Documente Academic
Documente Profesional
Documente Cultură
DOI 10.1007/5584_2016_81
# The Author(s) 2016
Luı́s Guedes-Martins
Abstract
Chronic hypertension is frequently encountered during pregnancy and
needs to be distinguished from other hypertensive complications of preg-
nancy, such as preeclampsia and gestational hypertension. The prevalence
of this pregnancy complication is attributable to the increased prevalence
of obesity and maternal age at childbearing. Women with chronic arterial
hypertension are at increased risk for several pregnancy complications,
including superimposed preeclampsia, caesarean delivery, preterm deliv-
ery <37 weeks gestation, birth weight <2500 g, neonatal unit admission,
and perinatal death. Therefore, specialized attention should be given to
these women as part of family planning before conception to provide
counseling about the pregnancy risks, to inform about surveillance of fetal
well-being, to determine the timing of delivery, and to optimize BP
control before, during, and after birth.
Keywords
Chronic arterial hypertension • Blood pressure • Pregnancy
Abbreviations
Table 1 The American College of Obstetricians and Gynecologists (ACOG) classification of hypertension during
pregnancy (The American College of Obstetricians and Gynecologists 2013)
Classification Definition
Preeclampsia/Eclampsia Occurrence of new-onset hypertension plus new-onset proteinuria. In the
absence of proteinuria, PE is diagnosed as HT in association with
thrombocytopenia (<100.000/microliter), impaired liver function (elevated
blood levels of liver transaminases to twice the normal concentration), the new
development of renal insufficiency (elevated serum creatinine greater than
1.1 mg/dL or a doubling of serum creatinine in the absence or other renal
disease), pulmonary edema, or new-onset cerebral or visual disturbances.
Eclampsia is the convulsive phase of the disorder and is among the more severe
manifestations of the disease.
Chronic arterial hypertension (of any High BP known to predate conception or detected before 20 weeks of
cause) gestation.
Chronic hypertension with Women with HT only in early gestation who develop proteinuria after
superimposed preeclampsia 20 weeks of gestation and women with proteinuria before 20 weeks of
gestation who have: (1) a sudden exacerbation of hypertension; (2) sudden
manifestation of other signs and symptoms, such as an increase in liver
enzymes to abnormal levels; (3) platelet levels below 100.000/microliter;
(4) right upper quadrant pain and severe headaches; (5) pulmonary congestion
or edema; (6) renal insufficiency; and (7) sudden, substantial, and sustained
increases in protein excretion. In the presence of organ dysfunction, this is
considered to be superimposed preeclampsia with severe features.
Gestational hypertension New-onset elevations of BP after 20 weeks of gestation, often near term, in the
absence of proteinuria. Failure of BP to normalize postpartum requires
changing the diagnosis to chronic hypertension.
BP blood pressure, HT hypertension, PE preeclampsia
Chronic Hypertension and Pregnancy
Adverse outcomes are particularly observed Table 2 Adverse pregnancy outcomes for women with
in women with cHT with uncontrolled severe chronic hypertension
hypertension, in those with target organ damage, Superimposed preeclampsia
and in those who are noncompliant with prenatal Caesarean delivery
visits. In addition, adverse outcomes are substan- Pre-term delivery (<37 weeks)
tially increased in women who develop Birth weight < 2500 g
Neonatal intensive care
superimposed preeclampsia, which complicates
Perinatal death
17–25 % of cHT pregnancies (vs. a 3–5 % pre-
Bramham et al. (2014)
eclampsia frequency described for the general
population) (Sibai 2002).
Superimposed preeclampsia is the most prev- frequencies of perinatal death and small-for-ges-
alent complication in pregnant women with tational-age newborns than do normotensive
chronic hypertension. Chappel and colleagues women (Rey and Couturier 1994).
