 Terminology and classification
 Risk factors
 Etiology
 Pathophysiology
 Prediction and prevention
 Management

 3.7 % of pregnancies
 16% of pregnancy-related deaths
 Eclampsia 1 in 2000 deliveries

 1. Gestational hypertension
 2. Preeclampsia
 3. Eclampsia
 4. Preeclampsia superimposed on chronic hypertension
(superimposed preeclampsia)
 5. Chronic hypertension

 BP >= 140/90 mmHg for first time during pregnancy
 No proteinuria
 BP returns to normal < 12 wk postpartum
 Final diagnosis made only postpartum
 May have other S&S of preeclampsia , eg. epigastric discomfort or thrombocytopenia

 Minimum criteria
 BP >= 140/90 mmHg after 20 wk gestation
 Proteinuria >= 300 mg/24hr or >=1+ dipstick
 Mild preeclampsia
 Severe preeclampsia

 BP >= 160/110 mmHg
 Proteinuria 5 g/24hr or >= 2+ dipstick (persistent)
 Cr > 1.2 mg/dl
 Platelets < 100,000 /mm3
 Microangiopathic hemolysis
 Elevated ALT or AST
 Persistent headache , visual disturbance , epigastric pain

 Seizures that cannot be attributed to other causes in a woman with preeclampsia
 Seizures are generalized
 May appear before , during or after labor
 10% develop after 48 hr postpartum

 New onset proteinuria >= 300mg/24 hr in hypertensive women but no proteinuria before 20 wk
 A sudden increase in proteinuria or BP or platelet count < 100,000 in women with hypertension and proteinuria before 20 wk

 BP >= 140/90 mmHg before pregnancy or diagnosed before 20 wk , not attributable to GTD or
 Hypertension first diagnosed after 20 wk and persistent after 12 wk postpartum

 Also called transient HT
 Final Dx : after delivery , by exclusion
 BP : resting BP , Korotkoff phase V is used to defined diastolic pressure
 GHT may later develop preeclampsia
 10% of eclamptic seizures develop before overt proteinuria is identified
 BP rise , increase both mother and fetus risks

 Described as “pregnancy-specific syndrome of reduced organ perfusion secondary to vasospasm and endothelial activation ”
 Proteinuria & glomerular pathology develop late in the course , pathophysiologic process begin as early as implantation

 Diastolic hypertension >= 95 , increase fetal death rate 3 fold
 Worsening proteinuria resulted in increasing preterm delivery
 Epigastric pain from hepatocellular necrosis , ischemia and edema that stretches Glisson capsule
 Thrombocytopenia from platelet activation & aggregation , microangiopathic hemolysis induced by severe vasospasm

 Hemoglobinemia , Hburia ,
Hyperbilirubinemia : indicative of severe disease
 Cardiac dysfunction , pulm edema , obvious IUGR : indicative of severe disease
 Severity of preeclampsia assess by freq & intensity of abnormalities

 1. Hypertension (>=140/90) is documented antecedent to pregnancy
 2. Hypertension is detected before 20 wk , unless there is GTD
 3. Hypertension persists long after delivery
 Additional previous Hx or family Hx of HT
 End organ damage : LVH , retinal change
 Risk abruption , IUGR , preterm & death

 Essential familial hypertension
 Obesity
 Arterial abnormalities
 Endocrine disorders
 Glomerulonephritis
 Renoprival hypertension
 Connective tissue disease
 PCKD
 ARF

 Nulliparous
 Advanced maternal age
 Race and ethnicity (genetic predisposition
& envoronmental factor)
 Multifetal gestation
 Obesity
 BMI > 35 kg/m 2

 Theory account for the observation : hypertensive disorder more likely to develop in :
 1. exposed to chorionic villi for first time
 2. exposed superabundance of chorionic villi (Twin ,mole)
 3. Preexisting vascular disease
 4. Genetic predisposition

 1. Abnormal trophoblastic invasion of uterine vessels
 2. Immunological intolerance between maternal and fetoplacental tissues
 3. Maternal maladaptation to cardiovascular or inflammatory changes of normal pregnancy
 4. Dietary deficiencies
 5. Genetic influences

 Normal implantation , uterine spiral arteries undergo extensive remodeling as they are invaded by endovascular trophoblasts
 Incomplete invasion (decidual vessels , not myometrial vessels) : preeclampsia

