Introduction
The American Heart Association (AHA) and the National Institutes of Health (NIH) annually publish statistics related to heart disease, stroke, and cardiovascular risk factors. The following expert analysis is a summary of adverse pregnancy outcomes (APOs) included for the first time in the AHA Heart Disease and Stroke Statistics 2021 Update published on January 27, 2021.¹

Adverse pregnancy outcomes (APOs) namely preeclampsia, gestational hypertension, and preterm-birth occur in 10-20% of pregnancies.² They are interrelated disorders and secondary to placental dysfunction and vascular abnormalities such as endothelial dysfunction, inflammation and vasospasm.² Of the total maternal mortality of 17.4 deaths per 100,000 live births, cardiovascular conditions account for 26.5% of total maternal mortality.³ Preventive care to improve pre-pregnancy cardiovascular health (CVH) is important to reduce morbidity, mortality, and health care costs.

The purpose of this expert analysis is to review and highlight the latest data from the AHA Heart Disease and Stroke Statistics 2021 Update on the association between APOs and long-term maternal CVH, as well as risk factors for developing APOs. 

Hypertensive Disorders of Pregnancy

• Hypertensive disorders of pregnancy (HDP) include gestational hypertension, preeclampsia, eclampsia and preeclampsia superimposed on chronic hypertension⁴ which occur in almost 10% of pregnancies in the United States.⁵ Compared to 2006-2010, the contribution of HDP towards maternal mortality has declined, whereas that of cardiovascular conditions has increased.⁶
• Several risk factors significantly elevate risk of HDP, especially that of preeclampsia. These include maternal age >35 years, prior preeclampsia, chronic hypertension, pre-pregnancy diabetes and/or obesity, polycystic ovarian syndrome (PCOS), prior stillbirth, multifetal pregnancy, nulliparity, chronic kidney disease (CKD), systemic lupus erythematosus (SLE), antiphospholipid antibody syndrome, and conception by assisted reproductive techniques.
• These risk factors should be identified at ≤16 weeks of gestation⁷ and according to United States Preventive Services Taskforce (USPSTF)/American College of Obstetricians and Gynecologists (ACOG) practice guidelines, aspirin (ASA) 81mg per day is recommended prophylaxis for women at high risk of preeclampsia starting from about 12 weeks of gestation.
• A population based Swedish registry that included female twin pairs with known zygosity found that for preeclampsia, the estimates of heritability and nonshared environmental effect were 0.54 (95% confidence interval 0 – 0.71) and 0.46 (0.29 – 0.67), respectively; corresponding estimates for gestational hypertension were 0.24 (0 – 0.53) and 0.76 (0.47 1.00), respectively. When considering both diseases as a single entity (pregnancy-induced hypertensive diseases), the heritability estimate was 0.47 (0.13 – 0.61). These results suggest that genetic factors are important in the development of preeclampsia as well as gestational hypertension;⁸ therefore, screening for a family history of preeclampsia may help identify women at increased risk.
• Preeclampsia and any HDP are associated with increased odds of various cardiovascular disease (CVD) in later life including chronic hypertension, atherosclerotic CVD, heart failure, atrial fibrillation as well as cardiovascular mortality.⁹
• The incidence of hypertension 2 to 7 years postpartum is high in females with any APO, but greater in those who experience more than one APO such as HDP, preterm birth (PTB) and stillbirth or a combination of these.¹⁰ With the proposed "dose dependent" effect of HDP, future risk of developing chronic hypertension depends on severity of hypertension in pregnancy.¹¹
• Kajantie et al. found that impact of preeclampsia persists beyond in-utero life leading to significant risk of stroke, however interestingly not coronary heart disease.¹² The off-springs of preeclamptic pregnancies also have increased CVD risk factors, higher systolic blood pressure (SBP), diastolic blood pressure (DBP) and body mass index (BMI) as shown in a meta-analysis by Andraweera et al.¹³

Preterm Birth

• This update also highlighted that the proportion of pre-term (<37 weeks) births (PTB) remained relatively unchanged from 9.93% to 10.02% from 2016 to 2018,¹ however PTB rates were higher among non-Hispanic Black females compared to non-Hispanic White and Hispanic females.¹⁴ Women entering the pregnancy with lower range stage 1 chronic hypertension are at increased risk for PTB as well as preeclampsia and stillbirth.¹⁵
• For infants born of preterm delivery, the gestational age is inversely associated with mortality¹⁶ and risk for premature coronary heart disease (CHD) in adulthood.¹⁷ Those who are born before 32 weeks' gestation also have higher risk for premature cerebrovascular disease.¹⁸
• In mothers PTB is associated with increased risk for traditional CVD risk factors later in life post-pregnancy, such as hypertension, type 2 diabetes mellitus, and hyperlipidemia.¹⁹ Women with a history of PTB have a 63% higher risk of future CVD as compared to those without.²⁰
• The Coronary Artery Risk Development in Young Adults Study (CARDIA) study showed women who had PTB had higher SBP and more coronary artery calcification (CAC) over 25 years of follow-up.²¹

SGA Delivery

• Percentage of small for gestational age (SGA) delivery with low-birth-weight <2500g has remained unchanged from 8% to 8.3% from 2014 to 2018.¹ Non-Hispanic Black and Asian females are more likely to have a pregnancy complicated with SGA compared to non-Hispanic White females.¹
• Risk for SGA delivery is elevated with even mild stage 1 hypertension.¹ Every 1mmHg rise in DBP from early to late pregnancy increases the risk of SGA by 2%.²² Pre-pregnancy underweight BMI and low gestational weight gain (GWG) are additional risk factors for an SGA delivery.²³
• SGA deliveries affect maternal CVH for years after post-partum period. Females with history of delivering a SGA offspring are at higher 10-year risk of CVD at 50 years of age.²⁴
• Birth weight also has impact on CVH later in adult life. The birth weights in cases of SGA deliveries were inversely associated with risks for all-cause mortality (moderate association) and CVD mortality (stronger association).²⁵