(2008) presented prospective contemporaneous As a corollary, an extensive systematic review
data on the outcome of pregnancies in women reporting meta-analyzed data from 55 studies of
with chronic hypertension. In their study approximately 800,000 pregnancies (Bramham
(Chappell et al. 2008), indices of maternal and et al. 2014) showed that adverse outcomes of
perinatal morbidity and mortality were deter- cHT pregnancy are common, and that review
mined using prospectively collected data for emphasized a need for adequate antenatal sur-
822 women with chronic hypertension. The inci- veillance (Table 2).
dence of superimposed preeclampsia was 22 % Bramham and colleagues (2014) reported that
with early onset preeclampsia (34 weeks gesta- women with chronic hypertension had high
tion) accounting for nearly half (44 %) of these pooled incidences of superimposed
cases (Chappell et al. 2008). Delivering an infant pre-eclampsia (25.9 %, CI95% 21.0–31.5 %),
<10th customized birthweight percentile com- caesarean delivery (41.4 %, CI95%
plicated 48 % (87/180) of those with 35.5–47.7 %), preterm delivery <37 weeks ges-
superimposed preeclampsia and 21 % (137/642) tation (28.1 % CI95% 22.6–34.4 %), birth weight
of those without (relative risk [RR] 2.30; 95 % <2500 g (16.9 %, CI95% 13.1–21.5 %), neonatal
confidence intervals [CI95%] 1.85–2.84) intensive care unit admission (20.5 %, CI95%
(Chappell et al. 2008). Delivery at <37 weeks 15.7–26.4 %), and perinatal death (4.0 %,
gestation occurred in 51 % of those with CI95% 2.9–5.4 %). In their systematic review,
superimposed preeclampsia (98 % of these iatro- the incidences of adverse outcomes showed sig-
genic) and 15 % of those without (66 % iatro- nificantly higher risks in those with cHT: the
genic) (RR 3.52; 95 % CI95% 2.79–4.45) relative risks were 7.7 (CI95% 5.7–10.1) for
(Chappell et al. 2008). The results obtained by superimposed pre-eclampsia compared with
Chappell and colleagues suggests that the preva- pre-eclampsia, 1.3 (CI95% 1.1–1.5) for caesarean
lence of infants born small for gestational age delivery, 2.7 (CI95% 1.9–3.6) for preterm deliv-
and preterm is considerably higher than back- ery <37 weeks gestation, 2.7 (CI95% 1.9–3.8) for
ground rates and is increased further in women birth weight <2500 g, 3.2 (CI95% 2.2–4.4) for
with superimposed preeclampsia (Chappell neonatal intensive care unit admission, and 4.2
et al. 2008). The results were similar to that (CI95% 2.7–6.5) for perinatal death (Bramham
reported by three previous, robust, observational et al. 2014). These results should guide
studies of women with chronic hypertension counseling, adequate drug treatment, and
(Rey and Couturier 1994; McCowan pre-pregnancy optimization of women affected
et al. 1996; Sibai et al. 1998). Nevertheless, by cHT (The American College of Obstetricians
even without superimposed preeclampsia, and Gynecologists 2013; Bramham et al. 2014).
women with cHT have significantly higher
Chronic Hypertension and Pregnancy
4 Prepregnancy Care of Women hypertension in women with cHT who seek pre-
with Chronic Hypertension conception counseling. Particularly, the presence
of resistant hypertension, hypokalemia (potas-
The American College of Obstetricians and sium levels less than 3.0 mEq/L), elevated
Gynecologists (2013) recommends preconcep- serum creatinine level (greater than 1.1 mg/dL)
tion explanation of the risks associated with and family history of kidney disease are impor-
chronic hypertension and education about the tant suggestive findings of secondary hyperten-
signs and symptoms of preeclampsia. The pres- sion. Additionally, if the urinalysis is positive for
ence of diabetes, obesity, kidney disease, history protein, then a 24-h urine collection for protein
of early preeclampsia, uncontrolled hyperten- analysis or measurement of spot urine protein-to-
sion, and secondary hypertension are considered creatinine ratio can be assessed (Côté
risk factors for the development of superimposed et al. 2008). This analysis might assist in the
preeclampsia (The American College of diagnosis of superimposed preeclampsia and
Obstetricians and Gynecologists 2013). How- can provide prognostic information about the
ever, some evidence suggests that in women development of fetal growth restriction when
with chronic hypertension, a history of pre- prepregnancy proteinuria is found (Seely and
eclampsia does not increase the rate of Ecker 2014; Sibai et al. 1998). The baseline
superimposed preeclampsia, but is associated concentrations of serum creatinine, electrolytes,
with an increased rate of delivery at <37 weeks uric acid, liver enzymes, and platelet count
(Sibai et al. 2011). The ACOG and the National should be documented before conception to use
Institute for Health and Care Excellence as comparators if superimposed preeclampsia is
guidelines guidance (2015) also recommends suspected (The American College of
pre-conception discontinuation of medications Obstetricians and Gynecologists 2013). The
with known fetal adverse effects, in particular ACOG task force recommendation (The Ameri-
angiotensin-converting enzyme (ACE) can College of Obstetricians and Gynecologists
inhibitors, angiotensin receptor blockers, miner- 2013) also suggests referral to a physician with
alocorticoid antagonists, and statins. expertise in treating hypertension if secondary
The Report of the National High Blood Pres- hypertension is suspected.
