Preeclampsia: What s old is new again Gene Chang, MD Maternal Fetal Medicine
Objectives Define Preeclampsia Review current guidelines Role of proteinuria Timing of delivery Seizure prevention Severe Hypertension
Real Disclosure Love-Hate Relationship with the new guidelines Preeclampsia as dichotomous disorder Gestational HTN doesn t get respect Change for sake of change Absence of real world providers
Honors High Pass Pass Marginal Fail A B C D F
Preeclampsia 60 Different names in English/40 in German Preeclampsia (Mild vs Severe) Pregnancy induced hypertension Preclampsia (Mild vs Severe) Gestational Hypertension Preeclampsia (without severe features vs severe) Gestational Hypertension
Pre-eclampsia
Rationale Incidence increasing 50-60,000 deaths worldwide annually In US for every death, 50-100 near-misses Less than optimal care in up to 80% Severe maternal complications Identification of severe preeclampsia Remains difficult Callaghan t al Am J Obstet Gynecol 2008 Kuklina et al. Obstet Gynecol 2009 Van Dillen et al. BJOG 2010
What is preeclampsia? In pregnancy, the onset of drowsy headaches with heaviness is bad Coacae Praenontiones, XXXI, No 523
Preeclampsia Defined Pregnancy Specific Hypertensive disorder Multisystem involvement Variable expression New onset HTN + Proteinuria Proteinuria is/was the critical finding Management based on this finding
Pre-eclampsia HTN +/- Proteinuria Everything Else HTN Proteinuria Edema HTN Proteinuria
Classification Mild Preeclampsia Never Mild Increased mortality Increased morbidity Rapid progression
Classification Mild preeclampsia false sense of security Preeclampsia without severe features Preecampsia with severe features
Classification Mild No Acute Maternal/Fetal Complications Severe Severe Maternal/Fetal Outcomes Term Delivery Baby fine Eclampsia Maternal Death Near term Delivery Prolonged stay Cesarean Complications HTN urgency Term SVD Mom fine Cesarean Section Near term delivery NICU stay Long-term morbidity Previable delivery Perinatal death
Hypertension New-onset HTN in 2 nd trimester BP measurement Seated Arm supported at level of right atrium Left lateral falsely lowers BP
Proteinuria International guidelines typically support 300mg Origin of this number is unclear Upper 95% Confidence limit: 260mg/24h 1 Threshold of 500mg/24hr or PCR 0.5 Possibly better predictor of outcome Relevant for outcome and/or hospitalization 1. Higby et al. Am J Obstet Gynecol 1994
Systematic Review Thangaratinam et al BMC 2009 Systematic Review Proteinuria as predictor for maternal/fetal complications Proteinuria poor predictor
Systematic Review Proteinuria poor predictor of complications Maternal outcomes studied HELLP Syndrome Abruption Eclampsia Small but significant increase in IUFD, SGA, NICU
PIERS Predetermined guidelines for assessment and management Continuous Quality Improvement Project Proteinuria doesn t singly predict adverse outcome JOGC 2011
946 women studied at risk for Preeclampsia Nested case-control study VIP Four groups compared P300 (300-499 mg/24hr) P500 (>500 mg/24h) GHTN CHTN PLoS One 2013
35 30 25 20 15 10 5 * * CHTN GHTN U300 U500 0 Severe HTN IV Meds Elevated Cr ICU Admit
Preeclampsia vs GHTN GHTN Preeclampsia Decision to use MgSO 4 Timing of delivery Gestational HTN may give false sense of security
748 pts with GHTN 24-35 w 46% Progressed to Preeclampsia 9.6% Severe Preeclampsia Barton AJOG 2001
Proteinuria Important but not that important Should not be sole trigger for delivery <34w Reflects what many already do? in patients 34-37w Pt w/controlled BP on Labetalol and 5gm/24hr Pt w/nonsevere HTN and 5gm/24hr
Timing of Delivery
HYPITAT 36-41 weeks gestation Gestational HTN or Mild Preeclampsia Immediate delivery Expectant management Inpt or outpt
HYPITAT Expectant group delivered for: HELLP >5g proteinuria Eclampsia NRFS PROM, MSAF >41w
HYPITAT Primary outcome: composite morbidity Eclampsia HELLP VTE Pulmonary edema Abruption Progression to severe disease
To Mg or not to Mg?
