Optimizing Pre-Pregnancy Cardiovascular Health to Improve Outcomes in Pregnant and Postpartum Individuals and Offspring: A Scientific Statement from the American Heart Association

Abstract

This statement summarizes the available preclinical, epidemiological, and clinical trial evidence that support the contributions of pre-pregnancy (and inter-pregnancy) cardiovascular health to risk of adverse pregnancy outcomes and cardiovascular disease in the birthing individual and offspring. Unfavorable cardiovascular health, as originally defined by the American Heart Association in 2010 and revised in 2022, is prevalent in reproductive-aged individuals. Significant disparities exist in ideal cardiovascular health by race and ethnicity, socioeconomic status, and geography. Because the biologic processes leading to adverse pregnancy outcomes begin prior to conception, interventions focused only during pregnancy may have limited impact on both the pregnant individual and offspring. Therefore, focused attention on pre-pregnancy as a critical life period for optimization of cardiovascular health is needed. This statement applies a life course and intergenerational framework to measure, modify, and monitor pre-pregnancy cardiovascular health. All clinicians who interact with pregnancy-capable individuals can emphasize optimization of cardiovascular health beginning early in childhood. Clinical trials are needed to investigate pre-pregnancy interventions to comprehensively target cardiovascular health. Beyond individual-level interventions, community-level interventions must include and engage key stakeholders (e.g., community leaders, birthing individuals, families) and target a broad range of antecedent psychosocial and social determinants. In addition, policy-level changes are needed to dismantle structural racism and to improve equitable and high-quality healthcare delivery, as many reproductive-aged individuals have inadequate, fragmented healthcare before and after pregnancy as well as between pregnancies (inter-pregnancy). Leveraging these opportunities to target cardiovascular health has potential to improve health across the life course and for subsequent generations.

Introduction

There is a growing burden of cardiovascular-related morbidity and mortality in pregnant and postpartum individuals in the United States (US).¹ Cardiovascular disease (CVD) is the leading cause of death during pregnancy and the postpartum period and represents 26.5% of pregnancy-related deaths.² This topic was the focus of a 2021American Heart Association (AHA) Policy Statement: Call to Action: Maternal Health and Saving Mothers, which outlined multi-level opportunities aimed at improving health literacy, public awareness, cultural competency, and bias reduction in optimizing maternal cardiovascular health (CVH).³

Currently, nearly 1 in 5 births is complicated by an adverse pregnancy outcome (APO), which includes hypertensive disorders of pregnancy (HDP), preterm birth (PTB), small-for-gestational age (SGA) birth, and gestational diabetes mellitus (GDM).^4,5 Over the past decade, rates of APOs have increased significantly, with a near doubling in rates of HDP.^4,5 There are persistent disparities with non-Hispanic Black individuals significantly more likely to experience APOs.⁶ Available data demonstrate a strong association between APOs and risk for subsequent CVD, which was detailed in a 2021AHA Scientific Statement: Adverse Pregnancy Outcomes and Cardiovascular Disease Risk.⁷ Among individuals who experience APOs, emerging data also identify higher risk of long-term kidney disease, which is itself an important risk factor for CVD.⁸ While the pathophysiology of pregnancy-related complications is complex and likely multifactorial in etiology, emerging data suggest these complications have, at least in part, pre-pregnancy origins. Thus, the pre-pregnancy period may be a critical window during which interventions have a great potential for benefit in birthing individuals and their offspring. Additionally, interventions in the postpartum/inter-pregnancy period may offer a unique opportunity to target the pre-pregnancy period before a subsequent pregnancy.

In this AHA Scientific Statement, we critically review the evidence for pre-pregnancy CVH as a key target to improve health of the birthing individual and offspring over the life course (Figure 1). We highlight the importance of a life course and inter-generational framework to assess and intervene on CVH. We offer considerations for multi-level interventions (e.g., individual, community, and societal) to equitably improve pre-pregnancy CVH. We anchor this discussion on the AHA’s construct of CVH. This was originally defined as the “Life’s Simple 7” in 2010, which integrates seven health factors (diet, physical activity, nonsmoking, body mass index, blood pressure, lipids, and glycemia), and has since been revised to the “Life’s Essential 8^™” incorporating sleep health as the 8^th metric (Table 1).^9,10 CVH is oriented on promotion of wellness with higher CVH scores (i.e. scores reflecting better health) associated with lower risk for a multitude of downstream cardiovascular and non-cardiovascular outcomes in non-pregnant and pregnant individuals.¹¹ The clinical relevance of the CVH construct as a key target in birthing individuals was recently highlighted in a joint Presidential Advisory from the AHA and the American College of Obstetricians and Gynecologists and highlights the pivotal role of primary care clinicians, pediatricians, obstetricians, and cardiologists in optimizing CVH of pregnancy-capable individuals.¹²

Figure 1.

