Hypertension In Pregnancy

Etiology

Conditions that reduce uteroplacental blood flow and vascular insufficiency, including pre-existing hypertension, renal disease, diabetes mellitus,  OSA, thrombophilia, and autoimmune disease, have demonstrated an increased risk for hypertensive disease in pregnancy. Additionally, women with a previous history of preeclampsia, previous history of HELLP syndrome, twin or other multiple pregnancies, BMI >30, autoimmune disease, are women who are more than 35 years of age, are first-time mothers, or have a mother or sister who has had gestational hypertension be at higher risk for developing gestational hypertension and are at an elevated risk of progressing to pre-eclampsia.[4][5][6]

Epidemiology

Hypertensive disorders complicate between 5% and 10% of all pregnancies. Pre-eclampsia complicates 2-8% of all pregnancies worldwide. In the US, the rate of pre-eclampsia increased by 25% between 1987 and 2004. The incidence of hypertension is increasing due to changes in maternal demographics (eg, advancing maternal age, increased pre-pregnancy weight). Eclampsia, however, has declined due to improved prenatal care and the increased use of antenatal therapies (eg, blood pressure control, magnesium seizure prophylaxis) as well as timely delivery by induction of labor or cesarean section, which serves as a cure for pre-eclampsia/eclampsia.[7][8]

Pathophysiology

The pathophysiology of hypertension in pregnancy is not completely understood. Current research demonstrates that improper trophoblast differentiation during endothelial invasion due to abnormal regulation and/or production of cytokines, adhesion molecules, major histocompatibility complex molecules, and metalloproteinases plays a key role in developing a gestational hypertensive disease. Abnormal regulation and/or production of these molecules leads to abnormal development and remodeling of spiral arteries in the deep myometrial tissues. This leads to placental hypoperfusion and ischemia. More recent research shows the role of antiangiogenic factors that are released by placental tissue to cause systemic endothelial dysfunction, which can result in systemic hypertension. Organ hypoperfusion from endothelial dysfunction is most commonly seen in the eyes, lungs, liver, kidneys, and peripheral vasculature. Overall, most experts agree that the underlying reason is multifactorial.[9]

History and Physical

Physical exam findings commonly noted with both chronic and gestational hypertension are limited to systolic blood pressure above 140 mmHg and/or diastolic blood pressure above 90 mmHg. Severe range blood pressures are above 160 mmHg systolic and/or 110 mmHg diastolic. An increase in edema is frequently noted in women with pre-eclampsia. Those demonstrating severe features may demonstrate cerebral symptoms (unremitting/severe headache, altered mental status), visual symptoms (scotomata, photophobia, blurred vision, or temporary blindness/visual field defect), pulmonary edema (dyspnea or rales on examination), renal impairment (water retention causing peripheral edema)or hepatic impairment (right upper quadrant pain). In HELLP syndrome, malaise and right upper quadrant pain occur in up to 90% of cases. Vomiting is also common.[10]

Evaluation

Chronic hypertension is diagnosed per ACC/AHA and ACOG guidelines as an in-office measurement with systolic blood pressure greater than 140mmHg or diastolic blood pressure greater than 90mmHg confirmed with either ambulatory blood pressure monitoring, home blood pressure monitoring, or blood pressure evaluation with serial office visits, with elevated pressures at least 4 hours apart before 20 weeks gestation.[11][12][13][14]

Gestational hypertension is defined per ACOG guidelines as blood pressure greater than or equal to 140mmHg systolic or 90mmHg diastolic on 2 separate occasions at least 4 hours apart after 20 weeks of pregnancy when previous blood pressure was normal. Alternatively, a patient with systolic blood pressure greater than 160mmHg or diastolic blood pressure greater than 110mmHg can be confirmed to have gestational hypertension if they have a similar pressure after a short interval. This is to ensure timely antihypertensive treatment. As mentioned above, clinical symptoms are usually only noted when blood pressure exceeds 160/110 and may signify end-organ damage.

Per ACOG guidelines, pre-eclampsia is defined as meeting either above hypertension criteria with greater than or equal to 300mg urine protein excretion in a 24-hour period or a protein/creatinine ratio of greater than or equal to 0.3. If the other methods are not available, a urine dipstick can be used, and proteinuria is defined as a protein reading of at least 1+.

The criteria for pre-eclampsia can also be met in the absence of proteinuria if one has new-onset hypertension with thrombocytopenia(platelets less than 100,000 x10(9)/L, renal insufficiency(double of baseline serum creatine or serum creatine >1.1mg/dL), pulmonary edema, impaired liver function (AST/ALT greater than twice upper limit of normal), or new-onset headache unresponsive to medications with no alternative cause.Pre-eclampsia can be superimposed with chronic hypertension or as advancement along the spectrum of gestational hypertensive disease. Per ACOG guidelines, systolic blood pressure of greater than 160mmHg or diastolic blood pressure greater than 110mmHg on 2 separate readings 4 hours apart or any severe range pressure that requires antihypertensive medication which by treatment guidelines is severe pressures separated by minutes(10-30 minutes).[15]

