Background: Pregnancy metabolic disruption is believed to be enhanced in obese women and lead to adverse outcomes in them and their offspring. The UK Pregnancies Better Eating and Activity Trial (UPBEAT), a randomised controlled trial of a lifestyle intervention in obese pregnant women, has already been shown to improve diet and physical activity. We used UPBEAT to determine (a) the magnitude of change in metabolic profiles in obese pregnant women and (b) the impact of a lifestyle intervention that successfully improved diet and physical activity on these profiles. Methods: Detailed targeted metabolic profiling, with quantification of 158 metabolic features (129 lipid measures, 9 glycerides and phospholipids, and 20 low-molecular weight metabolites) was completed on three occasions (~17-, 28- and 35-weeks of gestation) in the UPBEAT participants using NMR. Random intercept and random slope models were used to quantify metabolite changes in obese women using the control (usual care) group only (N = 577). The effect of the intervention was determined by comparing rates of metabolite change between those randomised to intervention and usual care, using intention to treat analyses (N = 1158). Results: There were adverse changes across pregnancy in most lipoprotein subclasses, lipids, glycerides, phospholipids, several fatty acids and glucose. All extremely large, very large, large, medium, small and very small VLDL particles increased by 2 to 3 standard deviation units (SD), with IDL, and large, medium and small LDL particles increasing by 1 to 2SD, between 16- and 36-weeks. Triglycerides increased by 3 to 4SD and glucose increased by 2SD, with more modest changes in other metabolites. The intervention reduced the rate of increase in extremely large, very large, large and medium VLDL, in particular those containing triglycerides. Triglyceride to phosphoglyceride ratio was reduced and there were improvements in fatty acid profiles (increases in the proportion of all fatty acids that were linoleic, omega-6 and polyunsaturated and decreases in the proportion of saturated). Conclusion: Systemic metabolism is markedly disrupted in obese pregnant women, but a lifestyle intervention that improved their diet and physical activity has beneficial effects on some of these profiles; these effects might have long-term benefit. Clinical trial registration ID # ISRCTN89971375.

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