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Hypertensive Disorders in Pregnancy. รองศาสตราจารย์ นายแพทย์ อติวุทธ กมุทมาศ. Scope. Terminology and classification Risk factors Etiology Pathophysiology Prediction and prevention Management. Incidence. 3.7 % of pregnancies 16% of pregnancy-related deaths Eclampsia 1 in 2000 deliveries.

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hypertensive disorders in pregnancy

Hypertensive Disorders in Pregnancy

รองศาสตราจารย์ นายแพทย์ อติวุทธ กมุทมาศ

scope
Scope
  • Terminology and classification
  • Risk factors
  • Etiology
  • Pathophysiology
  • Prediction and prevention
  • Management
incidence
Incidence
  • 3.7 % of pregnancies
  • 16% of pregnancy-related deaths
  • Eclampsia 1 in 2000 deliveries
classification by the working group of the nhbpep 2000
Classificationby the working group of the NHBPEP (2000)
  • 1. Gestational hypertension
  • 2. Preeclampsia
  • 3. Eclampsia
  • 4. Preeclampsia superimposed on chronic hypertension

(superimposed preeclampsia)

  • 5. Chronic hypertension
gestational hypertension
Gestationalhypertension
  • 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
preeclampsia
Preeclampsia
  • Minimum criteria
  • BP >= 140/90 mmHg after 20 wk gestation
  • Proteinuria >= 300 mg/24hr or >=1+ dipstick
  • Mild preeclampsia
  • Severe preeclampsia
severe 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
eclampsia
Eclampsia
  • 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
superimposed preeclampsia
Superimposed preeclampsia
  • 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
chronic hypertension
Chronichypertension
  • 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
gestational ht
GestationalHT
  • 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
preeclampsia13
Preeclampsia
  • 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
preeclampsia14
Preeclampsia
  • 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
preeclampsia15
Preeclampsia
  • 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
superimposed preeclampsia16
Superimposed preeclampsia
  • 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
underlying causes of cht
Underlying causes of CHT
  • Essential familial hypertension
  • Obesity
  • Arterial abnormalities
  • Endocrine disorders
  • Glomerulonephritis
  • Renoprival hypertension
  • Connective tissue disease
  • PCKD
  • ARF
risk factors for preeclampsia
Risk factorsfor preeclampsia
  • Nulliparous
  • Advanced maternal age
  • Race and ethnicity (genetic predisposition & envoronmental factor)
  • Multifetal gestation
  • Obesity
  • BMI > 35 kg/m2
etiology
Etiology
  • 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
etiology20
Etiology
  • 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
abnormal trophoblastic invasion
Abnormal trophoblastic invasion
  • Normal implantation , uterine spiral arteries undergo extensive remodeling as they are invaded by endovascular trophoblasts
  • Incomplete invasion (decidual vessels , not myometrial vessels) : preeclampsia
atherosis pathology
Atherosis : pathology
  • 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 implications for abnormal placentation
Placental growth factors : implications for abnormal placentation
  • 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
placental protein 13 pp 13
Placental protein 13 (PP-13)
  • PP-3 levels slowly increase during pregnancy
  • In 1st trimester , lower than normal were found in IUGR ,preeclampsia
  • In 2nd & 3rd 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
immunological factors
Immunological factors
  • 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
immunologic factors
Immunologic factors
  • 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
immunological factors28
Immunological factors
  • IL10 regulate s arterial pressure in early primate pregnancy
  • IL-10 & TNFα : 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
immunological factors29
Immunological factors
  • 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
vasculopathy inflammatory
Vasculopathy & inflammatory
  • Placental factors released by ischemic changes
  • Decidua activated , release noxious agents provoke endothelial cell injury
  • Endothelial cell dysfunction
  • Cytokines : TNFα , IL
vasculopathy inflammatory31
Vasculopathy & inflammatory
  • Oxidative stress (ROS , free radical) self-propagating lipid peroxides formation
  • Generate highly toxic radicals injure endothelial cells
  • Modify NO2 production
  • Interfere PG balance
vasculopathy inflammatory32
Vasculopathy & inflammatory
  • Oxidative stress : produce lipid-laden macrophage foam cells
  • Activation of microvascular coagulation : Thrombocytopenia
  • Increased capillary permeability : proteinuria and edema
angiogenic growth factors ht
Angiogenic growth factors & HT
  • 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
prostaglandin
Prostaglandin
  • Platelet activation : hallmark of SPE
  • Platelet PGH synthase 1-derived (PGHS1-derived) & 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
ps pc induce preeclampsia
PS/PC induce preeclampsia
  • 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
endothelin 1
Endothelin-1
  • 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
nutritional factors
Nutritional factors
  • 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
genetic factors
Genetic factors
  • 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 1β , Lymphotoxin α
genetics of preeclampsia
Genetics of preeclampsia
  • Familial predisposition
  • AGT(encode angiotensinogen) & NOS 3 (encode nitric oxide synthestase) genes mutation
  • Clin Genet 2003 : 64 : 96-103
is preeclampsia an infectious disease
Is preeclampsia an infectious disease?
  • 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
pathogenesis
Pathogenesis