Eclampsia refers to the pre-eclamptic patient who progresses to have generalized tonic-clonic seizures (typically intrapartum through up to 72 hours postpartum) secondary to her untreated/undertreated pre-eclampsia. Eclampsia occurs in approximately 2-3% of women with severe features who are not receiving anti-seizure prophylaxis. Up to 0.6% of women with preeclampsia without severe features develop eclampsia. Maternal complications occur in up to 70% of women experiencing eclamptic seizures, with maternal morbidity as high as 14%.HELLP syndrome is a severe form of pre-eclampsia, with the definition also being its namesake: hemolysis, elevated liver enzymes, and low platelet count. ACOG uses the following criteria: hemolysis as evident by LDH >600IU/L, liver injury from AST and/or AST >2 times the upper limit of normal, and thrombocytopenia of less than 100,000 x 10(9)/L.

Treatment / Management

Prophylaxis with 81mg aspirin is indicated for prevention initiated between 12-28 weeks and continued until delivery when 1 high-risk factor or 2 or more moderate risk factors. High-risk factors include a history of pre-eclampsia, chronic hypertension, diabetes type 1 or 2, renal disease, an autoimmune disease, especially systemic lupus erythematosus or antiphospholipid syndrome, or multifetal gestation. Moderate risk factors include nulliparity, more than 10 years pregnancy interval, BMI >30, low socioeconomic status, African American Race, family history in 1st-degree relative of preeclampsia, advanced maternal age(35+ at time of delivery), IUGR, or previous adverse pregnancy outcome.[16](B3)

Treatment/management of gestational and chronic hypertension in pregnancy is always indicated when blood pressures are in the severe range (>160/110) and last at least 15 minutes apart. ACOG does not recommend treatment with antihypertensives for mild range pressures unless they were on the medication for pre-gestational hypertension (chronic hypertension) before pregnancy. The treatment indication for chronic hypertension is 140/90 per ACOG. First-line therapies include labetalol, hydralazine, or nifedipine. Nifedipine is preferred if oral medication for acute oral treatment, and Nifedipine or oral labetalol is preferred in the outpatient setting. Thiazide diuretics can be continued if used to treat chronic hypertension before pregnancy. Hydralazine and clonidine have been used in certain circumstances but are not commonly used in the longitudinal treatment of gestational or chronic hypertension. ACE inhibitors, angiotensin receptor blockers, mineralocorticoid receptor antagonists, and nitroprusside are teratogenic and thus contraindicated in pregnancy. Nitroprusside can be used as a last resort in treatment-resistant hypertension. The treatment goal is 140-150/90-100mm Hg.[2][17][18]

If a patient is experiencing pre-eclampsia with severe features, magnesium seizure prophylaxis is indicated until after delivery, and the appropriate diuretic response is seen. If the EGA is between 24 0/7 weeks and 33 6/7 weeks and delivery is imminent due to pre-eclampsia, eclampsia, or other concerns, antenatal steroid therapy is indicated to promote fetal lung maturity. (note - some providers administer steroids in pregnancies up to 35 6/7 weeks EGA).[18]

When patients are diagnosed with chronic hypertension, gestational hypertension, or pre-eclampsia, increased monitoring is recommended as concern for intrauterine growth retardation, placental abruption, and poor placental/umbilical blood flow are concerns. Up to twice weekly BP monitoring may be indicated, frequently combined with the fetal non-stress test, amniotic fluid index evaluation, and laboratory evaluations. Abnormal findings on these evaluations may indicate the need for early delivery.[18]

Definitive treatment of gestational hypertension, pre-eclampsia, and eclampsia is delivery. Maternal sequelae of gestational hypertension, pre-eclampsia, and eclampsia resolve rapidly after delivery. Fetal development/maturity must be weighed against potential hypertensive/pre-eclamptic risks when determining that preterm delivery is indicated. ACOG guidelines recommend that scheduled delivery timing vary depending on the diagnosis. Delivery is indicated as early as at diagnosis after 34+0/7 weeks estimated gestational age (WEGA) in patients with pre-eclampsia with severe features or immediately if unstable maternal or fetal condition. Patients with gestational hypertension or pre-eclampsia without severe features might safely delay delivery until 37+0/7 WEGA or the time of diagnosis if after 37+0/7 WEGA with reassuring antepartum testing. Induction for chronic hypertension is recommended from 38 0/7 to 39 6/7 weeks gestation.[18]

Differential Diagnosis

The differential diagnoses for hypertension in pregnancy include the following:

• Antiphospholipid syndrome
• Aortic coarctation 
• Cushing syndrome
• Eclampsia
• Glomerulonephritis
• Hydatiform mole
• Conn syndrome
• Hyperthyroidism
• Malignant hypertension 

Complications

The complications that can manifest with hypertension in pregnancy are as follows:

• Eclamptic seizures 
• Intracranial hemorrhage
• Pulmonary edema
• Renal failure
• Coagulopathy
• Hemolysis
• Liver injury
• Thrombocytopenia
• Intra-uterine growth restriction
• Oligohydramnios
• Placental abruption
• Nonreassuring fetal status [18]