Adverse Pregnancy Outcomes and Postpartum Care as a Pathway to Future Health

Abstract

Adverse pregnancy outcomes (APOs) collectively represent the leading causes of maternal and neonatal morbidity and mortality. Beyond the potentially devastating impact of APOs during pregnancy and the puerperium, women diagnosed with APOs have a 2- to 4-fold increased risk of future cardiovascular disease. Fortunately, APOs occur at an opportune time, in early- to mid-adulthood, when primary and secondary prevention strategies can alter the disease trajectory and improve long-term health outcomes. This chapter takes a life-course approach to 1) the epidemiology of APOs, 2) evidence-based strategies for clinicians to manage APOs, and 3) future directions for APO research and clinical practice.

Introduction

Adverse pregnancy outcomes (APOs) collectively represent the leading causes of maternal and fetal morbidity and presage a 2- to 4-fold increased risk of future cardiovascular disease (CVD).¹ The American Heart Association’s 2011 guidelines for the prevention of CVD recommends screening for APO’s, including hypertensive disorders of pregnancy (HDP), gestational diabetes mellitus (GDM), preterm birth (PTB), and fetal growth restriction (FGR), as part of the CVD risk assessment.² Their most recent scientific statement in 2021 updates this list to include placental abruption, stillbirth, and miscarriage, because evidence has emerged that they also portend future CVD disease.³ In many cases, APOs may be the first expression of an increased risk for chronic disease, including cardiovascular, cardio-metabolic, and cardio-renal diseases.⁴ However, APOs and their associated chronic diseases may manifest via similar pathophysiologic processes at different times throughout life. Thus, it is unclear whether APOs genuinely contribute mechanistically to future adverse outcomes or simply indicate higher underlying risk. ⁵

The life-course approach can be a useful lens through which to view APOs. In this context, pregnancy is often analogized as a “maternal stress test” along the life-course continuum and may constitute a risk exposure during a critical window for a woman’s health. The life-course approach views an APO’s “inciting event” as a chain of integrated influences and acknowledges that the accumulation of risks that commonly occur together (i.e., chains of risk) can have an additive or modifying effect on both pregnancy and long-term health outcomes.^6-9 In an uncomplicated pregnancy (Figure 1A), there is typical/usual risk for disease or minimal accumulation of risk exposures before pregnancy (e.g., current or family history of chronic disease, prior APO, obesity), such that the body’s requisite adaptations to pregnancy stress the maternal physiology only to a degree. Routinely, the stress on the maternal systems resolves after delivery.⁶ Conversely, evidence suggests that women who experience an APO (Figure 1B) tend to have a higher-than-normal accumulation of risk exposures from birth. These “chains of risk” that cluster together may be significant contributors to existing disparities in APOs, and include factors such as race/ethnicity as a social construct representing the accumulated burden of marginalized people from racist polices and practices, low socioeconomic status, limited access to medical care, and family history of chronic disease.^10-12 It is postulated that the accumulation of exposures increases the allostatic load of the mother, such that the stress posed by pregnancy pushes the mother past a critical threshold into a disease state, resulting in an APO.¹³ Although these disease states largely appear to resolve postpartum (for example, most patients with gestational diabetes have a normal postpartum 2-hour GTT), patients are still at higher risk for future CVD.^14-16

Figure 1.

Life-course approach to adverse pregnancy outcomes (APO) and future disease risk for A) an uncomplicated pregnancy (grey line), B) an adverse pregnancy (red line) relative to an uncomplicated pregnancy (grey line), and C) shows the optimal/goal pregnancy (green dashed line) relative to the adverse (red line) and uncomplicated pregnancies (grey). Figure adapted from Rich-Edwards et al.⁶

Fortunately, adversity is not a foregone conclusion. Given that APOs occur at an opportune time in the life course, there is a tremendous opportunity to recognize and mitigate the effects of these exposures. The optimal paradigm (Figure 1C) would include a system where patients with similar pre-pregnancy accumulated risk exposure have an early intervention to mitigate the impact of the physiologic stresses of pregnancy, thereby preventing or lessening the severity of the APO. In addition, clinicians would partner with patients to employ aggressive postpartum strategies after delivery to prevent or delay the early-onset of disease. The purpose of this chapter is to review 1) The evidence linking APOs to future disease risk; 2) Evidence-based strategies to mitigate the effects of risk exposures both in the near-term (e.g., education, postpartum and transitional care, breastfeeding, and weight loss) and the long-term (e.g., clinician surveillance, exercise and nutrition, and pharmacologic therapy); and 3) Gaps in the existing literature and proposed future directions surrounding strategies to improve APOs and health outcomes across the life-course continuum.

