Successfully reported this slideshow.
We use your LinkedIn profile and activity data to personalize ads and to show you more relevant ads. You can change your ad preferences anytime.

prevention of Preeclampsia: An evidence based approach, 2015

3,966 views

Published on

prevention of Preeclampsia: An evidence based approach, 2015

Published in: Health & Medicine
  • DOWNLOAD FULL BOOKS, INTO AVAILABLE FORMAT ......................................................................................................................... ......................................................................................................................... ,DOWNLOAD FULL. PDF EBOOK here { https://tinyurl.com/yyxo9sk7 } ......................................................................................................................... ,DOWNLOAD FULL. EPUB Ebook here { https://tinyurl.com/yyxo9sk7 } ......................................................................................................................... ,DOWNLOAD FULL. doc Ebook here { https://tinyurl.com/yyxo9sk7 } ......................................................................................................................... ,DOWNLOAD FULL. PDF EBOOK here { https://tinyurl.com/yyxo9sk7 } ......................................................................................................................... ,DOWNLOAD FULL. EPUB Ebook here { https://tinyurl.com/yyxo9sk7 } ......................................................................................................................... ,DOWNLOAD FULL. doc Ebook here { https://tinyurl.com/yyxo9sk7 } ......................................................................................................................... ......................................................................................................................... ......................................................................................................................... .............. Browse by Genre Available eBooks ......................................................................................................................... Art, Biography, Business, Chick Lit, Children's, Christian, Classics, Comics, Contemporary, Cookbooks, Crime, Ebooks, Fantasy, Fiction, Graphic Novels, Historical Fiction, History, Horror, Humor And Comedy, Manga, Memoir, Music, Mystery, Non Fiction, Paranormal, Philosophy, Poetry, Psychology, Religion, Romance, Science, Science Fiction, Self Help, Suspense, Spirituality, Sports, Thriller, Travel, Young Adult,
       Reply 
    Are you sure you want to  Yes  No
    Your message goes here
  • DOWNLOAD FULL BOOKS, INTO AVAILABLE FORMAT ......................................................................................................................... ......................................................................................................................... 1.DOWNLOAD FULL. PDF EBOOK here { https://tinyurl.com/y3nhqquc } ......................................................................................................................... 1.DOWNLOAD FULL. EPUB Ebook here { https://tinyurl.com/y3nhqquc } ......................................................................................................................... 1.DOWNLOAD FULL. doc Ebook here { https://tinyurl.com/y3nhqquc } ......................................................................................................................... 1.DOWNLOAD FULL. PDF EBOOK here { https://tinyurl.com/y3nhqquc } ......................................................................................................................... 1.DOWNLOAD FULL. EPUB Ebook here { https://tinyurl.com/y3nhqquc } ......................................................................................................................... 1.DOWNLOAD FULL. doc Ebook here { https://tinyurl.com/y3nhqquc } ......................................................................................................................... ......................................................................................................................... ......................................................................................................................... .............. Browse by Genre Available eBooks ......................................................................................................................... Art, Biography, Business, Chick Lit, Children's, Christian, Classics, Comics, Contemporary, Cookbooks, Crime, Ebooks, Fantasy, Fiction, Graphic Novels, Historical Fiction, History, Horror, Humor And Comedy, Manga, Memoir, Music, Mystery, Non Fiction, Paranormal, Philosophy, Poetry, Psychology, Religion, Romance, Science, Science Fiction, Self Help, Suspense, Spirituality, Sports, Thriller, Travel, Young Adult,