sure Education Program Working Group on High
Blood Pressure in Pregnancy advises for the
assessment for ventricular hypertrophy, retinop- 5 Management of the Pregnant
athy and renal disease in women with history of with Chronic Arterial
hypertension for more than several years because Hypertension
target organ damage, especially renal disease,
can progress during pregnancy (Report of the For the general population with cHT, the use of
National High Blood Pressure Education Pro- home BP monitoring in daily clinical practice is a
gram Working Group on High Blood Pressure useful instrument as an aid to achieving targets
in Pregnancy 2000). In women with severe and monitoring responses to medication
hypertension of long duration (more than (Maldonado et al. 2009). For pregnant women
4 years), assessment of left ventricular function with chronic hypertension and poorly controlled
with echocardiography or electrocardiography is BP, the use of home BP monitoring is suggested,
considered good clinical practice (The American particularly in the second half of pregnancy when
College of Obstetricians and Gynecologists most superimposed preeclampsia occurs (The
2013). This recommendation is also enhanced American College of Obstetricians and
by the Canadian (Magee et al. 2014), Gynecologists 2013). In particular, ambulatory
Australasian and JNC 8 evidence guidelines for BP monitoring can be of special interest for
the management of high blood pressure in adults women with suspected white coat hypertension,
(James et al. 2014), reinforcing the importance of avoiding overtreatment of BP and unnecessary
looking for signs and symptoms of secondary adverse effects of treatment when not indicated
L. Guedes-Martins
(The American College of Obstetricians and However, with respect to the mothers, the
Gynecologists 2013; James et al. 2014). CHIPS findings are consistent with a meta-
Mild to moderate hypertension during preg- analysis of previous trials that showed that less-
nancy is a common finding. In daily clinical tight versus tight control increases the incidence
practice, antihypertensive drugs are often used of severe maternal hypertension (but not pre-
in the belief that lowering blood pressure will eclampsia) (Abalos et al. 2014; Magee
prevent progression to more severe disease and et al. 2015), which is considered a risk factor
thereby improve the outcome, reducing maternal for acute stroke during and outside of pregnancy
morbidity by limiting episodes of severe hyper- (James et al. 2014; Martin et al. 2005). The
tension (Seely and Ecker 2014; Abalos treatment of severe hypertension (systolic BP
et al. 2014). However, it remains unclear whether more than 160 mmHg and/or diastolic BP more
antihypertensive drug therapy for mild to moder- than 110 mmHg) is always recommended
ate hypertension during pregnancy is worthwhile because it is believed to reduce the risk of mater-
(Abalos et al. 2014). In addition, overly aggres- nal stroke and coronary events and to limit
sive antihypertensive treatment might decrease episodes of severe hypertension. However, the
fetoplacental perfusion, increase the risk of fetal exact goal ranges for BP targets during preg-
growth restriction (Seely and Ecker 2014; von nancy in women with chronic hypertension are
Dadelszen et al. 2000), and reproduce fetal not established.
effects of diseases related to placental bed The ACOG recommends antihypertensive
dysfunction. therapy for pregnant women with persistent
Recently, the Control of Hypertension in chronic hypertension with systolic BP of
Pregnancy Study (CHIPS) was designed to com- 160 mmHg or higher or diastolic BP of
pare tight control (the use of antihypertensive 105 mmHg or higher (The American College of
therapy to normalize BP) with less-tight control Obstetricians and Gynecologists 2013). For preg-
of non-proteinuric, non-severe hypertension in nant women with chronic hypertension treated
pregnancy with respect to perinatal and maternal with antihypertensive medication, the ACOG
outcomes (Magee et al. 2015). CHIPS was an suggests that BP levels be maintained between
open, international, randomized, multicenter 120 mmHg systolic and 80 mmHg diastolic, and
trial involving 987 women. The primary outcome 160 mmHg systolic and 105 mmHg diastolic.
