OBJECTIVE: The maternal metabolic environment in early pregnancy can influence fetal growth trajectories. Our objective was to identify interventions initiated in early pregnancy (< 20 weeks gestation) in pregnant individuals with risk factors for hyperglycemia and report their impact on primary (neonatal adiposity, small for gestational age, large for gestational age, macrosomia) and secondary outcomes (gestational weight gain, maternal hypertensive disorder, birth injury, NICU admission, preterm delivery, emergency cesarean section). DATA SOURCES: We searched Cochrane Central database, Medline, Embase, CINAHL databases, and clinicaltrials.gov (September 2024) for clinical trials published between 2009 and 2024. Search terms included the key words early OR during OR first trimester OR second trimester AND gestation OR pregnancy OR prenatal care AND insulin resistance OR metabolic health OR diabet* OR body composition OR obes* OR weight gain OR gestational diabetes OR hyperglycemia OR metabolic syndrome AND clinical trial. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials (RCTs) and other trials reporting interventions initiated before 20 weeks gestation in participants with singleton pregnancies at risk for hyperglycemia (overweight and/or obesity, history of type 2 diabetes, and/or history of GDM) that reported at least one primary outcome were included. Studies had to be conducted with humans in high income countries as defined by the World Bank, written in English. STUDY APPRAISAL AND SYNTHESIS METHODS: We used the Downs and Black checklist to evaluate the methodological quality and risk. Data was extracted independently and any questions were resolved through group discussion. Interventions were categorized and synthesized by type. RESULTS: 21,924 records were identified and 70 full-text articles met inclusion criteria. 65 articles were RCTs. Eight intervention categories were identified: diet only, physical activity or exercise only, diet and physical activity or exercise combined, lifestyle counseling, supplements, pharmaceuticals, early GDM screening, and mixed interventions. Only 12 studies reported statistically significant effects on primary neonatal outcomes. CONCLUSIONS: Interventions initiated in early pregnancy (< 20 weeks) among pregnant individuals at risk for hyperglycemia that include one or more of the following strategies can reduce risk of excess neonatal adiposity, macrosomia, large for gestational age and small for gestational age neonates: goal-setting and motivational strategies to improve diet and increase physical activity through individual and group sessions; lifestyle coaching that included behavioral techniques designed to empower participants by fostering autonomy in a supportive environment; structured group exercise classes three times per week; and personalized dietary recommendations.

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