The Diabetes in Early Pregnancy Study: beta-hydroxybutyrate levels in type 1 diabetic pregnancy compared with normal pregnancy. NICHD-Diabetes in Early Pregnancy Study Group (DIEP). National Institute of Child Health and Development.
OBJECTIVE
The objective was to assess relationships between beta-hydroxybutyrate (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.


METHODS
We analyzed beta-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 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 nondiabetic women by 12 weeks' gestation (P < 0.0001 at all times). beta-OHB was positively correlated with glucose levels (P < 0.0001) in diabetic mothers, probably reflecting degree of diabetic control. beta-OHB correlated inversely with glucose (P < 0.0003) (gestational week 6 only) in nondiabetic mothers, possibly reflecting caloric intake. beta-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. beta-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. beta-OHB levels were also generally lower in diabetic mothers of macrosomic infants, and week 12 ultrasound crown-rump measurements were inversely related to beta-OHB levels.


CONCLUSIONS
The lst trimester beta-OHB is significantly higher in diabetic than nondiabetic pregnant women. In both groups, beta-OHB tended to be lower, not higher, in mothers who had a malformed infant or pregnancy loss. beta-OHB was inversely related to crown-rump length and birth weight. The modest beta-OHB elevation in the 1st trimester of reasonably well-controlled diabetic pregnancy is not associated with malformations, probably because beta-OHB levels causing malformations in embryo culture models are 20- to 40-fold higher. The mechanism of the beta-OHB association with impaired fetal growth is unknown.
Jovanovic
L
L
Sansum Medical Research Institute, Santa Barbara, California 93105, USA. lois@sansumres.com
Metzger
B E
BE
Knopp
R H
RH
conley
M R
MR
Park
E
E
Lee
Y J
YJ
Simpson
J L
JL
Holmes
L
L
Aarons
J H
JH
Mills
J L
JL
D020155:3-Hydroxybutyric Acid / Q000097:blood*; D000022:Abortion, Spontaneous / Q000209:etiology; D000328:Adult; D015331:Cohort Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000150:complications; D005215:Fasting; D005260:Female; D005313:Fetal Death / Q000209:etiology; D005320:Fetal Macrosomia / Q000209:etiology; D006801:Humans; D006943:Hyperglycemia / Q000150:complications; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011254:Pregnancy in Diabetics / Q000097:blood* / Q000150:complications; D012307:Risk Factors
D020155:3-Hydroxybutyric Acid