Neonatal Development Research Articles

EarlyLife - Gut epithelial dynamics and function at the nexus of early life infection and longterm health

We spoke with Prof. Dr. Mathias Hornef about the ERC-funded EarlyLife project, which investigates how early-life infections impact the gut epithelium, microbiome, and immune system development in neonates. Using advanced techniques and mouse models, the project aims to uncover the influence of these infections on long-term health and disease susceptibility.

Changes in short-chain fatty acids affect brain development in mice with early life antibiotic-induced dysbacteriosis.

Early enteral nutrition and the gut microbiota profoundly influence neonatal brain development, with short-chain fatty acids (SCFAs) from the microbiota playing a pivotal role. Understanding the relationship between dysbiosis, SCFAs, and brain development is crucial. In this study, we investigated the impact of antibiotics on the concentration of SCFAs in neonatal feces. Additionally, we developed a model of gut dysbiosis in neonatal mice to examine the potential relationship between this imbalance, SCFAs production, and brain function development. We measured the SCFAs content in the feces of two groups of neonates, categorized based on whether antibiotics were used, and conducted the Neonatal Behavioral Neurological Assessment (NBNA) test on all neonates. Then we evaluated fecal SCFAs levels in neonates and neonatal mice post-antibiotic treatment using liquid chromatography-mass spectrometry (LC-MS) analysis. Morris water maze (MWM) tests assessed behavioral performance, and western blot analysis examined brain tissue-related proteins-neuron-specific enolase (NSE), ionized calcium binding adaptor molecule-1 (IBA1), and myelin basic proteins (MBP). The use of antibiotics did not affect the NBNA scores of the two groups of neonates, but it did reduce the SCFAs content in their feces. Antibiotic administration induced gut dysbiosis in mice, resulting in decreased IBA1 and MBP expression. Interventions to restore gut microbiota ameliorated these effects. Mice with dysbiosis displayed cognitive deficits in the MWM test. SCFAs levels decreased during dysbiosis, and increased upon microbiota recovery. Neonatal dysbiosis affects the microbiota-gut-brain axis, impairing cognitive function and nervous system development. Reduced SCFAs may contribute significantly to these alterations.

Dynamic upregulation of retinoic acid signal in the early postnatal murine heart promotes cardiomyocyte cell cycle exit and maturation

The adult mammalian heart has extremely limited cardiac regenerative capacity. Most cardiomyocytes live in a state of permanent cell-cycle arrest and are unable to re-enter the cycle. Cardiomyocytes switch from cell proliferation to a maturation state during neonatal development. Although several signaling pathways are involved in this transition, the molecular mechanisms by which these inputs coordinately regulate cardiomyocyte maturation are not fully understood. Retinoic acid (RA) plays a pivotal role in development, morphogenesis, and regeneration. Despite the importance of RA signaling in embryo heart development, little is known about its function in the early postnatal period. We found that mRNA expression of aldehyde dehydrogenase 1 family member A2 (Aldh1a2), which encodes the key enzyme for synthesizing all-trans retinoic acid (ATRA) and is an important regulator for RA signaling, was transiently upregulated in neonatal mouse ventricles. Single-cell transcriptome analysis and immunohistochemistry revealed that Aldh1a2 expression was enriched in cardiac fibroblasts during the early postnatal period. Administration of ATRA inhibited cardiomyocyte proliferation in cultured neonatal rat cardiomyocytes and human cardiomyocytes. RNA-seq analysis indicated that cell proliferation-related genes were downregulated in prenatal rat ventricular cardiomyocytes treated with ATRA, while cardiomyocyte maturation-related genes were upregulated. These findings suggest that RA signaling derived from cardiac fibroblasts is one of the key regulators of cardiomyocyte proliferation and maturation during neonatal heart development.

Changes in skin barrier over the first four days of life: a cross-sectional study.

