Hypertensive Disorders of Pregnancy

Case report You admitted a previously healthy nullipara at 36 weeks’ gestation who presented with new-onset periorbital edema and is found to have blood pressure readings of 150/100 to 155/105 mmHg, 4+ protein on urinary dipstick, modest (ie, less than 2-fold) elevations in her hepatic transaminases, a platelet count of 105,000/µL and a mildly (8th percentile) growth-restricted fetus.

Question? Does she have severe preeclampsia? Should you start parenteral magnesium sulfate? Should you give antihypertensive therapy? Is delivery indicated?

Hypertensive Disorders of Pregnancy most common medical complications of pregnancy, 5% to 10% of all pregnancies. 16% of maternal mortality in developed countries. Classification include: chronic hypertension (30%) hypertensive unique to pregnancy (70%) ( gestational hypertension and preeclampsia).

Hypertensive Disorders of Pregnancy The spectrum of disease ranges from non-severe to severe hypertension and multi organ dysfunction. The incidence is dependent on: maternal age, race, underlying medical conditions.

HTN BP 140/90 or greater at least two occasions at least 4 hours apart but no more than 1 week apart. in an upright position, after a 10-minute or longer rest period. For patients in the hospital, either the patient sitting up or in the left lateral position with the patient's arm at the level of the heart. Avoidance tobacco or caffeine for 30 minutes preceding the measurement Delta HTN

Abnormal proteinuria 300 mg or more of protein in 24 hours. The most accurate is obtained with a 24-hour urine collection. A value of 1+ or greater correlates with 30 mg/dL. Proteinuria by dipstick is defined as 1+ or more on at least two occasions at least 6 hours apart but no more than 1 week apart. 24-hour urine collection should be performed the diagnostic criteria . to use a clean sample, because blood, vaginal secretions, and bacteria can increase the amount of protein in urine.

Edema common finding in the gravid patient, (~50%) Lower extremity edema is the most typical form. Pathologic edema is seen in nondependent regions such as the face, hands, or lungs. Excessive, rapid weight gain of 2 pounds or more per week is another sign of fluid retention.

Classificationof Hypertension Gestational hypertension (most common) developing after 20 weeks gestation or during the first 24 hours postpartum without proteinuria or other signs of preeclampsia (46%___progress to preeclampcia Transient hypertension resolves by 12 weeks postpartum Preeclamsia or Eclampsia: Chronic HTN Superimpose preeclampsia

Classification of Hypertension Preeclamsia –Eclampsia developing after 20 weeks gestation with proteinuria; eclampsia is the occurrence of seizure activity without other identifiable causes Chronic hypertension prior to pregnancy, prior to 20 weeks gestation, or after 12 weeks postpartum Preeclampsia superimposed The development of preeclampsia or eclampsia in a woman with preexisting or chronic hypertension(New onset pr;increase pr,or HTN,or plt <100000)

Preeclampsia or eclampsia Multisystemic,unknown cause,only in pregnancy 2%-- 7% incidence higher in : nulliparous women twin gestation (14%) and previous preeclampsia (18%). symptoms are: headaches visual changes, epigastric or right upper quadrant pain nausea or vomiting.

Preeclampsia or eclampsia divided further into non-severe and severe . non-severe preeclampsia may progress to fulminant disease. A particularly severe form of preeclampsia is the HELLP syndrome

Criteria of Non-severe Preeclampsia SBP≥140 mm Hg and/or DBP ≥90 mm Hg on two occasions at least 4 hours apart, typically occurring after 20 weeks gestation (no more than 1 week apart). Proteinuria of 300 mg in a 24-hour urine collection or >1+ on two random sample urine dipsticks at least 6 hours apart (no more than 1 week apart).

Criteria of Severe Preeclampsia SBP ≥160 mm Hg and/or DBP ≥110 mm Hg Proteinuria Oliguria <500 cc in 24 hours Thrombocytopenia platelet count <100,000/mm3 Elevated liver function test results with persistent epigastric or right upper quadrant pain Pulmonary edema Persistent, severe cerebral or visual disturbances.

