Prenatal Influences Research Articles

Prenatal Acoustic Signals Influence Nestling Heat Shock Protein Response to Heat and Heterophil-to-Lymphocyte Ratio in a Desert Bird

Heat shock proteins (HSPs) are essential to cellular protection against heat stress. However, the causes of inter-individual variation in HSP regulation remain unclear. This study aimed to test the impact of early-life conditions on the HSP response to heat in zebra finches. In this arid-adapted bird, incubating parents emit “heat-calls” at high temperatures, which adaptively alter offspring’s phenotypes. Embryos were exposed to heat-calls or control-calls, and at 13 days post-hatch nestlings were separated into two different experiments to test responses to either chronic nest temperature (“in-nest” experiment) or an acute “heat-challenge”. Blood samples were collected to measure levels of heat shock cognate 70, heat shock protein 90α, corticosterone and the heterophil-to-lymphocyte (H/L) ratio. In the in-nest experiment, both HSPs were upregulated in response to increasing nest temperatures only in control-calls nestlings (HSC70: p = 0.010, HSP90α: p = 0.050), which also had a marginally higher H/L ratio overall than heat-call birds (p = 0.066). These results point to a higher heat sensitivity in control-call nestlings. Furthermore, comparing across experiments, only the H/L ratio differed, being higher in heat-challenged than in in-nest nestlings (p = 0.009). Overall, this study shows for the first time that a prenatal acoustic signal of heat affects the nestling HSP response to postnatal temperature.

Evaluating Maternal Risk Factors Impacting Fetal Intima-Media Thickness of the Abdominal Aorta Measured at 28 Weeks of Gestation.

Background and Objectives: Cardiovascular disease risk can exist in utero, influenced by maternal health factors. This study evaluates maternal characteristics and biochemical markers that correlate with the fetal intima-media thickness (IMT), aiming to identify interventions that could minimize prenatal influences on later cardiovascular disease. Methods: In this observational study approved by the Institutional Review Board at The Obstetrics and Gynecology Clinic of the Timisoara Municipal Emergency Hospital, we recruited pregnant women aged 15-40 years, divided into groups based on their lipid profiles and gestational diabetes risk. The data collection had, as its main focus, ultrasound measurements, along with demographic, clinical, and biochemical parameters. The IMT of the fetal abdominal aorta was measured at 28 weeks of gestation. Results: Notable differences were observed in the TNF-alpha levels (8.66 ± 3.87 pg/mL vs. 4.96 ± 3.37 pg/mL), hsCRP levels (0.94 ± 0.46 mg/L vs. 0.60 ± 0.52 mg/L), and the area under the curve (AUC) for hsCRP at 0.738 with a sensitivity of 84.41% and specificity of 79.01%. Compound score 2, integrating inflammatory markers and lipid profiles, exhibited a good diagnostic accuracy (AUC = 0.789) with a sensitivity of 86.35% and specificity of 81.42%. A regression analysis indicated strong associations of TNF-alpha and hsCRP with an increased fetal IMT, suggesting potential early markers of cardiovascular risk, presenting hazard ratios (HRs) of 2.21 (95% CI: 1.15-5.28) and 2.87 (95% CI: 1.11-4.23), respectively, both with p-values of less than 0.0001. Compound score 2 further indicated an increased risk (HR = 4.27; 95% CI: 1.19-8.32). Conclusions: Statistically significant correlations were found between an increased fetal IMT and elevated maternal inflammatory markers (TNF-alpha and hsCRP), suggesting that these could serve as early indicators of cardiovascular risk. This study supports the potential for targeted prenatal interventions to reduce cardiovascular risk factors from the fetal stage, emphasizing the importance of monitoring inflammatory markers in pregnant women at risk.

Prenatal influences across the life course: Biobehavioral mechanisms of development.

