rocha hypertensive disease in pregnancy

Frederico Rocha MD MSAssociate ProfessorDivision of Maternal-Fetal MedicineUniversity of California, San Francisco

Hypertensive disease

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Disclosures

None

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Objectives

Describe classification of HTN in pregnancy

Describe management goals in pregnancy

Brief review on prevention

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Hypertensive disorders in pregnancy

•Preeclampsia

•Gestational HTN

•Chronic (preexisting) HTN

•Superimposed preeclampsia

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CDC5

CA-PAMR: Chance to Alter Outcome Grouped Cause of Death; 2002-2004 (N=145)

Grouped Cause of Death Chance to Alter Outcome

Strong /Good (%)

Some(%)

None(%)

Total N (%)

Obstetric hemorrhage 69 25 6 16 (11)

Deep vein thrombosis/pulmonary embolism

53 40 7 15 (10)

Sepsis/infection 50 40 10 10 (7)

Preeclampsia/eclampsia 50 50 0 25 (17)

Cardiomyopathy and other cardiovascular causes

25 61 14 28 (19)

Cerebral vascular accident 22 0 78 9 (6)

Amniotic fluid embolism 0 87 13 15 (10)

All other causes of death 46 46 8 26 (18)

Total (%) 40 48 12 145 7

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Gestational hypertension

Development of hypertension after 20 wks

Previously normotensive

SBP > 140 mmHg or (not and/or)

DBP > 90 mmHg

Persistent for 4 hrs

BP returns to normal by 6 wks postpartum

No proteinuria/ no other preeclampsia features

Gestational Hypertension

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Most common cause of hypertension during pregnancy‐ 6 to 17 percent of healthy pregnancies

10 to 50% develop preeclampsia in one to five weeks

Unclear if GHTN and preeclampsia are independent diseases with a similar phenotype (hypertension) or if gestational hypertension is an early mild stage of preeclampsia

Gestational Hypertension

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Preeclampsia

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Gestational Hypertension + any one of the following:

Proteinuria ‐ > 300 mg/day or Protein/Cr > 0.3 mg/mg ‐ Dipstick ≥ 2+

Thrombocytopenia (less than 100,000) Impaired liver function (twice normal) Renal insufficiency (> 1.1 mg/dL or a doubling in absence of other

renal disease) Pulmonary edema New-onset and persistent headache Visual symptoms

Preeclampsia

Gestational Hypertension + any one of the following:

Proteinuria ‐ > 300 mg/day or Protein/Cr > 0.3 mg/mg ‐ Dipstick ≥ 2+

Thrombocytopenia (less than 100,000) Impaired liver function (twice normal) Renal insufficiency (> 1.1 mg/dL or a doubling in absence of other

renal disease) Pulmonary edema New-onset and persistent headache Visual symptoms

Preeclampsia with Severe Features

SBP >160 or DBP>110on 2 occasions at least 4 hours apart while the patient is on bedrest (unless

hypertensive therapy is initiated before this time)

OR

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Incidence - ~5 percent (US)

90% >34 weeks and postpartum

10% <34 weeks

Preeclampsia

Pathophysiology

Placental implantation with abnormal trophoblastic invasion of uterine vessels.

Immunological maladaptive tolerance between maternal, paternal (placental), and the fetus.

Maternal maladaptation to CV or inflammatory changes of normal pregnancy.

Genetic factors including inherited predisposing genes as well as epigenetic influences.

Williams Obstetrics 23rd Edition

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Williams Obstetrics 23rd Edition

Pathogenesis of preeclampsia

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End-organ injury

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Management

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Management: Gestational HTN or preeclampsia without severe features

Gestational HTN or preeclampsia without severe features:‐ serial assessment of maternal symptoms and fetal well being

‐ serial measurements of BP

‐ assessment of platelet counts, creatinine and liver enzymes (weekly)

Gestational hypertension:‐ Monitoring BP at least once weekly with proteinuria assessment

in the office

Persistent SBP < 160 mmHg or DBP <110 mmHg, anti-hypertensive medications not be administered

Strict bed rest should not be prescribed

Ultrasonography to assess fetal growth and antenatal testing to assess fetal status


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Less than 37 0/7 weeks: expectant management with maternal and fetal monitoring is suggested

Timing of Delivery: 37 0/7 weeks of gestation

Magnesium sulfate not be administered universally for the prevention of eclampsia

Group NNT

Severe Preeclampsia + SxS

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Severe Preeclampsia - SxS

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In developed countries

385

Mild preeclampsia 400

Prevention = MgSO4

Sibai 2005

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HYPITAT

IOL is associated with improved maternal outcome for women with non-severe hypertensive disease >37 weeks gestation.