       Reply 
    Are you sure you want to  Yes  No
    Your message goes here
  • Hello! Get Your Professional Job-Winning Resume Here - Check our website! https://vk.cc/818RFv
       Reply 
    Are you sure you want to  Yes  No
    Your message goes here

prevention of Preeclampsia: An evidence based approach, 2015

  1. 1. PREVENTION OF PREECLAMPSIA: An evidence based approach, 2015 Prof Aboubakr Elnashar Benha University Hospital, Egypt AboubakrElnashar
  2. 2. CONTENTS Introduction  Pathogenesis  Types of Prevention  Level of evidence Methods of prevention  Pharmacological  Diet and supplements  Other Recommendation AboubakrElnashar
  3. 3. INTRODUCTION •PE: •Syndrome of new onset of Hypertension and either Proteinuria or End organ dysfunction after 20 w in a previously normotensive woman AboubakrElnashar
  4. 4. Pathogenesis incompletely understood (Barton& Sibai, 2008). Hallmarks Impaired remodeling of uterine spiral arteries placental perfusion trophoblast differentiation& invasion Placental & endothelial dysfunction Immune maladaptation to paternal Ags Exaggerated systemic inflam response. production of antiangiogenic factors AboubakrElnashar
  5. 5. In PE: Impaired trophoblast differentiation& invasion AboubakrElnashar
  6. 6. Placental and endothelial dysfunction AboubakrElnashar
  7. 7. Risk factors Hypertension Reduced renal function Obesity, insulin resistance, diabetes History of PE Maternal genetic or acquired thrombophilias Pathogenesis Differs with various risk factors: PG Vs MG with previous PE preexisting vas dis preexisting DM or multifetal gestation. AboubakrElnashar
  8. 8. Why prevention of PE? There are no validated methods (biomarkers, clinical diagnostic tests, medical history) for prediction of PE. Maternal and perinatal morbidity and mortality: common The only effective treatment: Early delivery: preterm birth in many cases Prevention of PE: significant impact on maternal and infant health AboubakrElnashar
  9. 9. TYPES OF PREVENTION Primary Avoiding occurrence of the disease  Obese: achieve an ideal b wt before conception (Villamor& Cnattingius, 2006) No RCT  Ch hypertension: Control BP before conception. No RCT Pregestational DM: -Complete her family as early as possible& before vascular complications develop -Control DM before conception& throughout pregnancy AboubakrElnashar
  10. 10. Secondary Breaking off the disease process before emergence of obvious clinical disease {Etiology of the disease is unknown} To correct theoretical pathophysiology AboubakrElnashar
  11. 11. Tertiary Prevent complications of the disease close follow up of high risk women early diagnosis of PE followed by appropriate management may prevent some of the dangerous sequelae of the disease, such as eclamptic seizures and multiorgan failure. AboubakrElnashar
  12. 12. METHODS OF PREVENTION I. PHARMACOLOGIC 1. Low dose aspirin 2. Heparin 3. Anti hypertensive 4. Diuretics 5. Progestgen II. DIET & SUPPLEMENTS III. OTHER 1. Bed Rest 2. Life style changes 3. Exercise 4. Wt loss AboubakrElnashar
  13. 13. Cochrane Systematic Review Gold Standard' for high- quality systematic reviews AboubakrElnashar
  14. 14. I. PHARMACOLOGICAL 1. Low dose aspirin Rationale PE: increased platelet turnover increased platelet derived thromboxane levels low dose aspirin diminishes platelet thromboxane A2 synthesis while maintaining vascular wall prostacyclin synthesis: altering the balance in favor of prostacyclin AboubakrElnashar
  15. 15. I. Studies on moderate and high risk women low dose aspirin: effective modest reduction in risk of PE (0-3% in treated vs 12-35% in controls) other adverse pregnancy outcome: PTL, IUGR (by 10-20%). [Dekker et al, 2001].level 2 evidence (Cochrane SR, 2007 ) AboubakrElnashar
  16. 16.  When to start? ≤16 w significant reduction in: PE (RR 0.47, 95% CI 0.360.62; 7.6 vs 17.9%)  severe PE (RR 0.18, 95% CI 0.080.41; 1.5 vs 12.3%) IUGR (RR 0.46; 8.0 vs 17.6%) PTL (RR 0.35, 95% CI 0.220.57; 4.8 vs 13.4%) [Roberge et al, 2013; Meher et al, 2013]. AboubakrElnashar