We aimed to evaluate the trajectory of skin barrier properties in full-term newborns during the first four days after birth. Based on the MKNFOAD cohort (NCT02889081), transepidermal water loss (TEWL), stratum corneum hydration (SCH), skin pH, and sebum content at five anatomical sites (cheek, forehead, volar forearm, abdomen, and dorsal lower leg) were examined once within 96 h after birth in 384 full-term infants. Multivariable linear regression analysis was performed to assess variations in these skin barrier parameters with age adjusted for gestational age, neonate's sex, parents' allergy history, delivery mode, amniotic fluid characteristics, and birth weight. The regression coefficient (ß) and 95% confidence interval were reported. We analyzed a total of 384 neonates including 198 (51.6%) boys. TEWL values remained stable and showed no significant association with age (days). pH values exhibited a declining trend with age (p for trend <0.001). Both SCH values and sebum content grew with age (p for trend <0.001). During the first four days after birth, the skin TEWL remained stable, pH decreased, and the SCH and sebum content increased over time. These findings provide insights into the neonatal skin physiological development at the beginning of life. From birth to 96 h, TEWL was stable, pH showed a steep decline, SCH and sebum content increased. This study provides the first evidence of skin adaptation in the newborn due to changes in utero to after birth in the first 4 days of life in an Asian population. These findings will provide a new theoretical basis for neonatal skin physiology and clinical strategies for guiding newborn skin care.

Advances in DNA methylation of imprinted genes and folic acid regulation of growth and development.

DNA methylation is closely related to folate levels and acts as a mechanism linking developmental disorders to chronic diseases. Folic acid supplementation can impact DNA methylation levels of imprinted genes crucial for neonatal development. Imprinted genes are vital for regulating embryonic and postnatal fetal growth. This review summarizes imprinted genes, DNA methylation, folic acid's influence on growth and development and their correlation. It aims to provide a comprehensive overview of research advancements on imprinted genes, DNA methylation and folic acid regulation concerning growth and development.

Extracting and Characterizing Lactic Acid Bacteria from Human Milk

The greatest diet for babies is breast milk since it meets all of their nutritional needs and promotes healthy growth and development. Human milk contains thousands of different bacteria, the most prevalent ones being lactobacillus and Bifido bacterium. Since the use of probiotics is growing daily, it's important to comprehend their properties and health advantages. The combination of protein, fats, carbs, lipids, minerals, and vitamins found in breast milk helps to nourish an infant's body. Additionally, the bacteria in breast milk offer defense against infections. We will learn about lactic acid bacteria from this study so that we can commercially make probiotics from strains of these bacteria without utilizing lactose, as certain people are lactose intolerant and do not consume any lactose-containing products. The purpose of this article is to identify and isolate lactic acid bacteria while also discussing the advantages of probiotics for health. To understand the role lactic acid bacteria (LAB) from human milk play in the development and health of neonates, LAB must be extracted and identified. This study's objective was to identify, characterize, and segregate LAB strains from human milk samples obtained from nursing mothers in good health. The first isolation was carried out using selective medium, and then morphological, biochemical, and molecular characterization were performed. Through 16S rRNA gene sequencing, the isolates were identified. All things considered, the development of the neonatal gut microbiota and the overall health of infants depend on lactic acid bacteria (LAB). This review's objective is to gather the most recent data on the identification and isolation of LAB from human milk, with an emphasis on the techniques employed, the types of LAB discovered, and any potential health risks. Human milk is an essential source of beneficial bacteria, including several species of lactobacilli (LAB), due to its complex and dynamic nature. Our ability to isolate and accurately identify these germs has improved due to technological advancements in the molecular and microbiological sciences. This paper provides an extensive overview of the methods utilized to extract LAB from human milk, the genera and species that are commonly detected, and the implications of these findings for the nutrition and health of neonates.