Hypertension and Preeclampsia Intervention Trial At near Term

Multicenter, parallel, open-label randomized controlled trial

Singleton pregnancy at 36-41 WGA

GHTN or (mild) preeclampsia

Randomly allocated to either IOL or expectant monitoring‐ Eclampsia, HELLP, pulmonary edema, VTE & placental abruption

‐ Need for antihypertensive medications

‐ Progression to severe PEC, postpartum hemorrhage

IOL: 31% poor maternal outcome vs 44% in expectant arm‐ RR 0.71, 95% CI 0.59-0.86, p<0.0001

‐ No cases of maternal/neonatal death or eclampsia

Koopmans, 2009; NHBPEPWG Report 2000

Management: Preeclampsia with Severe features

Unstable maternal or fetal conditions (irrespective of GA): delivery soon after maternal stabilization ‐ – Uncontrollable severe BP

‐ – Eclampsia

‐ – Pulmonary edema

‐ – Placental abruption

‐ – DIC

‐ – NRFHT

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< 34 0/7 weeks with stable maternal and fetal conditions: continued pregnancy at facilities with adequate maternal and NICU resources

Administration of corticosteroids for fetal lung maturity if < 34 0/7 weeks:

Start antihypertensive therapy Sustained SBP >160 mmHg and/or DBP > 110 mmHg

Drugs of choice: Labetalol, Nifedipine and Hydralazine

IV Magnesium Sulfate – initial 24 h stabilization, during Labor and Delivery till 24 h PP

Neuraxial Anesthesia – Blunt sympathetic/pain component of BP


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Management: Post Partum

BP monitoring: 72 hours postpartum and again 7-10 days after delivery or earlier in women with symptoms.

Discharge instructions include information about the signs and symptoms of preeclampsia for ALL patients

New-onset hypertension associated with headaches or blurred vision or preeclampsia with severe hypertension: IV magnesium sulfate

Antihypertensive Therapy:

‐ Persistent hypertension: SBP >140 mm Hg and/or DBP >90 mm Hg - 2 occasions, 4h apart

‐ or

‐ 150mmHg systolic or 100mmHg diastolic once

Management: Post Partum

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Chronic Hypertension

• BP ≥ 140/90 at one of the following times:

‐ pre-pregnancy

‐ GA < 20 weeks

‐ > 12 weeks postpartum

Chronic Hypertension

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•Preeclampsia in a patient with a history of HTN before pregnancy or before 20 weeks of gestation

Chronic Hypertension With Superimposed Preeclampsia

20–50% of women with chronic hypertension may develop superimposed preeclampsia

In women with end-organ disease or secondary hypertension, the rate of superimposed preeclampsia has been reported to be as high as 75%

Chronic Hypertension With Superimposed Preeclampsia

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Hypertension

2017 ACC/AHA definition change:

Retrospective cohort study: 137 389 pregnancies

Hypertension increased ‐ from 10.3%to 28.1%

‐ net reclassification index of 20.8%for the identification of future preeclampsia

‐ and 3.8% for the identification of fetal/neonatal adverse events.

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It is reasonable to manage stage 1 as CHTN if diagnosed prior to pregnancy

Aspirin, compared with placebo, did not appear to lower the risk of preeclampsia among patients in the stage 1 hypertension group

Serum aspartate aminotransferase and alanine aminotransferase

Serum creatinine

Serum electrolytes (specifically potassium)

Blood urea nitrogen

Complete blood count

Spot urine protein/creatinine ratio or 24-hour urine for total protein and creatinine (to calculate creatinine clearance) as appropriate

Electrocardiogram or echocardiogram

Management: Chronic Hypertension

Baseline evaluation

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Features suggestive of secondary hypertension: refer to a physician with expertise in treating hypertension to direct the workup is suggested

Use of home BP monitoring is suggested

Suspected white coat hypertension - the use of ambulatory BP monitoring to confirm the diagnosis before the initiation of antihypertensive therapy


Chronic hypertension:

‐ US to screen for fetal growth restriction (32 weeks)

‐ Antenatal testing from 32 weeks

Chronic hypertension and no additional maternal or fetal complications, delivery before 38 0/7 weeks of gestation is not recommended.

