Atypical PET&Eclapmsia DR. SALAH ROSHDY,MD PROFESSOR.OF OBSTETRICS/GYNECOLOGY QASSIM COLLEGE OF MEDICINE Sohag University,Egypt
PRE: History Eclampsia - Preeclampsia Prenatal Care 2200 BC Egypt: pregnant women New concept in the 20th with fits century Eclampsia: Greek word: suddenly, flash 1902: Ballantyne. Pro- 1619: Varardus: first use of word maternity clinic. eclampsia 1910: USA. Nursing visits at 1843: Lever. Proteinuria. Swelling home. and convulsions: Nephritic 1920: Prenatal visits: check toxemia for hypertension, swelling, 1897: Vaquez. Hypertension proteinuria to detect : 1899: Strogonov: treatment, Preeclampsia sedation 1900s: prenatal care, preeclampsia
Maternal Mortality: A Global Tragedy Annually, 585,000 women die of pregnancy related complications Cur rent 99% in developing App roa ch world to Re ~ 1% in developed duc tion countries of Mat ern al Mor talit 3 y
Maternal Death Watch 380 women becomeEvery Minute... pregnant 190 women face unplanned or unwanted pregnancy 110 women experience a pregnancy related complication 40 women have an unsafe abortion 1 woman dies from a pregnancy-related complication 4
Global Causes of Maternal Mortality Hemorrhage 24.8% Infection 14.9% 19.8 24.8 Eclampsia 12.9%7.9 Obstructed Labor 6.9% 14.9 Unsafe Abortion 12.9 12.9% 6.9 12.9 Other Direct Causes 7.9% Indirect Causes 19.8%
Maternal Mortality USA: 15/100,000 live births Mali: 800/100,000 live births Hemorrhage Embolism Preeclampsia Infection
Hypertensive Disorders of Pregnancy 6-8% of all gestations Chronic Hypertension Pregnancy Induced (pre-existing or Hypertension undiagnosed prior to pregnancy)) PIH Preeclampsia (no (PIH with proteinuria) proteinuria) Severe HELLP Preeclampsia Eclampsia Syndrome AFLP
National High Blood Pressure Education ProgramClassification ( NHEP) 2000 1-Gestational hypertension. 2-Preeclampsia (mild, severe) 3-Eclampsia. 4-Superimposed preeclampsia upon chronic hypertension.5-Chronic hypertension with pregnancy.
Risk Factors for Pre-eclampsia Nulliparity Chronic renal disease Maternal age <16 or Antiphospholipid >40yrs syndrome (APLS) Multiple pregnancy Diabetes mellitus Family history of pre- Angiotensin gene T235 eclampsia or eclampsia Chronic (pre-existing) hypertension
PREECLAMPSIA Only occurs in humans Incidence 5 % of pregnancies. 200,000 Moms in USA 6 million World wide Leading cause of death & disability mothers and infants. 70,000 maternal deaths World wide every year Characterized by new onset of proteinuria and hypertension after 20 weeks of pregnancy Cause of Preeclampsia remains unknown.
PREECLAMPSIA No clinically useful screening test Antihypertensive therapy lowers the blood pressure but does not improve the fetal outcome. The only “cure” is delivery of the placenta.
The placenta – perhaps asas a result of ischemia –secretes a factor into thematernal circulationwhichproduces systemicendothelial dysfunction
ENDOTHELIAL DYSFUNCTION LEADS TO : Hypertension - disturbed endothelial control of vascular tone Proteinuria - increased glomerular vascular permeability Coagulopathy – abnormal expression of pro & anti coagulants Liver Dysfunction – ischemia & vasoconstriction
BIOMARKERS OF PLACENTAL DYSFUNCTION sVEGF R1 Soluble Vascular Endothelial Growth Factor Receptor 1 Also known as soluble fms-like tyrosine kinase 1 (sFlt-1) Anti-angiogenic protein Elevated in preeclampsia
BIOMARKERS OF PLACENTALDYSFUNCTION PlGF Placental Growth Factor Angiogenic protein, promotes angiogenesis Binds to VEGF Receptor (VEGF R1 and sVEGF R1) Free PlGF is reduced in preeclampsia
Normal Pregnancy Preeclampsia sVEGF R1PlGF sVEGF R1 PlGF Healthy endothelial cell Endothelial cell injury •Maintains vascular tone •Hypertension •Maintains glomerular filtration •Proteinuria •Maintains blood-brain barrier •Cerebral edema •Maintains anti-coagulant state •Coagulation/liver function abnormalities Anti-angiogenic state: anti↑ / pro↓
The Constant PathophysiologicalChanges Is Vascular endothelial: Damage +Dysfunction + Spasm
Possible mechanisms in Preeclampsia Friedman and Lindheimer,1999
Severe pre-eclampsia: symptoms, signs & diagnosticriteriaHeadachesVisual DisturbancesPulmonary OedemaHepatic DysfunctionRUQ or Epigastric PainOliguriaElevated CreatinineProteinuria of 5 g or more in 24 hrsSystolic BP > 160 to 180 mm HgDiastolic BP > 110 mm HgThrombocytopaenia or haemolysis
Clinical Course of Neglected Severe Pre-eclampsia CNSEyes SeizuresArteriolar Spasm Intracranial HaemorrhageRetinal Haemorrhage CVAPapilloedema EncephalopathyTransient Scotomata PancreasRespiratory System Ischaemic PancreatitisPulmonary OedemaARDS Kidneys Acute Renal FailureLiverSubcapsular Haemorrhage Uteroplacental CirculationHepatic Rupture IUGR AbruptionHaematopoietic System Fetal CompromiseHELLP Syndrome Fetal DemiseDIC
Case 1 A 20-year-old primigravida was hospitalized at 37 weeks with regular contractions. She had had irregular antenatal visits, which revealed no abnormality. She had a blood pressure (BP) between 130/80 and 100/60 mmHg on admission. Laboratory findings were unremarkable , with a trace of proteinuria in the urinalysis. She had no prodromes suggestive of hypertensive disease. She delivered a healthy female baby vaginally a few hours later, uneventfully.
