HepatitisHepatitis in Pregnancy in Pregnancy

Summary of physiological changes in the liver during pregnancy

• Increased:• Blood volume and cardiac ouput rise by 35%–50%• Alkaline phosphatase levels rise threefold or fourfold due to placental production• Clotting factor changes create a hypercoagulable state• Decreased:• Gallbladder contractility• Hemoglobin• Uric acid levels• Albumin, total protein, and antithrombin III concentrations• No change:• Liver aminotransferase levels (aspartate aminotransferase,

alanine aminotransferase, gamma-glutamyl transferase)• Bilirubin level• Prothrombin time

The impact of pregnancy on the hepatitis

• The course of most viral infections is not affected by pregnancy

• To made the pathogenetic conditionviral exacerbations and complicated

• The high incidence of severe hepatitis and hepatic coma

Hepatitis on pregnancy

• First trimester– Hyperemesis gravidarum increased– the high incidence of abortion and fetal

malformation– associated with the incidence of Down

syndrome

• Second and third trimesters– a higher incidence of hypertensive disorders in

pregnancy– a higher incidence of postpartum hemorrhage

Characteristics Hepatitis A Hepatitis B Hepatitis C

Virus type RNA DNA RNA

Virus size 27 nm 42 nm 30-60 nm

Incubation period 15 – 50 days 30 – 180 days 30 – 160 days

Transmission Fecal – oral Parentral or body fluid Parentral sporadic

Vertical transmission to fetus

Not observed Common Uncommon

Serologic diagnosisHepatitis A antibody IgM and IgG types

HBs Ag, HBs Ab, IgM, and IgG typesHBe Ag, Ab, Hepatitis B virus DNA

Hepatitis C antibodyRNA by PCR

Maximum infectivity ProdromeProdrome or HBe Ag Positive

HIV co- infected

Carrier state None 5 – 10% 50 – 85%

Acute clinical formsAsymptomatic to

fulminantAsymptomatic to fulminant

Asymptomatic to sever relapsing

Chronic clinical forms None

Chronic persistent hepatitisChronic active hepatitisCirrhosis

Chronic persistent hepatitisChronic active hepatitisCirrhosis

Vertical transmission of hepatitis virus

(Mainly by hepatitis B)

HAVHAV• There is no evidence that HAV causes birth

defects• There is no evidence of maternal-fetal

transmission• In rare circumstances in which the mother

has acute HAV infection at the time of delivery– immune serum globulin may be administered

to the infant• Even under these conditions, the risk of

transmission to the infant seems very small

• Anti-HAV IgG antibodies is not transmitted from infected mothers to newborn infants

HBVHBV• Evidence suggests that transmission of

HBV to infants is common – when mothers have acute infection in the third

trimester – when they are chronic carriers of HBV infection

and have positive results for HBeAg or HBV DNA

• The risk of transmission is highest in mothers who are HBeAg - positive at the time of delivery

• Newborn baby has a 90% likelihood of becoming infected.

• Approximately 25% of infected infants will become chronic carriers.

• The rate of vertical transmission of hepatitis C is less than 5%

• The risk is higher if the mother is co-infected with (HIV)– if she is viremic at the time of delivery

– if her viral DNA load is greater than 1 million copies/ml

– if the time from the rupture of membranes to delivery is more than 6 hours.

HCV

HEVHEV• Transmission occurs intrapartum and

peripartum through close contact of mother and neonate.

• Significant vertical transmission among HEV-RNA positive mothers of up to 50%.

• Among women with symptomatic infection the rate of transmission is up to 100%, with significant perinatal morbidity and mortality.

HGV• Most cases of hepatitis G are transferred

through contaminated blood products. • It is most commonly found among

individuals infected with hepatitis C or HIV. • Perinatal transmission does occur,

however, evidence suggests that it does not cause clinical disease in newborns.

• Currently no therapy is available other than prevention

DiagnosesDiagnoses• Epidemiological history• Clinical manifestations• Laboratory Studies : the most useful tests

– evaluation of urine bilirubin and urobilinogen, total and direct serum bilirubin, ALT and/or AST, alkaline phosphatase, prothrombin time, total protein, albumin, complete blood count, and in severe cases serum ammonia.

– the differential diagnosis with other forms of viral hepatitis requires serologic testing for a virus-specific diagnosis.

