The effect of a lifestyle intervention in obese pregnant women on gestational metabolic profiles: findings from the UK Pregnancies Better Eating and Activity Trial (UPBEAT) randomised controlled trial

Abstract

Background: Pregnancy is associated with widespread change in metabolism, which may be more marked in obese women. Whether lifestyle interventions in obese pregnant women improve pregnancy metabolic profiles remains unknown. Our objectives were to determine the magnitude of change in metabolic measures during obese pregnancy, to indirectly compare these to similar profiles in a general pregnant population, and to determine the impact of a lifestyle intervention on change in metabolic measures in obese pregnant women.

Methods: Data from a randomised controlled trial of 1158 obese (BMI ≥ 30 kg/m²) pregnant women recruited from six UK inner-city obstetric departments were used. Women were randomised to either the UPBEAT intervention, a tailored complex lifestyle intervention focused on improving diet and physical activity, or standard antenatal care (control group). UPBEAT has been shown to improve diet and physical activity during pregnancy and up to 6-months postnatally in obese women and to reduce offspring adiposity at 6-months; it did not affect risk of gestational diabetes (the primary outcome). Change in the concentrations of 158 metabolic measures (129 lipids, 9 glycerides and phospholipids, and 20 low-molecular weight metabolites), quantified three times during pregnancy, were compared using multilevel models. The role of chance was assessed with a false discovery rate of 5% adjusted p values.

Results: All very low-density lipoprotein (VLDL) particles increased by 1.5-3 standard deviation units (SD) whereas intermediate density lipoprotein and specific (large, medium and small) LDL particles increased by 1-2 SD, between 16 and 36 weeks' gestation. Triglycerides increased by 2-3 SD, with more modest changes in other metabolites. Indirect comparisons suggest that the magnitudes of change across pregnancy in these obese women were 2- to 3-fold larger than in unselected women (n = 4260 in cross-sectional and 583 in longitudinal analyses) from an independent, previously published, study. The intervention reduced the rate of increase in extremely large, very large, large and medium VLDL particles, particularly those containing triglycerides.

Conclusion: There are marked changes in lipids and lipoproteins and more modest changes in other metabolites across pregnancy in obese women, with some evidence that this is more marked than in unselected pregnant women. The UPBEAT lifestyle intervention may contribute to a healthier metabolic profile in obese pregnant women, but our results require replication.

Trial registration: UPBEAT was registered with Current Controlled Trials, ISRCTN89971375 , on July 23, 2008 (prior to recruitment).

Keywords: Pregnancy; RCT; lifestyle intervention; metabolomics; obesity.

Fig. 1

Participant flow

Fig. 2

Mean change in metabolic measures between 16 and 36 weeks of gestation in obese pregnant women receiving standard antenatal care (n = 577). Mean increase in standard deviation units for all metabolites that (a, b) increase or (c) decrease across pregnancy. a Mean increase in all (extremely large, very large, large, medium, small and very small) VLDL particle concentrations; all IDL particle concentrations; all (large, medium and small) LDL particle concentrations. b Mean increase in some (those that increased across pregnancy; very large, large, medium and small) HDL particle concentrations; most cholesterols; all glycerides and phospholipids; both apolipoproteins; all glycolysis-related metabolites; those amino acids, ketone bodies, fluid balance and inflammatory markers that increased across pregnancy. c Mean decrease in most (large, medium and small) HDL particle concentrations; HDL cholesterol; degree of unsaturation of fatty acids, the percentage of total fatty acids that were docosahexaenoic acid, omega-3, omega-6, and polyunsaturated fatty acids; some amino acids; glycerol; and albumin. Circles are the mean change in SD units for each metabolic measure between 16 and 36 weeks’ gestation, with the horizontal lines representing the 95% CIs for this change. Numeric results of the absolute change between 16 and 36 weeks’ gestation for each trait in SD and original units for control women only are shown in Additional file 1: Table S3. The mean value of each trait at 16 weeks and rate of change per 4 weeks between 16 and 36 weeks’ gestation for all women (n = 1158), with adjustment for randomised group, are shown in Additional file 1: Table S4. HDL high-density lipoprotein, IDL intermediate-density lipoprotein, LDL low-density lipoprotein, SD standard deviation, VLDL very low-density lipoprotein

Fig. 3

Effect of the UPBEAT intervention (difference in mean rate of change for each metabolic measure in SD units per 4 weeks of gestational age comparing those in the intervention arm to those receiving standard care) on mean rate of change in metabolic traits in SD units per 4 weeks (n = 1158). a The effect of the intervention for all (extremely large, very large, large, medium, small and very small) VLDL particle concentrations; all IDL particle concentrations; all (large, medium and small) LDL particle concentrations. b The effect of the intervention for all (very large, large, medium and small) HDL particle concentrations; lipoprotein particle sizes; all cholesterols; all glycerides and phospholipids; apolipoproteins; all fatty acids (absolute concentrations and percentages of total fatty acids). c The effect of the intervention for glycolysis-related metabolites; amino acids; ketone bodies; fluid balance and inflammatory markers. Circles are the difference in mean rate of change for each metabolic measure in SD units per 4 weeks of gestation comparing those randomised to intervention to those randomised to control (usual antenatal care) and horizontal lines are the 95% CIs for these differences. SDs were calculated from women in the control group. Results for the differences by randomised group for all traits in the original units (e.g. mmol/L) together with absolute p values are shown in Additional file 1: Table S5. * Results statistically significant at the conventional p < 0.05 after controlling for the false discovery rate. HDL high-density lipoprotein, IDL intermediate-density lipoprotein, LDL low-density lipoprotein, SD standard deviation, VLDL very low-density lipoprotein