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Objective: To characterize the epidemiology, identify trends in prevalence, seasonality, and risk factors for orofacial clefts (OFC), selecting the São Paulo state (SPS) population database. Design: A population-based study to estimate the OFC prevalence trends in recent years, stratified by maternal age and SPS geographical clusters. Setting: All live births (LB) with OFC in SPS from 2008-2019. Patients: 5342 cases of OFC among 7 301 636 LB. Interventions: Not applicable. Main outcome measures: OFC prevalence trends, annual percent change (APC) with a 95% confidence interval, and seasonality. Results: We found an OFC prevalence of 7.3/10 000LB in SPS, Brazil. Among all the cases, the majority were male (57.1%), Caucasian (65.4%), 77.8% born at term, 75.8% weight >2500 g, 97.1% singleton, and 63.9% of births were by cesarean section. From 2008-2019, SPS presented a stationary OFC prevalence trend; in São Paulo city, the highest APC was observed (0.05%); the maternal age group with the highest OFC prevalence rate was ≥35 years (9.2/10 000LB). We identified the existence of seasonal variation based on the conception date in the final months of the year, corresponding to the spring season (P <.001). Conclusion: OFC had a stationary prevalence trend in recent years, with the highest prevalence in the Central North Cluster and ≥35 years maternal age group. Seasonality was observed in the spring season, and congenital malformation of lips was the most common associated pathology. This population-based study is the first to summarize the current epidemiology of OFC in SPS. [ABSTRACT FROM AUTHOR]

Many expectant mothers use CBD to alleviate symptoms like nausea, insomnia, anxiety, and pain, despite limited research on its long-term effects. However, CBD passes through the placenta, affecting fetal development and impacting offspring behavior. We investigated how prenatal CBD exposure affects the insular cortex (IC), a brain region involved in emotional processing and linked to psychiatric disorders. The IC is divided into two territories: the anterior IC (aIC), processing socioemotional signals, and the posterior IC (pIC), specializing in interoception and pain perception. Pyramidal neurons in the aIC and pIC exhibit sex-specific electrophysiological properties, including variations in excitability and the excitatory/inhibitory balance. We investigated IC's cellular properties and synaptic strength in the offspring of both sexes from mice exposed to low-dose CBD during gestation (E5–E18; 3 mg/kg, s.c.). Prenatal CBD exposure induced sex-specific and territory-specific changes in the active and passive membrane properties, as well as intrinsic excitability and the excitatory/inhibitory balance, in the IC of adult offspring. The data indicate that in utero CBD exposure disrupts IC neuronal development, leading to a loss of functional distinction between IC territories. These findings may have significant implications for understanding the effects of CBD on emotional behaviors in offspring. [ABSTRACT FROM AUTHOR]

The climate crisis encompasses a constellation of risks that threaten human livelihoods, well‐being, and survival globally. In this article, we present a new framework based on bioecological and dynamic systems perspectives, and on evidence for conceptualizing how the distinctive dual time frame of both acute (e.g., extreme weather events) and chronic (e.g., ecological degradation) climate change‐related risks experienced prenatally and early in life across multiple ecological contexts can threaten human development. We conclude with a call to developmental researchers, practitioners, and policymakers to invest more efforts in understanding and addressing the climate crisis and its developmental consequences to ensure a sustainable future for all. [ABSTRACT FROM AUTHOR]

Given prior literature focused on the Developmental Origins of Health and Disease framework, there is strong rationale to hypothesize that reducing depression in the prenatal period will cause improvements in offspring cardiometabolic health. The current review outlines evidence that prenatal depression is associated with offspring cardiometabolic risk and health behaviors. We review evidence of these associations in humans and in nonhuman animals at multiple developmental periods, from the prenatal period (maternal preeclampsia, gestational diabetes), neonatal period (preterm birth, small size at birth), infancy (rapid weight gain), childhood and adolescence (high blood pressure, impaired glucose–insulin homeostasis, unfavorable lipid profiles, abdominal obesity), and into adulthood (diabetes, cardiovascular disease). In addition to these cardiometabolic outcomes, we focus on health behaviors associated with cardiometabolic risk, such as child eating behaviors, diet, physical activity, and sleep health. Our review focuses on child behaviors (e.g., emotional eating, preference for highly palatable foods, short sleep duration) and parenting behaviors (e.g., pressuring child to eat, modeling of health behaviors). These changes in health behaviors may be detected before changes to cardiometabolic outcomes, which may allow for early identification of and prevention for children at risk for poor adult cardiometabolic outcomes. We also discuss the methods of the ongoing Care Project, which is a randomized clinical trial to test whether reducing prenatal maternal depression improves offspring's cardiometabolic health and health behaviors in preschool. The goal of this review and the Care Project are to inform future research, interventions, and policies that support prenatal mental health and offspring cardiometabolic health. Public Significance Statement: Prenatal depression is pervasive and is associated with poorer offspring development and health. The current review synthesizes evidence of biological and behavioral pathways by which prenatal depression may influence offspring cardiometabolic health. We outline an ongoing study that tests whether reducing prenatal maternal depression improves offspring cardiometabolic health and health behaviors. [ABSTRACT FROM AUTHOR]

The potential maternal and foetal toxicity resulting from exposure to xylene at or below the allowable limit of 100 ppm during gestation is not thoroughly studied. The aim of this study was to investigate maternal and foetal outcomes following prenatal exposure to xylene during organogenesis. Pregnant Sprague Dawley (SD) rats were administered intraperitoneal (IP) corn oil (vehicle), 100, 500, and 1000 parts per million (ppm) of xylene from gestational day (GD) 6 until GD17. Clinical signs, maternal weight gain, and food consumption were recorded daily. A caesarean hysterectomy was performed on GD21 to assess the reproductive and foetal outcomes. Exposure to 1000 ppm of xylene caused a significant decrease in the maternal body weight and food consumption, and an increase in intrauterine foetal deaths. Foetal assessment revealed a significant decrease in foetal weight in both male and female foetuses of female rats treated with 500 and 1000 ppm. Male placental weight was significantly decreased in all xylene-treated groups, while 1000 ppm xylene significantly decreased female placental weight. Histologically, marked uterine inflammatory lesions, fibrosis of the liver and renal tissues, as well as increased placental glycogen content were observed. Immunohistochemistry revealed a significant increase in lipid peroxidation and apoptotic markers. Thus, the foeto-maternal toxicities of xylene have been shown to be mediated by a systemic inflammatory response that exacerbates intrauterine oxidative stress and impairs foeto-placental transfer, leading to an increase in foetal mortality. [ABSTRACT FROM AUTHOR]

During the second-to-third trimester, the neuronal pathways of the fetal brain experience rapid development, resulting in the complex architecture of the interwired network at birth. While diffusion MRI-based tractography has been employed to study the prenatal development of structural connectivity network (SCN) in preterm neonatal and postmortem fetal brains, the in utero development of SCN in the normal fetal brain remains largely unknown. In this study, we utilized in utero dMRI data from human fetuses of both sexes between 26 and 38 gestational weeks to investigate the developmental trajectories of the fetal brain SCN, focusing on intrahemispheric connections. Our analysis revealed significant increases in global efficiency, mean local efficiency, and clustering coefficient, along with significant decrease in shortest path length, while small-worldness persisted during the studied period, revealing balanced network integration and segregation. Widespread short-ranged connectivity strengthened significantly. The nodal strength developed in a posterior-to-anterior and medial-to-lateral order, reflecting a spatiotemporal gradient in cortical network connectivity development. Moreover, we observed distinct lateralization patterns in the fetal brain SCN. Globally, there was a leftward lateralization in network efficiency, clustering coefficient, and small-worldness. The regional lateralization patterns in most language, motor, and visual-related areas were consistent with prior knowledge, except for Wernicke’s area, indicating lateralized brain wiring is an innate property of the human brain starting from the fetal period. Our findings provided a comprehensive view of the development of the fetal brain SCN and its lateralization, as a normative template that may be used to characterize atypical development. [ABSTRACT FROM AUTHOR]

