**2.1.3.2 Pathophysiology**

Utero-placental ischemia: A combination of genetic and environmental factors results in inadequate invasion of uterine spiral arteries by placental trophoblasts resulting in inability of uterine vessels to transform from high resistance channels to a low resistance system. This results in utero-placental ischemia. In normal pregnancy Vascular endothelial growth factor (VEGF ) and Placental induced growth factor (PIGF) are made by placenta and circulate in high concentrations in the blood. VEGF is also synthesized by glomerular podocytes and vascular endothelial cells. VEGF and PIGF induce synthesis of nitric oxide and vasodilating prostacylin in endothelial cells decreasing vascular tone and blood pressure. In PIH the utero-placental ischemia results in oxidative stress and release of a soluble cytokine, the sFlt-1 (soluble fms-like tyrosine kinase-1). sFlt-1 is a potent antagonist of VEGF and PIGF. In PET concentrations of sFlt-1 rise in the 2nd trimester with a decrease in VEGF and PIGF. Overproduction of sFlt-1 explains increased susceptibility to PET in multiple gestation, hydantidiform mole, trisomy 13 and first pregnancy. In addition, increased concentration of circulating pre-ecclamptic factorsangiotensin 1 /Bradykinin B2 receptor heterodimers, agonistic antibodies to angiotensin I receptor(AT 1 receptor antibody) and soluble endoglin are seen in PET. (Maynard,S 2003; Venkatesha,S 2006; Zhou,C.C,2008; Levine, RJ 2006)

There is an imbalance of vasoconstrictors and vasodilator substances hence there is a state of generalized vasoconstriction in preeclampsia. The levels of prorenin, angiotensin, thromboxane and endothelin are high while the levels of vasodilator prostaglandin ie Prostacyclin, PGE2, nitric oxide and bradykinin are low. In normal pregnancy there is less sensitivity of vascular bed to the hypertensive effects of angiotensin but this is lost in preeclampsia.

A myriad of markers for generalized endothelial dysfunction are seen in preeclampsia which include von Willebrand factor, Platelet activating factor (PAF-1), Endothelin and cellular fibronectin.

The increase in blood volume, increased GFR and vasodilatation seen in normal pregnancy are lost in preeclampsia. Though the blood volume in preeclampsia is decreased there is an increase in effective circulating volume with suppressed renin and aldosterone with elevation of brain natriuretic peptide.

#### **2.1.3.3 Screening tests**

Laboratory evaluation helps to determine disease severity by characterizing the extent of end organ involvement.

Hematocrit — Hemoconcentration supports the diagnosis of preeclampsia but hemolysis, if present, can decrease the hematocrit.

Acute Kidney Injury in Pregnancy 157

preeclampsia has been exceeded. Serum creatinine alone can be used to monitor renal

**Treatment of hypertension** — Nonpharmacologic treatments include bed rest and alcohol avoidance. Weight loss and salt restriction are not recommended. ACE inhibitors are contraindicated. Diuretics in pregnancy lead to intravascular volume depletion, organ and placental hypoperfusion. They may be used with caution in presence of significant edema. If preeclampsia develops diuretics must be discontinued. Beta-blockers have no major contraindications, although neonatal bradycardia, hypoglycemia, and respiratory depression can occur. Labetalol is not associated with neonatal bradycardia and is used for hypertensive emergencies. Alpha-methyldopa is the drug of choice for hypertension. Clonidine is also used. Calcium channel blockers may cause tocolysis in 3rd trimester hence should be used only if hypertension is unresponsive to other medications. Hydralazine is a first-line agent for hypertensive emergencies. Experience with minoxidil and prazosin is limited. 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. Novel therapies are under investigation. L-arginine is the physiologic precursor for nitric oxide, which has been implicated in the pathogenesis of preeclampsia and is being tested. Another randomized trial showed that plasma volume