The Intergenerational Life Cycle of Cardiovascular Health and its Foundational Determinants

Table 1.

Cardiovascular Health Metrics and Scoring as Originally Defined in 2010 and Revised in 2022 for Non-Pregnant Adults by the American Heart Association

CARDIOVASCULAR HEALTH CONSTRUCT DEFINITION: 20108
	Ideal=2 Points	Intermediate=1 Point	Poor=0 Points
Diet, Healthy Eating Index-2015 score	80 – 100	40 – 79	0 – 39
Physical Activity, minutes per week moderate-to-vigorous leisure activity	≥150	>0 but <150	0
Smoking	Never or quit >12 months ago	Former, quit ≤12 months ago	Current
Body Mass Index, kg/m2	<25	25 – 29.9	≥30
Blood Pressure, mm Hg	<120/<80	Systolic 120–139 or diastolic 80–89 and not on blood pressure lowering medications	Systolic ≥140 or diastolic ≥90
Total Cholesterol, mg/dL	<200 without medication	200–239 or treated to <200	≥240
Fasting Glucose, mg/dL	<100 without medication	100–125 and not on glucose lowering medications	≥126
CARDIOVASCULAR HEALTH CONSTRUCT DEFINITION: 20229
	Ideal = 100 points	Suboptimal <100 points
Sleep health or average hours of sleep/night	7-<9	70 points: 6-<7 20 points: 4-<5 0 points: <4
Diet, Healthy Eating Index-2015 score or DASH (MEPA)	≥95th percentile (MEPA score 15–16)	80 points: 75th-94th percentile (MEPA 12–14) 25 points: 25th-49th percentile (MEPA 4–7) 0 points: 1st-24th percentile (MEPA 0–3)
Physical Activity, minutes per week moderate-to-vigorous leisure activity	≥150	80 points: 90–119 20 points: 1–29 0 points: 0
Smoking	Never smoker and no secondhand exposure in home	75 points: Former smoker, quit ≥5y 20 points: Former smoker, quit<1y, or inhaled NDS 0 current smoker Subtract 20 points for living with active indoor smoker in home (unless score is 0)
Body Mass Index, kg/m 2	<25	70 points: 25.0–29.9 30 points: 30.0–34.9 0 points: ≥40.0
Blood Pressure, mm Hg	<120/<80	75 points: 120–129/<80 25 points: 140–159 or 90–99 0 points: ≥160 or ≥100 Subtract 20 points if treated level
Non-HDL Cholesterol, mg/dL	<130	60 points: 130–159 20 points: 190–219 0 points: ≥220 Subtract 20 points if treated level
Fasting Glucose, mg/dL (HbA1c, %)	<100 (<5.7%) No history of diabetes	60 points: 100–125 (5.7–6.4%) 20 points: Diabetes (8.0–8.9%) 0 points: Diabetes (≥10.0%)

⁸Lloyd-Jones DM, Hong Y, Labarthe D, Mozaffarian D, Appel LJ, Van Horn L, Greenlund K, Daniels S, Nichol G, Tomaselli GF. Defining and setting national goals for cardiovascular health promotion and disease reduction: the American Heart Association’s strategic Impact Goal through 2020 and beyond. Circulation. 2010;121:586–613.

⁹Lloyd-Jones DM, Allen NB, Anderson CA, Black T, Brewer LC, Foraker RE, Grandner MA, Lavretsky H, Perak AM, Sharma G. Life’s Essential 8: Updating and Enhancing the American Heart Association’s Construct of Cardiovascular Health: A Presidential Advisory From the American Heart Association. Circulation. 2022:10.1161/CIR.0000000000001078.

For the purposes of this statement, we refer to individuals as “females” or “males” based on sex assigned at birth and “women” or “men” based on presumed gender identity, when these terms have been used in prior literature. There remains a dearth of data on CVH and its relationship with APOs and CVD in individuals with diverse gender identities.

Current Status of CVH in Birthing Individuals in the US

As of 2020, there were an estimated 64.5 million reproductive-aged (ages 15–44 years) females in the US.¹³ Approximately 3.5–4 million live births occur in the US annually, and by age 40 to 44 years, an estimated 86% of females in the US have given birth at least once.¹⁴

