Canadian Society of Internal Medicine Annual Meeting 2017 Toronto, ON Hypertension in Pregnancy (workshop) Dr. Shital Gandhi University of Toronto
CSIM Annual Meeting 2017 The following presentation represents the views of the speaker at the time of the presentation. This information is meant for educational purposes, and should not replace other sources of information or your medical judgment. Learning Objectives: • Master the classification to hypertensive disorders in pregnancy • Appreciate the role of the internist in the management and treatment of hypertension in pregnancy, preeclampsia, and post-pregnancy care • Discuss preeclampsia prevention • Understand early models of preeclampsia prediction • Review the medications that can be used safely to treat hypertension in pregnancy Dr. Shital Gandhi-HTN in pregnancy- Nov 1
CSIM Annual Meeting 2017 Conflict Disclosures Definition: A Conflict of Interest may occur in situations where the personal and professional interests of individuals may have actual, potential or apparent influence over their judgment and actions. “I have no conflicts to declare”
CLASSIFICATION OF HYPERTENSIVE DISORDERS IN PREGNANCY (SOGC 2014) Pre-existing (chronic) HTN • With co-morbid conditions • With preeclampsia Gestational HTN • With comorbid conditions • With preeclampsia Preeclampsia (PET=Preeclampsia-Toxemia) Other (transient, white coat, masked)
CASE 1 QUESTION 1 35 G1P0 at 8 weeks gestation with BP 145/95 mm Hg Which of the following is CORRECT? 1) She has Pre-existing or Chronic HTN 2) She has Gestational HTN 3) Lowering blood pressure will prevent Preeclampsia 4) There are no therapies to prevent Preeclampsia
HEMODYNAMIC CHANGES IN PREGNANCY Hypertension defined as BP > 140/90 mm Hg Systolic BP 160 100 Systolic BP 40 Gestational age 0 10 20 30 40 50 -20
CLASSIFICATION OF HYPERTENSIVE DISORDERS IN PREGNANCY (SOGC 2014) Pre-existing (chronic) HTN: HTN (> 140/90) detected prior to 20 weeks • With co-morbid conditions • With preeclampsia: risk is ~ 20% Gestational HTN • With comorbid conditions • With preeclampsia Preeclampsia Other (transient, white coat, masked)
CONTROL OF HTN IN PREGNANCY STUDY (CHIPS, NEJM 2015) No difference : pregnancy loss or NICU • RCT of 987 women with HTN • Non-proteinuric HTN (14-34 wks) • Intervention : “Tight” (DBP 85 mm Hg) vs “Less Tight” (DBP 100 mm Hg) • Rates of preeclampsia similar in both groups • Secondary outcome: serious maternal complications up to 6 weeks PP or until hospital discharge Target 130-155/80-105 mm Hg Target 130-140/80-90 mm Hg if diabetes, renal disease, etc
CASE 1 QUESTION 2 (TREATMENT) Which of the following are CORRECT? 1. Atenolol can be used to treat HTN in pregnancy 2. Labetalol can be used to treat HTN in pregnancy 3. Nifedipine is contra-indicated 4. Methyldopa dosing is once a day
SOGC 2014 Drug Typical Maximum per day Methyldopa 250-500 mg BID-QID 2 grams Labetalol 100-400 mg BID-QID 1200 mg Nifedipine XL 20-60 mg OD-BID 120 mg Hydralazine 10-50 mg TID ~200 mg
CASE 1 QUESTION 2 (TREATMENT) Which of the following are correct? 1. Atenolol can be used to treat HTN in pregnancy • Increased risk of growth restriction; cases of neonatal bradycardia 2. Labetalol can be used to treat HTN in pregnancy 3. Nifedipine is contra-indicated • Fine choice, just don’t have as much volume of data in pregnancy 4. Methyldopa dosing is once a day • Fine choice, cheap, but should be at least BID. Significant fatigue
CASE 1 QUESTION 3 (PREVENTION) Which of the following is CORRECT? 1. Aspirin prevents preeclampsia 2. Calcium supplementation prevents preeclampsia 3. Salt restriction does NOT prevent preeclampsia 4. Bedrest does NOT prevent preeclampsia 5. All of the above are CORRECT
ASPIRIN FOR THE PREVENTION OF PET Author Journal/Yr N Dose ASA GA Outcome (wks) Benigni NEJM/1986 35 60 mg <20 Longer pregnancy Higher birthweight Schiff NEJM/1989 35 100mg 28 Less “PIH” McParland Lancet/1990 100 75 mg <20 Less Proteinuric HTN Less low birth weight Italian Lancet/1993 1100 50 mg 16-32 No difference CLASP Lancet/1994 9364 60 mg 12-32 No difference in preeclampsia Less preterm NIH NEJM/1998 2539 60 mg 13-26 No difference Over 37,000 women in 55 trials have tried to address this question
ASPIRIN FOR PREECLAMPSIA What dose?