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Fetal cardiac anomalies, Calvarium hypoplasia, renal dysgenesis,1st trimester

Fetal renal toxicity 2nd and 3rd trimester

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There is no consensus as to the optimal blood pressure threshold for initiating therapy of nonsevere hypertension to prevent development of severe hypertension since the benefits and potential risks of treatment are not clear

When to start antihypertensives?

Antihypertensive treatment ‐ did not reduce the occurrence of preeclampsia, perinatal death,

preterm birth, or abruptio placentae (heterogeneity in study designs)

‐ associated with a 40 to 70 percent reduction in the occurrence of severe hypertension during pregnancy

‐ not associated with a reduction in stroke; however, this may reflect the low frequency of stroke in the study populations and lack of power to detect a difference in this outcome

‐ did not increase the frequency of delivery of a small for gestational age infant.

Summary of trials/meta-analysis

Lucy C. Chappell. Journal of the American Heart Association 2017.

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Chronic Hypertension and Pregnancy (CHAP)

large, multicentric, randomized controlled trial ‐ pregnant patients with blood pressures ranging between 140 and

159/90–104 mmHg.

‐ Randomized to the “antihypertensive therapy” arm to control their blood pressure to < 140/90 mmHg, or the “no antihypertensive or low-dose therapy” arm, with the goal of maintaining a blood pressure < 160/105 mmHg;

Approach to treatment CHTN

ACOG 2020‐ Initiate if: severe 160/110

FR 2021! or ISSHP and NICE‐ Initiate if 140/90

‐ Target BP: 110 to 140/80 to 95 mmHg

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White coat hypertension, defined as elevated blood pressure primarily in the presence of health care providers, may account for up to 15% of individuals with office hypertension,

Hypertension should not be considered entirely benign‐ 40% gestational HTN

‐ 8% will progress to preeclampsia

White Coat Hypertension

Prevention

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TXA2: potent platelet aggregator and vasoconstictor‐ Synthesized by endothelial cells, activated platelets &

macrophages

‐ Increased in women with PEC

Platelet function is blocked by ASA at doses ≥ 100mg

At doses ≤100mg, mainly PG synthesis is affected

In Theory: How does ASA prevent PEC?

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Effect of ASA on PEC prevention Reduced the risk of pre-eclampsia by 18% (36,716 women,

60 trials, RR 0.82, 95% CI 0.77 to 0.88; high-quality evidence),

NNT for one women to benefit: 61 (95% CI 45 to 92)

Effect of ASA on PEC prevention Meta-analyses of RCTs have reported contradictory results

‐ GA at the onset of treatment < or > 16 wga

‐ Dosing < or > than 100mg

Rolnik 2017: Aspirin for Evidence-based Preeclampsia Prevention trial (ASPRE)

‐ n = 1620, treatment of ASA 150mg qd vs placebo arms

‐ Initiated at 11-14 WGA, stopped at 36 WGA

‐ Decreased PT PEC by ~65% (4% in ASA arm, 1% in placebo arm)

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Presentation Title51

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ASPIRIN TRIAL

randomised, multicountry, double-masked, placebo-controlled trial of low-dose aspirin

(81 mg daily) initiated between 6 weeks and 0 days and 13 weeks and 6 days of pregnancy

nulliparous women with an ultrasound confirming gestational age and a singleton viable pregnancy

Early preterm delivery (<34 weeks) and hypertensive disorders* 0.38 (0.17–0.85) 0.015

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At UCSF…

● ≥ 1 High or ≥2 Moderate Risk Factors: 81-162 mg daily at bedtime

● 1 Moderate Risk Factor: 81mgdaily at bedtime

* Patients with obesitytheoretically may benefit from higher dose

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Eclampsia

HELLP

DIC

Hemorrhage

Sepsis

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Thank you!

[email protected]


Previous clinical trials documented effects of ASA upon lipoperoxides, α- and β-adrenergic receptors, and BP in clinically healthy subjects that are dependent on ASA circadian administration time

ASA produces a >30% inhibition of angiotensin II only when ingested at bedtime, in association with the documented administration-time-dependent effects of ASA on plasma renin activity

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Previous clinical trials documented effects of ASA upon lipoperoxides, α- and β-adrenergic receptors, and BP in clinically healthy subjects that are dependent on ASA circadian administration time

ASA produces a >30% inhibition of angiotensin II only when ingested at bedtime, in association with the documented administration-time-dependent effects of ASA on plasma renin activity

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Sibai AJOG 2009

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rocha hypertensive disease in pregnancy

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