Unfavorable CVH is prevalent in reproductive-aged young adults with very few people having ideal levels of all CVH metrics (<1%).^11,15 According to data from the National Health and Nutrition Examination Survey (2013–2016), the prevalence of having ideal levels in ≥5 of 7 CVH metrics (using the 2010 CVH scoring system) was 45.0% among adolescents aged 12 to 19 years, 31.6% among young adults aged 20 to 39 years, and 10.6% among adults aged 40 to 59 years.¹⁶ Sex-specific data suggest that CVH is slightly higher among females vs. males of reproductive age (e.g., for adults ≥20 years, 21.5% of females vs 18.4% of males have ≥5 of 7 CVH metrics ideal). Similar findings were reported in data from National Health and Nutrition Examination Survey 2013–2018 according to the revised 2022 CVH scoring system, with the mean CVH score (out of 100 possible points) in women of 68.1 (standard deviation [SD] 0.48) vs. men of 63.6 (SD 0.44). There are significant racial and ethnic disparities in CVH, with non-Hispanic Black females having lower mean CVH scores as well as worse values of most CVH metrics, including worse sleep quality, than women of other races and ethnicities.^17,18 Limited data are available for pre-pregnancy CVH in disaggregated Asian and Hispanic subgroups as well as American Indian and Alaskan Native individuals. This is particularly critical given high rates of maternal morbidity and mortality observed among American Indian and Alaskan Native individuals.¹⁹ As race and ethnicity are social constructs, these racial and ethnic differences have been attributed to differences in upstream social factors, such as education, income, and access to healthcare.¹¹ When examining individual CVH factors among reproductive-aged females, ~25% reported current smoking, ~40% had obesity, 9.3% hypertension, 4.5% diabetes, and up to 33% hyperlipidemia.^{11,15,20–22} Lack of awareness and control of CVD risk factors is an important problem in reproductive aged females; for example, of the 9.3% with hypertension and 4.5% with diabetes, approximately 17% and 30%, respectively, were unaware of these diagnoses, and about half did not achieve optimal blood pressure or glycemic control.²²

Maternal data on some CVH factors (pre-pregnancy body mass index, diabetes, hypertension, and smoking status based on a combination of self-recall and health records) are available from the National Center for Health Statistics for all live births in the US. Fewer than half of birthing individuals have favorable pre-pregnancy CVH (using an abbreviated CVH defined as absence of obesity, hypertension, diabetes, and smoking).²³ Further, pre-pregnancy CVH declined between 2011 to 2019 in all subgroups (race and ethnicity, geography, and socioeconomic status); lower CVH persisted among non-Hispanic Black females, pregnant individuals living in the South and Midwest US, and those with Medicaid insurance during pregnancy.^23,24 With regard to specific factors, fewer than 50% of birthing individuals in 2018 had a normal pre-pregnancy body mass index (18.5–24.9 kg/m²).^25,26 Levels of CVH metrics are highly correlated between pre-pregnancy and pregnancy.^15,27

Associations between Pre-Pregnancy CVH and APOs

Pre-pregnancy CVH and individual CVH metrics are associated with risk of APOs in many observational studies.^{11,25,28–37} Based on National Center for Health Statistics data, there is a consistent and graded association between worse pre-pregnancy CVH and APOs (PTB, SGA, and fetal death).²⁸ Adjusted relative risks for PTB with poor levels of pre-pregnancy CVH metrics in 1, 2, 3, or 4 metrics (overweight or obesity, diabetes, hypertension and smoking) were 1.15 (95% CI: 1.15, 1.16), 1.62 (1.61, 162), 2.85 (2.81, 2.90) and 3.89 (3.68, 4.10), respectively, compared with individuals with no poor pre-pregnancy CVH metrics.²⁸ Similar findings were observed in the multinational Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study, which found that lower CVH based on clinical factors at 28 weeks’ gestation was associated with higher risk of APOs (preeclampsia, SGA infant).³⁸

Among individual CVH metrics, pre-pregnancy dietary patterns are associated with risks for APOs with more healthy patterns associated with lower risk of GDM, PTB, SGA, and HDP.³⁹ Better pre-pregnancy fitness, assessed with a graded symptom-limited maximal exercise treadmill test, is associated with lower risk of GDM⁴⁰, and greater leisure-time physical activity at the beginning of pregnancy is also associated with lower risk for APOs.⁴¹ Obesity is also associated with APOs and estimated to have a population attributable fraction due to HDP of between 26.5%−30.3% in 2018 in the US.²⁵ In a meta-analysis, the odds ratio (OR) was 1.31 (95% CI, 1.11–1.53) for each 1 kg/m² increase in body mass index from the start of one pregnancy to the next associated with HDP.⁴² Pre-pregnancy blood pressure is associated with risk for HDP, and treatment of mild chronic hypertension starting in early pregnancy led to reduced risks for PTB, SGA, and preeclampsia in the recent Chronic Hypertension and Pregnancy (CHAP) trial.^43,44 Pre-pregnancy lipid levels (triglycerides, HDL-C) are associated with risk for GDM and HDP.⁴⁵ Pre-pregnancy glycemic status across the spectrum is associated with risk for large for gestational age, PTB, and HDP.^33,46 Poor sleep quality and duration are associated with adverse pregnancy outcomes, specifically GDM and HDP.^47,48 These data, which demonstrate a similar magnitude of associations between CVH and APOs across individual CVH metrics underscore the relevance of a strategy that comprehensively targets total CVH. Beyond the traditional CVH metrics, chronic kidney disease is an important risk factor for APOs and long-term CVD in birthing individuals.⁴⁹

