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pre-eclampsia/eclampsia

Hypertension, proteinuria & generalized edema after 20 weeks of gestation. Eclampsia includes the addition of tonic-clonic seizures. [3] Etiology: 1) not clearly understood 2) placental insufficiency is fundamental 3) possible abnormality of fetal side of placental circulation 4) placental neurokinin B may play a role [4] 5) mutant mineralocorticoid receptor may play a role [5] 5) risk factors a) highest risk factors [14,19] - history of preeclampsia - chronic hypertension - connective tissue disease/rheumatologic disease [6] - antiphospholipid antibody syndrome - multigestation (twins) - diabetes mellitus - obesity [19] - chronic renal failure b) moderate risk factors [14] - primigravida - family history of pre-eclampsia - renal insufficiency (serum creatinine > 1.4 mg/dL) [3] c) other risk factors - extremes of child-bearing age - polyhydramnios - erythroblastosis fetalis - hydatidiform mole (1st trimester) - vascular disease - pheochromocytoma d) no strong evidence supports a causal effect of vitamin D status on gestational hypertension or pre-eclampsia [25] Pathology: 1) maternal vascular hyper-reactivity a) may be caused by subclinical endothelial dysfunction unmasked by the cardiovascular stress of pregnancy [21] b) unlike normal pregnant women, those with pre-eclampsia are sensitive to pressor effects of angiotensin II 2) diminished glomerular filtration rate (GFR) 3) possible imbalance in ratio of TxA2 to PGI2 4) vasospasm & thrombosis 5) uteroplacental hypoperfusion 6) disordered endothelin metabolism 7) widespread effects on endothelial cells 8) decreased plasma volume 9) changes in capillary permeability favoring edema 10) renal Na+ retention 11) endotheliosis (renal lesion) a) generalized swelling of glomerular endothelial cells b) glomerular deposition of fibrinogen c) infiltration of lipid-laden macrophages 12) liver injury Genetics: - associated with defects in STOX1 gene (preeclampsia/eclampsia 4) - susceptibility associated with genetic variation in EPHX1 - predisposition associated with fetal inheritance of chromosomally integrated human herpesvirus 6 [30] Clinical manifestations: 1) headache 2) visual disturbances 3) abdominal pain +/- 4) chest pain* 5) dyspnea* 6) new onset hypertension - systolic BP > 140 mm Hg or diastolic BP > 90 mm Hg 7) proteinuria (> 300 mg/24 hr or > 300 mg/g creatinine) 8) rapidly worsening edema 9) development of convulsions defines eclampsia 10) generally occurs after 20th week of gestation* - 44% of cases occur postpartum [3] Diagnostic criteria: - >= 20 weeks of gestation - hypertension - blood pressure >= 140 mm Hg systolic or >= 90 mm Hg diastolic on 2 occasions >= 4 hours apart with previously normal blood pressure OR - blood pressure >= 160 mm Hg systolic or >= 100 mm Hg diastolic (confirmed immediately) AND - proteinuria - 24 hour urine protein >= 300 mg/24 hours OR - urine protein/creatinine ratio >= 300 mg/gram OR - urine dipstick reading of 1+ (urine protein measurement not available) [3] OR, in the absence of proteinuria - new onset hypertension AND - new onset of - thrombocytopenia (platelet count < 100,000/uL) OR - renal insufficiency in the absence of other kidney disease (serum creatinine > 1.1 mg/dL OR a doubling of serum creatinine) OR - liver dysfuction (elevation of serum transaminases to twice the upper limit of normal) OR - pulmonary edema OR - cerebral dysfunction or visual impairment [3] eclampsia includes the addition of seizures Laboratory: 1) more useful in the management of pre-eclampsia than the diagnosis 2) initial evaluation a) complete blood count (decreased platelet count*) b) urinalysis, urine protein: proteinuria (albuminuria) c) 24 hour urine protein > 300 mg/24 hours 1] proteinuria is a sign of disease progression 2] generally warrants hospitalization c) serum transaminases (mild increase in serum ALT, serum AST) d) serum uric acid (generally increased) - levels may correlate with severity of disease e) serum creatinine* f) pulse oximetry* [7] 3) other testing as indicated a) creatinine clearance b) 24 hour urine protein c) 24 hour urine vanillylmandelic acid (VMA) & metanephrines if suspecting pheochromocytoma 4) investigational - serum levels of soluble fms-like tyrosine kinase 1 (sFlt-1) are increased [18] - serum placental growth factor (PlGF) levels are decreased [18,27] Complications: 1) seizures (i.e. eclampsia) 2) HELLP syndrome (4-12%) [3] 3) risk factor for stroke later in life [11] 4) may increase risk for dementia later in life [26] 5) retinal disease later in life a) retinal detachment (RR=2.2) [21] b) non-diabetic retinopathy (RR=2.2-4.6) [21] c) diabetic retinopathy (RR=4.1-9.3) [21] d) risk greatest for severe pre-eclampsia or onset before 34 weeks gestation [21] 6) 2-fold increase in risk of congenital heart defects (16.7 vs 8.6 per 1000 infants) [17] 7) iscreased risk for ischemic heart disease &/or stroke (RR=1.3) in offspring of mothers with pre-eclampsia [32] 8) increased risk for later life chronic kidney disease, especially hypertensive nephropathy [28] & ESRD [29] Management: 1) pharmaceutical agents (diastolic BP > 100 mm Hg) a) methyldopa (drug of choice) b) intravenous labetalol or hydralazine or short-acting nifedipine (drugs of choice for hypertensive crisis) [3] c) diazoxide for hypertension refractory to hydralazine d) MgSO4 to prevent seizures (eclampsia) - intrapartum or post-partum - 4-6 g loading dose - continuous infusion of 2-3 g/hr to maintain serum Mg+2 level of 4-7 meq/L - continue for at least 24 hours after delivery [23] - cautions: - maternal respiratory paralysis - synergistic hypotensive effect with Ca+2 channel blockers - maintain diastolic pressure 90-105 mm Hg, MAP 105-126 - reduces risk of progression to eclampsia (50%) [15] - NNT = 90 for prevention of seizure [15] - may reduce risk of maternal mortality [15] - no benefit for infant [15] - 25% of women report adverse events [15] - flushing is most common adverse effect [15] - NNH = 200 for respiratory depression - NNH = 37 to necessitate C-section [15] e) beta blockers are controversial - labetolol is beta-blocker of choice f) Ca+2 channel blockers are promising g) nitroprusside is a last resort h) prazosin used in pregnant patients with pheochromocytoma i) diuretics are controversial j) peripartum fluid restriction may increase risk of acute renal failure in pregnancy [12] 2) pharmaceutical agents (prophylaxis in high-risk patients) - low dose aspirin 75-150 mg/day initiated at the end of the 1st trimester to inhibit formation of TxA2 - USPSTF recommends aspirin 81 mg/day in high-risk women [12,14] - low-dose aspirin reduces risks for preeclampsia by 24%, intrauterine growth restriction by 20%, & preterm birth by 14% [14] - low-dose aspirin 150 mg/day in high-risk women from 11-14 weeks gestation until 36 weeks gestation lowers risk [22] - discontinuation of aspirin at 24-28 weeks of gestation is noninferior to continuation until term if serum soluble fms-like tyrosine kinase-1 to serum placental growth factor (sFlt-1/PlGF) ratio is normal [33] - calcium supplements may be of benefit [13] 3) delivery of fetus a) progressive pre-eclampsia after 30th week of gestation b) worsening maternal conditions c) laboratory evidence of end-organ dysfunction - platelet count < 100,000/uL - elevated serum ALT, serum AST d) eclampsia e) HELLP syndrome f) deterioration of fetal conditions g) definitive therapy & treatment of choice h) delivery decision should not be based on the extent of proteinuria [11] i) if hypertensive crisis, stabilize blood pressure prior to delivery [3] - intravenous labetalol or hydralazine or short-acting nifedipine (drugs of choice for hypertensive crisis) [3] j) delivery of fetus at 37 weeks gestation optimizes maternal & fetal outcomes [3] 4) bedrest 5) diet: a) 1-2 g of calcium/day suggested, but no data to substantiate - calcium supplementation to prevent pre-eclampsia in populations where calcium intake is low [NGC, WHO] b) supplmental vitamin C or vitamin E to prevent eclampsia to prevent eclampsia is not recommended [11] 6) post delivery - ambulatory BP monitoring - identifies hypertension in more women than office-based measurement - identifies lack of night-time dip in systolic BP 7) screening: - screening with blood-pressure at every prenatal visit [20] Notes: * components of fullPIERS model predicting adverse maternal outcomes (see Clinical manifestations & Laboratory) [7]