MAGPIE Trial Multicenter international trial 10,141 randomized HTN and 1+ protein
2 frontal/severe ha Epigastric pain Blurred visiion Hyper-reflexia Irrespective of BP or pr oteinuria
MAGPIE NNT for Severe Preeclampsia: 63 NNT for Non-severe preeclampsi:a 91
Management of Severe Hypertension
Severe Hypertension Hydralazine: drug of choice >45 years Onset slow (10-20 minutes) Dose: 5-10 mg q20 mins (max 30 mg) Mom: Tachycardia, Hypotension, HA Neonate: thrombocytopenia, low platelets
Hydralazine: Metanalysis Metanalysis of RCT s 1966-2002 Short acting antihypertensives 21 trials (893 women) 8 with Hydralazine v. Nifedipine 5 with Hydralazine v. Labetalol BMJ 2003
Hydralazine: Metanalysis Hydralazine: Hypotension (13 trials): 3.29 [1.50-7.23] C/S (14 trials): 1.30 [1.08-1.59] Abruption (5 trials): 4.17 [1.19-14.28] Oliguria (3 trials): 2.04 [1.32-3.16] Adverse effect on FHR (12 trials): 2.04 [1.32-3.16] BMJ 2003
Severe Hypertension Labetalol Continuous infusion (1 mg/kg) More commonly IV Bolus Initial bolus not > 20 mg Dose (40, 80, 80, 80) every 15 minutes Max dose 300 mg Onset: 5 min, Peak: 10-20 min, Duration 6 hrs.
Severe Hypertension Nifedipine Oral Ca channel blocker Used for HTN and for tocolysis 10 mg PO q15-30 minutes (max 30 mg) Long Acting Nifedipine? Absorption 70-90 minutes Onset of action 45-90 minutes Consensus: lower BP w/in 30-60 minutes
Labetalol vs. Nifedipine Labetalol Advantages Significant hypotension uncommon No decrease in CO vs. B-blockers Disadvantages Many pts already taking labetalol 1% risk of arrhythmia 10 mg/min don t need telemetry 1 Frontiers in Bioscience 2007
Labetalol vs. Nifedipine Nifedipine Advantages Increases cardiac index 1 Minimal impact on uteroplacental blood flow Higher BP = Higher decrease 2 Selective renal arteriolar dilator 3 Disadvantages Concern over short-acting Nifedipine Risk of Interaction with MgSO4 1. Am J Ob Gyn 1999 2. Am J Med 1985 3. Nephrol Dial Transplant 1988
Labetalol vs. Nifedipine Mg Toxicity requiring Calcium Gluconate 0.5% (n = 162) Am J Ob Gyn 2005
Labetalol vs. Nifedipine Randomized Double Blind trial (50 pts) Nifedipine vs. Labetalol Time to achieve target BP 45 40 35 30 25 20 15 10 5 0 Time to achieve target BP Nifedipine Labetalol Am J Obstet Gynecol 1999
Severe Hypertension 1 st line agents Labetalol Nifedipine Avoid when: Known CV disease Age > 45 or IDDM > 15 years Hydralazine still a consideration
Severe Hypertension Use what you are comfortable with Use what is available
PP Management
PP: NSAIDS
NSAID s and HTN Pope et al Meta-analysis of 54 trials with 123 trial arms 1324 pts mean age 46 (29-62) Mean duration of therapy 15d (1-42) Mean increase in MAP 3.74 mmhg Pope et al. Arch Inter Med 1993
NSAID s and HTN Johnson et al 50 RCT s 771 subjects Mean age 47.6 Duration of treatment at least 1w Map increased 5mmHg Johnson AG et al. Arch Int Med 1994
NSAID s and HTN Sheridan et al 2005 Controlled observational study HTN on NSAID s vs. unexposed 184 users vs. 762 nonusers No significant difference in SBP or DBP
PP: Followup
PP: Followup 0.3% PP visits to ER related to HTN disorders Symptoms precede stroke and preeclampsia Hours to days No knowledge regarding benefit of Rx
Conclusions Pre-eclampsia Multisystem disorder Variable presentation Trust your clinical assessment of patients
Conclusions Proteinuria- important but not important Seizure prevention- clinical decision Timing of delivery- HYPITAT Hypertension- Severe and PP