**Assessment of fetal well-being** — A minimum of daily fetal movement counts and twice weekly fetal non stress testing with assessment of amniotic fluid volume, or biophysical profile is recommended. Early fetal growth restriction may be the first manifestation of preeclampsia or a sign of severe preeclampsia. Sonographic estimation of fetal weight should be performed to look for growth restriction and oligohydramnios at the time of diagnosis of preeclampsia and then repeated serially. Doppler velocimetry is useful for

**Delivery-** The decision to deliver the fetus is based upon gestational age, maternal and fetal

Mild PIH- Patients at term (>37 weeks) are delivered. Most experts advise that delivery should not be postponed beyond 40 weeks of gestation in any preeclamptic woman. Vaginal delivery is preferred at term if there are no contraindications. Cervical ripening agents should be considered in women with unfavorable cervices. Women with mild PIH with period of gestation <37 weeks can be managed expectantly. However maternal end-organ dysfunction and non reassuring tests of fetal well-being may be indications for delivery at any gestational age. Outpatient care is a cost-effective option for some women with mild preeclampsia. However these patients should comply with frequent maternal and fetal evaluations (every one to three days) and have ready access to medical care. Restricted activity is recommended; however, complete bed rest is not required. Hospitalization is needed in the event of fulminant progression to eclampsia, hypertensive crisis, abruptio placentae, or HELLP syndrome. Patients should be hospitalized immediately if they develop severe or persistent headache, visual changes, right upper quadrant or epigastric pain, nausea or vomiting, shortness of breath, or decreased urine output (ACOG 2000). As with any pregnancy, decreased fetal movement, vaginal bleeding, abdominal pain, rupture of

**Severe preeclampsia** — Severe preeclampsia is generally regarded as an indication for delivery, regardless of gestational age, to minimize the risk of development of maternal and fetal complications. Prolonged antepartum management at a tertiary care setting or in

expansion did not improve maternal or fetal outcome.

assessing fetal status if fetal growth restriction is present.

membranes, or uterine contractions should be reported immediately.

condition, and the severity of preeclampsia.

function.

Platelet count — Preeclampsia accounts for 21% of cases of maternal thrombocytopenia. Thrombocytopenia is usually moderate and platelet count rarely decreases to < 20,000/μL. Thrombocytopenia in patients with preeclampsia always correlates with the severity of the disease. It is considered a sign of worsening disease and is an indication for delivery.

Quantification of protein excretion — Excretion of 300 mg or more in 24 hours is necessary for diagnosis. It is suggested by at least 1+ protein on dipstick of two urine specimens collected at least four hours apart. A dipstick of 3+ or greater or 5 g or more per day is a criterion of severe disease.

Serum creatinine concentration — An elevated or rising level suggests severe disease.

Serum alanine and aspartate aminotransferase concentrations (ALT and AST) — Elevated or rising levels suggest hepatic dysfunction indicative of severe disease.

Serum lactate dehydrogenase (LDH) concentration — Microangiopathic hemolysis is suggested by an elevated LDH level and red cell fragmentation (schistocytes or helmet cells) on peripheral blood smear. Elevation of total bilirubin may also suggest hemolysis. Microangiopathic hemolysis is present in severe disease or HELLP syndrome (Hemolysis, Elevated Liver function tests, Low Platelets).

Serum uric acid concentration — It is often elevated in preeclampsia, but not diagnostic. High uric acid levels may be due to hypoxia or due to reduced GFR.

Fetal well-being is evaluated by a nonstress test or biophysical profile. In addition, the fetus is examined by ultrasound to evaluate growth and amniotic fluid volume. Assessment of umbilical artery Doppler flow may also aid in evaluation of the fetal condition.

Coagulation function tests (eg, prothrombin time, activated partial thromboplastin time, fibrinogen concentration) are usually normal if there is no thrombocytopenia or liver dysfunction, and therefore do not need to be monitored routinely.

Recently, urinary PlGF values and sFlt-1 values have shown great promise as a means of identifying preclinical preeclampsia .