HELLP syndrome hemolysis, elevated liver enzymes, and low platelet count. hypertension and proteinuria might be absent in 10% to 15% of women who develop HELLP

Risk Factors for Preeclampsia Nulliparity Chronic or vascular disease (pregestational diabetes, renal disease, chronic hypertension, rheumatic disease, connective tissue disease) Molar pregnancy Fetal hydrops Multifetal gestation Obesity and insulin resistance Prior pregnancy complicated by preeclampsia

Risk Factors for Preeclampsia Antiphospholipid antibody syndrome and thrombophilia Family history of preeclampsia or eclampsia Fetal aneuploidy ,Maternal infections, Maternal susceptibility genes, Extremes of maternal age , Partner-related factors

Etiologic Theories in Preeclampsia The syndrome is characterized by : vasospasm; hemoconcentration; and ischemic changes in the placenta, kidney, liver, and brain. These abnormalities usually are seen in women with severe preeclampsia.

Etiologic Theories in Preeclampsia Abnormal or increased immune response Genetic predisposition Abnormal coagulation or thrombophilias Abnormal angiogenesis Endothelial cell injury

Etiologic Theories in Preeclampsia Alterations in nitric oxide levels Increased oxygen free radicals Abnormal cytotrophoblast invasion Abnormal calcium metabolism Dietary deficiencies

Pathophysiology Cardiovascular intense vasoconstriction with segmental spasm in arterioles. alterations in the normal interactions of vasodilatory (prostacyclin, nitric oxide) and vasoconstrictive (thromboxane A2, endothelin) . higher arterial blood pressures (afterload). hemoconcentration: endothelial damage leak interstitial space, . lower intravascular volumes and less tolerance for the blood loss.

Hematologic thrombocytopenia (platelet count <100,000/mm3). The suggested pathophysiology likely is vascular endothelial damage or activation and higher levels of thromboxane A2. microangiopathic hemolysis, (HELLP) ( schistocytes and increased LDH levels). A low hematocrit may signify hemolysis, and a falsely high hematocrit may be due to hemoconcentration.

Renal Vasospasm renal perfusion GFR. (normal pregnancy: GFR is increased up to 50%). creatinine rarely rise above normal pregnancy levels (0.8 mg/dL). oliguria (defined as <500 cc in 24 hours) may occur due to renal insufficiency.(ATN). pathognomonic renal lesion in preeclampsia is called glomerular capillary endotheliosis, which is swelling of the glomerular capillary endothelial and mesangial cells.

Hepatic range from mildly elevated liver enzyme levels to subcapsular liver hematomas and hepatic rupture. 20% of maternal mortality in preeclampsia is related to hepatic complications. The pathologic liver lesions seen on autopsy are periportal hemorrhages, hepatocellular necrosis, ischemic lesions, intracellular fatty changes, and fibrin deposition

Central Nervous System Eclamptic convulsions major cause of maternal mortality. etiology of eclampsia : coagulopathy, fibrin deposition, and vasospasm. The most common finding in the brain is edema, posterior hemispheres edema&hemorrhage:. headaches and visual disturbances ( scotomata; blurred vision; and rarely, temporary blindness).

Fetus and Placenta hallmark placental lesion in preeclampsia is acute atherosis of decidual arteries. This is due in part to the abnormal adaptation of the spiral artery cytotrophoblast interface and results in poor perfusion. oligohydramnios; IUGR abruption fetal distress; fetal demise.

Prediction No good screening test. doppler ultrasonography: velocity of uterine blood flow in the second trimester. Abnormal velocity waveform is characterized by a high resistance index or an early diastolic notch (unilateral or bilateral). No for routine screening. .

Prediction Proposed Methods of Prediction of Preeclampsia Maternal serum uric acid levels Uterine artery Doppler determinations Elevated second-trimester MSAFP,hCG levels, inhibin A Elevated sFlt-1 and endoglin Reduced placental growth factors Plasma fibronectin values Midpregnancy blood pressure measurements Urinary calcium excretion Urinary kallikrein concentration Platelet activation Excessive weight gain Calcium-to-creatinine ratio

Prevention Diet and exercise ; protein or salt restriction No reduction Insufficient Magnesium or zinc Fish oil No effect Calcium Reduced high risk and with low baseline dietary ca Recommended for high risk of gestational hypertension and in communities with low intake Low-dose aspirin 19% preeclampsia; 16% neonatal deaths Consider in high-risk pregnancies Heparin Reduced in one trial Antioxidant vitamins (C, E) No Antihypertensive in chronic hypertension (I) severe HTN reduced by half; no reduction in preeclampsia

Management of non-severe preeclampsia Ideally, a patient who has preeclampsia should be hospitalized at the time of diagnosis. 24-hour urine collection for protein, hematocrit, platelet count, serum creatinine value, (AST) level. ultrasonography :AFI, fetal weight, gestational age.