Associations between Pre-Pregnancy CVH and Offspring Outcomes

Epidemiologic studies support the association between pre-pregnancy CVH in the birthing person and offspring health outcomes, broadly termed ‘the developmental origins of health and disease’.⁵⁰ As detailed above, pre-pregnancy CVH and individual CVH metrics are associated with risk for APOs; additionally, these APOs are associated with higher risks for premature CVD among exposed offspring.^14,51–56 As an example, PTB is associated with 53% higher adjusted hazards for premature ischemic heart disease by age 43 years in the offspring.⁵²

Longer-term studies are emerging to provide direct evidence for links between maternal pre-pregnancy CVH metrics and offspring CVD risk factors and even CVD events.^54,56–60 For example, pre-pregnancy type 2 diabetes was associated with an adjusted hazards ratio of 1.39 (1.23–1.57) for offspring premature CVD by age 40 years in a registry study.⁵⁶ No study has reported on maternal pre-pregnancy total CVH and offspring cardiovascular outcomes. While there are physiological changes to CVH metrics in pregnancy (e.g., increase in body mass index, glucose, lipids), data demonstrate that CVD risk factor levels measured pre-pregnancy were highly correlated with risk factor levels during pregnancy.²⁷ This suggests that associations between unfavorable CVH in pregnant individuals and in offspring may stem, at least in part, from the pre-pregnancy period.⁶¹ Of note, studies of maternal body mass index indicate that pre-pregnancy body mass index is more strongly associated with both APOs and offspring cardiovascular risk factors in adolescence compared with gestational weight gain.^34,35 However, whether the association between maternal CVH and offspring CVH is an epiphenomenon or the two are causally related requires further investigation.

Potential Pathophysiologic Mechanisms linking Pre-Pregnancy CVH and APOs

Several factors shed light on the potential pathophysiologic link between pre-pregnancy CVH and APOs. The periconceptional period before and after conception cover critical events: oocyte meiotic maturation, spermatozoa differentiation, fertilization, transition to the embryonic genome, resumption of mitotic cell cycles in the newly formed zygote, initial morphogenesis, and implantation. During this brief window, the genome is globally reprogrammed via extensive epigenetic reorganization, which determines lineage-specific gene expression—including divergence of placental and embryonic cell lineages—and establishment of metabolic controls for energy supply and growth.⁵⁰ In animal experiments, epigenetic modifications link the metabolic status of the pregnant animal to gene expression programs in the developing embryo and placenta.^62,63 As an example, in mice with obesity, the follicular fluid and oocyte are lipid-enriched, resulting in endoplasmic reticulum stress, protein misfolding, and increased mitochondrial respiration and reactive oxygen species generation, with dramatic implications for energy metabolism in the oocyte and subsequently the zygote.^64–66

Although animal and in vitro experiments provide much of the mechanistic data linking pre-pregnancy CVH metrics with maternal and offspring outcomes, parallel clinical observations align with these proposed periconceptional mechanisms. For example, in mice, transfer of one-cell zygotes from diabetic dams to control recipients demonstrates that exposures around fertilization are sufficient to permanently program postnatal phenotype; this experimental finding is mirrored by the clinical observation that in humans with diabetes, glycemic control must be achieved pre-pregnancy to reduce the risk of congenital anomalies and adverse neonatal outcomes.⁶⁷

The placenta, which develops soon after fertilization and implantation occur, is a major focus of studies underlying mechanisms of APOs. Placental malperfusion is central to a cascade of vascular injury in many APOs, is secondary to inappropriate vascular remodeling of uterine spinal arteries, and begins long before clinical manifestations of APOs are apparent.⁶⁸ This abnormal placental development has been proposed to be affected by the maternal environment, such as presence of pre-pregnancy CVD risk factors, with potential mechanisms related to angiogenesis and inflammation.^69–72 As such, APOs may reflect the unmasking of pre-existing CVD risk in response to the physiologic stress of pregnancy. Indeed, markers of vascular dysfunction (e.g., decreased arterial compliance, retinal microvascular constriction, diastolic dysfunction) before or in early pregnancy are associated with higher risk of APOs.^73–75 While not conclusive, these studies add to the evidence base that unfavorable pre-pregnancy CVH temporally precedes and contributes to APO risk. Advancing our mechanistic understanding of the underlying pathophysiology can inform the design of potential interventions. Lastly, establishing whether CVH and APOs are causally related is foundationally important to decrease the risk of APOs and future CVD by intervening on CVH.⁷⁶