#### **2.1.3.4 Management**

The definitive treatment of preeclampsia is delivery to prevent development of maternal or fetal complications from disease progression. Several groups have formulated guidelines for diagnosis, evaluation, and management of hypertensive disorders of pregnancy (NHBPEP. Report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy (2000), ACOG 2002).

**Laboratory follow-up** — The minimum laboratory evaluation should include platelet count, serum creatinine, and serum AST. These tests should be repeated once or twice weekly in women with mild preeclampsia to assess for disease progression, and more often if clinical signs and symptoms suggest worsening disease(ACOG 2000).The value of other tests is less clearly defined. A rising hematocrit can be useful to look for hemoconcentration, which suggests contraction of intravascular volume and progression to more severe disease, while a falling hematocrit may be a sign of hemolysis. An elevated serum LDH concentration is also a sign of hemolysis, and a marker of severe disease or HELLP syndrome. Hemolysis can be confirmed by observation of schistocytes and helmet cells on a blood smear .Quantification of protein excretion can be performed to determine whether the threshold for severe preeclampsia (5 g/24 hours) has been reached. Since several clinical studies have shown that neither the rate of increase nor the amount of proteinuria affects maternal or perinatal outcome in the setting of preeclampsia, repeated 24-hour urinary protein estimations are not useful once the threshold of 300 mg/24 hours for the diagnosis of

Platelet count — Preeclampsia accounts for 21% of cases of maternal thrombocytopenia. Thrombocytopenia is usually moderate and platelet count rarely decreases to < 20,000/μL. Thrombocytopenia in patients with preeclampsia always correlates with the severity of the

Quantification of protein excretion — Excretion of 300 mg or more in 24 hours is necessary for diagnosis. It is suggested by at least 1+ protein on dipstick of two urine specimens collected at least four hours apart. A dipstick of 3+ or greater or 5 g or more per day is a

Serum lactate dehydrogenase (LDH) concentration — Microangiopathic hemolysis is suggested by an elevated LDH level and red cell fragmentation (schistocytes or helmet cells) on peripheral blood smear. Elevation of total bilirubin may also suggest hemolysis. Microangiopathic hemolysis is present in severe disease or HELLP syndrome (Hemolysis,

Serum uric acid concentration — It is often elevated in preeclampsia, but not diagnostic.

Fetal well-being is evaluated by a nonstress test or biophysical profile. In addition, the fetus is examined by ultrasound to evaluate growth and amniotic fluid volume. Assessment of

Coagulation function tests (eg, prothrombin time, activated partial thromboplastin time, fibrinogen concentration) are usually normal if there is no thrombocytopenia or liver

Recently, urinary PlGF values and sFlt-1 values have shown great promise as a means of

The definitive treatment of preeclampsia is delivery to prevent development of maternal or fetal complications from disease progression. Several groups have formulated guidelines for diagnosis, evaluation, and management of hypertensive disorders of pregnancy (NHBPEP. Report of the National High Blood Pressure Education Program Working Group

**Laboratory follow-up** — The minimum laboratory evaluation should include platelet count, serum creatinine, and serum AST. These tests should be repeated once or twice weekly in women with mild preeclampsia to assess for disease progression, and more often if clinical signs and symptoms suggest worsening disease(ACOG 2000).The value of other tests is less clearly defined. A rising hematocrit can be useful to look for hemoconcentration, which suggests contraction of intravascular volume and progression to more severe disease, while a falling hematocrit may be a sign of hemolysis. An elevated serum LDH concentration is also a sign of hemolysis, and a marker of severe disease or HELLP syndrome. Hemolysis can be confirmed by observation of schistocytes and helmet cells on a blood smear .Quantification of protein excretion can be performed to determine whether the threshold for severe preeclampsia (5 g/24 hours) has been reached. Since several clinical studies have shown that neither the rate of increase nor the amount of proteinuria affects maternal or perinatal outcome in the setting of preeclampsia, repeated 24-hour urinary protein estimations are not useful once the threshold of 300 mg/24 hours for the diagnosis of

disease. It is considered a sign of worsening disease and is an indication for delivery.

