Chapter 53. Chronic Hypertension. Will Obs

 Chronic Hypertension

BS. Nguyễn Hồng Anh 

In reproductive-aged women, the prevalence o hypertension

approximates 6 percent (Centers or Disease Control and Prevention, 2017). Tus, not surprisingly, chronic hypertension

is one o the most common serious complications encountered during pregnancy. In one study o more than 56 million births, the incidence was 1.8 percent (Bateman, 2012).

Chronic hypertension complicated 2.3 percent o pregnancies

in data rom the Medicaid Analytic Extract (Bateman, 2015).

Despite an increasing prevalence rom 1970 to 2010, optimal

management has not been well studied (Ananth, 2019).

Chronic hypertension usually improves during early pregnancy. Tis is ollowed by variable behavior later in pregnancy

and may include development o superimposed preeclampsia.

Te latter carries signicant risks or maternal and perinatal

morbidity and mortality.

GENERAL CONSIDERATIONS

Blood pressure is a polygenic biological variant that diers

between populations. Numerous epigenetic actors also inuence penetrance dierences between individuals. Moreover,

clinical eatures such as increasing age and weight correlate positively with rising pressures. Last, resting blood pressure measurements do not reect daily activities. Tereore, adults have

a broad range o normal blood pressure values, which makes

dening hypertension difcult.

■ Definition and Classification

Chronic hypertension would logically be dened as some level

o sustained resting blood pressure that is associated with acute

or long-term adverse eects. Most consider 140/90 mm Hg

as the upper limit o normal. In the United States, these values were derived primarily rom lie insurance actuarial tables

constructed using data rom white adult males. Tese “norms”

disregard ethnicity, gender, and other covariants. Te importance o race is emphasized by Kotchen (2018), who cites

the incidence o hypertension—dened as blood pressure

>140/90 mm Hg—to be 34 percent in blacks, 29 percent in

whites, and 21 percent in Mexican Americans.

For many years, the Joint National Committee promulgated guidelines or diagnosis, classication, and management o chronic hypertension. Recently, a coalition led by

the American College o Cardiology and the American Heart

Association published criteria or the diagnosis o hypertension

(Table 53-1) (Whelton, 2018)

TABLE 53-1. Criteria for Diagnosis of Hypertension

■ Treatment and Benefits for

Nonpregnant Adults

Chronic hypertension accounts or nearly 15 percent o deaths

worldwide (Kotchen, 2018). Long term, hypertension raises

substantively the risk o cardiovascular disease, coronary heart

disease, congestive heart ailure, stroke, renal ailure, peripheral arterial disease, and mortality. Tese risks decline with

treatment o otherwise normal adults who have sustained

hypertension.

Based on these benets, current guidelines recommend antihypertensive therapy or stage 1 hypertension in nonpregnant

adults with risk actors or current or uture cardiovascular disease.

However, given the dierent diagnostic criteria in pregnancy (see

able 53-1), the best management or women being treated and

contemplating pregnancy, or those undergoing treatment who

become pregnant, or or those rst identied to have chronic

hypertension during pregnancy is unknown (American College

o Obstetricians and Gynecologists, 2018a; August, 2015). In

these women, the benets and saety o instituting antihypertensive therapy are less clear, as subsequently discussed.

■ Preconceptional Counseling

Women with chronic hypertension ideally undergo counseling beore pregnancy (American College o Obstetricians and

Gynecologists, 2018b). Initial questions ascertain hypertension duration, degree o blood pressure control, and current

therapy. Home measurement devices are checked or accuracy.

General health, daily activities, and dietary habits also are

assessed (Table 53-2). Women who require multiple medications or control or who have poorly controlled pressures carry

greater risk or adverse pregnancy outcomes. Patient counseling

should disclose maternal and etal risks, which are detailed in

later sections (pp. 946 and 948).

For hypertensive women with disease exceeding 5 years or

with comorbid diabetes, cardiovascular and renal unction are

assessed (August, 2015; Chahine, 2019). Renal unction is evaluated by serum creatinine measurement and urine spot protein/

creatinine ratio measurement. I the ratio is abnormally high

(>0.3), proteinuria can be urther quantied with a 24-hour

urine collection (Kuper, 2016; Morgan, 2016a).

Women with evidence o organ dysunction or those with

prior adverse events such as a stroke, myocardial inarction,

arrhythmias, or ventricular ailure carry markedly higher risks

or a recurrence or worsening dysunction during pregnancy.

Specic preconceptional guidance or these conditions is

ound in Chapters 63 (p. 1132) and 52 (p. 918), respectively.

Although poorly controlled hypertension is considered a contraindication or pregnancy by some, there is no consensus.

Women who maintain persistent systolic pressures ≥160 mm

Hg or diastolic pressures ≥110 mm Hg despite therapy; require

multiple antihypertensive agents; have a serum creatinine level

>2 mg/dL; or have a history o prior stroke, myocardial inarction, or cardiac ailure must be counseled regarding the marked

risks to themselves and to their etus. Tese are described in the

next sections.

PREGNANCY CONSIDERATIONS

■ Diagnosis and Evaluation

Chronic hypertension is diagnosed i it precedes pregnancy or

i it is identied beore 20 weeks’ gestation. Prior to this gestational age, preeclampsia is rarely seen (Chap 40, p. 690). Te

American College o Obstetricians and Gynecologists (2018a,

2020) denes hypertension as a systolic pressure ≥140 mm Hg or

a diastolic pressure ≥90 mm Hg (see able 53-1). In suspected

TABLE 53-2. Lifestyle Modifications for Hypertensive Patients

Weight reduction: BMI ≤25 kg/m2

Consume a dietary pattern that emphasizes intake of vegetables, fruits, and whole grains; includes low-fat dairy products,

poultry, fish, legumes, nontropical vegetable oils, and nuts; and limits sweets and red meats. Examples are DASH, USDA

Food Pattern, or the AHA Diet

Lower sodium intake: consume no more than 2400 mg/d; 1500 mg/d desirable

Engage in aerobic physical activity three to four sessions per week, lasting on average 40 minutes per session, and involving

moderate- to vigorous-intensity physical activity

Moderation of alcohol consumption: ≤1 drink daily (none when pregnant)

AHA = American Heart Association; DASH = Dietary Approaches to Stop Hypertension; USDA = United States Department

of Agriculture.