The influence of iron nutrition on the development of intestine and immune cell divergency in neonatal pigs

BackgroundAppropriate iron supplementation is essential for neonatal growth and development. However, there are few reports on the effects of iron overload on neonatal growth and immune homeostasis. Thus, the aim of this study was to investigate the effects of iron nutrition on neonatal growth and intestinal immunity by administering different levels of iron to neonatal pigs.ResultsWe found that iron deficiency and iron overload resulted in slow growth in neonatal pigs. Iron deficiency and iron overload led to down-regulation of jejunum intestinal barrier and antioxidant marker genes, and promoted CD8+ T cell differentiation in jejunum and mesenteric lymph nodes (MLN) of pigs, disrupting intestinal health. Moreover, iron levels altered serum iron and tissue iron status leading to disturbances in redox state, affecting host innate and adaptive immunity.ConclusionsThese findings emphasized the effect of iron nutrition on host health and elucidated the importance of iron in regulating redox state and immunity development. This study provided valuable insights into the regulation of redox state and immune function by iron metabolism in early life, thus contributing to the development of targeted interventions and nutritional strategies to optimize iron nutrition in neonates.

Socioeconomic status moderates associations between hippocampal development and cognition in preterms.

The hippocampus plays a critical role in cognitive networks. The anterior hippocampus is vulnerable to early-life stress and socioeconomic status (SES) with alterations persisting beyond childhood. How SES modifies the relationship between early hippocampal development and cognition remains poorly understood. This study examined associations between SES, structural and functional development of neonatal hippocampus, and 18-month cognition in very preterm neonates. In total, 179 preterm neonates were followed prospectively. Structural and resting-state functional MRI were obtained early-in-life and at term-equivalent age (median 32.9 and 41.1 weeks post-menstrual age) to calculate anterior and posterior hippocampal volumes and hippocampal functional connectivity strength. Eighteen-month cognition was assessed via Bayley-III. Longitudinal statistical analysis using generalized estimating equations, accounting for birth gestational age, post-menstrual age at scan, sex, and motion, was performed. SES, measured as maternal education level, modified associations between anterior but not posterior hippocampal volumes and 18-month cognition (interaction term p = 0.005), and between hippocampal connectivity and cognition (interaction term p = 0.05). Greater anterior hippocampal volumes and hippocampal connectivity were associated with higher cognitive scores only in the lowest SES group. Maternal education alone did not predict neonatal hippocampal volume from early-in-life and term. SES modified the relationship between neonatal hippocampal development and 18-month cognition in very preterm neonates. The lack of direct association between maternal education and neonatal hippocampal volumes indicates that socio-environmental factors beyond the neonatal period contribute to modifying the relationship between hippocampal development and cognition. These findings point toward opportunities to more equitably promote optimal neurodevelopmental outcomes in very preterm infants.

Proceedings of the 15th International Newborn Brain Conference: Fetal and/or neonatal brain development, both normal and abnormal.

Proceedings of the 15th International Newborn Brain Conference: Fetal and/or neonatal brain development, both normal and abnormal.

Hyperoxia exposure induces ferroptosis and apoptosis by downregulating PLAGL2 and repressing HIF-1α/VEGF signaling pathway in newborn alveolar typeII epithelial cell

ABSTRACT Backgroud Bronchopulmonary dysplasia (BPD) is one of the most important complications plaguing neonates and can lead to a variety of sequelae. the ability of the HIF-1α/VEGF signaling pathway to promote angiogenesis has an important role in neonatal lung development. Method Newborn rats were exposed to 85% oxygen. The effects of hyperoxia exposure on Pleomorphic Adenoma Gene like-2 (PLAGL2) and the HIF-1α/VEGF pathway in rats lung tissue were assessed through immunofluorescence and Western Blot analysis. In cell experiments, PLAGL2 was upregulated, and the effects of hyperoxia and PLAGL2 on cell viability were evaluated using scratch assays, CCK-8 assays, and EDU staining. The role of upregulated PLAGL2 in the HIF-1α/VEGF pathway was determined by Western Blot and RT–PCR. Apoptosis and ferroptosis effects were determined through flow cytometry and viability assays. Results Compared with the control group, the expression levels of PLAGL2, HIF-1α, VEGF, and SPC in lung tissues after 3, 7, and 14 days of hyperoxia exposure were all decreased. Furthermore, hyperoxia also inhibited the proliferation and motility of type II alveolar epithelial cells (AECII) and induced apoptosis in AECII. Upregulation of PLAGL2 restored the proliferation and motility of AECII and suppressed cell apoptosis and ferroptosis, while the HIF-1α/VEGF signaling pathway was also revived. Conclusions We confirmed the positive role of PLAGL2 and HIF-1α/VEGF signaling pathway in promoting BPD in hyperoxia conditions, and provided a promising therapeutic targets.

