GUIDE- DR.R.PATEL(MD)RMO –DR PARTHA

Complex medical disorders in pregnancy

DISCUSSION OF KEY CAUSES OF MATERNAL MORTALITY DUE TO PREEXISTING AND PREGNANCY SPECIFIC MEDICAL DISEASES.

INTRODUCTION

MATERNAL DEATH

• A FIFTH OF WORLDWIDE MATERNAL DEATH OCCUR IN INDIA.

• INDIAN MMR REDUCED FROM 212/10000 LIVE BIRTHS IN 2007 TO 178 (COMPARED TO 10/10000 IN UK) IN 2012.

• THE FIFTH UN MDG OF MMR 109/10000 NOT REACHED.

• DATA COLLECTED BY RGI SHOW THAT THE MAJORITY OF MATERNAL DEATHS IN INDIA ARE DUE TO “DIRECT”(OR OBSTETRIC) CAUSES PRIMARILY HAEMORRHAGE, HYPERTENSION AAND SEPSIS WITH 16% CLASSIFIED AS “INDIRECT” DUE TO MEDICAL DISEASES THAT ARE PREEXISTING OR OCCURING IN PREGNANCY.

USING THE WHO NEAR-MISS TOOL OVER A 10 YEAR PERIOD, A SINGLE CENTRE IN SOUTH INDIA SHOWED EVEN HIGHER VALUE OF 48.1% OF MATERNAL DEATHS AS DUE TO “INDIRECT” CAUSES

INDIRECT CAUSES OF MATERNAL DEATH SOUTH INDIAINDIRECT CAUSES OF MATERNAL DEATH

n

% of all maternal deaths

Maternal infectious and parasitic diseases(mainly pulm. TB,scrub typhus and malaria

35 16.5

cardiovascular 28 13.2Hepatic disorders 24 11.3hematological 6 2.8neurological 4 1.9respiratory 3 1.4renal 2 0.9Total 102 48.11Additional other maternal diseases classifiable elsewhere

67 31.6

DISORDERS AFFECTING PREGNANCY……………

CARDIAC DISEASES (VALVULAR HEART DISEASES, PREGNANCY WITH PROSTHETIC HEART VALVES, ANTICOAGULATION IN PREGNANCY, PERIPARTUM CARDIOMYOPATHY..)

HEPATIC DISEASES (HEPATITIS E VIRUS INFECTION, HELLP SYNDROME, ACUTE FATTY LIVER OF PREGNANCY, OBSTETRIC CHOLESTASIS..)

PRESCRIBING ( DRUG SAFETY)

CARDIAC DISEASE IN PREGNANCY

CARDIOVASCULAR DISORDERS

about 1% of pregnancies complicated by heart diseases

leading cause of maternal mortalityMortality rate 50% in case pulmonary hypertension

Physiologic adaptation to pregnancy

Increase blood volume on 40 -50 % Increase cardiac output 30-50% Decreased systemic vascular resistance The heart elevated upward and rotated forward

to the left Pulse increase about 10-15 beat/min after 14-20

weeks, palpitation Disturbed rhythm: arrhythmia, premature atrial

contractions, premature ventricalar systole Increase clot factors (VII, VIII, IX, X, fibrinogen) Cardiac output changes during labor and birth Intravascular volume changes just after childbirth

Cardiac hypertrophy

Physiologic adaptation to pregnancy

If cardiac changes are not well tolerated cardiac failure can develop during pregnancy, labour, postpartum

If myocardial disease develops, valvular disease exists or congenital heart defect is present, cardial decompensation is anticipated

Percent change in heart rate, stroke volume, and cardiac output measured in the lateral position throughout pregnancy compared with pregnancy values

Hemodynamic changes post partum

Blood shifting “auto-transfusion” (from the contracting uterus to

the systemic circulation)

Increase in effective blood volume

Substantial increase in LV filling pressure, SV and CO

Clinical deterioration

Blood loss during

delivery-

• HR and CO return to pre-labor values within 1 hour. MAP and SV within 24 hours.• Hemodynamic adaptation persists post partum and return to pre-pregnancy values within 12-24 weeks after delivery.