 Endothelial damage
 Insudation of plasma constituents into vessel walls
 Proliferation of myointimal cells
 Medial necrosis
 Lipid accumulation in myointimal cells & macrophages
 Aneurysmal dilatation
 Obstruction of spiral arteriole

 Placental growth factors : regulate vascular endothelial cell and trophoblast function
 Highly expressed in trophoblasts during normal pregnancy
 Significantly decreased in preeclampsia
 Asso with placental bed hypoxia & ischemia (Abnormal placentation)
 J Soc Gyn Investig 2003 : 10 : 178-88

 PP-3 levels slowly increase during pregnancy
 In 1 st trimester , lower than normal were found in IUGR ,preeclampsia
 In 2 nd & 3 rd trimester , higher than normal concentrations were found in preeclampsia , IUGR , preterm delivery
 Used for assess risk to develop placental insuff
 Placenta 2004 : 25 : 608-622

 Acute graft rejection
 Impaired formation of blocking antibodies to placental antigenic sites
 Lack of effective immunization in first pregnancies
 Lower proportion of Th1 , Th2 dominance

 Increased risk for first conception , new partner , conception very shortly after beginning sexual relation (5% if > 12mo)
 Any kind of previous pregnancy
(completed , spontaneous miscarriage or elective abortion) protective against preeclampsia
 Tolerate semi-allogenic graft through father’s alloantigen
 J. of Reprod Immunology 2003 (59) : 93-100



IL10 regulate s arterial pressure in early primate pregnancy
IL-10 & TNF
α
: vasodilation of early pregnancy


Anti-human IL-10 MAb caused significant increase in MAP
TNF-
α alone or combine with IL-10 not alter MAP
 Cytokine 29 (2005) 176-185

 Serum from preeclamptic pt contains IgG autoantibody
 Reacts with AT1 receptor
 AT1-AA induce signaling in vascular cells and trophoblasts
 Including AP-1 and NF-kB activation
 Results in tissue factor production , reactive oxygen species (ROS)generation
 Autoimmunity Reviews 4 (2005) : 61-65

 Placental factors released by ischemic changes
 Decidua activated , release noxious agents provoke endothelial cell injury


Endothelial cell dysfunction
Cytokines : TNF
α
, IL

 Oxidative stress (ROS , free radical) selfpropagating lipid peroxides formation
 Generate highly toxic radicals injure endothelial cells
 Modify NO2 production
 Interfere PG balance

 Oxidative stress : produce lipid-laden macrophage foam cells
 Activation of microvascular coagulation :
Thrombocytopenia
 Increased capillary permeability : proteinuria and edema

 HT : disease of inadequate or aberrant responses to angiogenic growth factors
 Preeclampsia is accompanied by high circulating levels of soluble VEGF receptor-1 (inactive complexes with VEGF + plGF)
 High AGF : contribute to peripheral & pulm edema , microalb , progression of atherosclerosis
 Angiogenesis 7 : 2004 : 193-201

 Platelet activation : hallmark of SPE
 Platelet PGH synthase 1-derived (PGHS1derived) & TxA2
 Low dose aspirin treatment decreased platelet aggregation & prevented thrombosis
 Decrease progesterone during parturition : sustain parturition
 J of Clin Inv , April 2005 : 115 : 986-995

 Phosphatidylserine (PS) 80% /
Phosphatidylcholine (PC) 20%
 Significant elevation in SBP
 Significant increase in TAT levels
 Significant decrease platelet counts
 Significant increase proteinuria
 Significant reduction in fetal & placental weight
 Semin Thromb Hemost. Jun2005 : 31 : 34-20

 Increased ET-1 in amniotic fluid & plasma of infant and mother in preeclampsia
 Asso with abnormal placentation

J Vet Intern Med. 2005 Jul-Aug : 19 : 594-8

 Dietary taboos : meat , protein , purines , fat , dairy products , salt
 Supplement of Zn , Ca , Mg prevent preeclampsia ?
 Fruits & vegetables : antioxidant
 Ascorbic acid intake < 85 mg/d , predispose preeclmapsia 2 fold
 Obesity increase risk preeclampsia

 Hereditary hypertension, preeclampsia , eclampsia
 Polygenic inheritance
 Asso with HLA-DR4
 Maternal Ab against fetal anti HLA-DR Ig
 Heterozygous for angiotensinogen gene variant T235
 Polymorphisms of genes for TNF , IL 1
β ,
Lymphotoxin α