Reducing Noise in the NICU.

In the neonatal intensive care unit (NICU), elevated noise negatively impacts the neurodevelopmental environment, interrupts sleep, and can affect brain development in neonates. The American Academy of Pediatrics recommends that noise levels in the NICU should not exceed 45dB. The project aims were to: (1) decrease average noise level by 10% from baseline and (2) decrease exposure to severe noise (>65dB) to <5% of the time. This quality improvement project was conducted during 2021-2022 as a pre/post observational design in a Level IV NICU in New York City. We monitored sound levels for 20-24h, 5d/wk. Quality improvement interventions included: novel approaches to staff education, visual cues for when noise thresholds were exceeded, parent education, including access to personal decibel meters, technical improvements to vital sign monitors and entry doors, and defined quiet times (HUSH) for 2h each 12-hour shift. Education efforts and technical improvements successfully reduced median noise levels within the stepdown unit ( P <.001), though not in the acute care NICU. In contrast, the implementation of 2-hour periods of enforced "quiet time" every 12h effectively reduced both median noise levels and the incidence of severe noise (>65dB) in both locations. The HUSH strategy may be a sustainable way to decrease noise in the NICU. Future projects should prioritize education and dedicated quiet times to align with recommended standards, while research should explore the long-term developmental impacts of excessive noise levels on neonatal growth.

Fibrinogen inhibits sonic hedgehog signaling and impairs neonatal cerebellar development after blood–brain barrier disruption

Cerebellar injury in preterm infants with central nervous system (CNS) hemorrhage results in lasting neurological deficits and an increased risk of autism. The impact of blood-induced pathways on cerebellar development remains largely unknown, so no specific treatments have been developed to counteract the harmful effects of blood after neurovascular damage in preterm infants. Here, we show that fibrinogen, a blood-clotting protein, plays a central role in impairing neonatal cerebellar development. Longitudinal MRI of preterm infants revealed that cerebellar bleeds were the most critical factor associated with poor cerebellar growth. Using inflammatory and hemorrhagic mouse models of neonatal cerebellar injury, we found that fibrinogen increased innate immune activation and impeded neurogenesis in the developing cerebellum. Fibrinogen inhibited sonic hedgehog (SHH) signaling, the main mitogenic pathway in cerebellar granule neuron progenitors (CGNPs), and was sufficient to disrupt cerebellar growth. Genetic fibrinogen depletion attenuated neuroinflammation, promoted CGNP proliferation, and preserved normal cerebellar development after neurovascular damage. Our findings suggest that fibrinogen alters the balance of SHH signaling in the neurovascular niche and may serve as a therapeutic target to mitigate developmental brain injury after CNS hemorrhage.