Increase in venous return(relief of caval compression)

HistoryExercise capacity

Current or past evidence of HFAssociated arrhythmias

Physical exam

Cardiac HemodynamicsSeverity of heart disease, PA pressures

Echo, MRI.

Exercise testingUseful if the history is inadequate to allow assessment of functional capacity

During pregnancyEvaluate once each trimester and whenever there is change in symptoms

Multidisciplinary approach, Fetal Echo

Befo

re c

once

ptio

n

During Labor & DeliveryMultidisciplinary approach (Obstetrician, Cardiologist, Anesthesiologist)

Tailor management to specific needs

CARDIAC DISEASE

1. Rheumatic 80- 90% of Heart Disease in pregnancy

2. Congenital 10-35% of HD in pregnancy

High-risk pregnancy

Pulmonary HTN and Eisenmenger’s syndrome. Symptomatic obstructive cardiac lesions:

■ MS,AS, PS, uncorrected coarctation of the aorta. Marfan’s Syndrome with dilated aortic

root(>45 mm) Systemic ventricular dysfunction with * NYHA class iii-iv * LVEF < 30 % Patients with prosthetic valves. Significant uncorrected Cyanotic Heart

Disease. Aortic dilatation more than 50 mm in aortic

disease associated with bicuspid aortic valve.

Contraindications to Pregnancy

Lesion Maternal death rate

(%)• Severe Pulmonary Hypertension 50• Severe obstructive lesions: AS,PS, HOCM, Coarctation.

17

• Systemic Ventricular Dysfunction, NYHA class III or IV

7

Maternal cardiac disease risk group

Group I (mortality rate 1%)■ Corrected tetralogy Fallot■ Pulmonic/tricuspid disease■ Mitral stenosis■ Patern ductus arteriosus■ Ventricular septal defect■ Atrial septal defect

Group II (mortality rate 5-15%)■ Mitral stenosis with atrial fibrillation■ Uncorrected tetralogy Fallot■ Aortic coarctation (uncomplicated)■ Marfan syndrome with normal aorta

Group III (mortality rate 20-50%)■ Aortic coarctation (complicated)■ Myocardial infarction■ Marfan syndrome with aortic involvement■ Pulmonary hypertension

The indications for Termination of pregnancy: Because of high maternal risks, MTP is indicated in:1.Eisenmenger’s syndrome.2.Marfan’s syndrome with aortic involvement3.Pulmonary hypertension.4.Coarctation of aorta with valvular involvement. •Termination should be done before 12 weeks of pregnancy.

Mitral Stenosis

The pressure gradient across the narrow valve increases secondary to the increased heart rate and blood volume

Left atrial pressure increases, back pressure into the lungs causes breathlessness, swelling in the legs and may lead to atrial arrhythmias.

Stretching of the atrium can also occur causing palpitations and arrhythmia.

MITRAL STENOSIS

90% During pregnancy CO increase obstruction worsens

Asymptomatic pt. symptomatic Symptoms of cardiac decompensations or pulmonary

edema appear as pregnancy progresses in Pt. with severe Mitral stenosis(valve diameter less

than 1 cm2) Atrial fibrillation exacerbate the change so it would be recommended to start pregnant women with moderate or severe MS on beta blockers in the 1st trimester aiming to keep the maternal heart rate at 60-70 beats/min.

Mitral Stenosis

Vaginal delivery can be permitted in most patients with judicious use of fluids and avoidance of supine and lithotomy positions.

Hemodynamic monitoring is recommended (Swan) and should be continued several hours following delivery

Treatment in presence of decompensation

Furosemide –to treat pulmonary edema Beta blockers—to control heart rate Digoxin—who cannot tolerate beta blockers, in AF. Prophylactic LMWH—enlarged left atrium, to

prevent atrial thrombus *** Surgical treatment– in persistent

decompensation or further deterioration. percutaneous balloon mitral valvoplasty if mitral valve is pliable without significant regurgitation.MVR in severely stenotic and calcified valve.

