Congenital anomalies are influenced by genetic and environmental factors. While interventions including folic acid supplementation have reduced neural tube defects, data on modifiable socio-demographic risk factors remain limited. This study aimed to assess variation in the prevalence of selected congenital anomalies across the United States according to socio-demographic factors. A population-based analysis was conducted using CDC-WONDER natality data from 2016 to 2023. Included anomalies were anencephaly, spina bifida, cyanotic heart disease, diaphragmatic hernia, omphalocele, gastroschisis, limb reduction, cleft lip/palate, Down syndrome, chromosomal disorders, and hypospadias. Associations with maternal age, BMI, race, tobacco use, diabetes, and fertility treatments were analyzed. Prevalence rates were calculated per 1000 live births. Relative risks (RRs) and 95% confidence intervals (CIs) were estimated. Joinpoint regression was used to assess annual percent changes (APCs), with p < 0.05 considered significant. Among 3,482,944 singleton live births in 2023, the overall prevalence of the selected congenital anomalies was 3.3 per 1000. Compared to Caucasian mothers, risk was lower in Asian (RR 0.57; 95% CI: 0.52-0.63) and Black (RR 0.81; 95% CI: 0.76-0.85) infants and higher in American Indian/Alaska Native infants. Significant risk factors included pre-pregnancy diabetes (RR 2.41; 95% CI: 2.16-2.69), maternal age > 45 (RR 2.95; 95% CI: 2.36-3.69), and tobacco use (RR 1.78; 95% CI: 1.64-1.94). A significant decline in prevalence was observed from 2016 to 2023 (APC: -0.6%; 95% CI: -1.1 to -0.2; p = 0.006). Significant disparities and modifiable maternal risk factors were associated with the prevalence of selected congenital anomalies in the U.S. from 2016 to 2023. A modest statistically significant decline in overall prevalence was observed during the study period, supporting the importance of continued national surveillance and targeted preconception and prenatal interventions to reduce risk and address inequities.

Non-syndromic cleft lip and palate (NSCLP) is a common congenital disability that causes morphological and functional abnormalities in the craniofacial region. Many studies have focused on clinical treatments and surgical aspects, but there has been limited investigation into the neural mechanisms in individuals with NSCLP. Therefore, it remains unclear whether developmental abnormalities in the brains of NSCLP fetuses exist. To investigate the presence of developmental abnormalities in the brains of NSCLP fetuses, we performed single-nucleus RNA sequencing (snRNA-seq) on the superior temporal plane (STP) from three NSCLP fetuses and three normal fetuses. Samples were collected at 17-23 gestational weeks. Real-time quantitative PCR (RT-qPCR) and immunofluorescence were performed to validate further phenotypes identified in the sequencing data. Following dimensionality reduction and clustering, we identified seven distinct cell types. Cell abundance changes revealed that excitatory neurons, inhibitory neurons, and astrocytes varied dramatically. We further identified the abnormally increased levels of oxidative phosphorylation (OXPHOS) and oxidative stress in the STP of NSCLP fetuses. Further investigation determined that a specific subpopulation of inhibitory neurons, InN6, is closely associated with altered OXPHOS and oxidative stress, potentially contributing to abnormal brain development in NSCLP. Finally, immunofluorescence and RT-qPCR results confirmed the abnormal increase in OXPHOS and oxidative stress in the NSCLP fetuses' brain. This study provides a single-cell atlas of STP in the NSCLP fetuses, revealing increased OXPHOS and oxidative stress in the NSCLP fetal brain. These findings provide new insights into the pathological mechanisms of the brain in NSCLP.