Evidence for Pre-Pregnancy and Inter-Pregnancy CVH Interventions

There are currently no large, randomized trials with sufficient power to test whether improving CVH before pregnancy will improve maternal and offspring outcomes (e.g., reduced frequency of APOs, severe maternal morbidity, maternal mortality). Available data rely on studies that have intervened on single risk factors, such as weight loss to reduce GDM risk, rather than comprehensive CVH promotion.⁷⁷ Randomized controlled trials that have focused on pre-pregnancy behavioral interventions have improved individual CVH metrics such as diet, smoking cessation, or body mass index prior to pregnancy.^78–84 In a cohort study of individuals with severe obesity, bariatric surgery prior to pregnancy was associated with substantially lower risks of GDM (OR 0.21 [0.12–0.36]) and HDP (OR 0.38 [0.27–0.53]) but higher risks of SGA (OR 2.18 [1.41–3.38].⁸⁵

Data are even more limited for longer-term maternal and offspring outcomes after pre-pregnancy interventions. Among two studies with 6-year postpartum follow-up after a randomized pre-pregnancy lifestyle intervention for individuals with obesity and infertility prior to fertility care, one found that mothers who successfully lost weight with the intervention had better cardiometabolic health 6 years postpartum compared with controls, and the other found that children of individuals who underwent the lifestyle intervention had better left ventricular structure and function.^86,87 However, data are limited by small sample sizes, attrition bias, and conflicting findings across studies for better CVH in offspring.^87,88

Postpartum interventions, especially those that result in weight loss, have been shown to improve CVH, but the consequences of these interventions on CVD outcomes in subsequent pregnancy are limited but could inform similar pre-pregnancy interventions. Among women with a history of preeclampsia, small trials focused on behavior changes have demonstrated improvement in physical activity postpartum.^89–91 Among women with a history of GDM, lifestyle interventions conducted in the year after delivery that targeted overweight/obesity resulted in modest weight loss, increased physical activity, and improved glycemic measures.⁹² Healthcare delivery strategies, such as transitional clinics for postpartum care after APOs, patient navigation, and integration of maternal care at pediatric visits have been suggested as potential opportunities to improve health, but have not yet been rigorously evaluated for their effects on CVH outcomes.^93–95

A Need for Clinical Trials Targeting Pre-Pregnancy CVH

The American College of Obstetricians and Gynecologists strongly advocates the assessment and promotion of preconception health behaviors and factors in persons of reproductive age.⁹⁶ However, as just reviewed, intervening on CVH prior to conception remains a critical research gap. If a trial promoting CVH yielded positive results in mitigating APOs and improving maternal and offspring outcomes, it could be practice changing and provide needed impetus for clinicians and reproductive-aged individuals to be more cognizant about achieving better CVH. At the population-level, primordial prevention with maintenance of ideal CVH is an overarching goal throughout the life course. Specifically, in the context of pre-pregnancy CVH, adolescence (prior to a first pregnancy) marks a critical transition in the life course when health behaviors are becoming more firmly established and distinct CVH trajectories are identifiable.⁹⁷

Key Considerations for Trial Design Focused on Clinical Outcomes

Multiple elements need to be considered in designing a trial that tests whether interventions initiated prior to pregnancy aimed at holistically promoting CVH will modify maternal and offspring outcomes. First, careful planning will be needed to recruit and retain a large, diverse sample population. Particular attention will need to be given to developing culturally cognizant strategies and to oversample individuals from groups who are underrepresented in clinical trials and who bear a disproportionate burden of unfavorable CVH, APOs and CVD. These groups include populations that are minoritized based on racial and ethnic identity, sexual and gender identity, and individuals with adverse social determinants of health. Within racial and ethnic groups, disaggregation of larger categories, such as Asian (e.g., Chinese, Filipina, Japanese, Korean, Vietnamese, Asian Indian) and Hispanic (e.g., Mexican, Puerto Rican, Central and South American) is necessary given the heterogeneity across subgroups. Rigorous collection of self-reported race and ethnicity, sexual and gender identity, and social determinants of health, along with strategies to ensure diversity and inclusion in recruitment will be important to understand generalizability of an intervention’s treatment effect regarding APOs and offspring outcomes in different populations.

Second, selection of inclusion criteria may need to focus on subsets of individuals who are capable of, open to, or actively seeking to become pregnant. To adequately power a study, it may be prudent to enrich the trial sample with a population at higher risk. For example, a trial could focus only on one metric, such as with overweight or obesity, given that this is the most prevalent risk factor for APOs in pregnant individuals. However, risk factors often co-occur in birthing and pregnant individuals and associations of maternal CVH with APOs and offspring CVH are not driven by any single CVH metric.^15,61 Therefore, inclusion criteria should consider selection of individuals based on unfavorable levels of multiple CVH metrics. A trial could be designed that exclude those at highest risk who already meet medical treatment thresholds for hypertension, diabetes, or hyperlipidemia, thereby focusing on the population with intermediate risk factor levels (elevated blood pressure not characterized as hypertension, prediabetes, borderline dyslipidemia) for whom interventions guidelines are especially lacking.

