Pregnancy leads to physiologic changes in renal and systemic hemodynamics that cause important alterations in acid-base, electrolyte, and kidney function.[1, 2] Understanding these changes is essential when evaluating pregnant women with kidney disease.
Disorders that cause acute kidney injury in early or late pregnancy generally fall into very different categories. It must also be remembered that pregnancies in women with underlying chronic kidney disease who require dialysis during pregnancy or who have previously undergone kidney transplantation pose unique sets of issues.[3]
Ideally, women with kidney disease or systemic diseases that would put them at risk during pregnancy should receive preconception counseling from physicians knowledgeable about the current literature related to pregnancy. The team of physicians who care for these patients is often led by an experienced specialist in high-risk, maternal-fetal obstetrics working with a nephrologist and/or others. Successful maternal and fetal outcomes for women with preexisting kidney disease, and those with onset of kidney disease during pregnancy, require a close working relationship among all physicians involved in the care of these patients.[4]
Go to Hypertension and Pregnancy, Preeclampsia, Hypertension, and Chronic Kidney Disease for more information on these topics.
The urinary system undergoes significant yet predictable physiologic and anatomic changes during normal pregnancy. It is essential to understand these changes to appropriately interpret common laboratory and diagnostic studies when evaluating kidney disease in women during pregnancy.
Kidney size increases by about 1-1.5 cm, primarily in the collecting system. Dilatation of the ureters and pelvis occurs and is presumed to be secondary to the smooth muscle–relaxing effect of progesterone. These changes may persist for up to 12 weeks postpartum and should not be misinterpreted as hydronephrosis if ultrasound of the kidneys is performed.
The glomerular filtration rate (GFR) increases immediately after conception to about 50% above baseline in the second trimester and then falls about 20% in the last trimester, resulting in significant hyperfiltration. Renal plasma flow also increases significantly in early pregnancy, causing the filtration fraction to fall in mid-pregnancy. As a result the normal serum creatinine level falls, so any value greater than 0.87 mg/dL should be considered abnormal.[5]
Similarly the value for blood urea nitrogen (BUN) falls. Renal plasma flow increases up to 85% in the second trimester due to an increase in cardiac output and increased renal vasodilation of the afferent and arteriole arterioles. These changes are particularly important, as a normal serum creatinine or BUN level in a pregnant woman may represent kidney disease.
Blood pressure falls shortly after conception due to peripheral vasodilation, mediated by nitric oxide synthesis and relaxin, and a resistance to the action of angiotensin II specific to normal pregnancy. There is a compensatory increase in heart rate and activation of the renin-angiotensin-aldosterone axis. Blood volume increases by 20%, and sodium retention of up to 900 mEq occurs. Although edema may therefore be benign in pregnancy, blood pressure greater than 120/80 mm Hg is not normal.
The osmotic threshold for arginine vasopressin resets downward, leading to lower serum sodium values. The higher GFR increases urate clearance, lowering serum uric acid values, and the filter load of glucose increases, which may result in renal glycosuria. Increased ventilation in pregnancy also causes a chronic respiratory alkalosis and an appropriate fall in the serum HCO3 value.
Although up to 300 mg per day of proteinuria can be normal in pregnancy, values above that may be an indication of worsening preexisting disease, de novo kidney disease, or the development of preeclampsia, particularly after 20 weeks' gestation.[4] In general, abnormal levels of proteinuria occurring before 20 weeks gestation signify underlying intrinsic kidney disease, rather than kidney disease specific to pregnancy. In non-gravid women, urinary protein excretion can be assessed using the urinary protein:creatinine ratio, but this may not be accurate in pregnancy and 24-hour urine protein measurement is necessary.
