Commentary on Pregnancy Report

Relative to the amount of research in the general area of hypertension and related regions, hypertension in pregnancy has received relatively minor attention. This is especially true in outcomes research, yet hypertensive disorders of pregnancy (HDP) remain one of the major causes of pregnancy-related maternal and fetal morbidity and mortality worldwide. Thus, due to the lack of outcome data, the amount of “strong evidence-based” guidelines has traditionally lagged in the hypertension field. Further contributing to this issue of a “data dearth” is that HDP encompasses a spectrum of disorders extending from chronic hypertension, gestational hypertension, preeclampsia/ eclampsia, and preeclampsia superimposed on chronic hypertension¹. Given this broad spectrum of associated diseases that all have hypertension as a common theme, guidance for the use of antihypertensive medications and management of blood pressure issues in pregnancy, specifically preeclampsia, has expanded beyond the use of central alpha-2 agonists such as methyldopa despite the absence of appropriately powered multicenter outcome trials.

More recently, in contrast to prior decades, the amount of research at both the basic and clinical level in pregnancy-associated hypertension, especially regarding understanding disease mechanisms has been extended. The current position paper by Garovic and colleagues of the American Heart Association provides a straightforward, well-written, and well-defended approach to various types of hypertension seen in pregnancy¹. It offers important updates in Hypertension and Pregnancy and is the most concise and up-to-date reference available written by experts in the field. As a former guideline writer of the Hypertension in Pregnancy Guidelines, my overall impression of this report is not only is it unbiased but provides a broad and fair overview of the international guidelines in this area². Moreover, it provides and solid rationale for the conclusion and recommendations reached. Hence, the reader will have a clear understanding of what the world consensus is on the spectrum of umbrella topics under hypertension in pregnancy.

New insights at both the basic and clinical level are critical to expanding our understanding and application of expansive pharmacology to bedside treatment. Unlike any other area of medicine, these treatments need to be safe for both the fetus and mother as well as help keep blood pressure (BP) in a safe range to allow the pregnancy to continue naturally. Additionally, this report presents a synthesis of the most current scientific evidence on the broad topic. This literature is relevant to the current controversies regarding HDP diagnostic and treatment strategies. It is a timely evaluation given that current trends indicating the incidence of HDP continues to increase due to advanced age at first pregnancy and increased prevalence of obesity and other cardio-metabolic risk factors¹. Cardiovascular diseases, including strokes and cardiomyopathy, now account for half of all maternal deaths³. Pregnancy-related stroke hospitalizations increased more than 60% from 1994 to 2011, and HDP associated stroke rates increased 2-fold compared to non-HDP related stroke⁴.

Most guidelines around the world are aligned in defining hypertension in pregnancy as a BP ≥140/90 mm Hg, including those from OB/GYN societies¹. However, the 2017 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults lowered the threshold for the diagnosis of Stage 1 hypertension to 130/80 mm Hg, from 140/90 mm Hg⁵. As noted earlier, this variability regarding the threshold for initiating antihypertensive treatment is due to uncertainty about the maternal benefits of lowering BP and the potential fetal risks from medication-induced reductions in uteroplacental circulation and in utero exposure to antihypertensive medications¹.

This critical review also examines the data on mechanisms of hypertension and preeclampsia, not just the epidemiology of the topic. It discusses the molecular and pathophysiological mechanisms of preeclampsia, as the etiologies are unknown. However, the authors provide a meaningful synthesis of the recent data and concepts by focusing on the interaction between factors from both maternal and placental pathways. One of their assertions is that the associated widespread endovascular damage and dysfunction may be long-lasting with a possible intergenerational effect¹.

The authors appropriately make a major point about prevention of preeclampsia and adverse maternal and fetal outcomes. They focus on several factors, including preconception health. In addition, lifestyle changes before and during pregnancy may ameliorate both maternal and fetal risks. The topics mentioned earlier are discussed extensively and are a critical social message contained in this analysis. The authors quote a meta-analysis of 44 randomized controlled trials reporting that dietary interventions reduce maternal gestational weight gain and improve pregnancy outcomes⁶. In addition to dietary intervention, the role of exercise has also been reported to reduce gestational hypertension and preeclampsia risk by 30 to 40%, respectively⁶. They also discuss antiplatelet therapy as a preventive measure. They note that low dose aspirin, starting between 12 and 16 weeks of gestation, reduces the risk of preeclampsia and related adverse outcomes by 10 to 20% in women at increased risk¹.

