AGT is used in Japan because it lowers the incidence of respiratory distress syndrome and periventricular leukomalacia in premature infants [10
]. Its use has increased recently due to the fact that it is now covered by insurance. On the other hand, maternal hyperglycemia is sometimes found as a serious side effect of AGT [11
], and it causes secondary ketoacidosis [6
]. Maternal acidosis is a critical problem for the child [12
]. Consequently, endocrinologists and obstetricians are very sensitive to glycemic control after AGT in pregnant women with diabetes mellitus. However, there are no guidelines that give an idea of the amount of insulin needed. Moreover, how to manage nondiabetic pregnant women during AGT is unclear. Cases that require AGT are those with threatened premature labor or pregnancy induced-hypertension, and delivery must be prolonged for 48 hours, the time it takes for the effects of AGT to appear. To this end, attempts are often made to forcibly suppress labor after AGT. In Japan, there is a tendency to use ritodrine hydrochloride, a beta-2 stimulant that readily changes blood glucose, to suppress labor in such cases. However, there have been no previous reports in the literature concerning management of blood glucose while using ritodrine hydrochloride during AGT. Overseas, magnesium sulfate is used to suppress labor, not ritodrine hydrochloride. Therefore, extrapolating overseas management of blood glucose during AGT directly to Japan would carry a large risk. Investigations unique to circumstances in Japan are necessary. The present study was conceived and planned based on these circumstances.
The results of the present study showed that 30
units/day of insulin were necessary in pregnant women with diabetes mellitus receiving AGT. This includes pregnant women who did not use insulin before AGT. We could not evaluate the amount of insulin necessary by type of diabetes mellitus due to the small sample size. However, the results suggested that those with type I diabetes mellitus required more insulin, due to the fact that the slope of the regression line was steeper. In pregnant women with diabetes mellitus, it was clear that AGT easily caused hyperglycemia. In the present investigation, the additional insulin was administered by subcutaneous bolus injection, but administration by continuous subcutaneous insulin infusion (CSII) should also be investigated in the future. However, as pointed out by Bouhanick et al. [13
], CSII in pregnant women with type 1 diabetes mellitus can cause decreased compliance in association with decreased subcutaneous blood flow, easily putting them at risk for ketoacidosis. Therefore, thorough investigation may be necessary before its widespread clinical application.
In nondiabetic pregnant women, as well, early morning fasting blood glucose after AGT increased at least 40
mg/dL on average. Furthermore, it was found that this hyperglycemia continued for 2 days. This hyperglycemia increased significantly in the group that used ritodrine, and the proportion of pregnant women in the ritodrine group whose early morning fasting blood glucose exceeded 120
mg/dL was 90%. The risk of developing hyperglycemia ≥120
mg/dL early in the morning while fasting on Day 1 after AGT was 11 times greater with use of ritodrine than without use of ritodrine. Fisher et al. reported that pregnant women were more prone to developing glucose intolerance during concomitant use of the beta stimulant oral terbutaline and AGT [5
]. Bernstein and Catalano reported a case of diabetic ketoacidosis during concomitant use of terbutaline and AGT in a pregnant woman with normal glucose tolerance [14
]. Based on the previous findings, concomitant use of AGT and a beta stimulant might increase the risk of glucose intolerance and diabetic ketoacidosis even in nondiabetic pregnant women. In particular, the fact that diabetic ketoacidosis occurred in 4/11 (36%) diabetic pregnant women with a blood glucose level <200
mg/dL shows that adequate attention should be paid when performing AGT [15
In conclusion, this study showed that 30 units of insulin were necessary when performing AGT in pregnant women with diabetes mellitus. In addition, an increase in blood glucose of 40
mg/dL was seen after AGT even in nondiabetic pregnant women. Blood glucose increased significantly in the group that also received ritodrine, and it was shown that the number of pregnant women who might develop ketoacidosis might increase 11-fold. Therefore, it may be necessary to adequately monitor blood glucose, when performing AGT, even in nondiabetic pregnant women.