2Summary 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 toplacental productionClotting factor changes create a hypercoagulable stateDecreased:Gallbladder contractilityHemoglobinUric acid levelsAlbumin, total protein, and antithrombin III concentrationsNo change:Liver aminotransferase levels (aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase)Bilirubin levelProthrombin time
3The impact of pregnancy on the hepatitis The course of most viral infections is not affected by pregnancyTo made the pathogenetic conditionviral exacerbations and complicatedThe high incidence of severe hepatitis and hepatic coma
4Hepatitis on pregnancy First trimesterHyperemesis gravidarum increasedthe high incidence of abortion and fetal malformationassociated with the incidence of Down syndromeSecond and third trimestersa higher incidence of hypertensive disorders in pregnancya higher incidence of postpartum hemorrhage
5Hepatitis A antibody IgM and IgG types Hepatitis CHepatitis BHepatitis ACharacteristicsRNADNAVirus type30-60 nm42 nm27 nmVirus size30 – 160 days30 – 180 days15 – 50 daysIncubation periodParentral sporadicParentral or body fluidFecal – oralTransmissionUncommonCommonNot observedVertical transmission to fetusHepatitis C antibodyRNA by PCRHBs Ag, HBs Ab, IgM, and IgG typesHBe Ag, Ab, Hepatitis B virus DNAHepatitis A antibody IgM and IgG typesSerologic diagnosisHIV co- infectedProdrome or HBe Ag PositiveProdromeMaximum infectivity50 – 85%5 – 10%NoneCarrier stateAsymptomatic to sever relapsingAsymptomatic to fulminantAcute clinical formsChronic persistent hepatitisChronic active hepatitisCirrhosisChronic clinical forms
6Vertical transmission of hepatitis virus (Mainly by hepatitis B)
7HAV There is no evidence that HAV causes birth defects There is no evidence of maternal-fetal transmissionIn rare circumstances in which the mother has acute HAV infection at the time of deliveryimmune serum globulin may be administered to the infantEven under these conditions, the risk of transmission to the infant seems very smallAnti-HAV IgG antibodies is not transmitted from infected mothers to newborn infants
8HBV Evidence suggests that transmission of HBV to infants is common when mothers have acute infection in the third trimesterwhen they are chronic carriers of HBV infection and have positive results for HBeAg or HBV DNAThe risk of transmission is highest in mothers who are HBeAg - positive at the time of deliveryNewborn baby has a 90% likelihood of becoming infected.Approximately 25% of infected infants will become chronic carriers.
9HCV 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 deliveryif her viral DNA load is greater than 1 million copies/mlif the time from the rupture of membranes to delivery is more than 6 hours.
10HEVTransmission 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.
11HGVMost 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
12Diagnoses Epidemiological history Clinical manifestations Laboratory Studies : the most useful testsevaluation 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
13Type of hepatitis during pregnancy Acute hepatitisChronic active hepatitisAcute severe hepatitis
14Differential Diagnosis of Liver Disease in Pregnancy SerumTransaminasesBilirubinCoagulopathyHistologyOther FeaturesAcute Hepatitis B>1000>5-Hepatocellular necrosisPotential for perinatal transmissionAcute Fatty Liver<500<5+Fatty infiltrationComa,renal failure, hypoglycemiaIntrahepatic Cholestasis<300<5, mostly directDilated bile canaliculiPruritis, increased bile acidsHELLP>500Variable periportal necrosisHTN, edema, thrombocytopenia
15Management of Acute Viral Hepatitis in Pregnancy Establish type by serologic testInstitute appropriate isolation and precautionsDetermine need for contact prophylaxis with scrum globulinpreparation and/or vaccineActivity: determined by toleranceDiet: patient preference, parentral if necessary Antiemetics:phenothiazines may be usedCorticostcroids: not indicatedImmunoprophylaxis of infant: if hepatitis B is present
16Acute severe hepatitis Diagnostic points Severe gastrointestinal symptomsRapidly deepening jaundiceHepatic encephalopathyLiver function :severely abnormalRenal failureCoagulopathy
17Guidelines for severe hepatitis Protect the liverPrevention of encephalopathyPrevention of DICPrevention of hepatorenal syndrome
18Six Responsibilities of Perinatal Hepatitis B Prevention Program Assure identification of ALL HBsAg positive women and their infantsAssure all exposed infants receive HBIG and 1st dose of hep. B vaccine w/in 12 hours of birthPreventionof PerinatalHepatitis BTransmissionAssure completion of 3 doses of hepatitis B vaccine and post vaccination testing of exposed infantsAssure that all susceptible household and sexual contacts are vaccinatedThis is an overview of the big picture of the programto accomplish the goal of eliminating perinatal hepatitis B.Conduct active surveillance, quality assurance, and outreach to improve program
19HBVTaking lamivudine before becoming pregnant and continuing to take it throughout the pregnancylower rates of transmission of the virus from mother to newbornLower transmission rates have also been seen in pregnant women with a high viral DNA load
20HBVThe 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.
21HCVThe mode of delivery does not seem to influence the rate of transmission from mother to childInfection prior to delivery has been shown to occur in as many as 33% of patientsAn elective cesarean section has been suggested for patients co-infected with HIVreduce maternal-fetal transmission by up to 60%
23Definition: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.Impt to know the difference between pre-existing DM that manifest during pregnancy vs. GDM. Each results in different consequences: effects of organogenesis. For women who develop GDM before 20 wks of gestation and have an elevated HgbA1c, they most likely have had pre-existing DM.
