Pregnancy

Question 1

Blood pressure in normal pregnancy

Answer 1

DBP ↓ by 7 to 10 mm Hg in early pregnancy, by as much as 20 mm Hg in midpregnancy. DBP returns to baseline by third trimester. Nondippers may indicate risk for preeclampsia.

Question 2

Blood pressure in normal pregnancy

Answer 2

SBP only ↓ slightly due to concurrent increase in cardiac output (↑30% to 40%) and ↓ in peripheral vascular resistance.

Question 3

HTN in pregnancy

Answer 3

BP > 140/90 mm Hg

NOTE: Per the US National High BP Education Program, patients with BP ≤ 140/90 mm Hg, but with increased SBP of >30 mm Hg or DBP > 15 mm Hg compared with prepregnancy BP, should be managed as high-risk patients.

Question 4

HTN in pregnancy

Answer 4

Chronic HTN:

Occurs before 20 weeks of gestation

May be primary or secondary HTN

Question 5

HTN in pregnancy

Answer 5

Gestational HTN:

Occurs de novo after 20 weeks and normalizes within 3 months postpartum

Gestational HTN may or may not present as preeclampsia/eclampsia.

Question 6

HTN in pregnancy

Answer 6

Preeclampsia is a severe form of gestational HTN with end organ dysfunction.

Question 7

The diagnosis of preeclampsia may be made if patient has one or more of the following

Answer 7

Urine protein to creatinine ratio > 0.3 g/g Cr.

SCr > 1.1 mg/dL.

Aspartate aminotransferase > 50 IU/L ± severe epigastric/right upper quadrant pain.

Question 8

The diagnosis of preeclampsia may be made if patient has one or more of the following

Answer 8

Neurologic symptoms

Thrombocytopenia and hemolysis

Fetal growth restriction

Question 9

Preeclampsia

Answer 9

NOTE: A fall in uric acid clearance is a key feature of preeclampsia. Serum uric acid levels > 5.5 mg/dL is a strong indicator of preeclampsia, and levels > 7.8 mg/dL is associated with increased maternal morbidity

Question 10

Preeclampsia

Answer 10

What happens in normal pregnancy:

Vascular endothelial growth factor (VEGF) and the transforming growth factor β-1 (TGFβ1) are required to maintain endothelial health in the kidney and placenta. VEGF and TGFβ1 exert their angiogenic and endothelial health-maintaining effects via binding to their respective receptors, VEGF receptor-1 and TGFβ1 receptor.

Vascular homeostasis is maintained by physiologic levels of VEGF and TGFβ1.

Question 11

Preeclampsia

Answer 11

What happens in preeclampsia/eclampsia:

There is excessive placental secretion of sFLt1 (soluble fms-like tyrosine kinase 1 which also binds to VEGF) and sEng (soluble endoglin, a truncated form of endoglin that is a cell surface receptor for TGFβ1). sFlt1 and sEng compete with endothelial receptors for VEGF and TGFβ1 for circulating VEGF and TGFβ1 respectively and deplete VEGF and TGFβ1 for endothelial cell surface binding and signaling to maintain healthy vasculature.

Question 12

Preeclampsia

Answer 12

Cont’d:
This results in endothelial cell dysfunction, decreased prostacyclin and NO production, and release of procoagulant protein.

Additionally, other proangiogenic factors such as placental growth factor (PlGF) and adiponectin are decreased.

Other antiangiogenic factors (e.g., endostatin) are increased.

Question 13

Preeclampsia

Answer 13

Use of logarithmic transformed sFLT-1/PlGF ratios is being evaluated to predict preeclampsia. Higher ratio → higher risk.

Histopathology: Glomerular tufts are described as “bloodless”; capillary lumina are narrowed due to endothelial cell swelling, referred to as “endotheliosis.” In contrast, capillary loops are wide open in normal glomeruli. Foam cells with lipid vacuoles may also be seen in this condition.

Question 14

Preeclampsia

Answer 14

Preeclampsia and future risk of cardiovascular disease: Meta-analyses suggest an increased cardiac risk, albeit small absolute risk.

Association may be related to risk factors common to both preeclampsia and cardiovascular disease (e.g., obesity, glucose intolerance, high BP, kidney disease)

Diffuse endothelial injury occurring during preeclampsia leads to increased risk.

Question 15

Eclampsia

Answer 15

Same pathogenesis as preeclampsia

Thought to be a form of posterior reversible encephalopathy syndrome (PRES)

Question 16

Hemolytic anemia, elevated liver tests low platelet (HELLP syndrome of pregnancy)

Answer 16

Clinical manifestations:

May occur in third trimester to post-partum, associated with gestational or preeclampsia/eclampsia

Symptoms: Midepigastric to right upper quadrant pain, malaise, nausea, vomiting

Maternal mortality: 1%

Question 17

Hemolytic anemia, elevated liver tests low platelet (HELLP syndrome of pregnancy)

Answer 17

Pathophysiology: Unknown; Long chain 3-hydroxyacyl-CoA-dehydrogenase deficiency of the child has been reported to be associated with both maternal HELLP and acute fatty liver of pregnancy.