META-ANALYSIS OF INDIVIDUAL PATIENT DATA ASKIE ET AL. LANCET 2007 RR 0.90 (95% CI 0.84-0.97) Reduced PET Reduced delivery <34 wks Reduced serious adverse outcome
EARLY ADMINISTRATION OF LOW DOSE ASA FOR THE PREVENTION OF TERM AND PRE-TERM PREECLAMPSIA: SYSTEMATIC REVIEW FETAL DIAGNOSIS AND THERAPY 2012 If initiated < 16 weeks gestation, RR 0.11, NNT 19
RECOMMENDATIONS REGARDING ASA ARE UNIVERSAL Governing body Who What When ACOG Prior early onset PET 60-80 mg Late first trimester NICE All high risk 75 mg < 16 weeks USPSTF High risk 81 mg 12 weeks AHA HTN, or prior 81 mg 12 weeks gestational HTN SOGC All high risk 81 mg < 16 weeks
PREECLAMPSIA: RISK FACTORS Demographics Before this This pregnancy T2/T3 Pregnancy Age >40 or <20 Previous PET Multiples Gestational HTN Family history Medical conditions Obesity Abnormal uterine Hypertension dopplers Diabetes Renal disease Family history CAD Antiphospholipid BP > 130/80 at initial Excessive weight gain antibody syndrome visit Low maternal BMI Short duration of sexual relationship > 10 years between pregnancies Reproductive technologies
IS MORE ASA BETTER?
CALCIUM SUPPLEMENTATION REDUCES THE RISK OF PREECLAMPSIA Cochrane Database of Systematic Reviews 4 AUG 2010 DOI: 10.1002/14651858.CD001059.pub3 http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD001059.pub3/full#CD001059-fig-0003
CASE 1 QUESTION 3 (PREVENTION) Which of the following is correct? 1. Aspirin prevents preeclampsia • We can debate the magnitude of effect, but it does help 2. Calcium supplementation prevents preeclampsia • In women with low calcium intake 3. Salt restriction does NOT prevent preeclampsia • True 4. Bedrest does NOT prevent preeclampsia • True 5. You can’t fool me. All of the above are CORRECT
CASE #1 (REVIEW) 35 G1P0 at 8 weeks gestation with BP 145/95 mm Hg Which of the following is CORRECT? 1) She almost certainly has Pre-existing or Chronic HTN • Yes, given the timing of detection 2) She almost certainly has Gestational HTN • No, it’s too soon 3) Anti-hypertensive medication will prevent Preeclampsia • No. RCT’s have shown that this will not effect rates of PET 4) There is nothing we can do to prevent Preeclampsia • Not true: ASA 81-150 mg, calcium if intake is low
CASE #2 35 G2P1L0 at 17 weeks gestation with BP 145/95 mm Hg (new) Which of the following is correct? 1) She has Pre-existing or Chronic HTN 2) She has Gestational HTN 3) I need more information
HEMODYNAMIC CHANGES IN PREGNANCY Systolic BP 160 100 Systolic BP 40 Gestational Age 0 10 20 30 40 50 -20
WHEN GUIDELINES DON’T ENCOMPASS PHYSIOLOGIC EXPECTATIONS In this situation, 3 possibilities: 1. There is a new medical cause of hypertension • Other secondary causes of HTN • SLE, HUS, APS, TTP 2. There is an atypical/early placental-mediated disorder • Very early onset preeclampsia • Molar pregnancy 3. Transient Hypertension
EARLY ONSET PREECLAMPSIA • High perinatal morbidity and mortality • Treatment of hypertension is important, but will not really affect fetal outcome • The internist should be aware of guarded fetal prognosis
CASE #2 35 G2P1L0 at 17 weeks gestation with BP 145/95 mm Hg (new) Which of the following is correct? 1) She has Pre-existing or Chronic HTN • Technically, the guidelines would lead us to this conclusion, but physiologically, it doesn’t fit 2) She has Gestational HTN • Technically, the guidelines would rule this out, but… 3) I need more information • Yes. Reviewing the course of blood pressure is important
CASE #3 35 G1P0 at 28 weeks gestation, BP 145/95 mm Hg (new) Which of the following is FALSE? 1. She has Gestational Hypertension 2. She is at increased risk of Preeclampsia 3. No proteinuria = No preeclampsia 4. The fetus requires additional monitoring
Systolic BP 160 100 Systolic BP 40 Gestational Age 0 10 20 30 40 50 -20
OUTCOMES IN “GESTATIONAL HYPERTENSION” Outcome Gestational HTN Preeclampsia (= no proteinuria) (= proteinuria) Mild Severe Mild Severe Delivery < 34 1 25 1.9 18.5 SGA (%) 6.9 21 10.2 18.5 Abruption 0.3 4.2 0.5 3.7 Perinatal death 0.5 0 1.0 1.8 Buchbinder Am J Ob Gynecol 2002 Hauth Obstet Gynecol 2000
NEW ONSET OF NON-PROTEINURIC HTN < 34 WEEKS PREDICTS HIGH RISK OF PREECLAMPSIA Gestational Hypertension at “Term” (> 37 weeks) • Outcome excellent Gestational Hypertension “remote from term” • Outcomes similar to preeclampsia • Time from diagnosis of Hypertension to diagnosis of preeclampsia ~ 5 weeks
PREECLAMPSIA (SOGC 2014) Gestational Hypertension (new onset after “20-ish” weeks) + • New proteinuria • One or more adverse conditions • One or more severe complications
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