 Familial predisposition
 AGT(encode angiotensinogen) & NOS 3
(encode nitric oxide synthestase) genes mutation
 Clin Genet 2003 : 64 : 96-103

 Analyze IgG Ab against HSV-2 , CMV ,
EBV , Toxoplasma gondii at first ANC
 Seronegative for HSV-2, CMV , EBV increased risk preeclampsia (OR 1.7 ,1.6,
3.5)
 Seronegative for Toxo not associated with increase risk preeclampsia (OR 1.0)
 Acta Obstet Gynecol Scand 2001 : 80 : 1036-8

 Vasospasm
 Endothelial cell activation

Increased pressor resonses

Prostaglandins

Nitric oxide

Endothelins

Angiogenic factors (VEGF , PIGF)

 Increased vascular reactivity to vasopressor
 Decrease PG I
2 production by endothelium
 Increase TxA
2 secretion by platelet
 Increased NO
2 synth by endothelium
 Decrease NO
2 synthease

Comparison of mean ATII infusion doses required to evoke a pressor response

 Endothelial damage
 Interstitial leakage
 Platelet & fibrinogen deposit
 Increase subendothelial a. resistance
 Decreased blood flow
 Ischemia necrosis , hemorrhage
 Multiorgan involvement

 Increase after load
 Preload diminish
 Endothelial activation with extravasation
 Decreased cardiac output
 Hemoconcentration from generalized vasoconstriction and endothelial dysfynction
 Decreased blood volume

 Thrombocytopenia from platelet activation
, aggregation & consumption
 Increased plt activating factor & thrombopoietin
 Clotting factors decrease
 Erythrocytes rapid hemolysis (increase
LDH , schizocyte , MAHA)

 Decrease plasma levels of renin , AT II , aldosterone
 DOC increase
 Vasopressin normal despite decreased plasma osmolality
 ANP increased
 Extracellular fluid : edema : endothelial injury , reduced oncotic pressure

 RPF & GFR reduced
 Uric acid elevated
 Creatinine clearance reduced , oliguria
 Diminished urinary Ca due to increased tubular reabsorption
 Urine sodium elevated
 Urine osmolality , U:P Cr , FE Na : prerenal mechanism

 Proteinuria : glomerulopathy : increased permeability : albumin , Hb , globulin , transferins
 Anatomical changes : glomeruli enlarge , capillary loops dilated & contracted , endothelial cells swollen fibrils deposit
(glomerular capillary endotheliosis)

 Renal tubular lesions : degenerative change , accumulation with casts
 ARF from ATN
 Oliguria , azotemia induced by hypovolemia
 Preeclampsia with ARF occur in HELLP syn rome ½ , placental abruption 1/3
 Rarely , irreversible renal cortical necrosis

 Periportal hemorrhage in liver periphery
 Elevated transaminase
 HELLP syndrome
 Bleeding cause hepatic rupture(mortality
30%) , subcapsular hematoma
 Conservative treatment
 Recombinant factor VIIa

 No strict definition
 Incidence 20% of severe preeclampsia or eclampsia
 Factors contributing to death : include stroke , coagulopathy , ARDS , ARF , sepsis
 Insufficient evidence : adjunctive steroid

 Headache & visual symptoms asso with eclampsia
 Two cerebral pathology related
 1. gross hemorrhage due to ruptured a. caused by severe HT
 2. more widespread , edema hyperemia , ischemia , thrombosis & hemorrhage caused by preeclampsia

 CT : hypodense area in cortex , correspond to petechial hemorrhage and infarctions
 Remarkable changes in area of distribution of posterior cerebral a.
 MRI : hyperperfusion due to vasogenic edema
 Eclampsia : 25% were area of infarction

 Transcranial doppler ultrasonography
 Preeclampsia : increase perfusion pressure , counter by increase cerebrovascular resistance(net no change)
 Eclampsia : loss of autoregulation , hyperperfusion similar to hypertensive encephalopathy
 Eclampsia caused by transient loss of cerebrovascular autoregulation

 Visual disturbance common in SPE
 It follows eclampsia in >10%
 Develop upto 1 wk or more after delivery
 Calle “Amaurosis”
 Extensive ocipital lobe vasogenic edema
 Resolve completely in all case
 Rare cerebral infarct or retinal a. ischemia
 Retinal detach : resolve within 1 wk