The authors appropriately spend time discussing BP, where and when to measure it, and how it differs from guidelines regarding the general population. The authors advocate home BPs, and if the patient is taught to take BP correctly, these are reliable and valuable data. Moreover, these home BP measurements among the general population are encouraged as well⁵. Of note, home BP measurements seem to be uniformly encouraged, as also recommended by The American College of Obstetricians and Gynecologists and the International Society for the Study of Hypertension in Pregnancy (ISSHP) in women with chronic or gestational hypertension, particularly when uncontrolled¹. The authors note that available information does not demonstrate a systematic difference between self and office BP measurements in pregnancy, which suggests appropriate treatment and diagnostic thresholds for self-monitoring during pregnancy may be equivalent to standard clinic thresholds.

This review article has an extensive discussion on secondary hypertension, causes of which are unappreciated in a pregnant woman. Given that secondary hypertension occurs in only about 10% of the estimated 83 million people with hypertension, it should strongly be considered in those with a maternal age <35 years, hypertension is severe or resistant, there is no family history of hypertension, or there are suggestive laboratory features, such as hypokalemia, elevated creatinine, or albuminuria early in pregnancy¹. The authors also discuss the increased prevalence of obesity in reproductive-aged women and the contribution of obstructive sleep apnea as a cause of secondary hypertension among pregnant women.

One distinction of this review compared to others is the discussion of postpartum hypertension and postpartum preeclampsia. The authors note that these entities are significant for two reasons: first, 80% of all maternal deaths occur within the first week postpartum, and HDP remains one of the leading causes; second, postpartum hypertension offers an opportunity to use medications and achieve BP goals without limitations related to their potential negative impacts on the fetus. However, the caveat to their assertion is that there are limitations. For example, if the mother is breastfeeding, some medications enter the breast milk and influence the baby’s heart rate and cardiovascular factors. They further note that the prevalence of postpartum hypertension may be as high as 8% in women without antepartum hypertension. Furthermore, this elevated BP may be present for up to six weeks post-delivery and up to three months post-delivery among those with preeclampsia.

The group summarizes the current recommended published guidelines worldwide addressing diagnosis and treatment of HDP. They note that differences among societies further demonstrate confusion in the field, which leads to failure to move forward to a unified guideline. However, most of the world’s BP guidelines on this topic seem to be unified. The ACOG, in their most recent update, appears to be the outlier. ACOG recommends antihypertensive therapy for women with preeclampsia and a sustained systolic BP ≥160 mm Hg and/or diastolic BP ≥110 mm Hg, and with chronic hypertension at a systolic BP ≥160 mmHg or diastolic BP ≥110 mm Hg, with 120-160/80-110 mm Hg as a treatment goal.

Internationally, most hypertension societies endorse a more aggressive approach for antihypertensive treatment, recommending therapy when BP is ≥140/90 mm Hg. As the authors note, therapeutic targets similar to the ACC/AHA target of 130/80 mmHg are recommended by the ISSHP, Hypertension Canada Guidelines, NICE, and the WHO¹. The question then arises why the diagnostic and treatment BP thresholds are higher in the U.S. than those recommended for non-pregnant individuals and, in comparison, to most international guidelines addressing HDP. The authors point out that while the ACOG authors provide a reasonable explanation for this BP divergence, the data on which they anchor their decisions are weak. Given new developments in the field of hypertension outside of pregnancy that support lower BP treatment targets, together with emerging data from more extensive clinical trials in pregnancy, this reviewer reinforces the working group’s stance of continued investigation to determine whether BP levels are similar to those recommended outside of pregnancy for initiation of therapy and as therapeutic targets are beneficial for the mother and safe and beneficial for the fetus. While waiting for more conclusive data and trials nearing completion, the working group endorses informed decision-making in partnership with the patient regarding whether to treat non-severe hypertension during pregnancy to targets like those recommended in non-pregnant individuals. The authors note that personalization of therapy is a rational approach by giving special attention to other risk factors related to hypertension-related adverse outcomes (such as pre-existing heart or kidney disease; obesity and Black race).

Lastly, the review team recommends, and this reviewer strongly agrees with, a multidisciplinary team approach. The management of hypertension in pregnancy requires multidisciplinary collaborations among obstetricians, maternal-fetal medicine specialists, neonatologists, nephrologists, hypertension specialists, cardiologists, anesthesiologists, pharmacists, nurses, and midwives cohesive and safe preconception, ante-, peri- and postpartum care. The authors point out that nurses and midwives in case management roles coordinate care and facilitate access to resources and services that improve health outcomes. Moreover, nursing recognition of maternal compromise during hospital admission using early warning scores, hypertension bundles, and toolkits ensures timely communication with a physician or advanced practice nurse. The authors argue that this interaction has reduced maternal mortality from hypertensive disorders.