Management of non-severe preeclampsia The only definitive cure for preeclampsia is delivery. The safety of the mother and a mature newborn. mild preeclampsia at term (>37 weeks), the general consensus is delivery who is preterm (<37 weeks), controversy respect level of activity, diet, antihypertensive medications, and delivery. Usually, these patients do not require immediate delivery, and expectant management is warranted If expectant management is chosen, the second question then becomes where to manage the patient in the hospital or at home

Criteria for Home Management of non-severe Preeclampsia Ability to comply with recommendations Normal laboratory tests No maternal symptoms Reassuring fetal status with appropriate growth

Maternal and Fetal Evaluation in non-severe Preeclampsia Maternal Daily weight Urine dipstick; 24-hour protein once weekly Monitoring for severe preeclampsia symptoms Prenatal visits twice per week Lab tests (liver function tests, hematocrit, platelet count once or twice per week) Fetal Daily fetal movement Nonstress test twice per week or biophysical profile once per week Ultrasound for growth every 3 to 4 weeks

Prompt Evaluation Signs and Symptoms of Preeclampsia That Warrant : Nausea and vomiting Persistent severe headache Right upper quadrant or epigastric pain Scotoma Blurred vision

Management of non-severe Preeclampsia Induction of labor is indicated in those patients with a favorable cervix At 37 weeks or beyond, if the cervix is unfavorable, two options: either cervical ripening and delivery continued expectant management with maternal and fetal evaluation. The preferred mode of delivery remains vaginal. A cesarean section should be performed for obstetric indications only

Management of non-severe Preeclampsia In the past, while in labor, patients with mild preeclampsia received intravenous magnesium sulfate (MgSO4) for seizure prophylaxis. There is no support in the literature for the need or the optimal timing to begin the MgSO4 infusion, and this should be left to the discretion of the physician. In mild the authors recommend to individualize each case for the use of MgSO4.

Management of non-severe Preeclampsia Pain management in labor should be individualized. Close monitoring of blood pressure intrapartum is necessary. Antihypertensive medications to keep blood pressure values below 160 / 110 mm Hg most commonly used intravenous medications for this purpose are labetalol and hydralazine. not to drop the blood pressure too rapidly, lead to reduced renal perfusion and reduced placental perfusion. who receive MgSO4 also are at risk for postpartum hemorrhage due to uterine atony.

Management of non-severe Preeclampsia Patients should be monitored closely for at least 12 to 24 hours postpartum. Postpartum eclampsia occurs in 25% of patients. It is not clear if MgSO4 should be continued in the postpartum period. There is no need for continued seizure prophylaxis beyond 24 hours postpartum

Maternal and Fetal Complications in Severe Preeclampsia Maternal Abruptio placentae (10%-40%) Disseminated coagulopathy/HELLP syndrome (10%-20%) Pulmonary edema/aspiration (2%-5%) Acute renal failure (1%-5%) Eclampsia (<1%) Liver failure or hemorrhage (<1%) Stroke (rare) Death (rare) Long-term cardiovascular morbidity

Maternal and Fetal Complications in Severe Preeclampsia Fetal Preterm delivery (15%-67%) Fetal growth restriction (10%-25%) Hypoxic neurologic injury (<1%) Perinatal death (1%-2%) Long-term cardiovascular morbidity associated with low birth weight

Management of severe Preeclampsia Any patient with severe preeclampsia should be admitted and observed initially in a labor and delivery unit Workup should include assessment for fetal well-being, monitoring of maternal blood pressures . Laboratory evaluation should include: 24-hour urine collection for total protein, hematocrit, platelet count, creatinine ,AST levels. Intravenous MgSO4 should be initiated at time of admission. initial ultrasonographic examination with umbilical artery Doppler studies for fetal growth and amniotic fluid index should be obtained as well.