Activation of the maternal immune system during gestation has been associated with an increased risk for neurodevelopmental disorders in the offspring, particularly schizophrenia and autism spectrum disorder. Microglia, the tissue-resident macrophages of the central nervous system, are implicated as potential mediators of this increased risk. Early in development, microglia start populating the embryonic central nervous system and in addition to their traditional role as immune responders under homeostatic conditions, microglia are also intricately involved in various early neurodevelopmental processes. The timing of immune activation may interfere with microglia functioning during early neurodevelopment, potentially leading to long-term consequences in postnatal life. In this review we will discuss the involvement of microglia in brain development during the prenatal and early postnatal stages of life, while also examining the effects of maternal immune activation on microglia and neurodevelopmental processes. Additionally, we discuss recent single cell RNA-sequencing studies focusing on microglia during prenatal development, and hypothesize how early life microglial priming, potentially through epigenetic reprogramming, may be related to neurodevelopmental disorders. [ABSTRACT FROM AUTHOR]

Objective: To determine the association between prenatal care and cleft lip with or without cleft palate (CL ± P) and examine differences in newborn complications among infants diagnosed with CL ± P as a function of prenatal care Design: Population-based retrospective cohort study Setting: 2018 United States National Vital Statistics System—Natality component (NVSS-N) was used to examine nationwide birth certificate data Participants: 3,414,338 infants from the 2018 National Vital Statistics System, of which 1,699 had CL ± P Main Outcome Measure: Diagnosis of CL ± P and presence of newborn complications as a function of prenatal care Results: Significant differences were found among various infant- and mother-specific variables when baseline comparisons were made between infants with and without CL ± P. After controlling for baseline differences, results indicated decreased odds of a diagnosis of CL ± P in cases where overall adequate prenatal care was obtained (OR =.841; 95% CI.757,.934), including prenatal care beginning in the 1st trimester (OR =.839; 95% CI.750,.939) and an adequate number of prenatal visits received (OR =.864; 95% CI.764,.976). Of infants with CL ± P, reduced odds of the infant admitted to the neonatal intensive care unit (OR =.777; 95% CI.613,.985) or transferred (OR =.601; 95% CI.407,.888) were apparent when adequate prenatal care was received. Conclusion: Results suggest adequate prenatal care not only reduces the likelihood of CL ± P in infants but may also decrease the severity of negative outcomes in infants diagnosed with CL ± P. These findings emphasize necessity for adequate prenatal care. [ABSTRACT FROM AUTHOR]

Objective: Determine interactions between geospatial and socioeconomic factors influencing cleft lip and/or cleft palate (CL/P) management and outcomes. Design: Retrospective review and outcomes analysis (n = 740). Setting: Urban academic tertiary care center. Patients: 740 patients undergoing primary (CL/P) surgery from 2009 to 2019. Main Outcomes Measures: Prenatal evaluation by plastic surgery, nasoalveolar molding, cleft lip adhesion, and age at CL/P surgery. Results: Prenatal evaluation by plastic surgery was predicted by the interaction between higher patient median block group income and shorter patient distance from the care center (OR = 1.07, p = 0.022). Nasoalveolar molding was also predicted by the interaction between higher patient median block group income and shorter distance from the care center (OR = 1.28, p = 0.016), whereas cleft lip adhesion was predicted by higher patient median block group income alone (OR = 0.41, p < 0.001). Lower patient median block group income predicted later age at cleft lip (β = −67.25, p = 0.011) and cleft palate (β = −46.35, p = 0.050) repair surgery. Conclusions: Distance from the care center and lower median income by block group interacted to significantly predict prenatal evaluation by plastic surgery and nasoalveolar molding for patients with CL/P at a large, urban, tertiary care center. Patients living farthest from the care center who received prenatal evaluation by plastic surgery or who underwent nasoalveolar molding had higher median block group income. Future work will determine mechanisms perpetuating these barriers to care. [ABSTRACT FROM AUTHOR]

Objective: Some studies have suggested that introducing a second-trimester anomaly scan (SAS) leads to increased rates of termination of pregnancy (TOP) in fetuses with orofacial clefts (OFCs). The aim of this study was to evaluate the impact of a nationwide introduction of SAS on the prevalence of live births with OFCs in the Netherlands. Design: Retrospective cohort study. Setting: Tertiary setting. Population: Included in the study were all patients diagnosed with OFCs as recorded in the "Dutch Association for Cleft Palate Anomalies" database between 1997 and 2019. Interventions: Patients were divided into three categories: cleft lip with or without alveolus (CL/A), cleft lip, alveolus and palate (CLAP) and cleft palate (CP) based on anatomical landmarks at the first consultation. Main outcome measures: Prevalence rates of OFCs before and after the nationwide introduction of the SAS on January 1, 2007 were compared. Result: Overall, 1899 patients were diagnosed with CL/A, 2586 with CLAP and 2927 with CP. The prevalence of clefts before and after introduction of the SAS did not differ (P = 0.85). The prevalence of CL/A decreased (P = 0.04), and that of CLAP decreased (P = 0.01) and that of CP increased (P = 0.02). Conclusions: This study demonstrates a significant decrease in the prevalence of CL/A and CLAP after introduction of the SAS. However, due to an increase in CP, the prevalence of all patients born with OFCs has not changed in the Netherlands between 1997 and 2019. [ABSTRACT FROM AUTHOR]

The intricate formation of the palate involves a series of complex events, yet its mechanistic basis remains uncertain. To explore major cell populations in the palate and their roles during development, we constructed a spatiotemporal transcription landscape of palatal cells. Palate samples from C57BL/6 J mice at embryonic days 12.5 (E12.5), 14.5 (E14.5), and 16.5 (E16.5) underwent single-cell RNA sequencing (scRNA-seq) to identify distinct cell subsets. In addition, spatial enhanced resolution omics-sequencing (stereo-seq) was used to characterize the spatial distribution of these subsets. Integrating scRNA-seq and stereo-seq with CellTrek annotated mesenchymal and epithelial cellular components of the palate during development. Furthermore, cellular communication networks between these cell subpopulations were analyzed to discover intercellular signaling during palate development. From the analysis of the middle palate, both mesenchymal and epithelial populations were spatially segregated into 3 domains. The middle palate mesenchymal subpopulations were associated with tooth formation, ossification, and tissue remodeling, with initial state cell populations located proximal to the dental lamina. The nasal epithelium of the palatal shelf exhibited richer humoral immune responses than the oral side. Specific enrichment of Tgfβ3 and Pthlh signals in the midline epithelial seam at E14.5 suggested a role in epithelial–mesenchymal transition. In summary, this study provides high-resolution transcriptomic information, contributing to a deeper mechanistic understanding of palate biology and pathophysiology. [ABSTRACT FROM AUTHOR]

