Abstract
Purpose
Hypertensive disorders of pregnancy are increasing in prevalence and associated with significant maternal and perinatal morbidity and mortality.
Recent Findings
Increased emphasis has been placed recently on the use of out-of-office (i.e., home and ambulatory) blood pressure (BP) monitoring to diagnose and manage hypertension in the general population. Current guidelines offer limited recommendations on the use of out-of-office BP monitoring during pregnancy and postpartum.
Summary
This review will discuss the recent literature on BP measurement outside of the office and its use for screening, diagnosis, and treatment in pregnancy and postpartum, and will illuminate areas for future research.
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Introduction
Hypertensive disorders of pregnancy (HDP) are among the most commonly encountered conditions in pregnancy, affecting up to 20% of pregnancies, and their prevalence is rising [1••, 2, 3]. HDP are classified as chronic hypertension (HTN) (diagnosed prior to pregnancy or before 20 weeks gestation), gestational HTN (isolated HTN diagnosed at 20 weeks gestation or later), preeclampsia/eclampsia [increase in blood pressure (BP) with concomitant proteinuria or organ damage], and preeclampsia superimposed on chronic HTN [4•] (Table 1). HDP are associated not only with an increased risk of adverse maternal and perinatal outcomes, some of which may be preventable with BP control during pregnancy, but also with an increased risk of future HTN, diabetes, stroke, and cardiovascular disease (CVD) [1••, 2, 5,6,7,8,9, 10•, 11•, 12, 13••, 14, 15••, 16, 17, 18••]. HTN often persists or worsens in the postpartum period and can also arise de novo in the first days to weeks following delivery [19•, 20, 21]. HTN is the leading cause of postpartum readmission in the United States [22]. Women with elevated postpartum BP and postpartum preeclampsia, in particular those with severe HTN, are at an increased risk of stroke, seizures, heart failure, and death [5, 7]. The early identification and treatment of women at risk for these adverse HTN-related events during pregnancy and in the puerperium is likely to meaningfully reduce maternal morbidity and mortality.
Out of Office Blood Pressure Measurement During Pregnancy
The accurate determination of BP during pregnancy is essential, as both under- and over-treatment of HTN may result in harm to the mother and/or fetus [23••, 24]. Inadequate treatment increases the risk of placental abruption and maternal stroke, while over-treatment with antihypertensive medication can potentially reduce placental perfusion pressure resulting in placental insufficiency, fetal growth restriction, and premature delivery [1••, 25,26,27,28]. Currently, decisions surrounding antihypertensive therapy for most individuals with HTN, regardless of pregnancy status, are primarily based on office BP which is only a brief snapshot and a poor surrogate for a patient’s “true” BP [29, 30]. There is increasing interest in the use of out-of-office BP to guide BP management in non-pregnant adults. As out-of-office BP represents BP in the natural environment, it could reflect placental perfusion pressure better than office BP and may be a target for therapy during pregnancy as well. Out-of-office BP monitoring includes ambulatory BP monitoring (ABPM), which records BP measurements every 15 to 30 min over 24 h, and home BP monitoring (HBPM) which requires a patient to self-measure BP at least twice daily for 3–7 days (Table 2). ABPM and HBPM can also be used to identify phenotypes defined by a mismatch between office and out-of-office BP [31, 32]. In some individuals not taking antihypertensive medications, BP outside of the office is lower than office BP, termed white coat HTN, while in others it may be higher outside of the office, a phenomenon called masked HTN.
Accuracy of BP Devices in Pregnancy
Of note, the hemodynamic changes and peripheral edema associated with pregnancy, and preeclampsia in particular, may affect the accuracy of the algorithms used by oscillometric devices to measure BP [23••, 33••]. As such, guidelines recommend separately validating BP measurement devices for accuracy among pregnant women [34,35,36, 37••]. A systematic review of validation studies of office, ambulatory, and home BP measurement devices in pregnant women found 61% of devices specifically validated for use in pregnancy passed the validation study, though only 34% of studies were performed without any protocol violation [38••]. There are currently few ABPM or HBPM devices that have been consistently validated for accuracy in women with preeclampsia [38••, 39]. These devices are listed in Table 2.