was a composite of pregnancy loss (defined as The NHBPEP (Report of the National High
miscarriage, ectopic pregnancy, pregnancy ter- Blood Pressure Education Program Working
mination, stillbirth, or neonatal death) or high- Group on High Blood Pressure in Pregnancy
level neonatal care (defined as greater-than-nor- 2000) working group considers tapering antihy-
mal newborn care) for more than 48 h until pertensive medications and reinstituting or
28 days of life or until discharge home, which- increasing the dose of antihypertensive drugs if
ever was later. The secondary outcome was seri- BP is >150–160 mmHg systolic or
ous maternal complications occurring up to >100–110 mmHg diastolic. Additionally, the
6 weeks postpartum or until hospital discharge, JNC-8 suggests continuing medication if there
whichever was later (Martin et al. 2005). This is target-organ damage or a previous requirement
randomized trial showed that less-tight control of for multiple antihypertensive agents for BP con-
maternal hypertension in pregnancy compared trol, and if medication is stopped, instituting
with tight control resulted in no significant dif- pharmacological treatment if BP is
ference in the risk of adverse perinatal outcomes, >150–160 mmHg systolic or >100–110 mmHg
as assessed by the rates of perinatal death or diastolic (James et al. 2014). The Society of
high-level neonatal care for more than 48 h (pri- Obstetricians and Gynaecologists of Canada
mary outcome) (Brown et al. 2000). Addition- (Magee et al. 2014) recommends treatment if
ally, less-tight (vs. tight) control did not BP is >159 mmHg systolic or >109 mmHg dia-
significantly increase the risk of overall serious stolic to reduce maternal risk with a target of
maternal complications (secondary outcome). <156 mmHg systolic and <106 mmHg diastolic
Chronic Hypertension and Pregnancy
in patients without cardiovascular risk factors. (The American College of Obstetricians and
Finally, the Australasian Society for the Study Gynecologists 2013).
of Hypertension in Pregnancy (Brown
et al. 2000) suggests antihypertensive therapy in
cases of BP >170 mmHg systolic or
6 Antihypertensive Agents
>110 mmHg diastolic with a recommended tar-
in Pregnancy
get of 120–140 mmHg systolic and 80–90 mmHg
diastolic.
The more commonly used antihypertensive
For women who enter pregnancy and receive
agents with an acceptable safety profile in preg-
antihypertensive therapy prior to conception,
nancy and their Food and Drug Administration
there are scarce or absent data to guide decisions
(FDA) classification are illustrated in Table 3.
regarding continuing or discontinuing therapy
Methyldopa has been widely used in preg- Gynecologists 2013). Oral nifedipine, the most
nancy, seems safe to use, and is probably prefer- commonly prescribed calcium channel blocker,
able to other drugs from the point of view of the is also a suitable option for the treatment of
neonate and child (Cockburn et al. 1982). For hypertension in pregnancy/postpartum (Firoz
infants born to mothers with chronic hyperten- et al. 2014).
sion, compared with those with mothers are Diuretics, generally considered second-line
treated by methyldopa alone, those whose drugs for the treatment of hypertension in preg-
mothers are treated by beta-blockers appear to nancy, can be especially useful in women with
be at increased risk of being small for gestational salt-sensitive hypertension (The American Col-
age (SGA) and being hospitalized during infancy lege of Obstetricians and Gynecologists 2013).
(Xie et al. 2014). Methyldopa, a centrally acting Dose adjustments to minimize the adverse effects
alpha-2 adrenergic agonist, is considered a first- and risks, such as hypokalemia and intravascular
line drug for the treatment of hypertension in volume depletion, are recommended (The Amer-
pregnancy (Seely and Ecker 2014), with no ican College of Obstetricians and Gynecologists
apparent adverse effects on uteroplacental hemo- 2013).
dynamics (Montan et al. 1993), birth weight, Clonidine has a similar mechanism of action
neonatal complications, and development at as methyldopa and appears to be a safe antihy-
1 year after delivery (Mutch et al. 1977). pertensive agent in pregnancy (Horvath
Beta-blockers are also commonly used during et al. 1985; Rothberger et al. 2010). Clonidine
the first trimester of pregnancy, and data is particularly useful for patients who cannot take
concerning the risks of congenital anomalies in an oral antihypertensive drug because it is avail-
offspring have not been summarized. Based on a able as a transdermal patch (Table 3).
