Agenesis of the inferior vena cava (IVC) is a rare congenital anomaly that is associated with the development of extensive collateral circulation with the aim of compensating for the inadequate return of blood to the right ventricle. This collateral circulation predisposes to the emergence of venous hypertension with stasis and thrombus formation. Most cases are asymptomatic and are diagnosed incidentally. We report the case of a 28-year-old man who presented with bilateral deep vein thrombosis (DVT) as the first manifestation of agenesis of the IVC. We decided to maintain anticoagulation for an indefinite period of time after a multidisciplinary discussion. IVC agenesis should be considered a cause of DVT in young men, with bilateral and proximal thrombosis and without other risk factors. The rarity of the condition makes its therapeutic approach complex.

One hundred and forty bitches and their offspring (689 puppies) were involved in this study. The influence of different maternal features such as age, breed (brachycephalic/non-brachycephalic), previous births (primiparous/multiparous), health status (complete/incomplete) and litter size over the type of cesarean sections (scheduled/emergency), the neonatal survival, and the incidence of congenital malformations were also examined. Scheduled cesareans were predominant (104/140), of which 90 % were brachycephalic breeds and females were mostly between 2 and 4 years old (54.8 %), multiparous (88.4 %) and with a correct health status (67.3 %). Emergency cesarean sections mainly involved non-brachycephalic breeds (80 %) and were carried out mostly in females under 4 years of age (72.2 %), primiparous (77.7 %), with incomplete health status and a large litter size (47.2 %). Perinatal mortality was notably higher in emergency C-sections (3.25 % and 13.3 %, scheduled and emergency C-sections, respectively); the highest incidence of neonatal mortality was recorded in young females (<2, 2-4 years old), primiparous and with incomplete health status. Congenital anomalies were observed in 4.50 % (31/689) of the puppies, with anasarca (38.71 %) and cleft palate (29.03 %) being the most frequently observed malformations. A higher incidence of congenital malformations was detected in puppies from dams with incomplete sanitary health and from inbreeding cross. Overall, the study provides valuable insights into the complex interplay between maternal characteristics and cesarean outcomes. Appropriate genetic selection, good sanitary health conditions, and the age of the reproducers, are pivotal factors in planning for gestation and improving the survival of neonates.

UNASSIGNED: Whether hepatitis B virus (HBV) infection of women prior to pregnancy can influence risk of congenital malformations in offspring remains controversial. We assessed the association between them by considering congenital malformations in the aggregate as well as risk of organs systems using a large national sample of Chinese women.
UNASSIGNED: We performed a record-linkage cohort study of women who participated in National Free Preconception Health Examination Project, between January 1, 2010, and December 31, 2019 for whom data on congenital malformations in their offspring were available from the National Population-Based Birth Defects Surveillance Network. A total of 498,968 linked records were obtained, of which 127,371 were excluded because HBV status before pregnancy was unknown, the records involved multiple pregnancies, or pre-pregnancy examinations were conducted after conception. Based on pre-pregnancy status, mothers were assigned to two categories of HBsAg- or HBsAg+ and, in certain analyses, to three categories of HBsAg-, HBsAg+/HBeAg- or HBsAg+/HBeAg+. Potential associations of serological status with risk of congenital malformations, considered separately or in aggregate, were explored using multilevel logistic regression. Factors that might influence such associations were also explored.
UNASSIGNED: Among the 371,597 women analyzed, 21,482 (5.78%) were HBsAg+ before pregnancy, and 8333 (2.24%) had a fetus or child diagnosed with congenital malformations, composed of 7744 HBsAg- women and 589 HBsAg+ women. HBsAg+ status was associated with increased risk of congenital malformations in the aggregate (OR 1.14, 95% CI 1.03-1.25) and of cardiovascular malformations specifically (OR 1.18, 95% CI 1.03-1.35). HBsAg+/HBeAg- status was associated with significantly higher risk of cardiovascular malformations (OR 1.19, 95% CI 1.01-1.39) as well as reproductive malformations (OR 1.51, 95% CI 1.02-2.23). Associations between HBsAg+ status before pregnancy and risk of congenital malformations was modified by alanine aminotransferase activity (P interaction < 0.05).
UNASSIGNED: Prepregnancy HBV infection might be associated with fetal malformations. This association needs further investigation to confirm whether it is a causal association, and assess whether antiviral therapy of women with HBsAg+ planning to conceive might reduce the risk of fetal malformations.
UNASSIGNED: The National Health Commission of the People\'s Republic of China, China; Science and Technology Department of Sichuan Province, China; and the Ministry of Science and Technology of the People\'s Republic of China.