  17. 17. Rate of reduction PE (RR 0.76, 95% CI 0.620.95; 9.5 vs 11.4%) IUGR (RR 0.80, CI 0.650.99; 7.7 vs 8.6%) PTL (RR 0.86, CI 0.760.98; 21.7 vs 24.4%), but not perinatal mortality [Henderson et al, 2014 United States Preventive Services Task Force (USPSTF) ]. Risk reductions of 10% for PE, IUGR, and PTL Absolute risk reductions for PE: 2-5% IUGR: 1-5% PTL: 2-4% AboubakrElnashar
  18. 18. II. Unselected nulliparous women little or no benefit [Sibai et al, 1993] no effect on incidence of FGR, or length of gestation [Subtil et al, 2003]. 1. Although nulliparity is a risk factor for PE, prevalence rates are relatively low (4%) compared with moderate to high risk groups (8-30%) [Henderson et al, 2014]. 2. Pathogenesis of PE in nulliparous is different from that in women with previous PE or preexisting vascular disease [Sibai et al, 2005]. AboubakrElnashar
  19. 19. III. Studies on women with abnormal uterine artery Doppler (UAD) Abnormal UAD: identified women who are likely to develop PE and IUGR [Subtil et al, 2003]. PE: 6 vs 1% IUGR: 18 vs 8% low dose aspirin of abnormal UAD: Did not reduce the incidence of PE PE occurred in 2% of patients in each group. Did not reduce the incidence of IUGR. AboubakrElnashar
  20. 20. Limitations of this trial: 1. low dose aspirin started late (22 -25 w), after significant pathologic changes had already occurred in the uteroplacental vasculature 2. low rate of PE may have precluded finding a significant reduction in disease. AboubakrElnashar
  21. 21.  low dose aspirin at or before 16 w: reduced the risk of  PE (RR 0.6, 95% CI 0.4–0.8)  Severe PE (RR 0.3, 95% CI 0.1–0.7) [Villa et al, 2013].  Routine Doppler surveillance has not been proven. AboubakrElnashar
  22. 22. Guidelines ACOG, 2013 low dose aspirin not recommended for women at low risk for PE. Recommend in high risk women: women with history of : early onset PE superimposed PE plus delivery at <34 w or PE in >1 pregnancy. AboubakrElnashar
  23. 23. Cochrane SR, 2000 NNT For moderate and high risk women: 59 to 167 to prevent one case of PE 44 to 200 to prevent one PTL 125 to over 10,000 to prevent one perinatal death AboubakrElnashar
  24. 24. NICE, 2010 low dose (75 mg) aspirin for  1 high risk factor for PE chronic hypertension kidney disease diabetes autoimmune disease hypertension in previous pregnancy OR 2 moderate risk factors for PE age ≥40 y first pregnancy multiple gestation >10 y between pregnancies, BMI≥35 kg/m at presentation family history of PE AboubakrElnashar
  25. 25. American College of Chest Physicians, 2012  low dose aspirin starting from 2nd T and continuing throughout pregnancy in women considered to be at risk for PE. American Heart Association, 2014 low dose aspirin from the 12th w until delivery women with chronic primary or secondary hypertension or previous pregnanc y related hypertension AboubakrElnashar
  26. 26. US Preventive Services Task Force (USPSTF) 2014 Low dose aspirin: ≥1 high risk factors absolute risk for PE ≥ 8%. {No validated methods (biomarkers, clinical diagnostic tests, medical history) for identifying women at high risk for PE} 81 mg/d at 12 w Discontinue 5 to 10 days before expected delivery {diminish the risk of bleeding during delivery} [Hirsh et al, 2008} AboubakrElnashar
  27. 27. Management of worsening PE Low dose aspirin little or no benefit in women who already have developed PIH [CLASP study, 1994]. {At this late stage 1. aspirin does not prevent progression to more severe disease 2. ±exacerbate a bleeding diathesis in patients with the HELLP syndrome}. AboubakrElnashar
  28. 28. 2. Heparin Rationale The preeclamptic placenta: features of uteroplacental ischemia increased syncytial knots and intervillous fibrin distal villous hypoplasia, villous infarcts decidual necrosis spiral artery abnormalities including acute atherosis, mural hypertrophy, and luminal thrombosis/fibrous obliteration. AboubakrElnashar
  29. 29. LMWH women with a history of early onset, severe PE: reduce risk of recurrence lower quality evidence [Mello et al, 2005]. AboubakrElnashar
  30. 30. Women with and without thrombophilia with previous late onset, non severe PE and previous mildly SFGA (B wt between 5th and 10th percentile) should not be offered LMWH to prevent recurrent placenta mediated pregnancy complications The best available evidence did not show a clear benefit [Rodger et al, MA, 2014]. LMWH is not recommended for reducing the risk of PE in either the general population or in those with PE in a previous pregnancy. AboubakrElnashar
