HTN in Pregnancy

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Presented by Family Medicine Resident Dr. Chen
Reference: Hypertension in Pregnancy & Women of Childbearing Age Am J Med. 2009 Oct

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HTN in Pregnancy

  1. 1. Hypertension in Pregnancy and Women of Childbearing Age American Journal of Medicine 2009
  2. 2. 林小姐 <ul><li>33 y/o woman with essential HTN </li></ul><ul><li>Regularly f/u at your OPD </li></ul><ul><li>BP currently well controlled with ACEI + CCB </li></ul><ul><li>She tells you today that she plans on getting pregnant this year </li></ul>我要去度蜜月了,哈哈!! What do you do??
  3. 3. 呂太太 <ul><li>34 y/o woman with no past Hx </li></ul><ul><li>G1P0, GA8wks </li></ul><ul><li>BP 145/95 incidentally found on health checkup </li></ul><ul><li>Denied other specific discomfort </li></ul>What do you do?? 什麼?我有高血壓?
  4. 4. Women… <ul><li>Women tend to have lower BP then men </li></ul><ul><li>Age delay in developing HTN in women  most women do not require HTN Rx during childbearing years </li></ul><ul><li>↑ of obesity & metabolic syndrome  ↑ number of young women with HTN </li></ul>
  5. 5. <ul><li>Joint National Committee 7 (JNC7) classification of HTN and Rx goals: same regardless of age or gender </li></ul>
  6. 6. <ul><li>Challenge in Rx HTN in the woman of childbearing age: selection of medications </li></ul><ul><ul><li>many drugs have potential teratogenicity </li></ul></ul><ul><li>Several clinical hypertensive disorders are associated with pregnancy </li></ul><ul><ul><li>Appropriate diagnosis and timely intervention needed to reduce fetal and maternal M&M </li></ul></ul>
  7. 8. Rx of essential HTN in women of childbearing age Part 1
  8. 9. <ul><li>If fresh case, workup for secondary causes of HTN: endocrine, renal… </li></ul><ul><li>Ask about contraceptive use: hormonal contraceptive use – common cause of HTN! </li></ul>
  9. 10. <ul><li>Women of childbearing age with Class I HTN likely need no medical Rx </li></ul><ul><li>Try lifestyle modification and exercise Rx </li></ul><ul><ul><li>Most preg. women can tolerate some degree of exercise </li></ul></ul><ul><ul><li>Exercise can ↓ gestational HTN and risk of preeclampsia / eclampsia </li></ul></ul>
  10. 11. FDA pregnancy drug categories A Adequate and well-controlled studies have failed to demonstrate a risk to the fetus in the first trimester of pregnancy B Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women OR Animal studies have shown an adverse effect, but adequate and well-controlled studies in pregnant women have failed to demonstrate a risk to the fetus in any trimester. C Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans , but potential benefits may warrant use of the drug in pregnant women despite potential risks. D There is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks. X Studies in animals or humans have demonstrated fetal abnormalities and/or there is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience, and the risks involved in use of the drug in pregnant women clearly outweigh potential benefits.
  11. 12. In choosing the medication… <ul><li>Caution! In women who may be or who are planning to become pregnant </li></ul><ul><li>FDA guidelines regarding safety </li></ul><ul><ul><li>Drugs with significant risk for fetal effects are classified as class D or have a black box recommendation – should be avoided! </li></ul></ul>
  12. 13. <ul><li>Many drugs fall into ambiguous category </li></ul><ul><li>American Heart Association, American College of Cardiology, American College of ObGyn have developed recommendations </li></ul><ul><li>Minimal risk in pregnancy  good option! </li></ul>
  13. 14. <ul><li>ACEI & ARB 不要用 </li></ul><ul><ul><li>Associated with renal agenesis & fetal demise </li></ul></ul><ul><ul><li>If pregnancy occurs during Rx with ACEI/ARB  stop immediately </li></ul></ul><ul><ul><li>Counseling and contraceptive education beforehand </li></ul></ul>
  14. 15. 林小姐 <ul><li>33 y/o woman with essential HTN </li></ul><ul><li>Regularly f/u at your OPD </li></ul><ul><li>BP currently well controlled with ACEI + CCB </li></ul><ul><li>She tells you today that she plans on getting pregnant this year </li></ul>我要去度蜜月了,哈哈!!