This article aims to determine how quality of life (QoL) is defined and assessed in cases of severe craniofacial anomalies, as well as the impact such considerations may have on the treatment of a neonate with these conditions with respect to palliative neonatal care. Our literature review found insufficient evidence to suggest that craniofacial anomalies result in consistently poor QoL. Based on these findings and in line with the current acceptable standards for the ethical care of neonates, with the exception of rare cases, resuscitative efforts should always be performed on patients with isolated craniofacial anomalies, as demonstrated in the management of this reported patient. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the local incidence of orofacial cleft (OFC) encountered in fetal morphology scan and prenatal diagnosis, genetic etiology of fetuses with or without other structural abnormalities, and their pregnancy outcomes. Design: Retrospective cohort study. Setting: Two maternal fetal medicine units, tertiary hospitals, Hong Kong. Participants: All pregnant women with antenatal diagnosis of fetal OFC between January 2016 and December 2020 (N = 66). Results: OFC has an incidence of 0.13% among pregnancies in Hong Kong and 28.8% (19/66) were syndromic cleft that exhibited other fetal structural anomalies. There were 55 cases (84.6%) who opted for invasive prenatal diagnostic testing. Genetic defects were identified in 25.8% (17/66) of this cohort, including 14 pathogenic variants. The detection rate in the syndromic cases is 68.4% (13/19) which was significantly higher than 8.5% (4/47) among non-syndromic cases. Aneuploidies would be the most common cause, accounting for 9.1% (6/66). Chromosomal microarray analysis (CMA) provided an incremental diagnostic yield of 6.1% compared to conventional karyotyping. A total of 29 live births including 3 cases of a variant of uncertain significance and 26 cases without genetic abnormalities detected have continued pregnancy to birth. There were 87.5% (21/24) without detectable pathogenic genetic abnormality reported good long-term outcomes. The chance of OFC fetuses having a good long-term outcome was significantly higher if no genomic variant was detected (P <.001). Conclusions: Invasive prenatal tests with CMA should be offered to pregnancies with OFC regardless of the type. It has provided incremental diagnostic yield over conventional karyotyping and helped in prenatal and genetic counseling. A negative result in non-syndromic OFC favors couples to keep the pregnancy. [ABSTRACT FROM AUTHOR]

This study aimed to examine the features of the mesonephric system in fourteen (14) dromedary camel fetuses. Standard anatomical, histological, histochemical and scanning electron microscopic procedures were applied to investigate the role of the camel's mesonephros as a secretory system and hematopoietic center. In early development, the mesonephros occupied a large field of the abdominal cavity, expanded by lateral symmetry from the diaphragm to the pelvic cavity in the dorso-sublumbar regions. At 112 days of gestation, the mesonephros regressed at the cranial extremities. In the early stages of development, the mesonephros was enclosed by a thin capsule of mesenchymal connective tissue; irregular mesonephric tubules with large lumens lined with simple cuboidal cells interspersed with tiny blood vessels; and a few hemopoietic cells were discovered near the periphery of the mesonephros. With advanced development, giant glomeruli with a parietal layer lined with a simple columnar epithelium were seen in the ventral and associated boundary between the mesonephros and the developing gonads. Glycogen and alkaline phosphatase elicited an intense response in the capsule, the mesonephric tubule epithelium, renal tubule system, blood vessels, and hemopoietic cells, which was expected and contributed to water conservation and urine concentration. Scanning electron microscopy revealed that the outer surface of the mesonephros had an oval-brain shape. Based on the findings, the camel’s mesonephric system had a secretory function and served as a hematopoietic center. The morphology and development of the camel’s mesonephric system were comparable to those of other mammalian species, however, with unique traits and characteristics.

Many expectant mothers use CBD to alleviate symptoms like nausea, insomnia, anxiety, and pain, despite limited research on its long-term effects. However, CBD passes through the placenta, affecting fetal development and impacting offspring behavior. We investigated how prenatal CBD exposure affects the insular cortex (IC), a brain region involved in emotional processing and linked to psychiatric disorders. The IC is divided into two territories: the anterior IC (aIC), processing socioemotional signals, and the posterior IC (pIC), specializing in interoception and pain perception. Pyramidal neurons in the aIC and pIC exhibit sex-specific electrophysiological properties, including variations in excitability and the excitatory/inhibitory balance. We investigated IC’s cellular properties and synaptic strength in the offspring of both sexes from mice exposed to low-dose CBD during gestation (E5–E18; 3 mg/kg, s.c.). Prenatal CBD exposure induced sex-specific and territory-specific changes in the active and passive membrane properties, as well as intrinsic excitability and the excitatory/inhibitory balance, in the IC of adult offspring. The data indicate that in utero CBD exposure disrupts IC neuronal development, leading to a loss of functional distinction between IC territories. These findings may have significant implications for understanding the effects of CBD on emotional behaviors in offspring.

This study examined whether pregnant women alter their alcohol consumption upon pregnancy awareness and any additive effect of a maternal history of child abuse and pregnancy-related anxiety in predicting antenatal alcohol consumption. Pregnant women (N = 548, M = 31.44, SD = 4.58) completed an online survey consisting of the Pregnancy-related Anxiety Scale, Adverse Childhood Experience Questionnaire, questions on alcohol consumption and demographics. The Wilcoxon test examined difference scores between pre-pregnancy awareness and post-awareness drinking. More women reduced or ceased drinking after pregnancy awareness (M = 0.15, SD = 1.03) than before pregnancy recognition (M = 3.12, SD = 3.91). Only two women increased their alcohol consumption, with 140 reporting no change. In the hierarchical regression analysis, child abuse was not significant in the model, whereas pregnancy-related anxiety predicted alcohol consumption, with pre-pregnancy drinking the strongest predictor. There was no significant interaction effect between pregnancy-related anxiety and child abuse. While limited by a cross-sectional design and single questions to assess alcohol intake, our findings are consistent with extant literature. Findings related to child abuse were not significant, and likely due to low prevalence in the sample, Despite this, we further established that pregnancy-related anxiety remains a significant predictor of antenatal drinking regardless of how much alcohol a woman may consume pre-pregnancy. This relationship may be explained by drinking used to cope with pregnancy-related anxieties. While current guidelines recommend alcohol screening, many women may not accurately report their alcohol intake screening for pregnancy-related anxiety may provide an avenue to identify women more at risk of drinking during pregnancy. [ABSTRACT FROM AUTHOR]