Aortic Stenosis AS lead to obstruction to

left ventricular ejection Mild AS is usually

tolerated Moderate to severe AS is

likely to be associated with symptomatic deterioration during pregnancy

Women with valve area <1.0 should consider valve replacement prior to pregnancy

Aortic Stenosis

Symptoms often develop in the 2nd and 3rd trimester■ Exertional dyspnea■ Chest pain■ Syncope

Fetal effects included■ Intrauterine growth retardation■ Premature delivery■ Reduced birth weight■ Increase in cardiac defects

Marfan Syndrome Autosomal dominant genetic disorder

characterized■ weakness of the connective tissue, ■ resulting in joint deformities, ■ ocular lens dislocation, ■ weakness of aortic wall and root

Mitral valve prolapse (90%) Aortic insufficiency (25%)

risk of aortic dissection and rupturing

Pregnancy in patients with Marfan poses 2 problems■ Cardiovascular complications of the

mother■ Risk of having a child who inherits

Marfan’s syndrome

Cardiovascular problems■ Dilation of the ascending aorta,

may lead to development of aortic regurgitation and heart failure

■ Proximal and distal dissections of the aorta with possible involvement of the coronaries

Marfan’s Syndrome

Management■Vigorous physical activity should be avoided

■Beta blockers (reduces the rate of aortic dilation)

■If substantial dilation/dissection should occur, depending on the stage of pregnancy therapeutic abortion, early delivery or surgical intervention should be considered

Eisenmenger Syndrome

Right-to-left or bidirectional shunting at atrial or ventricular level and combined with elevated pulmonary vascular resistance

High risk of maternal (30-50%) and fetal (50%) morbidity and mortality

Pregnancy is contraindicated (contraception or termination of pregnancy)

Death usually (75%) occurs between the first few days and weeks after delivery, but the cause is unclear

Eisenmenger Syndrome

Patients should be monitored closely for any signs of deterioration

Early elective hospitalization is recommended Activity is strictly limited Hemodynamic monitoring is required Anticoagulant??? Prophylaxis of hypovolemia Oxygen Epidural analgesia

PROSTHETIC VALVES AND PREGNANCY

Anticoagulation

Valve replacement

Mechanical Valves and Anticoagulation during Pregnancy

Heparin may not prevent valve thrombosis: ?how much ?route.

Adequate anticoagulation difficult. Heparin can produce osteoporosis. Warfarin can cause embryopathy. Baby ASA safe + probably beneficial.1-4% mortality in pregnant women with mechanical valve prosthesis, Whatever

the anticoagulation regimen. No Ideal Solution

ANTI-Xa LEVELS for maintenance of effective anticoagulation with LMWHINDICATION FOR THERAPEUTIC LMWH

PEAK anti-Xa LEVEL (4 HRS POST DOSE ) (RECOMMENDED(IU/ML)

VENOUS THROMBOEMBOLISM 0.6-0.9

AORTIC METAL VALVE 0.8-1.0

MITRAL METAL VALVE 1.0-1.2

Warfarin vs. HeparinWarfarin Crosses the placenta. ↑early abortion,

prematurity, and embryopathy when used in 1st trimester (6th–12th weeks).

CNS & Eye abnormalities (2nd & 3rd trimester).

Bleeding in the fetus (especially at delivery)■ Should be stopped

before delivery.

Heparin

Does not cross the placenta No teratogenicity No fetal bleeding

Twice daily SC injection Risk of osteoporosis

■ <2% symptomatic fractures.■ but 30% decrease in bone density.

Risk for thrombocytopenia ↑↑ Risk of thrombosis

“warfarin embryopathy”: Nasal hypoplasia, Bone epiphysis, optic atrophy, blindness, seizures. Overall risk around 5%. Decreases with the use of UFH in the first 3 months

Low-dose ASA

The additional use of low-dose aspirin should be considered, particularly in

Women with high-risk valves. Patients with cyanosis. Patients with intra-cardiac shunts. Women with previous TIAs and/or strokes. And women with atrial fibrillation.

LMWH

Do not cross the placenta. Do not require frequent PTT

monitoring and have a longer half-life than UFH.