  • Vasospasm
  • Endothelial cell activation
    • Increased pressor resonses
    • Prostaglandins
    • Nitric oxide
    • Endothelins
    • Angiogenic factors (VEGF , PIGF)
pathogenesis43
Pathogenesis
  • Increased vascular reactivity to vasopressor
  • Decrease PG I2 production by endothelium
  • Increase TxA2 secretion by platelet
  • Increased NO2 synth by endothelium
  • Decrease NO2 synthease
pathophysiology
Pathophysiology
  • Endothelial damage
  • Interstitial leakage
  • Platelet & fibrinogen deposit
  • Increase subendothelial a. resistance
  • Decreased blood flow
  • Ischemia necrosis , hemorrhage
  • Multiorgan involvement
cardiovascular system
Cardiovascular system
  • Increase after load
  • Preload diminish
  • Endothelial activation with extravasation
  • Decreased cardiac output
  • Hemoconcentration from generalized vasoconstriction and endothelial dysfynction
  • Decreased blood volume
blood and coagulation
Blood and coagulation
  • Thrombocytopenia from platelet activation , aggregation & consumption
  • Increased plt activating factor & thrombopoietin
  • Clotting factors decrease
  • Erythrocytes rapid hemolysis (increase LDH , schizocyte , MAHA)
volume homeostasis
Volume homeostasis
  • 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
kidney
Kidney
  • 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
kidney50
Kidney
  • Proteinuria : glomerulopathy : increased permeability : albumin , Hb , globulin , transferins
  • Anatomical changes : glomeruli enlarge , capillary loops dilated & contracted , endothelial cells swollen fibrils deposit (glomerular capillary endotheliosis)
kidney51
Kidney
  • Renal tubular lesions : degenerative change , accumulation with casts
  • ARF from ATN
  • Oliguria , azotemia induced by hypovolemia
  • Preeclampsia with ARF occur in HELLP syndrome ½ , placental abruption 1/3
  • Rarely , irreversible renal cortical necrosis
liver
Liver
  • Periportal hemorrhage in liver periphery
  • Elevated transaminase
  • HELLP syndrome
  • Bleeding cause hepatic rupture(mortality 30%) , subcapsular hematoma
  • Conservative treatment
  • Recombinant factor VIIa
hellp syndrome
HELLP syndrome
  • No strict definition
  • Incidence 20% of severe preeclampsia or eclampsia
  • Factors contributing to death : include stroke , coagulopathy , ARDS , ARF , sepsis
  • Insufficient evidence : adjunctive steroid
brain
Brain
  • 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 & hemorrhagecaused by preeclampsia
neuroimaging
Neuroimaging
  • 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
cerebral blood flow
Cerebral blood flow
  • 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
blindness
Blindness
  • Visual disturbance common in SPE
  • It follows eclampsia in >10%
  • Develop upto 1 wk or more after delivery
  • Called “Amaurosis”
  • Extensive ocipital lobe vasogenic edema
  • Resolve completely in all case
  • Rare cerebral infarct or retinal a. ischemia
  • Retinal detach : resolve within 1 wk
cerebral edema
Cerebral edema
  • Widespread vasogenic edema
  • S&S : Lethargy , confusion , blurred vision , coma
  • Waxed & waned
  • Rx : Manitol , Dexamethasone
uteroplacental perfusion
Uteroplacental perfusion
  • 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
prediction
Prediction
  • Biological , biochemical & biophysical markers
  • To identify markers of
    • faulty placentation
    • reduced placental perfusion ,
    • endothelial cell activation & dysfunction ,
    • activation of coagulation
roll over test
Roll-over test
  • 28-32 wk
  • Abnormally sensitive to infused angiotensin II
  • Positive predictive value 33%
uric acid
Uric acid
  • Decreased renal urate excretion in preeclampsia
  • Serum uric acid exceeding 5.9 at 24 wk (PPV 33%)
  • Not useful in differentiating GHT from preeclampsia
fibronectin
Fibronectin
  • Endothelial cell activation
  • Low sensitivity 69%
  • Positive predictive vaules 12%
  • Higher levels by 12 wks (PPV 29% NPV 98%)
coagulation activation
Coagulation activation
  • 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
oxidative stress
Oxidative stress
  • 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
cytokines
Cytokines
  • Released by vascular endothelium & leukocytes , and macrophages & lymphocytes at decidua
  • Interleukin , TNF α, CRP : inflammatory response
  • Possibly predictive preeclampsia
placental peptides
Placental peptides
  • 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 1st trimester : high risk
fetal dna
Fetal DNA
  • Fetal DNA in maternal serum
  • At the time endothelial activation , fetal cells released into maternal circulation
  • Elevations after 28 wk indicate impending disease
uterine artery doppler
Uterine artery doppler
  • 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%
slide71
hCG
  • 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
inhibin a and activin a
Inhibin A and Activin A
  • 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
vasoactive
Vasoactive
  • Decrease active renin , AT I & I , aldosterone , activity of ACE in 3rd 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
prevention
Prevention
  • 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
low milk intake risk preeclmpsia
Low milk intake risk preeclmpsia
  • 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
calcium supplement
Calcium supplement
  • 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
aspirin
Aspirin
  • 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
aspirin in historical risk
Aspirin in historical risk
  • 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
antiplatelet prevent preeclampsia
Antiplatelet prevent preeclampsia
  • 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
antiplatelet prevent preeclampsia80
Antiplatelet prevent preeclampsia
  • 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
