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Hepatitis 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 Hepatitis A antibody IgM and IgG types HBs Ag, HBs Ab, IgM, and IgG types HBe Ag, Ab, Hepatitis B virus DNA Hepatitis C antibody RNA by PCR Prodrome Prodrome or HBe Ag Positive HIV co- infected None 5 – 10% 50 – 85% Asymptomatic to fulminant Asymptomatic to fulminant Asymptomatic to sever relapsing Serologic diagnosis Maximum infectivity Carrier state Acute clinical forms Chronic clinical forms None Chronic persistent hepatitis Chronic active hepatitis Cirrhosis Chronic persistent hepatitis Chronic active hepatitis Cirrhosis Vertical transmission of hepatitis virus (Mainly by hepatitis B) HAV • 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 HBV • 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. HCV • 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. HEV • 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 Diagnoses • 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 Disease in Pregnancy Serum Transaminas es Bilirubin Coagulo pathy Histology Other Features Acute Hepatitis B >1000 >5 - Hepatocellu lar 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 hepatitis Diagnostic 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 Six Responsibilities of Perinatal Hepatitis B Prevention Program 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 Prevention hours of birth of Perinatal Hepatitis B Transmission Assure that all susceptible household and sexual contacts are vaccinated Assure completion of 3 doses of hepatitis B vaccine and post vaccination testing of exposed infants Conduct active surveillance, quality assurance, and outreach to improve program HBV • 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 HBV • 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 Diabetes Definition: • 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. Classification of Diabetes Diabetes in pregnancy Pre-existing diabetes IDDM (Type1) NIDDM (Type2) Gestational diabetes Pre-existing diabetes True GDM Classification of Diabetes in 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: Hypoglycemia Infection Ketoacidosis Deterioration in retinopathy’ Increased proteinuria+edema Miscarriage Polyhydramnio Shoulder dystocia Preeclampsia Increased caesarean rate Future type 2 diabetes Fetal: Congenital abnormalities Increased neonatal and perinatal mortality Macrosomia Birth trauma Late stillbirth Neonatal hypoglycemia Polycythemia Jaundice Hyperbilirubinemia RISK FACTORS FOR GDM Previous diagnosis of GDM A strong FH of type 2 DM Previous delivery of a macrosomic infant Member of a high-risk population (Aboriginal, Hispanic, South Asian, Asian or African descent) Age 35 years Obesity (BMI 30 kg/m2) Polycystic ovarian syndrome and / or hirsutism Acanthosis nigricans Corticosteroid 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: • 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) SCREENING 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 day 1hPG=7.8-10.2 1hPG10.3 75-g OGTT. Measure FPG, 1hPG, 2hPG GDM IGT of pregnancy If 2 values are met or exceeded If 1 value is met or exceeded FPG 5.3 1hPG10.6 2hPG 8.9 Gestational diabetes Diagnosis • WHO criteria 1998, 75 gm glucose fasting Impaired fasting glucose IGT DM 6.1-6.9 <or =7 >or = 7 2 hr (mmol/L) and or 7.8-11 > or=11.1 Dx of GDM with Use of a 100 gram Oral Glucose Load Management • 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. Management 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. Management • Blood glucose monitoring • Diet • Exercise Physical activity should be encouraged • Insulin • Oral Hypoglycemic Medications Know your blood sugar level & keep it under control • 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 breakfast 3. 1 or 2 hours after lunch 4. 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. 36 of 42 Dietary 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 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 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 wellbeing. Delivery • Timing and mode of delivery individualised • Early delivery may be indicated for: • women with poor glycemic control • pregnancies complicated by fetal abnormalities Otherwise, 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 Delivery No indications to pursue delivery before 40 weeks in patients with good glycemic control… *Unless other maternal or fetal indications are present Intrapartum 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 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. Postpartum 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-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. Thanks four your listening