Third, interventions tested should include multiple components that include a focus on health behavior changes (e.g., diet, exercise) with or without pharmacotherapies based on options known to be safe during pregnancy. For example, while statins have long been avoided in pregnancy, there is growing consensus that some agents (i.e., hydrophilic statins, such as pravastatin) may be safe and may reduce risk of APOs.^98,99 However, it is not known whether particular components of CVH are most salient to focus upon in order to improve pregnancy and long-term outcomes. To inform optimal trial design, foundational work, including feasibility studies to test recruitment approaches, retention strategies, and acceptability of interventions, will be needed. One hypothetical trial is outlined using the “PICOTS” framework in Table 2 and is meant as a single example for what could be considered.

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

Targeting Stress to Promote CVH

Psychological health, stress, and resilience are inextricably linked with CVH and are identified as foundational determinants in optimizing CVH by the AHA.¹⁰ This is based on robust evidence of the association between stress and health outcomes, which include APOs and CVD.^100,101 Racism is a structural driver of disproportionate burden of psychosocial stress, and racial and ethnic minoritized women have different life experiences, such as repeated episodes of discrimination, which are associated with unfavorable CVH and risk of APOs, compared with White women. Chronic exposures to stress cumulatively over the life course leads to weathering, increased allostatic load (i.e., cumulative biologic stress) and impaired health.^102–104 One coping mechanism among Black women, named the “Superwoman schema”¹⁰⁵ because of the need to display strength in the face of chronic adversity, may also negatively impact maternal health outcomes.^106,107 Culturally responsive stress reduction and mindfulness-based interventions^108–111 that are sensitive to systemic barriers may offer a means to buffer stress and reduce maladaptive coping. Interventions targeting stress in the pre-pregnancy period to improve maternal health outcomes is a critical evidence gap and should be considered in the context of multi-level policy changes that simultaneously address structural and systemic barriers to optimal health.

Digital Technologies to Promote CVH

Given that adolescents and young adults are frequent users of digital technologies (e.g., smartphones, social media, mobile apps), leveraging these tools to deliver counseling could be an effective method to promote pre-pregnancy CVH.¹¹² Digital health interventions may offer increased accessibility to support socioeconomically disadvantaged individuals, who often have more barriers to healthcare access and in-person visits. The integration of digital, face-to-face and telephone interactions with healthcare teams may increase engagement with healthy behavior change interventions for sustainability and long-term impact.¹¹² In one study, a health information tool was used to screen for 102 health risks and deliver tailored pre-pregnancy counseling to empower high-risk Black individuals toward improving pre-pregnancy health across a variety of domains, including emotional and mental health, nutrition and activity, and substance use.^83,84 The tool included a conversational agent, “Gabby”, who provided culturally sensitive and empathetic pre-pregnancy risk assessment and increased the proportion of individuals engaged in behavior change through person-centered decision making and goal setting. Social marketing campaigns through media outlets have shown promise in increasing awareness of the importance of pre-pregnancy health and existing maternal health outcomes disparities.^107,113 Further adaptation of evidence-based mobile health (mHealth) lifestyle interventions promoting ideal CVH^107,113 to focus on pre-pregnancy health should also be studied.

Community-Engaged Design and Implementation of Pre-Pregnancy CVH Interventions

To achieve health equity among birthing individuals, attentive design of community-based interventions is crucial and will require community-centered engagement at every stage of the research process. This is especially imperative for populations with an increased frequency of unfavorable CVH, including individuals from racial and ethnic minoritized groups who have intersecting barriers to optimal health due to social determinants of health before, during, and after pregnancy.^107,114

Innovative strategies that are culturally cognizant and recognize sociocultural and environmental contexts to optimize CVH are needed. For example, Black women are significantly more likely than White women to have unfavorable CVH with multiple, pre-pregnancy cardiovascular risk factors (e.g., obesity, diabetes) and risk is higher among individuals within lower economic strata.^115,116 Hispanic/Latinx women, and in particular those from certain subgroups (e.g., Puerto Rican women), may experience a disproportionate burden of adverse social determinants of health, such as poor healthcare access and quality and language barriers, that contribute to disparate risk of APOs and CVD,.¹¹⁷ In the limited data that are available from birthing individuals from Asian subgroups, Asian Indian compared with White pregnant individuals have a higher risk of GDM. Thus, consideration of sociocultural context of individuals from varying backgrounds, including consideration of nativity and acculturation along with experience of structural barriers (e.g., racism, built environment, health care access) is of key importance when designing interventions. Specifically, tailoring and adaption through user-centered and participatory approaches can bolster interventions’ effectiveness and relevance.

