Maternal periconceptional factors affect the risk of spina bifida-affected pregnancies: an Italian case-control study

Abstract Purpose Neural tube defects, including spina bifida and anencephaly, are the second most common birth defects with an incidence in Italy of 0.4-1/1,000. Information on factors playing a role in the pathogenesis of spina bifida is based on populations with different exposures, lifestyle, social and cultural habits compared to Italian people. Our objective was to fill this gap by using data from a casecontrol interview study carried out at the G. Gaslini Children's Hospital, Genoa, from 2000 to 2008. Methods We surveyed questionnaires from 133 case mothers and 273 control women providing information on periconceptional risk factors. Univariate and multivariate logistic regression analyses were used to estimate risks by odds ratios (ORs) and 95% confidence intervals (95% CIs). Results Univariate results suggest that birth order, low maternal educational level, age, smoking habits, alcohol consumption, high caffeine intake, lack of folate supplementation, low and high calorie diet, occasional consumption of fruit and vegetables, high emotional stress, and environmental pollution are associated with an increased spina bifida risk. Nevertheless, high caffeine intake (OR= 10.82; 95% CI, 3.78-31), low calorie diet (OR=5.15; 95% CI, 1.79-14), occasional consumption of fruit and vegetables (OR=3.38; 95% CI, 1.67-6.82), alcohol consumption (OR=3.05; 95% CI, 1.24-7.50) and, above all, lack of folate supplementation at any time of pregnancy (OR= 20.54; 95% CI, 5.41-77) mainly determined spina bifida risk in the multivariate analysis. Conclusion Our findings point out that a common underlying mechanism, a disturbed folate/homocysteine metabolism, may be causative for the burden of spina bifida in the Italian population

Investigating the Paracrine Role of Perinatal Derivatives: Human Amniotic Fluid Stem Cell-Extracellular Vesicles Show Promising Transient Potential for Cardiomyocyte Renewal

Cardiomyocyte renewal represents an unmet clinical need for cardiac regeneration. Stem cell paracrine therapy has attracted increasing attention to resurge rescue mechanisms within the heart. We previously characterized the paracrine effects that human amniotic fluid-derived stem cells (hAFSC) can exert to provide cardioprotection and enhance cardiac repair in preclinical models of myocardial ischemia and cardiotoxicity. Here, we analyze whether hAFSC secretome formulations, namely, hAFSC conditioned medium (hAFSC-CM) over extracellular vesicles (hAFSC-EVs) separated from it, can induce cardiomyocyte renewal. c-KIT+ hAFSC were obtained by leftover samples of II trimester prenatal amniocentesis (fetal hAFSC) and from clinical waste III trimester amniotic fluid during scheduled C-section procedures (perinatal hAFSC). hAFSC were primed under 1% O2 to enrich hAFSC-CM and EVs with cardioactive factors. Neonatal mouse ventricular cardiomyocytes (mNVCM) were isolated from cardiac tissue of R26pFUCCI2 mice with cell cycle fluorescent tagging by mutually exclusive nuclear signal. mNVCM were stimulated by fetal versus perinatal hAFSC-CM and hAFSC-EVs to identify the most promising formulation for in vivo assessment in a R26pFUCCI2 neonatal mouse model of myocardial infarction (MI) via intraperitoneal delivery. While the perinatal hAFSC secretome did not provide any significant cardiogenic effect, fetal hAFSC-EVs significantly sustained mNVCM transition from S to M phase by 2-fold, while triggering cytokinesis by 4.5-fold over vehicle-treated cells. Treated mNVCM showed disorganized expression of cardiac alpha-actinin, suggesting cytoskeletal re-arrangements prior to cell renewal, with a 40% significant downregulation of Cofilin-2 and a positive trend of polymerized F-Actin. Fetal hAFSC-EVs increased cardiomyocyte cell cycle progression by 1.8-fold in the 4-day-old neonatal left ventricle myocardium short term after MI; however, such effect was lost at the later stage. Fetal hAFSC-EVs were enriched with a short isoform of Agrin, a mediator of neonatal heart regeneration acting by YAP-related signaling; yet in vitro application of YAP inhibitor verteporfin partially affected EV paracrine stimulation on mNVCM. EVs secreted by developmentally juvenile fetal hAFSC can support cardiomyocyte renewal to some extension, via intercellular conveyance of candidates possibly involving Agrin in combination with other factors. These perinatal derivative promising cardiogenic effects need further investigation to define their specific mechanism of action and enhance their potential translation into therapeutic opportunity

Acute presentation of fetal hypertrophic cardiomyopathy in a type 1 diabetic pregnancy

acute presentation of fetal hypertrophic cardiomiopathy in a type 1 diabetic pregnancy case report and study with doppler