Malformations in infants of diabetic mothers

Abstract

Maternal insulin-dependent diabetes has long been associated with congenital malformations. As other causes of mortality and morbidity have been eliminated or reduced, malformations have become increasingly prominent. Although there is not universal agreement, the great majority of investigators find a two- to threefold increase in malformations in infants of insulin-dependent diabetic mothers. This increase is not seen in infants of gestational diabetics. It probably is not present in women whose diabetes can be controlled by diet or oral hypoglycemic agents. The risk does not appear to be primarily genetic since diabetic fathers do not have an increased number of malformed offspring. Most studies show a generalized increase in malformations involving multiple organ systems. Multiple malformations seem to be more common in diabetic than non-diabetic infants. Caudal regression has the strongest association with diabetes, occurring roughly 200 times more frequently in infants of diabetic mothers than in other infants. The teratogenic mechanism in diabetes is not known. Hyperglycemia may be important but human studies focusing on the period of organogenesis are lacking. Hypoglycemia has also been suggested based mainly on animal experiments. Insulin appears unlikely. Numerous other factors including vascular disease, hypoxia, ketone and amino acid abnormalities, glycosylation of proteins, or hormone imbalances could be teratogenic. None has been studied in sufficient detail to make a judgment. A large-scale prospective study is required to determine early fetal loss rates, correlate metabolic status during organogenesis with outcome, and assess the effect of diabetic control on malformation rates.

Maternal diabetes modulates dental epithelial stem cells proliferation and self-renewal in offspring through apurinic/apyrimidinicendonuclease 1-mediated DNA methylation

“…A number of studies have shown that the maternal environment, in particular hyperglycaemia during pregnancy, can alter foetal development, affecting organ formation and increasing the risk of diseases such as neural tube defects, cardiovascular disease, obesity, diabetes, and cancer in the offspring via epigenetic mechanisms313233343536373839. In the present study, we established a maternal gestational diabetes rat model to determine its effects on tooth development in offspring and to study the mechanisms associated with these effects.…”

Pregnancy environment, and not preconception, leads to fetal growth restriction and congenital abnormalities associated with diabetes

“…Studies of congenital anomalies in infants of diabetic mothers have shown cardiovascular, genitourinary, musculoskeletal, and other malformations. Available data suggest that the most affected are the cardiovascular and central nervous systems (reviewed by 6,[44][45][46] ). Although caudal regression was reported having the strongest association with diabetes, it is quite rare.…”

Effectiveness of Insulin Analogs Compared with Human Insulins in Pregnant Women with Diabetes Mellitus: Systematic Review and Meta-analysis

“…Hyperglycemia during pregnancy may interfere on fetal organogenesis, leading to congenital abnormalities. 47,48 It remains unclear if the use of insulin analogs during pregnancy might increase the risk of congenital malformations. A population retrospective cohort study did not show the increase of congenital abnormalities in women with previous diabetes that were exposed to insulin analogs on the first trimester of pregnancy, with a significant reduction of congenital cardiac defects.…”