological, functional (by echocardiography), and electrophysiological long-term outcomes. Given the known differences in cardiac pathologies between males (M) and females (F), we focused on the role of sex in cardiac remodeling. Results Our data showed that both sexes exhibited a similar left ventricular weight/body weight ratio at the age of 12 weeks, indicating comparable left ventricle (LV) enlargement as a response to AAC (increase by 103 ± 9 % in M AAC and 99 ± 10 % in F AAC vs. sham-operated animals). However, the right ventricular weight/body weight and lung/ body weight ratios, indicative of LV failing, differed significantly between sexes with better values in F AAC. The favorable cardiac remodeling in F AAC was corroborated by significantly smaller LV systolic and diastolic diameters, along with a lower amount of myocardial fibrosis. Using optical mapping, we revealed preserved longitudinal and transversal conduction velocities (CVL; CVT) in females (CVL 104 ± 8 vs. 109 ± 8 cm/s and CVT 66 ± 7 vs. 59 ± 6 cm/s in F AAC and F Sham, respectively). However, compared to M Sham, the conduction velocities in M AAC showed a significant decrease (CVL 80 ± 3 vs. 92 ± 3 cm/s and CVT 35 ± 2 vs. 54 ± 3 cm/s). Similarly, the amount of connexion 43 (Cx43) and its phosphorylated state (Cx43Ser368) was preserved in F AAC while exhibiting a decrease in M AAC compared to the sham-operated controls. Thus, electrophysiological findings implicate that while the adult M AAC underwent pro-arrhythmogenic remodeling due to the elevated workload, the adult F AAC preserved physiological conduction properties. Conclusion Our data showed different consequences of the increased pressure load exposed from early after birth to the adult M and F heart. These findings highlighted the involvement of both sexes in cardiac studies.

A review of the risk factors for Autism

Abstract Background Autism Spectrum Disorder (or Autism) is a neurodevelopmental and neurological condition, with prevalence of 1 in 100 children globally. This review examines the most common factors associated with Autism. Methods We conducted a scoping review of factors associated with an increased risk of developing Autism. These included genetic predisposition, parental age, gender, birth complications and morbidities due to other medical conditions. Results Evidence from twin studies shows a 90% genetic predisposition towards Autism - with 102 genes strongly associated with Autism, including SCN1A and SLC6A1. There are also genetic syndromes and chromosomal disorders associated with Autism, including Fragile X syndrome and Tuberous Sclerosis complex (TSC). Several studies have demonstrated an increased risk with advanced parental age (&amp;gt;35 years) (e.g., fathers &amp;gt;50 years are 2.2 times more likely to have a child with Autism than those &amp;lt;30 years). Other factors include infections during pregnancy (e.g. immune dysfunction) and gestational diabetes. Prematurity, such as low birth weight (&amp;lt;1500g) and low gestational age (&amp;lt;32 weeks) are also associated with an increased risk of Autism. With regard to gender, boys are more likely to be diagnosed with Autism - gender ratio of 3:1 and 4:1 has been reported in different populations. Abnormalities in brain development during early prenatal or postnatal periods may increase the risk of Autism. These abnormalities can lead to social, communication, and behavioural challenges characteristic of Autism. Conclusions Autism is a complex and heterogeneous condition that likely arises from a combination of factors such as genetic susceptibility and pre- and postnatal factors. An understanding of these factors is important for early detection, intervention, and support for children to improve their quality of life and reduce morbidity. Key messages • Risk factors associated with an increased risk of developing Autism include genetic predisposition, parental age, gender, birth complications and other comorbidities. • There is need to increase awareness of the risk factors of Autism to improve quality of life.

Exploring mothers' perspectives on the early mother-infant relationship to inform midwifery practice: A qualitative study

BackgroundThe mother-infant relationship plays a crucial role in individual and community health. The nature of the mother-infant relationship can influence the social and emotional development of the infant, impacting their lifelong health. Midwives are key in providing health promotion for women and babies and are ideally placed to support women during the early development of the mother-infant relationship. AimsThis study aimed to explore new mothers' perspectives on developing the early mother-infant relationship to inform midwifery practice. MethodsThis study is phase one of a mixed-method, exploratory sequential design project. In this phase, 14 women were interviewed within six weeks of birth to explore experiences that influenced the developing relationship with their baby. To support reflection women were provided with a visual prompt activity. These interviews informed the co-design workshops to develop an intervention to support midwives to promote the early mother infant relationship. A research protocol was published prior to undertaking the study, however as this research did not seek to modify or measure any heath related outcomes it was not registered as a clinical trial. ResultsKey themes from the interviews included: making moments that matter; the role of the village; feeling like I'm winning; supportive health professionals, and forming a new family. These themes underpinned strategies to support the mother-infant relationship. ConclusionThe findings from this study offer ways for midwives to support the emerging mother-infant relationship during the early postnatal period. Facilitating mothers to engage with their baby as well as integrating key people is important. Midwives also play a key role in building maternal confidence and competence. Further research is needed to embed and evaluate strategies in midwifery practice.