Question 18

Hemolytic anemia, elevated liver tests low platelet (HELLP syndrome of pregnancy)

Answer 18

Diagnosis: hemolysis, serum lactate dehydrogenase > 600 IU/L; serum aspartate aminotransferase > 70 IU/L; and thrombocytopenia with platelet count < 100,000-150,000/μL. Twenty percent of patients may also have disseminated intravascular coagulation.

Question 19

Hemolytic anemia, elevated liver tests low platelet (HELLP syndrome of pregnancy)

Answer 19

Treatment: antihypertensive therapy similar to preeclampsia, magnesium sulfate, blood transfusion and fresh frozen plasma as needed, embolization for hepatic hemorrhage, intravenous fluid support.

Question 20

Treatment of HTN in Pregnancy

Answer 20

For chronic hypertensive patients:

Continue pre-pregnancy antihypertensive medications except ACEI/ARB/aldosterone antagonist to maintain SBP between 120 to 160 mm Hg and DBP between 80 to 105 mm Hg. For patients with chronic HTN and end organ damage, maintain BP < 140/90 mm Hg.

Question 21

Treatment of HTN in Pregnancy

Answer 21

For new-onset HTN:

Treat when SBP > 160 mm Hg or,

DBP > 110 mm Hg.

Question 22

Treatment of HTN in Pregnancy

Answer 22

Common agents to treat nonsevere HTN in pregnancy:

Methyldopa: 250 to 500 mg b.i.d. to q.i.d., maximum 2 g/d

Labetalol: 100 to 400 mg orally b.i.d. to t.i.d. (maximum 1,200 mg/d)

Nifedipine, extended release: 30 to 60 mg orally daily to b.i.d.

Question 23

Treatment of HTN in Pregnancy

Answer 23

Common agents used to treat severe HTN, that is BP > 160/110 mm Hg:

Labetalol (intravenous then switch or oral): avoid in asthma or heart failure. Inform neonatologist regarding possible neonatal bradycardia.

Nifedipine (oral): associated with reflex tachycardia

Hydralazine (intravenous or intramuscular): may increase risk of maternal hypotension

Question 24

Treatment of HTN in Pregnancy

Answer 24

Other treatment options for severe HTN:

Nitroglycerin

Diazoxide (1.5 mg IV) may be comparable to hydralazine (5 mg IV)

Question 25

Treatment of HTN in Pregnancy

Answer 25

For preeclampsia:

Control BP with agents suggested for HTN in pregnancy above.

NOTE: Diuretics should not be used in preeclampsia/eclampsia. Similarly, salt restriction is not recommended in preeclampsia/eclampsia.

Magnesium sulfate:

May lead to a transient decrease in BP at 30 minutes following 2 to 5 g IV dose

NOTE: Magnesium has a synergistic hypotensive effect with CCB (e.g., nifedipine): this effect may be reversed with intravenous calcium (i.e. 10-20 mL of 10% calcium chloride over 10 minutes, repeat up to 4 times q 20 minutes as needed).

Question 26

Treatment of HTN in Pregnancy

Answer 26

For eclampsia:

Magnesium sulfate as suggested for preeclampsia

Treat HTN with agents that do not cause cerebral vasodilation. Labetalol is acceptable. Nicardipine has favorable cerebral hemodynamic effects. Both hydralazine and nifedipine vasodilate cerebral vasculature. However, this should not be the sole criteria for antihypertensive medication selection.

Captopril may be used for severe postpartum HTN if no breast-feeding.

For preeclampsia without severe features, observation and delivery at 37 weeks is suggested.

Question 27

Definitions

Answer 27

Preeclampsia is a condition of pregnancy characterized by high blood pressure (hypertension) and protein in the urine (proteinuria). … Eclampsia is the development of seizures in a woman with severe preeclampsia. It has a 2% mortality (death) rate. There is no cure for preeclampsia except for delivery of the baby.

Question 28

Pre/eclampsia

Answer 28

Onset: After 20 weeks
Proteinuria: Yes after 20 weeks
Other Abnormalities: increased LFTs and LDH, decreased albumin, hemolysis, and thrombocytopenia.

Question 29

Chronic HTN

Answer 29

Onset: Prior to 20 weeks
Proteinuria: Yes prior to 20 weeks
Other Abnormalities: EKG or ECHO evidence of LVH