Bacteriuria is more likely to occur during pregnancy because of the dilated collecting system and delayed emptying, urinary stasis, and vesicoureteral reflux. Pregnant women with asymptomatic bacteriuria have always been considered at risk for the development of urinary tract infections (UTI), which could evolve into pyelonephritis in about one third of cases, so therapy has traditionally been recommended for asymptomatic bacteriuria in pregnancy. However, a more recent review of asymptomatic bacteriuria by the US Preventive Services Task Force concluded that screening and treatment of asymptomatic bacteriuria has only moderate net benefit in reducing perinatal complications, because the incidence of pyelonephritis in patients with untreated asymptomatic bacteriuria has been low in recent decades.[6]
If asymptomatic bacteriuria is treated, one can use a 3-day course of amoxicillin, a cephalosporin, or nitrofurantoin. Trimethoprim-sulfamethoxazole, tetracyclines, and fluoroquinolones should not be used.
Acute kidney injury (AKI) is not common in pregnancy, and kidney injury requiring dialysis is very rare in pregnancy. Data from Canada reported an incidence of pregnancy-related AKI of 2.68 per 10,000 deliveries. AKI requiring dialysis in pregnancy or postpartum occur in 1 per 10,000 pregnant women, but it is associated with increased mortality.[7] It is therefore important that clinicians who are asked to care for patients with this unusual complication be aware that while an acute reduction in GFR may result from any of the causes seen in the non-gravid state, a number of disorders are specific to pregnancy.
Pregnancy-specific kidney disorders generally can be organized into those occurring in early pregnancy and those occurring in late pregnancy.[8] Disorders arising in early pregnancy include the following:
Disorders arising in late pregnancy, almost all of which are usually specific to pregnancy, include the following:
The following conditions should also be considered in evaluating acute kidney injury in pregnancy:
Obstructive uropathy should be considered in the setting of moderate or severe dilatation of the collecting system in women with oliguria or anuria. The most likely causes are the gravid uterus, polyhydramnios, kidney stones, and enlarged uterine fibroids. Obstructive uropathy usually resolves with delivery, although ureteral stenting may be required preterm.
In pregnancy, 1,25 di-hydroxycholecaliferol (vitamin D) levels are elevated due to increased production by the kidneys and placenta, resulting in hypercalciuria. This results in an increased risk of nephrolithiasis along with an increased risk of urinary tract infection. Ultrasonography is the primary diagnostic imaging modality used, and ureteral stenting may be necessary if the stones cannot be passed.
Women with anticardiolipin antibodies and the lupus anticoagulant are at risk of fetal loss and worsening renal function. All pregnant women with lupus should be screened for antiphospholipid antibodies and anti-Ro/SSA and anti-La/SSB antibodies. Treatment with low-dose aspirin or heparin should be considered but depends on the antibody levels, the risk of pre-eclampsia,and any previous obstetric history of early fetal loss and/or thrombosis.
While prerenal azotemia can be caused by any cause of volume depletion during pregnancy, one of the more important causes is hyperemesis gravidarum. Hyperemesis gravidarum can be diagnosed by the history of persistent vomiting and is typically associated with metabolic alkalosis. Treatment consists of antiemetic therapy and volume replacement with intravenous normal saline and often potassium. Less commonly, hemorrhage associated with spontaneous abortion can also result in prerenal azotemia.
Acute tubular necrosis (ATN) in the first trimester is most likely to be caused by hemorrhage from spontaneous abortion or shock secondary to septic abortion. Septic abortion is most commonly due to gram-negative sepsis, primarily Escherichia coli, although in some cases, Clostridium perfringens is responsible, which can cause myonecrosis of the uterus and myoglobinuria. ATN due to these conditions is often more severe and more likely to require temporary dialysis until renal function recovers. ATN can also be caused by other causes seen in the non-gravid state, or by severe volume depletion from hyperemesis gravidarum.
The diagnosis of ATN should be suspected in the setting of septic abortion, and the diagnosis can be confirmed by urinalysis showing granular casts and urinary indices with an elevated fractional excretion of sodium. Treatment includes fluid resuscitation and pressors for hypotension; antibiotics; and, if necessary, dialysis.
