THE DIABETES IN EARLY-PREGNANCY STUDY - BETA-HYDROXYBUTYRATE LEVELS IN TYPE-1 DIABETIC PREGNANCY COMPARED WITH NORMAL-PREGNANCY

OBJECTIVE - The objective was to assess relationships between beta-hyd roxybutyrate (beta-OHB) level and pregnancy outcome in human pregnancy in light of the fact that high levels of beta-OHB cause malformations and growth retardation in in vitro studies. RESEARCH DESIGN AND METHO DS - We analyzed beta-OHB in prospectively collected specimens from th e 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 = 316-312) pregnant women. RESULTS - Levels o f beta-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 no ndiabetic women by 12 weeks' gestation (P < 0.0001 at all times). beta -OHB was positively correlated with glucose levels (P < 0.0001) in dia betic mothers, probably reflecting degree of diabetic control. beta-OH B correlated inversely with glucose (P < 0.0003) (gestational week 6 o nly) in nondiabetic mothers, possibly reflecting caloric intake. beta- OHB tended to be lower (not higher) in diabetic and nondiabetic mother s with malformed infants or pregnancy losses, but the difference was n ot statistically significant. beta-OHB in diabetic mothers at 8, 10, a nd 12 weeks correlated inversely with birthweight (P = 0.004-0.02), ev en after adjusting for maternal glucose levels. beta-OHB levels were a lso generally lower in diabetic mothers of macrosomic infants, and wee k 12 ultrasound crown-rump measurements were inversely related to beta -OHB levels. CONCLUSIONS - The 1st trimester beta-OHB is significantly higher in diabetic than nondiabetic pregnant women. In both groups, b eta-OHB tended to be lower, not higher, in mothers who had a malformed infant or pregnancy loss. beta-OHB was inversely related to crown-rum p length and birth weight. The modest beta-OHB elevation in the 1st tr imester of reasonably well-controlled diabetic pregnancy is not associ ated with malformations, probably because beta-OHB levels causing malf ormations in embryo culture models are 20- to 40-fold higher. The mech anism of the beta-OHB association with impaired fetal growth is unknow n.