The diabetes in early pregnancy study: β-Hydroxybutyrate levels in type 1 diabetic pregnancy compared with normal pregnancy

OBJECTIVE - The objective was to assess relationships between β- hydroxybutyrate (β-OHB) level and pregnancy outcome in human pregnancy in light of the fact that high levels of β-OHB cause malformations and growth retardation in in vitro studies. RESEARCH DESIGN AND METHODS - We analyzed β-OHB in prospectively collected specimens from the National Institute of Child Health and Human Development-Diabetes in Early Pregnancy Study, in gestational weeks 6-12 in diabetic (n = 204-239) and nondiabetic (n = 316- 332) pregnant women. RESULTS - Levels of β-OHB in diabetic women were 2.5- fold higher than in nondiabetic pregnant women at 6 weeks' gestation and declined to 1.6-fold above nondiabetic women by 12 weeks' gestation (P < 0.0001 at all times). β-OHB was positively correlated with glucose levels (P < 0.0001) in diabetic mothers, probably reflecting degree of diabetic control. β-OHB correlated inversely with glucose (P < 0.0003) (gestational week 6 only) in nondiabetic mothers, possibly reflecting caloric intake. β- OHB tended to be lower (not higher) in diabetic and nondiabetic mothers with malformed infants or pregnancy losses, but the difference was not statistically significant. β-OHB in diabetic mothers at 8, 10, and 12 weeks correlated inversely with birth weight (P = 0.004-0.02), even after adjusting for maternal glucose levels. β-OHB levels were also generally lower in diabetic mothers of macrosomic infants, and week 12 ultrasound crown-rump measurements were inversely related to β-OHB levels. CONCLUSIONS - The 1st trimester β-OHB is significantly higher in diabetic than nondiabetic pregnant women. In both groups, β-OHB tended to be lower, not higher, in mothers who had a malformed infant or pregnancy loss. β-OHB was inversely related to crown-rump length and birth weight. The modest β-OHB elevation in the 1st trimester of reasonably well-controlled diabetic pregnancy is not associated with malformations, probably because β-OHB levels causing malformations in embryo culture models are 20- to 40-fold higher. The mechanism of the β-OHB association with impaired fetal growth is unknown.