Summarized from Kotchen, 2018; Whelton, 2018.

cases o “white-coat” hypertension, serial ambulatory monitoring can be considered. In some women without overt chronic

hypertension, a history o repeated pregnancies complicated by

gestational hypertension, with or without preeclampsia, may be

elicited. Either is a risk actor or latent chronic hypertension.

Tis is especially true or prior preeclampsia and particularly or

early-onset preeclampsia (van Eerden, 2018). In many ways,

gestational hypertension is analogous to gestational diabetes.

Women with the ormer have a chronic hypertensive diathesis, in

which heredity and epigenetics play a major role.

Although uncommon, secondary causes o hypertension are

always a possibility in aected women. Tus, chronic renal disease, obstructive sleep apnea, connective tissue disease, primary

aldosteronism, Cushing syndrome, pheochromocytoma, and

myriad other causes are considered during evaluation (American

College o Obstetricians and Gynecologists, 2018a). Tat said,

most pregnant women with antecedent hypertension will have

otherwise uncomplicated disease. Te hypertensive disorders that

uniquely complicate pregnancy are discussed in Chapter 40.

■ Risk Factors

Several actors increase the likelihood that pregnant women

will have chronic hypertension. Tree o those most requently

cited are ethnicity, obesity, and diabetes. As previously noted,

black women are more commonly aected. Related to this,

hundreds o blood pressure–related phenotypes and genomic

regions have been identied (Ward, 2015). Obesity may raise

the prevalence o chronic hypertension tenold (Chap. 51, p.

904). In addition, obese women are more likely to develop

superimposed preeclampsia (Ornaghi, 2018).

Te metabolic syndrome is a clinical cluster that includes

hypertension, high blood sugar, excess at at the waist, and abnormal cholesterol or triglyceride levels. Tis constellation is a risk

marker or superimposed preeclampsia and or persistent postpartum hypertension (Jeyabalan, 2015). Diabetes is also prevalent in

chronically hypertensive women, and its interplay with obesity

and preeclampsia is prominent (Leon, 2016). Te most requent

comorbidities associated with chronic hypertension are pregestational diabetes—6.6 percent, thyroid disorders—4.1 percent, and

collagen vascular disease—0.6 percent (Bateman, 2012).

■ Physiological Effects of Chronic Hypertension

Blood pressure decreases in the rst trimester due to a 30-percent

drop in systemic vascular resistance. In most women with chronic

hypertension, this decline is ollowed by a rise in blood pressure

during the third trimester (Fig. 53-1). Women with chronic

hypertension have persistently elevated vascular resistance and

possibly reduced intravascular volume expansion (ihtonen,

2007). Moreover, in women with superimposed preeclampsia,

arterial mechanical properties are most marked (Hibbard, 2015).

ADVERSE PREGNANCY EFFECTS

Chronic hypertension is associated with adverse maternal and

perinatal outcomes listed in Table 53-3. Rates o these complications positively correlate with the severity and duration o

prepregnancy hypertension. Elevated blood pressure dened by

criteria in able 53-1 may herald adverse outcomes similar to

those in women with chronic hypertension dened by criteria o

the American College o Obstetricians and Gynecologists (Keene,

2019; Sutton, 2018). Development o superimposed preeclampsia, particularly early-onset disease, is especially dangerous.

■ Maternal Morbidity and Mortality

Most women with satisactorily controlled hypertension and no

end-organ damage will do well in pregnancy. Complications

are more likely with severe baseline hypertension and documented end-organ damage, especially ventricular hypertrophy

and hypertensive glomerulosclerosis (Ambia, 2018, 2019; Morgan, 2016b). Women with chronic hypertension have higher

rates o stroke, pulmonary edema, and renal ailure (Gilbert,

2007; Zokie, 2018). Tese observations were veried in the

report rom the Nationwide Patient Sample (Bateman, 2012).

140

120

Blood pressure (mm Hg)

100

80

60

160

40

10 15 20 25 30 35 40

Gestational age (weeks)

Chronic hypertension

Normal pregnancy

FIGURE 53-1 Mean systolic and diastolic blood pressures across

pregnancy in 107 untreated chronically hypertensive women

(yellow) compared with blood pressures across pregnancy in 4589

healthy nulliparas (blue). (Data from August, 2015; Levine, 1997;

Sibai, 1990.)

TABLE 53-3. Some Adverse Effects of Chronic

Hypertension on Maternal and

Perinatal Outcomes

Maternal Perinatal

Superimposed preeclampsia Stillbirth

HELLP syndrome Fetal-growth restriction

Placental abruption Preterm delivery

Pulmonary edema Neonatal death

Stroke Neonatal morbidity

Acute kidney injury Congenital anomalies

Heart failure

Hypertensive cardiomyopathy

Myocardial infarction

Maternal death

HELLP = hemolysis, elevated liver enzyme levels, low

platelet count.

In this study, hypertension complications included pulmonary

edema—1.5 per 1000, stroke—2.7 per 1000, mechanical ventilation—3.8 per 1000, acute kidney injury—5.9 per 1000,

and maternal mortality—0.4 per 1000. In another report,

the maternal mortality rate was greater in women with severe

hypertension (Akbar, 2019). Peripartum cardiomyopathy is

another associated risk (Cunningham, 2019).