Introduction. Elucidation of the sources of human orbital bones, clarification of the sequence of their ossification will allow to create a morphological basis for effective interpretation of the data of fetal condition monitoring, will contribute to early diagnosis of variants of the structure and possible malformations of the head, organ of vision and related structures. The aim of the study. The aim of this work was to find out the sources of origin, the chronology of ossification, the characteristics of age-related topographic and anatomical changes in the bones of the orbit. Material and methods. 18 series of histological sections of samples of human embryos and pre-fetuses at the age of 4-12 weeks of intrauterine development (4,0-80,0 mm parietal-coccygeal length) and samples of 12 fetuses at the age of 4-9 months of intrauterine development (130,0-450. 0 mm parietal-calcaneal length) using a complex of morphological research methods (anthropometry, morphometry, preparation of histological sections, dissection, three-dimensional reconstruction of series of histological sections and computer tomography, statistical analysis). The study was conducted in accordance with the main provisions of the European Union Convention on Human Rights and Biomedicine (1997), as well as the Helsinki Declaration on Ethical Principles of Medical Research Involving Human Subjects (1964-2008), EU Directive No. 609 (1986), Order of the Ministry of Health of Ukraine dated 23.09.2009 No. 690. The work was carried out within the framework of the initiative research work of the Department of Histology, Cytology and Embryology of the Bukovinian State Medical University «Structural and functional peculiarities of tissues and organs in ontogenesis, regularities of variant, constitutional, sex and age-related and comparative human morphology». State registration number: 0121U110121. Deadlines: 01.2021-12.2025. The Results. The first signs of the appearance of ossification centers around the main nervous and visceral contents of the rudiment of the orbit are determined in 6-week-old embryos in the form of seven cartilaginous bone models, and the first centers of ossification among the rudiments of bones participating in the formation of the orbit are found in the rudiment of the maxilla. In the 6th month of intrauterine development, the processes of ossification of the frontal, sphenoid, ethmoid and maxillary bones begin. At the end of the 8th month of intrauterine development, due to the ossification processes of the lesser wing of the sphenoid and frontal bones, the orbit acquires features of a definitive structure. From the beginning of the fetal period of human ontogenesis, ossification of the structures of the sphenoid bone continues, which leads to morphological transformations of the orbit in 5-month fetuses - it is separated from the sphenopalatine and infratemporal fossa by a bone layer, the optic canal is formed, and in 6-month fetuses processes of ossification of the frontal, sphenoid, ethmoid and maxillary bones, and Müller's orbital muscle changes its structure into a fibrous one. The analysis of the age-related dynamics of the morphometric parameters of the orbit during the fetal period of intrauterine development made it possible to establish the peculiarities of changes in its diameter, circumference and area, which are expressed by mathematical functions: diameter of the orbit, mm = -0. 2285+0.4704*x; circumference of the orbit, mm = -0.2924+1.4595*x; area of the orbit, mm2 = -87.8597+8.0387*x, where x is the age of the human fetus in weeks. Conclusion. The critical periods of the development of the orbit are the 6th month of prenatal ontogenesis, during which there is an uneven growth rate of the horizontal size of the orbit in relation to the vertical one, and its shape returns to the mesoconchal, which was previously observed in fetuses, as well as the 8th month, during which the growth of all parameters of the orbit slows down due to intensive processes of organogenesis of its visceral structures. [ABSTRACT FROM AUTHOR]

Background: Many cleft centers incorporate NasoAlveolar Molding (NAM) into their presurgical treatment protocols. However, there are limited data on eligible patients who do not receive or complete NAM. This study characterizes the demographics associated with non-utilization or completion of NAM. Methods: A single-institution retrospective review was performed of all patients with cleft lip and alveolus undergoing primary unilateral and bilateral cleft lip repair from 2012-2020. Patients were grouped based on utilization or non-utilization of NAM. Demographic and treatment data were collected, including documented reasons for not pursuing or completing NAM. Results: Of 230 eligible patients, 61 patients (27%) did not undergo or complete NAM (no-NAM). In this group, 37 (60.7%) received no presurgical intervention, 12 (19.7%) received presurgical nostril retainers, 3 (4.9%) received lip taping, 1 (1.6%) received a combination of taping/nostril retainers, and 8 (13.1%) discontinued NAM. The most common reasons for not receiving NAM were sufficiently aligned cleft alveolus (21.3%), medical complexity (16.4%), late presentation (16.4%), and alveolar notching (18%). Compared to the NAM group, the no-NAM group had significantly lower rates of prenatal cleft diagnosis/consult, and significantly higher proportion of non-married and non-English speaking caregivers. Multivariable analysis controlling for insurance type, primary language, prenatal consult, marital status, and age at first appointment found that age at first appointment is the only statistically significant predictor of NAM utilization (P <.001). Conclusions: Common reasons for non-utilization of NAM include well-aligned cleft alveolus, medical complexity, and late presentation. Early presentation is an important modifiable factor affecting rates of NAM utilization. [ABSTRACT FROM AUTHOR]

Abstract Background The maternal microbiota modulates fetal development, but the mechanisms of these earliest host-microbe interactions are unclear. To investigate the developmental impacts of maternal microbial metabolites, we compared full-term fetuses from germ-free and specific pathogen-free mouse dams by gene expression profiling and non-targeted metabolomics. Results In the fetal intestine, critical genes mediating host-microbe interactions, innate immunity, and epithelial barrier were differentially expressed. Interferon and inflammatory signaling genes were downregulated in the intestines and brains of the fetuses from germ-free dams. The expression of genes related to neural system development and function, translation and RNA metabolism, and regulation of energy metabolism were significantly affected. The gene coding for the insulin-degrading enzyme (Ide) was most significantly downregulated in all tissues. In the placenta, genes coding for prolactin and other essential regulators of pregnancy were downregulated in germ-free dams. These impacts on gene expression were strongly associated with microbially modulated metabolite concentrations in the fetal tissues. Aryl sulfates and other aryl hydrocarbon receptor ligands, the trimethylated compounds TMAO and 5-AVAB, Glu-Trp and other dipeptides, fatty acid derivatives, and the tRNA nucleobase queuine were among the compounds strongly associated with gene expression differences. A sex difference was observed in the fetal responses to maternal microbial status: more genes were differentially regulated in male fetuses than in females. Conclusions The maternal microbiota has a major impact on the developing fetus, with male fetuses potentially more susceptible to microbial modulation. The expression of genes important for the immune system, neurophysiology, translation, and energy metabolism are strongly affected by the maternal microbial status already before birth. These impacts are associated with microbially modulated metabolites. We identified several microbial metabolites which have not been previously observed in this context. Many of the potentially important metabolites remain to be identified.

In European populations, the birth season significantly correlates with many biological features. It is thus possible that the observed clinical effects of bone metabolism disorders are a partial consequence of bone mineral density (BMD), modified by the season of prenatal development (the birth season). The aim of this study was to evaluate the relationship between the birth season and BMD among Polish women in perimenopausal age. A total of 653 Polish women aged 50.0–59.9 years were included in the study. BMDs of lumbar vertebrae were measured by dual-energy x-ray absorptiometry. Statistical analyses were based on measured lumbar BMD values, age, and body mass index (BMI). The analysis of variance (ANOVA) was applied to evaluate the season-related differentiation of mineral density of lumbar vertebrae. BMDs of lumbar vertebrae negatively correlated with age and positively with BMI. We regressed BMD on age and BMI and used the residuals as a measure of age- and BMI-independent lumbar BMD values. The ANOVA results showed that women born in summer had significantly lower BMD of the L1 vertebra compared to those born in autumn, regardless of age and BMI. The results of our study indicate the need to extend the group of risk factors for osteoporosis in Central Europeans with the season of woman’s birth.

