JAUNDICE IN PREGNANCY

INCIDENCE IN INDIA 1 IN 1000

CAUSES
PREGNANCY INDUCED LIVER DISEASE
HYPEREMESIS GRAVIDARUM OBSTETRIC CHOLESTASIS AFLP PREECLAMPSIA AND HELLP SYNDROME

COINCIDENTAL LIVER DISEASE

VIRAL HEPATITIS (Hep A MC World wide) DRUG INDUCED JAUNDICE

PREGNANCY SUPERIMPOSED ON C/C LIVER DISEASE

CONGENITAL HYPERBILURUBINEMIA CIRRHOSIS C/C HEPATITIS

PHYSIOLOGY
RBC- HAEME-BILIVERDIN-BILIRUBIN-Bound

to aibumin-LIVER-Conjugated with 2 molecules of glucoronide(UDP transferase)canaliculi-extrahepatic bile duct-CBD-SITERMINAL ILEUM-bacterial actionUROBILINOGEN-Liver via enterohepatic circulation.

CLASSIFICATION
HEMOLYTIC JAUNDICE

HEMOLYSIS LEADS TO INCREASE IN UNCONJUGATED BILIRUBIN MAINLY SEEN IN HEMOLYTIC ANEMIAS , HELLP SYNDROME.. CONGENITAL HYPERBILIRUBINEMIA INCREASED UNCONJUGATED BILIRUBIN 1. IN GILBERT SYNDROME -DUE TO DECREASED LEVELS OF UDP TRANSFERASE. PREGNANCY, INTER CURRENT ILLNESS, FASTING CAUSES WORSENING OF JAUNDICE. LFT NORMAL EXCEPT SERUM BILIRUBIN. 2. CRIGGLER NAJJAR SYNDROME -PRESENT AT

AR- ABSENCE OF UDPT AD-DECREASED UDPT

CONJUGATED HYPER BILIRUBINEMIA

1.DUBIN JOHNSON SYNDROME - AR MUTATION IN MRP2 GENE, RESPONSIBLE FOR TRANSPORTING WIDE RANGE OF COMPOUNDS OUT OF THE HEPATOCYTE ACROSS THE CANALICULAR BORDER INCLUDING BILIRUBIN AND BILE SALT. MILD JAUNDICE 2. ROTORS SYNDROME AD IN BOTH CONDITIONS , BILIUBINURIA(+)

CHOLESTATIC JAUNDICE CHOLESTASIS IS DUE TO FAILURE TO EXCRETE BILE FROM HEPATOCYTES , CANALICULUS, (INTRAHEPATIC) OR THE CBD (EXTRAHEPATIC) DUE TO ACQUIRED DAMAGE OR OBSTRUCTION.SO CHOLESTEROL , BILIRUBIN , BILE SALT , PL, etc ACCUMULATE IN BLOOD ALP INCREASES. INTRA HEPATIC CHOLESTASIS DUE TO ABNORMALITIES AT CELLULAR LEVEL . Eg. VIRAL HEPATITIS, DRUG REACTIONS, ALCOHOL ABUSE, CIRRHOSIS, OC, AFLP, HYPEREMESIS GRAVIDARUM EXTRAHEPATIC CHOLESTASIS DUE TO OBSTRUCTION TO FLOW OF BILE AT ANY POINT BEYOND THE CANALICULUS SEEN IN GALL STONES, BILIARY STRUCTURE, PANCREATIC MALIGNANCY etc. PALE STOOLS,DARK URINE, CONGENITAL HYPERBILIRUMINARIA.

MANAGEMENT
PREPREGNANCY Jaundice due to conditions with implications for pregnancy should be discussed. PRENATAL Identify the type of jaundice and its cause. Interdisciplinary management depends on cause

LABOUR & DELIVERY Plan early delivery if this will improve the outcome. Avoid regional anaesthesia if coagulopathy present. POST NATAL Confirm resolution of jaundice. Longterm management depends on the cause.

OBSTETRIC CHOLESTASIS
AETIOLOGY CHOLESTASIS EFFECT OF PREGNANCY DUE TO INCREASED LEVELS OF ESTROGEN. MORE COMMONLY IN THIRD TRIMESTER WHEN ESTROGEN LEVELS ARE HIGHEST

CLINICAL FEATURES
GENERALISED PRURITUS WITHOUT A RASH

PREDILICTION FOR PALMS, SOLES AND TRUNK RARELY JAUNDICE MAY FOLLOW PRURITUS AFTER 2-4 WKS.