Renal cortical necrosis (RCN) is a rare cause of severe AKI. RCN is more likely to be a cause of AKI in developing countries but even there, the incidence is falling.[9] Post-abortal sepsis is a common cause of RCN in developing countries, while abruptio placentae is responsible for RCN in 50%-60% of cases in pregnancy in developed countries. Other obstetric causes of RCN include puerperal sepsis, eclampsia, obstetric hemorrhage, intrauterine death, and thrombotic microangiopathy of pregnancy. Primary disseminated intravascular coagulation in the setting of severe renal ischemia is the most likely initiating event.[10]
RCN presents as gross hematuria, flank pain, and severe oliguria/anuria requiring renal replacement therapy. The diagnosis can usually be confirmed by demonstrating a radiolucent rim in the cortex on computed tomography (CT) scans. Recovery from RCN typically requires months and renal functional recovery is usually incomplete.[10]
Unlike the non-gravid condition, acute pyelonephritis in pregnancy may result in a reduced GFR that can be reversed with treatment of the underlying infection. Acute pyelonephritis most commonly occurs during the second trimester, with the predominant pathogen being E coli. Treatment often requires hospitalization and the administration of intravenous antibiotics and intravenous fluid administration. Ceftriaxone is an appropriate choice for initial therapy.
Although thrombotic thrombocytopenic purpura (TTP) and hemolytic-uremic syndrome represent a spectrum of disease that includes microangiopathic hemolytic anemia, thrombocytopenia, and AKI, TTP is more likely to occur in the first trimester, when the anemia and thrombocytopenia are the predominant features and kidney injury may not be severe. Patients may have a severe deficiency of ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13). Plasma exchange or plasmapheresis is the primary treatment, along with the use of high-dose corticosteroids.[11]
Although the most important causes of kidney injury in late pregnancy are preeclampsia and the associated disorders eclampsia and HELLP (hemolysis, elevated liver enzyme levels, low platelet count) syndrome, they will be discussed with the hypertensive disorders of pregnancy.
Although, as previously discussed, ATN can occur in early pregnancy, it can arise in late pregnancy as well. In the latter instance, ATN most commonly results from preeclampsia, but it can also be caused by HELLP syndrome or by uterine hemorrhage with abruptio placentae. ATN should be suspected from the clinical situation and confirmed by urinalysis showing granular casts and an elevated fractional excretion of sodium.
Acute fatty liver of pregnancy is a rare disorder characterized by the onset of abdominal pain and jaundice, typically occurring after week 34 of gestation. The pathogenesis involves microvesicular fatty infiltration of hepatocytes, which may be related to defective mitochondrial beta-oxidation of fatty acid.
The diagnosis is established via the clinical presentation and laboratory studies. Hyperbilirubinemia is the predominant laboratory abnormality (see Bilirubin), with mild elevations of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels also occurring. Severe cases may result in hypoglycemia, coagulation abnormalities, and even fulminant hepatic failure. Most women with this disorder have AKI but only a small percentage require dialysis.
Ultrasound imaging may demonstrate homogeneous fatty infiltrate without focal infiltrates. CT may show a hypodense fatty liver compared with the spleen.
Treatment consists of immediate delivery and supportive care. While most patients recover completely, fulminant hepatic failure requires liver transplantation.[12, 13]
Both TTP and HUS are characterized by occlusion of arterioles and capillaries by fibrin, resulting in hemolysis and thrombocytopenia. TTP is usually associated with a deficiency of ADAMTS-13, may occur in both early and late pregancy, and is treated with plasma exchange and/or fresh frozen plasma infusions. Atypical HUS (aHUS) is caused by activation of the alternative complement pathway, most often due to genetic mutations of complement-regulating protein, and usually presents in late pregnancy associated with AKI. Eculizimab, which inhibits the membrane attack complex, is the definitive treatment for aHUS.[14]
Currently, most cases of AKI occur in the postpartum rather than the postabortal period, reflecting a decline in septic abortions and improvements in prenatal care.[7, 14] Postpartum AKI, TTP, and HUS represent overlapping syndromes that have in common severe hypertension, microangiopathic hemolytic anemia, thrombocytopenia, and AKI.[15]
Patients with postpartum AKI usually present days to weeks following a normal delivery, with severe hypertension, hemolytic anemia, thrombocytopenia, and kidney failure. This disorder may also be related to retained placental fragments. HUS may be difficult to differentiate from severe preeclampsia or HELLP syndrome and may require postpartum kidney biopsy for diagnosis.
