Neurodevelopmental biology, coupled with the application of advanced histological, imaging, molecular, cellular, biochemical, and genetic approaches, has provided new insights into these intricate genetic, cellular, and molecular events. During telencephalic development, specific neural progenitor cells (NPCs) proliferate, differentiate into numerous cell types, migrate to their apposite positions, and form an integrated circuitry. Critical disturbance to this dynamic process via genetic and environmental risk can cause neurological disorders and disability. The phosphatidylinositol-3-OH kinase (PI3K)-Akt-mammalian target of rapamycin (mTOR) signaling cascade contributes to mediate various cellular processes, including cell proliferation and growth, and nutrient uptake. In light of its critical function, dysregulation of this node has been regarded as a root cause of several neurodevelopmental diseases, such as megalencephaly (“big brain”), microcephaly (“small brain”), autism spectrum disorders, intellectual disability, schizophrenia, and epilepsy. In this review, particular emphasis will be given to the PI3K-Akt-mTOR signaling pathway and their paramount importance in neurodevelopment of the cerebral neocortex, because of its critical roles in complex cognition, emotional regulation, language, and behaviors.

Epidemiological studies have reported conflicting results regarding the association between maternal folic acid supplementation and the risk of congenital heart defects (CHDs). However, a meta-analysis of the association between maternal folic acid supplementation and CHDs in offspring has not been conducted. We searched the MEDLINE and EMBASE databases for articles cataloged between their inceptions and October 10, 2014 and identified relevant published studies that assessed the association between maternal folate supplementation and the risk of CHDs. Study-specific relative risk estimates were pooled using random-effects or fixed-effects models. Out of the 1,606 articles found in our initial literature searches, a total of 1 randomized controlled trial, 1 cohort study and 16 case-control studies were included in our final meta-analysis. The overall results of this meta-analysis provide evidence that maternal folate supplementation is associated with a significantly decreased risk of CHDs (RR = 0.72, 95% CI: 0.63–0.82). Statistically significant heterogeneity was detected (Q= 82.48,P< 0.001,I²= 79.4%). We conducted stratified and meta-regression analyses to identify the origin of the heterogeneity among the studies and a Galbraith plot was generated to graphically assess the sources of heterogeneity. This meta-analysis provides a robust estimate of the positive association between maternal folate supplementation and a decreased risk of CHDs.

We conducted this meta-analysis to address the open question of a possible association between maternal socioeconomic status and congenital heart defects (CHDs). We searched MEDLINE and EMBASE from their inception to January 1, 2014 for case-control and cohort studies that assessed the association between maternal socioeconomic status and the risk of CHDs. Study-specific relative risk estimates were polled according to random-effect or fixed-effect models. From 3343 references, a total of 31 case-control studies and 2 cohort studies were enrolled in this meta-analysis, including more than 50,000 cases. We observed that maternal educational attainment, family income and maternal occupation were negatively associated with an 11% (pooled RR = 1.11, 95% CI: 1.03, 1.21), 5% (pooled RR = 1.05, 95% CI: 1.01, 1.09) and 51% (pooled RR = 1.51, 95% CI: 1.02, 2.24) increased risk of CHDs, respectively. In a subgroup analysis by geographic region, the results were inconsistent for the European region (RR = 1.29, 95% CI: 0.99–1.69) and USA/Canada region (RR = 1.06, 95% CI: 0.97, 1.16) in maternal educational attainment. In summary, this meta-analysis suggests that a lower degree of maternal socioeconomic status is modestly associated with an increased risk of CHDs. However, further investigations are needed to confirm the association.

The prognosis of children with congenital heart defects(CHDs) continues to improve with advancing surgical techniques; however, lack of information about modifiable risk factors for malformations in cardiovascular development impeded the prevention of CHDs. We investigated an association between maternal lifestyle factors and the risk of CHDs, because epidemiological studies have reported conflicting results regarding maternal lifestyle factors and the risk of CHDs recently. A review published on 2007 provided a summary of maternal exposures associated with an increased risk of CHDs. As part of noninherited risk factors, we conducted a brief overview of studies on the evidence linking common maternal lifestyle factors, specifically smoking, alcohol, illicit drugs, caffeine, body mass index and psychological factors to the development of CHDs in offspring. Women who smoke and have an excessive body mass index(BMI) during pregnancy are suspected to be associated with CHDs in offspring. Our findings could cause public health policy makers to pay more attention to women at risk and could be used in the development of population-based prevention strategies to reduce the incidence and burden of CHDs. However, more prospective studies are needed to investigate the association between maternal lifestyle factors and CHDs.

Leucocyte telomere length (LTL) has been reported to be linked to ageing, cancer and cardiovascular disease (CVD). This study aimed to explore the association between LTL and CVD risk in a nationally representative sample of U.S. adults. Complex associations, including nonlinearity and interaction, were also examined. A total of 7,378 subjects from the National Health and Nutrition Examination Survey (NHANES) 1999–2002 were collected. Telomere length was detected from DNA samples and expressed as the mean T/S ratio (telomere repeats per single-copy gene). We performed multiple logistic regression models and interactive analysis to explore the associations between LTL and CVD risk by adjusting for potential confounders. We also performed a sensitivity analysis to investigate the robustness of our results. Among all participants, LTL was associated with the risk of CVD (OR = 0.79, 95% CI: 0.63~0.98, P = 0.033) in a linear manner rather than in a nonlinear manner (P = 0.874). Interaction effects of LTL with both education (P = 0.017) and hypertension (P = 0.007) were observed. Furthermore, using subgroup analyses, protective effects of LTL on CVD risk were found in females and in individuals who were college graduates or above, had serum cotinine >10 ng/ml, did not have hypertension, or had normal white blood cell levels. LTL is linearly inversely associated with CVD risk in the general population of the United States.