INVESTIGATIONS
ELEVATED SERUM BILE ACIDS,

TRANSAMINASE SERUM BILIRUBIN MAY BE RAISED BUT USUALLY NOT MORE THAN 5 g/dl ALP NONSPECIFIC

MATERNAL AND FETAL RISK

MATERNAL RISK
PRURITUS CAN BE A VERY DISTRESSING SYMPTOM MATERNAL MORBIDITY DUE TO MALABSORPTION AND Vit K DEFICIENCY LEADING TO PROLONGATION OF CLOTTING TIME AND PPH IF THE SYMPTOMS / BIOCHEMICAL ABNORMALITIES PROLONG FOR >3 MONTHS POSTPARTUM, WOMAN SHOULD BE REFERRED TO A HEPATOLOGIST 90% RISK OF RECURRENCE

FETAL RISK
SPONTANEOUS PREMATURITY FETAL DISTRESS ( MSAF/CTG ABNORMALITY ) IUD DUE TO ANOXIA ASSOCIATED WITH INCREASED SERUM BILE ACIDS ( >40 mol/L ) RARELY FETAL COAGULOPATHY WITH Vit K DEFICIENCY

MANAGEMENT
PREPREGNANCY If previous history of OC , advise of recurrence risk of 90% Obtain biliary tract USG to exclude other pathology PRENATAL Confirm the diagnosis with S. bile acid, ALT,AST measurement Exclude viral infections including hep C , autoimmune hep and other causes of biliary obstrn.

 Treat maternal symptoms initially with simple

topical measures ( aqueous cream with menthol) Consider UCDA 500mg bid for women with severe symptoms Consider oral vit K to reduce the risk of PPH Dexamethasone 12mg daily x 7 days , with a gradual reduction in the dose over subsequent 3 days ( problem of possible fetal adverse neurological effects of repeated doses ) Cholestyramine , guargum Monitor fetal well being , though it does not predict at risk fetus

LABOUR AND DELIVERY Consider elective delivery at 37 38 wks Maintain vigilance for PPH POSTNATAL Monitor biochemical resolution Vit K supplement for baby Use OCP only with close clinical and biochemical monitoring , 27% of cases have cyclical or OCP induced pruritus Consider referral to to hepatologist if symptoms& biochemical abnormalities persists.

AFLP
RARE BUT DANGEROUS DISORDER CLINICAL SYMPTOMS AND SIGNS ARE NOT

SPECIFIC DEFINED AS ACUTE LIVER FAILURE WITH REDUCED HEPATIC METABOLIC CAPACITY IN THE ABSENCE OF OTHER CAUSES HISTOLOGICALLY THERE WILL BE PANLOBULAR MICROVESICULAR STEATOSIS AND INTRA HEPATIC CHOLESTASIS

AETIOLOGY
ASSOCIATE WITH FIRST PREGNANCY ,

MALE FETUSES , PREECLAMPSIA , MATERNAL OBESITY, MULTIPLE PREGNANCIES MANY OF THESE WOMEN ARE CARRYING FETUSES WHO ARE HOMOZYGOUS FOR FATTY ACID OXIDATION DEFECTS (LCHAD DEFICIENCY). IN ADDITION THE WOMEN ARE HETEROZYGOUS FOR THIS DEFECT

DIAGNOSIS
SWANSEA CRITERIA PRESENCE OF MORE THAN 5 DIAGNOSTIC
. VOMITING ABDOMINAL PAIN POLYDIPSIA AND POLYURIA ENCEPHALOPATHY ELEVATED TRANSAMINASES (>42 IU/L) ELEVATED BILIRUBIN (>14mol/L) HYPOGLYCEMIA (<4 mmol/L) ELEVATED URATE (340mol/L)

RENAL IMPAIREMENT (CREATININE > 150mol/L) ELEVATED AMMONIA (>47mol/L) LEUCOCYTOSIS COAGULOPATHY (PT > 14 sec, apTT > 34 sec ) ASCITES/ BRIGHT LIVER ON ULTRASOUND SCAN MICROVESICULAR STEATOSIS ON LIVER BIOPSY

ONE OF THE KEYS TO THE DIAGNOSIS OF AFLP IS THE RAPIDITY WITH WHICH LFT CAN DETERIORATE IN THE AGGRESSIVE PHASE OF THE DISEASE.