Kidney biopsy in HUS demonstrates glomerular thrombi and fibrin deposition, and fibrinoid necrosis of arterioles. When HUS is suspected, treatment should be initiated with plasma exchange or plasmapheresis. The value of corticosteroid therapy for HUS remains unclear.
In general, patients with chronic kidney disease (CKD) have reduced fertility. Only about 1.5% of women on long-term dialysis become pregnant. However, fertility improves significantly following kidney transplantation.
Historically, pregnancy has been regarded as posing very high risk to women with underlying kidney disease. However, the risk depends on the degree of kidney disease, the underlying disorder, and associated complications such as hypertension and proteinuria. It can therefore be difficult to predict the outcome in an individual patient.[16, 17]
Nevertheless, sufficient data are available to provide appropriate guidelines for counseling and following these patients during pregnancy. Many women with kidney disease, such as those with only mild reductions in GFR or those with well-functioning kidney transplants, can safely deliver healthy children with limited maternal risk.
During pregnancy, most women with CKD who are not on dialysis experience hypertension (25%) and increased proteinuria (50%). They may also have a decrease in GFR during pregnancy, which is often but not always reversible.
Women with CKD are at increased risk for fetal loss, intrauterine growth retardation, and early labor compared with women with normal renal function, especially if they experience an acute onset of kidney disease, nephrotic syndrome, or hypertension. Additionally, high maternal BUN levels can act as an osmotic diuretic in the fetal kidney and can cause early labor and fetal loss.
Progression of the underlying maternal disease depends less on the specific disease than on its severity. While it has been reported that one third of women with moderate kidney disease (GFR < 70 mL/min or serum creatinine > 1.4 mg/dL) are at risk for more rapid declines of renal function than are patients with less severe CKD, a more recent review showed that a GFR less than 40 mL/min and proteinuria greater than 1 g/day before conception are more likely to be associated with poor maternal and fetal outcomes.[18]
Nephrotic syndrome and the acute onset of kidney disease may also be risk factors for a poor outcome. Dilated afferent arterioles associated with hypertension in pregnancy can further increase the already elevated intraglomerular pressures.
If kidney function deteriorates quickly in early pregnancy, especially with no apparent cause, kidney biopsy should be considered. This procedure can be performed safely during pregnancy.
Glomerular diseases such as membranoproliferative glomerulonephritis, focal glomerulosclerosis, and reflux nephropathy have been associated with poorer renal outcomes; however, there are many factors—including hypertension, glomerular filtration rate, proteinuria, and treatment—that may factor into individual cases. In addition, women with autosomal dominant polycystic kidney disease who are hypertensive have a high risk for fetal and maternal complications, whereas women who are normotensive with mild kidney disease usually have uncomplicated pregnancies.
Systemic lupus erythematosus
The best pregnancy outcomes in women with systemic lupus erythematosus (SLE) occur in those who have had stable, inactive lupus for 6 months or longer before conception.[19] Lupus nephritis in pregnancy usually presents as proteinuria, hypertension, and falling GFR, making the distinction from preeclampsia very difficult. However, low complement levels may be helpful in distinguishing between women with preeclampsia and patients with active lupus nephritis.
All pregnant patients with SLE should be screened for anti-SSA (Ro) antibodies, due to the risk of congenital heart block. Treatment is problematic, because cyclophosphamide and mycophenolate mofetil, agents used in lupus therapy, are potentially teratogenic in early pregnancy. Any pregnant lupus patients at risk for pre-eclampsia should be started on low-dose aspirin at 12 weeks.[20]
See Systemic Lupus Erythematosus and Pregnancy.
Diabetes mellitus
Women with subclinical or mild diabetic nephropathy with only microalbuminuria or minimal proteinuria, a well-preserved GFR, and normal or only minimally elevated blood pressure may have transient increases in proteinuria and blood pressure. These women do not have significant progression of their renal failure. In women with moderate diabetic nephropathy and lower creatinine clearances prior to conception, however, renal function may significantly worsen during and after pregnancy and may not recover completely.
