Case 5

Dr Barik

A 35-year-old woman elder primi and has a 5-year history of hypertension wants to become pregnant. She has stopped using contraception. Her only medication is lisinopril at a dose of 10 mg per day. Her blood pressure is 124/68 mm Hg,and her body-mass index (the weight in kilograms divided by the square of the heightin meters) is 27.

A 35-year-old woman elder primi and has a 5-year history of hypertension wants to become pregnant. She has stopped using contraception. Her only medication is lisinopril at a dose of 10 mg per day. Her blood pressure is 124/68 mm Hg,and her body-mass index (the weight in kilograms divided by the square of the heightin meters) is 27.

Pregnancy-related deaths(3201 in US, 1991-1997-16%Pregnancy-related deaths(3201 in US, 1991-1997-16%

Chronic hypertensionHypertension (blood pressure ≥140 mm Hg systolic or ≥90 mm Hg diastolic) present before pregnancy or that is diagnosed before the 20th week of gestation

Gestational hypertension

New hypertension with a blood pressure of 140/90 mm Hg on two separate occasions, without proteinuria, arising de novo after the 20th week of pregnancy. Blood pressure normalizes by 12 weeks post partum.

Preeclampsia superimposed on chronic hypertension Increased blood pressure above the patient's baseline, a change in proteinuria, or evidence of end-organ dysfunction

Preeclampsia-eclampsia

Proteinuria (>0.3 g during 24 hours or ++ in two urine samples) in addition to new hypertension. Edema is no longer included in the diagnosis because of poor specificity. When proteinuria is absent, suspect the disease when increased blood pressure is associated with headache, blurred vision, abdominal pain, low platelets, or abnormal liver enzymes.

Classification of Hypertension in PregnancyFrom Gifford RW, August PA, Cunningham G, et al: Report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy. Am J Obstet Gynecol 183:S1, 2000

Classification of Hypertension in PregnancyFrom Gifford RW, August PA, Cunningham G, et al: Report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy. Am J Obstet Gynecol 183:S1, 2000

DiagnosisGestational Hypertension – 3.7% in 150,000 (National Center for Health Statics, 2001)

Gestational Hypertension – 3.7% in 150,000 (National Center for Health Statics, 2001)

CHRONIC HYPERTENSIONCHRONIC HYPERTENSION

•BP ≥140/90 mmHg before pregnancy or diagnosed before 20weeks’ gestation (not attributable to gestational trophoblastic disease) or•Hypertension first diagnosed after 20weeks’ gestation and persistent after 12weeks’ postpartum

•BP ≥140/90 mmHg before pregnancy or diagnosed before 20weeks’ gestation (not attributable to gestational trophoblastic disease) or•Hypertension first diagnosed after 20weeks’ gestation and persistent after 12weeks’ postpartum

Underlying hypertension-Essential familial hypertension (90%)

•BP≥ 140/90mmHg for first time during pregnancy

•No proteinuria

•BP returns to normal < 12 weeks’ postpartum

•Final diagnosis made only postpartum

•May have other signs or symptoms of preeclampsia, for example, epigastric discomfort or thrombocytopenia

•BP≥ 140/90mmHg for first time during pregnancy

•No proteinuria

•BP returns to normal < 12 weeks’ postpartum

•Final diagnosis made only postpartum

•May have other signs or symptoms of preeclampsia, for example, epigastric discomfort or thrombocytopenia

Essential familial hypertension (hypertensive vascular disease)ObesityAtrterial abnormalities

Renovascular hypertensionCoarctation of the aorta

Endocrine diordersDiabetes mellitusCushing syndromePrimary aldosteronismPheochromocytomaThyrotoxicosis

Glomerulonephritis (acute and chronic)Renoprival hypertension

Chronic glomerulonephritisChronic renal insufficiencyDiabetic nephropathy

Connetive tissue diseaseLupus erythematosusSystemic sclorosisPeriarteritis nodosa

Polycystic kidney diseaseAcute renal failure

Essential familial hypertension (hypertensive vascular disease)ObesityAtrterial abnormalities

Renovascular hypertensionCoarctation of the aorta

Endocrine diordersDiabetes mellitusCushing syndromePrimary aldosteronismPheochromocytomaThyrotoxicosis

Glomerulonephritis (acute and chronic)Renoprival hypertension

Chronic glomerulonephritisChronic renal insufficiencyDiabetic nephropathy

Connetive tissue diseaseLupus erythematosusSystemic sclorosisPeriarteritis nodosa

Polycystic kidney diseaseAcute renal failure

Nulliparous womenIncidence : 5% (wide variation)Influence by Parity, race, ethnicity, genetic predispositionNulliparous