Adverse pregnancy outcomes and future health

The evidence linking each APO to future disease risk is reviewed in this section with a summary of disease prevalence, prominent risk factors, and specific future disease risks in Table 1.

Table 1.

Summary of prevalence, risk factors, and future risk associated with adverse pregnancy outcomes

Adverse Pregnancy Outcomes (APO) & Definition	Prevalence, % of pregnancies	APO’s Risk factors	APO’s Future Risk for Chronic Disease
Hypertensive Disorders of Pregnancy (HDP) chronic hypertension, gestational hypertension, pre-eclampsia, or eclampsia	Global: 4 - 25 % 71 U.S.: 11 % 71	High risk: prior HDP, multifetal gestation, renal disease, autoimmune disease, chronic hypertension, diabetes (type 1 or type 2). 67 Moderate risk: first pregnancy, advanced maternal age (> 35 years), BMI > 30 kg/m2, family history of hypertension, polycystic ovary syndrome.67	Cardiovascular: Hypertension, fatal and nonfatal coronary heart disease, fatal and nonfatal stroke, heart failure, multimorbidity72, 19 Cardio-metabolic: Type 2 diabetes, metabolic syndrome Cardio-renal: chronic kidney disease, end-stage renal disease, multi-morbidity 20, 21
Gestational Diabetes (GDM) Glucose intolerance 1st diagnosed in pregnancy	Global: 7 - 10% 73 U.S.: 6-14% 74	Prior GDM, obesity, family history of diabetes, race/ethnicity, advanced maternal age, polycystic ovary syndrome 75,76	Cardiovascular: Non-invasive cardiac diagnostic procedures (e.g., insertion of a stent or stress test), simple cardiovascular events (e.g., angina pectoris), and CVD-related hospitalizations. 24,77 Cardio-metabolic: Type 2 diabetes, metabolic syndrome
*Fetal Growth Restriction (FGR) Estimated fetal weight <10th% on standardized growth curve	Global: 10% U.S.: 10%	Advanced maternal age; elevated diastolic blood pressure; folic acid deficiency, parity, and smoking, pregestational diabetes, autoimmune disorders 28,78	Cardiovascular: Hypertension, coronary heart disease, stroke, heart failure, CVD hospitalizations29,78
Preterm Birth (PTB) Delivery after 20.0 weeks and before 37.0 weeks gestation	Global: 11% U.S.: 10.1% 79	Prior PTB, Black race, Hispanic ethnicity, maternal age < 20 years, body mass index < 20.0 kg/m2, maternal weight gain < 0.5kg/week, inadequate or no prenatal care, and illicit drug use. 80	Cardiovascular: Hypertension, coronary heart disease, stroke, heart failure, coronary artery disease, overall CVD mortality 72, 19
Placental Abruption Premature separation of the placenta from the uterus prior to delivery	Global: 1% 81 US: 0.6 – 1.0%81	Prior placental abruption, prior PTB, hypertension, and HDP; Advanced maternal age > 40 years; early rupture of membranes; smoking, illicit drug use 81	Cardiovascular: hypertension, coronary heart disease, stroke, coronary heart disease33
Pregnancy Loss Stillbirth-Fetal death ≥ 20 weeks gestation and prior to delivery Miscarriage-pregnancy loss prior to 20 weeks gestation	Global: 1% - Stillbirth 10 – 15% - miscarriage US: < 1% Stillbirth 10 – 15% - miscarriage	HDP, GDM, pre-gestational diabetes, obesity, lupus, renal disease, thyroid disorders, FGR, cholestasis of pregnancy.	Cardiovascular: Coronary heart disease, stroke, coronary heart disease 16 Cardio-metabolic: Type 2 diabetes 36 Cardio-renal: chronic kidney disease, end-stage renal disease 37

^*Many studies use Small for Gestational Age (SGA), which is birthweight <10^th%

Abbreviations: BMI = Body Mass Index

Multi-morbidity = two or more related conditions.