See Diabetes Mellitus and Pregnancy.
Pregnant patients with kidney disease are often under the care of a maternal-fetal specialist who has advanced training in high-risk obstetrics. These patients receive frequent obstetric follow-up that includes careful blood pressure monitoring, renal function testing, and 24-hour urine protein collections. Consultation with a nephrologist often occurs, particularly for patients with more advanced disease and those with progressive renal failure.
Almost all patients with significant kidney disease and/or hypertension in late pregnancy, or when the likelihood of fetal viability is very high, are delivered and then can be managed as non-gravid patients. If progressive renal failure occurs either in early pregnancy or before fetal viability can be assured, however, dialysis may need to be considered.[21]
Significant changes in dialysis care are required when managing a pregnant woman on hemodialysis. Nephrological management involves the intensification of dialysis dose, management of electrolytes, volume status, anemia, and bone care. Obstetric care concentrated on optimization and surveillance of fetal well-being and growth.[22]
Dialysis should be initiated when the serum creatinine level is 3.5-5.0 mg/dL or the GFR is below 20 mL/min. Fetal outcome is improved with longer, more frequent hemodialysis sessions, which usually involves 20 hours of dialysis per week. Daily dialysis is more likely to prevent hypotension and significant metabolic shifts.
Dialysis should aim to keep BUN levels below 50 mg/dL, because controlling uremia may avoid polyhydramnios, control hypertension, and improve the mother's nutritional status. Peritoneal dialysis with smaller volumes and frequent exchanges can also be done to achieve these same goals.
Anemia should be treated with erythropoietin-stimulating agents and careful attention to iron therapy. Nutritional support that allows weight gains of 0.3 to 0.5 kg/wk should be maintained in the second and third trimesters.
Although fertility is significantly impaired in women with end-stage renal disease, pregnancy may still occur.[23] Most women on dialysis are anovulatory, with either irregular or no menses, which can result in significant delays in the diagnosis of pregnancy in those who do conceive. In addition, the spontaneous abortion rate for pregnant women who require dialysis is approximately 50%. For pregnancies that continue, however, the fetal survival rate is as high as 71%.
Pregnancy in women following kidney transplantation has become commonplace. Transplantation restores fertility, and although most women with kidney transplants can deliver successfully, there is a higher risk of miscarriage, therapeutic abortion, stillbirth, ectopic pregnancy, preterm birth, low birthweight babies, and neonatal death.
Recommendations regarding health status for pregnancy in kidney transplant recipients include the following[24] :
Recommended immunosuppression in kidney transplant recipients includes the following:
The following are complication risks in kidney transplant recipients:
Hypertension is the most common medical complication of pregnancy, occurring in up to 10% of pregnancies globally. Hypertension is more common in young primiparous women and older multiparous women. The presence of a hypertensive disorder of pregnancy is associated with significant maternal and/or fetal mortality and morbidity and is the leading cause of premature birth.
Hypertension in pregnancy is defined as a blood pressure of at least 140 mmHg (systolic) or 90 mmHg (diastolic) on at least two measurements, ideally separated by a period of rest. Severe hypertension is defined as a blood pressure of greater than 160–170/110 mmHg. Systolic hypertension of greater than 180 mmHg is a medical emergency.[25]
The National High Blood Pressure Education Program classifies hypertensive disorders of pregnancy as follows[3, 26] :
Although each condition increases the risk of maternal and neonatal morbidity, the greatest risks are associated with preeclampsia, either de novo or in the setting of chronic hypertension. The diagnostic criteria for these disorders vary somewhat among published international guidelines, particularly in the discrimination between preeclampsia and gestational hypertension, and in setting the definition of severe preeclampsia.[25]
Chronic hypertension is defined as a pre-pregnancy blood pressure of greater than 140/90 mm Hg or as hypertension occurring before 20 weeks’ gestation.[27] The definition may also include some hypertension with minimal proteinuria diagnosed during pregnancy that does not resolve with delivery. These women may be diagnosed with preeclampsia, but on kidney biopsy some of them, particularly those who are multiparous, have been shown to have nephrosclerosis rather than preeclampsia.[28]
Chronic hypertension increases the risk of preeclampsia, abruptio placentae, intrauterine growth retardation, and second-trimester fetal death. However, treating mild to moderately elevated blood pressure does not benefit the fetus or prevent preeclampsia. Overtreatment may cause adverse perinatal outcomes resulting from placental hypoperfusion, so medication is reserved for women with blood pressure persistently greater than 150/100 mm Hg.