Serum creatinine concentration — An elevated or rising level suggests severe disease. Serum alanine and aspartate aminotransferase concentrations (ALT and AST) — Elevated or

rising levels suggest hepatic dysfunction indicative of severe disease.

High uric acid levels may be due to hypoxia or due to reduced GFR.

dysfunction, and therefore do not need to be monitored routinely.

on High Blood Pressure in Pregnancy (2000), ACOG 2002).

umbilical artery Doppler flow may also aid in evaluation of the fetal condition.

criterion of severe disease.

Elevated Liver function tests, Low Platelets).

identifying preclinical preeclampsia .

**2.1.3.4 Management** 

preeclampsia has been exceeded. Serum creatinine alone can be used to monitor renal function.

**Treatment of hypertension** — Nonpharmacologic treatments include bed rest and alcohol avoidance. Weight loss and salt restriction are not recommended. ACE inhibitors are contraindicated. Diuretics in pregnancy lead to intravascular volume depletion, organ and placental hypoperfusion. They may be used with caution in presence of significant edema. If preeclampsia develops diuretics must be discontinued. Beta-blockers have no major contraindications, although neonatal bradycardia, hypoglycemia, and respiratory depression can occur. Labetalol is not associated with neonatal bradycardia and is used for hypertensive emergencies. Alpha-methyldopa is the drug of choice for hypertension. Clonidine is also used. Calcium channel blockers may cause tocolysis in 3rd trimester hence should be used only if hypertension is unresponsive to other medications. Hydralazine is a first-line agent for hypertensive emergencies. Experience with minoxidil and prazosin is limited. 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. Novel therapies are under investigation. L-arginine is the physiologic precursor for nitric oxide, which has been implicated in the pathogenesis of preeclampsia and is being tested. Another randomized trial showed that plasma volume expansion did not improve maternal or fetal outcome.

**Assessment of fetal well-being** — A minimum of daily fetal movement counts and twice weekly fetal non stress testing with assessment of amniotic fluid volume, or biophysical profile is recommended. Early fetal growth restriction may be the first manifestation of preeclampsia or a sign of severe preeclampsia. Sonographic estimation of fetal weight should be performed to look for growth restriction and oligohydramnios at the time of diagnosis of preeclampsia and then repeated serially. Doppler velocimetry is useful for assessing fetal status if fetal growth restriction is present.

**Delivery-** The decision to deliver the fetus is based upon gestational age, maternal and fetal condition, and the severity of preeclampsia.

Mild PIH- Patients at term (>37 weeks) are delivered. Most experts advise that delivery should not be postponed beyond 40 weeks of gestation in any preeclamptic woman. Vaginal delivery is preferred at term if there are no contraindications. Cervical ripening agents should be considered in women with unfavorable cervices. Women with mild PIH with period of gestation <37 weeks can be managed expectantly. However maternal end-organ dysfunction and non reassuring tests of fetal well-being may be indications for delivery at any gestational age. Outpatient care is a cost-effective option for some women with mild preeclampsia. However these patients should comply with frequent maternal and fetal evaluations (every one to three days) and have ready access to medical care. Restricted activity is recommended; however, complete bed rest is not required. Hospitalization is needed in the event of fulminant progression to eclampsia, hypertensive crisis, abruptio placentae, or HELLP syndrome. Patients should be hospitalized immediately if they develop severe or persistent headache, visual changes, right upper quadrant or epigastric pain, nausea or vomiting, shortness of breath, or decreased urine output (ACOG 2000). As with any pregnancy, decreased fetal movement, vaginal bleeding, abdominal pain, rupture of membranes, or uterine contractions should be reported immediately.

