BACKGROUND: This report details the effect of LIFE-Mom's multicomponent lifestyle interventions on physical activity (PA) and inactivity time across pregnancy (2nd and 3rd trimesters) and their effect on gestational weight gain (GWG) and maternal/neonatal outcomes, a pre-specified secondary analysis. METHODS: Pregnant people with BMI >= 25 kg/m2 were randomized to lifestyle interventions with dietary and PA counseling or standard care. PA and inactivity time measured by accelerometry and metabolic and inflammatory biomarkers measured in fasting blood are reported in 522 pregnant people at baseline and end of pregnancy. Generalized linear models with and without covariates were used to evaluate group differences (interventionversus control) and, separately, time differences (total sample with both groups combined). RESULTS: Although there were statistically significant differences in vigorous activity between the intervention and control group (p = 0.024), there were no clinically meaningful differences in PA. In the combined sample, moderate to vigorous PA (MVPA) significantly decreased across pregnancy (mean +/- SD: 72.9 +/- 29.1 min/day versus 63.9 +/- 28.1 min/day; p < 0.0001), and inactivity time increased (617.5 min/day (573.5 to 659.6) versus 630.4 min/day (56.7 to 679.9); p < 0.0001). Increased inactivity time was associated with a less favorable maternal milieu (biomarker Z-scores) for pro-inflammatory (0.2 +/- 0.1; p = 0.003) and cardiometabolic markers (0.1 +/- 0.07; p = 0.030). CONCLUSIONS: Physical activity declined over the course of pregnancy, though the intervention group experienced a smaller reduction in activity levels. Our results linked increased inactivity time to maternal metabolic dysregulation and inflammation. Further research is needed to determine if intensive interventions reducing inactivity can improve maternal health and weight outcomes in pregnant people with overweight and obesity. TRIAL REGISTRATION: NCT01545934, NCT01616147, NCT01771133, NCT01631747, NCT01768793, NCT01610752, and NCT01812694.

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