  15. 16. Normal hemodynamic changes in Pregnancy Part 2
  16. 17. <ul><li>First 20 wks of pregnancy: intravascular volume ↑ 30~40% </li></ul><ul><li>Red cell mass also ↑ by 20% </li></ul><ul><li>↑ intravascular vol & neurohormone changes  relative vasodilation  ↑ placental perfusion </li></ul><ul><li>Maternal HR ↑ 10beats/min </li></ul><ul><li>Cardiac output ↑ 30% </li></ul><ul><li>O2 consumptoion ↑ 30% </li></ul><ul><li>GA20wks, uterus may impinge on inf. vena cava  position dependent ↓ pre-load </li></ul>
  17. 19. <ul><li>因 relative vasodilation 的緣故,原本懷孕前血壓偏高的病人懷孕後反而血壓正常了! </li></ul><ul><li>BP control in p’t with essential HTN does not ↓ risk for preeclampsia/eclampsia </li></ul><ul><li>No successful intervention for prevention of preeclampsia </li></ul>
  18. 20. Approach to HTN during pregnancy Part 3
  19. 21. <ul><li>Pregnant women should receive regular BP monitoring </li></ul><ul><li>Comparison of classification: </li></ul><ul><li>When to start HTN Rx: varies internationally </li></ul>JNC7 ACOG Stage I 140~159/90~99 Mild 140~159/ 90~109 Stage II >160/100 Severe > 160/110
  20. 22. <ul><li>Little evidence to support aggressive Rx for BP <160/110mmHg </li></ul><ul><li>Individualized Rx for the patient’s condition </li></ul><ul><ul><li>P’t with chronic HTN may tolerate higher BP without complication </li></ul></ul><ul><ul><li>Marked ↑ in arterial hemorrhagic events occurs when BP>160/110mmHg  assoc. with mortality rate of 50% </li></ul></ul>
  21. 23. Evaluation and Rx of severe HTN <ul><li>Similar to that of HTN urgency/emergency </li></ul><ul><li>If end-organ damage or neurological compromise  aggressive & rapid Rx </li></ul><ul><li>Safety of the mother comes first </li></ul><ul><li>Early delivery may be considered, esp. in eclampsia </li></ul>
  22. 24. Goal of Rx <ul><li>目標是希望可以快速把血壓降下來: </li></ul><ul><ul><li>25% ↓ in mean arterial pressure within 2 hrs of presentation </li></ul></ul><ul><ul><li>160/110 mmHg within next couple of hours </li></ul></ul><ul><li>也不能降太快: Reduction of >25% BP may cause </li></ul><ul><ul><li>maternal end-organ hypoperfusion (CVA, MI) </li></ul></ul><ul><ul><li>placental ischemia  fetal compromise </li></ul></ul>
  23. 25. Medical treatment <ul><li>First-line agents: L-methyldopa (Aldomet), Labetalol (Trandate), Nifedipine (Adalat) </li></ul><ul><ul><li>Methyldopa : The only Class B drug for HTN often the 1 st med used </li></ul></ul><ul><ul><li>Labetalol use ↑ but some studies show association with fetal growth restriction </li></ul></ul>
  24. 26. <ul><li>Beta-blockers: 安全的 </li></ul><ul><ul><li>esp. Labetalol </li></ul></ul><ul><ul><li>Selective beta-blockers can also be used, but due to less vasodilatory activity  ↑ risk of bradycardia </li></ul></ul><ul><ul><li>High dose of BB associated with transient neonatal hypoglycemia </li></ul></ul>
  25. 27. <ul><li>CCB: 應該是安全的! </li></ul><ul><ul><li>Likely safe during pregancy </li></ul></ul><ul><ul><li>Most data regarding Nifedipine (Adalat), but also some reports w/ Nicardipine, Isradipine, Verapamil, Felodipine </li></ul></ul>
  26. 28. <ul><ul><li>CCB: </li></ul></ul><ul><ul><li>Theoretical concerns in early pregnancy: many embryogenesis processes are Ca dependent </li></ul></ul><ul><ul><li>Largest randomized trial to date: no significant risk </li></ul></ul><ul><ul><li>Adjust starting dose & frequency (due to ↑renal & hepatic clearance) </li></ul></ul><ul><ul><li>Case reports of neuromuscular blockage with CCB + MgSO4 use… 要注意 </li></ul></ul>