• Type of hepatitis during pregnancy

Type of hepatitis during pregnancy

• Acute hepatitis

• Chronic active hepatitis

• Acute severe hepatitis

Differential Diagnosis of Liver Differential Diagnosis of Liver Disease in PregnancyDisease in Pregnancy

SerumTransaminases

Bilirubin Coagulopathy

Histology Other Features

Acute Hepatitis B

>1000 >5 - Hepatocellular necrosis

Potential for perinatal transmission

Acute Fatty Liver

<500 <5 + Fatty infiltration

Coma, renal failure, hypoglycemia

Intrahepatic Cholestasis

<300 <5, mostly direct

- Dilated bile canaliculi

Pruritis, increased bile acids

HELLP >500 <5 + Variable periportal necrosis

HTN, edema, thrombocytopenia

Management of Acute Viral Hepatitis in Pregnancy

Establish type by serologic test

Institute appropriate isolation and precautions

Determine need for contact prophylaxis with scrum globulin

preparation and/or vaccine

Activity: determined by tolerance

Diet: patient preference, parentral if necessary Antiemetics: phenothiazines may be used

Corticostcroids: not indicated

Immunoprophylaxis of infant: if hepatitis B is present

Acute severe hepatitisDiagnostic points

• Severe gastrointestinal symptoms• Rapidly deepening jaundice• Hepatic encephalopathy• Liver function :severely abnormal• Renal failure• Coagulopathy

Guidelines for severe hepatitis

• Protect the liver• Prevention of encephalopathy• Prevention of DIC• Prevention of hepatorenal syndrome

Assure identification of ALL HBsAg positive women and

their infants

Assure all exposed infants receive HBIG and 1st dose of hep.

B vaccine w/in 12 hours of birth

Prevention of

Perinatal Hepatitis B

Transmission

Conduct active surveillance, quality

assurance, and outreach to improve program

Assurecompletion of 3 doses of hepatitis B vaccine and post vaccination testing of exposed infants

Assure that all susceptible household and sexual contacts are vaccinated

Six Responsibilities of Perinatal Hepatitis B Prevention Program

HBVHBV• Taking lamivudine before becoming

pregnant and continuing to take it throughout the pregnancy

• lower rates of transmission of the virus from mother to newborn

• Lower transmission rates have also been seen in pregnant women with a high viral DNA load

HBVHBV• The administration of hyperimmune

globulin and HBV vaccine protects 90% to 95% of infants from HBV infection.

• It is recommended that 0.5 ml, of HBIG be given at birth and that three doses of HBV vaccine be given beginning at birth.

HCV• The mode of delivery does not seem to

influence the rate of transmission from mother to child

• Infection prior to delivery has been shown to occur in as many as 33% of patients

• An elective cesarean section has been suggested for patients co-infected with HIV– reduce maternal-fetal transmission by up to

60%

Gestational DiabetesGestational Diabetes

DefinitionDefinition::• CHO intolerance of variable severity

that begins or is first recognized during pregnancy.

• Applies regardless of whether insulin is used for treatment or the condition persists after pregnancy.

• Does not exclude the possibility that unrecognized glucose intolerance may have antedated the pregnancy.

Diabetes in pregnancy

Pre-existing diabetes Gestational diabetes

Pre-existing diabetesIDDM

(Type1)NIDDM(Type2)

True GDM

Classification of DiabetesClassification of Diabetes

Classification of Diabetes in Classification of Diabetes in Pregnancy Pregnancy

• Class A: Abnormal GTT at

any age or of any duration treated only by diet therapy

• A1 -Diet Controlled

GDM• A2 -Insulin-treated

GDM

Complications of pregnancy in GDM

Maternal:HypoglycemiaInfectionKetoacidosisDeterioration in retinopathy’Increased proteinuria+edemaMiscarriagePolyhydramnioShoulder dystociaPreeclampsiaIncreased caesarean rateFuture type 2 diabetes

Fetal: Congenital abnormalitiesIncreased neonatal and

perinatal mortalityMacrosomiaBirth traumaLate stillbirthNeonatal hypoglycemiaPolycythemiaJaundiceHyperbilirubinemia

RISK FACTORS FOR GDMPrevious diagnosis of GDMA strong FH of type 2 DMPrevious delivery of a macrosomic

infantMember of a high-risk population

(Aboriginal, Hispanic, South Asian, Asian or African descent)

Age 35 yearsObesity (BMI 30 kg/m2)Polycystic ovarian syndrome and / or

hirsutismAcanthosis nigricansCorticosteroid use

Screening-cont:

Women (at low risk) with ALL of the following characteristics need not be screened with a laboratory blood glucose test.

• Less than 25 years of age• Normal body weight with BMI < 25• No first degree relative with DM• Not a member of an ethnic group at increased

risk for type 2 DM: women of Hispanic, African, Native American, South or East Asian or Pacific Islands ancestry

• No hx of abnormal glucose metabolism• No hx of poor obstetric outcome

Screening-cont:Screening-cont:• For women who do not meet the above

criteria, screening should be conducted at 24 -28 wks of gestation with use of a 50 g one hour oral glucose load

• An abnormal one hour screening test with a venous plasma glucose of >140 mg/dL necessitates a full diagnostic 75g three hours oral glucose tolerance test (GTT)

All pregnant women between 24 and 28 weeksIf multiple risk factors are present, assess during

each trimester.

