INCIDENCE OF MALFORMATIONS AMONG

INFANTS OF DIABETIC MOTHERS 

There are numerous studies which have suggested that infants of insulin requiring diabetic women are at a high risk for malformations, with the greatest association occurring with increasing severity of glucose concentration during organogenesis. This suggests that the adverse metabolic environment is due to hyperglycemia, hypoglycemia, hyperketonemia as well as others.
 

Ref.

Number

Percentage

(1)
(2)
(3)
(4)

44/791
11/142
9/106

5.6%
7.7%
8.5%
13.9%

Several studies have attempted to answer the question of the relationship between maternal glucose control and the incidence of congenital malformations.
 

MALFORMATION RATES


By Level Of Maternal Hemoglobin A1c

Ref.

A1c level

Percentage with
major malformations

(5)

£ 6.9
7.0-8.5
³ 8.6

0%
5.1%
22.4%

(2)

£ 7.9
9.0-8.9
³ 10.0

3.2%
8.1%
23.5%

Most evidence suggests that hyperglycemia is the major teratogenic factor during organogenesis (6). One hypothesis suggests that hyperglycemia produces yolk sac failure (visceral yolk sac exposed to excess D-glucose show decrease numbers of rough endoplasmic reticulum, ribosomes and mitochondria as well as functionally impaired protein transport) (7).

Hyperglycemia may also channel excess glucose along unconventional pathways, one of which involves the conversion of glucose into sorbitol (polyol pathway). Sorbitol is associated with ocular, neural and renal malformations in animal models (8).
 

 

 

REFERENCES
  1. Pedersen J, Pedersen LM. Prognosis of the outcome of pregnancies in diabetics: A new classification. Acta Endocrinol 1965;50:70-78.
  2. Ylinen K, Aula P, Stenman U-H et.al. Risk of minor and major malformations in diabetics with hemoglobin A1c values in early pregnancy. BMJ 1984;289:345-346.
  3. Simpson JL, Elias S, Martin AO et.al. Diabetes in pregnancy, Northwestern University Series (1977-1981). Am J Obstet Gynecol 1983;146:263-270.
  4. Vandheim C. Pregnancy with diabetes: Washington State, 1979-1980. Ann Arbor, MI, University Microfilms International, 1983.
  5. Miller E, Hare JW, Cloherty JP et.al. Elevated maternal hemoglobin A1c in early pregnancy and major congenital anomalies in infants of diabetic mothers. N Engl J Med 1988;304:1331-1333.
  6. Engle MJ, Langan Sm, Sanders RL et.al. The effects of insulin and hyperglycemia on surfactant phospholipid biosynthesis in organotype cultures of type II pneumocytes. Biochim Biophys Acta 1983;753:6-13.
  7. Reece EA, Pinter E, Leranth CZ et.al. Ultrastructural analysis of malformations of the embryonic neural axis induced by in vitro hyperglycemic conditions. Teratology 1985;32:363-373.
  8. Shafrir E. Polyol pathway and fetal malformations: A search for the right mode of prevention. Isr J Med Sci 1990;26:573-574.