Cultural Practices of Mothers and Babies during the Postnatal Period: A Qualitative Study in Rural Bangladesh

This study describes the experiences of women in rural Bangladesh, and the cultural practices related to how they take care of themselves and their babies, in the early postnatal period. Data were gathered through immersion in the field for six months, participant observation, document collection and in-depth interview techniques to gain a deep understanding of women’s everyday lives and practices during the postnatal period. In-depth interviews were undertaken with 28 mothers who had had at least one live child within the five years before the date of data collection, in Purba Sharifabad village of the Barisal Division in Bangladesh. The key findings of this study highlight the role of culture in the experiences of women during the postnatal period, and reveal that cultural practices, beliefs and traditions are deeply embedded in the lives of rural women. This study focuses on cultural practices which have an effect on the choices of women regarding care and support from healthcare facilities. Culture, together with poverty and low levels of education, leads them to resist healthcare from a skilled birth attendant and encourages them to believe in and trust traditional care practices during the postnatal period. Therefore, the findings of this study may contribute to future policies, planning, programs and research in Bangladesh by providing an understanding of the importance of culturally and socially rooted traditional beliefs and cultural practices. These need to be addressed for maternal and newborn healthcare initiatives to be effective, particularly in rural Bangladesh.

Comparison of intestinal and pharyngeal microbiota in preterm infants on the first day of life and the characteristics of pharyngeal microbiota in infants delivered by cesarean section or vaginally.

This study aimed to explore the distribution of intestinal and pharyngeal microbiota on the first day of life in preterm infants and compare the composition of microbiota in infants delivered by cesarean section or vaginally. This study included 44 late preterm infants with a gestational age of 34-36 + 6 weeks. Stool and throat swab samples were collected from the preterm infants on the first day of life. The infants were divided into cesarean section and vaginal delivery groups. Illumina NovaSeq high-throughput sequencing technology was used to sequence the V3-V4 hypervariable region of the 16S rRNA gene of all bacteria in the samples. Venn diagram was used to identify shared operational taxonomic units (OTUs) in the intestines and pharynges. Microbial analysis was conducted at the phylum and genus levels, and α and β diversity comparisons were performed. (1) Gestational age may have significantly affected the microbial colonization of the intestines and pharynges of preterm infants on the first day after birth (p ≤ 0.001). (2) More OTUs were detected in the pharynx than in the intestines, both have a total of 819 shared OTUs. Proteobacteria, Firmicutes, and Bacteroidota were the dominant phyla in both. At the genus level, Streptococcus had a lower relative abundance in stool samples (0.5%) compared to throat samples (0.5% vs. 22.2%, p = 0.003). 3) The relative abundance of Streptococcus in pharyngeal samples was 26.2% in the cesarean section group much higher than the 3.8% in the vaginal delivery group (p = 0.01). The early postnatal period is a critical time for the establishment of an infant's microbiota. Gestational age at birth may influence microbial colonization, while birth weight, gender, and mode of delivery do not. The intestinal and pharyngeal microbiota composition of preterm infants on the first day after birth showed high similarity, but larger samples are needed for further validation.

Chronic kidney disease associated with extremely premature birth and extremely low birth weight may progress through the burden of growth.

Chronic kidney disease associated with low birth weight and/or premature birth (L/P-CKD) in infants may result from a decreased number of nephrons at birth. These infants may develop acute kidney injury due to exposure to nephrotoxic substances or other events during nephrogenesis in early infancy. Nonetheless, L/P-CKD progression remains unclear. We present three cases of L/P-CKD diagnosed after neonatal intensive care unit (NICU) discharge. Three patients were born extremely prematurely (gestational age, 24-26weeks) with extremely low birth weight (606-906g). They were admitted to the NICU (117-311days) anad received several nephrotoxic medications during the early postnatal period. They showed elevated serum creatinine levels at 4weeks after birth, which decreased to normal levels at NICU discharge. Proteinuria was first detected during adolescence (10-15years) on annual school urine screening, with a remarkable increase in their height (18 - 50.8cm), without known episodes of urinary tract infection, dehydration, lifestyle-related issues, such as excessive salt/protein intake, and extreme lack of exercise that might have caused kidney damage. Their kidneys were smaller than normal on renal ultrasonography. Open renal biopsy findings indicated glomerulomegaly and perihilar glomerulosclerosis in two of the three patients, suggesting glomerular hypertension. The remarkable differences between the body height before CKD and the timing of diagnosis of CKD could contribute to the progress of CKD. Long-term follow-up of low birth weight and extremely premature infants, from NICU discharge until adulthood, should be established.