Despite the well-established importance of prenatal experiences for offspring health throughout the lifespan, our understanding of prenatal influences on psychological outcomes faces challenges due to a wide-ranging and somewhat fragmented literature. Here, we introduce the special issue of Developmental Psychology, "Prenatal Influences Across the Life Course: Biobehavioral Mechanisms of Development," which draws together a broad collection of 12 empirical studies and one review article. These studies illustrate the diversity in biobehavioral mechanisms and biopsychosocial processes that help explain the long-term impacts of prenatal experiences on human development. Collectively, these studies help to disentangle sources of influence across different life stages (e.g., prenatal from genetic, preconception, and/or postnatal influences) and fill key gaps in the literature, such as the inclusion of minoritized populations currently underrepresented in research, the role of fathers, and protective mechanisms. The research featured in this special issue underscores both the long reach of prenatal influences on child and adolescent development as well as the challenges in observing specific biological mediators given that prenatal risks are currently operationalized as specific or broad cumulative measures. In an effort to organize this complex literature, we propose a guiding framework for how to conceptualize the continued integration of the prenatal environment into the field of developmental psychology. This framework broadens the prevailing dichotomous view of prenatal mechanisms as cumulative or specific to articulate a dimensional approach focused on adaptation. We anticipate that such an approach may uncover meaningful and observable biobehavioral mechanisms of prenatal influence on offspring development in the future. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Early risk for child externalising symptoms: Examining genetic, prenatal, temperamental and parental influences.

This study utilized the Early Growth and Development Study (N = 561 adoptive children; 57.2% male, 55.3% White), a study of children adopted at birth, to examine heritable (birth parent psychopathology) and prenatal risk (prenatal maternal distress and smoking during pregnancy), infant negative affectivity, adoptive parent over-reactivity and warmth as independent predictors of childhood externalizing symptoms. The current study evaluated if: (1) infant negative affectivity and over-reactive parenting are candidate mediators for the effects of heritable and prenatal risk on externalizing symptoms and (2) parental warmth weakens the influence of heritable risk, prenatal risk, negative affectivity, and over-reactive parenting on externalizing symptoms. There were main effects of heritable risk, infant negative affectivity, and over-reactive parenting on child externalizing symptoms. The study found no support for the hypothesized mediation and moderation effects, suggesting that targeting parental over-reactivity rather than warmth would be more effective in reducing risk for childhood externalizing symptoms.

Examining timing effects in the intergenerational transmission of anxiety and depressive symptoms: A genetically informed study.

The present study examined genetic, prenatal, and postnatal environmental pathways in the intergenerational transmission of anxiety and depressive symptoms from parents to early adolescents (when these symptoms start to increase), while considering timing effects of exposure to parent anxiety and depressive symptoms postnatally. The sample was from the Early Growth and Development Study, including 561 adopted children (57% male, 55% White, 13% Black/African American, 11% Hispanic/Latine, 20% multiracial, 1% other; 407 provided data in early adolescence) and their birth (BP) and adoptive parents (AP). Using a trait-state-occasion model with eight assessments from child ages 9 months to 11 years, we partitioned trait-like AP anxiety and depressive symptoms from time-specific fluctuations of AP anxiety and depressive symptoms. Offspring anxiety and depressive symptoms were assessed at 11 years (while controlling for similar symptoms at 4.5 years). Results suggested that time-specific fluctuations of AP1 (mostly mothers) anxiety/depressive symptoms in infancy (9 months) were indirectly associated with offspring anxiety/depressive symptoms at 11 years via offspring anxiety/depressive symptoms at 4.5 years; time-specific fluctuations of AP1 anxiety/depressive symptoms at child age 11 years were concurrently associated with offspring anxiety/depressive symptoms at 11 years. AP2 (mostly fathers) anxiety/depressive symptoms were not associated with offspring symptoms. Genetic and prenatal influences measured by BP internalizing problems were not associated with offspring symptoms. Results suggested infancy and early adolescence as developmental periods when children are susceptible to influences of parent anxiety and depressive symptoms. Preventive interventions should consider time-specific fluctuations in parent anxiety and depressive symptoms during these developmental periods. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Intrauterine Growth Restriction: Need to Improve Diagnostic Accuracy and Evidence for a Key Role of Oxidative Stress in Neonatal and Long-Term Sequelae.

