H YPERTENSION IN P REGNANCY Ayoub innabi

There are four major hypertensive disorders related to pregnancy: -Pre- eclampsia Eclampsia HELLP -Chronic/preexisting hypertension -Preeclampsia superimposed upon chronic/preexisting hypertension -Gestational hypertension DEFINITIONS OF PREGNANCY-RELATED HYPERTENSIVE DISORDERS: —

C HRONIC / PREEXISTING HYPERTENSION Systolic pressure ≥140 mmHg and/or diastolic pressure ≥90 mmHg -That antedates pregnancy or is present before the 20th week of pregnancy (on at least two occasions) or persists longer than 12 weeks postpartum. -It can be primary (essential hypertension) or secondary to a variety of medical disorders

P REECLAMPSIA SUPERIMPOSED UPON CHRONIC / PREEXISTING HYPERTENSION Superimposed preeclampsia is defined by the new onset of proteinuria after 20 weeks of gestation in a woman with chronic/preexisting hypertension.

G ESTATIONAL HYPERTENSION Gestational hypertension refers to hypertension without proteinuria or other signs/symptoms of preeclampsia that develops after 20 weeks of gestation. It should resolve by 12 weeks postpartum. If it persists beyond 12 weeks postpartum, the diagnosis is revised to chronic/preexisting hypertension that was masked by the physiologic decrease in blood pressure that occurs in early pregnancy.

C RITERIA FOR G ESTATIONAL H YPERTENSION Systolic blood pressure ≥140 mmHg OR Diastolic blood pressure ≥ 90 mmHg AND no proteinuria Developing AFTER the 20th week of gestation in women known to be normotensive before pregnancy. - Blood pressure should be elevated on at least two occasions at least six hours apart.

P RE - ECLAMPSIA

D EFINITIONS : Preeclampsia — refers to the new onset of hypertension and proteinuria after 20 weeks of gestation in a previously normotensive woman.

D EFINITIONS :  Preeclampsia can be classified as ‘severe’ when: - Severe hypertension, - or severe proteinuria, - or other signs/symptoms of end-organ injury are present.  In the absence of any of these findings, preeclampsia can be classified as ‘mild.’ In this commonly used system, there is no ‘moderate’ classification.

C RITERIA FOR D IAGNOSIS OF P REECLAMPSIA : Systolic blood pressure ≥140 mmHg or Diastolic blood pressure ≥90 mmHg and Proteinuria ≥0.3 grams in a 24-hour urine specimen

I NCIDENCE Preeclampsia occurs in up to 7.5 percent of pregnancies worldwide

R ISK F ACTORS OF P RE - ECLAMPSIA Maternal Factors: 1. Demographic criteria: o Primagravida o Age extremes ( 34 years). o Black race o High body mass index (≥26.1) o Male partner whose mother had preeclampsia 2- Medical complications: o DM, Chronic HTN, Pre-existing renal disease, thrombophilia, Antiphospholipid antibody syndrome. 3- Past Hx or FHx of pregnancy-induced HTN. 12

R ISK F ACTORS OF P RE - ECLAMPSIA Fetal factors: o Hydatidiform mole o > 1 fetus o fetal hydrops o Unexplained fetal growth restriction

R ISK F ACTORS OF P RE - ECLAMPSIA -A past history of preeclampsia – Risk 7-fold - Primigravid state is a significant predisposing factor. One theory is that these women may have had limited recent exposure to paternal antigens, which may play a role in the pathogenesis of the disease. -A family history of preeclampsia in a first degree relative, suggesting a heritable mechanism in some cases. The father of the baby may contribute to the increased risk, as the paternal contribution to fetal genes may have a role in defective placentation and subsequent preeclampsia. - Women who smoke cigarettes have a lower risk of preeclampsia than nonsmokers.

M ECHANISMS BEHIND PREECLAMPSIA Not certain. Numerous maternal, paternal, and fetal factors have been implicated in development. The factors currently considered to be the most important include the following:  Maternal immunologic intolerance  Abnormal placental implantation  Genetic, nutritional, and environmental factors  Cardiovascular and inflammatory changes

P ATHOGENESIS OF P RE - ECLAMPSIA As the term toxemia indicates, the search for a toxin has been long fruitless. Uteroplacental ischemia is the center to the development of disease, results in production of toxin that enters circulation  widespread endothelial dysfunction. 16

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S EVERE PRE - ECLAMPSIA Less common. Can be diagnosed on basis of: Severe HTN (BP ≥ 160 / 110 mm Hg) on two occasions at least six hours apart. OR Severe proteinuria (3-4+ dipstick OR > 5 g / 24 hr) alone without symptoms. OR Only mild HTN + proteinuria if signs and symptoms are present: 18