 Widespread vasogenic edema
 S&S : Lethargy , confusion , blurred vision
, coma
 Waxed & waned
 Rx : Manitol , Dexamethasone

 Compromised uteroplacental perfusion from vasospasm
 Mean diameter of myometrial spiral arterioles decrease
 Doppler flow velocity of uterine artery
 Ring-like : higher in peripheral than in central vessels
 Preeclampsia was higher resistance

 Biological , biochemical & biophysical markers
 To identify markers of
 faulty placentation
 reduced placental perfusion ,
 endothelial cell activation & dysfunction ,
 activation of coagulation

 28-32 wk
 Abnormally sensitive to infused angiotensin II
 Positive predictive value 33%

 Decreased renal urate excretion in preeclampsia
 Serum uric acid exceeding 5.9 at 24 wk
(PPV 33%)
 Not useful in differentiating GHT from preeclampsia

 Endothelial cell activation
 Low sensitivity 69%
 Positive predictive vaules 12%
 Higher levels by 12 wks (PPV 29% NPV
98%)

 Thrombocytopenia and platelet dysfunction
 Increased destruction cause platelet volumes increase (younger platelet)
 Preeclampsia : PAI-1 increase increased relative to PAI-2 because of endothelial cell dysfunction

 Increased levels of lipid peroxides
 Prooxidants : iron , transferin , ferritin , TG
, FFA , lipoprotein
 Antioxidants : ascorbic acid , vitamin E
 Hyperhomocysteinemia in mid pregnancy risk for atherosclerosis , 3-4 fold risk preeclampsia , influenced by folic acid supplement

 Released by vascular endothelium & leukocytes , and macrophages & lymphocytes at decidua
 Interleukin , TNF
α
, CRP : inflammatory response
 Possibly predictive preeclampsia

 Corticotropin-releasing hormone , hCG ,
Activin A , inhibin A
 Variably elevated depend on duration & severity of preeclampsia
 Overlap with normal pregnancy
 VEGF and PIGF : regulate placental development , both antagonized by sFlt1
 Excessive sFlt1 , PIGF in 1 st trimester : high risk

 Fetal DNA in maternal serum
 At the time endothelial activation , fetal cells released into maternal circulation
 Elevations after 28 wk indicate impending disease

 Impaired trophoblastic invasion of spiral arteries , leading to reduction in uteroplacental blood flow
 8-22 wk , sensitivity 78% , PPV 28% , unreliable in low risk pregnancies
 Combined inhibin A & activin A , sensitivity
86%
 Combined hCG & AFP , sensitivity 2-40%

 hCG in second trimester , > 2.0 MoM
 Sensitivity 23.7%
 Specificity 89.4%
 Relative risk 2.54
 Positive predictive value 9.5%
 Negative predictive value 96.6%
 Endocrine Reviews , April2002 : 23 : 230-257

 Activin A : control trophoblast differentiation in first trimester : high in preeclampsia
 Inhibin A 15-19 wk , > 2.0 MoM
 Sensitivity 48.6%
 Specificity 23.6%
 Activin A more sensitive than inhibin A at
21-25 wk
 Endocrine Reviews , April2002 : 23 : 230-257

 Decrease active renin , AT I & I , aldosterone , activity of ACE in 3 rd trim
 AT II infused test : positive at less than 10 ng/kg
 Ratio inactive urinary kallikrein /urine creatinine at 16-20 wk : lower 5 fold in who developed preeclampsia
 Endocrine Reviews , April2002 : 23 : 230-257

 Salt restriction : ineffective
 Inappropriate diuretic therapy
 Low dietary calcium increased risk GHT
 Fish oil capsules : modify abnormal PG balance : ineffective
 Low dose aspirin (60mg) : ineffective
 Antioxidants : vitamin C & E : reduced endothelial cell activation , reduction in preeclampsia

 Case control study
 Mean milk intake per day in preeclampsia
< control group
 Drinking more than 5 glasses per day has evident protective effect of developing preeclampsia (odd ratio 0.1)
 Eur J of Obs & Gyn & Repro Bio 105 (2002) 11-14