Acute treatment of severe hypertension Hydralazine 5-“10 mg i.v. every 20 min 30 mga Labetalol 20-40 mg i.v. every 10-15 min 220 mga Avoid in women with asthma or congestive heart failure Nifedipine 10-20 mg p.o. every 30 min 50 mga Long-term treatment of hypertension Methyldopa 250 mg b.i.d. 4 g/d 100 mg b.i.d. 2,400 mg/d Atenolol 50 mg q.d. 100 mg/d Associated with IUGR

Propanolol 40 mg b.i.d. 640 mg/d thyroid disease Hydralazine 10 mg t.i.d. 100 mg/d left ventricular hypertrophy Nifedipine 10 mg b.i.d. 120 mg/d women with diabetes Diltiazem 120-180 mg q.d. 540 mg/d Thiazide diuretic 12.5 mg b.i.d. 50 mg/d CHF; may be added as second agent; not to be used if preeclampsia develops or IUGR is present ACE inhibitors/ARB Not to be used after 16-“18 wk

Management of severe Preeclampsia delivery is considered in all women with severe preeclampsia prolonging the pregnancy may be hazardous to the mother with little benefit to the fetus. In patients at 33 to 34 weeks gestation, steroids should be administered and delivery planned within 48 hours unless otherwise indicated.

Management of severe Preeclampsia In patients with severe prematurity , expectant management significantly improves neonatal outcome. The goal in these patients is to gain at least 48 hours that glucocorticoids can be administered for fetal benefit. They should be counseled regarding the risks and benefits of expectant management

Management of severe Preeclampsia Ultrasonography for fetal growth every 2 to 3 weeks. Maternal laboratory evaluation should be done daily or every other day. If a stable maternal and fetal course is maintained, expectant management continued until 34 weeks. The development of any worsening change in maternal or fetal status warrants delivery regardless of gestational age. A woman with a nonviable fetus should be terminated. above 23 weeks, expectant

Management of severe Preeclampsia Maternal blood pressure control Medications orally or by the intravenous route management of acute hypertension are hydralazine and labetalol. avoid a sudden drop blood pressure precipitating cerebral ischemia, decreased renal perfusion, and decreased placental perfusion.

Intrapartum management Include: close blood pressure control, continuous fetal monitoring, and intravenous MgSO4 administration. urinary catheter should be placed in order to closely monitor fluid balance. Urine output should be >100 cc every 4 hours. A trial of labor is indicated in patients with severe preeclampsia. Pain management ( Epidural anesthesia is a reasonable option), uterine atony while receiving continuous MgSO4 infusion. Methylergonovine (Methergine) is contraindicated in these patients.

MgSO4 continue for 24 hours postpartum. monitor blood pressure, reflexes, and fluid status.

Expeditious Delivery in Severe Preeclampsia Maternal Uncontrolled severe hypertension (160 /110 mm Hg) despite maximum doses of antihypertensive (i.v. labetalol [220 mg], hydralazine, and oral nifedepine) Eclampsia or persistent cerebral symptoms Pulmonary edema Placenta abruption Thrombocytopenia (platelet count less than 100,000) or elevated liver enzymes (HELLP syndrome) Serum creatinine of 1.2 mg/dL or more or oliguria (<0.5 mL/kg per hour)

Expeditious Delivery within 48-72 Hours in Severe Preeclampsia Fetal Severe fetal growth restriction (<5th percentile for gestational age) Persistant oligohydramnios (amniotic fluid index of <5 cm on at least two occasions >24 hours apart) Umbilical artery Doppler studies with persistent reverse end-diastolic flow Biophysical profile <4 on two occasions at 4 hours apart Repetitive late deceleration or severe variable deceleration or loss of variability

Diagnosis of HELLP Syndrome Hemolysis Abnormal peripheral smear LDH >600 U/L Bilirubin >1.2 mg/dL Elevated liver enzymes Serum AST >70 U/L LDH >600 U/L Low platelets Platelet count <100,000/mm3

Differential Diagnosis of HELLP Syndrome Acute fatty liver of pregnancy Appendicitis Cerebral hemorrhage Diabetes insipidus Gallbladder disease Gastroenteritis Glomerulonephritis Hemolytic uremic syndrome Hyperemesis gravidarum Idiopathic thrombocytopenia Pancreatitis Pyelonephritis Systemic lupus erythematosus Thrombophilias Thrombotic thrombocytopenic purpura Viral hepatitis, including herpes

Eclampsia much higher in developing countries. major cause of maternal and perinatal morbidity and mortality worldwide. wide spectrum of signs and symptoms, from mild isolated hypertension to multiorgan failure. Prevention of eclampsia is one of the goals in treating preeclamptic patients with MgSO4

Management of Eclampsia During seizure, the main therapy is supportive care. avoiding injury, maintaining oxygenation, minimizing the risk of aspiration. Most seizures are self-limited, lasting 1 to 2 minutes. hypoxia or acidosis both in mother and fetus. MgSO4 is the drug of choice for the prevention 10% of eclamptic women receiving MgSO4 will have further seizures.