Hypertensive disorders of pregnancy (HDP)

HDP is associated with a higher risk for CVD through what is likely a complex interplay between metabolic syndrome, persistent endothelial dysfunction, underlying susceptibility, altered myocardial structure and function, and other risk factors predisposing one to later cardiovascular sequelae.¹⁷ The risk of heart failure, stroke, and death due to CVD was notably higher in the first 10 years after pregnancy among women with HDP,¹⁸ which is frequently associated with chronic hypertension (HTN) (relative risk (RR) = 3.70; 95% CI: 2.70 – 5.05). However, HDP has also been associated with a higher risk for fatal and nonfatal CHD (RR = 2.26; 95% CI: 1.86 – 2.52), heart failure (RR = 4.19; 95% CI: 2.09 – 8.38) and fatal and nonfatal stroke (RR = 1.81; 95% CI:1.45 – 2.27).¹⁹

Women who experience HDP may also be more likely to manifest systemic vascular damage and subsequent renal disease later in life. Garovic and colleagues recently examined the risk of multi-morbidity using medical records from 9,872 pregnancies in a Minnesota county between 1976 and 1982. Multi-morbidity was defined as the co-occurrence of two or more of the following conditions: cardiac arrhythmias, coronary heart disease (CHD), heart failure (HF), stroke, chronic kidney disease, dementia, hyperlipidemia, HTN, and type 2 diabetes (T2D).²⁰ Interestingly, when compared to the reference group, women with a history of HDP demonstrated a higher risk for multi-morbidity (hazard ratio (HR) = 1.25; 95%CI: 1.15 – 1.35) and chronic kidney disease (HR = 2.41; 95%CI: 1.54 – 3.87). Vikse et al. reviewed the Medical Birth Registry of Norway and determined that, among parous women, preeclampsia was associated with a higher risk of developing end-stage renal disease (ESRD) (RR= 4.7; 95%CI: 3.6 – 6.1).²¹

Gestational diabetes (GDM)

GDM poses a significant threat to a woman’s long-term cardiometabolic health, increasing her risk for T2D and metabolic syndrome.^15,16 More than 20% of women with GDM will develop T2D within 5 years of pregnancy, and a recent meta-analysis by Li and colleagues found that the long-term rate of development of T2D after GDM was linear: 20% at 10 years, 30% at 20 years, 40% at 30 years, 50% at 40 years, and 60% at 50 years. Similarly, a well-established link exists between GDM and the development of metabolic syndrome. Retnakaran et al. found that among 487 women who completed oral glucose tolerance testing in pregnancy and cardiometabolic screening 3 months postpartum, women with GDM were more likely to have metabolic syndrome at 3 months postpartum (20% by International Diabetes Federation (IDF) criteria and 16.8% by AHA criteria), compared to those with normal glucose tolerance (10% by IDF and 8.9% by AHA;p =0.046).²²

The pathophysiology of developing CVD after GDM may be analogous to developing CVD following T2D, which most commonly involves atherosclerosis and hypercholesterolemia. Consistent with this theory, studies have found that women with a history of GDM tend to have more risk factors for CVD than women without prior GDM.²³ However, evidence has emerged that GDM may increase the future risk for CVD, independent of T2D or metabolic syndrome. A systematic review of the literature by Kramer et al. indicates that women with GDM have a two-fold higher risk of future cardiovascular events (RR = 1.98; 95%CI:1.57 – 2.50), even when excluding those women who developed T2D (RR = 1.56; 95%CI 1.04 – 2.32).²⁴

Fetal growth restriction (FGR) and preterm birth (PTB)

Recent systematic reviews and large population registries from European countries²⁵ have demonstrated that FGR, PTB, and delivery of an infant whose birth weight is <10^th percentile, termed small-for-gestational-age (SGA), are associated with increased risk of future adverse maternal cardiovascular outcomes.^26,27 It has been postulated that interactions between the maternal unit and fetal-placental processes may program future maternal disease risk.²⁸ In a large birth registry study of >920,000 primiparous births from Swedish women, a team of epidemiologists found that, compared to mothers of non-SGA full-term infants, women with PTB had increased risk for CVD over the follow-up period (median 11.8 years), which was higher in women with earlier deliveries (HR, range 1.39 (95%CI 1.22 – 1.58) to 2.57 (95%CI 1.97 – 3.34)). Women with SGA infants also had higher rates of CVD that were proportional to SGA severity (HR range 1.38 (95% CI 1.15 –1.65) to 3.40 (95% CI 2.26 –5.11)).²⁹ Further, there appeared to be a synergistic effect between birthweight and gestational age (p<0.001), such that women giving birth to an SGA infant with a PTB had a 3-fold higher risk for CVD during follow-up than women without either FGR or PTB alone.²⁹