 Reduction in high BP (RR 0.58)
 The effect greater among women at high risk of developing HT and those with low baseline dietary calcium (RR 0.47 & 0.38)
 Reduction risk of preeclampsia (RR 0.35)
 The effect greatest in women at high risk of developing HT and those with low baseline dietary calcium (RR 0.22 & 0.29)
 The Cochrane database of systematic reviews 2002

 Significant benefit in reducing preeclampsia (odds ratio 0.55)
 Baseline risk of preeclampsia in women with abnormal uterine a doppler was 16%
 Obs & Gyn Nov 2001 : 92 : 861-6

 Hx risk : Hx preclampsia ,CHT , DM , renal disease , FH of preeclampsia
 Significant benefit in reducing perinatal death (OR 0.79) & preeclampsia (OR
0.86)
 Reduction in rates of spontaneous preterm birth (OR 0.86)
 Increase of mean birth weight
 No increase risk of placental abruption
 Obs & Gyn ,Jun 2003 : 101 : 1319-32

 19% reduction in risk of preeclampsia (RR
0.81)
 Greater reduction in risk of preeclampsia in aspirin >75 mg/d (RR 0.49 VS RR 0.86)
 7% reduction in risk of preterm delivery
(RR 0.84)
 16% reduction in baby deaths (RR 0.84)
 8% reduction in SGA babies (RR 0.92)
 The Cochrane Database of Systematic Reviews 2003

 For high risk (previous SPE , DM , CHT , renal dis , autoimmune disease) : 27% reduction in risk of preeclampsia
 For mod risk (first preg , mild rise BP no proteinuria , abnormal uterine a doppler, positive roll over test , multiple preg , FH
SPE , teenage) : 15% reduction
 Started before implantation & trophoblast invasion ,crucial time before 16 or 12 wk
 The Cochrane Database of Systematic Reviews 2003

 Either at high risk of preeclampsia or with established preeclampsia
 No difference in risk of stillbirth , neonatal death , perinatal death , preterm birth ,
IUGR & birthweight
 Decrease risk of developing clinical preeclampsia (RR 0.44) using fixed-effect models (no diff using random-effects models)
 The Cochrane Database of systematic Reviews 2005

 Dosage : above recommended dietary intake of 7 mg of alpha-TE (daily 400 iu or
800 iu)
 GA : no difference in risk of stillbirth , preterm birth ,IUGR & preeclampsia between before to 20 wk and both before
& after 20 wk
 No difference side-effect (acne , transient weakness, skin rash)
 The Cochrane Database of systematic Reviews 2005

 No difference in risk of stillbirth , perinatal death, IUGR , birthweight
 Increase risk of preterm birth (RR 1.38)
 Heterogeneity : Decreased preeclampsia
(RR 0.47)
 Dosage : above RDI of 60 mg (500 ,
1000mg)
 GA : no difference before & after 20 wk
 The Cochrane Database of Systematic Reviews 2005

 39% reduction in risk of preeclampsia (RR
0.61)
 Reduced risk of SGA infant (RR 0.64)
 More preterm birth (RR 1.38)
 No difference in develop preeclampsia among low & high risk (RR 0.66 & 0.44)
 GA : no diff (<20wk VS before & after
20wk)
 The Cochrane Database of systematic Reviews 2005

 Reduce dietary salt intake vs continue a normal diet
 No effect in preeclampsia (RR 1.11)
 Insuffient evidence for reliable conclusions about effect of advice to reduce diet salt
 The Cochrane Database of Systematic reviews 2005

 Reduction in risk of preeclampsia in supplemented groups ( 200 ug & 5 mg/d)
 In low serum folate pregnancy & women with Hx preeclampsia
 Odd ratios of preeclampsia no diff between receive folic 200 ug VS 5 mg/d
(0.46 VS 0.59)
 Ped & Perinatal Epid 2005: 19 : 112-124

 Early prenatal detection
 Antepartum hospital management
 Termination of pregnancy
 Antihypertensive drug therapy
 Delayed delivery with SPE

 Early preeclampsia without overt HT : increased surveillance
 New-onset diastolic BP 81-89 mmHg or sudden abnormal wt gain (> 2 lb/wk during
3 rd trimester)
 OPD surveillance unless overt HT , proteinuria , visual disturbances or epigastric discomfort

 Admit if new onset HT , esp persistent or worsening HT or develop proteinuria
 Detail examine : headache , visual disturbances , epigastric pain , wt gain
 Wt , OD
 Proteinuria at least every 2 d
 BP q 4 hr , except midnight & morning
 Cr , Hct , plt , liver enz.