**Severe preeclampsia** — Severe preeclampsia is generally regarded as an indication for delivery, regardless of gestational age, to minimize the risk of development of maternal and fetal complications. Prolonged antepartum management at a tertiary care setting or in

Acute Kidney Injury in Pregnancy 159

**Postpartum course** -Vital signs are monitored every two hours while the patient remains on magnesium sulphate and laboratory tests are repeated until two consecutive sets of data are normal. Hypertension and proteinuria due to preeclampsia resolve postpartum, often within a few days, but sometimes take few weeks or rarely a year or more. Antihypertensive medications can be discontinued when blood pressure returns to normal levels. Elevated blood pressures that remain 12 weeks postpartum are unlikely to be related to preeclampsia and may require long-term treatment. Vasoconstriction and endothelial dysfunction resolve

**Postpartum preeclampsia** Pre eclampsia /eclampsia occurring more than two days and less than six weeks after delivery. It is important to exclude other diagnoses, especially when symptoms suggest the possibility of central nervous system pathology. Late postpartum eclampsia is defined as eclamptic seizures developing greater than 48 hours, but less than four weeks postpartum). Controversial prevention strategies include calcium

HELLP syndrome is a variant of severe preeclampsia, first described by Dr. Louis Weinstein in 1982. About 15 to 20 percent of affected patients do not have antecedent hypertension or proteinuria, leading some experts to believe that HELLP is a separate disorder from preeclampsia [Sibai BM1986, Reubinoff BE, 1991]. Both severe preeclampsia and HELLP syndrome may be associated with other hepatic manifestations, including infarction, hemorrhage, and rupture. HELLP develops in approximately 1 to 2 per 1000 pregnancies overall and in 10 to 20 percent of women with severe preeclampsia/ eclampsia. The majority of cases are diagnosed between 28 and 36 weeks of gestation with 70 percent occurring prior to delivery [Sibai BM, Ramadan MK 1993]. Of these patients, approximately 80 percent are diagnosed prior to 37 weeks of gestation and fewer than 3 percent develop the disease between 17 and 20 weeks of gestation. The disease presents postpartum in 30 percent, usually within 48 hours of delivery, but occasionally as long as seven days after birth. Only 20 percent of postpartum patients with HELLP have evidence

There is no consensus regarding the degree of laboratory abnormality diagnostic of HELLP syndrome. Some studies use AST (and/or ALT) and LDH values above the upper limit of normal, while others require elevations of at least two standard deviations above the mean. Due to differences in assays used to measure these enzymes, an elevated value in one hospital may be near normal in another.HELLP syndrome and severe preeclampsia are probably part of a disease spectrum. A precise definition of HELLP is necessary for research purposes and for predicting maternal complications. We require the presence of all of the

Microangiopathic hemolytic anemia with characteristic schistocytes (also called helmet cells) on blood smear. Other signs suggestive of hemolysis include an elevated LDH or indirect

Platelet count ≤100,000 cells/microL .HELLP syndrome accounts for 21% of maternal

bilirubin and a low serum haptoglobin concentration (≤25 mg/dL).

Serum LDH ≥600 IU/L or total bilirubin ≥1.2 mg/dL

supplementation, fish oils, sodium restriction, low-dose aspirin and antioxidants.

**2.1.4 Hemolysis, elevated liver enzymes, low platelets –HELLP syndrome** 

over a few days.

of preeclampsia antepartum.

following criteria to diagnose HELLP.

thrombocytopenia in pregnancy.