Intrauterine growth restriction (IUGR) and being small for gestational age (SGA) are two distinct conditions with different implications for short- and long-term child development. SGA is present if the estimated fetal or birth weight is below the tenth percentile. IUGR can be identified by additional abnormalities (pathological Doppler sonography, oligohydramnion, lack of growth in the interval, estimated weight below the third percentile) and can also be present in fetuses and neonates with weights above the tenth percentile. There is a need to differentiate between IUGR and SGA whenever possible, as IUGR in particular is associated with greater perinatal morbidity, prematurity and mortality, as well as an increased risk for diseases in later life. Recognizing fetuses and newborns being "at risk" in order to monitor them accordingly and deliver them in good time, as well as to provide adequate follow up care to ameliorate adverse sequelae is still challenging. This review article discusses approaches to differentiate IUGR from SGA and further increase diagnostic accuracy. Since adverse prenatal influences increase but individually optimized further child development decreases the risk of later diseases, we also discuss the need for interdisciplinary follow-up strategies during childhood. Moreover, we present current concepts of pathophysiology, with a focus on oxidative stress and consecutive inflammatory and metabolic changes as key molecular mechanisms of adverse sequelae, and look at future scientific opportunities and challenges. Most importantly, awareness needs to be raised that pre- and postnatal care of IUGR neonates should be regarded as a continuum.

Prenatal influences on postnatal neuroplasticity: Integrating DOHaD and sensitive/critical period frameworks to understand biological embedding in early development.

Early environments can have significant and lasting effects on brain, body, and behavior across the lifecourse. Here, we address current research efforts to understand how experiences impact neurodevelopment with a new perspective integrating two well-known conceptual frameworks - the Developmental Origins of Health and Disease (DOHaD) and sensitive/critical period frameworks. Specifically, we consider how prenatal experiences characterized in the DOHaD model impact two key neurobiological mechanisms of sensitive/critical periods for adapting to and learning from the postnatal environment. We draw from both animal and human research to summarize the current state of knowledge on how particular prenatal substance exposures (psychoactive substances and heavy metals) and nutritional profiles (protein-energy malnutrition and iron deficiency) each differentially impact brain circuits' excitation/GABAergic inhibition balance and myelination. Finally, we highlight new research directions that emerge from this integrated framework, including testing how prenatal environments alter sensitive/critical period timing and learning and identifying potential promotional/buffering prenatal exposures to impact postnatal sensitive/critical periods. We hope this integrative framework considering prenatal influences on postnatal neuroplasticity will stimulate new research to understand how early environments have lasting consequences on our brains, behavior, and health.

Recognizing, Evaluating, and Prioritizing the Fundamental Factors Influencing the Growing Prevalence of Transgender and Non-Binary Gender Identity in the Pediatric Population

This review observes the growing demographic of individuals identifying as transgender or non-binary, which currently represents approximately 1.3% (depending on the source) of the U.S. population. This population is shown to skew younger.Environmental xenobiotics, particularly those containing endocrine-disrupting chemicals (EDCs), are scrutinized for their role in affecting hormonal regulation crucial for gender identity differentiation. The research also highlights how exposure to pharmaceuticals with endocrine-disrupting properties may induce atypical patterns in gender identity development, suggesting that a variety of exogenous elements could impact neuroendocrine sexual differentiation.Medical disorders associated with altered androgen levels, such as congenital adrenal hyperplasia (CAH) and androgen insensitivity syndrome (AIS), are considered for their potential influence on gender identity from a biological perspective. Moreover, the role of diet and nutrition, particularly plant-based diets rich in phytoestrogens and conditions linked to obesity and metabolic syndrome, are explored for their effects on hormonal balance and, consequently, gender identity expression.This review acknowledges the significant impact of media representation and societal norms on shaping attitudes concerning gender expression and identity.The article points to psychological assessments and somatic markers as tools to explore prenatal hormone influences on gender identity, though emphasizing that they are not definitive. Furthermore, genetic and epigenetic findings offer a more in-depth understanding but lack diagnostic application. The identification and recognition of transgender and non-binary individuals continue to be self-determined processes that defy objective measurement by current medical standards.