Dangerous blood pressure elevation can develop with

chronic hypertension. Systolic pressure ≥160 mm Hg or

diastolic pressure ≥110 mm Hg will rapidly cause renal or

cardiopulmonary dysunction or cerebral hemorrhage (Clark,

2012). In addition to hypertensive heart ailure mentioned

above, coronary artery and aortic dissection have been described

(Faden, 2016; Weissman-Brenner, 2004). With superimposed

preeclampsia or eclampsia, the maternal prognosis is poor

unless the pregnancy is ended (Becker, 2018). Placental abruption is a common and serious complication (p. 946).

Chronic hypertension is associated with a veold higher risk

or maternal death (Gilbert, 2007). In the United States rom

2011 to 2013, hypertensive disorders, including chronic hypertension and preeclampsia syndrome, accounted or 7.4 percent

o 2009 pregnancy-related deaths (Creanga, 2017). Undoubtedly related were other causes o death such as cardiovascular conditions—15.5 percent, cerebrovascular accidents—6.6

percent, and cardiomyopathy—11 percent. Moodley (2007)

reported similar ndings in 3406 maternal deaths rom South

Arica.

■ Superimposed Preeclampsia

Te reported incidence o superimposed preeclampsia varies rom 20 to 50 percent because it is not precisely dened

(American College o Obstetricians and Gynecologists, 2018a,

2020; Bramham, 2016; Moussa, 2017). In a Maternal-Fetal

Medicine Units Network trial, superimposed preeclampsia was

diagnosed in 25 percent o hypertensive gravidas (Caritis,

1998). August and colleagues (2015) hypothesize that this

predilection may stem rom similar genetic, biochemical, and

metabolic abnormalities.

Te risk or superimposed preeclampsia positively correlates

with the severity o baseline hypertension and the need or

antihypertensive therapy (Ankumah, 2014; Morgan, 2016a).

Preliminary observations indicate that pregnant women with

initial blood pressures ≥130/80 mm Hg early in pregnancy

have excessive rates o preeclampsia (Greiner, 2020; Keene,

2019; Roman, 2020). Moreover, compared with women who

do not develop preeclampsia, these pressures nadir earlier in

gestation (Fig. 53-2) (Morgan, 2016a). Te preeclampsia risk is

even greater i end-organ damage, such as baseline proteinuria,

is present.

Prediction

Tus ar, individual predictive tests or superimposed preeclampsia have been disappointing (Conde-Agudelo, 2015;

Correa, 2016). First-trimester serum markers used or aneuploidy screening are one group (Chap. 17, p. 338). O these,

inhibin A levels are reduced in patients destined to develop

preeclampsia, but its low sensitivity makes it clinically

unuseul (Sibai, 2008; Zeeman, 2003). Similarly, maternal

serum pregnancy-associated plasma protein-A (PAPP-A) levels

are decreased in the rst trimester o pregnancies that are later

complicated by preeclampsia (an, 2018). O angiogenic and

antiangiogenic actors, low plasma levels o placental growth

actor (PlGF) and high levels o soluble ms-like tyrosine

kinase-1 (sFlt-1) have been associated with superimposed

preeclampsia development (Binder 2020; Nzelu, 2020). Last,

the umbilical artery pulsatility index appears to be elevated

in the rst trimester o these pregnancies (O’Gorman, 2016).

Combining all these actors may be useul in predicting superimposed preeclampsia (O’Gorman, 2016; Stepan, 2020).

Prevention

rials using various medications to prevent preeclampsia in

women with chronic hypertension show little or no benet.

Low-dose aspirin has been evaluated most requently (Mol,

2016; Sta, 2015). Te U.S. Preventive Services ask Force

concluded with “moderate certainty” that treatment with lowdose aspirin or chronically hypertensive women at high risk

or preeclampsia is benecial (Henderson, 2014). Te American College o Obstetricians and Gynecologists (2018a) subsequently recommended initiating 81 mg between 12 and

28 weeks’ gestation and continuing therapy until delivery or

these at-risk gravidas.

Antioxidants to prevent preeclampsia have been studied.

Spinnato and coworkers (2007) randomly assigned 311 women

with chronic hypertension to treatment with vitamins C and E

or with a placebo. A similar number in both groups developed

preeclampsia—17 versus 20 percent, respectively.

Placental Abruption

Chronic hypertension increases the risk two- to threeold or

premature placental separation. Tis event’s harms are detailed

in Chapter 43 (p. 753). Te general obstetrical population risk

is 1 abruption in 200 to 300 pregnancies, and in women with

90

35

Mean arterial pressure (mm Hg)

40

95

100

105

100

115

Preeclampsia

No preeclampsia

Gestational age (weeks)

0 5 10 15 20 25 30

FIGURE 53-2 Blood pressure trends in treated, chronically hypertensive women with and without superimposed preeclampsia.

Mean maternal pressures (MAPs) at entry (p = 0.002) and throughout gestation (p <0.001) are significantly different for each group.

MAP nadir at 23.3 weeks (95% CI, 22.5–24.1) for superimposed preeclampsia versus 26.4 weeks (95% CI, 22.5–27.6) for those without

preeclampsia is significant (3.1 weeks, 95% CI, 2.3–4.3).948

Section 12

Medical and Surgical Complications

chronic hypertension, this rises to 1 in 60 to 120 pregnancies

(Ankumah, 2014; Cruz, 2011; Magee, 2015). Most abruptions

aect women with worsening hypertension or superimposed

preeclampsia. Vigil-De Gracia and associates (2004) reported

an 8.4-percent risk in women with severe hypertension.

