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World J Diabetes. Dec 15, 2012; 3(12): 196-200
Published online Dec 15, 2012. doi: 10.4239/wjd.v3.i12.196
Frontiers in research on maternal diabetes-induced neural tube defects: Past, present and future
Shyamasundar Sukanya, Boon Huat Bay, Samuel Sam Wah Tay, S Thameem Dheen
Shyamasundar Sukanya, Boon Huat Bay, Samuel Sam Wah Tay, S Thameem Dheen, Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore
Author contributions: Sukanya S and Dheen ST mainly wrote this mini review; Bay BH and Tay SSW were involved in discussion and provided intellectual inputs.
Correspondence to: S Thameem Dheen, Associate Professor, Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Blk MD10, 4 Medical Drive, Singapore 117597, Singapore. antstd@nus.edu.sg
Telephone: +65-6516-3217 Fax: +65-6778-7643
Received: July 18, 2012
Revised: November 2, 2012
Accepted: December 1, 2012
Published online: December 15, 2012
Abstract

Diabetes mellitus rightly regarded as a silent-epidemic is continually on the rise and estimated to have a global prevalence of 6.4 % as of 2010. Diabetes during pregnancy is a well known risk factor for congenital anomalies in various organ systems that contribute to neonatal mortality, including cardiovascular, gastrointestinal, genitourinary and neurological systems, among which the neural tube defects are frequently reported. Over the last two to three decades, several groups around the world have focussed on identifying the molecular cues and cellular changes resulting in altered gene expression and the morphological defects and in diabetic pregnancy. In recent years, the focus has gradually shifted to looking at pre-programmed changes and activation of epigenetic mechanisms that cause altered gene expression. While several theories such as oxidative stress, hypoxia, and apoptosis triggered due to hyperglycemic conditions have been proposed and proven for being the cause for these defects, the exact mechanism or the link between how high glucose can alter gene expression/transcriptome and activate epigenetic mechanisms is largely unknown. Although preconceptual control of diabetes, (i.e., managing glucose levels during pregnancy), and in utero therapies has been proposed as an effective solution for managing diabetes during pregnancy, the impact that a fluctuating glycemic index can have on foetal development has not been evaluated in detail. A tight glycemic control started before pregnancy has shown to reduce the incidence of congenital abnormalities in diabetic mothers. On the other hand, a tight glycemic control after organogenesis and embryogenesis have begun may prove insufficient to prevent or reverse the onset of congenital defects. The importance of determining the extent to which glycemic levels in diabetic mothers should be regulated is critical as foetal hypoglycemia has also been shown to be teratogenic. Finally, the major question remaining is if this whole issue is negligible and not worthy of investigation as the efficient management of diabetes during pregnancy is well in place in many countries.

Keywords: Maternal diabetes; Congenital anomalies; Neural tube defects; Hyperglycemia; Hypoxia; Oxidative stress; Neural stem cells; Epigenetics; Epigenome