PTB is also independently associated with a 1.4- to 2-fold increased risk of CVD.³⁰ Moreover, the risk for adverse outcomes is higher for those with recurrent PTBs. A national cohort of Swedish singleton deliveries between 1973 and 2015 (>2 million pregnancies) by Crump et al. found that, compared with full-term deliveries, women with preterm deliveries had a higher risk of HTN within 10 years of the index pregnancy (adjusted hazard ratio (HR (aHR) = 1.67; 95%CI: 1.61–1.74).²⁵ This risk of HTN persisted at least 43 years after delivery, independent of shared familial traits. A recent meta-analysis of 10 large cohort studies with a follow-up time of 12 – 35 years showed that spontaneous PTB was associated with an increased risk of developing or dying from CHD (adjusted hazard ratio aHR = 1.38, 95%CI 1.22–1.57), stroke (aHR 1.71; 95%CI 1.53–1.91), and overall CVD (aHR = 2.01; 95%CI 1.52–2.65).³¹

Placental abruption

The progression from abruption to CVD likely mirrors HDP, whereby vascular damage and other factors coalesce to increase susceptibility to CVD. In a recent meta-analysis of 11 large cohort studies, which included > 6 million pregnancies between 1967 and 2016 (1.1% abruption rate), those who experienced placental abruption had almost twice the risk of CVD-related morbidity and mortality (RR = 1.76; 95%CI:1.24 – 2.50).³² In addition, abruption was associated with higher mortality from CHD (RR = 2.64; 95% CI: 1.57 – 4.44) and stroke (RR = 1.70; 95%CI: 1.19 – 2.42). A retrospective national birth registry study of more than 2 million singleton births from Norway (1967 – 2002) and Sweden (1973 –2003), with a 1.1% incidence of abruption, found that women with placental abruption had an increased risk of CVD-related mortality (aHR = 1.8; 95 %CI: 1.3 – 2.4), even after excluding those with pre-gestational diabetes or hypertension, HDP, and GDM.³³ Of note, CVD mortality was not higher with recurrence of abruption (aHR = 1.7; 95%CI: 1.2 – 2.3) compared to a single abruption (aHR = 1.8 ; 95%CI: 1.3 – 2.4). The highest incidence of CVD was among women with both an abruption and PTB (HR = 2.3; 95%CI: 1.6 – 3.3).³³

Miscarriage

There is compelling evidence that miscarriage is associated with adverse future cardiovascular and cardiometabolic outcomes. The Nurses’ Health Study II recently analyzed the records of >1.9 million women with an average follow-up time of 23 years. Women with a history of miscarriage (i.e., spontaneous pregnancy loss before 6 months of gestation) had a higher risk for CHD (HR =1.21; 95%CI: 1.10 – 1.33) and stroke (HR = 1.23; 95%CI: 1.01 – 1.44).³⁴ CVD risk increased in a dose-dependent manner with a greater number of miscarriages (HR = 1.34 for > 2 miscarriages vs. HR = 1.18 for 1 miscarriages), and was also greater among women who were younger at the time of their miscarriage (HR = 1.4 for age < 23 years, vs. HR = 1.25 for age 24-23 vs. HR = 1.03 for age> 30 years).³⁴ Recurrent miscarriage (n > 3) was associated with a significantly higher risk of CHD (aHR = 5.06; 95%CI: 1.26 -20.29).³⁵ Kharazmi et al. also examined the risk for future T2D among women with prior pregnancy loss in a sample of >13,000 women with 10-year follow-up. Recurrent miscarriages were associated with a nearly 2-fold higher risk for T2D (aOR = 1.85; 95%CI: 1.17 – 2.93).³⁶

Stillbirth

Few studies investigate the effect of stillbirth on long-term health outcomes, which may be because stillbirth was only recently added to the list of APOs that associate with CVD. Nevertheless, recent publications reveal an independent association of stillbirth with future cardiovascular and cardio-renal disease. Kharazmi et al. examined medical records for > 11,000 women in a cohort with a stillbirth incidence of 2%. After accounting for confounding health conditions, parity, and lifestyle factors, each stillbirth increased a woman’s risk for CHD (aHR = 2.32; 95%CI: 1.19 – 4.50).³⁵ A large population-based cohort study using birth registry data from over 1.9 million Swedish women (0.7% stillbirth incidence) found that women with at least one stillbirth (i.e., pregnancy loss after 28 weeks gestation) had a significantly higher risk for developing both chronic kidney disease (aHR = 1.26; 95%CI: 1.09 – 1.45) and end-stage renal disease (aHR = 2.25; 95%CI: 1.55 - 3.25), independent of HDP, SGA, smoking, obesity, and co-morbidities.³⁷ Further studies are needed to fully elucidate the disease risk posed by stillbirth.