2013 systematic review of 13 population-based Angiotensin converting enzyme (ACE)
case control cohort studies examining the risk of inhibitors, angiotensin II receptor blockers
congenital malformations, first-trimester oral (ARB) and direct renin inhibitors are
β-blocker use showed no increased odds of all or contraindicated during pregnancy. When mater-
major congenital anomalies (OR ¼ 1.00; CI95% nal exposure is in the second and third trimester,
0.91–1.10). However, in analyses examining they are associated with renal abnormalities,
organ-specific malformations, increased odds of adverse pregnancy outcomes, oligohydramnios,
cardiovascular defects (OR ¼ 2.01; CI95% fetal growth restriction, skull hypoplasia, and
1.18–3.42), cleft lip/palate (OR ¼ 3.11; CI95% fetal death, and first trimester exposure has been
1.79–5.43), and neural tube defects (OR ¼ 3.56; associated with fetal cardiac abnormalities (Coo-
CI95% 1.19–10.67) were observed. The effects on per et al. 2006).
severe hypospadias were non-significant. The Hydralazine, labetalol, and calcium channel
authors concluded that causality is difficult to blockers are among the medications that were
interpret given the small number of heterogeneous recommended for urgent lowering of BP in preg-
studies and possibility of biases. Additionally, nant women with chronic hypertension (The
given the frequency of this exposure in pregnancy, American College of Obstetricians and
further research is needed (Yakoob et al. 2013). Gynecologists 2013; Duley et al. 2013). Based
Labetalol is a beta-blocker with alpha-blocking on the results of a recent, robust Cochrane sys-
activity commonly used in pregnancy, with no tematic review, evidence is inadequate to dem-
significant differences in perinatal outcomes onstrate the superior safety or efficacy of any of
when compared with placebo or methyldopa these medications (Duley et al. 2013). The
(Sibai et al. 1990). authors state that until better evidence is avail-
Calcium channel blockers are considered to able, the choice of antihypertensive should
be safe for use in pregnancy although they are a depend on the clinician’s experience and
class of drugs that has not been extensively stud- familiarity with a particular drug, on what is
ied in pregnant women with chronic hyperten- known about adverse effects, and on the patient’s
sion (The American College of Obstetricians and preferences (Duley et al. 2013).
Chronic Hypertension and Pregnancy
Nitroprusside is the agent of resort for urgent with chronic hypertension. However, there is
control of refractory severe hypertension. It is some evidence that low-dose aspirin initiated in
recommended that its use should be limited to early pregnancy is an efficient method of reduc-
emergency situations during a short period of ing the incidence of preeclampsia (Duley
time. Although under suspicion (Sass et al. 2007; Bujold et al. 2010; Askie
et al. 2007), at present there is insufficient evi- et al. 2007). Therefore, for women with chronic
dence for definitive conclusions about any direct hypertension who are at a greatly increased risk
association between sodium nitroprusside use of adverse pregnancy outcomes (history of early
and fetal demise (Magee et al. 2014; Sass onset preeclampsia and preterm delivery at
et al. 2007). <34 weeks of gestation or preeclampsia in
A systematic review with the purpose to more than one prior pregnancy), the ACOG
establish which antihypertensive medications recommends initiating the administration of
are safe for use while breastfeeding indicated daily low-dose aspirin (60–80 mg) beginning in
that ACE inhibitors, methyldopa, beta-blockers the late first trimester. Further information is
with high protein binding, and some calcium required to assess which women are most likely
channel blockers all appear to be safe treatments to benefit when treatment is best started, and at
of hypertension in a nursing mother (Beardmore what dose (Duley et al. 2007).
et al. 2002).
and to optimize BP control before, during, and Major congenital malformations after first-trimester
after birth. exposure to ACE inhibitors. N Engl J Med 354
(23):2443–2451
Côté AM, Brown MA, Lam E, von Dadelszen P, Firoz T,
Competing Financial Interests The author declares no Liston RM, Magee LA (2008) Diagnostic accuracy of
conflicts of interest. urinary spot protein:creatinine ratio for proteinuria in
hypertensive pregnant women: systematic review.
BMJ 336(7651):1003–1006
Danaei G, Finucane MM, Lin JK, Singh GM, Paciorek CJ,
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