Prenatal and postnatal influences on behavioral development in a mouse model of preconceptional stress

Depression during pregnancy is detrimental for the wellbeing of the expectant mother and can exert long-term consequences on the offspring's development and mental health. In this context, both the gestational environment and the postpartum milieu may be negatively affected by the depressive pathology. It is, however, challenging to assess whether the contributions of prenatal and postnatal depression exposure are distinct, interactive, or cumulative, as it is unclear whether antenatal effects are due to direct effects on fetal development or because antenatal symptoms continue postnatally. Preclinical models have sought to answer this question by implementing stressors that induce a depressive-like state in the dams during pregnancy and studying the effects on the offspring. The aim of our present study was to disentangle the contribution of direct stress in utero from possible changes in maternal behavior in a novel model of preconceptional stress based on social isolation rearing (SIR). Using a cross-fostering paradigm in this model, we show that while SIR leads to subtle changes in maternal behavior, the behavioral changes observed in the offspring are driven by a complex interaction between sex, and prenatal and postnatal maternal factors. Indeed, male offspring are more sensitive to the prenatal environment, as demonstrated by behavioral and transcriptional changes driven by their birth mother, while females are likely affected by more complex interactions between the pre and the postpartum milieu, as suggested by the important impact of their surrogate foster mother. Taken together, our findings suggest that male and female offspring have different time-windows and behavioral domains of susceptibility to maternal preconceptional stress, and thus underscore the importance of including both sexes when investigating the mechanisms that mediate the negative consequences of exposure to such stressor.

The Effects of Environmental Exposure on Epigenetic Modifications in Allergic Diseases.

Allergic diseases are one of the most common chronic conditions and their prevalence is on the rise. Environmental exposure, primarily prenatal and early life influences, affect the risk for the development and specific phenotypes of allergic diseases via epigenetic mechanisms. Exposure to pollutants, microorganisms and parasites, tobacco smoke and certain aspects of diet are known to drive epigenetic changes that are essential for immune regulation (e.g., the shift toward T helper 2-Th2 cell polarization and decrease in regulatory T-cell (Treg) differentiation). DNA methylation and histone modifications can modify immune programming related to either pro-allergic interleukin 4 (IL-4), interleukin 13 (IL-13) or counter-regulatory interferon γ (IFN-γ) production. Differential expression of small non-coding RNAs has also been linked to the risk for allergic diseases and associated with air pollution. Certain exposures and associated epigenetic mechanisms play a role in the susceptibility to allergic conditions and specific clinical manifestations of the disease, while others are thought to have a protective role against the development of allergic diseases, such as maternal and early postnatal microbial diversity, maternal helminth infections and dietary supplementation with polyunsaturated fatty acids and vitamin D. Epigenetic mechanisms are also known to be involved in mediating the response to common treatment in allergic diseases, for example, changes in histone acetylation of proinflammatory genes and in the expression of certain microRNAs are associated with the response to inhaled corticosteroids in asthma. Gaining better insight into the epigenetic regulation of allergic diseases may ultimately lead to significant improvements in the management of these conditions, earlier and more precise diagnostics, optimization of current treatment regimes, and the implementation of novel therapeutic options and prevention strategies in the near future.

Sex and age factors of mental development of children born to mothers with epilepsy

Mother’s epilepsy is a risk factor for the neurocognitive development of the child, since it belongs to a group of chronic diseases and constant medication, even during pregnancy, is a Author for correspondence. 46 Вестник СПбГУ. Психология. 2024. Т. 14. Вып. 1 vital for patients with epilepsy. It carries various risks, which include intrauterine growth restrictions, congenital malformations, negative effects on cognitive functions and an increased risk of mental retardation of the child. That is why the bulk of research is focused on the effect of certain antiepileptic drugs on the physical development of the child. However, researchers rarely carry out comprehensive assessment of the influence of prenatal, perinatal and age-related factors of the child’s development, and this area remains unstudied. This article presents the results of a study of sex and age factors of mental development and adaptation of children born to mothers with epilepsy. The study involved 176 people: 88 children aged from 3 to 9 years and their mothers suffering from epilepsy. As a result, it was found that the male fetus was more vulnerable to prenatal influences: boys had more pronounced disorders of mental development (motor awkwardness, hyperactivity, attention deficit, oral speech disorders) and adaptation (socialization disorders, emotional-volitional disorders, aggressiveness and oppositional reactions, behavior problems). Some of disorders of mental development (delay in the development of speech, praxis and logical thinking) were compensated with child’s age and secondary disorders — adaptation problems (socialization disorders, somatic and internalization problems, isolation and anxiety) became more significant. Disorders of mental development in children are caused not only by the toxic effects of medication taken by the mother, but also depend on the form and severity of mother’s epilepsy before and during pregnancy, her concomitant diseases, as well as the type of feeding of the child in the first year of life.