■ Perinatal Morbidity and Mortality

Rates o almost all adverse perinatal outcomes are greater in

women with chronic hypertension than in normotensive gravidas. Tose who develop preeclampsia have substantially higher

adverse outcome rates. As shown in Figure 53-3, adverse outcome rates rise incrementally with increasing blood pressures

(Ankumah, 2014). Tere is evidence to suggest that chronic

hypertension—treated or untreated—is associated with congenital anomalies (Battarbee, 2020). Data rom untreated

women help tease away drug eects on organogenesis. Bateman

and coworkers (2015) ound an odds ratio o 1.5 or cardiac

deects. A systematic review noted a comparable risk ratio o

1.4 (Ramakrishnan, 2015). From one large birth deect study,

ve cases o etal esophageal atresia were ound in those with

untreated hypertension and yielded an adjusted odds ratio o

3.2 (van Gelder, 2015).

Te stillbirth requency with chronic hypertension is substantively greater, and common etiologies include superimposed

severe preeclampsia, abruption, and etal-growth restriction.

Rates range rom 15 to 24 deaths per 1000 births (Ahmad,

2012; Ankumah, 2014; Bateman, 2012). Low-birthweight neonates also are common and result rom etal-growth restriction,

indicated preterm delivery, or both (see Fig. 53-3).

Te incidence o etal-growth restriction averages 20 percent. Zetterström and colleagues (2006) reported a 2.5-old risk

or etal-growth restriction in 2754 chronically hypertensive

Swedish women compared with the risk in normotensive gravidas. Another study o 1609 Dutch nulliparas showed a 1.3-old

greater risk (Broekhuijsen, 2012). As with other complications,

etal-growth dysunction is more likely in those who develop

superimposed preeclampsia. In one study, the incidence o

growth-restricted etuses born to women with superimposed

preeclampsia was almost 50 percent compared with only 21 percent in chronically hypertensive women without preeclampsia

(Chappell, 2008). Last, women with chronic hypertension

severe enough to warrant treatment had an 11-percent incidence o etal-growth restriction sufciently severe to yield

birthweights ≤3rd percentile (Morgan, 2016a). Tus, neonates born to these women have a correspondingly high rate o

intensive-care unit (ICU) admission.

All o these adverse perinatal eects o chronic hypertension contribute to the greater perinatal mortality rate, which

is two- to ourold higher than the rate in nonaected gravidas

(American College o Obstetricians and Gynecologists, 2018a).

Stratied by severity, the perinatal death rate was 31 per 1000

births in those with mild hypertension, 72 per 1000 births

with moderate disease, and 100 per 1000 births in women with

severe chronic hypertension (Ankumah, 2014). In a study rom

Parkland Hospital, the perinatal mortality rate was 32 per 1000

births in women with hypertension severe enough to require

treatment (Morgan, 2016a). As expected, the highest rates are

in women who develop superimposed preeclampsia, or whom

the risk doubles (Al Khala, 2021; Grover, 2021).

I diabetes coexists with chronic hypertension, preterm

delivery, etal-growth restriction, and perinatal mortality rates

are increased even more (Yanit, 2012). Last, children born to

women with chronic hypertension have long-term endocrine

and metabolic morbidities, specically obesity (Imterat, 2020).

Tis epigenetic eect o hypertension and o other maternal

chronic diseases is detailed in Chapter 47 (p. 831).

MANAGEMENT DURING PREGNANCY

Chronic hypertension management aims to prevent moderate

or severe hypertension, to delay or dampen superimposed preeclampsia, and to reduce rates o adverse maternal or perinatal

outcomes. Blood pressure sel-monitoring is encouraged, but or

accuracy, automated devices must be properly calibrated (Whelton, 2018). Dietary counseling and reduction o behaviors such

as tobacco, alcohol, cocaine, or other substance use serve as

early interventions. A low-sodium diet and low-dose aspirin are

others (Battarbee, 2020; Chaemsaithong, 2020). Last, pharmacologic therapy is instituted to maintain blood pressures within

suitable ranges, which are outlined later (p. 951).

Some women—especially those with long-term or untreated

hypertension—have complications that raise the risk o adverse

pregnancy events. Concentric ventricular hypertrophy and proteinuria are concerns in these women. (Ambia, 2017, 2019; Kim,

2016; Morgan, 2016a,b). Tus, early in prenatal care, cardiovascular and renal baseline unctions are assessed with echocardiogram and a 24-hour urine collection or protein measurement.

■ Antihypertensive Drugs

reatment o hypertension during pregnancy has included

every drug class, but inormation is still limited regarding saety

and efcacy (American College o Obstetricians and Gynecologists 2013, 2018a). Some commonly used drugs are listed in

Table 53-4 and the ollowing summary is abstracted rom several sources, including the 2020 Prescribers’ Digital Reerence.

Possible etal eects o many o these drugs are also discussed

in Chapter 8.

FIGURE 53-3 Frequency of selected adverse maternal and perinatal outcomes by blood pressure stratification in women with mild

chronic hypertension. SGA = small for gestational age.Chronic Hypertension 949

CHAPTER 53

Adrenergic Receptor–Blocking Agents

Peripherally acting β-adrenergic-receptor blockers cause a generalized decline in sympathetic tone and lower cardiac output.

Examples are propranolol (Inderal) and metoprolol (Lopressor,

oprol). Atenolol is not recommended because o its link with

etal-growth restriction (Bello, 2021). Labetalol (Normodyne)

is an α/β-adrenergic blocker that is considered sae. Clonidine

(Catapres) and α-methyldopa (Aldomet) act centrally by reducing sympathetic outow to eect a generalized decreased vascular tone. Drugs in this class most requently used in pregnancy

are methyldopa and labetalol (American College o Obstetricians and Gynecologists, 2018a).