MATERNAL AND FETAL PROGNOSIS

MATERNAL DEATH MAY BE DUE TO FULMINANT HEPATIC FAILURE

DIC ENCEPHALOPATHY IN SEVERE DISEASE FETAL PROGNOSIS IS POOR. IF THE FETUS SURVIVE IT MAY DEVELOP RYE LIKE SYNDROME OF HEPATIC ENCEPHALOPATHY AND SEVERE HYPOGLYCEMIA DUE TO DEFECT IN BETA FATTY ACID OXIDN

MANAGEMENT OF ACUTE FATTY LIVER SYNDROME

PREPREGNANCY
None, unless previous pregnancy is affected,in which case, confirm previous diagnosis, check LFTs ,advise risk of recurrence. Consider screening for LCHAD deficiency

PRENATAL
If previous AFLP, check baseline LFT : advise to report any new symptoms; start home testing for urinary protein from 24 wk ; monitor BP every 2 wk. Establish diagnosis , resuscitate Intensive care / high dependency setting Provide supportive therapy Plan delivery or end pregnancy

LABOUR AND DELIVERY maternal resuscitation by correction of hypoglycemia fluid balance coagulopathy Use multidisciplinary approach ideally in liaison with liver unit to manage liver failure Use intensive fetal monitoring Perform urgent delivery when maternal condition is stabilised , vaginal delivery preferable Maintain meticulous hemostasis

POSTNATAL Continue intensive care management Watch for postpartum wound hematoma formation and sepsis , PPH Recurrence risk is difficult to estimate perhaps as high as 10 to 20% Support contraceptive measures Full hepatic recovery expected without further sequelae , occasionally emergency liver transplant needed Paediatricians to consider screening baby for LCHAD deficiency

HYPEREMESIS GRAVIDARUM
SEVERE NAUSEA & INTRACTABLE VOMITING. 0.5-1% AETIOLOGY

1.ENDOCRINE- DUE TO INCREASED hCG 2.INFECTIONS- H. PYLORI 3.UPPER GI DYSMOTILITY DUE TO SMOOTH M RELAXN EFFECT OF PROGESTERONE. 4.PSYCHOLOGICAL 5.LIVER DYSFUNCTION 6.ALTERED LIPID METABOLISM 7.IMMUNOLOGICAL

PATHOLOGY
1.METABOLIC CHANGES STARVATION-GLYCOGEN DEPLETION& MOBILISN OF FAT STORES-INCREASE IN KB. INCREASED PROTEIN METABOLISM- BUN IF PROLONGED HYPOGLYCEMIA,HYPO PROTEINEMIA,HYPOVITAMINOSIS & FINALLY HEP DYSFUN 2.BIOCHEMICAL VOMITING &DEHYDRN CAN LEAD TO HYPONATREMIA,HYPOKALEMIA &HYPOCHLOREMIA. 3.HAEMATOLOGICAL HEMOCONC DUE TO DEHYDRN

INVESTIGATIONS
1.URINE ANALYSIS OLIGURIA, SP.GRAVITY. IN KB, ACIDIC PH 2.HEMATOLOGICAL & BIOCHEMICAL INCREASE IN HAEMATOCRIT ,B.UREA HYPONATREMIA,HYPOKALEMIA ABN LFT 3.USG CONFIRMS A VIABLE I/U GESTN R/O MOLAR & MULTIPLE PREGNANCY

DIFF DIAGNOSIS
1. LIVER DYSFUN 2. PEPTIC ULCER 3. SEVERE GASTRO ESOPHAGEAL REFLUX

D/S 4. PSYCHOLOGICAL PROBLEMS

COMPLICATIONS
MATERNAL

ELECTROLYTE IMBALANCE LIVER DYSFUN RENAL ABNORMALITIES STRESS ULCERS IN STOMACH MALLORY WEISS TEARS IN ESOPHAGUS VITAMIN DEFICIENCY- WERNICKE ENCEPHALOPATHY, KORSAKOFFS PSYCHOSIS,PERIPHERAL NEURITIS,VIT K DEFICIENCY. FETAL IUGR

MANAGEMENT
PREPREGNANCY Discuss recurrence risk Give advise on treatment options and provide psychological support at an earlier stage Give folate supplements PRENATAL Remember alternative diagnosis Rehydrate with IVF and electrolyte therapy Supplement nutrients and vit ( thiamine)

 Consult dietician , provide parenteral nutrition in

extreme cases Provide psychological and social support Provide thromboprophylaxis if needed Treatment

First line conventional anti emetics Alternative agents corticosteroids 5-HT3 antagonist if no response

Provide fetal growth surveillance

LABOUR AND DEIVERY Woman on corticosteroids prenatally should have IV hydro cortisone to cover labour / delivery .

POSTNATAL Review nutritional status Wean off steroids Discuss contraception