Summary

Overall, these data provide compelling evidence that APOs are associated with future adverse cardiovascular, cardiometabolic, and cardio-renal diseases.³⁸ While acknowledging the stress this can create for patients and their families, it is equally important to emphasize that this knowledge can be used to “reframe” the window to future health to envision a life where chronic disease is not a foregone conclusion.

Evidence-based strategies to mitigate risk

Concrete actions can reduce CVD risk among patients with APOs. This section presents approaches broadly known to reduce CVD. Most postpartum APO intervention research has focused on patients with a history of HDP or GDM, so notations are included when the evidence is associated with a specific APO.

Managing the 4^th trimester and beyond for patients with APOs

Postpartum care is integral to optimizing acute health outcomes in birthing people and allows for robust screening and continued management of comorbid conditions while facilitating recovery in the puerperium. Unfortunately, this critical period is complicated by numerous barriers to optimal care, including 1) lack of childcare, 2) experience of discrimination in perinatal care, 3) clinician time limitations, 4) knowledge gaps about the link between APOs and future CVD, 5) postpartum loss of health insurance, and 6) failure of the healthcare system to facilitate postpartum transition to primary care.^39-41 The primary focus here will be on risk-reduction strategies employed by patients and their OB/GYN team in the postpartum period. However, an important healthcare system-level intervention of Multi-disciplinary Postpartum Transitional Clinics can overcome some barriers associated with the postpartum/primary care transition. Most transitional clinics strive to perform a CVD risk assessment and counseling after an APO, ensure blood pressure stability in women with HDP, and facilitate the transition to longitudinal primary care. Such clinics have successfully increased physical activity, weight loss, nutrition counseling, and primary care continuity.

In addition to the comprehensive 4^th trimester care guidelines recommended by the American College of Obstetricians and Gynecologists,⁴² an APO history warrants cardiometabolic disease-specific counseling and screening. Table 2 summarizes postpartum clinical management recommendations for patients with APOs. It is incumbent upon OB/GYN clinicians to sensitively counsel patients about the association between APOs and future CVD risk, the need for close primary care follow-up, and potential risk-reducing strategies.

Table 2.

Summary of Recommendations: Postpartum Cardiovascular Risk-Reduction Strategy for Patients with Prior APO

Early Postpartum Period:* denotes conversation should begin antepartum Clearly document APO history in medical record, link to future CVD, recommendations and counseling 7-10 day Postpartum Check-in, either by phone or in person *Counseling: Patients with HDP: Strict preeclampsia precautions, daily self-measured blood pressure at home with goal <120/80 mm Hg, blood pressure check within 7-10 days postpartum Patients with GDM: schedule OGTT and postpartum appointment; May consider immediate postpartum GTT prior to hospital discharge to increase testing uptake. Begin discussing potential benefits of metformin to delay or prevent type 2 diabetes and programs like the National Diabetes Prevention Program (available at many YMCAs or online) Link between APO and future CVD; encourage that there are strategies to potentially reduce this risk Lactation: Benefits extend beyond baby to both short- and long-term improved maternal cardiovascular health Lifestyle: Incorporating a combination of nutrition, physical activity, health education, and goal setting led by health professionals are associated with greatest success for gestational weight loss. Refer to nutritionist, exercise program or DPP (if GDM or pre-diabetes) for specific guidance and accountability. Advise regarding association between postpartum weight retention and obesity, type 2 diabetes, and CVD. Contraception Counseling: ask patients about future plans for their family and use shared decision making to develop plan; discuss adequate birth spacing to decrease the risk of preterm birth and other outcomes related to short interval spacing. Primary Care Transition: establish plan for long-term follow-up and make appropriate referrals or send a pregnancy summary with APO history to the patient’s primary care physician. 4-12 weeks postpartum Comprehensive postpartum visit per ACOG guidelines82 to include the following Cardiometabolic Risk Assessment with attention to possible impact of social determinants of health: Continue aforementioned counseling conversations Medication Monitoring Medical History: Smoking, physical activity, breastfeeding; history of hypertension, diabetes, or CVD; first degree relative with history of CVD, hypertension, or diabetes Physical Exam: Resting blood pressure, heart rate, BMI, and waist circumference Laboratory Testing: Lipid profile, diabetes screening with fasting blood glucose or HbA1c, urine protein:creatinine ratio Mental Health: Early and frequent assessment for postpartum depression, anxiety, or other mental health condition GDM: 4-12 week OGTT Results: →Diabetes: refer to primary care or endocrinology for management. Advise of importance of optimizing of blood sugars before any planned pregnancy to decrease the risk of fetal malformations and miscarriage with pre-pregnancy visit. →Not Diabetes OGTT Results →Normal-Repeat testing every 3 years (usually with HbA1C) →Pre-diabetes/Impaired Fasting Glucose/Impaired Glucose Tolerance: Repeat testing at least every 1 year (usually with HbA1C) Repeat testing before any planned pregnancy with pre-pregnancy visit. Refer to National Diabetes Prevention Program (available at many YMCAs and through online programs) and/or recommend starting metformin.

