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 nondiabetic 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.An association between diabetes mellitus in women and congenital malformations in their offspring has been suspected since the nineteenth century. In 1885, LeCorché reported two infants of diabetic mothers with hydrocephalus. The prognosis for diabetic women prior to the discovery of insulin was poor, however, and few women delivered successfully. It was not until better control of hyperglycemia, close monitoring in the last months of pregnancy, and early delivery for fetal distress were instituted that salvage rates in diabetic pregnancies improved substantially. At this point, the full impact of congenital malformations was appreciated.Despite better management, the incidence of congenital malformations has not decreased over the past 25 years (Soler, '76 NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript distress syndrome as the leading cause of death in some diabetes centers (Soler, '76). This has stimulated investigators to examine the relationship between maternal diabetes and malformations. EVIDENCE THAT INFANTS OF DIABETIC MOTHERS HAVE HIGHER MALFORMATION RATESEvidence that infants of diabetic mothers have higher malformation rates has accumulated over the last several decades. Initially, centers reporting their experience with diabetic pregnancies noted high malformation rates in the...

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Protection by free oxygen radical scavenging enzymes against glucose-induced embryonic malformations in vitro

“…For a diabetic woman the risk of bearing a malformed child is 2-3 times higher than for a normal woman [1], and compared with normal pregnancies a greater proportion of the congenital malformations in diabetic pregnancies are lethal [2][3][4]. The exact pathogenesis of the malformations is at present unknown.…”

Planning and preparation for pregnancy among women with and without a history of infertility

“…Congenital defects typical for diabetes, such as caudal regression syndrome or central nervous system, often are due to hyperglycemia before pregnancy especially among obese women and not detected type 2 diabetes [18]. Many studies demonstrate the importance of pregnancy planning in women with pregestational diabetes, but also among women with other metabolic disturbances.…”

“…Many studies demonstrate the importance of pregnancy planning in women with pregestational diabetes, but also among women with other metabolic disturbances. It turned out that both normalization of glucose levels during pregnancy and neonatal outcomes were better in women who planned their pregnancy [18,19]. Maintaining normal glycemia, especially in the first trimester, is essential for preventing congenital defects [18].…”