Methyldopa, labetalol, and nifedipine are the most commonly used oral agents to treat severe chronic hypertension in pregnancy. Angiotensin II receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs) are contraindicated in pregnancy due to the risk of intrauterine growth restriction, neonatal renal failure, and oligohydramnios.[29]
Women with chronic hypertension should be monitored for intrauterine growth restriction with serial ultrasonography after fetal viability.
Preeclampsia is a multiorgan disease process characterized by hypertension and proteinuria or one of the following features, which are diagnostic when they develop in the setting of new-onset hypertension after 20 weeks' gestation: thrombocytopenia, renal insufficiency, impaired liver function, pulmonary edema, or cerebral or visual symptoms.[29]
Clinically, preeclampsia usually begins after 32 weeks of pregnancy, although it may occur earlier in women with preexisting renal disease of hypertension (see Pregnancy and Underlying Renal Disease). Other disorders should be considered when hypertension and proteinuria occur before 20 weeks. Eclampsia is defined as the occurrence of seizures in women with preeclampsia.
The major features of preeclampsia are uteroplacentalhypoperfusion and fetal ischemia due to inadequate embryonal trophoblast invasion of the uterine wall and of the spiral arteries into the placenta. This results in failure of cytotrophoblastic epithelial-to-endothelial transformation and a subsequent lack of adhesion molecules, integrins, and cadherins.
Treatment of mild preeclampsia includes bed rest and antihypertensive therapy, but more severe disease is treated with magnesium, to prevent seizures, and/or delivery.
Women who have preeclampsia with severe features require hospitalization for careful monitoring. Treatment goals are as follows[29] :
Preeclampsia typically resolves within 10 days postpartum.
Underlying essential hypertension, diabetes mellitus, kidney disease, twin pregnancies, antiphospholipid syndrome, fetal hydrops, insulin resistance, and factor V Leiden are all risk factors for the development of preeclampsia. A Cochrane review concluded that low-dose aspirin can reduce the risk preeclampsia and its complications, primarily in high-risk patients, though further studies are suggested as to which patients should be treated and what dose should be used.[30]
Increasing levels of soluble fms-like tyrosine kinase-1 (sFlt1), a circulating antiangiogenic factor, can antagonize the angiogenic and vasodilatory effects of vascular endothelial and placental growth factors.[31] This may impair placentation by preventing angiogenesis and may stimulate endothelial dysfunction, manifested as systemic vasoconstriction and coagulopathy. Rising levels of soluble endoglin and an increase in the ratio of sFlt1 to uterine placental growth factor have been reported as markers that may predict the development of preeclampsia and differentiate preeclampsia from other causes of hypertension and proteinuria.
In normal pregnancy, there is resistance to the action of angiotensin II, which is associated with a lower density of angiotensin II receptors. In preeclampsia, however, there is an increased sensitivity to the vasopressor effects of angiotensin II. In addition, it has been shown that an increased synthesis of endothelin and thromboxane occurs, predisposing the patient to platelet aggregation and intravascular clotting, and that the synthesis of prostacyclin and nitric acid decreases, all of which may contribute to the resulting uteroplacental insufficiency.