8490 The mRNA for the Nonsyndromic Deafness Gene Atp2b2 Is Reduced Following Developmental Hypothyroidism

Abstract Disclosure: E.A. Gregersen: None. R.P. Peeters: None. D. Forrest: None. D.S. Sharlin: None. Thyroid hormone (TH) is essential for auditory system development. In rodent models, low levels of TH during the early postnatal period delay cochlear tissue remodeling and alter ion channel function required for normal auditory function. TH receptors are ligand-dependent transcription factors that regulate gene expression. Considering this, auditory deficits observed in hypothyroidism are thought to be largely the result of altered expression of specific TH target genes. However, few TH-regulated genes in the developing cochlea have been reported. TH is reported to impact calcium signaling in several tissues, but whether regulators of calcium signaling are altered following developmental hypothyroidism in the cochlea is largely unexplored. In this report, we investigated the spatial and temporal expression of the ATPase, Ca++ transporting, plasma membrane 2 (Atp2b2) gene in a mouse model of developmental hypothyroidism. Timed-pregnant dams were treated with thyroid gland inhibitors to induce developmental TH insufficiency from embryonic day 12.5 (E12.5) through post-natal day 15 (P15). Untreated timed-pregnant dams served as euthyroid controls. Control and experimental cochleae were collected over a developmental period ranging from embryonic day 18.5 (E18.5) through P15. Cochleae were then processed to detect Atp2b2 mRNA by in situ hybridization or quantitative real-time PCR. In situ hybridization showed that Atp2b2 localizes to inner and outer hair cells as expected, but Atp2b2 was also observed at lower levels in the greater epithelial ridge and spiral ganglion. Quantification of Atp2b2 mRNA revealed an effect of postnatal day and treatment on Atp2b2. In euthyroid animals, Atp2b2 expression gradually increased until P10, then decreased slightly by P15. In hypothyroid animals, Atp2b2 mRNA was consistently decreased (2-2.5 fold). Hypothyroidism similarly impacted expression regardless of sex. The reduction in Atp2b2 mRNA expression in the hypothyroid animals suggests that Atp2b2 is developmentally regulated in part by thyroid hormone signaling. This study characterizes the relationship between TH and Atp2b2 expression during early cochlear development while providing insight into abnormal cochlear development due to hypothyroidism. Presentation: 6/3/2024

Dysregulating mTORC1-4E-BP2 signaling in GABAergic interneurons impairs hippocampus-dependent learning and memory.

Memory formation is contingent on molecular and structural changes in neurons in response to learning stimuli-a process known as neuronal plasticity. The initiation step of mRNA translation is a gatekeeper of long-term memory by controlling the production of plasticity-related proteins in the brain. The mechanistic target of rapamycin complex 1 (mTORC1) controls mRNA translation, mainly through phosphorylation of the eukaryotic initiation factor 4E (eIF4E)-binding proteins (4E-BPs) and ribosomal protein S6 kinases (S6Ks). mTORC1 signaling decreases throughout brain development, starting from the early postnatal period. Here, we discovered that in mice, the age-dependent decrease in mTORC1 signaling occurs selectively in excitatory but not inhibitory neurons. Using a gene conditional knockout (cKO) strategy, we demonstrate that either up- or downregulating the mTORC1-4E-BP2 axis in GAD65 inhibitory interneurons, but not excitatory neurons, results in long-term object recognition and object location memory deficits. Our data indicate that the mTORC1 pathway in inhibitory but not excitatory neurons plays a key role in memory formation.

Investigation of factors associated with delayed initiation of breastfeeding in Papua New Guinea: a cross-sectional study

BackgroundBreastfeeding within the first hour of birth is critical for newborn survival. However, in Papua New Guinea (PNG), about 40% of newborns are not breastfed within the first hour of...

Epigenetic Modifications and Neuroplasticity in the Pathogenesis of Depression: A Focus on Early Life Stress.

Major depressive disorder (MDD) is a debilitating mental illness, and it is considered to be one of the leading causes of disability globally. The etiology of MDD is multifactorial, involving an interplay between biological, psychological, and social factors. Early life represents a critical period for development. Exposure to adverse childhood experiences is a major contributor to the global burden of disease and disability, doubling the risk of developing MDD later in life. Evidence suggests that stressful events experienced during that timeframe play a major role in the emergence of MDD, leading to epigenetic modifications, which might, in turn, influence brain structure, function, and behavior. Neuroplasticity seems to be a primary pathogenetic mechanism of MDD, and, similarly to epigenetic mechanisms, it is particularly sensitive to stress in the early postnatal period. In this review, we will collect and discuss recent studies supporting the role of epigenetics and neuroplasticity in the pathogenesis of MDD, with a focus on early life stress (ELS). We believe that understanding the epigenetic mechanisms by which ELS affects neuroplasticity offers potential pathways for identifying novel therapeutic targets for MDD, ultimately aiming to improve treatment outcomes for this debilitating disorder.