Visual Abstract

Background: Insulin resistance in pregnancy may be related to ketone synthesis. Data on ketone production in pregnancy and whether they are associated with gestational diabetes (GDM) risk is limited.

Methods: A matched case-control study of 107 GDM cases and 214 controls was conducted within the NICHD Fetal Growth Studies-Singleton Cohort. Beta hydroxybutyrate (BOH, mmol/L) was measured 4 times in plasma collected at gestational weeks (GW) 10-14, 15-26 (fasted), 23-31, and 33-39. GDM diagnosis and glucose challenge test (GCT) results were extracted from medical records. Prevalence of undetectable (<0.1), detectable (0.1-<0.2), elevated (0.2-<0.4), and ketoacidosis (≥0.4) BOH were estimated irrespective of GDM. Prospective associations of BOH at GW 10-14 and 15-26 with GDM were estimated using conditional logistic regression; associations with GCT results were estimated using weighted linear regression with robust variance.

Results: Percent of women with undetectable, detectable, elevated, and ketoacidosis BOH was 41%, 47%, 10%, and 2% at GW 10-14; 37%, 46%, 15%, and 2% at GW 15-26; 48%, 43%, 9%, and 0% at GW 23-31; and 37%, 57%, 6%, 0% at GW 33-39. Ketoacidosis at 10-14 GW was associated with higher GCT levels (Table).

Conclusions: Although few women develop ketoacidosis in pregnancy, detectable ketone levels are common in pregnancy. First trimester ketoacidosis was prospectively associated with higher GCT glucose at GDM screening.


S. Hinkle: None. S. F. Yisahak: None. S. Zhao: None. M. Y. Tsai: None. C. Zhang: None.


Eunice Kennedy Shriver National Institute of Child Health and Human Development

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at