Effectiveness and relevance can also be optimized through engagement with community steering committees or advisory boards with key stakeholders and participants from the target population.^118–123 This will also facilitate the design of interventions that maximize strengths and resources present within communities to promote an asset-based approach that empowers marginalized communities. For example, the harnessing of civic engagement and community advocacy as a means to collectively address health disparities has resulted in improved cardiovascular risk factors (e.g., blood pressure, physical activity) in Black women.^124,125 There is also evidence to support integration of similar models fostering volunteerism to promote favorable CVH among Hispanic/Latinx females.¹²⁶ Such interventions can incorporate peer leaders (such as community health workers or Promotoras) who serve as role models and provide social support to promote CVH.^127–129 Meeting women in the community by embedding place-based interventions within their neighborhoods – at venues such as hair salons, churches, public housing, college campuses, and workplaces – is another potential strategy to promote CVH.^115,116,130 Further investigation is needed to understand how incorporating interpersonal relationships and social supports through partners, friends, and community may also optimize interventions.

Addressing Structural Determinants of CVH with Policy-Level Interventions

To substantially improve pre-pregnancy CVH and downstream maternal and offspring outcomes among racial and ethnic minoritized groups, the wider influence of multifaceted structural and social determinants of health must be acknowledged and addressed. This requires a sincere appreciation that optimizing opportunities for CVH is not solely an individual responsibility but requires health system and societal-level interventions. There is well-established evidence that structural inequities such as disenfranchised neighborhoods and physical environments, the wealth gap, inadequate access to quality healthcare, and food and housing insecurity are barriers for optimal CVH.^131,132 Dismantling structural racism and discriminatory policies, the root causes of disparities in CVH and APOs, is therefore critical.^131,133 Building CVH-promoting environments and contexts that support optimal CVH for all birthing individuals requires will for policy change.¹³⁴ Policy-level interventions are needed to ensure social and reproductive justice and enable health over the life course, including during the continuum of pre-pregnancy and perinatal care.^135,136 Making ideal CVH the social norm in a community can be achieved with the integration of equitable opportunities to maintain healthier lifestyle practices, such as increasing access to healthier and affordable foods (local supermarkets, grocery stores), greener and walkable neighborhoods, free or subsidized fitness center memberships, and safe and proximate parks and recreational facilities.¹³⁵ Enhancing economic empowerment and investment in neighborhoods through access to employment and education opportunities can profoundly influence the CVH and well-being of socioeconomically disadvantaged individuals^107,134,137 as these factors are directly linked to access to high quality healthcare. The Black Maternal Health Caucus through the Black Maternal Health Momnibus has introduced legislation to address the maternal health crisis through community partnerships, perinatal healthcare workforce diversity, digital tools, and optimized healthcare coverage models that promote continuity and access (e.g., pre- and inter-pregnancy care) to improve quality of care and mitigate disparities.¹⁰⁷ Given data that lacking preconception health insurance is associated with lower levels of pregnancy care, later prenatal care initiation, and lower levels of postpartum care, ensuring uninterrupted access remains a critical gap with insurance transitions or “churn” being common before and after childbirth.^138,139 Multi-level interventions will be needed that are tailored to the unique stages of the pre-pregnancy period. Potential examples are outlined in Table 3.

Table 3.

Tailored Interventions to Promote Cardiovascular Health at Various Pre-Pregnancy Life Stages and Across Ecological Levels

	Pre-Pregnancy Life Stages
	People with no current intention to become pregnant (Includes adolescents)		People with intention to become pregnant (pre-pregnancy)		People with intention to become pregnant again (inter-pregnancy)
Individual	Lifestyle coaching Stress reduction Sleep interventions Weight loss pharmacotherapy/bariatric surgery Text-based interventions		In addition to those for people with no current intention to become pregnant, Lifestyle-based weight loss interventions Pharmacotherapy safe during pregnancy to achieve optimal risk factor control		Lifestyle-based interventions for people with a history of APOs Pharmacotherapy among individuals after a history of APOs (e.g., metformin or GLP-1RA after gestational diabetes) Cognitive behavioral therapy and pharmacologic therapy for postpartum depression
Community	Civic engagement		Peer-led support groups		Peer-led parenting groups Home visiting programs focused on stress, postpartum depression
Population	Social marketing campaigns to raise awareness about CVH promotion Built environment changes (e.g., access to healthy foods, green spaces)
Policy	Dismantle structural racism Fair housing practices Access to education, equitable employment opportunities, and paid family leave Healthcare workforce diversity Continuous health insurance coverage to ensure high-quality pre-pregnancy counseling and minimize interruptions in access

APOs adverse pregnancy outcomes; CVH cardiovascular health; GLP-1RA glucagon-like peptide-1 receptor agonists; SNAP supplemental nutrition assistance program; WIC Special supplemental nutrition program for women, infants, and children;

