1. Hypertension in Pregnancy: Clinical Update Meredith Birsner MD Robert Atlas MD On behalf of Maryland Maternal Mortality Review Committee

2. No disclosures

3. Abbreviations O ACEi: ACE (angiotensin converting enzyme) inhibitor O ARB: angiotension receptor blocker O BMI: body mass index O BP: blood pressure O BPP: biophysical profile O cHTN: chronic hypertension O DBP: diastolic blood pressure O FGR: fetal growth restriction O GA: gestational age O gHTN: gestational hypertension O HELLP: hemolysis, elevated liver enzymes, low platelets O HTN: hypertension O NST: non-stress test O PEC: preeclampsia O PTD: preterm delivery O ROM: rupture of membranes O SBP: systolic blood pressure O UA: umbilical artery (Dopplers)

4. Background: local O Action item from 2012 review O Preeclampsia: leading cause of pregnancy- associated deaths 2007-2012 O 12 deaths O Mean age: 31.6 O Race: AA (5), Caucasian (4), Hisp (2), Asian (1) O 5 primigravidas O 3 with late or no prenatal care O Mean PPD: 4.6 O Mechanism of death: ICH (6), Hemorrhage/DIC (2), cardiomyopathy/PE (2), hypertensive cardiovascular disease (1), liver capsule rupture/DIC (1)

5. 2007-2012 PEC deaths O Committee focus: O Delay in recognition/diagnosis O Variation in treatment O Lack of recognition postpartum

6. Background: national O ACOG Task Force on Hypertension in Pregnancy O Obstet Gynecol. 2013 Nov;122(5):1122-31

7. Evidence evaluation: GRADE O Grading of Recommendations Assessment, Development and Evaluation Working group O Approach: function of expert task forces and working groups is to evaluate available evidence regarding a clinical decision that, because of limited time and resources, would be difficult for the average health care provider to accomplish; then, makes recommendations consistent with typical pt values and preferences O Evidence quality: very low, low, moderate, high

8. Strength of recommendations O Strong: so well supported that it would be the approach for virtually all patients O Could be the basis for health care policy O Qualified: appropriate for most patients but might not be optimal for some patients O Provider and patient are encouraged to work together to arrive at a decision based on values and judgment and underlying health condition of a particular patient in a particular situation

9. Summary of strength and quality of recommendations There are no recommendations supported by very low evidence in this document All high quality evidence in this document is given strong recommendation (6) All low quality recommendations are qualified (23) Comprises the majority of recommendations (23)

10. Strong recommendations based on high-quality evidence (6) 1. Administration of vitamin C or E to prevent PEC is not recommended 2. For women with eclampsia, magnesium is recommended 3. For women with PEC with severe features, magnesium is recommended to prevent eclampsia intra- and postpartum

11. Strong recommendations based on high-quality evidence (6) 4. For women with PEC with severe features receiving expectant management at ≤34 weeks, administration of corticosteroids for lung maturity is recommended 5. For women with superimposed PEC receiving expectant management at ≤34 weeks, administration of corticosteroids for lung maturity is recommended 6. For women with previable HELLP, deliver shortly after initial maternal stabilization

12. Document highlights by chapter

13. Document breakdown O Chapter 1: Classification of hypertensive disorders O Chapter 2: Establishing the diagnosis of preeclampsia and eclampsia O Chapter 3: Prediction of preeclampsia (1) O Chapter 4: Prevention of preeclampsia (4) O Chapter 5: Management of preeclampsia and HELLP syndrome (30) O Chapter 6: Management of women with prior preeclampsia (1) O Chapter 7: Chronic hypertension in pregnancy and superimposed preeclampsia (22) O Chapter 8: Later-life cardiovascular disease in women with prior preeclampsia (1) O Chapter 9: Patient education (1) O Chapter 10: State of the science and research recommendations

14. Chapter 1: Classification of hypertensive disorders

16. Definition of preeclampsia O Eliminated dependence on proteinuria for diagnosis of PEC O PEC defined as HTN plus O Thrombocytopenia (platelets <100K) O Impaired liver function (2x normal) O New onset renal insufficiency (Cr >1.1 or doubled in the absence of other renal disease) O Pulmonary edema O New-onset cerebral or visual disturbances O Why is this important? O Can diagnose PEC without proteinuria!