Poverty and neighborhood opportunity effects on neonate DNAm developmental age.

Children from families with low socioeconomic status (SES), as determined by income, experience several negative outcomes, such as higher rates of newborn mortality and behavioral issues. Moreover, associations between DNA methylation and low income or poverty status are evident beginning at birth, suggesting prenatal influences on offspring development. Recent evidence suggests neighborhood opportunities may protect against some of the health consequences of living in low income households. The goal of this study was to assess whether neighborhood opportunities moderate associations between household income (HI) and neonate developmental maturity as measured with DNA methylation. Umbilical cord blood DNA methylation data was available in 198 mother-neonate pairs from the larger CANDLE cohort. Gestational age acceleration was calculated using an epigenetic clock designed for neonates. Prenatal HI and neighborhood opportunities measured with the Childhood Opportunity Index (COI) were regressed on gestational age acceleration controlling for sex, race, and cellular composition. Higher HI was associated with higher gestational age acceleration (B = .145, t = 4.969, p = 1.56x10-6, 95% CI [.087, .202]). Contrary to expectation, an interaction emerged showing higher neighborhood educational opportunity was associated with lower gestational age acceleration at birth for neonates with mothers living in moderate to high HI (B = -.048, t = -2.08, p = .03, 95% CI [-.092, -.002]). Female neonates showed higher gestational age acceleration at birth compared to males. However, within males, being born into neighborhoods with higher social and economic opportunity was associated with higher gestational age acceleration. Prenatal HI and neighborhood qualities may affect gestational age acceleration at birth. Therefore, policy makers should consider neighborhood qualities as one opportunity to mitigate prenatal developmental effects of HI.

Fingerprint patterns in relation to an altered neurodevelopment in patients with autism spectrum disorder

AbstractDermatoglyphic patterns are permanently established and matured before the 24th week of gestation. Their frequencies and localization might be a good indicator of developmental instability in individuals with an altered neurodevelopment and show potential as biomarkers of autism spectrum disorder (ASD). In this study, fingerprint pattern counts and fluctuating asymmetry in the distribution of patterns are compared between 67 boys diagnosed with ASD (aged 5.11 ± 2.51 years) and 83 control boys (aged 8.58 ± 3.14 years). Boys with ASD had a higher rate of discordance in their fingerprint patterns (p = .0026), showing more often bilateral differences in the occurrence of certain patterns. A chi‐square test revealed that the difference in pattern frequencies between boys with ASD and the control group is the most significant in frequencies of whorls, tented arches, and ulnar loops. Boys with ASD have significantly fewer ulnar loops, significantly more whorls, and tented arches in the right hand. The achieved results are in favor of the suggestion that prenatal influences, which play a role in the development of bilateral differences in fingerprint patterns up to the 24th week of gestation, may be a potential cause of an altered neurodevelopment in ASD individuals.

Stratification of Amniotic Fluid Cells and Amniotic Fluid by Sex Opens Up New Perspectives on Fetal Health.

Amniotic fluid is essential for fetus wellbeing and is used to monitor pregnancy and predict fetal outcomes. Sex affects health and medicine from the beginning of life, but knowledge of its influence on cell-depleted amniotic fluid (AF) and amniotic fluid cells (AFCs) is still neglected. We evaluated sex-related differences in AF and in AFCs to extend personalized medicine to prenatal life. AFCs and AF were obtained from healthy Caucasian pregnant women who underwent amniocentesis at the 16th-18th week of gestation for advanced maternal age. In the AF, inflammation biomarkers (TNFα, IL6, IL8, and IL4), malondialdehyde, nitrites, amino acids, and acylcarnitines were measured. Estrogen receptors and cell fate (autophagy, apoptosis, senescence) were measured in AFCs. TNFα, IL8, and IL4 were higher in female AF, whereas IL6, nitrites, and MDA were similar. Valine was higher in male AF, whereas several acylcarnitines were sexually different, suggesting a mitochondrial involvement in establishing sex differences. Female AFCs displayed higher expression of ERα protein and a higher ERα/ERβ ratio. The ratio of LC3II/I, an index of autophagy, was higher in female AFCs, while LC3 gene was similar in both sexes. No significant sex differences were found in the expression of the lysosomal protein LAMP1, while p62 was higher in male AFCs. LAMP1 gene was upregulated in male AFCs, while p62 gene was upregulated in female ones. Finally, caspase 9 activity and senescence linked to telomeres were higher in female AFCs, while caspase 3 and β-galactosidase activities were similar. This study supports the idea that sex differences start very early in prenatal life and influence specific parameters, suggesting that it may be relevant to appreciate sex differences to cover knowledge gaps. This might lead to improving the diagnosis of risk prediction for pregnancy complications and achieving a more satisfactory monitoring of fetus health, even preventing future diseases in adulthood.

