Pregnancy-Related Hypertension

Chapter: Pregnancy-Related Hypertension
McMaster Section Editor(s): Christine M. Ribic, Karen C.Y. To
Section Editor(s) in Interna Szczeklika: Franciszek Kokot, Robert Drabczyk
McMaster Author(s): Ray Naden, Serena Gundy
Author(s) in Interna Szczeklika: Władysław Sułowicz, Tomasz Stompór
Additional Information

Etiology and PathogenesisTop

During pregnancy the maternal cardiovascular system undergoes several major physiologic changes. As early as 8 weeks’ gestation, peripheral vasodilatation can lead to a fall in systemic vascular resistance. To mitigate this effect, maternal cardiac output steadily increases, reaching upwards of 50% above the prepregnancy levels by weeks 20 to 24. As there is usually a lag in compensation, maternal blood pressure often falls by 10 to 15 mm Hg of systolic blood pressure (SBP), reaching a nadir around 20 to 22 weeks’ gestation before slowly rising back up to prepregnancy levels by term. After delivery, blood pressure may transiently decrease before peaking after 3 to 5 days.

Despite these physiologic changes, hypertension is one of the most common medical problems encountered in pregnancy. Complicating 5% to 10% of all pregnancies, certain etiologies are associated with significant maternal and fetal morbidity and mortality, requiring prompt identification, intervention, and management.

ClassificationTop

Classification of hypertension in pregnancy:

1) Preexisting hypertension: Chronic hypertension diagnosed before pregnancy or hypertension occurring before 20 weeks’ gestation. It may also present as persistent hypertension >3 to 6 months into the postpartum period.

a) Essential hypertension: No secondary cause identified.

b) Secondary hypertension (hypertension with an identifiable cause): Consider endocrine, renal, cardiac, or vascular abnormalities, depending on the clinical presentation.

2) Gestational hypertension: Hypertension identified after 20 weeks’ gestation without other features of preeclampsia; it may evolve into preeclampsia.

3) Preeclampsia: Hypertension occurring after 20 weeks’ gestation with proteinuria and/or end-organ dysfunction.

a) De novo preeclampsia: New-onset hypertension and proteinuria or end-organ dysfunction.

b) Preexisting hypertension with superimposed preeclampsia: Worsening hypertension with new or worsening proteinuria or end-organ dysfunction.

c) Preexisting proteinuria with superimposed preeclampsia: New or worsening hypertension with worsening proteinuria or end-organ dysfunction; this is often due to chronic kidney disease, and the diagnosis of superimposed preeclampsia is complex. Involvement of a specialist in renal disease in pregnancy is advisable.

DiagnosisTop

Blood pressure should be taken in a sitting rather than a supine position, as the gravid uterus may decrease venous return to the heart and produce abnormal increases or decreases in blood pressure. Measurements should be taken with a manual sphygmomanometer. Ensure the cuff size is appropriate for the patient so as not to overestimate the measurement (such as can occur with a cuff size too small). Phase V (disappearance) rather than phase IV (muffling) of Korotkoff sounds should be used.

The diagnosis of hypertension in pregnancy is made when the patient has at least 2 readings >140/90 mm Hg, taken in the office or hospital, measured at least 15 minutes apart.

Isolated office (white coat) hypertension may be revealed by home blood-pressure measurement. If there is any conflict between home and office readings, a 24-hour ambulatory blood-pressure monitor can be considered.

All patients with hypertension diagnosed before or during pregnancy should be followed closely by an obstetrician. Baseline blood tests to look for causes of secondary hypertension and exclude end-organ involvement should be ordered at the first visit at which hypertension is diagnosed.

The issue of when to search for a possible cause of secondary hypertension (see Essential Hypertension) is not always clear. The need for other tests may be prompted by the clinical features or clinical course. At a minimum, electrolytes, creatinine (estimated glomerular filtration rate), and urinalysis should be ordered. It is our practice to also obtain a complete blood count and liver function tests to use as a baseline or, in the case of patients at >20 weeks’ gestation, to exclude end-organ involvement from preeclampsia. Further information may be taken into account when judging the need for additional investigations (Table. Screening for secondary causes of…).