C ON ’ T  Resp : Plum. Edema, cyanosis.  Renal : Proteinuria, ↑ Serum creatinine, Oliguria <500 mL in 24 hours.  Hepatic : ↑ LFTs  Neurologic : visual disturbance (i.e. scotomas, loss of peripheral vision), headache, convulsions.  Symptoms of liver capsule distention: Right upper quadrant or epigastric pain Nausea, vomiting.  Hematologic : thrombocytopenia, microangiopathic hemolysis.  Fetal growth restriction 19

E CLAMPSIA [ Latin = convulsions] = Unexplained tonic-clonic seizures + Mild / severe pre-eclampsia. Most often occurs intra-partum, but can also occur ante-partum & post-partum. 20

An eclamptic seizure is typically tonic-clonic – lasts 60 to 75 seconds. Symptoms that may occur before the seizure include persistent frontal or occipital headache, blurred vision, photophobia, right upper quadrant or epigastric pain, and altered mental status. In up to one-third of cases, there is no proteinuria or blood pressure is less than 140/90 mmHg prior to the seizure

S UMMARY OF MATERNAL AND NEONATAL OUTCOMES IN ECLAMPISA Abruption 7 to 10 % DIC 7 to 11% Pulmonary edema 3 to 5 % Acute renal failure 5 to 9% Aspiration pneumonia 2 to 3 % Cardiopulmonary arrest 2 to 5 % Liver hematoma 1% HELLP syndrome 10 to 15% Perinatal death 5.6 to 11.8% Preterm birth 50%

C ON ’ T HELLP syndrome : o Type of severe pre-eclampsia. o H emolysis + E levated L iver enzymes + L ow P latelets. 23

S IGNS AND S YMPTOMS  Severe hypertension (systolic blood pressure ≥160 mm Hg or diastolic ≥110 mm Hg on two occasions at least six hours apart)  Persistent and/or severe headache,  Visual abnormalities (scotomata, photophobia, blurred vision, or temporary blindness [rare])  Upper abdominal or epigastric pain  Nausea, vomiting  Oliguria  Dyspnea, retrosternal chest pain  Fetal growth restriction  Oligohydramnios  Altered mental status

L ABORATORY ABNORMALITIES  Hemoconcentration  Microangiopathic hemolytic anemia (abnormal peripheral smear, elevated bilirubin, or low serum haptoglobin levels U/L)  Thrombocytopenia (<100,000/microL)  Elevated serum creatinine concentration (>1.3 mg/dL)  Elevated liver enzymes (twice the upper limit of normal)  Severe proteinuria (≥5 grams in 24 hours)

A TYPICAL PRESENTATION Include any of the following: Onset of signs/symptoms at <20 weeks of gestation Hypertension or proteinuria (but not both) with or without characteristic signs and symptoms of severe preeclampsia Delayed postpartum onset or exacerbation of disease (>2 days postpartum)

C OMPLICATIONS Maternal: 1. Cerebral hemorrhage (50% of deaths). 2. LVF / Pulm. edema. 3. Liver / renal dysfunction. 4. Seizures. 5. DIC. 6. Abruptio placenta: ante-partum painful vaginal bleeding. Fetal: Mainly due to placental insufficiency: 1. Fetal loss. 2. IUGR. 3. Prematurity. 27

M ANAGEMENT OF PRE - ECLAMPSIA The optimal management of a woman with preeclampsia depends on: - Gestational age. - Disease severity. Because delivery is the only cure for preeclampsia, clinicians must try to minimize maternal risk while maximizing fetal maturity.

M ANAGEMENT OF PRE - ECLAMPSIA Deliveries with mild preeclampsia are often induced after 37 weeks' gestation. Before this, the immature fetus is treated with expectant management with corticosteroids to accelerate lung maturity in preparation for early delivery. In patients with severe preeclampsia, induction of delivery should be considered after 34 weeks' gestation. In these cases, the severity of disease must be weighed against the risks of infant prematurity.

C ARE IN M ILD P REECLAMPSIA Hospitalized and monitored carefully A pregnancy complicated by mild preeclampsia at or beyond 37 weeks should be delivered  Delivery is recommended if a patient is at 34 weeks' gestation or more and has: Ruptured membranes, Abnormal fetal testing, Progressive labor, or Fetal growth restriction in the setting of mild preeclampsia.

C ARE IN M ILD P REECLAMPSIA Expectant management of women with mild preeclampsia consists of: Frequent laboratory monitoring (platelet count, liver and renal function tests), Assessment of maternal blood pressure and symptoms, and Evaluation of fetal growth and well-being.