17. Classification of hypertensive disorders of pregnancy O Preeclampsia-Eclampsia O Gestational hypertension O BP elevation after 20 weeks gestation in the absence of proteinuria or systemic findings O Chronic hypertension O Hypertension that predates pregnancy O Chronic hypertension with superimposed preeclampsia

18. Diagnosis of proteinuria O Urine protein/creatinine ratio of ≥ 0.3 diagnostic of proteinuria O Important because can speed diagnosis & eliminate 24h study O 24h study still has some clinical utility in equivocal situations O Dipsticks discouraged unless other methods not available O Remain useful for office-based screening

20. Chapter 2: Establishing the diagnosis of preeclampsia and eclampsia

21. Technique of BP measurement O Comfortably seated, legs uncrossed, back & arm supported O Middle of cuff on upper arm is at level of R atrium (midpoint of sternum) O Instruct pt to relax and not talk during measurement O 5 mins should elapse before 1st reading is taken O If need to retake, allow “several minutes” to elapse O L lateral positioning discouraged b/c will falsely lower BP readings (cuff will be above heart)

22. Diagnosis O Eliminates “mild PEC” and“severe PEC” O Renames the former as “PEC” and the latter as “PEC with severe features” O 5g protein/24h and fetal growth restriction no longer diagnostic of “severe” O Why? Minimal relationship between quantity of proteinuria and pregnancy outcome O Also because FGR is managed similarly in pregnant women with and without preeclampsia

24. Chapter 3: Prediction of Preeclampsia

25. Risk factors Screening to predict PEC beyond history to evaluate for risk factors is not recommended.

26. Chapter 4: Prevention of preeclampsia

27. Aspirin O Late first trimester initiation of daily low- dose (60-80mg) aspirin for women with hx early-onset PEC and PTD 1 pregnancy O Appears to be safe with no major adverse effects O No guidance on specific GA to start other than late first trimester

28. Chapter 5: Management of preeclampsia and HELLP syndrome

29. Maternal surveillance for gHTN or PEC without severe features O Daily kick counts O Twice weekly blood pressure O Labs at least once weekly O Monitor gHTN weekly for proteinuria until diagnosed O Review warning symptoms at dx and every visit

30. Fetal surveillance in gHTN or PEC without severe features O Growth ultrasounds q3 weeks O AFI at least once weekly O NST once weekly for gHTN (twice weekly for PEC without severe features) O Frequency not defined in the executive summary but reads: “for PEC without severe features, use of ultrasonography to assess fetal growth and antenatal testing to assess fetal status is suggested”

32. Delivery indications for gHTN or PEC without severe features O 37 weeks or more O Suspected abruption O 34 weeks plus O Progressive labor or ROM O Estimated fetal weight <5%ile O Oligohydramnios (persistent AFI <5cm) O Persistent BPP 6/10 or less

33. Other points of management for PEC and HELLP O Blood pressure: don’t treat gHTN for SBP <160 or DBP <110 O Strict bedrest should not be prescribed for gHTN or PEC without severe features O Big push nationally against bedrest

34. Other points of management for PEC and HELLP O Use growth ultrasounds for PEC: if FGR found, UA Dopplers are recommended O Deliver gHTN and PEC without severe features after 37w

35. Other points of management for PEC and HELLP O Magnesium not recommended universally for PEC with SBP <160, DBP <110, and no maternal symptoms O But treat preeclampsia with severe features O Treat severe HTN (SBP >160, DBP >110)

36. Other points of management for PEC and HELLP O For PEC, delivery decisions should not be based on amount of or change in proteinuria O No worse outcomes O Do not hold magnesium intraoperatively O Long half life (5h) O Expectant management: daily NST and kick counts, BPP 2x/week, serial growth q2 weeks

37. Management of preeclampsia with severe features <34 weeks O Observe in Labor and Delivery for first 24-48 hours O Corticosteroids, magnesium sulfate prophylaxis, and antihypertensive medications O Ultrasonography, monitoring of fetal heart rate, symptoms, and laboratory tests

39. Maternal contraindications to expectant management, DIC, or partial HELLP

40. Fetal contraindications to expectant management

41. What constitutes appropriate expectant management? O Facilities with adequate maternal and neonatal intensive care resources O Fetal viability-33 weeks 6 days gestation O Inpatient only and stop magnesium sulfate O Daily maternal-fetal tests O Vital signs, symptoms, and blood tests O Oral anti-hypertensive drugs

42. Postpartum surveillance O For gHTN, PEC, or superimposed PEC, monitor blood pressure in hospital (or equivalent outpatient surveillance) for at least 72h postpartum and again 7-10d postpartum (earlier if symptoms)

43. Discharge instructions O All postpartum women should receive discharge instructions which include information about PEC signs and symptoms and importance of prompt reporting to provider

44. Postpartum hypertension O Give magnesium for postpartum women with new-onset HTN with headaches, blurred vision, or PEC with severe HTN O Stricter criteria for treating persistent postpartum HTN O SBP ≥ 150, DBP ≥ 100, 2 occasions at least 4-6h apart O Treat persistent SBP ≥ 160 or DBP ≥ 110 within 1h