25Classification of Diabetes in Pregnancy Class A:Abnormal GTT at any age or of any duration treated only by diet therapyA1-Diet Controlled GDMA2-Insulin-treated GDM
26Complications of pregnancy in GDM Maternal:HypoglycemiaInfectionKetoacidosisDeterioration in retinopathy’Increased proteinuria+edemaMiscarriagePolyhydramnioShoulder dystociaPreeclampsiaIncreased caesarean rateFuture type 2 diabetesFetal:Congenital abnormalitiesIncreased neonatal and perinatal mortalityMacrosomiaBirth traumaLate stillbirthNeonatal hypoglycemiaPolycythemiaJaundiceHyperbilirubinemia
27RISK FACTORS FOR GDM Previous diagnosis of GDM A 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
28Screening-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 ageNormal body weight with BMI < 25No first degree relative with DMNot 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 ancestryNo hx of abnormal glucose metabolismNo hx of poor obstetric outcome
29Screening-cont:For women who do not meet the above criteria, screening should be conducted at wks of gestation with use of a 50 g one hour oral glucose loadAn 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)a 50 g one hour oral glucose load, administered without regard to the time of the day or the time of last meal.A value of 200 mg/dL on screening is so likely to be associated with the dx of GDM that the GTT need not to be performed and treatment can be started.
30SCREENING SCREENING All pregnant women between 24 and 28 weeks If multiple risk factors are present, assess during each trimester.1hPG following 50-g glucose load at any time of day1hPG10.31hPG=75-g OGTT. Measure FPG, 1hPG, 2hPGIf 2 values are met or exceededFPG 5.31hPG10.62hPG 8.9GDMIGT of pregnancyIf 1 value is met or exceeded
31Gestational diabetes Diagnosis WHO criteria 1998,75 gm glucosefasting hr (mmol/L)Impaired fasting glucoseIGT <or = andDM >or = or > or=11.1
32Dx of GDM with Use of a 100 gram Oral Glucose Load (performed after an overnight fast with the patient consuming her usual unrestricted daily diet in the 3 days preceding the test)Two or more abnormal values are diagnostic for GDM.
33Management 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.A multidisciplinary approach with a dietitian, a nurse, a diabetic educator, a social worker and a physician is used.
34ManagementThe glycemic targets associated with the best pregnancy outcome in GDM are:Preprandial < 5.3 mmol/L1-hour postprandial < 7.8 mmol/L2-hour postprandial < 6.7 mmol/LWomen with GDM should carry out frequent fasting and postprandial home blood glucose monitoring in order to achieve glycemic targets.
35Management Blood glucose monitoring Diet Exercise Insulin Physical activity should be encouragedInsulinOral Hypoglycemic Medications
36Know your blood sugar level & keep it under control You may have to test four times a day:In the morning before eating breakfast, referred to as the Fasting glucose level1 or 2 hours after breakfast1 or 2 hours after lunch1 or 2 hours after dinnerYou 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.36 of 4236
37Dietary TherapyNutrition 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
38Insulin RegimenPt 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 > mg/dL or 2 hr value > 120 mg/dL, insulin therapy needs to be initiated.The goal of insulin therapy is to maintain glucose levels below the above values.
39Antepartum TestingFirst 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.If fetal macrosomnia is detected, with accelerated growth of the fetal abdominal circumference, and fetal wt estimated >4500 g, cesarean delivery should be considered to reduce the risk of shoulder dystocia.
40Delivery Timing and mode of delivery individualised Early delivery may be indicated for:women with poor glycemic controlpregnancies complicated by fetal abnormalitiesOtherwise, pregnancies are allowed to go to term.If delivery is scheduled before 39 wks gestation, an amniocentesis to assess for fetal lung maturity is performed.If corticosteroids are used to accelerate lung maturity, insulin requirement needs to be increased in the next 5 days.[Transient hyperglycemia; the steroid effect begins approximately 12 hours after the first dose and may last for five days. Blood glucose conc is checked q1-2 for 48 hrs after betamethasone is administered.][Elective early delivery was done in the past to prevent fetal death. No longer necessary given better glycemic control and better methods of fetal surveillance.]In pts with well controlled GDM, there is no evidence to support routine delivery before 40 wks of gestation.There is also no data to support cesarean delivery purely on the basis of GDM. If estimated fetal wt >4500 g, cesarean delivery may be considered since it may reduce the likelihood of permanent brachial plexus injury in the infant. (3)
41Delivery 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
42What is a reasonable approach? Offer elective C-sectionEstimated fetal weight >4,500gPatient history and pelvimetryDiscuss risks and benefits
43DeliveryNo indications to pursue delivery before 40 weeks in patients with good glycemic control…*Unless other maternal or fetal indications are present
44IntrapartumThe 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 mg/dL.Observe infant closely for hypoglycemia, hypocalcemia, and hyperbilirubinemia after birth.
45Postpartum Care After 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.Insulin requirements decrease rapidly after delivery. As insulin resistance quickly resolves, so does the need for insulin. Women who are dx with GDM early in gestation who are obese and have required insulin/glyburide therapy are most likely to demonstrate persistent glucose intolerance or DM.
46Postpartum Care-cont: Follow up:Per American Diabetes Association, a 75 g two hours oral GTT should be performed 6-8 wks after delivery.
47Postpartum 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.