Total :7.6% / severe : 3.3% (Hauth, 2000)

Risk factorChronic hypertension, multifetal gestation, maternal old age(>35 yrs), obesity, African-American ethnicity

Nulliparous womenIncidence : 5% (wide variation)Influence by Parity, race, ethnicity, genetic predispositionNulliparous

Total :7.6% / severe : 3.3% (Hauth, 2000)

Risk factorChronic hypertension, multifetal gestation, maternal old age(>35 yrs), obesity, African-American ethnicity

INCIDENCE

BMI (Kg/m2)Morbidity (%) <19.8 4.3 >3513.3Gestation

twin13 single 5

BMI (Kg/m2)Morbidity (%) <19.8 4.3 >3513.3Gestation

twin13 single 5

FACTOR RISK RATIO

Renal disease 20:1

Chronic hypertension 10:1

Antiphospholipid syndrome 10:1

Family history of PIH 5:1

Twin gestation 4:1

Nulliparity 3:1

Age > 40 3:1

Diabetes mellitus 2:1

African American 1.5:1

New-onset proteinuria≥ 300mg/24hours in hypertensive women but no proteinuria before 20 weeks’ gestation.

A sudden increase in proteinuria or blood pressure or platelet count <100,000/mm3 in women with hypertension and roteinuria before 20weeks’ gestation

New-onset proteinuria≥ 300mg/24hours in hypertensive women but no proteinuria before 20 weeks’ gestation.

A sudden increase in proteinuria or blood pressure or platelet count <100,000/mm3 in women with hypertension and roteinuria before 20weeks’ gestation

Treatment of mild to moderate chronic hypertension neither benefits the fetus nor prevents preeclampsia.

Excessively lowering blood pressure may result in decreased placental perfusion and adverse perinatal outcomes.

When BP is 150 to 180/100 to 110 mm Hg, pharmacologic treatment is needed to prevent maternal end-organ damage.

Treatment of mild to moderate chronic hypertension neither benefits the fetus nor prevents preeclampsia.

Excessively lowering blood pressure may result in decreased placental perfusion and adverse perinatal outcomes.

When BP is 150 to 180/100 to 110 mm Hg, pharmacologic treatment is needed to prevent maternal end-organ damage.

Antihypertensive Therapy Prior to Antihypertensive Therapy Prior to and During Pregnancyand During Pregnancy

1.1. What is the proper management of young women What is the proper management of young women with mild hypertension?with mild hypertension?

2.2. What are the benefits of treating mild What are the benefits of treating mild hypertension in pregnancy?hypertension in pregnancy?

3.3. Is pharmacological treatment of mild Is pharmacological treatment of mild hypertension harmful to mothers, fetuses, and hypertension harmful to mothers, fetuses, and infants?infants?

4.4. Are particular antihypertensive drugs more Are particular antihypertensive drugs more ffective or harmful than others? ffective or harmful than others?

1.1. What is the proper management of young women What is the proper management of young women with mild hypertension?with mild hypertension?

2.2. What are the benefits of treating mild What are the benefits of treating mild hypertension in pregnancy?hypertension in pregnancy?

3.3. Is pharmacological treatment of mild Is pharmacological treatment of mild hypertension harmful to mothers, fetuses, and hypertension harmful to mothers, fetuses, and infants?infants?

4.4. Are particular antihypertensive drugs more Are particular antihypertensive drugs more ffective or harmful than others? ffective or harmful than others?

What Are the Benefits of Treating What Are the Benefits of Treating Mild Hypertension in Pregnancy?Mild Hypertension in Pregnancy?What Are the Benefits of Treating What Are the Benefits of Treating Mild Hypertension in Pregnancy?Mild Hypertension in Pregnancy?

Data are insufficient to either prove or Data are insufficient to either prove or disprove effects in perinatal outcomedisprove effects in perinatal outcome

• All trials had inadequate sample sizeAll trials had inadequate sample size• Most were unblindedMost were unblinded• Few women enrolled in first trimesterFew women enrolled in first trimester• 15 different drugs or combinations were 15 different drugs or combinations were

studiedstudied

Definite need for multicenter trialsDefinite need for multicenter trials

What is the Proper Management of What is the Proper Management of Young Women with Hypertension?Young Women with Hypertension?