Management of the Eclamptic Patient Avoid injury Padded bedside rails Physical restraints Maintain oxygenation to mother and fetus Oxygen at 8-10 L per minute by face mask Monitor oxygenation and metabolic status with transcutaneous pulse oximetry or arterial blood gas measurements Minimize aspiration Lateral decubitus position Suctioning of vomitus and oral secretions Obtain chest x-ray after cessation of convulsion to rule out aspiration Initiate MgSO4 to prevent recurrent seizures Control severe hypertension Initiate the delivery process

Management of the Eclamptic Patient abnormalities in the fetal heart rate pattern. bradycardia, decreased variability, late decelerations, and reflex tachycardia. These abnormalities typically resolve within 5 to 10 minutes after the convulsion. not to proceed directly to cesarean Stabilization of the mother is the priority. . If prolonged signs of fetal compromise occur indicating possible abruptio placentae, consideration should be given to proceed with operative delivery. Vaginal delivery is the preferred route after an eclamptic seizure. Induction of labor should be performed with oxytocin or prostaglandins. maintained on MgSO4 throughout her labor.

Regimens of Magnesium Sulfate in eclampsia Loading dosage: -4-6 g i.v. over 20-30 min (6 g of 50% solution diluted in 150 cc D5W) Maintenance dosage: Additional 2 g over 5-10 min (1-2 times) can be given with persistent convulsions If convulsions persist (2% of cases), give 250 mg sodium amobarbital i.v. over 5 min In status eclampticus: intubation and muscular paralysis Intramuscular dosage: 10 g i.m. (20 mL of 50% MgSO4, one half of the dose in each buttock

Clinical Finding Serum Level Loss of patellar reflex 10meq/l Feeling of warmth, flushing Double vision Somnolence Slurred speech Muscular paralysis Respiratory difficulty >10meq/l Cardiac arrest

Management of Magnesium Toxicity Discontinue MgSO4 infusion Begin supplemental oxygen administration Obtain serum magnesium level Administer 1 g calcium gluconate (10 cc 10% calcium gluconate) by slow intravenous push Repeat calcium gluconate administration, if necessary If respiratory arrest occurs, begin cardiopulmonary resuscitation.

chronic hypertension The management differs for the low-risk group versus the high-risk group. low-risk group have, by definition, mild hypertension without evidence of organ damage. The high-risk group has either severe hypertension (SBP 160 /110 mm Hg) or mild hypertension with evidence of organ involvement.

chronic hypertension Low risk: Weekly nonstress tests should begin at 34 weeks. increased to twice weekly with evidence of growth restriction or oligohydramnios. low-risk group may continue their pregnancies up to 41 weeks,

chronic hypertension high-risk : use of antihypertensive pharmacotherapy. first-trimester 24-hour urine collection for total protein level. visits in the first and second trimesters should be every 2 to 3 weeks then weekly in the third trimester if clinically indicated. ultrasonography for estimated fetal weight and amniotic fluid volume every 4 weeks starting at 26 weeks. Weekly nonstress testing or biophysical profile assessments should begin at 28 weeks.

chronic hypertension low-risk chronic hypertension who do not develop superimposed preeclampsia have pregnancy outcomes similar to those of the general population. Antihypertensive not affect perinatal outcome and is not necessary, if the SBP reaches 160 /105 mm Hg, or target organ damage develops. 24-hour urine for protein determination in the first trimester at least monthly visits in the first and second trimester .Visits should be every 1 to 2 weeks after 32 weeks, looking carefully for the development of superimposed preeclampsia. ultrasonography for fetal growth and amniotic fluid assessment every 4 weeks beginning at 32 weeks,

chronic hypertension visits and fetal testing may need to be increased dependent on (increasing HTN, superimposed preeclampsia, decreased AF volume, or IUGR. superimposed preeclampsia is suspected or uncontrolled hypertension develops, the patient should be hospitalized, preferably at a tertiary care center. timing of delivery is dependent on complications and gestational age. In general, pregnancies in patients with high-risk chronic hypertension should not be continued past 40 weeks.