HELLP (Hemolysis, Elevated Liver enzyme levels, Low Platelet count) syndrome occurs in less than 1% of pregnancies but in 20% of pregnancies complicated by preeclampsia. HELLP syndrome may present at term (18%), preterm (53%, including 11% before 27 weeks' gestation), or postpartum (30%). HELLP syndrome should be considered in patients who do not have classic preeclampsia symptoms because 12% to 18% of women with the condition are normotensive and 13% do not have proteinuria. Although HELLP syndrome may be considered a subtype of preeclampsia, atypical HELLP syndrome can be diagnosed without meeting the blood pressure criteria for the diagnosis of preeclampsia.[29] .
Typically, renal blood flow and GFR fall with a decreased urate clearance and increased calcium reabsorption, leading to hyperuricemia and hypocalciuria. Hyperuricemia may correlate with the severity of preeclampsia. Histopathologically, there is swelling of the glomerular endothelial cells, referred to as glomeruloendotheliosis. These lesions can resolve as early as 4 weeks after delivery.
Initial therapy for mild preeclampsia (blood pressure < 140/90 mm Hg, proteinuria < 500 mg/24h with normal renal function, serum urate < 4.5 mg/dL) is bed rest until fetal size and maturation are adequate. Although the blood pressure level at which to treat hypertension is not defined, the first-line treatment agents are methyldopa and labetalol. Hydralazine can be used for more severe hypertension; diuretics should be avoided. Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) are contraindicated.
To prevent seizures, magnesium sulfate should be used.[29] After 32 weeks' gestation, delivery is the definitive treatment of preeclampsia when there is worsening disease, as evidenced by uncontrolled hypertension, headaches, or hyperreflexia. Eclampsia or HELLP syndrome is always an indication for delivery. For more information, see Preeclampsia.
Preeclampsia superimposed on chronic hypertension is more likely to occur in older women or those with underlying kidney disease. This condition is difficult to distinguish from worsening hypertension in pregnancy, but should be suspected if a woman who had hypertension before 20 weeks' gestation develops any of the following in the second half of pregnancy:
Other clues to the diagnosis are hyperuricemia and increased serum creatinine.
Gestational hypertension is defined as hypertension that appears after midterm, is not associated with proteinuria, and resolves after delivery. Risk factors for this condition are a family history of hypertension, obesity, and multiparity.
In approximately 25% of cases, gestational hypertension may progress to preeclampsia; consequently, these women require monitoring throughout pregnancy. Assessment for proteinuria, laboratory tests for organ dysfunction, and ultrasound to assess fetal growth is warranted for women presenting with asymptomatic new-onset hypertension after 20 weeks.[25]
Postpartum, women who have had gestational hypertension are at risk for developing chronic hypertension and future cardiovascular disease. In addition, children of these women may have higher blood pressures.
The goal of drug therapy is to reduce fetal morbidity and mortality by preventing severe hypertension and/or preeclampsia. For mild hypertension, the central alpha agonist methyldopa is the first-line therapy, based on a long record of effectiveness and safe fetal outcomes. Labetalol is an effective alternative.
Hydralazine can be used for more severe hypertension, commonly in combination with methyldopa or beta-blockers. Beta-blockers, particularly atenolol, may cause fetal bradycardia in the first trimester, but these agents can be used safely later in pregnancy.
A 2013 Cochrane review of drugs for treatment of very severe hypertension in pregnancy found that patients were less likely to have persistent hypertension when calcium channel blockers were used, as compared with hydralazine, though there were insufficient data for comparing the effectiveness of different agents.[32] These researchers concluded that the choice of agent should depend on the physician's experience, though they recommended against the use of nimodipine.
Diuretic agents are generally not recommended but can be continued if they are effectively controlling the patient’s chronic hypertension. These drugs should not be used in superimposed preeclampsia.
Most importantly, angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) are contraindicated in pregnancy, because they have been associated with increased fetal loss in animal studies; these agents have also been associated with fetal renal tubular dysplasia, oligohydramnios, perinatal acute renal failure, and other congenital anomalies.
First-trimester exposure to ACEIs has been associated with an increased risk of major congenital malformations. It is therefore important to provide appropriate counseling to women of childbearing age who may be using ACEIs or ARBs for the treatment of their hypertension.