Mutations in the TP63 gene cause several syndromic disorders, including ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) syndrome, characterized by severe skin erosions, cleft palate, and ectodermal dysplasia. These mutations often affect the carboxy-terminal sterile-α-motif (SAM) domain of the p63 protein, leading to domain misfolding, protein aggregation, and impaired transcriptional activity. To dissect the molecular mechanisms underlying AEC pathogenesis, we investigated primary keratinocytes derived from p63L514F mutant mice, which carry a SAM domain mutation associated with AEC syndrome. p63L514F keratinocytes exhibited significantly reduced proliferation compared to wild-type controls, as indicated by decreased 5-ethynyl-2'-deoxyuridine (EdU) incorporation, decreased Cyclin D1 and Cyclin D2 expression, and an increase in the cell-cycle inhibitors p21 and p27. Furthermore, p63L514F keratinocytes showed increased cell death, elevated reactive oxygen species (ROS) levels, and a decreased reduced (GSH) and oxidized (GSSG) glutathione (GSH/GSSG) ratio, indicating oxidative stress. This stress response was accompanied by a marked reduction in Solute Carrier Family 7 Member 11 (Slc7a11), a critical regulator of antioxidant defense. We further identified Slc7a11 as a likely direct transcriptional target of p63: p63 depletion reduced Slc7a11 expression, and chromatin immunoprecipitation uncovered an evolutionary conserved p63-binding enhancer upstream of the Slc7a11 promoter. Together, our findings demonstrate that p63 mutations causative of AEC syndrome impair keratinocyte proliferation, promote cell death via oxidative stress, and compromised antioxidant defenses, revealing a dual role for p63 in sustaining skin homeostasis.

Birth defects constitute a significant public health issue worldwide, yet there is a lack of comprehensive population-based data for the Chinese population. We analyzed data from the China National Population-based Birth Defects Surveillance System from 2007 to 2021, we calculated the prevalence rates of selected birth defects, stratified by maternal residence, geographic region, maternal age, and infant sex. The Joinpoint regression model was utilized to assess trends and annual percent changes in prevalence. From 2007 to 2021, significant downward trends in prevalence were observed for neural tube defects (NTDs), hydrocephalus, cleft lip with or without palate (CL/P), limb reduction defects (LRD), omphalocele, Down syndrome, and tetralogy of Fallot (TOF). Conversely, upward trends were identified for hypospadias, cleft palate (CP), microtia/anotia, polydactyly, syndactyly, ventricular septal defect (VSD), atrial septal defect/patent foramen ovale (ASD/PFO), and patent ductus arteriosus (PDA). Younger mothers exhibited a higher prevalence of hydrocephalus, gastroschisis, CL/P, and polydactyly, while anotia/microtia, Down syndrome, and congenital heart diseases (CHDs) were more common in mothers aged 35 years or older. Significant variations in the prevalence of anencephalus, spina bifida, CL/P, anorectal atresia/stenosis, hypospadias, polydactyly, syndactyly, VSD, ASD/PFO, and PDA were found across different maternal residences and geographic regions. This study highlights the diverse trends and prevalence patterns of major birth defects, underscoring the necessity for defect-specific public health interventions.

Herpes zoster is an infectious skin disease caused by the reactivation of the varicella zoster virus (VZV), which has been latent in the posterior root ganglia of the spinal cord or cranial ganglia for an extended period. Neurological complications caused by herpes zoster include aseptic meningitis, white matter disease, peripheral motor neuropathy, and Guillain-Barré syndrome. However, reduced unilateral sweating caused by the VZV is very rare. This article reports the case of a 34-year-old woman who was admitted to our hospital with sore throat, dizziness, and reduced sweating on the left side of her body. Physical examination found herpes lesions on the left upper lip and left external ear canal (scabbed) and reduced sweating on the left side of the body. Head magnetic resonance imaging (MRI) with contrast showed no abnormalities. After a lumbar puncture, the patient was diagnosed with viral meningitis by VZV infection. The electromyographic skin sympathetic reflex indicated damage to the left sympathetic nerve. Secondary unilateral sweating reduction is a rare neurological complication of herpes zoster, caused by damage to the autonomic nervous system. Literature review and comprehensive examination indicated that the reduced unilateral sweating was due to the activation of latent herpes zoster virus in the autonomic ganglia which has damaged the autonomic nervous system. For patients who exhibit acute hemibody sweat reduction, doctors should consider the possibility of secondary autonomic nervous system damage caused by herpes zoster.