15q24.1 microdeletion syndrome is a recently described condition often resulting from non-allelic homologous recombination (NAHR). Typical clinical features include pre and post-natal growth retardation, facial dysmorphism, developmental delay and intellectual disability. Nonspecific urogenital, skeletal, and digit abnormalities may be present, although other congenital malformations are less frequent. Consequently, only one case was reported prenatally, complicating the genotype-phenotype correlation and the genetic counseling. We identified prenatally a second case, presenting with cerebral abnormalities including hydrocephaly, macrocephaly, cerebellum hypoplasia, vermis hypoplasia, rhombencephalosynapsis, right kidney agenesis with left kidney duplication and micropenis. Genome-wide aCGH assay allowed a diagnosis at 26 weeks of amenorrhea revealing a 1.6 Mb interstitial deletion on the long arm of chromosome 15 at 15q24.1-q24.2 (arr[GRCh37] 15q24.1q24.2(74,399,112_76,019,966)x1). A deep review of the literature was undertaken to further delineate the prenatal clinical features and the candidate genes involved in the phenotype. Cerebral malformations are typically nonspecific, but microcephaly appears to be the most frequent in postnatal cases. Our case is the first reported with a frank cerebellar involvement.

Observational studies have suggested an association between air pollutants and congenital malformations; however, conclusions are inconsistent and the causal associations have not been elucidated. In this study, based on publicly available genetic data, a two-sample Mendelian randomization (MR) was applied to explore the associations between particulate matter 2.5 (PM2.5), NOX, NO2 levels and 11 congenital malformations. Inverse variance weighted (IVW), MR-Egger and weighted median were used as analytical methods, with IVW being the main method. A series of sensitivity analyses were used to verify the robustness of the results. For significant associations, multivariable MR (MVMR) was utilized to explore possible mediating effects. The IVW results showed that PM2.5 was associated with congenital malformations of digestive system (OR = 7.72, 95 %CI = 2.33-25.54, P = 8.11E-4) and multiple systems (OR = 8.63, 95 %CI = 1.02-73.43, P = 0.048) risks; NOX was associated with circulatory system (OR = 4.65, 95 %CI = 1.15-18.86, P = 0.031) and cardiac septal defects (OR = 14.09, 95 %CI = 1.62-122.59, P = 0.017) risks; NO2 was correlated with digestive system (OR = 27.12, 95 %CI = 1.81-407.07, P = 0.017) and cardiac septal defects (OR = 22.57, 95 %CI = 2.50-203.45, P = 0.005) risks. Further MVMR analyses suggest that there may be interactions in the effects of these air pollutants on congenital malformations. In conclusion, this study demonstrated a causal association between air pollution and congenital malformations from a genetic perspective.

Klippel-Feil syndrome (KFS) is a rare congenital disorder characterized by the fusion of cervical vertebrae, limiting neck mobility, and often presenting with clinical manifestations such as neck pain, stiffness, and neurological deficits. While the classical presentation of KFS includes a \"clinical triad\" comprising a shortened neck, a low posterior hairline, and limited cervical motion, not all patients exhibit all three features. This case report presents an 81-year-old male with the complete KFS triad and underscores the diagnostic challenges and management strategies associated with this condition. Despite the rarity of KFS, understanding it is crucial for clinicians due to its profound implications on patient management and quality of life. This case emphasizes the importance of clinical suspicion in Internal Medicine, showcasing how an isolated presentation may often be a manifestation of an underlying congenital condition.

Previous research examining bipolar-disorder (BD) and pregnancy/neonatal outcomes yielded mixed results, were mostly derived from Western countries and rarely delineated effect between disorder and mood-stabilizers. This population-based study identified women age 15-50 years who delivered first/singleton child in 2003-2018 in Hong Kong, utilizing territory-wide medical-record database of public healthcare services. Propensity-score weighted logistic-regression analyses adjusted for confounders were employed to examine risk of adverse pregnancy, delivery and neonatal outcomes associated with BD and mood-stabilizers (lithium, anticonvulsants and antipsychotics). Exploratory unadjusted-analyses were conducted to assess risk for congenital-malformations. Of 465,069 women, 302 had BD-diagnosis, including 168 redeemed ≥ 1 prescription of mood-stabilizers during pregnancy (treated-BD) and 134 gestationally-unexposed to mood-stabilizers (untreated-BD). BD was significantly-associated with increased risk of gestational-diabetes (adjusted-odds-ratio: 1.75 [95 % CI: 1.15-2.70]) and maternal somatic hospitalization ≤ 90 days post-discharge from index-delivery (2.12 [1.19-3.90]). In treatment status-stratified analyses, treated-BD women exhibited significantly-increased rate of gestational-diabetes (2.09 [1.21-3.70]) relative to controls (non-BD and gestationally-unexposed to mood-stabilizers). No significant association of BD or mood-stabilizers with other adverse outcomes was observed. Overall, our findings indicate that BD and mood-stabilizers are not associated with most adverse pregnancy, delivery and neonatal outcomes. Further research clarifying comparative safety of individual mood-stabilizing agents on pregnancy/neonatal outcomes is required.