vitamin e supplement
Vitamin E supplement
  • 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
vitamin e supplement82
Vitamin E supplement
  • 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
vitamin c supplement
Vitamin C supplement
  • 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
antioxidant
Antioxidant
  • 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
dietary salt
Dietary salt
  • 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
folic acid supplement
Folic acid supplement
  • 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
management
Management
  • Early prenatal detection
  • Antepartum hospital management
  • Termination of pregnancy
  • Antihypertensive drug therapy
  • Delayed delivery with SPE
early prenatal detection
Early prenatal detection
  • Early preeclampsia without overt HT : increased surveillance
  • New-onset diastolic BP 81-89 mmHg or sudden abnormal wt gain (> 2 lb/wk during 3rd trimester)
  • OPD surveillance unless overt HT , proteinuria , visual disturbances or epigastric discomfort
antepartum management
Antepartum management
  • 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.
antepartum management90
Antepartum management
  • 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
termination of pregnancy
Termination of pregnancy
  • 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
termination of pregnancy92
Termination of pregnancy
  • 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%
antihypertensive drug
Antihypertensive drug
  • To prolong pregnancy , or modify perinatal outcomes
  • Labetolol :
    • lower mean BP,
    • no difference : mean pregnancy prolongation , birthweight , c/s rate
    • IUGR 2 fold
antihypertensive drug94
Antihypertensive drug
  • 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
antihypertensive drug96
Antihypertensive drug
  • ACEI should avoid in 2nd & 3rd 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
Nicardipine
  • 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
delayed delivery with spe
Delayed delivery with SPE
  • 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
delayed delivery with spe99
Delayed delivery with SPE
  • 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
comment
comment
  • 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
delayed delivery with spe102
Delayed delivery with SPE
  • 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
intervention vs expecntant
Intervention VS Expecntant
  • 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
glucocorticoids
Glucocorticoids
  • 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
eclampsia105
Eclampsia
  • 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%)
eclampsia107
Eclampsia
  • 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
eclampsia108
Eclampsia
  • 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
eclampsia109
Eclampsia
  • 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
eclampsia110
Eclampsia
  • 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%
treatment
treatment
  • 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
continuous iv regimen
Continuous IV regimen
  • 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
intermittent intramuscular
Intermittent intramuscular
  • 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
mgso4
MgSO4
  • 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
mgso4117
MgSO4
  • 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
mgso4118
MgSO4
  • Acute cardiovascular effect
  • Decrease MAP
  • Increase CO 13%
  • Decrease SVR
  • Transient nausea & flushing
  • Persist for only 15 min
mgso4119
MgSO4
  • 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)
mgso4120
MgSO4
  • 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
compared with anticonvulsants
Compared with anticonvulsants
  • 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
mgso4 other anticonvulsant
MgSO4 & other anticonvulsant
  • 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
mgso4 other anticonvulsant123
MgSO4 & other anticonvulsant
  • 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
mgso4 other anticonvulsant124
MgSO4 & other anticonvulsant
  • 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
mgso4125
MgSO4
  • 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
antihypertensive
Antihypertensive
  • 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
antihypertensives
Antihypertensives
  • Labetolol : IV α1& 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
antihypertensives129
Antihypertensives
  • 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
antihypertensives130
Antihypertensives
  • 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
persistent postpartum ht
Persistent postpartum HT
  • 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
persistent postpartum ht132
Persistent postpartum HT
  • Atypical syndrome in which SPE-eclampsia 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 hyperosmotic agents
Diuretics & hyperosmotic agents
  • 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
fluid therapy
Fluid therapy
  • 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 expander
Plasma volume expander
  • 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
pulmonary edema
Pulmonary edema
  • 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
invasive monitoring
Invasive monitoring
  • 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
delivery
Delivery
  • 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
analgesia anesthesia
Analgesia & anesthesia
  • 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
long term consequence
Long-term consequence
  • 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
long term consequence142
Long-term consequence
  • 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