**Diagnosis and classification of HELLP syndrome** 

consultation with a maternal-fetal medicine specialist may be considered in few women under 32 to 34 weeks of gestation. However, women who develop severe preeclampsia at or beyond 32 to 34 weeks of gestation should be delivered at an institution with appropriate facilities. Hyaline membrane disease is common in preterm infants of preeclamptic women. Therefore, antenatal corticosteroids (betamethasone) to promote fetal lung maturity should be administered to women less than 34 weeks of gestation since preterm delivery is common. Even in preterm delivery vaginal delivery may be attempted. Cervical ripening agents may be used prior to induction if the cervix is not favorable. However, a prolonged induction should be avoided. Some authors recommend cesarean delivery for women with severe preeclampsia who are under 30 weeks of gestation . Management of severe preeclampsia- or eclampsia-related pulmonary edema includes treatment of the severe preeclampsia or eclampsia, supplemental oxygen, and fluid restriction. Diuresis is indicated if there is fluid overload but care should be taken to avoid further intravascular volume depletion. Mechanical ventilation may be necessary. Close, continuous maternal-fetal monitoring is indicated intrapartum to identify worsening hypertension, deteriorating maternal hepatic, renal, cardiopulmonary, or hematologic function, and uteroplacental insufficiency or abruptio placentae (often manifested by fetal bradycardia/or vaginal bleeding). The vitals should be monitored every hour and preeclampsia laboratory tests should be repeated every six hours. Epidural anaesthesia should be avoided in presence of thrombocytopenia. Invasive hemodynamic monitoring can be useful in complicated patients. Anticonvulsant therapy is generally initiated during labor or while administering corticosteroids or prostaglandins prior to planned delivery. Therapy is continued for 24 hours postpartum (range 12 to 48 hours). Magnesium sulfate is the drug of choice for the prevention of eclampsia and prevention of recurrent eclamptic seizures. It is more effective than Phenytoin or Nimodipine or lytic cocktail ( mixture of chlorpromazine, promethazine and pethidine) . Magnesium causes vasodilatation of the cerebral vasculature, inhibition of platelet aggregation, protection of endothelial cells from damage by free radicals, prevention of calcium ion entry into ischemic cells, decreasing the release of acetylcholine at motor end plates within the neuromuscular junction, and as a competitive antagonist to the glutamate N-methyl-D-aspartate receptor (which is epileptogenic). Anticonvulsant therapy is also used for prevention of seizures in women with mild preeclampsia, but its role in this setting is controversial. The magnesium sulfate dose is 4 g intravenously as a loading dose then 1 g/h, or 5 g intramuscularly into each buttock followed by 5 g intramuscularly every four hours. Hypotension is the major concern from regional anesthesia since preeclamptic women have depleted intravascular volumes.

**Outcome** — The major adverse outcomes associated with preeclampsia are related to maternal central nervous system, hepatic, and renal dysfunction (eg, cerebral hemorrhage, hepatic rupture, renal failure), bleeding related to thrombocytopenia, preterm delivery, fetal growth restriction, abruptio placentae, and perinatal death. Factors that influence outcome include gestational age at onset and delivery, severity of disease, and whether there are coexisting conditions present, such as multiple gestation, diabetes mellitus, renal disease, thrombophilia, or preexisting hypertension. There is approximately one maternal death due to preeclampsia-eclampsia per 100,000 live births, with a case-fatality rate of 6.4 deaths per 10,000 cases in US. In mild preeclampsia neonatal outcomes are generally good and comparable to those of normotensive women. Risk of recurrence in subsequent pregnancy depends upon severity of disease, gestational age at onset and gestational age at delivery.

