Abstract: © The Author(s) 2025. Background: Precision prevention involves tailoring interventions to the unique characteristics of a group or individual to maximize their effectiveness. In this study, we examined the role of participant characteristics in the effectiveness of lifestyle interventions to optimize gestational weight gain (GWG). Methods: We searched Medline, Embase, and PubMed, from inception up to March 2025, to identify randomized and non-randomized controlled trials of lifestyle interventions (diet, physical activity, or combined) commencing before or during pregnancy. Participant characteristics, including age, race/ethnicity, body mass index (BMI), employment status, fasting low- and high-density lipoprotein cholesterol (HDL-C) were assessed. Mean differences (MD) in GWG were pooled using the random-effect model. Meta-regression and subgroup analysis were conducted by participant characteristics (e.g., BMI). Results: A total of 86 studies with 28,270 participants were included in this systematic review and meta-analysis. All lifestyle intervention types significantly reduced GWG. Combined lifestyle interventions initiated at first (MD −0.68; 95% confidence interval [CI]: −1.28, −0.07) and early second (13–17 weeks) trimester (MD −0.83; 95% CI: −1.46, −0.20) provide better effectiveness in optimizing GWG. Diet-only interventions significantly reduced GWG only in participants with normal BMI (MD −1.33 kg; CI: −1.75, −1.91) compared to the other BMI categories. Combined diet and physical activity interventions reduce excessive GWG in women with higher baseline HDL-C (β −0.04; 95% CI −0.06, −0.01). Conclusions: Lifestyle interventions reduced excessive GWG, with possible differential effects by intervention initiation time, BMI, and HDL-C. Future studies should consider physiological as well as social characteristics, in line with a holistic framework for precision medicine.
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