Whole-body hypothermia in mild neonatal encephalopathy: protocol for a multicentre phase III randomised controlled trial

BackgroundMild hypoxic ischemic encephalopathy is associated with sub optimal cognition and learning difficulties at school age. Although whole-body hypothermia reduces death and disability after moderate or severe encephalopathy in high-income countries, the safety and efficacy of hypothermia in mild encephalopathy is not known. The cooling in mild encephalopathy (COMET) trial will examine if whole-body hypothermia improves cognitive development of neonates with mild encephalopathy.MethodsThe COMET trial is a phase III multicentre open label two-arm randomised controlled trial with masked outcome assessments. A total of 426 neonates with mild encephalopathy will be recruited from 50 to 60 NHS hospitals over 2 ½ years following parental consent. The neonates will be randomised to 72 h of whole-body hypothermia (33.5 ± 0.5 C) or normothermia (37.0 ± 0.5 C) within six hours or age. Prior to the recruitment front line clinical staff will be trained and certified on expanded modified Sarnat staging for encephalopathy. The neurological assessment of all screened and recruited cases will be video recorded and centrally assessed for quality assurance. If recruitment occurs at a non-cooling centre, neonates in both arms will be transferred to a cooling centre for continued care, after randomisation. All neonates will have continuous amplitude integrated electroencephalography (aEEG) at least for the first 48 h to monitor for seizures. Predefined safety outcomes will be documented, and data collected to assess resource utilization of health care. A central team masked to trial group allocation will assess neurodevelopmental outcomes at 2 years of age. The primary outcome is mean difference in composite cognitive scores on Bayley scales of Infant and Toddler development 4th Edition.DiscussionThe COMET trial will establish the safety and efficacy of whole-body hypothermia for mild hypoxic ischaemic encephalopathy and inform national and international guidelines in high income countries. It will also provide an economic assessment of whole-body hypothermia therapy for mild encephalopathy in the NHS on cost-effectiveness grounds.Trial registration numberNCT05889507 June 5, 2023.

Metabolic and Microbial Dysregulation in Preterm Infants with Neonatal Respiratory Distress Syndrome: An Early Developmental Perspective.

Neonatal respiratory distress syndrome (NRDS) is one of the most severe respiratory disorders in preterm infants (PTIs) due to immature lung development. To delineate the serum metabolic alterations and gut microbiota variations in NRDS and assess their implications on neonatal development, we enrolled 13 NRDS neonates and 12 PTIs and collected fecal and serum specimens after birth. Longitudinal fecal sampling was conducted weekly for a month in NRDS neonates. NRDS neonates were characterized by notably reduced gestational ages and birth weights and a higher rate of asphyxia at birth relative to PTIs. Early postnatal disturbances in tryptophan metabolism were evident in the NRDS group, concomitant with elevated relative abundance of Haemophilus, Fusicatenibacter, and Vibrio. Integrative multiomics analyses revealed an inverse relationship between tryptophan concentrations and Blautia abundance. At one-week old, NRDS neonates exhibited cortisol regulation anomalies and augmented hepatic catabolism. Sequential microbial profiling revealed distinct gut microbiota evolution in NRDS subjects, characterized by a general reduction in potentially pathogenic bacteria. The acute perinatal stress of NRDS leads to mitochondrial compromise, hormonal imbalance, and delayed gut microbiota evolution. Despite the short duration of NRDS, its impact on neonatal development is significant and requires extended attention.

Noninvasive microvascular imaging in newborn rats using high-frequency ultrafast ultrasound

Ultrasound imaging stands as the predominant modality for neonatal health assessment, with recent advancements in ultrafast Doppler (μDoppler) technology offering significant promise in fields such as neonatal brain imaging. Combining μDoppler with high-frequency ultrasound (HF-μDoppler) presents a potential efficient avenue to enhance in vivo microvascular imaging in small animals, notably newborn rats, a crucial preclinical animal model for neonatal disease and development research. It is necessary to verify the imaging performance of HF-μDoppler in preclinical trials. This study investigates the microvascular imaging capabilities of HF-μDoppler using a 30 MHz high-frequency linear array probe in newborn rats. Results demonstrate the clarity of cerebral microvascular imaging in rats aged 1 to 7 postnatal days, extending to whole-body microvascular imaging, encompassing the central nervous system, including the brain and spinal cord. In conclusion, HF-μDoppler technology emerges as a reliable imaging tool, offering a new perspective for preclinical investigations into neonatal diseases and development.