Long-term Refer patients with APOs to a primary care physician to employ long-term risk-reduction strategy. Those only seeing OB/GYN should, at a minimum, have screening at regular intervals with primary care referral for any abnormal findings. Annual well-patient visit for CVD prevention Family history, screen for CVD risk factors, lifestyle counseling Family planning counseling and contraception, if desired; Recommend pre-pregnancy visit and counseling to optimize pregnancy outcomes, as appropriate; Folate supplementation prior to pregnancy Elicit pregnancy history for every pregnancy capable patient, including history of APO, counsel about potential risks, and manage medical care accordingly. CVD Screening Blood pressure screening annually Assess cardiometabolic risk by screening for the following CVD risk factors every 4-6 years: Traditional: smoking, hypertension, diabetes, lipids (total cholesterol, high-density lipoprotein cholesterol) Non-traditional64,83,84: APOs, Polcystic ovarian syndrome, functional hypothalamic amenorrhea, oral contraceptives, hormone replacement, autoimmune inflammatory diseases (Rheumatoid arthritis, systemic lupus erythematosus, scleroderma), breast cancer; these non-traditional factors can guide initiation of preventive medications, such as statins and antitelet drugs

Patients with pregnancies complicated by APOs may be optimized with an individualized follow-up schedule, including contact with a clinician within 7-10 days of hospital discharge to monitor physical and mental well-being. Emphasis should be given to psychosocial stress, a significant risk factor for cardiometabolic disease and the potential impact of the social determinants of health on the patient’s well-being and future health.⁴³

Cardiometabolic screening

All patients with APO’s should have a comprehensive CVD risk assessment within 12 weeks postpartum, including a detailed medical history, physical exam, biochemical testing (lipid profile, diabetes screening with fasting blood glucose, HbA1c, or OGTT if GDM, urine protein assessment, and nutrition assessment (Table 2).⁴⁴ The optimal timing of this assessment is unclear, except for an OGTT for patients with GDM. Early screening within 3 months postpartum can be initiated by the obstetric care clinician, as this may be a more accessible approach for patients to complete follow-up. Unfortunately, many biochemical markers may remain elevated for several months after delivery, such that earlier tests may overstate long-term CVD risk. A more realistic picture of cardiometabolic risk may be present ~ 6 months postpartum, but additional study is required in this area.

Blood pressure management

Patients with HDP warrant vigilant postpartum blood pressure management. Not only are postpartum complications of HDP a leading cause of readmissions, but there is emerging evidence that poorly controlled blood pressure in the puerperium negatively influences cardiovascular remodeling and can lead to persistently elevated blood pressures that accelerate lifetime CVD risk trajectory. The Self-Management of Postnatal Hypertension (SNAP-HT) trial randomized patients to usual care or postpartum self-blood pressure management with a validated home blood pressure cuff.⁴⁵ Patients transmitted daily measurements by mobile phone to a telemonitoring service that used automated replies to advise medication titration at pre-specified targets or to immediately contact their care team for high values. Daily self-monitoring continued until medications were discontinued and the patient remained normotensive for 5 days, at which time weekly home measurements were taken for the trial duration. Patients in the self-monitoring arm had improved blood pressure control with a quicker return to the normal range within 6 weeks postpartum, compared with standard care.⁴⁵ This benefit persisted through 3-4 years postpartum with a 7 mm Hg reduction in diastolic blood pressure among those randomized to self-monitoring—a reduction expected to reduce future CVD risk by >30% compared to the usual care group. ⁴⁵ The SNAP-HT findings underscore the importance of attentive postpartum blood pressure management and home surveillance, both for postpartum and long-term morbidity and mortality reduction. Choice of medication for postpartum management balances ease of dosing (prefer once daily), lactation safety, and cost to the patient. We commonly use a thiazide diuretic, nifedipine, amlodipine, or enalapril. Of note, enalapril is safe with lactation, but ACE inhibitors have been associated with fetal anomalies so patient should be counselled and offered reliable contraception if enalapril is prescribed.

