COMMENTARY

Discoveries in Diabetic Embryogenesis

Thomas R. Moore, MD

Disclosures

November 16, 2022

Many issues surrounding pregnancy care of women with preexisting diabetes remain challenging, especially in light of the relentless increase in maternal morbidity and mortality in the United States and globally. Rising rates of death and severe morbidity in diabetic women have continued despite significant advances in insulin pharmacology and administration technology.

However, despite these advances in glucose monitoring and insulin administration, fetal mortality and childhood morbidity rates continue to climb. This is because critical fetal structural anomalies arise from developmental errors occurring in the embryonic period – between 2 and 13 weeks of gestation – a time when most women with preexisting diabetes are just entering into prenatal care, often with suboptimal glycemic control.

Thomas R. Moore, MD

Thus, significant future progress in reducing fetal mortality and childhood disability in infants of diabetic mothers will depend upon effective interventions in the first trimester while embryogenesis and critical organ formation are underway.

In this issue of Ob.Gyn. News, the editor of Master Class in Obstetrics, E. Albert Reece MD, PhD, MBA, steps into the role of coauthor. He and his research colleague Peixin Yang, PhD, present exciting insights into the cellular mechanisms underlying structural birth defects in infants of diabetic mothers – especially cardiac and neural tube defects – and also provide a glimpse into some potentially effective maternal pharmacologic interventions. After appropriate human trials, these interventions could be effectively applied from the time of a positive pregnancy test with potentially dramatic results.

Dr. Reece and Dr. Yang, who lead the Center for the Study of Birth Defects at the University of Maryland School of Medicine, share their impressive accumulation of data from embryos of pregnant diabetic rodents. They demonstrate convincingly that, in first-trimester rodent embryos, maternal hyperglycemia induces excessive apoptosis, which in turn leads to structural defects in critical fetal organs. They further found that maternal hyperglycemia reduces embryonic autophagosomes – the developmentally essential organelles that remove abnormal or damaged cells during embryo formation.

These investigators also identified reactivators of these organelles which, when administered maternally in the first trimester, significantly reduced the incidence of neural tube defects. Thus, for optimal development of diabetes-affected embryos, first-trimester administration of reactivators of autophagy could offer a significant, life-changing intervention in the foreseeable future.

Dr. Moore is professor emeritus of maternal-fetal medicine and chair emeritus in the department of obstetrics, gynecology, and reproductive sciences at UC San Diego Health. He reported no disclosures.

*This story was updated on Nov. 3, 2022.

This article originally appeared on MDedge.com, part of the Medscape Professional Network.

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