Translational 3D-Cell Culture Model to Assess Hyperoxia Effects on Human Neonatal Airway Epithelial Cells.

The preterm neonatal airway epithelium is constantly exposed to environmental stressors. One of these stressors in neonates with lung disease includes oxygen (O2) tension higher than the ambient atmosphere - termed hyperoxia (>21% O2). The effect of hyperoxia on the airway depends on various factors, including the developmental stage of the airway, the degree of hyperoxia, and the duration of exposure, with variable exposures potentially leading to unique phenotypes. While there has been extensive research on the effect of hyperoxia on neonatal lung alveolarization and airway hyperreactivity, little is known about the short and long-term underlying effect of hyperoxia on human neonatal airway epithelial cells. A major reason for this is the scarcity of an effective in vitro model to study human neonatal airway epithelial development and function. Here, we describe a method for isolating and expanding human neonatal tracheal airway epithelial cells (nTAECs) utilizing human neonatal tracheal aspirates and culturing these cells in air-liquid interface (ALI) culture. We demonstrate that nTAECs form a mature polarized cell-monolayer in ALI culture and undergo mucociliary differentiation. We also present a method for moderate hyperoxia exposure of the cell monolayer in ALI culture using a specialized incubator. Additionally, we describe an assay to measure cellular oxidative stress following hyperoxia exposure in ALI culture using fluorescent quantification, which confirms that moderate hyperoxia exposure induces cellular oxidative stress but does not cause significant cell membrane damage or apoptosis. This model can potentially be used to simulate clinically relevant hyperoxia exposure encountered by neonatal airways in the Neonatal Intensive Care Unit (NICU) and used to study the short and long-lasting effects of O2 on neonatal airway epithelial programming. Studies using this model could be utilized to explore ways to mitigate early-life oxidative injury to developing airways, which is implicated in the development of long-term airway diseases in former premature infants.

Arginine vasopressin activates serotonergic neurons in the dorsal raphe nucleus during neonatal development in vitro and in vivo

Birth stress is a risk factor for psychiatric disorders and associated with exaggerated release of the stress hormone arginine vasopressin (AVP) into circulation and in the brain. In perinatal hippocampus, AVP activates GABAergic interneurons which leads to suppression of spontaneous network events and suggests a protective function of AVP on cortical networks during birth. However, the role of AVP in developing subcortical networks is not known. Here we tested the effect of AVP on the dorsal raphe nucleus (DRN) 5-hydroxytryptamine (5-HT, serotonin) system in male and female neonatal rats, since early 5-HT homeostasis is critical for the development of cortical brain regions and emotional behaviors. We show that AVP is strongly excitatory in neonatal DRN: it increases excitatory synaptic inputs of 5-HT neurons via V1A receptors in vitro and promotes their action potential firing through a combination of its effect on glutamatergic synaptic transmission and a direct effect on the excitability of these neurons. Furthermore, we identified two major firing patterns of neonatal 5-HT neurons in vivo, tonic regular firing and low frequency oscillations of regular spike trains and confirmed that these neurons are also activated by AVP in vivo. Finally, we show that the sparse vasopressinergic innervation in neonatal DRN originates exclusively from cell groups in medial amygdala and bed nucleus of stria terminalis. Hyperactivation of the neonatal 5-HT system by AVP during birth stress may impact its own functional development and affect the maturation of cortical target regions, which may increase the risk for psychiatric conditions later on.

Lower Hemoglobin Levels as a Risk Factor for the Development of Retinopathy of Prematurity.