Calcium Channel–Blocking Agents

Tese drugs are divided into three subclasses based on their

calcium-channel actions. Common agents include niedipine (Procardia, Adalat)—a dihydropyridine—and verapamil

(Calan)—a phenylalkyl amine derivative. Tese agents have

negative inotropic eects and thus worsen ventricular dysunction and congestive heart ailure. Teoretically, they may potentiate the vasoactive actions o magnesium sulate administered

or eclampsia neuroprophylaxis. Webster and coworkers (2017)

ound niedipine equally eective as labetalol or treatment o

chronic hypertension in pregnancy. However, those treated with

niedipine advantageously had less blood pressure variation than

those treated with labetalol (Shawkat, 2018). Although data are

limited, calcium channel–blocking agents appear to be sae therapy or chronic hypertension during pregnancy (American College o Obstetricians and Gynecologists, 2018a; Briggs, 2022).

Diuretics

Tiazide diuretics are sulonamides, and these were the rst drug

group used to successully treat chronic hypertension. Tese

agents and loop-acting diuretics such as urosemide (Lasix) are

commonly used in nonpregnant patients. Short term, they provide sodium and water diuresis with volume depletion. Over

time, there is sodium escape, and volume depletion partially

corrects. Some aspect o lowered peripheral vascular resistance

likely contributes to their eectiveness in reducing long-term

morbidity (Umans, 2015).

Tiazide drugs may be mildly diabetogenic, and the normal expected volume expansion o pregnancy may be curtailed

(Sibai, 1984). Although rates o adverse perinatal outcomes are

not greater with diuretic use, concerns have curtailed diuretic

use as rst-line therapy or chronic hypertension in pregnancy

and particularly ater 20 weeks’ gestation (Working Group

Report, 2000). Overall, thiazide diuretics are considered sae in

pregnancy (Briggs, 2022).

Vasodilators

Hydralazine (Apresoline) relaxes arterial smooth muscle and has

been used parenterally or decades to saely treat severe peripartum hypertension (Chap. 41, p. 722). However, oral hydralazine monotherapy or chronic hypertension is not generally

used because o its weak antihypertensive eects and resultant

tachycardia. It is employed as an eective vasodilator adjunct

or long-term use with other antihypertensives in women with

chronic renal insufciency or ventricular dysunction.

Angiotensin-Converting Enzyme Inhibitors

Tese drugs inhibit the conversion o angiotensin-I to the

potent vasoconstrictor angiotensin-II. Tey can cause severe

etal malormations when given in the second and third trimesters. Tese include oligohydramnios, hypocalvaria, and renal

dysunction (Chap. 8, p. 150). Some preliminary studies also

suggest teratogenic eects (Hoeltzenbein, 2018). Tey are not

recommended at any time during pregnancy (Briggs, 2022).

Angiotensin-receptor blockers act in a similar manner. However, instead o blocking the production o angiotensin-II, they

inhibit binding to its receptor. Tey are presumed to have the

same adverse etal eects as angiotensin-converting enzyme

inhibitors and also are contraindicated in pregnancy.

TABLE 53-4. Some Antihypertensive Drugs Used for Treatment of Chronic Hypertension

During Pregnancya

Drug Comment

Adrenergic-receptor agentsb

β-blockers: propranolol, metoprolol

α/β-blocker: labetalol

α-agonist: methyldopa

Avoid with asthma, decompensated heart function

Less effective for severe hypertension; sedative side effects

Calcium-channel blocking agentsb

Nifedipine, amlodipine, verapamil Avoid with tachycardia

Diureticc

Hydrochlorothiazide Begin before 20 weeks’ gestation

Vasodilating agentc

Hydralazine Hypertension complicated by cardiac or renal

dysfunction; less effective with severe hypertension

aDrugs compatible with pregnancy (Briggs, 2022).

bFirst-line agents.

cSecond-line agents.950

Section 12

Medical and Surgical Complications

■ Antihypertensive Treatment in Pregnancy

Mild or Moderate Hypertension

Initiating or continuing prepregnancy antihypertensive treatment during pregnancy is debatable or women with mild or

moderate hypertension (see able 53-1). In older observational

reports, most pregnancy outcomes were generally good in

women with untreated mild to moderate hypertension. However, these studies were relatively small and had widely varying inclusion and outcome criteria. More recently, a Cochrane

review o approximately 5000 women with mild to moderate

hypertension reported that the risk or severe hypertension in

these individuals with initially milder hypertension declined

with therapy (Abalos, 2018). Te requencies o superimposed

preeclampsia, preterm birth, small-or-gestational age newborns, and perinatal mortality, however, did not dier.

Lowering blood pressure can theoretically decrease uteroplacental perusion and lead to small-or-gestational age neonates.

von Dadelszen and coworkers (2000) ound that the decline in

mean arterial pressure associated with antihypertensive therapy

was linked to a higher requency o small-or-gestational age

newborns. Other studies both conrm and reute these ndings

(Mitchell, 2019; Morgan, 2020). In two o the larger randomized trials, the incidence o growth restriction was not higher

in women randomly assigned to treatment (Gruppo di Studio

Ipertensione in Gravidanza, 1998; Sibai, 1990). Conversely,

worsening blood pressure itsel is associated with abnormal etal

growth. Also, some suggest that the drugs have a direct etal

action (Umans, 2015). Tereore, the question regarding treatment o mild to moderate chronic hypertension in pregnancy

is yet to be resolved.