1hPG following 50-g glucose load at any time of day

1hPG10.3

1hPG=7.8-10.2

75-g OGTT. Measure FPG, 1hPG, 2hPG

FPG 5.31hPG10.62hPG 8.9

SCREENING

If 2 values are met or exceeded

If 1 value is met or exceeded

GDM

IGT of pregnancy

SCREENING

Gestational diabetesGestational diabetesDiagnosisDiagnosis

• WHO criteria 1998,

75 gm glucose fasting 2 hr (mmol/L)

Impaired fasting glucose 6.1-6.9 IGT <or =7 and 7.8-11 DM >or = 7 or > or=11.1

Dx of GDM with Use of a 100 Dx of GDM with Use of a 100 gram Oral Glucose Loadgram Oral Glucose Load

ManagementManagement• The goal is to prevent adverse

pregnancy outcomes.• A multidisciplinary approach is used.• Patient is seen every 1-2 wks until 36

wks gestation and then weekly. • Patient is asked to keep an accurate

diary of their blood glucose concentration.

ManagementManagement

The glycemic targets associated with the best pregnancy outcome in GDM are: Preprandial < 5.3 mmol/L 1-hour postprandial < 7.8 mmol/L 2-hour postprandial < 6.7 mmol/L

Women with GDM should carry out frequent fasting and postprandial home blood glucose monitoring in order to achieve glycemic targets.

ManagementManagement

• Blood glucose monitoring• Diet• Exercise

Physical activity should be encouraged

• Insulin• Oral Hypoglycemic

Medications

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Know your blood sugar level Know your blood sugar level & keep it under & keep it under

controlcontrol• You may have to test four times a day:

1. In the morning before eating breakfast, referred to as the Fasting glucose level

2. 1 or 2 hours after breakfast3. 1 or 2 hours after lunch4. 1 or 2 hours after dinner

• You may also have to test your glucose level before you go to bed at night. This is referred to as your nighttime or nocturnal glucose test.

Dietary TherapyDietary Therapy Nutrition therapy is the primary treatment of

GDM, although evidence on the optimal diet is

lacking.

Carbohydrate intake should be distributed over

3 meals and at least 3 snacks (one of which

should be at bedtime).

Hypocaloric diets are not recommended.

Refer to a dietitian

Insulin RegimenInsulin Regimen• Pt should check their fasting glucose and a

1 hour or 2 hour postprandial glucose level after each meal, for a total of four determinations each day.

• If the fasting value is > 95 mg/dL, or 1 hr value > 130-140 mg/dL or 2 hr value > 120 mg/dL, insulin therapy needs to be initiated.

Antepartum TestingAntepartum Testing• First trimester u/s

and a fetal echo to assess congenital cardiac anomalies.

• Second trimester u/s to assess fetal growth.

• Twice weekly testing NSTs and amniotic fluid volume determination beginning at 32 wks gestation to assess fetal well-being.

Delivery • Timing and mode of delivery

individualised• Early delivery may be indicated for:• women with poor glycemic control• pregnancies complicated by fetal

abnormalitiesOtherwise, pregnancies are allowed to

go to term.

Delivery• Most common complication =

shoulder dystocia•31% of neonates weighing >4,000g*

• Data does not support the use of C-section to avoid birth trauma

*13% error rate estimating fetal weight by untrasound

What is a reasonable approach?

Offer elective C-section • Estimated fetal weight >4,500g• Patient history and pelvimetry

• Discuss risks and benefits

No indications to pursue delivery before 40 weeks in patients with

good glycemic control…

*Unless other maternal or fetal indications are present

Delivery

IntrapartumIntrapartum The goal is to maintain normoglycemia

in order to prevent neonatal hypoglycemia.

• Check patient’s glucose q1-2 hours.• Start insulin drip to maintain a glucose

level of between 80 - 110 mg/dL.• Observe infant closely for

hypoglycemia, hypocalcemia, and hyperbilirubinemia after birth.

Postpartum CarePostpartum CareAfter delivery:• Measure blood glucose. -fasting blood glucose concentrations

should be <105 mg/dL and one hour postprandial concentrations should be < 140 mg/dL.

• Administer one half of the pre-delivery dose before starting regular food intake.

Postpartum Care-contPostpartum Care-cont::

Follow up:• Per American Diabetes Association, a 75 g

two hours oral GTT should be performed 6-8 wks after delivery.

Postpartum Care-contPostpartum Care-cont::Follow up:• If the pt’s postpartum GTT is normal, she

should be re-evaluated at a minimum of 3 years interval with a fasting glucose.

• All pts should be encouraged to exercise and lose wt.

• All pts should be evaluated for glucose intolerance or DM before a subsequent pregnancy.

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