No report that addressed the effect of blood No report that addressed the effect of blood pressure control before conception on fetal pressure control before conception on fetal outcomesoutcomes

Women of reproductive age are excluded from Women of reproductive age are excluded from randomized trialsrandomized trials

Only 3 trials in women aged 30-54 yearsOnly 3 trials in women aged 30-54 years

• 8,565 studied8,565 studied

• Little data in women < 40 yearsLittle data in women < 40 years

1616

Acute Medical Therapy

• Hydralazine• Labetalol• Nifedipine• Nitroprusside• Clonidine

• Hydralazine• Labetalol• Nifedipine• Nitroprusside• Clonidine

HydralazineHydralazine

• Dose: 5-10 mg every 20 minutes• Onset: 10-20 minutes• Duration: 3-8 hours• Side effects: headache, flushing, tachycardia,

lupus like symptoms• Mechanism: peripheral vasodilator

• Dose: 5-10 mg every 20 minutes• Onset: 10-20 minutes• Duration: 3-8 hours• Side effects: headache, flushing, tachycardia,

lupus like symptoms• Mechanism: peripheral vasodilator

Labetalol

• Dose: 20 mg, then 40, then 80 every 20 minutes, for a total of 220mg

• Onset: 1-2 minutes• Duration: 6-16 hours• Side effects: hypotension• Mechanism: Alpha and Beta blockade

• Dose: 20 mg, then 40, then 80 every 20 minutes, for a total of 220mg

• Onset: 1-2 minutes• Duration: 6-16 hours• Side effects: hypotension• Mechanism: Alpha and Beta blockade

Nifedipine

• Dose: 10 mg po, not sublingual• Onset: 5-10 minutes• Duration: 4-8 hours• Side effects: chest pain, headache, tachycardia• Mechanism: CA channel blockade

• Dose: 10 mg po, not sublingual• Onset: 5-10 minutes• Duration: 4-8 hours• Side effects: chest pain, headache, tachycardia• Mechanism: CA channel blockade

Clonidine

• Dose: 1 mg po• Onset: 10-20 minutes• Duration: 4-6 hours• Side effects: unpredictable, avoid rapid

withdrawal• Mechanism: Alpha agonist, works centrally

• Dose: 1 mg po• Onset: 10-20 minutes• Duration: 4-6 hours• Side effects: unpredictable, avoid rapid

withdrawal• Mechanism: Alpha agonist, works centrally

NitroprussideNitroprusside

• Dose: 0.2 – 0.8 mg/min IV• Onset: 1-2 minutes• Duration: 3-5 minutes• Side effects: cyanide accumulation,

hypotension• Mechanism: direct vasodilator

• Dose: 0.2 – 0.8 mg/min IV• Onset: 1-2 minutes• Duration: 3-5 minutes• Side effects: cyanide accumulation,

hypotension• Mechanism: direct vasodilator

Seizure Prophylaxis

• Magnesium sulfate• Loading dose of 4 to 6 g diluted in 100 mL of

normal saline, given IV over 15 to 20 minutes, followed by a continuous infusion of 1-2 g per hour

• Monitor urine output, RR and DTR’s• With renal dysfunction, may require a lower

dose

• Magnesium sulfate• Loading dose of 4 to 6 g diluted in 100 mL of

normal saline, given IV over 15 to 20 minutes, followed by a continuous infusion of 1-2 g per hour

• Monitor urine output, RR and DTR’s• With renal dysfunction, may require a lower

dose

• Low-dose aspirin (75 to 81 mg daily) has small to moderate benefits for the prevention of preeclampsia (NNT = 72), preterm delivery (NNT = 74), and fetal death (NNT = 243). The benefit of aspirin is greatest (NNT = 19) for prevention of preeclampsia in women at highest risk (previous severe preeclampsia, diabetes, chronic hypertension, renal disease, or autoimmune disease). – B

• For women with mild preeclampsia, delivery is generally not indicated until 37 to 38 weeks of gestation and should occur by 40 weeks. – C

KEY RECOMMENDATIONS FOR PRACTICE

• In women without end-organ damage, chronic hypertension in pregnancy does not require treatment unless the patient's blood pressure is persistently greater than 150 to 180/100 to 110 mm Hg. – C

• Calcium supplementation decreases the incidence of hypertension and preeclampsia, respectively, among all women (NNT = 11 and NNT = 20), women at high risk of hypertensive disorders (NNT = 2 and NNT = 6), and women with low calcium intake (NNT = 6 and NNT = 13). – A

• In women without end-organ damage, chronic hypertension in pregnancy does not require treatment unless the patient's blood pressure is persistently greater than 150 to 180/100 to 110 mm Hg. – C

• Calcium supplementation decreases the incidence of hypertension and preeclampsia, respectively, among all women (NNT = 11 and NNT = 20), women at high risk of hypertensive disorders (NNT = 2 and NNT = 6), and women with low calcium intake (NNT = 6 and NNT = 13). – A