The Role of Out-Of-Office Blood Pressure Measurement in Pregnancy
Screening for and Diagnosing HTN in Pregnancy
The United States Preventive Services Task Force (USPSTF) recently released a statement recommending providers obtain BP measurements during each prenatal care visit throughout the duration of pregnancy to screen for preeclampsia [40]. This recommendation is based on evidence that demonstrates the potential benefit from early detection of preeclampsia outweighs any potential harm associated with HTN treatment. There are currently no recommendations or guidelines from any society recommending the use of out-of-office BP measurement as a screening tool for HDP.
In men and non-pregnant women with elevated office BP, both the USPSTF and the American College of Cardiology (ACC)/American Heart Association (AHA) recommend obtaining BP measurements outside of the office setting to confirm the diagnosis of HTN prior to initiating treatment [41, 42]. As out-of-office BP measurements have been shown to be consistently lower than office BP measurements, a different BP threshold has been established for elevated out-of-office BP and out-of-office HTN in non-pregnant adults. In contrast, two studies of HBPM in pregnancy found office and home measurements were similar in pregnant women [43, 44], while another found home measurements to be higher than office BP [45]. Despite several studies examining BP trends over the course of pregnancy using HBPM and ABPM, there are currently limited data describing ideal diagnostic out-of-office cut-points for HDP [46,47,48,49,50,51,52,53]. A recent study by Mikami et al. attempted to fill this gap and recommends trimester specific BP cut-off values in pregnancy that are lower than those recommended in non-pregnant adults [54]. Ideally, further studies examining HBPM values and maternal-fetal outcomes are needed before a definitive out-of-office BP threshold for the diagnosis of HDP can be recommended.
White Coat HTN in Pregnancy
Currently, the only recommended use of ABPM in pregnancy is to confirm a diagnosis of suspected white coat HTN prior to initiating antihypertensive medication [1••]. Limited available data suggests that white coat HTN may affect from 30 to 70% of pregnant women [55, 56]. Compared to women with sustained HTN, defined as elevated office and out-of-office BP, women with white coat HTN had better pregnancy outcomes [57,58,59]. However, these studies were small, enrolled few women on antihypertensive medication, utilized ABPM devices of questionable validity in pregnancy, and did not adjust for potential confounders. These studies also found pregnant women with white coat HTN are not at increased risk for developing preeclampsia and have neonatal birth weights, rates of intrauterine growth restriction (IUGR), and hospital length of stay similar to women with sustained normotension (non-elevated office BP and non-elevated ambulatory BP). Cesarean section rates in women with white coat HTN are similar to those with sustained HTN (elevated office BP and elevated ambulatory BP), suggesting that office BP readings affect the decision-making processes leading to induction of labor and may lead to unnecessary cesarean deliveries. Although these studies suggest that identifying white coat HTN is important in pregnancy, most of these studies did not use ABPM devices that were specifically validated in pregnancy and their findings should be interpreted with caution.
Despite recommendations to use ABPM in pregnancy to diagnose white coat HTN, HBPM could be used in a similar manner. Although, as previously mentioned, diagnostic cut-offs for normative values of BP on HBPM during pregnancy have not been thoroughly vetted, several home BP monitors have been validated for use in pregnant women and can be utilized to identify women with elevated office BP and non-elevated out-of-office BP [38••, 60,61,62]. There are several advantages to the use of HBPM over ABPM for assessing white coat phenomena in pregnant women. Compared to ABPM, which is worn for only 24 h, HBPM captures “true” BP over a longer period of time, it has better reproducibility, is well tolerated, and does not interfere with sleep. HBPM is also more widely available and less costly than ABPM [63].
Masked Hypertension in Pregnancy
Although data are limited, approximately 33% of pregnant women with a history of HDP, diabetes, or active smoking who are not taking antihypertensive medications have been reported to have elevated out-of-office BP on ABPM, despite normal office BP [64••, 65]. Masked HTN in non-pregnant adults is an area of active investigation, as its presence is associated with a cardiovascular risk profile similar to that of office HTN [66]. Hermida et al. reported lower rates of preterm delivery and IUGR in women with masked HTN when office BP was normal compared to when office BP was elevated [65]. Future research is needed to better define the prevalence of masked HTN, use of HBPM vs. ABPM for diagnosis, and the associations of masked HTN with clinical endpoints in pregnancy.