  31. 31. 3. Antihypertensive drugs Severe hypertension (D≥110 mmHg or S ≥160 mmHg) : reduces the risk of stroke Moderate hypertension (D100 to 109 mmHg or S 150 to 159 mmHg): ±reduce this risk. Mild to moderate hypertension: Halving in the risk of developing severe hypertension No difference in the risk of developing PE or proteinuria (Cochrane SR, 2007) AboubakrElnashar
  32. 32. lowering BP Not reduce the risk of PE or abruption Not improve fetal or pregnancy outcome Not decrease incidence of moderate and severe hypertension. (Cochrane SR 2007) AboubakrElnashar
  33. 33. 4. Diuretics No reduction in the incidence of PE or perinatal mortality May have deleterious effects: reduced renal & placental perfusion. (Cochrane SR, 2007 ) AboubakrElnashar
  34. 34. 5. Progesterone Insufficient evidence for preventing PE (Cochrane SR 2006) progesterone should not be used for this purpose in clinical practice at present. AboubakrElnashar
  35. 35. II. DIET AND SUPPLEMENTS Minerals:  Calcium  Mg  Zn Vit:  C and or E  D  Folic acid  B2  B6  Garlic  Salt restriction  Pr and energy restriction  Vegetables, fruits, and vegetable oils  Fish oil  Nitric acid donors  Antioxidants AboubakrElnashar
  36. 36. Minerals 1. Calcium supplementation RDA: for elemental calcium in USA: 1000 mg/d in pregnant and lactating women 19 to 50 y of age (1300 mg for girls 14 to 18 y); this is the same for lactating and nonlactating women of the same age. AboubakrElnashar
  37. 37. Calcium supplementation (≥ 1 g/d): significant reduction in PE particularly for women with low calcium diets. (Cochrane SR, 214) PTL AboubakrElnashar
  38. 38. Calcium supplementation (1 g/d) halved the risk of  PE (RR 0.45, 95% CI 0.310.65) hypertension (RR 0.65, 95% CI 0.530.81). The reduction in risk ratio was greatest for women at high risk of PE (RR 0.22, 95% CI 0.120.42), those with low baseline calcium intake (RR 0.36, 95% CI 0.200.65). low risk women with adequate dietary calcium intake: no benefit [Hofmeyr et al, 2014]. AboubakrElnashar
  39. 39. WHO Guidelines 2011 1.5–2.0 g elemental calcium/d for pregnant women in areas with low dietary calcium. AboubakrElnashar
  40. 40. Calcium supplementation <1 g daily: Significant reduction in risk of PE but the trials were small and most had a high risk of bias or other methodological limitations (Hofmeyr et al, 2014) In settings of low dietary calcium where high- dose supplementation is not feasible: lower-dose supplements (500 to 600 mg/d) might be considered in preference to no supplementation. (Cochrane SR, 214) AboubakrElnashar
  41. 41. 2. Magnesium Rationale: Mg is beneficial for the prevention& tt of severe PE& E Decreased intracellular Mg in PE 365 mg& 500 mg No effect (Cochrane SR, 2004 ) 3. Zinc Zinc concentrations are reduced in PE RCT: No benefit (Jonsson et al, 1996) AboubakrElnashar
  42. 42. Vitamins 1. C and/ or E Rationale: PET: imbalance of oxidant & antioxidant activity: multi organ endothelial dysfunction AboubakrElnashar
  43. 43. Vit C (1,000 mg/d) and/ or vit E (400 IU/ d) for high risk for PE No prevention slightly increased  gestational hypertension (RR 1.11, 95% CI 1.051.17) LBW infants (RR 1.73, 95% CI) [McCance et al, 2010; CondeAgudelo et al, 2011] Not recommend for prevention or tt of PE. level 2 evidence (Cochrane SR, 2015) AboubakrElnashar
  44. 44. 2. Vitamin D supplements Rationale: Vit D deficiency: increased risk of PE [Bodnar et al, 2007; Robinson et al, 2010, observation study] Vit D supplementation (10 to 15 microg/d [400 to 600 IU/d]) 29% reduction of PE [Haugen et al, observation study,2009; Hyppönen et al, 2014)  No association [Shand et al, Prospective Cohort study. 2010,} The quality of evidence is insufficient (Hyppönen et al, MA, 2014) Pregnant women who do not have regular effective sun exposure should consume 600 IU of vit D daily. AboubakrElnashar
  45. 45. 3. Folic acid Controversial [Wen eta l, 2013]. Regardless, periconceptional folic acid supplementation is recommended to reduce NTD 4. Vit B2 {Deficiency of vit B2 may cause biochemical changes simulating abnormalities of PE} No evidence (Shrama& Mittal, 2006). 5. Vit B6 No enough evidence (Cochrane SR, 2015) AboubakrElnashar
  46. 46. 1. Fish oil Observational studies: beneficial effects (Sørensen et al, 1993) •{inhibition of platelet thromboxane A2 without affecting prostacyclin: shifting the balance toward a reduced platelet aggregation and increased VD}. RCT: No benefit (Olsen et al, 2000; Olsen et al, 2000 ; Villar et al, 2004, RCT, Cochrane SR, 2006]. High doses: increase the risk of PIH (Olafasdottir et al, 2006). Not recommended for the prevention of PE AboubakrElnashar