Depression in the next generation is related with maternal behaviors: A cross-comparison by alternating rat's mother care.

This study investigated the potential impacts of depressive rats' maternal behavior as an early life stress on the outcome of offspring as an adulthood. Offspring from the same mother were divided into two groups, half of them were fostered or remained by a depressive mother, and the other half remained or fostered by a control mother, respectively. The results showed that offspring fostered by depressive mothers presented significant depressive behaviors. Meanwhile, depressive mothers engaged in more grooming during the light cycle, but less off-the-pup behavior during the dark phase. In conclusion, offspring exposed to a postnatal depressive maternal environment developed a depressive-like behavior. Contrarily, postpartum maternal behaviors play an essential role, which might determine the outcome of the next generation. Furthermore, the appropriate timing of postpartum maternal caring sequences, which might eliminate prenatal stressful influences, was recognized and might be a promising approach for reducing children's predisposition to mental disorders in their life time.

Differential effects of prenatal psychological distress and positive mental health on offspring socioemotional development from infancy to adolescence: ameta-analysis.

The impact of prenatal maternal mental health on offspring socioemotional development is substantial and enduring. Existing literature primarily focuses on the effects of psychological distress during pregnancy, emphasizing adverse child outcomes. Recent studies, however, highlight the unique impact of positive maternal mental health on child outcomes. To elucidate the differential associations of maternal psychological distress and positive mental health during pregnancy with child outcomes, we conducted a systematic literature search and random-effects meta-analyses on studies investigating the associations of prenatal maternal mental health with child socioemotional development. Our analyses, comprising 74 studies with 321,966 mother-child dyads across 21 countries, revealed significant associations of prenatal psychological distress with both adverse and positive child socioemotional outcomes. Notably, the effect sizes for the association of psychological distress with positive child outcomes were smaller compared to adverse outcomes. Positive prenatal mental health, on the other hand, was significantly associated with positive socioemotional outcomes but not adverse outcomes. This meta-analysis highlights the independence of negative and positive prenatal mental health constructs and their distinct relationships with child socioemotional development. The findings underscore the importance of considering the positive spectrum of maternal mental health and developmental outcomes to enhance our understanding of prenatal influences on child development. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=335227, identifier CRD42022335227.

Latent class analysis of maternal depression from pregnancy through early childhood: Differences in children's executive functions.

Prenatal and postpartum depression are highly prevalent worldwide, and emerging evidence suggests they contribute to impairments in children's executive functions. Studies of maternal depression, however, have focused on the postpartum and postnatal periods with relatively less consideration of prenatal influences on child development. This study of the large population-based Avon Longitudinal Study of Parents and Children U.K. cohort estimates latent classes of maternal depression across the prenatal, postpartum, and postnatal periods to capture heterogeneity in the developmental timing and length of maternal depression, as well as to test whether latent classes differ in children's executive function impairments in middle childhood. Repeated measures latent class analysis yielded five groups demonstrating unique patterns of change in maternal depression from pregnancy through early childhood (n = 13,624). Latent classes differed in executive functions at age 8 among a subsample of children (n = 6,870). Children exposed to chronic maternal depression beginning in utero showed the most impairments in inhibitory control while accounting for child sex, verbal IQ, parents' highest education level, and average family income in childhood. The critical roles of the timing and length of children's exposure to maternal depression are discussed in relation to executive function development, prevention, and intervention. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Brain effects of gestating germ-free persist in mouse neonates despite acquisition of a microbiota at birth.

