The epidemic nature of diabetes mellitus in different regions is reviewed. The Middle East and North Africa region has the highest prevalence of diabetes in adults (10.9%) whereas, the Western Pacific region has the highest number of adults diagnosed with diabetes and has countries with the highest prevalence of diabetes (37.5%). Different classes of diabetes mellitus, type 1, type 2, gestational diabetes and other types of diabetes mellitus are compared in terms of diagnostic criteria, etiology and genetics. The molecular genetics of diabetes received extensive attention in recent years by many prominent investigators and research groups in the biomedical field. A large array of mutations and single nucleotide polymorphisms in genes that play a role in the various steps and pathways involved in glucose metabolism and the development, control and function of pancreatic cells at various levels are reviewed. The major advances in the molecular understanding of diabetes in relation to the different types of diabetes in comparison to the previous understanding in this field are briefly reviewed here. Despite the accumulation of extensive data at the molecular and cellular levels, the mechanism of diabetes development and complications are still not fully understood. Definitely, more extensive research is needed in this field that will eventually reflect on the ultimate objective to improve diagnoses, therapy and minimize the chance of chronic complications development.

Diabetes mellitus: The epidemic of the century

Neural tube defects are severe congenital malformations affecting around one in every 1000 pregnancies. An innovation in clinical management has come from the finding that closure of open spina bifida lesions in utero can diminish neurological dysfunction in children. Primary prevention with folic acid has been enhanced through introduction of mandatory food fortification in some countries, although not yet in the UK. Genetic predisposition accounts for most of the risk of neural tube defects, and genes that regulate folate one-carbon metabolism and planar cell polarity have been strongly implicated. The sequence of human neural tube closure events remains controversial, but studies of mouse models of neural tube defects show that anencephaly, open spina bifida, and craniorachischisis result from failure of primary neurulation, whereas skin-covered spinal dysraphism results from defective secondary neurulation. Other malformations, such as encephalocele, are likely to be postneurulation disorders.

https://www.thelancet.com/pdfs/journals/laneur/PIIS1474-4422(13)70110-8.pdf

Neural tube defects: recent advances, unsolved questions, and controversies

Background: The Zika virus (ZIKV) caused a large outbreak in the Americas leading to the declaration of a Public Health Emergency of International Concern in February 2016. A causal relation between infection and adverse congenital outcomes such as microcephaly was declared by the World Health Organization (WHO) informed by a systematic review structured according to a framework of ten dimensions of causality, based on the work of Bradford Hill. Subsequently, the evidence has continued to accumulate, which we incorporate in regular updates of the original work, rendering it a living systematic review. Methods: We present an update of our living systematic review on the causal relation between ZIKV infection and adverse congenital outcomes and between ZIKV and GBS for four dimensions of causality: strength of association, dose-response, specificity, and consistency. We assess the evidence published between January 18, 2017 and July 1, 2019. Results: We found that the strength of association between ZIKV infection and adverse outcomes from case-control studies differs according to whether exposure to ZIKV is assessed in the mother (OR 3.8, 95% CI: 1.7-8.7, I 2=19.8%) or the foetus/infant (OR 37.4, 95% CI: 11.0-127.1, I 2=0%). In cohort studies, the risk of congenital abnormalities was 3.5 times higher after ZIKV infection (95% CI: 0.9-13.5, I 2=0%). The strength of association between ZIKV infection and GBS was higher in studies that enrolled controls from hospital (OR: 55.8, 95% CI: 17.2-181.7, I 2=0%) than in studies that enrolled controls at random from the same community or household (OR: 2.0, 95% CI: 0.8-5.4, I 2=74.6%). In case-control studies, selection of controls from hospitals could have biased results. Conclusions: The conclusions that ZIKV infection causes adverse congenital outcomes and GBS are reinforced with the evidence published between January 18, 2017 and July 1, 2019.

/pdf/zika-virus-infection-as-a-cause-of-congenital-brain-2y8wx5ggbi.pdf

Zika Virus Infection as a Cause of Congenital Brain Abnormalities and Guillain-Barré Syndrome: Systematic Review.

Neural tube defects (NTDs), including spina bifida and anencephaly, are severe birth defects of the central nervous system that originate during embryonic development when the neural tube fails to close completely. Human NTDs are multifactorial, with contributions from both genetic and environmental factors. The genetic basis is not yet well understood, but several nongenetic risk factors have been identified as have possibilities for prevention by maternal folic acid supplementation. Mechanisms underlying neural tube closure and NTDs may be informed by experimental models, which have revealed numerous genes whose abnormal function causes NTDs and have provided details of critical cellular and morphological events whose regulation is essential for closure. Such models also provide an opportunity to investigate potential risk factors and to develop novel preventive therapies.