The development of the spleen in newborn male Wistar rats exposed to low-dose endocrine disruptor dichlorodiphenyltrichloroethane during the prenatal period was studied. Histological examination of the spleen revealed a more active development of periarterial lymphoid sheaths and lower granulocyte content in the organ. Cytofluorimetry showed a significantly lower content of B cells. Thus, low-dose exposure of the endocrine disruptor dichlorodiphenyltrichloroethane on the developing organism during the prenatal period induced changes in spleen morphogenesis resulting in extensive development of lymphoid formations and a lower intensity of lymphocyte and granulocyte differentiation. [ABSTRACT FROM AUTHOR]

Background: The maternal microbiota modulates fetal development, but the mechanisms of these earliest host-microbe interactions are unclear. To investigate the developmental impacts of maternal microbial metabolites, we compared full-term fetuses from germ-free and specific pathogen-free mouse dams by gene expression profiling and non-targeted metabolomics. Results: In the fetal intestine, critical genes mediating host-microbe interactions, innate immunity, and epithelial barrier were differentially expressed. Interferon and inflammatory signaling genes were downregulated in the intestines and brains of the fetuses from germ-free dams. The expression of genes related to neural system development and function, translation and RNA metabolism, and regulation of energy metabolism were significantly affected. The gene coding for the insulin-degrading enzyme (Ide) was most significantly downregulated in all tissues. In the placenta, genes coding for prolactin and other essential regulators of pregnancy were downregulated in germ-free dams. These impacts on gene expression were strongly associated with microbially modulated metabolite concentrations in the fetal tissues. Aryl sulfates and other aryl hydrocarbon receptor ligands, the trimethylated compounds TMAO and 5-AVAB, Glu-Trp and other dipeptides, fatty acid derivatives, and the tRNA nucleobase queuine were among the compounds strongly associated with gene expression differences. A sex difference was observed in the fetal responses to maternal microbial status: more genes were differentially regulated in male fetuses than in females. Conclusions: The maternal microbiota has a major impact on the developing fetus, with male fetuses potentially more susceptible to microbial modulation. The expression of genes important for the immune system, neurophysiology, translation, and energy metabolism are strongly affected by the maternal microbial status already before birth. These impacts are associated with microbially modulated metabolites. We identified several microbial metabolites which have not been previously observed in this context. Many of the potentially important metabolites remain to be identified. [ABSTRACT FROM AUTHOR]

Objective : To assess the clinical impacts of prenatal consultation with a multidisciplinary cleft team on infants with cleft lip with or without cleft palate (CL ± P). Design : Retrospective cases series. Setting : Tertiary pediatric hospital. Patients : Infants with CL ± P whose mothers received prenatal consultation with a pediatric otolaryngology team from June 2005 to December 2019 were identified. A random sample of infants with CL ± P without prenatal consultation from June 2005 to December 2019 was also identified. Main Outcome Measures : The primary outcomes were the length of hospitalization during the first 12 weeks of life, timing of surgical repair, length of postsurgical hospitalization, and number of unplanned clinic visits and phone calls for feeding evaluation. Results : Time to cleft lip repair differed significantly between the 2 groups with repair performed at 13.4 (±0.9) weeks for the prenatal consultation group (n = 73) and 15.3 (±2.1) weeks for the control group (n = 80), (P <.05). If hospitalization was required for feeding difficulties during the first 12 weeks of life, length of stay was 4.9 (± 1.7) days for infants with prenatal consultation and 11.5 (± 7.2) days for control infants (P <.05). Unplanned clinic visits with a speech-language pathologist (SLP) for feeding difficulties were needed for 2.7% of prenatal consultation infants and 11.3% of control infants (P <.05). Conclusions : Prenatal consultation regarding CL ± P resulted in infants with decreased duration of early hospitalizations, earlier cleft lip repair, and decreased engagement with the SLP feeding clinic for feeding difficulties when compared with infants without prenatal consultation. [ABSTRACT FROM AUTHOR]

In European populations, the birth season significantly correlates with many biological features. It is thus possible that the observed clinical effects of bone metabolism disorders are a partial consequence of bone mineral density (BMD), modified by the season of prenatal development (the birth season). The aim of this study was to evaluate the relationship between the birth season and BMD among Polish women in perimenopausal age. A total of 653 Polish women aged 50.0-59.9 years were included in the study. BMDs of lumbar vertebrae were measured by dual-energy x-ray absorptiometry. Statistical analyses were based on measured lumbar BMD values, age, and body mass index (BMI). The analysis of variance (ANOVA) was applied to evaluate the season-related differentiation of mineral density of lumbar vertebrae. BMDs of lumbar vertebrae negatively correlated with age and positively with BMI. We regressed BMD on age and BMI and used the residuals as a measure of age- and BMI-independent lumbar BMD values. The ANOVA results showed that women born in summer had significantly lower BMD of the L1 vertebra compared to those born in autumn, regardless of age and BMI. The results of our study indicate the need to extend the group of risk factors for osteoporosis in Central Europeans with the season of woman's birth. [ABSTRACT FROM AUTHOR]

Fetal life and infancy are extremely sensitive to adverse environmental conditions. This study aimed to assess the effect of exposure to a natural disaster (cyclone Aila) in utero or during infancy on fine and gross motor functions in preadolescent Indian children. The study was conducted in West Bengal, India, and included approximately 700 children (7–10 years old) who were prenatally or postnatally exposed to cyclone Aila and a nonaffected group. Anthropometric measures included height, weight, and birthweight. Socioeconomic status was based on parental education, family size, and income. Motor functions were assessed using the short form of Bruininks–Oseretsky Test of Motor Proficiency (BOT‐2). Statistical analyses included, for example, generalized linear models. There were no differences in motor functions relative to the timing of the exposure (trimester) during pregnancy. Compared to the controls, prenatal Aila exposure resulted in poorer performance in all BOT‐2 subtests, except for fine motor precision, strength, and balance (the last in boys), while postnatal Aila exposure, compared to the controls, resulted in poorer performance in manual dexterity, bilateral coordination, balance (girls only), and speed and agility. Early life exposure to a natural disaster has long‐term adverse effect on motor proficiency in children. By inference, the welfare of pregnant women and infants should be of particular concern for emergency and health services during an environmental cataclysm. [ABSTRACT FROM AUTHOR]

Aim: The aim of the present study was to demonstrate the existence of uniform sexual dimorphism in some radioulnar contrasts between different finger ridge counts within the same hand in a large set of populations, thus confirming the universal nature of this dimorphism in humans.Subjects and methods: We analysed individual finger ridge counts (10 values on each hand) of both hands from archival sources (mainly the Brehme-Jantz database). In total, these included 4412 adults from 21 population samples covering all permanently inhabited continents and encompassing very different and geographically distant human populations. We calculated the contrasts (differences) of all pairs of ridge counts (45 per hand) and used diverse methods to assess the direction and degree of dimorphism of them across all population samples.Results: The highest sexual dimorphism was observed for nine contrasts involving the ridge count of the dermatoglyphic pattern on the radial side of the second finger of the right hand (R2r). Among these contrasts, we then found four that had the same direction of dimorphism in all 21 populations. The most dimorphic was the contrast R1rR2r – the difference between the ridge count of the radial side of the thumb and the radial side of the index finger.Discussion: Thus, these dermatoglyphic traits can be further investigated as potential markers of prenatal sex differentiation from ca. 10th week of intrauterine development. However, it will be useful to address the detailed factors and mechanisms for differences in the degree of dimorphism of these traits in different populations.