At birth, mammals experience a massive colonization by microorganisms. We previously reported that newborn mice gestated and born germ-free (GF) have increased microglial labeling and alterations in developmental neuronal cell death in the hippocampus and hypothalamus, as well as greater forebrain volume and body weight when compared to conventionally colonized (CC) mice. To test whether these effects are solely due to differences in postnatal microbial exposure, or instead may be programmed in utero, we cross-fostered GF newborns immediately after birth to CC dams (GF→CC) and compared them to offspring fostered within the same microbiota status (CC→CC, GF→GF). Because key developmental events (including microglial colonization and neuronal cell death) shape the brain during the first postnatal week, we collected brains on postnatal day (P) 7. To track gut bacterial colonization, colonic content was also collected and subjected to 16S rRNA qPCR and Illumina sequencing. In the brains of GF→GF mice, we replicated most of the effects seen previously in GF mice. Interestingly, the GF brain phenotype persisted in GF→CC offspring for almost all measures. In contrast, total bacterial load did not differ between the CC→CC and GF→CC groups on P7, and bacterial community composition was also very similar, with a few exceptions. Thus, GF→CC offspring had altered brain development during at least the first 7 days after birth despite a largely normal microbiota. This suggests that prenatal influences of gestating in an altered microbial environment programs neonatal brain development.

Adult attention deficit hyperactivity disorder: a comprehensive review.

Attention deficit hyperactivity disorder (ADHD) is a common childhood disorder, with only 2-3% prevalence into adulthood. The epidemiology and proposed causes of ADHD are multifactorial, including genetic, prenatal and environmental influences. The diagnosis of ADHD is often complicated by masking coping mechanisms, an overlap of symptoms with other, more commonly diagnosed disorders. Traditionally, it has been treated with stimulant medications. Non-stimulant options often target norepinephrine and dopamine regulation and are preferred in cases of comorbid substance use disorder, anxiety and other complicating factors, due to an improved side-effect profile and patient preference. They include atomoxetine and viloxazine. The latter, Viloxazine, in the form of extended-release capsules, is the first novel, non-stimulant option approved for adults with ADHD, in the past two decades. Its therapeutic effects are predominantly produced by its action as a norepinephrine reuptake inhibitor and may also modulate the serotonergic system. Viloxazine is relatively safe and effective in treating other disorders such as depression, anxiety, epilepsy and substance use disorder. Its pharmacokinetics includes metabolization by CYP enzymes. As antiepileptics inhibit CYP1A2, therefore, a special consideration would be needed, when co-administering with anti-epileptic drugs. Similarly, individuals with liver or cardiovascular disease and a personal or family history of bipolar disorder require close monitoring, while on this medication. A thorough review of the history, mechanism of action, pharmacokinetics and drug-drug interactions has been presented here, with special attention on treatment in adults with comorbid conditions. This study conducted an all-language literature search on Medline, Cochrane, Embase, and Google Scholar until December 2022. The following search strings and Medical Subject Headings (MeSH) terms were used: "Viloxazine," "ADHD," "Stimulants," and "adult ADHD." We explored the literature on the growing knowledge of Viloxazine. A thorough review of the history, mechanism of action, pharmacokinetics, and drug-drug interactions are reviewed here with special attention on treatment in adults with comorbid conditions.

Environmental contaminants, endocrine disruption, and transgender: Can "born that way" in some cases be toxicologically real?

Gender is viewed by many as strictly binary based on a collection of body traits typical of a female or male phenotype, presence of a genotype that includes at least one copy of a Y chromosome, or ability to produce either egg or sperm cells. A growing non-binary view is that these descriptors, while compelling, may nonetheless fail to accurately capture an individual's true gender. The position of the American Psychological Association (APA) agrees with this view and is that transgender people are a defendable and real part of the human population. The considerable diversity of transgender expression then argues against any unitary or simple explanations, however, prenatal hormone levels, genetic influences, and early and later life experiences have been suggested as playing roles in development of transgender identities. The present review considers existing and emerging toxicologic data that may also support an environmental chemical contribution to some transgender identities, and suggest the possibility of a growing nonbinary brain gender continuum in the human population.