T REATMENT OF H YPERTENSION The use of antihypertensive drugs to control mildly elevated blood pressure in the setting of preeclampsia does not alter the course of the disease or diminish perinatal morbidity or mortality, and should be avoided. Sodium restriction and diuretics have no role in routine therapy

C ARE IN S EVERE P REECLAMPSIA When severe preeclampsia is diagnosed after 34 weeks' gestation, delivery is most appropriate. But if patient appears to be stable, and if the fetal condition is reassuring, expectant management may be considered.

C RITERIA FOR DELIVERY  Women with severe preeclampsia who are managed expectantly must be delivered under the following circumstances:  Nonreassuring fetal heart status  Uncontrollable BP  Oligohydramnios, with amniotic fluid index (AFI) of less than 5 cm  Severe intrauterine growth restriction in which the estimated fetal weight is less than 5%  Oliguria (< 500 mL/24 h)  Serum creatinine level of at least 1.5 mg/dL  Pulmonary edema  Shortness of breath or chest pain with pulse oximetry of < 94% on room air  Headache that is persistent and severe  Right upper quadrant tenderness  Development of HELLP syndrome

A CUTE T REATMENT OF S EVERE H YPERTENSION IN P REGNANCY  Hydralazine :  Direct peripheral arteriolar vasodilator  In the past, was widely used as the first-line treatment for acute hypertension in pregnancy.  Slow onset of action (10-20 min), peaks approximately after 20 minutes  IV bolus dose of 5-10 mg, depending on the severity of hypertension, may be administered every 20 minutes up to a maximum dose of 30 mg.  S/E: headache, nausea, and vomiting. May result in maternal hypotension, resulting in nonreassuring fetal heart rate tracing

A CUTE T REATMENT OF S EVERE H YPERTENSION IN P REGNANCY Labetalol : Selective alpha blocker and nonselective beta blocker; produces vasodilatation. 20 mg IV with repeat doses (40, 80, 80, and 80 mg) every 10 minutes. Maximum dose of 300 mg. Decreases in BP after 5 minutes (in contrast to hydralazine). Decreases supraventricular rhythm and slows the heart rate, reducing myocardial oxygen consumption. No change in afterload is observed after treatment with labetalol. S/E dizziness, nausea, and headaches. Oral maintenance dose can be started after IV

A CUTE T REATMENT OF S EVERE H YPERTENSION IN P REGNANCY Calcium channel blockers : Arteriolar smooth muscle; vasodilatation by blocking calcium entry into the cells. Nifedipine is the oral calcium channel blocker that is used in the management of hypertension in pregnancy. 10 mg PO every minutes, max 3 doses. S/E: tachycardia, palpitations, and headaches. Avoid CCB with MgSO4 Postpartum in patients with preeclampsia, for BP control.

A CUTE T REATMENT OF S EVERE H YPERTENSION IN P REGNANCY Sodium Nitroprusside In a severe hypertensive emergency, given when others failed to lower BP, Release of nitric oxide; vasodilation. Preload and afterload decreased. Onset of action is rapid Severe rebound hypertension may result. Cyanide poisoning may occur in the fetus. Should be reserved for postpartum care or just before the delivery of the fetus

S EIZURE P ROPHYLAXIS  Recommended for women with severe preeclampsia  Less clear benefit in mild preeclampsia  Magnesium sulfate rather than phenytoin is recommended for seizure prophylaxis.  A loading dose of 6 grams magnesium sulfate intravenously over 15 to 20 minutes followed by 2 grams per hour as a continuous infusion.  The maintenance dose (but not the loading dose) should be adjusted in women with renal insufficiency.

M G SO4 T OXICITY  Calcium gluconate (1 gram intravenously over 5 to 10 minutes) should be administered to counteract life-threatening symptoms of magnesium toxicity.  Magnesium toxicity is related to serum concentration:  Loss of deep tendon reflexes occurs at 8 to 10 mEq/L,  Respiratory paralysis at 10 to 15 mEq/L,  Cardiac arrest at 20 to 25 mEq/L.

P ROGNOSIS  Morbidity and Mortality  Worldwide, preeclampsia and eclampsia responsible for approximately 14% of maternal deaths/year (50,000-75,000).  Morbidity and mortality in preeclampsia and eclampsia are related to the following conditions:  Systemic endothelial dysfunction  Vasospasm and small-vessel thrombosis leading to tissue and organ ischemia  CNS events, such as seizures, strokes, and hemorrhage  Acute tubular necrosis  Coagulopathies  Placental abruption in the mother

R ECURRENCE  Recurrence risk of preeclampsia: approximately 10%.  Previous history of severe preeclampsia (including HELLP syndrome and/or eclampsia), recurrence risk of preeclampsia is 20%.  Recurrence risk of HELLP syndrome is 5% and of eclampsia is 2%.  Earlier disease during the index pregnancy, higher chance of recurrence.  If before 30 weeks' gestation, recurrence may be as high as 40%

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