 Evaluate fetal size , AF
 Reduced physical activity
 Sedative not prescribed
 Ample , not excess, protein & calories diet
 Sodium & fluid intake not limit or forced
 Further Mg depend on : severity , GA , condition of Cx

 Delivery is the cure for preeclampsia
 Headache , visual disturbances or epigastric pain : indicative convulsions
 Oliguria : ominous sign
 SPE : objectives to forestall convulsions , prevent intracranial hemorrhage , & serious vital organ damage

 Preterm : conservative justified in mild case , F/U NST or BPP
 Mod or severe preeclampsia : prompt delivery :



IV oxytocin , preinduction withprostaglandin or osmotic dilator , c/s if indicated
 Induction of labor not harmful to infants , but unsuccessful 35%

 To prolong pregnancy , or modify perinatal outcomes
 Labetolol :
 lower mean BP,
 no difference : mean pregnancy prolongation , birthweight , c/s rate

IUGR 2 fold

 RCT :
β blocker (Labetolol) , calcium channel blockers (Nifedipine , Isradipine) no benefit
 Meta-analysis : treatment induced decrease maternal BP , may adversely affect fetal growth
 Prophylactic atenolol decrease incidence preeclampsia

 ACEI should avoid in 2 nd & 3 rd trimester
 Complication : oligohydram , IUGR , bony malformations , limb contractures , persistent PDA , pulm hypoplasia , RDS , prolonged neonatal hypotension , neonatal death
 Early preg taken ACEI : discontinued as soon as possible

 Nicardipine start 3 mg/hr ,titrate , max 3-9 mg/hr
 Target DBP < 100 or < 90 in HELLP syndrome pt
 Median time to obtained target 23 min
 Delivery postponed 4.7 days
 Potential use for second line drug when other antiHT drugs failed
 J. of hypertension : Dec 2005 : 23 : 2319-20

 SPE remote from term
 Conservative or expectant management in selected group
 Sibai 1985 : SPE 18-27 wk : perinatal mortality 87% , no mothers died , placental abruption eclampsia , consumptive coagulopathy , RF , encephalopathy , intracerebral hemorrhage , ruptured hepatic hematoma

 Sibai 1994 : SPE 28-32 wk (exclude
HELLP) : prolonged mean of 15.4 d : sustained 4% placental abruption
 Abramovici 1999 :



 better neonatal outcomes in SPE ,
IUGR not relate to severity of disease ,
IUGR affected survival infants , median elapsed time 0 , 1 , 2 days in HELLP , partial , & SPE

 1. interval very short
 2. GA difference betw SPE & HELLP syndrome relate to timing of onset of disease itself
 3. IUGR prevalent in severe disease , adverse affect infant survival
 4. overlook maternal safety

 Vigil 2003 : bed rest , MgSO4 48 hr , bolus antihypertensive drug , volume expansion
, & Dexa
 Indications for delivery : uncontrollable BP
, fetal distress , placental abruption , renal failure , HELLP synd , persistent symptom
 Average pregnancy prolong 8d
 No maternal deaths , 6 stillbirth , 11 placental abruption , 28 IUGR

 Insufficient data for reliable conclusions on maternal outcome
 For baby : insufficient reliable conclusions on stillbirth or death after delivery (RR
1.50)
 More RDS (RR 2.3) , NEC (RR5.5)
 Less likely to SGA (RR 0.36)
 The Cochrane Database of Systematic Reviews 2002

 Not worsen maternal HT
 Decrease RDS , improve fetal survival
 No evidence : benefit to ameliorate severity of HELLP syndrome
 Transient improve hematological lab : platelet counts
 2 Maternal death , 18 stillbirth

 Preeclampsia complicated by generalized tonic-clonic convulsions
 Fatal coma without convulsions also call
 Major complications included placental abruption (10%) , neuro deficit (7%) , aspiration pneumonia (7%) , pulm edema
(5%) , arrest (4%) , ARF (4%) , death (1%)

 Appear before , during , or after labor
 Most common in last trimester
 Shift in incidence toward postpartum
 Usually begin in facial twitch , entire body rigid , generalized muscle contraction , jaw open & close violently
 Diaphragm fixed , resp halted , then long deep stertorous inhalation