  47. 47. 2. Nitric oxide donors Rationale Preeclamptic women may be deficient in nitric oxide, which mediates VD and inhibits platelet aggregation Nitric oxide donors: glyceryl trinitrate did not prevent PE (Cochrane SR, 2007). AboubakrElnashar
  48. 48. L arginine Substrate for synthesis of nitric oxide.  Reduction in PE (RR: 0.34, 95% CI: 0.21-0.55)  PTL (RR: 0.48 and 95% CI: 0.28 to 0.81). (Dorniak-Wall et al, MA, 2014) AboubakrElnashar
  49. 49. 3. Antioxidants Rationale PE has been described as a two stage process: 1. reduced placental perfusion followed by 2. release of placental factors: trigger maternal endothelial cell dysfunction [Roberts et al, 1999]. Oxidative stress: endothelial cell dysfunction. Evidence does not support routine antioxidant supplementation to reduce the risk of PE level 2 evidence (Cochrane Library 2008 ) AboubakrElnashar
  50. 50. Diet 1. Garlic Insufficient evidence to recommend for preventing PE (Cochrane Library 2006 ) 2. Dietary sodium restriction No significant differences (Cochrane Library 2005 ) salt consumption during pregnancy should remain a matter of personal preference. AboubakrElnashar
  51. 51. 3. Protein and energy restriction (in obese women) [Cochrane SR, 2005]. 4. High intake of vegetables, fruits, and vegetable oils [Brantsaeter et al, 2009]. AboubakrElnashar
  52. 52. 1.Daily Bed rest Rest (4-6 h/d) for women with normal BP ± reduce risk of PE (level 2 evidence) (Cochrane Library 2006 ) ± reflect bias and/or random error rather than a true effect. Current evidence is insufficient to support recommending rest or reduced activity to women for preventing PE and its complications. Whether women rest during pregnancy should therefore be a matter of personal choice. III. OTHER AboubakrElnashar
  53. 53. Rest for women with hypertension during pregnancy one small trial: reduced risk of severe hypertension and PTL Need to be confirmed in larger trials. Insufficient evidence to provide clear guidance for clinical practice: bed rest should not be recommended routinely for hypertension in pregnancy (Cochrane SR, 2005) AboubakrElnashar
  54. 54. 2. Life-style changes High job stress: greater risk of PE (Sharma& Mittal, 2006) •Reducing job stress may be beneficial in the prevention of PE AboubakrElnashar
  55. 55. 3. Regular prenatal exercise Rationale: (Weissgerber et al, 2004) Stimulation of placental growth Reduction of oxidative stress Reversal of maternal endothelial dysfunction Aerobic exercise= cardiovascular exercise=any sustained rhythmic activity that involves large muscle groups: makes the lungs work harder as the body's need for oxygen is increased. AboubakrElnashar
  56. 56. Aerobic exercise: (of regular Moderate intensity) Insufficient evidence (Cochrane Library 2006) Stretching exercises more effective at reducing the risk of PE than walking (University of North Carolina,2008) protective effect (OR 6.34, 95% CI 0.7255.37,p= 0.09). Insufficient evidence [Kasawara et al, SR, 2012]. AboubakrElnashar
  57. 57. 4. Weight loss Rationale: Maternal obesity: an increased risk of PE Bariatric surgery: significantly reduces the risk of PE [Maggard SR, 2008]. In women with PE: weight loss between pregnancies reduced the risk of recurrent PE [Mostello et al, 2010]. AboubakrElnashar
  58. 58. Smoking Reduced risk for PE (Sibai et al, 2005). {Nicotine inhibition of interleukin-2& tumor necrosis factor Effects of nicotine on angiogenic proteins}. abnormal fetal growth preterm birth Abruption Adverse effects on maternal health. AboubakrElnashar
  59. 59. RECOMMENDATIONS Prevention of PE is important Low dose aspirin Recommended for women at moderate to high risk of developing PE (Grade 2B). Not recommended for women at low risk (Grade 1A). AboubakrElnashar
  60. 60. A modest reduction in the risk of PE, IUGR and PTL 81 mg/d is recommended (Grade 2B), beginning at the end of 1st T. discontinued 5 to 10 days before expected delivery AboubakrElnashar
  61. 61. Routine calcium supplementation above the recommended daily allowance (1000 mg/d) for healthy, nulliparous women is not recommended to prevent PE (Grade 1A). There may be a benefit for PE prevention in high risk populations or in those consuming a low calcium diet. AboubakrElnashar
  62. 62. Vit C and E supplementation is not recommended to prevent PE (Grade 1A) Fish oil is not recommended for preventing PE (Grade 1A). AboubakrElnashar
  63. 63. 250 lectures 3092 members AboubakrElnashar

×