Neural tube defects.

https://obgyn.onlinelibrary.wiley.com/doi/pdf/10.1111/1471-0528.15306

Placenta Praevia and Placenta Accreta: Diagnosis and Management: Green-top Guideline No. 27a.

Advanced Maternal Age

The authors test single nucleotide polymorphisms (SNPs) in coding sequences of 12 candidate genes involved in glucose metabolism and obesity for associations with spina bifida. Genotyping was performed on 507 children with spina bifida and their parents plus anonymous control DNAs from Hispanic and Caucasian individuals. The transmission disequilibrium test was performed to test for genetic associations between transmission of alleles and spina bifida in the offspring (P < .05). A statistically significant association between Lys481 of HK1 (G allele), Arg109Lys of LEPR (G allele), and Pro196 of GLUT1 (A allele) was found ( P = .019, .039, and .040, respectively). Three SNPs on 3 genes involved with glucose metabolism and obesity may be associated with increased susceptibility to spina bifida.

Genes in Glucose Metabolism and Association With Spina Bifida

The neonatal risks of late-preterm and early-term births are well established, and the potential neonatal complications associated with elective delivery at less than 39 0/7 weeks of gestation are well described. However, there are a number of maternal, fetal, and placental complications in which either a late-preterm or earlyterm delivery is warranted. The timing of delivery in such cases must balance the maternal and newborn risks of late-preterm and early-term delivery with the risks associated with further continuation of pregnancy. Deferring delivery to the 39th week is not recommended if there is a medical or obstetric indication for earlier delivery. If there is a clear indication for a late-preterm or early-term delivery for either maternal or newborn benefit, then delivery should occur regardless of the results of lung maturity testing. Conversely, if delivery could be delayed safely in the context of an immature lung profile result, then no clear indication for a late-preterm or early-term delivery exists. Also, there remain several conditions for which data to guide delivery timing are not available. Some examples of these conditions include uterine dehiscence or chronic placental abruption. Delivery timing in these circumstances should be individualized and based on the current clinical situation. This Committee Opinion is being revised to include frequent obstetric conditions that would necessitate delivery before 39 weeks of gestation and to apply the most up-to-date evidence supporting delivery recommendations.

Medically-Indicated Late Preterm and Early Term Delivery

Rate of wound complications with enoxaparin use among women at high risk for postpartum thrombosis.

BACKGROUND

A common and severe neural tube defect (NTD) phenotype, myelomeningocele (MM), results from the defective closure of the caudal end of the neural tube with herniation of the spinal cord and meninges through the vertebral column. The exact mechanisms for NTDs are unknown, but excessive oxidative stress, particularly in association with maternal diabetes, has been postulated as a mechanism for MM.



Methods

The SNPlex Genotyping (ABI, Foster City, CA) platform was used to investigate single nucleotide polymorphisms (SNPs) across the superoxide dismutase (SOD) 1 and 2 genes to assess their association with MM risk. The study population included 329 trio (affected child and both parents) and 281 duo (affected child and one parent) families. Only cases with documented MM were studied. Seventeen SNPs across the SOD1 and SOD2 genes met the quality-control criteria to be considered for statistical analysis. Genetic association was assessed using the family-based transmission disequilibrium test in PLINK (a genome association analysis toolset).



RESULTS

Four SNPs in the SOD1 gene (rs 202446, rs202447, rs4816405, and rs2070424) and one SNP in the SOD2 gene (s 5746105) appeared to be associated with MM risk in our population. After adjusting for multiple testing, these SNPs remained significant.



CONCLUSION

This study provides the first genetic evidence to support association of myelomeningocele with superoxide scavenging. The rare alleles of the five specific SNPs within SOD1 and SOD2 appear to confer a protective effect on the susceptibility for MM risk in the MM population tested. Further evaluation of the roles of superoxide scavenging and neural tube development is warranted. Birth Defects Research (Part A) 2012. © 2012 Wiley Periodicals, Inc.

Christina Davidson

Papers

Advanced Maternal Age

Genes in Glucose Metabolism and Association With Spina Bifida

Medically-Indicated Late Preterm and Early Term Delivery

Rate of wound complications with enoxaparin use among women at high risk for postpartum thrombosis.

Association of copper-zinc superoxide dismutase (SOD1) and manganese superoxide dismutase (SOD2) genes with nonsyndromic myelomeningocele.