Valproate is the most effective medication for generalised epilepsies, and several specific epilepsy syndromes. For some people, it will be the only medication to establish seizure remission, and withdrawing it carries risks of seizure recurrence and Sudden Unexpected Death in Epilepsy (SUDEP). It is also of proven efficacy for bipolar disorder and migraine prevention. Guidelines based on observational and epidemiological studies stress that maternal valproate related teratogenicity and neurodevelopmental effects are significantly higher than for other antiseizure medications (ASMs). It should, therefore, only be used if other medications are ineffective and after balancing the teratogenicity risk. Regulatory restrictions have changed prescribing practices and reduced valproate use. The number of other medications that must be trialled in the different conditions for which valproate has effectiveness and the consequences of the lack of efficacy of those drugs leading to significant harm including death remains unexplored. Risk minimisation measures (RMMs) for valproate, chiefly Pregnancy Prevention practices (PPP), consider foetal risk and not risk to people living with epilepsy. In the United Kingdom (UK), limitations relating to valproate use in all people < 55 years commenced in January 2024. While the evidence in child-bearing women is not disputed, the data in males are based on animal models, case reports, and one commissioned, unpublished, non-peer reviewed report unavailable to the UK public, stakeholder charities or professionals. Evidence suggests that 30-40% of people switching from valproate have breakthrough seizures. Thus, an estimated 21,000-28000 people in the UK will imminently be exposed to the potential hazards of breakthrough seizures, including death. There is little government investment in monitoring the effects of these changes to valproate prescribing on patient health and quality of life. This review summarises the history of valproate regulation, evidence underpinning it and argues how the latest regulations in the UK do not align with the country\'s medical regulatory bodies ethical principles nor with the Montgomery principles of informed patient choice and autonomy. It dissects how such regulations infringe Common Law principles, nor give due regard for patient outcomes beyond reproduction. The paper looks to provide recommendations to redress these concerns while appreciating the core need for such governance to emerge in the first place.

Previous studies examining antidepressants and congenital-malformations were primarily conducted in western countries, and many were constrained by important methodological limitations. This population-based study identified 465,069 women (including 1,705 redeemed ≥1 prescription of antidepressants during first-trimester) aged 15-50 years who delivered their first and singleton child between 2003 and 2018 in a predominantly-Chinese population in Hong Kong, using territory-wide medical-record database of public-healthcare services, and employed propensity-score fine-stratification-weighted logistic-regression analyses to evaluate risk of any major and organ/system-specific congenital-malformations following first-trimester exposure to antidepressants. Major malformation overall was not associated with any antidepressant (weighted-odds-ratio wOR, 0.88 [95 %CI, 0.44-1.76]), specific drug-class, or individual antidepressants. Exposure to any antidepressant was associated with increased risk of cardiac (wOR, 1.82 [95 %CI, 1.07-3.12]) and respiratory anomalies (wOR,4.11 [95 %CI, 1.61-10.45]). Exposure to selective-serotonin-reuptake-inhibitors (SSRI) and multiple-AD-classes were associated with respiratory and cardiac anomalies, respectively. However, these identified associations were not consistently affirmed across sensitivity analyses, precluding firm conclusion. Observed associations of specific cardiac defects with serotonin-norepinephrine-reuptake-inhibitors (SNRI), tricyclic-antidepressants (TCA) and multiple-AD-classes were noted with wide confidence-intervals, suggesting imprecise estimation. Overall, our findings suggest that first-trimester antidepressant exposure was not robustly associated with increased risk of congenital-malformations. Further research clarifying comparative safety of individual antidepressants on specific malformations is warranted.

UNASSIGNED: Mesenchymal stem cells (MSCs) from gestational tissues represent promising strategies for in utero treatment of congenital malformations, but plasticity and required high-risk surgical procedures limit their use. Here we propose natural exosomes (EXOs) isolated from amniotic fluid-MSCs (AF-MSCs), and their mimetic counterparts (MIMs), as valid, stable, and minimally invasive therapeutic alternatives.
UNASSIGNED: MIMs were generated from AF-MSCs by combining sequential filtration steps through filter membranes with different porosity and size exclusion chromatography columns. Physiochemical and molecular characterization was performed to compare them to EXOs released from the same number of cells. The possibility to exploit both formulations as mRNA-therapeutics was explored by evaluating cell uptake (using two different cell types, fibroblasts, and macrophages) and mRNA functionality overtime in an in vitro experimental setting as well as in an ex vivo, whole embryo culture using pregnant C57BL6 dams.
UNASSIGNED: Molecular and physiochemical characterization showed no differences between EXOs and MIMs, with MIMs determining a 3-fold greater yield. MIMs delivered a more intense and prolonged expression of mRNA encoding for green fluorescent protein (GFP) in macrophages and fibroblasts. An ex-vivo whole embryo culture demonstrated that MIMs mainly accumulate at the level of the yolk sac, while EXOs reach the embryo.
UNASSIGNED: The present data confirms the potential application of EXOs for the prenatal repair of neural tube defects and proposes MIMs as prospective vehicles to prevent congenital malformations caused by in utero exposure to drugs.