The vitreous body of the eye of human fetuses contains serum albumin (SA) and alpha-fetoprotein (AFP), which is normally characteristic of human embryos and fetuses. In the second trimester, both proteins are found in the vitreous body at a concentration comparable to that in the blood serum, after which their content decreases sharply. In this analytical review, taking into account the biological properties of SA and AFP, the role of these proteins in the processes of growth and differentiation of the structures of the developing eye is discussed. [ABSTRACT FROM AUTHOR]

Simple Summary: The circadian clock is a prominent regulator of physiology. Most studies so far have investigated its role in health and disease in adult subjects and animals. However, circadian clock characteristics change over one's lifetime. This review describes how the clock develops during pregnancy and infancy, how it evolves in childhood and adolescence and, finally, how its function is impacted by aging, with a special focus on the female reproductive system. Understanding those changes can contribute to adapting behavioral and medical interventions to the patients' age and sex-specific needs. Most lifeforms on earth use endogenous, so-called circadian clocks to adapt to 24-h cycles in environmental demands driven by the planet's rotation around its axis. Interactions with the environment change over the course of a lifetime, and so does regulation of the circadian clock system. In this review, we summarize how circadian clocks develop in humans and experimental rodents during embryonic development, how they mature after birth and what changes occur during puberty, adolescence and with increasing age. Special emphasis is laid on the circadian regulation of reproductive systems as major organizers of life segments and life span. We discuss differences in sexes and outline potential areas for future research. Finally, potential options for medical applications of lifespan chronobiology are discussed. [ABSTRACT FROM AUTHOR]

Aim: The aim of the present study was to demonstrate the existence of uniform sexual dimorphism in some radioulnar contrasts between different finger ridge counts within the same hand in a large set of populations, thus confirming the universal nature of this dimorphism in humans.Subjects and methods: We analysed individual finger ridge counts (10 values on each hand) of both hands from archival sources (mainly the Brehme-Jantz database). In total, these included 4412 adults from 21 population samples covering all permanently inhabited continents and encompassing very different and geographically distant human populations. We calculated the contrasts (differences) of all pairs of ridge counts (45 per hand) and used diverse methods to assess the direction and degree of dimorphism of them across all population samples.Results: The highest sexual dimorphism was observed for nine contrasts involving the ridge count of the dermatoglyphic pattern on the radial side of the second finger of the right hand (R2r). Among these contrasts, we then found four that had the same direction of dimorphism in all 21 populations. The most dimorphic was the contrast R1rR2r – the difference between the ridge count of the radial side of the thumb and the radial side of the index finger.Discussion: Thus, these dermatoglyphic traits can be further investigated as potential markers of prenatal sex differentiation from ca. 10th week of intrauterine development. However, it will be useful to address the detailed factors and mechanisms for differences in the degree of dimorphism of these traits in different populations. [ABSTRACT FROM AUTHOR]

The developmental origins of handedness remain elusive, though very early emergence suggests individual differences manifesting in utero could play an important role. Prenatal testosterone and Vitamin D exposure are considered, yet findings and interpretations remain equivocal. We examined n = 767 offspring from a population-based pregnancy cohort (The Raine Study) for whom early biological data and childhood/adolescent handedness data were available. We tested whether 18-week maternal circulatory Vitamin D (25[OH]D), and testosterone and estradiol from umbilical cord blood sampled at birth predicted variance in direction of hand preference (right/left), along with right- and left-hand speed, and the strength and direction of relative hand skill as measured by a finger-tapping task completed at 10 (Y10) and/or 16 (Y16) years. Although higher concentrations of Vitamin D predicted more leftward and less lateralized (regardless of direction) relative hand skill profiles, taken as a whole, statistically significant findings typically did not replicate across time-point (Y10/Y16) or sex (male/female) and were rarely detected across different (bivariate/multivariate) levels of analysis. Considering the number of statistical tests and generally inconsistent findings, our results suggest that perinatal testosterone and estradiol contribute minimally, if at all, to subsequent variance in handedness. Vitamin D, however, may be of interest in future studies. [ABSTRACT FROM AUTHOR]

The immune system establishes during the prenatal period from distinct waves of stem and progenitor cells and continuously adapts to the needs and challenges of early postnatal and adult life. Fetal immune development not only lays the foundation for postnatal immunity but establishes functional populations of tissue-resident immune cells that are instrumental for fetal immune responses amidst organ growth and maturation. This review aims to discuss current knowledge about the development and function of tissue-resident immune populations during fetal life, focusing on the brain, lung, and gastrointestinal tract as sites with distinct developmental trajectories. While recent progress using system-level approaches has shed light on the fetal immune landscape, further work is required to describe precise roles of prenatal immune populations and their migration and adaptation to respective organ environments. Defining points of prenatal susceptibility to environmental challenges will support the search for potential therapeutic targets to positively impact postnatal health. [ABSTRACT FROM AUTHOR]

Innate lymphoid cells (ILCs) harbor tissue-resident properties in border zones, such as the mucosal membranes and the skin. ILCs exert a wide range of biological functions, including inflammatory response, maintenance of tissue homeostasis, and metabolism. Since its discovery, tremendous effort has been made to clarify the nature of ILCs, and scientific progress revealed that progenitor cells of ILC can produce ILC subsets that are functionally reminiscent of T-cell subsets such as Th1, Th2, and Th17. Thus, now it comes to the notion that ILC progenitors are considered an innate version of naïve T cells. Another important discovery was that ILC progenitors in the different tissues undergo different modes of differentiation pathways. Furthermore, during the embryonic phase, progenitor cells in different developmental chronologies give rise to the unique spectra of immune cells and cause a wave to replenish the immune cells in tissues. This observation leads to the concept of layered immunity, which explains the ontology of some cell populations, such as B-1a cells, γδ T cells, and tissue-resident macrophages. Thus, recent reports in ILC biology posed a possibility that the concept of layered immunity might disentangle the complexity of ILC heterogeneity. In this review, we compare ILC ontogeny in the bone marrow with those of embryonic tissues, such as the fetal liver and embryonic thymus, to disentangle ILC heterogeneity in light of layered immunity. [ABSTRACT FROM AUTHOR]

• Human cortical NPCs show a significant transcriptional response to IFNγ treatment. • This response is attenuated in cortical NPCs from schizophrenia patients. • The abnormal transcriptional response is driven by mitochondrial and synaptic genes. • Cortical NPCs do not show significant transcriptional response to IL-1β treatment. Maternal immune activation (MIA) during prenatal development is an environmental risk factor for psychiatric disorders including schizophrenia (SZ). Converging lines of evidence from human and animal model studies suggest that elevated cytokine levels in the maternal and fetal compartments are an important indication of the mechanisms driving this association. However, there is variability in susceptibility to the psychiatric risk conferred by MIA, likely influenced by genetic factors. How MIA interacts with a genetic profile susceptible to SZ is challenging to test in animal models. To address this gap, we examined whether differential gene expression responses occur in forebrain-lineage neural progenitor cells (NPCs) derived from human induced pluripotent stem cells (hiPSC) generated from three individuals with a diagnosis of schizophrenia and three healthy controls. Following acute (24 h) treatment with either interferon-gamma (IFNγ; 25 ng/μl) or interleukin (IL)-1β (10 ng/μl), we identified, by RNA sequencing, 3380 differentially expressed genes (DEGs) in the IFNγ-treated control lines (compared to untreated controls), and 1980 DEGs in IFNγ-treated SZ lines (compared to untreated SZ lines). Out of 4137 genes that responded significantly to IFNγ across all lines, 1223 were common to both SZ and control lines. The 2914 genes that appeared to respond differentially to IFNγ treatment in SZ lines were subjected to a further test of significance (multiple testing correction applied to the interaction effect between IFNγ treatment and SZ diagnosis), yielding 359 genes that passed the significance threshold. There were no differentially expressed genes in the IL-1β-treatment conditions after Benjamini-Hochberg correction. Gene set enrichment analysis however showed that IL-1β impacts immune function and neuronal differentiation. Overall, our data suggest that a) SZ NPCs show an attenuated transcriptional response to IFNγ treatment compared to controls; b) Due to low IL-1β receptor expression in NPCs, NPC cultures appear to be less responsive to IL-1β than IFNγ; and c) the genes differentially regulated in SZ lines – in the face of a cytokine challenge – are primarily associated with mitochondrial, "loss-of-function", pre- and post-synaptic gene sets. Our findings particularly highlight the role of early synaptic development in the association between maternal immune activation and schizophrenia risk. [ABSTRACT FROM AUTHOR]