 Duration of coma variable
 Hypercarbia , lactic acidemia , fetal brady cardia
 High fever
 Proteinuria
 Diminished urine output , hemoglobinuria
 Pronounced edema
 Proteinuria & edema disappear within 1 wk
 BP return within a few days to 2 wk PP

 Pulmonary edema from aspiration pneumonitis or heart failure
 Death from massive cerebral hemorrhage
 Hemiplegia from sublethal hemorrhage
 Blindness from retinal detachment or occipital lobe ischemia & edema
 Persistent coma due to uncal herniation
 Rarely eclampsia followed by psychosis

 Differential diagnosis : epilepsy , encephalitis , meningitis , cerebral tumor , cysticercosis , ruptured cerebral aneurysm
 Prognosis always serious
 6% of Maternal death relate to eclampsia
 Among PIH patient , maternal death 16%

 1. control of convulsions using IV MgSO4
 2. Intermittent IV or oral of antihypertensive drug to lower Diastolic
BP <100
 3. Avoidance of diuretics , limit IV fluid adminstration , avoid hyperosmotic agents
 4. Delivery

 4-6 gm MgSO4 dilute in 100 ml fluid , admin over 15-20 min
 Begin 2 g/hr in 100 ml IV maintenance
 Measure Mg level at 4-6 hr , adjust level between 4-7 mEq/L
 MgSO4 discontinued 24 hr after delivery

 Give 4 g MgSO4 IV , rate not exceed 1 g/min
 Follow with 10 g MgSO4 : 5 g injected each buttock through 3 inch long , 20 gauge needle , (add 1 ml of 2% lidocaine)
 If convulsions persist after 15 min , give 2 g more IV slowly
 Give 5 g MgSO4 IM q 4 hr
 MgSO4 discontinue 24 hr after delivery

 Effective anticonvulsant without producing
CNS depression in either mother or infant
 Not given to treat HT
 Exert specific on cerebral cortex
 10-15% after MgSO4 : subsequent convulsion
 Sodium amobarbital & thiopental , if excessive agitate in postconvulsion state
 In Eclampsia , admin for 24 hr after onset of convulsion

 Almost totally cleared by renal excretion
 Monitor urine output , DTR , RR
 Maintained level 4-7 mEq/L
 IM & IV regimen , no significant difference
Mg level
 Mg 10 mEq/L : patellar reflex disappear
 > 10 mEq/L : respiratory depression
 > 12 mEq/L : respiratory paralysis & arrest
 Cr >1.3 : half dose MgSO4

 Acute cardiovascular effect
 Decrease MAP
 Increase CO 13%
 Decrease SVR
 Transient nausea & flushing
 Persist for only 15 min

 Uterine effects
 Depress myometrial contractility
 Inh calcium entry to myometrial cell
 Dose dependent : at least 8-10 mEq/L
 No uterine effect , when given for prophylaxis eclampsia (oxytocin stimulation of labor , admit to delivery intervals , route of delivery)

 Fetal effects
 Promptly cross placenta
 Neonatal depression occurs only if severe hypermagnesemia at delivery
 Decrease in beat-to-beat variability
 Possible protective effect against cerebral palsy in VLBW infants
 Substantial gross motor dysfunction reduced
 No serious harmful effects

 MgSO4 reduce recurrent sz 50% compared to diazepam , reduce maternal
& perinatal morbidity (not sig)
 Maternal mortality reduced compared to phenytoin (not sig) , less neonatal intubation & NICU admission
 Prevent eclamptic sz superior to phenytoin
 Lower risk placental abruption

 Compared with placebo
 Reduce risk eclampsia (RR 0.41)
 Reduce risk of dying (RR 0.56)
 More Side effect (flushing) (24% VS 5%)
 Reduce risk placental abruption (RR 0.64)
 5% Increase risk c/s
 No difference in stillbirth or neonatal death
(RR 1.04)
 The Cochrane Database of Systematic Reviews 2003

 Compared to phenytoin
 Better Reduce risk of eclampsia (RR 0.05)
 Increase risk c/s (RR 1.21)
 Compared to diazepam
 Too small for any reliable conclusions
 The Cochrane Database of Systematic Reviews 2003