consultation with a maternal-fetal medicine specialist may be considered in few women under 32 to 34 weeks of gestation. However, women who develop severe preeclampsia at or beyond 32 to 34 weeks of gestation should be delivered at an institution with appropriate facilities. Hyaline membrane disease is common in preterm infants of preeclamptic women. Therefore, antenatal corticosteroids (betamethasone) to promote fetal lung maturity should be administered to women less than 34 weeks of gestation since preterm delivery is common. Even in preterm delivery vaginal delivery may be attempted. Cervical ripening agents may be used prior to induction if the cervix is not favorable. However, a prolonged induction should be avoided. Some authors recommend cesarean delivery for women with severe preeclampsia who are under 30 weeks of gestation . Management of severe preeclampsia- or eclampsia-related pulmonary edema includes treatment of the severe preeclampsia or eclampsia, supplemental oxygen, and fluid restriction. Diuresis is indicated if there is fluid overload but care should be taken to avoid further intravascular volume depletion. Mechanical ventilation may be necessary. Close, continuous maternal-fetal monitoring is indicated intrapartum to identify worsening hypertension, deteriorating maternal hepatic, renal, cardiopulmonary, or hematologic function, and uteroplacental insufficiency or abruptio placentae (often manifested by fetal bradycardia/or vaginal bleeding). The vitals should be monitored every hour and preeclampsia laboratory tests should be repeated every six hours. Epidural anaesthesia should be avoided in presence of thrombocytopenia. Invasive hemodynamic monitoring can be useful in complicated patients. Anticonvulsant therapy is generally initiated during labor or while administering corticosteroids or prostaglandins prior to planned delivery. Therapy is continued for 24 hours postpartum (range 12 to 48 hours). Magnesium sulfate is the drug of choice for the prevention of eclampsia and prevention of recurrent eclamptic seizures. It is more effective than Phenytoin or Nimodipine or lytic cocktail ( mixture of chlorpromazine, promethazine and pethidine) . Magnesium causes vasodilatation of the cerebral vasculature, inhibition of platelet aggregation, protection of endothelial cells from damage by free radicals, prevention of calcium ion entry into ischemic cells, decreasing the release of acetylcholine at motor end plates within the neuromuscular junction, and as a competitive antagonist to the glutamate N-methyl-D-aspartate receptor (which is epileptogenic). Anticonvulsant therapy is also used for prevention of seizures in women with mild preeclampsia, but its role in this setting is controversial. The magnesium sulfate dose is 4 g intravenously as a loading dose then 1 g/h, or 5 g intramuscularly into each buttock followed by 5 g intramuscularly every four hours. Hypotension is the major concern from regional anesthesia since preeclamptic women have

**Outcome** — The major adverse outcomes associated with preeclampsia are related to maternal central nervous system, hepatic, and renal dysfunction (eg, cerebral hemorrhage, hepatic rupture, renal failure), bleeding related to thrombocytopenia, preterm delivery, fetal growth restriction, abruptio placentae, and perinatal death. Factors that influence outcome include gestational age at onset and delivery, severity of disease, and whether there are coexisting conditions present, such as multiple gestation, diabetes mellitus, renal disease, thrombophilia, or preexisting hypertension. There is approximately one maternal death due to preeclampsia-eclampsia per 100,000 live births, with a case-fatality rate of 6.4 deaths per 10,000 cases in US. In mild preeclampsia neonatal outcomes are generally good and comparable to those of normotensive women. Risk of recurrence in subsequent pregnancy depends upon severity of disease, gestational age at onset and gestational age

depleted intravascular volumes.

at delivery.

**Postpartum course** -Vital signs are monitored every two hours while the patient remains on magnesium sulphate and laboratory tests are repeated until two consecutive sets of data are normal. Hypertension and proteinuria due to preeclampsia resolve postpartum, often within a few days, but sometimes take few weeks or rarely a year or more. Antihypertensive medications can be discontinued when blood pressure returns to normal levels. Elevated blood pressures that remain 12 weeks postpartum are unlikely to be related to preeclampsia and may require long-term treatment. Vasoconstriction and endothelial dysfunction resolve over a few days.

**Postpartum preeclampsia** Pre eclampsia /eclampsia occurring more than two days and less than six weeks after delivery. It is important to exclude other diagnoses, especially when symptoms suggest the possibility of central nervous system pathology. Late postpartum eclampsia is defined as eclamptic seizures developing greater than 48 hours, but less than four weeks postpartum). Controversial prevention strategies include calcium supplementation, fish oils, sodium restriction, low-dose aspirin and antioxidants.