Severe Chronic Hypertension

As classied by the American College o Obstetricians and

Gynecologists (2018a), severe hypertension includes a systolic

pressure ≥160 mm Hg or a diastolic pressure ≥110 mm Hg.

reatment should be initiated or persistent severe hypertension to reduce maternal morbidity and mortality risks (Akbar,

2019). In women with cardiovascular or renal end-organ damage, treatment may be instituted at systolic pressures ≥140 to

150 mm Hg or diastolic pressures ≥90 to 100 mm Hg in an

attempt to mitigate urther damage.

Women whose hypertension is severe enough to require

antihypertensive therapy or cause end-organ damage carry

an increased risk or superimposed preeclampsia. In an older

study, Sibai and coworkers (1986) described outcomes rom 44

pregnancies in women whose blood pressure at 6 to 11 weeks’

gestation was ≥170/110 mm Hg. All were given oral treatment

with α-methyldopa and hydralazine to maintain pressures

<160/110 mm Hg. Hal o these women developed superimposed preeclampsia, and all adverse perinatal outcomes were

in this group. Conversely, those women with severe chronic

hypertension who did not develop superimposed preeclampsia

had reasonably good outcomes. Morgan and colleagues (2016a)

conrmed these ndings in their study o 447 women requiring

treatment or chronic hypertension prior to 20 weeks.

Cardiac abnormalities and renal insufciency resulting rom

uncontrolled hypertension raise the risk or adverse pregnancy

outcomes. Women with baseline proteinuria >300 mg/d have

higher rates o superimposed preeclampsia, preterm birth, and

small-or-gestational age neonates compared with those whose

24-hour protein excretion is <300 mg/d (Table 53-5) (Morgan, 2016b). Abnormal cardiac remodeling and let ventricular

hypertrophy also are associated with superimposed preeclampsia, preterm birth, and neonatal ICU admission (Ambia, 2018,

2019).

“Tight Control”

During the past decade, the concept o tight control o blood

pressure has been advocated to optimize maternal and perinatal outcomes. Such control is analogous to that o glycemic

control or diabetes management. Te observational study by

TABLE 53-5. Selected Pregnancy Outcomes in Women with Chronic

Hypertension with and without Baseline Proteinuriaa and

Who Were Treated During Pregnancy

Outcome

Baseline

Proteinuriaa No Proteinuria p value

Superimposed preeclampsia 79% 49% <0.001

Abruption 0 1% 0.45

EGA at delivery (mean)b 35.1 ± 4.3 wk 37.2 ± 3.3 wk <0.001

≤30 weeks

≤34 weeks

≤37 weeks

18%

34%

48%

6%

17%

26%

0.001

0.005

0.002

Birthweight (mean)b

≤3rd percentile

≤10th percentile

2379 ± 1028 g

20%

41%

2814 ± 807 g

9%

22%

<0.001

0.01

<0.001

Perinatal mortality 36/1000 31/1000 0.47

aDefined as ≥300 mg/d protein excretion before 20 weeks’ gestation.

bMean ± standard deviations.

EGA = estimated gestational age.Chronic Hypertension 951

CHAPTER 53

Ankumah and colleagues (2014) noted earlier lends credence

to tighter blood pressure control. Tey showed that the adverse

pregnancy outcome risk was lower when blood pressures beore

20 weeks’ gestation were <140 mm Hg compared with higherpressure categories and increasing blood pressures.

Unortunately, those observations were not conrmed.

Magee and associates (2015) randomized 987 women to

either less-tight or tight control o hypertension. Except or

a lower rate o severe hypertension in the tightly controlled

group, other outcomes between these two groups did not dier

(Table 53-6). Analyzing the same cohort, no gestational age

was identied at which tight control was preerable (Pels,

2018). A systematic review reported similar results (Panaitesc,

2017). At this time, no proven benets or risks are attributed

to “tight”—target diastolic pressure <85 mm Hg—versus

“less-tight”—target diastolic pressure <100 mm Hg—control

o chronic hypertension during pregnancy (American College

o Obstetricians and Gynecologists (2018a). A randomized

trial—Project CHAP—is ongoing to help address this question

(U.S. National Library o Medicine, 2020).

Recommendations for Therapy

Until the treatment o uncomplicated mild to moderate chronic

hypertension in pregnancy is conrmed to have benets, it

seems reasonable to ollow the guidelines o the American College o Obstetricians and Gynecologists (2018a) and the Society

or Maternal-Fetal Medicine (2015). Tus, pregnant women

with severe hypertension must be treated or maternal neuro-,

cardio-, and renoprotection. reatment is also mandatory or

women with prior adverse outcomes such as a stroke, myocardial inarction, and evidence or cardiac or renal dysunction.

Many nd it reasonable to begin antihypertensive treatment in otherwise healthy pregnant women with persistent

systolic pressures >150 mm Hg or diastolic pressures >95 to

100 mm Hg (August, 2015; Webster, 2017). Drugs commonly

used are listed in able 53-4. At Parkland Hospital, we initiate treatment with antihypertensive agents at blood pressures

≥150/100 mm Hg. Our preerred regimens include monotherapy with a β-blocking drug such as labetalol or a calcium

channel–blocking agent such as niedipine or amlodipine (Norvasc). Adjunct therapy with a thiazide diuretic seems reasonable

or women in the rst hal o pregnancy. Tis is more bene-

cial in black women, in whom the prevalence o salt-sensitive

chronic hypertension is high.

Controversy surrounds women who present early in pregnancy and who are already taking antihypertensive drugs (Rezk,

2016). According to the American College o Obstetricians

and Gynecologists (2018a) and the Society or Maternal-Fetal

Medicine (2015), or women with mild to moderate hypertension, it is reasonable to discontinue medications during the rst

trimester and to restart them i blood pressures approach the

severe range. At Parkland Hospital, we continue treatment i

the woman is already taking medications when she presents or

prenatal care. As exceptions, angiotensin-converting enzyme

inhibitors and angiotensin-receptor blockers are stopped.

