Never Say Never in Medicine

Confessions of an old dog

For over two decades I have religiously clung to the notion that maternal hyperglycemia is the root of all evil in pregnancies complicated by diabetes (1). To this end, I have valiantly waved the flag for universal screening for gestational diabetes (2), intensified glucose monitoring (3,4), and intensified insulin delivery for all women with hyperglycemia in pregnancy (5). In addition, I championed absolute normalization of blood glucose to mimic the levels documented in a normal population of pregnant women, as recently reported by Parretti et al. (6). Despite the fact that I have been a coauthor on articles that suggest that normalization of blood glucose may be associated with an increased risk of small-for-gestational-age infants (7), I have tended to ignore or explain away this finding even when the evidence has been convincing. This old dog became an ostrich. Her head was in the sand despite examples of definitive studies that showed that there is an increased prevalence of small-for-dates (<10th percentile birth weight) infants in programs of “tight control.” The landmark article of Langer et al. (8) showed the relationship between optimal levels of glycemic control and perinatal outcome in a prospective study of 334 gestational diabetic women and 334 control subjects matched for obesity, race, and parity. Three groups were identified on the basis of mean blood glucose level throughout pregnancy (low, ≤86; mid, 87–104; and high, ≥105 mg/dl). The low group had a significantly higher prevalence of small-for-gestational-age infants (20%). In contrast, the prevalence of large-for-gestational-age infants was 21-fold higher in the high mean blood glucose category than in the low mean blood glucose category (24 vs. 1.4%, P < 0.0001). In the control group, the overall prevalence was only 11% for small-for-gestational-age infants and only 12% for large-for-gestational-age infants. They concluded that a relationship …