Objective: To characterize the epidemiology, identify trends in prevalence, seasonality, and risk factors for orofacial clefts (OFC), selecting the São Paulo state (SPS) population database., Design: A population-based study to estimate the OFC prevalence trends in recent years, stratified by maternal age and SPS geographical clusters., Setting: All live births (LB) with OFC in SPS from 2008-2019., Patients: 5342 cases of OFC among 7 301 636 LB., Interventions: Not applicable., Main Outcome Measures: OFC prevalence trends, annual percent change (APC) with a 95% confidence interval, and seasonality., Results: We found an OFC prevalence of 7.3/10 000LB in SPS, Brazil. Among all the cases, the majority were male (57.1%), Caucasian (65.4%), 77.8% born at term, 75.8% weight >2500 g, 97.1% singleton, and 63.9% of births were by cesarean section. From 2008-2019, SPS presented a stationary OFC prevalence trend; in São Paulo city, the highest APC was observed (0.05%); the maternal age group with the highest OFC prevalence rate was ≥35 years (9.2/10 000LB). We identified the existence of seasonal variation based on the conception date in the final months of the year, corresponding to the spring season ( P  < .001)., Conclusion: OFC had a stationary prevalence trend in recent years, with the highest prevalence in the Central North Cluster and ≥35 years maternal age group. Seasonality was observed in the spring season, and congenital malformation of lips was the most common associated pathology. This population-based study is the first to summarize the current epidemiology of OFC in SPS., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Duchenne muscular dystrophy (DMD) is a severe degenerative muscle disease caused by mutations in the DMD gene, which encodes dystrophin. Despite its initial description in the late 19th century by French neurologist Guillaume Duchenne de Boulogne, and identification of causal DMD genetic mutations in the 1980s, therapeutics remain challenging. The current standard of care is corticosteroid treatment, which delays the progression of muscle dysfunction but is associated with significant adverse effects. Emerging therapeutic approaches, including AAV-mediated gene transfer, CRISPR gene editing, and small molecule interventions, are under development but face considerable obstacles. Although DMD is viewed as a progressive muscle disease, muscle damage and abnormal molecular signatures are already evident during fetal myogenesis. This early onset of pathology suggests that the limited success of current therapies may partly be due to their administration after aberrant embryonic myogenesis has occurred in the absence of dystrophin. Consequently, identifying optimal therapeutic strategies and intervention windows for DMD may depend on a better understanding of the earliest DMD disease mechanisms. As newer techniques are applied, the field is gaining increasingly detailed insights into the early muscle developmental abnormalities in DMD. A comprehensive understanding of the initial events in DMD pathogenesis and progression will facilitate the generation and testing of effective therapeutic interventions., (© 2024 Wiley Periodicals LLC.)

Although certain metals can reach their highest concentrations in tissues of newly hatched nestlings, their sources have yet to be fully elucidated. Evidence for the differentiation of body reserves, including some chemical elements, during avian embryonic life and early post-hatching period is limited mostly to studies on poultry. Here, we present novel findings on the bioaccumulation and egg-to-nestling transfer of 10 minerals and metals, including non-essential potentially toxic chemical elements (Cu, Ni Cd, Pb, Zn, Ag, Mg, Fe, Co and Ca) in the tissues of the gastrointestinal tract (GT), whole body (WB) and carcass (CA) of nestlings of a small passerine bird, the Eurasian Reed Warbler Acrocephalus scirpaceus, breeding in an intensively fertilized fishpond habitat. Our findings show that concentrations of metals that are relevant to contaminated systems (Cu, Ni, Cd, Pb, Zn, Fe and Co) are the highest in GT tissues across all the nestling age classes examined (from hatching to day 9 of life). The important question emerged from our findings: why the hatchlings were characterized by higher metal concentrations in GT, WB and CA compared to older nestlings. We suggest that the prenatal accumulation of chemical elements assimilated from egg contents, and their subsequent utilization for building various tissues/internal organs by the growing embryo, is a reasonable explanation for this finding. More specifically, the potential functional mechanism explaining the highest concentrations of some trace metals in hatchlings seems to be associated with an extremely high rate of utilization of residual yolk metal resources that survived from the embryonic until the post-natal period. On the basis of our own work and literature data, we identified a presumable significant discrepancy in the actual rate of egg-to-nestling and egg-to-embryo metal transfer due to the eggshell being ignored (a commonly occurrence), and only the egg contents being treated as the basic repository of chemical elements for developing embryos. Much more research is needed on the prenatal assimilation and subsequent accumulation of chemical elements in a developing avian embryo, representing both the transition from near-to-hatching embryos to hatchlings, and then to older nestlings., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

With the purpose of understanding the psychological and relational meanings of the experience of motherhood in the face of toxoplasmosis, a clinical-qualitative study was carried out performing semi-directed interviews with five mothers of babies with toxoplasmosis. The information was submitted to Content Analysis, and the results demonstrated that the psychological meanings include both the presence of difficulties and suffering and the potentiality of the babies and the establishment of emotional mother-baby bonds. Relative to the relational meanings, the importance of support networks was identified, emphasizing the role of family members, health services, and religiosity as sources of support in facing difficulties. However, it was identified that the care is provided primordially to the babies, with the emotional assistance to mothers being insufficient. In conclusion, it stands out that each mother experienced toxoplasmosis from their possibilities and available support network, which affected the establishment of the mother-baby bond. [ABSTRACT FROM AUTHOR]

Prenatal metabolism exerts profound effects on development. The first stool of the newborn, meconium, provides a window into the prenatal metabolic environment. The objective of this study was to examine the feasibility of meconium as a novel matrix to quantify prenatal steroid levels. We quantified parameters of analytical interest regarding the use of meconium, including sample stability. We hypothesized that meconium steroid content would differ by sex, prompting analysis of meconium to test effects of prenatal steroid metabolism. Meconium from 193 newborns enrolled in the Early Autism Risk Longitudinal Investigation (EARLI) study, including 107 males, and 86 females, were analyzed by isotope dilution-liquid chromatography-high resolution mass spectrometry (ID-LC-HRMS) while blinded to identity for testosterone (T), androstenedione (AD), and dehydroepiandrosterone (DHEA). Steroid levels were compared by sex, and investigations of potential trends resulting from sample storage or processing was conducted. The unconjugated steroid content of meconium in ng/g (mean, standard deviation) was for males: T (2.67, 8.99), AD (20.01, 28.12), DHEA (13.96, 23.57) and for females: T (0.82, 1.63), AD (22.32, 24.38), DHEA (21.06, 43.49). T was higher in meconium from males (p=0.0333), and DHEA was higher in meconium from females (p=0.0202). 6 female and 3 male T values were below the limit of detection. No extreme variability in hydration or trend in steroid levels by storage time was detected. Sexually dimorphic levels of hormones may reflect gestational differentiation, and future studies should consider meconium analysis.