Some women will have persistently worrisome hypertension despite usual therapy. In these women, development o

superimposed preeclampsia becomes a primary concern and is

detailed next. Other possibilities include inaccurate blood pressure measurements, suboptimal treatment, illicit drug use, and

antagonizing substances such as chronic ingestion o nonsteroidal

antiinammatory drugs (NSAIDs) (Moser, 2006; Sowers, 2005).

■ Superimposed Preeclampsia

As discussed in Chapter 40 (p. 690), conditions that support

the diagnosis o superimposed preeclampsia include worsening

hypertension, new-onset proteinuria, neurological symptoms

such as severe headaches and visual disturbances, generalized

edema, oliguria, and certainly, convulsions or pulmonary edema.

Tese same criteria apply to women with chronic hypertension.

However, preeclampsia can be difcult to diagnose in a

chronically hypertensive woman. First, blood pressures may

increase during pregnancy in women with chronic hypertension

alone and without superimposed preeclampsia. Tis is most

commonly encountered near the end o the second trimester.

In the absence o other supporting criteria or superimposed

preeclampsia, this likely represents the higher end o the normal

blood-pressure curve shown in Figure 53-1. In such women, i

preeclampsia is excluded, it is reasonable to begin or to increase

the dose o antihypertensive therapy.

As a second diagnostic obstacle, many chronically hypertensive patients have preexisting end-organ damage and laboratory

values that mimic preeclampsia. New-onset proteinuria is consistent with the diagnosis o superimposed preeclampsia. However, this is not applicable to women who have underlying renal

disease with chronic proteinuria (Cunningham, 1990; Morgan,

2016b). In these women, diagnosing superimposed preeclampsia based on worsening proteinuria is problematic. Laboratory

abnormalities that support preeclampsia include rising serum

creatinine or hepatic transaminase levels, thrombocytopenia, or

any o the acets o HELLP (hemolysis, elevated liver enzyme

levels, low platelet count) syndrome. For women with chronic

TABLE 53-6. Selected Maternal and Perinatal Outcomes

in Pregnant Women with Chronic

Hypertension According to Less-Tight

versus Tight Control

Outcome

Less-Tight

Control Tight Control

Maternal

Placental abruption

Severe hypertensiona

Preeclampsia

HELLP syndrome

2.2%

41%

49%

1.8%

2.3%

28%

46%

0.4%

Perinatal

Deaths

Weight <10th percentile

Weight <3rd percentile

Respiratory problem

28/1000

16%

4.7%

17%

23/1000

20%

5.3%

14%

a

p <0.001, all other comparisons p >0.05.

HELLP = hemolysis, elevated liver enzyme levels, low

platelet count.952

Section 12

Medical and Surgical Complications

hypertension and superimposed preeclampsia with severe eatures, magnesium sulate or maternal neuroprophylaxis is recommended (Chap. 41, p. 719).

Expectant Management of Early-Onset Preeclampsia

Given that 40 to 50 percent o cases o superimposed preeclampsia develop early and beore 37 weeks, considerations or expectant management to allow etal maturation may be reasonable

(Harper, 2016). However, most maternal outcomes are better

when women with superimposed preeclampsia are delivered,

even when the etus is markedly preterm. Increased risk or placental abruption, cerebral hemorrhage, and peripartum heart ailure attend delivery delays (Cunningham, 1986, 2005; Martin,

2005). And prolonged expectant management is associated with

an increased risk o maternal cardiac disease in the ensuing years

(Rosenbloom, 2020). In a study rom Magee-Women’s Hospital,

42 o 68 careully selected women with a median gestational age

o 31.6 weeks were expectantly managed (Samuel, 2011). Despite

liberal criteria to mandate delivery, 17 percent o these mothers

developed either placental abruption or pulmonary edema. Te

latency period was extended by a mean o 10 days. Tere were no

perinatal deaths, however, neonatal outcomes were no better than

those in the group delivered immediately. Women with superimposed preeclampsia beore 34 weeks’ gestation may be candidates

or expectant management at acilities with adequate maternal

and neonatal ICU resources (American College o Obstetricians

and Gynecologists, 2018a). At Parkland Hospital, we pursue

delivery when superimposed preeclampsia is diagnosed.

■ Fetal Assessment

Because o greater stillbirth and etal-growth restriction risks,

antepartum etal surveillance is recommended or women with

chronic hypertension. However, data are limited regarding

which subpopulations with chronic hypertension benet most.

Te ideal test, testing interval, and gestational age o initiation

are other unknowns (American College o Obstetricians and

Gynecologists, 2018a; Freeman, 2008).

All women with chronic hypertension should undergo a

sonographic etal-growth assessment in the third trimester.

Additionally, Chahine and colleagues (2019) recommend that

women with low-risk disease undergo weekly antepartum testing. Tey dened low-risk by our criteria: (1) women ≤35

years o age, (2) mild- to moderate-range blood pressures not

requiring medication, (3) no prior hypertension-related adverse

pregnancy outcomes, and (4) no end-organ damage. For antepartum testing, a nonstress test or a biophysical prole is suitable (Chap. 20, p. 392).

Women with high-risk disease ail to meet these our criteria. For them, sonography and antepartum testing are considered earlier, and the value o these tools to assess etal-growth

restriction is detailed in Chapter 47 (p. 830). One surveillance

algorithm or suspected etal-growth restriction is outlined in

Figure 47-6 (p. 829).

■ Delivery Timing

For women with mild to moderate chronic hypertension who

have an otherwise uncomplicated pregnancy, the American

College o Obstetricians and Gynecologists (2018a) recommends waiting or delivery until 37 to 38 weeks’ gestation.