Related

HELLP syndrome

Specific

eclampsia

General

pregnancy-induced hypertension; gestational hypertension (PIH) hypertension & proteinuria

Database Correlations

OMIM 189800

References

  1. Saunders Manual of Medical Practice, Rakel (ed), WB Saunders, Philadelphia, 1996, pg 504-506
  2. Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 485
  3. Medical Knowledge Self Assessment Program (MKSAP) 11, 16, 17. 19. American College of Physicians, Philadelphia 1998, 2012, 2015, 2021 - Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022
  4. Journal Watch 20(14):112, 2000 Page et al Excessive placental secretion of neurokinin B during the third trimester causes pre-eclampsia. Nature 405:797, 2000 PMID: 10866201
  5. Journal Watch 20(16):130, 2000 Geller DS et al Activating mineralocorticoid receptor mutation in hypertension exacerbated by pregnancy. Science 289:119, 2000 PMID: 10884226
  6. Journal Watch 24(14):115, 2004 Wolfberg AJ, Lee-Parritz A, Peller AJ, Lieberman ES. Association of rheumatologic disease with preeclampsia. Obstet Gynecol. 2004 Jun;103(6):1190-3. PMID: 15172851
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  15. The NNT: Magnesium Sulfate for Women with Preeclampsia http://www.thennt.com/nnt/magnesium-for-pre-eclampia/ - Duley L et al Magnesium sulphate and other anticonvulsants for women with pre-eclampsia. Cochrane Database Syst Rev. 2010 Nov 10;(11):CD000025 PMID: 21069663
  16. American College of Obsetricians & Gynecologists Hypertension in Pregnancy http://www.acog.org/Resources%20And%20Publications/Task%20Force%20and%20Work%20Group%20Reports/Hypertension%20in%20Pregnancy.aspx
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  20. U.S. Preventive Services Task Force (USPSTF) Draft Recommendation Statement. Preeclampsia: Screening. https://www.uspreventiveservicestaskforce.org/Page/Document/draft-recommendation-statement167/preeclampsia-screening1 - Parikh NI, Gonzalez J Preeclampsia and Hypertension. Courting a Long While: Time to Make It Official JAMA Intern Med. Published online April 25, 2017. PMID: 28444352 http://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2619524 - Sperling JD, Gossett DR Screening for Preeclampsia and the USPSTF Recommendations. JAMA. 2017;317(16):1629-1630 PMID: 28444259 http://jamanetwork.com/journals/jama/fullarticle/2620067 - Henderson JT, Thompson JH, Burda BU et al Preeclampsia Screening. Evidence Report and Systematic Review for the US Preventive Services Task Force. JAMA. 2017;317(16):1668-1683 PMID: 28444285 http://jamanetwork.com/journals/jama/fullarticle/2620094 - Sperling JD, Gossett DR Screening for Preeclampsia and the USPSTF Recommendations. JAMA. 2017;317(16):1629-1630 PMID: 28444259 http://jamanetwork.com/journals/jama/fullarticle/2620067
  21. Barbieri RL After Preeclampsia, Keep an Eye on the Eyes. Physician's First Watch, Dec 23, 2016 David G. Fairchild, MD, MPH, Editor-in-Chief Massachusetts Medical Society http://www.jwatch.org - Auger N, Fraser WD, Paradis G et al. Preeclampsia and long-term risk of maternal retinal disorders. Obstet Gynecol. 2017 Jan;129(1):42-49 PMID: 27926640
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  33. Mendoza M, Bonacina E, Garcia-Manau P et al Aspirin Discontinuation at 24 to 28 Weeks' Gestation in Pregnancies at High Risk of Preterm Preeclampsia. A Randomized Clinical Trial. JAMA. 2023;329(7):542-550 PMID: 36809321 PMCID: PMC9945069 (available on 2023-08-21) https://jamanetwork.com/journals/jama/fullarticle/2801678