45. Chapter 6: management of women with prior preeclampsia

46. Prior preeclampsia O Preconception counseling and assessment suggested for women with PEC in prior preeclampsia

47. Evaluation and management of women at risk of preeclampsia recurrence: preconception and by trimester

49. Preconception O Identify risk factors (type 2 diabetes mellitus, obesity, HTN, family history) O Review outcome of previous pregnancy (abruption, fetal death, fetal growth restriction, gestational age at delivery) O Perform baseline metabolic profile and urinalysis O Optimize maternal health O Supplement with folic acid

50. First trimester O Perform the following: O Ultrasonography for gestational age and fetal number O Baseline metabolic profile and complete blood count O Baseline urinalysis O Continue folic acid supplementation O Offer first-trimester combined screening O Offer low-dose aspirin initiation O For women with prior preeclampsia that led to delivery <34 weeks gestation or occurring in ≥ 1 pregnancy O In late first trimester

51. Second trimester O Counsel patients about signs and symptoms of preeclampsia beginning at 20 weeks of gestation; reinforce this with printed handouts O Monitor for signs and symptoms of preeclampsia O Monitor BP at prenatal visits, with nursing contacts, or home O Perform ultrasonography at 18-22 weeks for fetal anomaly evaluation O Hospitalize for severe gestational hypertension, severe fetal growth restriction, or recurrent preeclampsia

52. Third trimester O Monitor for signs and symptoms of preeclampsia O Monitor BP at prenatal visits, with nursing contacts, or home O Perform the following as indicated by clinical situation: O Laboratory testing O Serial ultrasonography for fetal growth and amniotic fluid assessment O Umbilical artery Doppler with nonstress test, BPP, or both O Hospitalize for severe gestational hypertension or recurrent preeclampsia

53. Chapter 7: Chronic hypertension in pregnancy and superimposed preeclampsia

54. Home/ambulatory monitoring O Home BP monitoring for women with cHTN and poorly controlled BP O Ambulatory BP monitoring for women with suspected white coat HTN to confirm diagnosis before initiating anti-hypertensive therapy

55. BP treatment O Treat pregnant women with persistent cHTN with SBP ≥ 160 or DBP ≥105 O Don’t treat for less if no end-organ damage O Goal 120-160/80-105

56. Antihypertensive agents

57. Choice of medications Theoretical concern of combined use of nifedipine and IV magnesium sulfate resulting in hypotension and neuromuscular blockade (both are calcium antagonists) One review concluded that combined use does not increase such risks Plausible so careful monitoring of women receiving both is advisable Choice/route should be primarily based on physician familiarity and experience, adverse effects and contraindications, local availability, and cost. Labetalol, nifedipine, or methyldopa recommended above all other anti-hypertensive drugs

58. Contraindicated medications O For (nonpregnant) women of reproductive age with cHTN, use of ACEi, ARBs, renin inhibitors, and mineralocorticoid receptor antagonists NOT recommended unless compelling reason (ex. proteinuric renal disease)

59. Aspirin O Late first trimester initiation of daily low- dose (60-80mg) aspirin for women with cHTN at greatly increased risk of adverse outcomes (hx early onset PEC and PTD at 1 pregnancy)

60. Delivery considerations for cHTN O Do not deliver cHTN with no additional maternal or fetal complications <38w O Isolated, uncomplicated chronic hypertension without superimposed preeclampsia O Give magnesium (intra- and postpartum) for cHTN with superimposed PEC with severe features O For superimposed PEC without severe features, and stable maternal and fetal conditions, expectant management until 37 weeks

61. Diagnosis of superimposed preeclampsia LIKELY O Sudden increase in BP that was previously well-controlled, or escalation of antihypertensive medications to control BP O New onset of proteinuria or a sudden increase in proteinuria in a woman with known proteinuria before or early in pregnancy

62. Diagnosis of superimposed preeclampsia ESTABLISHED O Severe-range BP despite escalation of antihypertensive therapy O Thrombocytopenia (platelets <100K) O Elevated liver transaminases (two times the upper limit of normal concentration for a particular laboratory) O New-onset and worsening renal insufficiency O Pulmonary edema O Persistent cerebral or visual disturbances

63. Chapter 8: Later-life cardiovascular disease in women with prior preeclampsia

64. Later-life considerations O For women with history of PEC who delivered <37 weeks or recurrent PEC: yearly assessment of blood pressure, lipids, fasting blood glucose, BMI

66. Chapter 9: Patient education

70. Thank you! Please contact us with any questions: mbirsne1@Jhmi.edu ratlas@mdmercy.com State Maternal Mortality Review (MMR) Program: http://phpa.dhmh.maryland.gov/mch/SitePages/mmr.aspx