Women taking antihypertensive drugs are not delivered beore

370/7 weeks, and those not receiving drug treatment are delivered no earlier than 380/7 weeks. A nationally convened consensus committee recommended consideration or delivery at 38

to 39 weeks, that is, ≥37 completed weeks (Spong, 2011). A

large population-based Canadian study showed similar results

(Ram, 2018). Expectant management beyond 39 weeks’ gestation is associated with an increasing incidence o severe preeclampsia, and planned delivery beore 37 weeks was associated

with a rise in rates o adverse neonatal outcomes (Harper, 206).

For women who have etal-growth restriction, the decision

to deliver incorporates clinical judgment. Maternal health is

balanced against estimated etal weight, gestational age, and

chance o neonatal survival.

■ Intrapartum Considerations

For women with chronic hypertension, obstetrical actors dictate delivery route. Magnesium sulate is not given unless there

is superimposed severe preeclampsia. Epidural analgesia is ideal

but does not substantively lower blood pressure. A trial o labor

induction is preerable, and many o these women will deliver

vaginally (Alexander, 1999; Atkinson, 1995). Similarly, or the

growth-restricted etus, delivery route is based on obstetrical

actors. However, many etuses with growth restriction exhibit

nonreassuring etal heart rate patterns and require cesarean

delivery (McKinney, 2016).

For women with superimposed preeclampsia, intrapartum

management mirrors that described in Chapter 41 (p. 719).

Tese women may have a longer rst-stage labor (BregandWhite, 2017). Epidural analgesia or labor and delivery is

optimal, but it is not provided with the intent to treat hypertension (Lucas, 2001). Tat said, women with superimposed

preeclampsia are more sensitive to the acute hypotensive eects

o epidural analgesia (Vricella, 2012). Magnesium sulate neuroprophylaxis is initiated or eclampsia prevention. Severe

hypertension—diastolic blood pressure ≥110 mm Hg or

systolic pressure ≥160 mm Hg—is treated with either intravenous hydralazine, intravenous labetalol, or oral niedipine.

Some preer to treat women when the diastolic pressure reaches

100 to 105 mm Hg. Vigil-De Gracia and coworkers (2006)

randomly assigned 200 gravidas to receive intravenous hydralazine or labetalol to acutely lower severe high blood pressure.

Outcomes were similar except or signicantly higher rates o

maternal palpitations and tachycardia with hydralazine and signicantly greater rates o neonatal hypotension and bradycardia

with labetalol.

■ Postpartum Care

Prevention and management o adverse postpartum complications is similar in women with severe chronic hypertension

and in those with severe preeclampsia–eclampsia. For persistent severe hypertension, consideration is given to causes such

as pheochromocytoma or Cushing disease (Sibai, 2012). In

women with chronic end-organ damage, certain complicationsChronic Hypertension 953

CHAPTER 53

are more common. Tese include cerebral or pulmonary edema,

heart ailure, renal dysunction, or cerebral hemorrhage, especially within the rst 48 hours ater delivery. Tese requently

are preceded by sudden elevations o mean arterial blood pressure, especially o the systolic component (Cunningham, 2000,

2005; Martin, 2005).

Following delivery, as maternal peripheral resistance rises,

let ventricular workload also grows. Tis elevation is urther

aggravated by appreciable and pathological amounts o interstitial uid that are mobilized to be excreted as endothelial disruption rom preeclampsia resolves. In these women, sudden

hypertension—either moderate or severe—may exacerbate diastolic dysunction, cause systolic dysunction, and lead to pulmonary edema (Cunningham, 1986; Gandhi, 2001). Prompt

hypertension control, along with urosemide-evoked diuresis,

usually quickly resolves pulmonary edema.

Te antihypertensive regimen given antepartum may be

continued in the puerperium. In untreated women, labetalol or niedipine can also be used or persistent hypertension (Sharma, 2017). It also is possible in many women to

orestall postpartum hypertension by administering intravenous or oral urosemide to augment normal postpartum

diuresis. In one study, 20 mg oral urosemide given daily or

5 days to postpartum women with severe preeclampsia aided

blood pressure control (Ascarelli, 2005). A recent randomized trial showed that daily urosemide decreased the need

or antihypertensive therapy at hospital discharge (Perdigao,

2020). Daily weights are helpul in this regard. On average,

a woman should weigh 15 pounds less immediately ater

delivery. Excessive extracellular uid can then be estimated

by comparing her last prenatal weight plus 15 pounds against

the puerpera’s current weight.

Some evidence supports that chronic ingestion o NSAIDs

in the puerperium elevates blood pressure in women with

severe preeclampsia (Vigil-De Gracia, 2017). Tis may not be

problematic i these drugs are given only intermittently and

as needed (Blue, 2018). Postpartum admission rates or severe

hypertension approximate 1.5 percent (Chornock, 2021).

Discussion o postpartum contraception may begin prior to

delivery. As described in Chapter 38 (p. 672), certain methods

are less ideal or contraindicated or some women with chronic

hypertension. Moreover, or puerpera at highest risk or uture

pregnancy complications, the Society or Maternal–Fetal Medicine (2019) encourages immediate postpartum long-acting

reversible contraceptive (LARC) insertion or suitable candidates.

■ LongTerm Prognosis

Women with chronic hypertension are at high risk or lietime

cardiovascular complications, especially when accompanied

by diabetes, obesity, and the metabolic syndrome. Persistent

hypertension 3 years ater severe preeclampsia was associated

with a thicker let-ventricular septum compared with women

who became normotensive (Vaught, 2019). Te lietime cardiovascular morbidity and mortality risks associated with

hypertensive disorders o pregnancy are discussed in Chapter

41 (p. 726) (Wu, 2021).

R

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