  27. 29. <ul><li>Diuretics: 應該是安全的!但是… </li></ul><ul><ul><li>? Plasma volume↓  ↓ uteroplacental perfusion? </li></ul></ul><ul><ul><li>uteroplacental perfusion ↓ less likely if p’t prev treated with Thiazide diuretics </li></ul></ul><ul><ul><li>Not usually first choice medication </li></ul></ul>
  28. 30. <ul><li>ACEI & ARB 不要用 </li></ul><ul><ul><li>Associated with renal agenesis & fetal demise </li></ul></ul><ul><ul><li>IUGR, IUFD </li></ul></ul><ul><ul><li>Oligohydramnios </li></ul></ul><ul><ul><li>PDA </li></ul></ul><ul><ul><li>Pulmonary hypoplasia </li></ul></ul>
  29. 31. HTN drugs for use during pregnancy Apresolin 0.5 amp IM PRN Q20~30min if SBP>170mmHg or DBP>110mmHg Trandate Adalat Aprezin Apresolin Hydrochlorothiazide
  30. 32. Hypertensive disorders of pregnancy Part 4
  31. 33. Classification: Working Group of the NHBPEP (2000) <ul><li>Platelets < 100,000/mm 3 </li></ul><ul><li>Microangiopathic hem </li></ul><ul><li>olysis (↑eased LDH) </li></ul><ul><li>Elevated ALT or AST </li></ul><ul><li>Persistent headache or other cerebral or visual disturbance </li></ul><ul><li>Persistent epigastric pain </li></ul><ul><li>Final diagnosis made only postpartum </li></ul><ul><li>May have other signs or symptoms of preeclampsia, e.g. epigastric discomfort or thrombocytopenia </li></ul>
  32. 34. 徐小姐 <ul><li>29 y/o woman </li></ul><ul><li>G1P0, GA33wks </li></ul><ul><li>No HTN noted on previous checkups </li></ul><ul><li>BP 142/100 found on routine checkup </li></ul><ul><li>Dipstick: 1+ proteinuria </li></ul>What do you do?? 徐小姐 你血壓有點高喔…
  33. 35. <ul><li>Development of HTN after GA 20wks without evidence of preeclampsia (no proteinuria) </li></ul><ul><li>Occurs in 6% of pregnancies </li></ul><ul><li>Progesses to preclampsia 15~45% of cases </li></ul><ul><li>Final diagnosis made only postpartum </li></ul>
  34. 36. <ul><li>HTN present before GA20wks </li></ul><ul><li>HTN persistent after 12wks postpartum </li></ul><ul><li>Occurs in 3% of all pregnancies </li></ul><ul><li>Essential HTN most common </li></ul><ul><li>More prevalent in African Americans, the obese, advanced maternal age (>35yrs) </li></ul>
  35. 37. <ul><li>New-onset HTN (>GA20wks) with proteinuria </li></ul><ul><li>Proteinuria: </li></ul><ul><ul><li>≥ 300mg/24hrs or dipstick ≥ 1+ </li></ul></ul><ul><li>Can occur anytime during gestation or postpartum </li></ul><ul><li>Up to 1/3 cases occur in 6wks after delivery </li></ul><ul><li>4% of all pregnancies </li></ul>
  36. 38. Pathophysiology of preeclampsia <ul><li>Abnormal placental implantation  placental hypoperfusion </li></ul>Image source:  Medscape - Pathophysiology of preeclampsia and resulting symptoms
  37. 39. <ul><li>Severity of preeclampsia: </li></ul><ul><li>Mild preeclampsia </li></ul><ul><li>Severe preeclampsia </li></ul><ul><ul><li>Hypertension (> 160/100mmHg) </li></ul></ul><ul><ul><li>Proteinuria (>5g/24hrs) </li></ul></ul><ul><ul><li>Neurological Sx (seizures, headache) </li></ul></ul><ul><ul><li>Renal compromise (oliguria, ↑ Cr) </li></ul></ul><ul><ul><li>HELLP syndrome </li></ul></ul><ul><ul><li>Fetal growth restriction (< 10 th percentile) </li></ul></ul>
  38. 40. <ul><li>HELLP syndrome </li></ul><ul><ul><li>H epatic dysfunction or hemolysis </li></ul></ul><ul><ul><li>E levated L iver enzymes </li></ul></ul><ul><ul><li>L ow P latelet count </li></ul></ul>
  39. 41. <ul><li>Eclampsia. Subcapsular hematoma dissecting under Glisson's capsule in a fatal case of eclampsia </li></ul><ul><li>Kumar: Robbins and Cotran Pathologic Basis of Disease, Professional Edition , 8th ed. 2009 </li></ul>