During organogenesis in the developing goat embryo, a four-chamber stomach is formed from an extension of the primary intestine. Due to histological and morphological changes, each chamber of the stomach takes on characteristic features associated with its function. The histological structure of the stomach wall consists of four layers, the mucosa, submucosa, tunica muscularis and serosa. This work presents the current state of knowledge of the changes observed in each layer of the developing stomach and its morphogenesis in the prenatal period. Practical applications of this information in prenatal ultrasound diagnostics in goats are suggested as well.

The effect of mild prenatal stress in mice, leading to an increase in the placental serotonin level, on the formation of adaptive behavior in male offspring at the age of 35 days was studied. It was shown that, in BalbC mice, daily immobilization for 1 h during the period from 11 to 14 days of pregnancy led to an increase in placental and fetal serotonin levels on the 15th day of prenatal development. According to "resident–intruder" behavioral test, the prenatally stressed mice showed more reactive behavior in adulthood and low tendency to defend their territory. Thus, placental serotonin, formed under the stress condition, may act as a mediator between the environment and the fetuses and determine the adaptive behavior of offspring. [ABSTRACT FROM AUTHOR]

Objective: To determine the prevalence and odds ratios for cleft lip and/or palate (CL/P) among infants prenatally exposed to opioids with or without neonatal opioid withdrawal syndrome (NOWS). Design: This study represents an exploratory, retrospective cohort study design of newborn medical health records from 2011 to 2016. Setting: Records were drawn from a regional health system located in South Central Appalachia. Population and Study Sample: The original population yielded 3 cohorts of infants: (1) infants with opioid exposure (OE) but not requiring pharmacological intervention (OE; N = 168); (2) infants with NOWS requiring pharmacological intervention (N = 294); and (3) infants with no opioid exposure (NOE; N = 16 090), the primary comparison group. Main Outcome: Infants in the NOWS and OE groups showed significantly increased prevalence and odds ratios for CL/P when compared to those in the NOE group. Results: Prevalence rates per 1000 live births for infants with OE (35.71) and infants with NOWS (6.80) were significantly higher than those for infants with NOE (1.37). Comparison of infants with OE to the NOE group revealed significantly increased odds for CL/P, isolated cleft palate (CP), cleft lip (CL), and cleft lip and palate (CLP) (27.05, 41.81, 19.26, 19.37, respectively; all P s <.008). The odds ratios for infants with NOWS compared to the NOE group were significantly higher for CL/P and CP (5.00 and 10.98, respectively; P s <.03) but not for CL and CLP. Conclusion: The results provide additional evidence that prenatal OE should be considered among the critical environmental risk factors that can contribute to CL/P. [ABSTRACT FROM AUTHOR]

DNA methylation (DNAm) is a key epigenetic regulator of gene expression across development. The developing prenatal brain is a highly dynamic tissue, but our understanding of key drivers of epigenetic variability across development is limited. We, therefore, assessed genomic methylation at over 39 million sites in the prenatal cortex using whole-genome bisulfite sequencing and found loci and regions in which methylation levels are dynamic across development. We saw that DNAm at these loci was associated with nearby gene expression and enriched for enhancer chromatin states in prenatal brain tissue. Additionally, these loci were enriched for genes associated with neuropsychiatric disorders and genes involved with neurogenesis. We also found autosomal differences in DNAm between the sexes during prenatal development, though these have less clear functional consequences. We lastly confirmed that the dynamic methylation at this critical period is specifically CpG methylation, with generally low levels of CpH methylation. Our findings provide detailed insight into prenatal brain development as well as clues to the pathogenesis of psychiatric traits seen later in life.

AbstractObjective To provide the reference biometric measurements of the normal foetal brain by prenatal MRI and describe the distribution of measurements in the foetuses with ventricular septal defect (VSD).Methods This retrospective study analysed the biometric measurements of 218 foetuses between 18 − 37 gestational weeks with normal MRI findings from July 2014 to August 2019, as well as 18 foetuses with VSD. The measurements included fronto-occipital diameter (FOD), biparietal diameter (BPD), and transverse cerebellar diameter (TCD). All the prenatal MRI examinations have been taken on the same 1.5 T MR unit with a standard protocol of the foetal brain. All the linear measurements of the foetal brain were obtained on the T2-weighted imaging. The distribution of measurements in 18 foetuses with VSD was plotted on centile curves.Results The reference data were presented in mean, standard deviation, 95% predicted confidence intervals, and the 3rd, 10th, 25th, 50th, 75th, 90th, 97th centiles at each gestational age. The value of TCD in 56% (10/18 cases) foetuses with VSD was lower than the 3rd centile, and the rate for FOD and BPD was 33% (6/18 cases) and 22% (4/18 cases) separately. On the curves, most VSD cases with measurements lower than the 3rd centile were in relatively early gestational stage (≤28 weeks).Conclusions We have presented reference linear biometry of the foetal brain by prenatal MRI from 18 to 37 gestational weeks, which could help us to interpret and monitor the brain development for foetuses with VSD and other congenital heart diseases.Key messages:We have presented reference linear biometry of the foetal brain by prenatal MRI from 18 to 37 gestational weeks in multiple statistical methods: mean and standard deviation; 95% predicted confidence intervals and the 3rd, 10th, 25th, 50th, 75th, 90th, 97th centiles.Our data showed that the involvement of the brain in VSD may be not globally, but regionally, and the cerebellum may be more possible to be involved.We speculated that the earlier the VSD diagnosed the worse the brain involved, which might suggest a poor outcome and necessary follow-up.

With the advent of powerful imaging instruments, the prenatal behaviour of vertebrates has been discovered to be far more complex than previously believed, especially concerning humans, other mammals and birds. Surprisingly, the fetal behaviour of squamate reptiles (lizards, snakes and amphisbaenians), a group of over 11 000 extant species, are largely understudied. Using ultrasonography, 18 late-term pregnant copperhead snakes (Agkistrodon contortrix) from a single population were inspected for fecundity (number of fetuses). Unexpectedly, during the ultrasound procedure that involved 97 fetuses, we observed sinusoidal tail movements in 11 individuals from eight different copperhead mothers. These movements were indistinguishable from caudal luring, a mimetic ambush predatory strategy which is exhibited by newborn copperheads and other snakes. Caudal luring is initiated shortly after birth and is employed to attract susceptible vertebrate prey. Using the same ultrasound equipment and methods, we tested for this behaviour in two species of rattlesnakes (genus Crotalus) not known to caudal lure and none of the late-term fetuses showed any type of tail movements. Prenatal movements in humans and other vertebrates are known to be important for musculoskeletal and sensorimotor development. The fetal behaviours we describe for copperheads, and possibly other snakes, may be similarly important and influence early survival and subsequent fitness.