Unanswered Questions and Future Directions

A growing body of evidence supports associations between CVH-APO and APO-CVD and builds upon the well-established pathways that are known to exist between CVH-CVD across the life course and intergenerationally. However, important knowledge gaps (a selection of which is presented in Table 4) in the epidemiology and pathophysiology of CVH as well as effective interventional strategies to promote CVH remain. A central question that remains is whether the associations between CVH-APOs-CVD are epiphenomena or causally related; this question has direct consequences for the design of prevention and treatment strategies to improve CVH in order to decrease the frequency of APOs and risk of CVD. Specifically, it is not known whether APOs are a marker or mediator of the CVH-CVD relationship. Indeed, there are likely multiple direct and indirect pathways by which CVH may influence maternal and offspring CVH. This supports an emphasis on primordial prevention to preserve or improve CVH beginning in childhood; however, it is not known whether specific metrics in the CVH construct are most salient to focus upon at different life stages (e.g., pre-pregnancy to reduce risk of APOs). Similarly, it is not known whether strategies that reduce the frequency of APOs, by virtue of that reduction, also improve long-term health outcomes for the birthing individual and offspring. Observational evidence for several shared pathways at the CVH-APO-CVD intersection support that the protection conferred by higher CVH for both APO and CVD risk reduction may be “more than the sum of its parts.”^10,38,61 However, individual-level promotion of pre-pregnancy CVH will be limited among individuals with unintended pregnancies, which account for nearly half of all pregnancies; unintended pregnancies are disproportionately higher among low-income and racially and ethnic minoritized females who are also at greater risk of poor CVH and CVD.¹⁴⁰ This emphasizes that population health and policy level interventions are key, which include strategies to equitably reduce unintended pregnancies (e.g., access to desired long-acting reversible contraceptives, implementation of the One Key Question^R) as well as targeting CVH beginning early in the life course before the reproductive years.¹⁴¹

Table 4.

Key Knowledge Gaps in Mechanistic Pathways, Effective Interventions, and Implementation of Strategies to Equitably Promote Pre-Pregnancy Cardiovascular Health

Pathophysiology	What are the pathophysiologic mechanisms and pathways linking pre-pregnancy CVH, adverse pregnancy outcomes, and cardiovascular disease? Could proteomic markers assessed prior to pregnancy identify individuals at highest risk of adverse pregnancy outcomes for whom increased surveillance or intensive risk factor modification may reduce risk of APOs? Are there mechanistic targets that can inform novel therapeutic development to improve pre-pregnancy CVH and pregnancy outcomes?
Interventional Research	Which metrics of the CVH construct are most salient to target in a multi-component intervention in the pre-pregnancy period to improve maternal and offspring outcomes? Should thresholds for treatment of cardiovascular risk factors be different in pregnancy-capable individuals with hypertension (e.g., goal BP level <130/80 mm Hg vs. <140/90 mm Hg pre-pregnancy)? How should interventions be designed to incorporate and address social determinants of health, psychological health, and stress to improve pre-pregnancy CVH? How should we identify individuals at highest absolute risk (e.g., low CVH, biomarkers) to prioritize for testing interventions? Do interventions targeting the interpregnancy period improve outcomes of the subsequent pregnancy and offspring? Do interventions targeting pre-pregnancy CVH reduce the risk of long-term kidney disease?
Dissemination and Implementation Research	Is the proposed intervention adaptable for resource-limited populations? Is the proposed intervention culturally tailored to maximize benefit in diverse communities? Can technology-based approaches (e.g., virtual reminders, mHealth) optimize delivery of interventions to improve pre-pregnancy CVH?
Health Equity Considerations	Can healthcare system-based models that provide patient navigation and peer support to address barriers that exist help to optimize pre-pregnancy cardiovascular health? What are optimal strategies to ensure equitable recruitment of individuals who do not have routine healthcare access, particularly in the pre-pregnancy period? What strategies are most effective in engaging key stakeholders from communities from the beginning of intervention development to process improvement in the implementation phases? Are interventions generalizable to different populations, including across race and ethnicity, socioeconomic status, and gender identity?

Conclusions

There exists substantial opportunity to improve health across the life course and generations by targeting pre-pregnancy CVH in the birthing individual. Numerous epidemiologic studies demonstrate that CVH is a risk factor for both APOs and CVD in the birthing individual and offspring. Animal models and in vitro experiments suggest a strong link between pre-pregnancy CVH, APOs, and CVD. Poor pre-pregnancy CVH is highly prevalent in reproductive aged-individuals and disproportionately so among individuals with higher burden of adverse social factors. Identification of individuals with unfavorable CVH before pregnancy, as early in the life course as childhood and adolescence, is a necessary first step to increase awareness of risk. Clinical trial data are needed to demonstrate whether CVH interventions beginning prior to pregnancy will modify maternal and offspring outcomes including APOs and CVD. Unfavorable CVH has been associated with a broad range of antecedent individual-level and structural determinants. Therefore, effective interventions should consider multi-level approaches at the individual-, community-, and societal-level. Persistent racial, ethnic, and socioeconomic disparities illustrate the critical importance of future investigations ensuring that proposed interventions are created, implemented, and evaluated with an equity focus. The pre-pregnancy period offers a unique window of opportunity to address the growing public health burden of APOs and interrupt the intergenerational transmission of poor CVH.