Lactation

Lactation is a powerful tool to facilitate recovery from the physiologic stress test of pregnancy. Patients who lactate for at least 6 months have significantly lower fasting blood glucose, lipid profile, insulin resistance, blood pressure, and C-reactive protein. Among patients with APOs, increased length of breastfeeding significantly decreased the likelihood of metabolic syndrome (aOR = 0.89; 95%CI: 0.79 – 0.99), abnormal fasting glucose (aOR = 0.79; 95%CI: 0.64 – 0.96), and the ratio of total to HDL cholesterol (aOR = −0.06; 95% CI: −0.10 – −0.03).⁴⁶ Specific to patients with GDM, those who lactate have improved glycemic control, ⁴⁷ and a longer duration of breastfeeding is associated with both lower rates of T2D and pre-diabetes.⁴⁸ Benefits associated with lactation seem to endure over the long term. A recent meta-analysis of over 1 million parous concluded that the risk reduction for all CVD outcomes progressively increases with the duration of lactation from 0-12 months.⁴⁹

Lifestyle

Postpartum weight retention significantly increases a person’s lifetime weight gain trajectory and risk for obesity, T2D, and CVD later. Lifestyle interventions during pregnancy have successfully curbed postpartum weight retention for women with a normal BMI, but the same has not held true for women with obesity.⁵⁰ Consistent with prior literature, a prospective cohort study of women with obesity from 6-16 weeks gestation through 1 year postpartum showed no difference in gestational weight gain between patients who lost and retained pregnancy weight through 12 months postpartum. ⁵¹ However, women with postpartum weight loss reduced energy intake after delivery by 300 kcal/d, while those who retained weight increased energy intake by 250 kcal/d. This study found no difference in breastfeeding duration, eating behavior, or other metabolic markers and concluded that postpartum weight retention results from increased energy intake instead of decreased energy expenditure.⁵¹ Taken together, these data suggest that the period up to one year postpartum is a critical time to lose excess gestational weight and curb the impact of long-term weight retention.

Healthy eating:

Most postpartum lifestyle interventions include a combination of dietary modification and/or physical activity with health education and personalized goals. Patients’ dietary intake can be assessed by food frequency questionnaires and evaluated using indices, such as the Mediterranean Diet Score⁵² or Rate Your Plate⁵³ to inform counseling. The diets with the most significant evidence for CVD protection include the Dietary Approaches to Stop Hypertension (DASH),⁵⁴ Mediterranean diet,⁵⁵ and plant-based diets,⁵⁶ of which have been shown to reduce CVD risk by ~20-40%.

Healthy moving:

The 2018 Physical Activity Guidelines for Americans recommend 150 minutes of moderate-intensity aerobic activity spread throughout the week during pregnancy and the postpartum period and continued vigorous activity for those who engaged in it pre-pregnancy.⁵⁷ Postpartum lifestyle intervention studies have shown significant improvements in gestational weight loss compared to usual care.⁵⁸ However, recruitment and retention rates were low across nearly all studies due to many of the barriers mentioned above to postpartum care.⁵⁹ Successful postpartum weight loss interventions are typically delivered by health professionals (e.g., dietitians, exercise physiologists) and combine diet and physical activity (compared to physical activity only).⁶⁰ There are also technology-mediated postpartum weight loss interventions, many of which were effective.⁶¹

Pharmacologic treatment:

Lifestyle interventions should be considered the first line risk-reduction strategy for patients with APOs, but there is an important role for pharmacologic therapies, particularly for some patients with a history of GDM, hyperlipidemia, and persistently elevated blood pressures.

The Diabetes Prevention Program (DPP) randomized 2,190 patients with impaired glucose tolerance and an elevated BMI to either 1) standard lifestyle with metformin, standard lifestyle with placebo, or 3) intensive lifestyle intervention.⁶² Among patients with a history of GDM (n = 350), intensive lifestyle modification and metformin, respectively, reduced the incidence of T2D by 53% and 50% after 3 years ⁶² and by 35% and 40% after 10 years.⁶³ For patients with no history of GDM (n = 1,416), lifestyle intervention reduced the risk of T2D by 49%, but metformin did not lead to a significant risk reduction (14%). Patients with GDM in the DPP study were randomized, on average, 12 years after their GDM diagnosis. Therefore, these findings may not apply to women at the highest risk and progress to type 2 diabetes in the first decade after pregnancy. In summary, intensive lifestyle modification is more effective than metformin therapy in preventing or delaying the onset of T2D for patients without a history of GDM, but either intervention represents a promising strategy for patients with GDM.