 Compared to Nimodipine
 Lower risk of eclampsia (RR 0.33)
 Increase respiratory problem (RR 3.61)
 Greater need for additional antihypertensive drugs (RR 1.19)
 No difference in morbidity
 The Cochrane Database of Systematic Reviews 2003

 Sz rate in preeclampsia , no sz prophylaxis 3.9% -> reduced to 1.5%
 Mild preeclampsia , estimated risk without prophylaxis 1 in 100 , & not asso with severe maternal morbidity
 Do not given sz prophylaxis in MPE

 Hydralazine suggested if persistent systolic > 160 , or diastolic > 105 mmHg
(NHBPEP2000)
 5-10 mg doses at 15-20 min inervals
 Satisfactory response ante or intrapartum : diastolic 90-100
 Seldom another antihypertensive needed
 FHR deceleration when BP fell to 110/80

 Labetolol : IV
α
1
& nonselective
β
-blocker
 Lower BP more rapidly , associated tachycardia
 NHBPEP(2000) : recommends 20 mg IV bolus , if not effective within 10 min , followed by 40 mg , then 80 mg q 10 min but not exceed 220 mg total dose per episode treated

 Nifedipine 10 mg Oral , repeated in 30 min
, if necessary (NHBPEP 2000)
 Fewer dose required to achieve BP control without increased adverse effects
 Sublingual : potent & rapid : cerebrovascular ischemia , MI , conduction disturbance , death
 Not superior to other hypertensives

 Verapamil IV 5-10 mg/hr
 Nimodipine IV & oral
 Ketanserin IV (selective 5-HT blocker)
 Nitroprusside not recommend unless no response , continuous IV , start 0.25 ug/kg/min , increase to 5 ug/kg/min , fetal cyanide toxicity may occur after 4 hr

 Hydralazine 10-25 mg IM q 4-6 hr
 If HT persists or recur : oral labetolol or thiazide diuretic are given
 Two mechanisms :

1. Underlying chronic hypertension ,

2. Mobilization of edema fluid

 Atypical syndrome in which SPEeclampsia persists despite delivery
 Single or multiple plasma exchange
 Plasma exchange performed in postpartum women with HELLP syndrome
 Very few women : persistent Hypertension
, thrombocytopenia and renal dysfunction due to thrombotic microangiopathy

 Diuretics : deplete intravascular volume , compromise placental perfusion , limited used to pulmonary edema
 Hyperosmotic agents : leaks of agents through capillaries into lungs & brain promote accumulation of edema

 LRS , rate 60 ml to 125 ml/hr
 Unless unusual fluid loss : N/V , diarrhea , excessive blood loss
 Oligria : maternal blood volume constricted
, admin IV fluid more vigorously
 Women with eclampsia already has excessive extracelular fluid

 Plasma volume expansion for treatment of preeclampsia
 Compared colloid with no plasma volume expansion
 Insufficient evidence for any reliable effect
 The Cochrane Database of Systematic Reviews 1999

 Most often do so postpartum
 Aspiration should be exclude
 Majority have cardiac failure
 Decrease plasma oncotic pressure , increase extravascular oncotic pressure , increase capillary permeability , hemoconcentration , reduced CVP , PCWP
 Excessive colloid & cyrstalloid cause pulm edema

 Use of pulmonary artery catheterization
 Reserved for women with severe cardiac disease , renal disease , refractory hypertension , oliguria , pulmonary edema
 Pulmonary edema by more than one mechanism
 If questionable pulmonary edema : furosemide IV , hydralazine IV

 After eclamptic sz , labor often ensues spontaneously or can be induced successfully even in remote from term
 Because lack of normal pregnancy hypervolemia , so less tolerant of blood loss at delivery

 In the past , SAB , EB were avoid
 GA caused by tracheal intubation, sudden
HT ,pulm edema , intracranial hge
 Epidural preferred : no serious maternal or fetal complication , lower MAP , Cardiac output not fall

 More prone to hypertensive complications in future pregnancies
 Earlier diagnosed , greater recurrence
 Diagnose before 30 wk , recur 40%
 Recurrence rate for women with 1 episode of HELLP 5%
 Subsequent preeclampsia , high incidence of preterm , IUGR , placental abruption , c/s delivery

 Multiparous develop preeclampsia , increased risk recur in subsequent pregnancy compared with nulliparas
 Early-onset SPE may have underlying thrombophilias , complicate subsequent pregnancies
 Preeclampsia not cause chronic hypertension