Peripartum Cardiomyopathy A form of dilated CMP with LV systolic dysfunction that results in the signs and symptoms of heart failure

Criteria■ Development in last month of pregnancy or the first

5 months after delivery■ Absence of heart disease prior to last month of

pregnancy■ Absence of identifiable cause of heart failure■ LV systolic dysfunction

Etiology is unknown Theories

■ Genetic predisposition■ Autoimmunity■ Viral infection

Peripartum Cardiomyopathy

Associated risk factors:■ Age - over 35■ twin pregnancy■ gestational hypertension■ Multiparity■ African-american race■ use of tocolytic therapy

Mortality rate 25-50%

Peripartum Cardiomyopathy Clinical findings

■ Left ventricular failure Dyspnea Fatigue Edema Enlarged heart Tachycardia arrhythmias

Management■Acute heart failure treatment with O2, ,diuretics,

digoxin and vasodilators (hydralazine is safe)■Because of the increased incidence of

thromboembolic events, anticoagulation therapy is recommended

Pregnancy result in case of Cardiovascular Disorders

miscarriages Preterm labor and birth IUGR Congenital heart lesions (4-16%) Maternal mortality

HEPATIC DISEAES HELLP SYNDROME ACUTE FATTY LIVER OF PREGNANCY OBSTETRIC CHOLESTASIS HEPATITIS E VIRUS INFECTION

HELLP SYNDROMEHEMOLYSIS

ELEVATED LIVER ENZYMES( TRANSAMINASES ARE MILDLY RAISED,AST>70 U/L)

LOW PLATELETS (<100*10^9/L)

HELLP syndromethought to be a severe form of pre-eclamptic liver dysfunction but it can occur in normotensive patients as well.

Majority of patients with HELLP syndrome present in 3rd trimester, but up to 1/4th of these patients can present only in the immediate post-partum period.

Antenatal pre-eclampsia is known to occur in most of these patients with postpartum presentation.Absence of hemolysis; i.e. ELLP syndromeand partial HELLP syndrome are other diagnosesthat can be entertained.Partial HELLP syndrome

elevated liver enzymes (serum aspartateaminotransferase > 40 U/L),low platelets (<150*109/L)with or without evidence of hemolysis.

Severe thrombocytopeniaportends poor prognosis and urgent need formanagement.

Abnormally elevated prothrombin time Signifies an underlying DIC

Haemolytic uremic syndrome and thromboticthrombocytopenic purpuraalbeit uncommon in pregnancy, are

other mimicsof HELLP syndrome.

PrognosisMaternal mortality

0 to 15%.Maternal morbidity

acute renal failure, hepatic infarct, hepatic hematoma, hepatic rupture,

disseminated intravascular coagulation,

post-partum hemorrhage,

Pulmonary edema and rarely liver cell failure.

The mortality in patients with any of these severe complications is higher.There are usually no long term maternal

complications.

Management1. close monitoring2. optimisation of blood pressure3. seizure prophylaxis with MgSO4.4. Delivery

only definitive management.The decision to deliver is to be balanced with fetal maturityurgent delivery

near term (>34 weeks)fetal distressSystemic complications as DICrenal failure etc.

5. delivery be delayed with careful monitoring. Only in a small subset with mild/asymptomatic HELLP syndrome in early pregnancy

6. Steroidsshould be considered only for fetal lung maturity.

7. The route of deliveryusually by Caesarean sectionbut is decided by the Obstetricians on a case-to-case basis.

Acute fatty liver of pregnancy

Rare1 in 7000 to 1 in 20,000 pregnancies

Potentially lethalfor both the mother and fetus, especially if diagnosis is delayed.

Commoner in:primigravidae (although this predilection is notas marked as in pre-eclampsia).

An association withmale fetuses (ratio 3:1)multiple pregnancy (20% of cases).Maternal mortality:10% to 20%

Perinatal mortality:20% to 30%

DiagnosisDD:

HELLP syndrome

Profound hypoglycaemia (70%)Marked hyperuricaemia (which is out of proportion to the other features of preeclampsia (90%)Coagulopathy (90%) in the absence ofthrombocytopenia.

ABOUBAKR ELNASHAR

ManagementExpeditious delivery:

improved prognosis for mother and baby.Multidisciplinary team in an intensive care setting.Coagulopathy and hypoglycaemia

should be treated aggressively before delivery.Large amounts of 50% glucose may be needed to correct the hypoglycaemiafresh frozen plasma and albumin should begiven as necessary.