Pregnancy Loss

• Stillbirth and late fetal death (>28 weeks of gestation) rates were stable from 2014 to 2016; however, non-Hispanic Black females and females >35 years of age are at higher risk for stillbirth. Women with preexisting cardiovascular disease, diabetes, or hypertension have greater odds of stillbirth.²⁶
• Women who have spontaneous abortions as opposed to induced abortions are more likely to have hypertension, type 2 diabetes mellitus, and hyperlipidemia.²⁷
• Maternal genetic factors, especially thrombophilias and fetal genetic factors such as aneuploidy are known risk factors for stillbirth.
• Women with history of pregnancy loss may have greater risk for incident CVD in later life as well as higher levels of risk factors for CVD (hypertension, diabetes, higher BMI).²⁸

Conclusion
Several risk factors pre-pregnancy play roles in development of APOs, including adverse levels of CVH (e.g. BMI, SBP, glucose). Specifically, history of chronic CVD risk factors present in pre-pregnancy significantly increase the risk of HDP,⁷ PTB,¹⁵ SGA,¹⁵ and stillbirth.²⁶ This highlights the importance of monitoring and optimizing CVH pre-pregnancy and screening of CVD risk factors routinely before and during each pregnancy and the importance of preventive care for young women. Focusing on traditional CVD risk factor burden in women desiring pregnancy is of paramount importance and should ideally happen during preconception counseling or alternatively in the post-partum time frame.

APOs are associated with an increased risk of development of CVD in later life.^{10,11,19-21,24,25} Obtaining a detailed obstetric history from women in all age groups will identify CVD risk factors and can focus attention on modification of these risk factors. Maternal complications of APOs extend beyond the gestational period and into the adult life.

References

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3. Creanga AA, Berg CJ, Syverson C, Seed K, Bruce FC, Callaghan WM. Pregnancy-related mortality in the United States, 2006-2010. Obstet Gynecol 2015;125:5–12.
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12. Kajantie E, Eriksson JG, Osmond C, Thornburg K, Barker DJP. Pre-eclampsia is associated with increased risk of stroke in the adult off-spring: the Helsinki Birth Cohort Study. Stroke 2009;40:1176–80.
13. Andraweera PH, Lassi ZS. Cardiovascular risk factors in offspring of pre-eclamptic pregnancies: systematic review and meta-analysis. J Pediatr 2019;208:104–113.e6.
14. Martin JA, Hamilton BE, Osterman MJK. Births in the United States, 2018. NCHS Data Brief 2019:1–8.
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18. Ueda P, Cnattingius S, Stephansson O, Ingelsson E, Ludvigsson JF, Bonamy AKE. Cerebrovascular and ischemic heart disease in young adults born preterm: a population-based Swedish cohort study. Eur J Epidemiol 2014;29:253–60.
19. Tanz LJ, Stuart JJ, Williams PL, et al. Preterm delivery and maternal cardiovascular disease risk factors: the Nurses' Health Study II. J Womens Health (Larchmt) 2019;28:677–85.
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21. Catov JM, Snyder GG, Fraser A, et al. Blood pressure patterns and subsequent coronary artery calcification in women who delivered preterm births. Hypertension 2018;72:159–66.
22. Wikström AK, Gunnarsdottir J, Nelander M, Simic M, Stephansson O, Cnattingius S. Prehypertension in pregnancy and risks of small for gestational age infant and stillbirth. Hypertension 2016;67:640–46.
23. Santos S, Voerman E, Amiano P, et al. Impact of maternal body mass index and gestational weight gain on pregnancy complications: an individual participant data meta-analysis of European, North American and Australian cohorts. BJOG 2019;126:984–95.
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25. Risnes KR, Vatten LJ, Baker JL, et al. Birthweight and mortality in adulthood: a systematic review and meta-analysis. Int J Epidemiol 2011;40:647–61.
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Clinical Topics: Arrhythmias and Clinical EP, Congenital Heart Disease and Pediatric Cardiology, Diabetes and Cardiometabolic Disease, Dyslipidemia, Heart Failure and Cardiomyopathies, Prevention, Atrial Fibrillation/Supraventricular Arrhythmias, CHD and Pediatrics and Arrhythmias, CHD and Pediatrics and Prevention, CHD and Pediatrics and Quality Improvement, Acute Heart Failure, Hypertension

Keywords: Dyslipidemias, Pregnancy, Hypertension, Pregnancy-Induced, Cardiovascular Diseases, Birth Weight, Premature Birth, Body Mass Index, Polycystic Ovary Syndrome, Pre-Eclampsia, Blood Pressure, Gestational Age, Pregnancy Outcome, Abortion, Spontaneous, Diabetes Mellitus, Type 2, Stillbirth, African Americans, American Heart Association, Live Birth, Maternal Mortality, Atrial Fibrillation, Hyperlipidemias, Antiphospholipid Syndrome, Aspirin, Coronary Vessels, Confidence Intervals, Maternal Age, Follow-Up Studies, Eclampsia, Risk Factors, Postpartum Period, Abortion, Induced, Cerebrovascular Disorders, Infant, Low Birth Weight, Stroke, Coronary Disease, Heart Failure, Obesity, Reproductive Techniques, Assisted, Renal Insufficiency, Chronic, Fertilization, Health Care Costs, Lupus Erythematosus, Systemic, Aneuploidy, Inflammation, National Institutes of Health (U.S.), Registries, Thrombophilia

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