  40. 42. Treatment of preeclampsia <ul><li>Ultimate therapy for preeclampsia/ eclampsia: delivery of the baby </li></ul><ul><li>Development of HTN is related to placental hyperperfusion  placental response to hypoperfusion  Not directly related to BP  Rx of BP will not prevent sequalae of preeclampsia/eclampsia! </li></ul>
  41. 43. <ul><li>Management plan for patients with mild preeclampsia </li></ul><ul><li>Gabbe: Obstetrics: Normal and Problem Pregnancies, 5th ed. 2007 </li></ul>
  42. 44. <ul><li>Management plan for patients with severe preeclampsia </li></ul><ul><li>Gabbe: Obstetrics: Normal and Problem Pregnancies, 5th ed. 2007 </li></ul>
  43. 45. <ul><li>MgSO4 prevents seizure </li></ul><ul><ul><li>Alter membrane permeability  ↑ seizure threshold </li></ul></ul><ul><ul><li>P’t with sev. preeclampsia should be Rx with MgSO4 during labor ~ 24hrs after delivery (majority of seizures occur during this period) </li></ul></ul><ul><ul><li>MgSO4 may also ↓ BP (transient) </li></ul></ul><ul><ul><li>MgSO4 (2g) x 2 Amps + D5W 1 Amp IV push slowly > 15' (Loading Dose) </li></ul></ul><ul><ul><li>MgSO4 (2g) x 5 Amps + D5W 400ml IVD (maintain dose) 60 cc/hr (1.2g/hr) </li></ul></ul><ul><ul><li>Check BP and DTR Q4H </li></ul></ul>
  44. 46. <ul><li>Narrow safety range, beware of intoxication </li></ul><ul><ul><li>Monitor p’t DTR, RR, and blood Mg level </li></ul></ul><ul><ul><li>Use Ca gluconate in case of intoxication </li></ul></ul><ul><li>Valium (Phenytoin) 10~15 mg/kg IV slow push may also be used </li></ul><ul><ul><li>May cause fetal acidosis & low Apgar score </li></ul></ul>Mg response 1~2 mg/dl Normal range during pregnancy 4~8 mg/dl Therapeutic range 9~12 mg/dl DTR gone 15~17 mg/dl Respiratory depression 30~35 mg/dl Cardiac arrest
  45. 47. <ul><li>Preeclampsia + seizure = eclampsia </li></ul><ul><li>Usually grand mal, generalized tonic-clonic seizure </li></ul><ul><li>大部分 postpartum eclampsia 發生在產後 24hrs 內 </li></ul>
  46. 48. <ul><li>New-onset proteinuria ≥ 300 mg/24 hrs in HTN women but no proteinuria before GA 20wks </li></ul><ul><li>sudden ↑ proteinuria or BP or platelet count < 100,000/mm 3 in women with HTN & proteinuria before GA 20wks </li></ul>
  47. 49. <ul><li>Most p’ts w/ severe preeclampsia will require BP Rx for at least 6 wks </li></ul><ul><li>Ask about reproductive & breastfeeding plans </li></ul><ul><li>P’t w/ preeclampsia Hx have ↑ risk of </li></ul><ul><ul><li>x2 risk of developing HTN </li></ul></ul><ul><ul><li>x2~5 risk of ischemic stroke </li></ul></ul><ul><ul><li>May also have ↑ risk of CAD </li></ul></ul>
  48. 50. 徐小姐 <ul><li>29 y/o woman </li></ul><ul><li>G1P0, GA33wks </li></ul><ul><li>No HTN noted on previous checkups </li></ul><ul><li>BP 142/100 found on routine checkup </li></ul><ul><li>Dipstick: 1+ proteinuria </li></ul>Preeclampsia 徐小姐 你血壓有點高喔…
  49. 51. 本院作法 : 收入院 indication <ul><li>在門診用口服藥物血壓仍控制不佳 </li></ul><ul><li>出現 severe preeclampsia  收入院打 MgSO4 </li></ul><ul><li>可能需要 termination or 催生 ( 先收進來打 betamethasone) </li></ul><ul><li>Fetal compromise (e.g. IUGR, oligohydramnios, S/D ratio >3, biophysical profile 不好 , non-reassuring FHB )  收進來 fetal monitoring </li></ul>
  50. 52. Rx of HTN during breastfeeding Part 5
  51. 53. <ul><li>Hemodynamics return to normal within 3~5 wks of delivery </li></ul><ul><li>If BP still ↑ 3~5days after delivery  Rx should be continued/initiated </li></ul>
