Table 2.

Design of One Potential Clinical Trial to Test Whether Promoting Cardiovascular Health Pre-Pregnancy Improves Outcomes in Pregnant and Postpartum Individuals and Offspring – Using the PICOTS Framework

P opulation	Pregnancy-capable individuals open to or actively seeking to become pregnant, with consideration for the following Ages: 25–44 years old CVH metrics: with overweight or obesity and intermediate levels for blood pressure, glucose, and cholesterol who do not currently meet criteria for pharmacotherapy Exclusions: history of infertility Inclusive of transgender and gender diverse individuals Oversample individuals with adverse social determinants of health (e.g., household income at greater than 200% of the federal poverty level, receiving WIC support) Oversample racial and ethnic minoritized groups (e.g., Black, Hispanic, and Asian American/Native Hawaiian/Pacific Islander individuals) Oversample individuals with prior adverse pregnancy outcomes to further increase study power
I ntervention	Moderate-intensity lifestyle intervention targeting multiple CVH factors (diet, physical activity, sleep) Adjunctive pharmacotherapy at CV risk factor levels below current standard of care for pharmacologic intervention: BP >120/80 Fasting blood glucose >100 mg/dL or HbA1c >5.7% Non-HDL cholesterol >160 mg/dl or total cholesterol/HDL ratio >5
C omparison	Standard of care, including provision of relevant health information on promoting CVH and referral to clinicians if any abnormal CVH metrics
O utcome	Co-Primary Outcomes Maternal composite outcome consisting of: Preeclampsia Gestational hypertension Gestational diabetes Severe maternal morbidity (e.g., acute myocardial infarction, cardiac arrest, heart failure) Pregnancy-related mortality Offspring composite outcome consisting of: Fetal death Preterm birth Small for gestational age Secondary Outcomes Individual components of the above composite outcomes Rigorous data collection and reporting of subgroup analyses based on sociodemographic factors (e.g., race and ethnicity, gender identity)
T iming	5-year trial phase with 4 years of enrollment and an additional year of follow-up (average follow up 3 years, with a range of 1–5 years).
S etting	Pragmatic trial that leverages healthcare systems such as Federally Qualified Health Centers, Indian Health Services clinics, and HMOs, and/or large research networks

BP blood pressure; CVH cardiovascular health; HDL high density lipoprotein; HMOs Health Maintenance Organizations; WIC supplemental nutrition program for women, infants, and children