Case 1 At 4 h after delivery, she developed a generalized convulsion, lasting 23 min, despite being normotensive,and soon after this she had two other seizures. MgSO4 was given . Following the seizures, her BP ranged between 140/90 and 100/60 mmHg . Slight increases in the liver function tests and LDH values and slight decreases in hemoglobin and platelets were detected .
Case 1 Computed tomography (CT) was completely normal. Subsequently, she had three more seizures and another 2-g bolus of MgSO4 was infused over 35 min and continued for the following 24 h, during which she suffered no further convulsion. The next day, a 24 h urine sample revealed 330 mg proteinuria; cranial magnetic resonance imaging (MRI) showed no abnormality.
Case 2 A 20-year-old nulligravida was admitted with regular contractions at 37 weeks gestation. All her prenatal visits had been normal, including BP, which was recorded as 120/80 to 110/70 mmHg. There was no prodrome of hypertensive disease and no laboratory abnormality, including platelet count, liver enzymes, LDH, electrolytes, and glucose, although proteinuria (3+) on dipstick was noticed on admission.
Case 2 She delivered a 2800-g male fetus vaginally, uneventfully. Following the delivery, her BP increased suddenly to 150/100 to 140/100 mmHg. Then, she had a generalized seizure lasting 5-10 s. Then, 2 h later, she developed sudden blindness, an occipital headache, and myoclonic seizures, particularly involving the right upper extremity.
Case 2 The postictal BP was around 160/120 mmHg. MgSO4 was given for 24 h as the patient seemed to have atypical eclampsia. She had no seizure subsequently. Her BP remained high for a few days, ranging between 150/100 and 140/90 mmHg and normalized on postpartum day 3, with 930 mg/dL proteinuria in the 24 h urine collected postpartum. Cranial MRI was unremarkable.
Case 3 A 31-year-old multipara presented with contractions at 33 weeks gestation with the cervix 2 cm dilated and 40% effaced. Her BP was 110/70 to 110/60 mmHg on admission. Her CBC,routine biochemical tests, and coagulation studies were normal, but she had a dipstick proteinuria of 3+.
Case 3 On admission, the intrapartum fetal heart rate recording revealed poor variability and late decelerations. An emergency Cesarean delivery was performed for fetal distress and a male fetus weighing 1900 g was delivered with APGAR scores of 4 and 6 at 1 and 5 min, respectively. The baby was admitted to the intensive care unit for respiratory distress syndrome
Case 3 The placenta was atrophic, but not abrupted. Then, 2 h postoperatively, the mother became hypertensive, with a BP of 160/100 to 150/100 mmHg, a severe headache and visual blurring. A MgSO4 infusion was started with a loading dose over 20 minutes, followed by a maintenance dose of 2 g/h as a continuous intravenous infusion for 24 h. Three days later, she became normotensive and her complaints resolved.