Statin therapy is a powerful CVD risk-reducing therapy for patients with atherosclerotic cardiovascular disease or severe hypercholesterolemia (LDL ≥190 mg/dl). Among patients over 40 years old, statins are also an evidence-based primary prevention strategy among patients with diabetes mellitus and high risk for ASCVD (≥20% over 10 years).⁶⁴ (Table 2).⁶⁴ A shared-decision making approach can be used to design an individualized prevention strategy, with a discussion of statins and antiplatelet medications, in this setting.

Finally, the 2017 ACC/AHA guideline recommends a therapeutic blood pressure target of <130/80 for CVD risk reduction.⁶⁵ Of note, ACOG recommends titrating medications in the postpartum period to achieve a blood pressure <150/100 among patients with chronic hypertension,⁶⁶ but no target is mentioned in the Practice Bulletin on Gestational Hypertension and Preeclampsia.⁶⁷ Findings from studies, such as the previously mentioned SNAP-HT trial, suggest that more aggressive control may lead to a quicker return to the normal range within 6 weeks postpartum and a long-term reduction in diastolic blood pressure,⁶⁸ but further study is needed.

Postpartum to primary care transition

The transition from postpartum to primary care is encumbered by many of the same barriers faced in the early postpartum period. In addition to the loss of health insurance for many patients, obstetric electronic medical records are often difficult to access, even within the same healthcare system, and a seamless hand-off of care from obstetric to primary care clinicians often does not occur. Obstetricians should take special care to ensure that patients with APOs transition to primary care. Referrals should be made for patients without established primary care relationships, or warm hand-offs should be given back to the patient’s primary care physician. The OB/GYN’s documentation in the medical record should include a summary of the APO, pregnancy course, and counseling.⁴¹

Primary care physicians are likely best equipped to manage long-term CVD risk-reduction strategies for patients with APOs. However, OB/GYNs still have an important role given that 1) Many patients will have more regular contact with OB/GYN’s rather than their primary care physicians, and 2) OB/GYNs are more likely to elicit a thorough pregnancy history, including a history of APOs, that may otherwise be unknown to the care team.

Since 2011, the American Heart Association (AHA) has recommended screening for a history of APOs among birthing-capable people.¹⁶ Clinicians may not have access to pregnancy records documenting APOs, but encouraging patients to relay their obstetric history is an important step in reducing these care gaps. Patients have excellent recall of pregnancy complications and their baby’s birthweight, but the questions about APOs are often not asked or appropriately followed up.⁶⁹ A study showed that obstetricians are significantly more likely than internists to elicit a pregnancy history and recognize the importance of a history of APOs, such as preeclampsia. However, if a history of preeclampsia is elicited, internists are more likely to know what to do with this information and order appropriate screening tests.⁷⁰

Pre-pregnancy care

It is worth noting that postpartum care is often also pre-pregnancy care. It is important to explore patients’ vision for their future family and support them in planning accordingly with tools such as contraception, knowledge about pregnancy spacing, and risks associated with a brief interpregnancy interval ≤6 to 18 months. Patients desiring future fertility should be counseled about folic acid supplementation initiated before pregnancy. Their medical co-morbidities and medication list should be reviewed and optimized. Potentially teratogenic medications should be discussed with an effective contraception plan in place.

Future directions and research opportunities

Significant knowledge gaps remain regarding the most effective strategies to quantify and mitigate CVD risk after APOs. Future studies require a multi-center, life-course approach in a diverse population that considers the contribution of APOs and the influence of pre-pregnancy and postpartum exposures. This chapter explored many of the overlapping risks and outcomes shared by APOs, but additional study is required to understand the time course and characteristics of lifestyle modifications that reduce lifetime CVD risk among this population. Likewise, further research on pharmacotherapy, in concert with lifestyle interventions, likely offers promise. GDM and HDP have consumed the majority of resources for APO prevention. Still, more data are needed to guide treatment and prevention strategies for patients with FGR, PTB, and pregnancy loss. Finally, each APO likely has its own unique phenotypes that manifest as different risk profiles during pregnancy and beyond, and these require further refinement and understanding so that APOs are not treated as a monolith.

In conclusion, APOs are markers of risk that present an opportunity to view pregnant women and birthing people’s life course through a different lens. As OB/GYN clinicians, this optimism should be reflected in our counseling during what otherwise often feels like a catastrophic event in pregnancy. It is important to remember that the 4^th trimester can also improve pregnancy outcomes because it is often a prequel to the subsequent 1^st trimester. This chapter primarily focused on the patient and clinician level, but interventions at the organizational and policy level are critical to addressing the many challenges mentioned throughout this chapter (e.g., lack of childcare, loss of health insurance, fragmented medical record systems) that hinder optimal postpartum care for patients with APOs.