  52. 54. Drugs often prescribed during lactation
  53. 55. Take Home Messages
  54. 56. In the pregnant patient… <ul><li>Regular screening for HTN is needed </li></ul><ul><li>Rx is aimed at avoiding intracranial hemorrhage & stroke ( BP: 160/110mmHg ) </li></ul><ul><li>First-line agents: L-methyldopa (Aldomet), Labetalol (Trandate), Nifedipine (Adalat), Apresolin (Aprezin) </li></ul><ul><li>Development of preeclampsia may affect risk of developing HTN, stroke, and CAD </li></ul><ul><li>Only cure for preeclampsia: delivery! </li></ul>
  55. 57. Thank You <ul><li>References </li></ul><ul><li>Hypertension in Pregnancy & Women of Childbearing Age Am J Med. 2009 Oct;122(10)890-5 </li></ul><ul><li>Hypertensive Disorders of Pregnancy Am Fam Physician. 2008 Jul 1;78(1):93-100 </li></ul><ul><li>Hypertensive Pregnancy Disorders - Current Concepts J Clin Hypertens (Greenwich). 2007 Jul;9(7)560-6 </li></ul><ul><li>MedScape website </li></ul><ul><li>Obstetrics and Gynecology at a Glance </li></ul><ul><li>Gabbe: Obstetrics: Normal and Problem Pregnancies, 5th ed. 2007 </li></ul>
  56. 58. Conditions mimicking preeclampsia / eclampsia <ul><li>Similar presentation </li></ul><ul><ul><li>Acute fatty liver of pregnancy </li></ul></ul><ul><ul><li>TTP-HUS </li></ul></ul><ul><ul><li>SLE with flare-up </li></ul></ul>
  57. 59. <ul><ul><li>Autosomal recessive inheritance </li></ul></ul><ul><ul><li>1/10,000 pregnancies </li></ul></ul><ul><ul><li>Presents in late pregnancy (GA 27~40wks) </li></ul></ul><ul><ul><li>Susp due to fetal 3-hydoxyacyl-coenzyme A dehydrogenase, defect in mitochondrial function </li></ul></ul>Acute fatty liver of pregnancy 1
  58. 60. <ul><li>Presenation </li></ul><ul><ul><li>Progressive fatigue, malaise, anorexia, nausea/vomiting, mid-epigastric or RUQ pain, jaundice </li></ul></ul><ul><ul><li>Mental status change, fever, HTN, proteinuria, severe hyperglycemia, coagulopathy are common </li></ul></ul><ul><li>U/S, CT, MRI  fatty infiltration of liver </li></ul><ul><ul><li>CT diagnostic only in 50% cases </li></ul></ul><ul><ul><li>Biopsy not usually performed </li></ul></ul>
  59. 61. <ul><li>Pentad has significant overlap w/ eclampsia </li></ul><ul><ul><li>Thrombocytopenia </li></ul></ul><ul><ul><li>Migcroangiopathic hemolytic anemia </li></ul></ul><ul><ul><li>Neurologic abnormalities </li></ul></ul><ul><ul><li>Fever </li></ul></ul><ul><ul><li>Renal dysfunction </li></ul></ul><ul><li>Suggestive of TTP-HUS if: Early onset HTN or HELLP before GA20wks </li></ul>Thrombotic thrombocytopenic purpura and Hemolytic uremic syndrome 2
  60. 62. <ul><ul><li>Women with SLE may have underlying HTN, proteinuria & microscopic hematuria </li></ul></ul><ul><ul><li>Flares occur in 25~30% of pregnant women </li></ul></ul><ul><ul><li>Present with thrombocytopenia, ↓ renal function, severe HTN, fever, skin lesions </li></ul></ul><ul><ul><li>Lupus cerebritis occurs seldomly  Sx similar to eclampsia </li></ul></ul><ul><ul><li>May exhibit HELLP lab data </li></ul></ul><ul><ul><li>DDx: ↓ complement levels, antiphospholipid Ab (30~40%) </li></ul></ul>SLE with flare-up 3
  61. 63. <ul><li>P’ts with SLE should receive baseline renal function testing & 24-hr urine test early in pregnancy & if Sx develop </li></ul><ul><li>P’t with early-onset (< 32 wks) severe preeclampsia should be tested for underlying autoimmune Dz (SLE, antiphospholipid syndrome, inherited/acquired thrombophilia) </li></ul>

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