Management and TreatmentTop

General Approach

Regardless of the etiology of hypertension (preeclampsia, preexisting, gestational), the pharmacologic treatment of hypertension in pregnancy is approached in a similar manner. However, unlike the management of nonpregnant patients, the decision to treat hypertension must consider the risks and benefits to both mother and fetus. For this reason, the initiation of antihypertensive therapy should always be undertaken in consultation with an obstetrician. It is also vital to determine the etiology of the hypertension (primary, secondary, pregnancy-related) so that the clinical course and prognosis may be appropriately predicted.

1. General recommendations: Blood pressure levels, gestational age, and the presence of maternal and fetal comorbidities and complications must be taken into consideration.

1) Advise avoiding the supine position when lying down, as it may increase vasoconstriction.

2) Recommend maintaining a normal diet without salt restriction.

3) Normal physical activity need not be limited. Bed rest, unless in the setting of severely uncontrolled hypertension and/or severe preeclampsia, is not indicated.

2. Target blood pressure and levels at which to start antihypertensive treatment are controversial. On the one hand, maternal risk of cerebral hemorrhage increases with blood pressures >160/110 mm Hg; on the other, aggressive lowering of blood pressure may run the risk of compromising the uteroplacental blood supply due to reduced perfusion pressure into this largely passive vascular bed. Most clinicians will initiate treatment at levels >140 to 150 mm Hg SBP and >90 to 100 mm Hg diastolic blood pressure (DBP). A target DBP between 85 and 100 mm Hg in women with preexisting or pregnancy-induced hypertension (without preeclampsia) can be considered a safe zone for both mother and fetus. We suggest a target between 130 and 150 mm Hg SBP and 85 and 100 mm Hg DBP, recognizing that women with blood pressures closer to 150/100 mm Hg run an increased risk of developing severe hypertension and that slightly lower targets may also be reasonable.Evidence 1Weak recommendation (benefits likely outweigh downsides, but the balance is close or uncertain; an alternative course of action may be better for some patients). Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to imprecision and indirectness. The CHIPS trial indicated that there is no difference in maternal or fetal outcome between patients for whom the target diastolic blood pressure was <100 mm Hg (less tight) versus those whose target was <85 mm Hg (tight) except for a greater frequency of severe hypertension (>160/110 mm Hg) in the former group. All patients in the CHIPS trial had either preexisting hypertension or essential hypertension at enrolment. Magee LA, von Dadelszen P, Rey E, et al. Less-tight versus tight control of hypertension in pregnancy. N Engl J Med. 2015 Jan 29;372(5):407-17. doi: 10.1056/NEJMoa1404595. PubMed PMID: 25629739.

3. Treatment of mild to moderate hypertension in pregnancy: First-line antihypertensive therapies include nifedipine, labetalol, or methyldopa (Table. Oral drugs for the management…). These agents can be used alone or in combination as required. Second-line therapies (a fourth agent is rarely necessary) can include metoprolol and prazosin. Hydrochlorothiazide should be avoided if there is concern regarding a low amniotic fluid volume or in the setting of preeclampsia. Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers are contraindicated.

4. Treatment of severe hypertension in pregnancy: Although there is a divergence in opinion regarding the optimal blood pressure cutoff at which to initiate medications and target treatment, a blood pressure of 160 mm Hg SBP or 110 DBP should always be treated. In such cases, both maternal and fetal well-being must be assessed and hospital admission considered. Medications including intravenous labetalol, oral short-acting nifedipine, or intravenous hydralazine can be used. Our preference is to use short-acting nifedipine, as it has been found to be as effective and safe as intravenous labetalol and does not require a parenteral route.Evidence 2Weak recommendation (benefits likely outweigh downsides, but the balance is close or uncertain; an alternative course of action may be better for some patients). Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to imprecision. Shekhar S, Sharma C, Thakur S, Verma S. Oral nifedipine or intravenous labetalol for hypertensive emergency in pregnancy: a randomized controlled trial. Obstet Gynecol. 2013 Nov;122(5):1057-63. doi: 10.1097/AOG.0b013e3182a9ea68. PubMed PMID: 24104790. Shekhar S, Gupta N, Kirubakaran R, Pareek P. Oral nifedipine versus intravenous labetalol for severe hypertension during pregnancy: a systematic review and meta-analysis. BJOG. 2016 Jan;123(1):40-7. doi: 10.1111/1471-0528.13463. Epub 2015 Jun 26. Review. PubMed PMID: 26113232. We prefer not to use hydralazine if other options are available. With all these drugs, small doses repeated every 30 to 40 minutes until the target blood pressure is reached are the safest regimen; this allows the full effect of each incremental dose to be seen and avoids overdose and an inappropriate reduction in perfusion pressure (all 3 of these drugs have an onset within 20 minutes and a peak effect within 40 minutes, whether given orally or intravenously). Medication doses: Table. Drugs for the treatment of….

