Discussion
obesity, LGA, weight gain, GDM, hormone-sensitive lipase
GDM, OBESITY, EARLY PREGNANCY
In this cohort of women with overweight and obesity at 28 weeks’ gestation of pregnancy, with a median habitual dietary carbohydrate intake of 155 g/day, maternal fasting serum B-OHB levels ranged from 22.2 to 296.5 μmol/l (0.0222–0.297 mmol/l). While this is below 500 μmol/l or 0.5 mmol/l, which is the level considered to be normal, it is within the range of levels that has previously been associated with reduced childhood IQ (70–250 μmol/l or 0.07–0.25 mmol/l) [We found that in pregnant women with overweight and obesity, routine daily carbohydrate consumption from early pregnancy through to 28 weeks’ gestation was not correlated with fasting serum B-OHB levels. This finding remained after exclusion of women with GDM, suggesting the lack of correlation is not related to women’s carbohydrate tolerance. In addition, women with habitual low carbohydrate intake did not have higher serum B-OHB levels than those with high carbohydrate intake. This is despite the mean carbohydrate intake in the LC group being 119 g/day and hence 30% below the recommendation of ≥175 g/day, and the mean carbohydrate intake in the HC group being 207 g/day and 18% above the recommended minimum intake. The variability in fasting serum B-OHB levels cannot therefore be explained by habitual carbohydrate intake.Amongst women with normoglycaemic pregnancies, those with higher serum B-OHB levels had lower fasting insulin and C-peptide levels. One explanation for this could be the inhibitory effect that insulin has on ketone production. The production of ketones involves two processes: first lipolysis, where lipids (mostly from adipose tissue stores) are broken down into fatty acids and glycerol, and second ketogenesis, where fatty acids are converted to ketones in the liver. Lipolysis is inhibited by insulin through inhibition of intracellular hormone-sensitive lipase [This is the first study to evaluate the relationship between maternal ketone levels and habitual daily carbohydrate intake. Most previous studies looking at the effects of low-carbohydrate diets in pregnancy have been trials evaluating the effectiveness of carbohydrate restriction for glucose management in women with GDM. In one study, women on a low-carbohydrate diet (carbohydrate intake comprising less than 42% of total daily energy) had lower need for pharmacological treatment of their GDM and a lower incidence of large for gestational age (LGA) infants than women on a high-carbohydrate diet (carbohydrate intake greater than 45% of total daily energy) [Limitations of this study include the fact that dietary data was self-reported in a questionnaire, meaning there is a risk of recall bias. Given that the median weight gain in our cohort was 8 kg (4.7–12 kg) but the reported median energy intake is only 6136 kJ/day (4918–7489), it is very likely that the participants were underreporting their energy intake, as this is common in pregnant women with obesity [While women were advised to fast for 9.5–12 h, the exact length of each woman’s fast prior to serum blood collection was not recorded. Serum B-OHB levels rise in pregnancy during fasting, with significant differences in serum B-OHB between pregnant and non-pregnant women first seen at 16 h into an overnight fast [Our finding that habitual daily carbohydrate intake is not correlated with fasting serum B-OHB levels in pregnancy is important. Current guidelines which recommend that women should consume a minimum of 175 g/day of carbohydrate are based on calculations rather than on clinical evidence. This is the first study to assess whether daily carbohydrate intake affects serum B-OHB levels. Our findings challenge the current dietary recommendations that women should consume a minimum amount of carbohydrate every day, since only a single participant of the 34 who consumed the recommended amount of carbohydrate had undetectable B-OHB levels whereas the other 33 had detectable levels (Fig. Representation of the B-OHB levels according to carbohydrate intake in the study cohort. The recommended daily carbohydrate intake of ≥175 g/day, covering 97.5% of the estimated daily needs of the maternal and fetal brain consumption, and the estimated mean requirements of 135 g/day, covering the maternal and fetal brain needs of 50% of the population, are indicated by the vertical bars. The shaded area represents the desired carbohydrate intake and B-OHB levels