Retinopathy of prematurity (ROP) is an important cause of visual morbidity among preterm infants. The objective of the study was to assess the relationship between the initial hematological parameters of the complete blood count (CBC) and ROP development in preterm neonates. This retrospective cohort study was conducted in a neonatal intensive care unit in Odisha. The hematological parameters of the CBC conducted within the first 48 hours of age, demographic characteristics, neonatal morbidities, and ROP screening findings of preterm neonates (gestational age <34 weeks) were analyzed. Independent risk factors associated with ROP development were identified in a multivariate logistic regression model. A total of 43 (29.1%) out of 148 neonates had any of the ROP stages (stage 1-26, 2-08, and 3-09). Birth weight (aOR 0.003; 95% CI 0.00, 0.11);hemoglobin (Hb) level (aOR 0.70; 95% CI 0.54, 0.90); presence of respiratory distress syndrome (RDS) (aOR 7.61; 95% CI 1.5, 36.39); and need for packed red blood cell (PRBC) transfusion (aOR 4.26; 95% CI 1.1, 16.44) were independently associated withROP development. The odds of ROP were higher among the neonates with initial Hb 10.5-15.4 g/dL (OR (95% CI) 3.7(1.5, 8.9), p=0.003) and for neonates with Hb 15.4-17.3 g/dL (OR (95% CI)2.5(1.01, 6.16), p=0.047) in comparison to neonates with initial Hb >17.3 g/dL. Preterm neonates with a lower level of Hb during the early postnatal days are at higher risk for ROP development and need to be prioritized for screening.

Neonatal microbiota colonization drives maturation of primary and secondary goblet cell mediated protection in the pre-weaning colon.

In the distal colon, mucus secreting goblet cells primarily confer protection from luminal microorganisms via generation of a sterile inner mucus layer barrier structure. Bacteria-sensing sentinel goblet cells provide a secondary defensive mechanism that orchestrates mucus secretion in response to microbes that breach the mucus barrier. Previous reports have identified mucus barrier deficiencies in adult germ-free mice, thus implicating a fundamental role for the microbiota in programming mucus barrier generation. In this study, we have investigated the natural neonatal development of the mucus barrier and sentinel goblet cell-dependent secretory responses upon postnatal colonization. Combined in vivo and ex vivo analyses of pre- and post-weaning colonic mucus barrier and sentinel goblet cell maturation demonstrated a sequential microbiota-dependent development of these primary and secondary goblet cell-intrinsic protective functions, with dynamic changes in mucus processing dependent on innate immune signalling via MyD88, and development of functional sentinel goblet cells dependent on the NADPH/Dual oxidase family member Duox2. Our findings therefore identify new mechanisms of microbiota-goblet cell regulatory interaction and highlight the critical importance of the pre-weaning period for the normal development of colonic barrier function.

Prenatal Social Determinants of Health: Narrative review of maternal environments and neonatal brain development.

The Social Determinants of Health, a set of social factors including socioeconomic status, community context, and neighborhood safety among others, are well-known predictors of mental and physical health across the lifespan. Recent research has begun to establish the importance of these social factors at the earliest points of brain development, including during the prenatal period. Prenatal socioeconomic status, perceived stress, and neighborhood safety have all been reported to impact neonatal brain structure and function, with exploratory work suggesting subsequent effects on infant and child behavior. Secondary effects of the Social Determinants of Health, such as maternal sleep and psychopathology during pregnancy, have also been established as important predictors of infant brain development. This research not only establishes prenatal Social Determinants of Health as important predictors of future outcomes but may be effectively applied even before birth. Future research replicating and extending the effects in this nascent literature has great potential to produce more specific and mechanistic understanding of the social factors that shape early neurobehavioral development. IMPACT: This review synthesizes the research to date examining the effects of the Social Determinants of Health during the prenatal period and neonatal brain outcomes. Structural, functional, and diffusion-based imaging methodologies are included along with the limited literature assessing subsequent infant behavior. The degree to which results converge between studies is discussed, in combination with the methodological and sampling considerations that may contribute to divergence in study results. Several future directions are identified, including new theoretical approaches to assessing the impact of the Social Determinants of Health during the perinatal period.