5. Postpartum management: After delivery, maternal blood pressure often declines before rising once more between days 3 to 5 postpartum, sometimes to levels higher than in pregnancy. Although this will often settle out to prepregnancy values within the following weeks, women who have had a pregnancy complicated by hypertension may be particularly vulnerable to this postpartum surge, requiring an adjustment or addition of medication to prevent severe hypertension. All women with hypertension during pregnancy must be followed closely in the postpartum period. The use of nonsteroidal anti-inflammatory drugs for analgesia should be avoided, as it may aggravate hypertension. Women with new or sudden worsening of hypertension with any associated signs and symptoms of end-organ dysfunction should be carefully assessed for postpartum preeclampsia.

Antihypertensives used in pregnancy may be continued, as labetalol, nifedipine, and methyldopa are all considered safe in breastfeeding. However, ACEIs—particularly enalapril and quinapril—are both effective and safe and have the particular advantage that they have been shown not to cross into breast milk in an active form. Transition to prepregnancy medications may also be considered in the postpartum period.

TablesTop

Table. Screening for secondary causes of hypertension at initial assessment

Study

Red flags

First-order testing

Creatinine

Evidence of renal impairment

Electrolytes (potassium)

Hypokalemia suggesting potential mineralocorticoid excess

Midstream urine

Evidence of proteinuria or hematuria suggesting a renal etiology

Urine PCR or 24-hour urine collection for protein

If midstream urine is positive for proteinuria, recommend for baseline and quantitative assessment

Second-order testinga

Renal ultrasound with Doppler

If sudden-onset or worsening hypertension, presence of abdominal bruit, resistance to >3 drugs, recurrent pulmonary edema

Sleep study

If evidence of sleep apnea in history (headache, nocturnal choking and gasping, early morning fatigue, snoring)

Plasma renin and aldosterone

If evidence of spontaneous hypokalemia (K <3.5 mmol/L) or hypokalemia with diuretics, resistance to >3 drugs, incidental adrenal adenoma

Urine metanephrines

If severe >180/110 mm Hg refractory hypertension, symptoms of catecholamine excess (headaches, palpitations, sweating, panic attacks, orthostatic syncope), hypertension triggered by beta-blockers, history of multiple endocrine neoplasia 2A or 2b or an adrenal mass

Thyroid-stimulating hormone

If evidence of hypo- or hyperthyroidism on clinical assessment

a Only undertaken if signs and symptoms present (see Essential Hypertension).

PCR, protein-to-creatinine ratio.

Table. Oral drugs for the management of hypertension in pregnancy

Drug

Starting dose

Maximum dose

Onset of action

Adverse effects

Special indications and notes

Labetalol

100 mg bid

500 mg qid

20‑40 min

Headache; avoid in uncontrolled asthma

Often requires tid or qid dosing in pregnancy; safe for breastfeeding

Nifedipine (slow release)

20 mg bid

60 mg bid

20‑40 min

Peripheral edema

Safe for breastfeeding

Methyldopa

250 mg bid

1 g qid

1‑3 h

Fatigue; avoid in uncontrolled depression

Safe for breastfeeding

bid, 2 times a day; qid, 4 times a day; tid, 3 times a day.

Table. Drugs for the treatment of hypertensive emergencies in pregnancy

Drug

Dose

Onset/duration of action

Adverse effects

Special indications

Labetalol

20‑40 mg IV bolus every 20+ min

10‑20 min/3‑6 h

Vomiting, scalp tingling, burning sensation in the throat, dizziness, AV block

In most hypertensive emergencies except for acute heart failure

Nifedipine (short acting)

10 mg po every 20+ min

10‑20 min/3‑6 h

Headache, facial flushing

 

Nitroglycerin

5‑100 microg/min as IV infusion

2‑5 min/5-10 min

Headache, vomiting, methemoglobinemia, developing tolerance with prolonged use

Myocardial ischemia or pulmonary edema

Hydralazine

10 mg IV bolus every 20+ min

10‑20 min/1‑4 h

Tachycardia, flushing, headache, vomiting, worsening of angina pectoris

Eclampsia

AV, atrioventricular; IV, intravenous administration; po, oral administration.

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