Hypertensive Disease of Pregnancy

 

Hypertensive Disease in Pregnancy

Clinical Cases Applicability: Chronic Hypertension, Preeclampsia (PreE), Eclampsia, HELLP, AFLP

Learning Objectives:

• Describe the physiology of normal regulation of blood pressure in pregnancy

• Understand proposed pathophysiology of preeclampsia and associated end organ damage

• Compare and contrast the pharmacology of anti-hypertensive medications used in pregnancy

• Describe the mechanism of action of magnesium in the prevention of recurrent eclamptic seizures

Clinical Presentation: Patient with chronic hypertension develops worsening hypertension in the third trimester; a

nulliparous patient has an eclamptic seizure in the third trimester; a laboring patient presents with new onset hypertension

and proteinuria

Review the spectrum of hypertensive diseases in pregnancy (Review the corresponding videos for

APGO Medical Student Educational Topics 8 and 18)

• Preeclampsia-eclampsia

• Chronic hypertension

• Chronic hypertension with superimposed preeclampsia

• Gestational hypertension

How does the physiology of pregnancy regulate maternal blood pressure?

• Placental vascular bed remodeling in early pregnancy

• Increased capacitance and decreased resistance to flow in placental bed

• Progesterone effect on smooth muscle, and thus BP; natural history throughout pregnancy

How does the pathophysiology of preeclampsia alter the normal regulation of maternal blood

pressure?

• Predisposing Factors

• Although mechanisms not entirely clear, appears to be two stage evolution—

o First, lack of remodeling of spiral arteriole intima by cytotrophoblastic cells, less capacitance

o Second, placental hypoxia damages syncytium; along with altered proangiogenic and antiangiogenic balance,

increased maternal oxidative stress, and endothelial and immunological dysfunction leading to maternal end

organ damage. Endothelial damage demonstrated before overt disease.

§ Kidney – inactivation free-VEGF > endotheliosis > proteinuria

• Another theory – disorder of immunity and inflammation. Particles shed from syncytial surface are increased in PreE

and trigger the exaggerated inflammatory response

• Several other factors – endothelin, nitric oxide, oxidative stress, and hemeoxygenase—have been implicated in the

inflammatory response leading to preE and are discussed in the comprehensive ACOG 2013 report on Hypertension

in Pregnancy, Chapter 10

Describe the mechanism of action and pharmacology of common antihypertensives used in

pregnancy

• Methyldopa, Labetalol, and long acting Nifedipine are most often used to treat chronic hypertension in pregnancy.

Women may be continued on Hydrochlorathiazide if used for treatment of chronic hypertension pregnancy.

• Intravenous Labetalol, Hydralazine, and immediate release Nifedipine are most often used to treat acute severe

hypertension.

• Treatment of chronic hypertension in pregnancy decreases the risk of severe hypertension and associated maternal

cardiovascular, neural and renal effects, but has not been proven to decrease the risk of preeclampsia, eclampsia,

preterm birth, abruption, fetal growth restriction, or perinatal/maternal mortality.

• Certain antihypertensives are best avoided in pregnancy:

o Angiotensin Converting Enzyme(ACE) Inhibitors (ex. Captopril), Angiotensin II Receptor Blockers, and Direct

Renin Inhibitors are associated with renal abnormalities when used in second half of pregnancy.

o Mineralocorticoid Receptor Agonists (ex. Spironolactone) block the renin angiotensin aldosterone system and

act as diuretics. The anti-androgenic activity is of concern for possible feminization of male fetuses.

• Postpartum, choose an antihypertensive with the lowest transfer to breast milk. Beta blockers (specifically

propranolol), alpha/beta blockers (specifically labetolol and metoprolol), calcium channel blockers, and ACE inhibitors

are considered safe during lactation as less than 2% enters the breast milk.

By what mechanism of action does magnesium prevent recurrent preeclamptic seizures?

• Mg+2 competes with Ca+2 for calcium channels blocking intracellular flow of Ca+2 needed to initiate neuronal firing;

raising the threshold for neuronal triggering of seizure activity.

• The mechanism of action of magnesium sulfate is thought to trigger cerebral vasodilation, thus reducing ischemia

generated by cerebral vasospasm during an eclamptic event.

• The calcium antagonistic effects of magnesium can also affect the cerebral endothelium that forms the blood-brain

barrier. Decreased cell calcium inhibits endothelial contraction and opening of tight junctions that are linked to the

actin cytoskeleton.

• Concerns for use of magnesium and toxicity – therapeutic serum magnesium concentration range is considered to be

4 to 8 mg/dL. Signs of toxicity start with the loss of patellar deep tendon reflexes, weakness, double vision, and

dysarthria. Respiratory depression/or arrest can occur with levels >14 mg/dL

Figures:

Table 1 Spectrum of Hypertensive Disorders

Hypertension Category Timing Definition Notes

Preeclampsia-eclampsia After 20 weeks gestation, most

often near term;

May develop in the postpartum

period

New onset hypertension* and new

onset proteinuria**;

In absence of proteinuria,

hypertension plus severe features

such as: thrombocytopenia

(<100,000), impaired liver function

(transaminases > 2x normal), new

renal insufficiency (Cr > 1.1mg/dL),

pulmonary edema, or new onset

cerebral or visual disturbances

*Hypertension is defined as SBP >

140 mmHg, DBP > 90 mmHg, or

both. Mild until > 160/110 mmHg.

Usually two readings at least 4

hours apart, unless severe

requiring treatment

** Proteinuria diagnosed if > 300

mg in 24 hours or urine

protein/creatinine ratio > 3.0

May develop in the postpartum

period

Chronic hypertension Prior to conception or

diagnosed before 20 weeks

gestation

Systolic BP > 140 mmHg, Diastolic

BP > 90 mmHg, or both.

Chronic hypertension with

superimposed preeclampsia

After 20 weeks gestation;

May develop in the postpartum

period

Hypertension only before 20 weeks

and develop proteinuria after 20

weeks; or

Well controlled hypertension with

proteinuria before 20 weeks with

sudden exacerbation of hypertension

after 20 weeks; or

Hypertension before 20 weeks with

development of severe feature(s)

after 20 weeks

Gestational hypertension After 20 weeks gestation;

May develop in the postpartum

period

New onset hypertension without

proteinuria or other severe feature(s)

Figure 1

Figure 2

References:

1. Williams Obstetrics, 24th edition. 2014

2. ACOG Hypertension in Pregnancy, 2013