When to Perform BP Monitoring in Pregnancy
Several hemodynamic adaptations occur as pregnancy progresses. Vasodilation and a drop in systemic vascular resistance are a hallmark of the first trimester, following which cardiac output and heart rate increase. In pregnancies not affected by HDP, BP increases in the third trimester and may normalize to a pre-pregnancy value by term. To monitor for the development of HDP, BP is checked at least monthly in all pregnant women as a routine part of obstetric practice, and more frequently in women with elevated BP [1••]. Current American College of Obstetrics and Gynecology (ACOG) recommendations for the use of HBPM in pregnancy include at least weekly home measurement in women with gestational HTN, and its use is also suggested for women with chronic HTN and poorly controlled blood pressure [1••]. It is important to note that similar to office BP measurement, proper HBPM technique including correct cuff size and positioning as well as an adequate rest period and the use of repeated measurements is required for accuracy. ABPM is less likely to be affected by measurement error as the devices are fitted in the office and programmed to obtain BP at fixed intervals over 24 h.
Monitoring Response to Antihypertensive Therapy
Evidence from randomized controlled trials shows that antihypertensive medications can reduce the risk of CVD events and mortality among men and non-pregnant women with HTN [42]. However, few well-designed studies have been conducted examining the effects of antihypertensive medication on maternal and fetal outcomes in pregnant women with HTN [11•, 67, 68]. Expert opinion from guidelines indicates that pregnant women should be treated with antihypertensive medications for systolic/diastolic office BP ≥ 160/105–110 mmHg. However, the effects of antihypertensive medication in pregnant women with mild to moderate HTN (systolic/diastolic OBP < 160/105–110 mmHg) are controversial [69, 70]. There may be unintended harm of antihypertensive medication to the fetus during pregnancy because of a reduction in plasma volume, electrolyte disturbance, decreased uteroplacental blood flow, or fetal growth retardation. A meta-analysis of studies including 4723 pregnant women with mild to moderate HTN was inconclusive regarding whether antihypertensive medication had a benefit or harm on important pregnancy outcomes beyond reducing progression to severe HTN, such as preeclampsia, small for gestational age babies, preterm birth, and fetal death [71]. The Control of Hypertension in Pregnancy Study (CHIPS) found no significant difference in maternal or fetal outcomes between tight BP control (target diastolic OBP of 85 mmHg) and a more lenient (less-tight) strategy (target diastolic OBP of 100 mmHg) in 987 women with HTN at enrollment, defined as a diastolic OBP of 90–105 mmHg or 85–105 mmHg if taking antihypertensive medications [11•]. There were no differences in the risk of pregnancy loss, need for high-level neonatal care, or overall maternal complications between the groups, although more women in the less-tight control group were more likely to have severe HTN. Additional ongoing studies are examining the effectiveness and safety of a BP treatment strategy for mild chronic HTN during pregnancy to a goal recommended for non-pregnant adults (systolic/diastolic OBP < 140/90 mmHg) as compared with no treatment unless HTN is severe.
Future studies investigating the conduct of HBPM and ABPM in pregnant women who are taking antihypertensive medication are needed to clarify how office BP and out-of-office BP should be factored into balanced management of HTN in pregnancy. For example, the relatively high prevalence of white coat HTN with its associated benign prognosis must be balanced against missing masked HTN with a potentially treatable excessive risk.
Role of Out-of-Office Blood Pressure Measurement in the Postpartum Period
There is a paucity of data regarding the evaluation and management of BP in the postpartum period (first 6–12 weeks following delivery when the physiologic changes due to pregnancy recede [72]. In a group of 203 women with planned postpartum inpatient stays of 1 week or longer, 12% of previously normotensive women became hypertensive and > 50% of women with HDP had a systolic/diastolic BP ≥ 150/100 mmHg [20, 21] in the postpartum period. A more recent study examining women admitted for cesarean section of a singleton pregnancy found 18.6% of women developed postpartum HTN, and 41.8% of these cases were de novo HTN [19•]. Guidelines suggest BP monitoring in the first 72 h postpartum and 7 to 10 days after delivery for women with HDP, although the supporting evidence is of poor quality [1••]. In practice, many women, especially those with mild HTN, may be discharged prior to 72 h and may not return for a BP check until a routine 6-week postpartum visit, resulting in missed opportunities for BP measurement and management.