Atypical preeclampsiaGestational hypertension plus 1 of the following items: Gestational proteinuria Symptoms of preeclampsia plus 1 of the following items: Hemolysis Symptoms of preeclampsia Hemolysis Thrombocytopenia ( Thrombocytopenia 100,000/mm3) Elevated liver enzymes Early signs and symptoms of Elevated liver enzymes (2 times preeclampsia-eclampsia at 20 the upper limit of the normal weeks of gestation value for Late postpartum preeclampsia- aspartate aminotransferase or eclampsia ( 48 hours after alanine aminotransferase) delivery)
Signs and symptoms Right upper quadrant painSigns and pain Epigastric symptoms results consistent with Retrosternalpreeclampsia chest pain Nausea and vomiting Shortness of breath/congestive heart failure Headaches (not responsive to analgesics) Visual changes Altered mental status Bleeding from mucosal membranes Jaundice
laboratory test results consistentwith preeclampsia Persistent proteinuria( 300 mg/24 h) Platelet count ( 100,000/mm3) Liver enzymes (aspartate aminotransferase or alanine aminotransferase) 2 times the upper limit of normal Serum creatinine ( 1.2 mg/dL) Lactic dehydrogenase 2 times the upper limit of normal
Hypertension in Pregnancy Chronic GestationalClinical Findings Hypertension Hypertension PreeclampsiaOnset < 20 weeks Third ≥ 20 weeks trimesterDegree Mild or severe Mild Mild or severeProteinuria Absent Absent Usually presentUric acid > 5.5 mg/dl Rare Absent Usually presentHemoconcentration Absent Absent Severe diseaseThrombocytopenia Absent Absent Severe diseaseHepatic dysfunction Absent Absent Severe disease
CLINICAL CHARACTERISTICS AND LABORATORY TESTS USED TO DISCRIMINATEPREECLAMPSIA FROM CHRONIC HYPERTENSION PREECLAMPSIA CHRONIC HYPERTENSIONAge Extremes of age Older (≥30 years)Parity Nulliparous Often multiparousTime of diagnosis of After 20 weeks Before 20 weekshypertensionMaternal risk factors for Yes NopreeclampsiaHypertension/preeclampsia Yes Yesin prior pregnanciesProteinuria (>300 mg/24hrs) Yes NoSerum uric acid Elevated (≥5.5 mg/dl) Normal to lowElevated liver enzymes Yes NoThrombocytopenia Yes NoHeadache, blurred vision, Yes Noepigastric abdominal painPersistent hypertension No Yes>12 weeks postpartum
ManagementObjective termination of pregnancy with the least possible trauma to mother and fetus birth of an infant who subsequently thrives complete restoration of health to the mother
Termination of pregnancy Delivery is the cure for preeclampsia The prime objectives To forestall convulsion To prevent intracranial hemorrhage To prevent serious damage to vital organs To deliver a healthy infant
Management of pre-eclampsia Sibai et al. Lancet 365:785-99, 2005.
Elective cesarean delivery Labor induction to effect vaginal delivery has traditionally been considered to be in the best interest of the mother Several concerns have led some practitioners to advocate cesarean delivery Unfavorable cervix precluding successful induction of labor Perceived sense of urgency because of the severity of preeclampsia The need to coordinate neonatal intensive care
LONG-TERM IMPLICATIONS FOR WOMEN WITHPREECLAMPSIA Increased incidence of salt-sensitive HTN (Sibai et al, AJOG 1991, Wilson et al, BMJ 2003) Increased risk for cardiovascular mortality (Irgens et al, BMJ 2001, Funai E et al, Epidemiology 2005, Arnadottir et al, BJOG 2005) Increased incidence of chronic renal disease reports of focal sclerosis, increased incidence of renal biopsies, ESRD- Norwegian study – Vikse et al, JASN 2006, NEJM 2008
Why do we need early diagnosis? For rule-in Frequent follow-up with MFM specialist Early measures may help Steroids for fetal maturation Specific interventions are under investigation Aid obstetrician in the decision of when to deliver (emergency delivery is often needed to save both baby and mother) For rule-out Keep baby in utero Eliminate unnecessary intervention Peace of mind for both patient and physician
In conclusion The absence of hypertension or proteinuria should not preclude diagnosing preeclampsia/eclampsia. Eclampsia or fetal distress may be an unusual presenting scenario in atypical cases before the detection of overt hypertension or proteinuria.
In conclusion Even minor clues in diagnoses, such as a marginally elevated BP or trace proteinuria, may be critical for appropriate, timely management. Obstetricians should be aware of atypical presentations,maintain a high level of suspicion, and be ready to take immediate steps.
Conclusion Moreover, valuable time should not be spent conducting detailed investigations. The most common cause of convulsions in association with hypertension or proteinuria during pregnancy or immediately postpartum is eclampsia. However, late postpartum eclampsia is defined as eclampsia that occurs more than 48 h, but less than four weeks, after delivery
Conclusion All patients with atypical-onset eclampsia should undergo a neurological evaluation to rule out the presence of neurologic causes of seizures . Cerebral imaging is indicated for patients with focal neurologic signs, such as hemiparesis, an unconscious state, and prolonged coma.
Conclusion Additionally, cerebral imaging may be helpful in patients who have an atypical presentation of eclampsia (onset before 20 weeks or more than 48 h after delivery, refractory to magnesium sulfate therapy, and recurrent seizures).