The best markers of severity:– Prothrombin time– Glucose– Acidosis and raised lactate– Encephalopathy.

Plasmapheresishas been used in some cases.

N-acetylcysteine (NAC)an antioxidant and glutathione precursor,promotes selective inactivation of free radicalslogical tt in hepatic failure

Multiple system failure:ventilation and dialysis.

Clinical features1. Pruritus:SevereLimbs& trunk, particularly the palms &soles2nd 3rdhalh of pregnancy (usually during the T) .2. Insomnia andcommon.3. ±Excoriations

malaise:

No rash.4. LFT:abnormal.5. ± dark urine, anorexia6. Malabsorption of fatsteatorrhoea.

Diagnosisexclusion. 3 steps:By

1.2.a.

History of pruritus without rashAbnormal liver function testsTransaminases:

Moderate (<3fold) elevation(ALT is the most sensitive)b. Alkaline phosphatase:Raised beyond normal pregnancy valuesc. Gamma-glutamyl transpeptidase (ƔGT):Raised in 20%d. Bilirubin:Mild elevation: less commone. Serum total bile acid: IncreasedPrimary bile acids (cholic acid& chenodeoxycholicmay increase 10 to100-fold

acid):

3. Exclusion of other causes ofliver function.a. Liver ultrasound:Gallstones without evidence of obstruction does not exclude a

itching& abnormal

extra-hepaticdiagnosis of OC

Gallstones are common in women with OCb. Viral serology:for hepatitis A, B, C & E, EBV, CMVc. Liver autoantibodies:for pre-existing liver disease:anti-smooth muscle anti body: chronichepatitis

active

anti-mitochondrial antibodies: primary biliarycirrhosis.

Aboubakr Elnashar

Factors affecting:1. Maternal symptoms or transaminase levels:relation.2. Serum maternal bile acids:<40 micromol/I: No increase in fetal risk Risk of fetal complications (PTL, asphyxia, meconium) increased by 1-2% per additional micromol/l of serum bile acids.

No

Management1. Counselling

:Risks to the fetusClose surveillance.2. Liver function tests:Including prothrombin3. Fetal well-being Monitored at frequent CTGUS:Fetal growth Liquor volume

time& bile acids: weekly.

intervals.

umbilical artery Doppler blood-flow

4. Deliveryat 37-38 w, or when fetal lung maturity is evident{decrease perinatal mortality}.Close monitoring during induction&risk of fetal distress}

labour {high

The neonate should receive i.m. vit K

DRUGS

TOPICAL EMOLLIENTS like CALAMINE

VIT K(10 mg ORALLY/DAY) ANTI HISTAMINES URSO DEOXYCHOLIC ACID(UDCA) RIFAMPICIN

HEPATITISE

INFECTION

HEPATITIS E INFECTION CAN BE

64

UNEVENTFUL• In general, hepatitis E is a self-limiting viral infection

followed by recovery. Prolonged viraemia or faecal shedding are unusual and chronic infection does not occur.

• Occasionally, a fulminant form of hepatitis develops, with overall patient population mortality rates ranging between 0.5% - 4.0%. Fulminant hepatitis occurs more frequently in pregnancy and regularly induces a mortality rate of 20% among pregnant women in the 3rd trimester.

Hepatitis E - Clinical Features

Incubation period:

Case-fatality rate:

Illness severity: increases with age

Chronic sequelae: none identified

Average 40 daysRange 15-60 days

Overall, 1%-3%Pregnant women,15%-25%

• Among pregnant women, the case fatality rate is 20%, and this rate increases during the second and third trimesters. Reported causes of death include encephalopathy and disseminated intravascular coagulation. The rate of fulminant hepatic failure in infected pregnant women is high.

HIGHER FATALITIES IN PREGNANT WOMEN

• Liver transplant recipients may be at a greater risk for HEV infection, which can lead to chronic hepatitis. However, if the patient has antibodies against HEV, the risk of reactivation is extremely low

LIVER TRANSPLANT PATIENTS AT RISK

HEPATITIS CAN GO INTO CHRONIC PHASE IN IMMUNOSUPPRESSED.

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