Postpartum HTN, both in isolation and as a manifestation of preeclampsia, is one of the most important risk factors for the development of postpartum stroke [73]. Intracerebral hemorrhage is the single greatest cause of death in women with preeclampsia [74]. Recent efforts to redefine and optimize postpartum care into a continuum propose that all women have contact with a provider within the first 3 weeks postpartum, and those with HTN should have their BP evaluated in 3–10 days [75]. An approach to monitoring postpartum BP after discharge that minimizes patient burden and office visits may enhance identification of women with poorly controlled BP, and prevent potential adverse HTN-related events. HBPM is affordable, widely available, well-tolerated, easy to use, and validated to capture BP over an extended period of time [63]. HBPM also has the potential to minimize unnecessary visits for office BP measurement. As such, the measurement of out-of-office BP using HBPM may play an essential role in postpartum care.
Knowledge Gaps
Several important knowledge gaps and a lack of well-validated devices in women with preeclampsia limit the widespread use of out-of-office BP measurement for the management of HDP. ACOG guidelines endorse the use of HBPM throughout pregnancy in women with HTN, but do not specify how HBPM should be performed [1••]. There are scarce data on the minimum duration of HBPM required to reliably estimate mean home BP. Additionally, the long-term adherence to and tolerability of HBPM in pregnancy is unknown. A few prior studies of HBPM have found short-term adherence rates ranging from 73 to 96% (days to weeks) [45, 56, 76••], but long-term (weeks to months) adherence to HBPM has not been examined. Thus, the best approach for conducting HBPM in women with HDP remains unknown.
In addition to a lack of well-validated ABPM devices for use in pregnancy, there is a need for a head to head evaluation of the use of ABPM vs. HBPM to examine their respective sensitivities and specificities for the diagnosis of white coat and masked HTN, and the relation with important maternal-neonatal outcomes. These knowledge gaps have important potential clinical implications for pregnant women, and answering them could provide valuable information regarding the optimal use of out-of-office BP measurement in pregnancy.
There are many knowledge gaps in the monitoring, diagnosis, and treatment of postpartum HTN. There are scant contemporary data on the normal postpartum range of blood pressure. As a result, it is currently unclear who is at risk for the development of de novo postpartum HTN and could benefit from out-of-office BP measurement. Additionally, future studies of postpartum BP are needed to determine optimal postpartum target BP level and medication escalation/de-escalation treatment strategies.
Future Directions
Currently, clinicians rely primarily on office BP to make decisions on initiating and adjusting antihypertensive medication in pregnancy. However, out-of-office BP measurement offers a promising target for future studies of BP management in pregnant and postpartum women with HTN. Presently, it is unknown whether a reduction in ambulatory BP during treatment with antihypertensive medication has a stronger association with perinatal outcomes than OBP.
Conclusions
HTN is an increasingly common complication of pregnancy and the postpartum period that is associated with substantial maternal-perinatal morbidity and mortality. Pregnancy is associated with dynamic BP changes, and the accurate measurement of BP is critically important for the well-being of the mother and fetus [23••, 24]. The adjunctive use of out-of-office BP monitoring may help identify pregnant women with masked hypertension who may derive the most benefit from antihypertensive medication intensification, as well as women with white coat phenomena in whom antihypertensive medication intensification may be detrimental. Out-of-office BP measurement, including the use of home and ambulatory monitoring, is an invaluable tool to aid in guiding the diagnosis and management of HDP. The potentially high prevalence of white coat HTN and its benign prognosis in pregnancy, and the possible harm associated with antihypertensive medication on perinatal outcomes highlight the benefits of using out-of-office BP in addition to office BP to guide HTN diagnosis and treatment in pregnancy.
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Sources of Funding
This work was supported by K23-HL136853 (NAB) KL2TR001874 (EM) from the NIH and NCATS and K24 HL125704 (DS) from the National Heart, Lung, and Blood Institute (NHLBI) at the National Institutes of Health (NIH).
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Bello, N.A., Miller, E., Cleary, K. et al. Out of Office Blood Pressure Measurement in Pregnancy and the Postpartum Period. Curr Hypertens Rep 20, 101 (2018). https://doi.org/10.1007/s11906-018-0901-z
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DOI: https://doi.org/10.1007/s11906-018-0901-z