Gastroenterology and Hepatology Board Review: Pearls of Wisdom, Third Edition

Section IX MISCELLANEOUS TOPICS

CHAPTER 60. Gastrointestinal and Hepatobiliary Disorders in Pregnancy

Erika Boroff, MD and Elizabeth Carey, MD

Image True/False: Dietary micronutrient supplementation is a more important determinant of birth weight than overall calorie intake during pregnancy.

False. Calorie intake is the most important determinant of birth weight. Micronutrients do not significantly affect birth weight or duration of pregnancy in well-nourished women in developed countries. However, a multivitamin supplement is recommended for pregnant patients who do not consume a varied diet.

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Table 60-1. Recommended Daily Allowances for Nonpregnant and Pregnant Women

Image What are the excess energy requirements (kcal/day) during pregnancy and lactation?

Pregnancy increases energy requirements by 300 kcal/day during the second and third trimesters. Lactation increases energy requirements by 500 kcal/day.

Image True/False: Activity of inflammatory bowel disease at conception affects the likelihood of disease flare during pregnancy.

True. When conception occurs during a period of remission, one-third of patients will relapse during their pregnancy. When conception occurs during a period of active disease however, two-thirds of patients will experience persistently active disease, and of these, two-thirds will note disease progression. There does not appear to be increased risk of flare during the postpartum period if stable patients are continued on medical therapy.

Image What are the risks to the pregnancy when inflammatory bowel disease is active at the time of conception?

Increased risk of preterm birth (odds ratio [OR] 1.87, 95% confidence interval [CI] 1.52 to 2.31) and low birth weight (OR 2.1; 95% CI 1.38 to 3.19). The risk is higher for infants born to mothers with severe colitis during the pregnancy.

There is no clear evidence for an increased risk of congenital abnormalities or stillbirth; however, if surgery is required to treat refractory disease or fulminant colitis, fetal mortality is high (18%–40%).

Image True/False: Spontaneous vaginal delivery should be avoided in all pregnant women with inflammatory bowel disease (IBD).

False. In general, the decision to have a C-section should be based purely on obstetrical factors, with two exceptions: 1) the presence of active perianal disease at the time of delivery, and 2) the presence of an ileal pouch anal anastomosis (IPAA). Although the presence of an IPAA does not mandate a C-section, pouch function may deteriorate during pregnancy, particularly in the third trimester, and there is a theoretical concern that if there is damage to the anal sphincter during vaginal delivery, this can negatively impact pouch function over subsequent years. The patient should discuss with her obstetrician and her surgeon the risks to pouch function over the long term, before deciding on the planned mode of delivery.

Image True/False: Inflammatory bowel disease has no effect on fertility.

False. The effect of IBD on fertility depends on the activity of the disease at the time of attempted conception. Women with quiescent Crohn’s disease (CD) and ulcerative colitis (UC) have similar fertility rates to that of the general population. In contrast, active CD is associated with reduced fertility. In addition, abdominal or pelvic surgery for CD and colectomy with IPAA for UC are associated with a reduction in fertility (threefold decrease for IPAA).

Image True/False: All IBD medications should be stopped in those trying to conceive and those who become pregnant.

False. Most IBD medications are considered low risk during pregnancy and lactation, with the exception of methotrexate and thalidomide which are teratogenic. Low-risk medications should be continued throughout the pregnancy, as discontinuation of such medications at conception may precipitate a disease flare, which is associated with poorer pregnancy outcomes. General consensus for anti-TNF therapy is that they should be continued through conception and the first and second trimesters of pregnancy. If a patient is in remission, consider discontinuing the medication in the latter half of the third trimester, unless the patient is being treated with certolizumab, in which case, the medication can be continued until delivery.

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Table 60-2. Medications Used in the Treatment of Inflammatory Bowel Disease

Image What is the most common cause of upper gastrointestinal bleeding during pregnancy?

Mallory–Weiss tear, followed by erosive esophagitis.

Image What is the most frequent cause of an acute abdomen in pregnancy?

Appendicitis, followed by cholecystitis and intestinal obstruction. Appendicitis occurs in roughly 1 of every 766 pregnancies. Perforated appendicitis increases fetal mortality compared with cases of uncomplicated appendicitis (6%–37%). Symptoms may be atypical as the appendix is displaced out of the pelvis by the gravid uterus, and abdominal distention may delay peritoneal irritation and peritoneal signs.

Image What is the differential diagnosis of acute onset abdominal pain in pregnancy?

Gastrointestinal, genitourinary, and gynecologic disorders including appendicitis, cholelithiasis, pancreatitis, small- bowel obstruction, infectious disease, inflammatory bowel disease, nephrolithiasis, urinary tract infection, ectopic pregnancy, ovarian torsion, and ovarian vein thrombosis.

Image Describe the clinical presentations of gallstone disease during pregnancy.

Most patients with symptomatic gallstones will report biliary-like abdominal pain. Although nausea and vomiting are common in pregnancy, abdominal pain should trigger further evaluation. The presence of fever, leukocytosis, and an ill appearing patient are suggestive of acute cholecystitis. A positive sonographic Murphy’s sign carries a positive predictive value of 92%.

Image During which trimester of pregnancy is pancreatitis most likely to occur?

Third trimester, with increasing incidence with gestational age. Gallstone pancreatitis is the most common cause (66% of cases), and carries a better prognosis than alcoholic or hypertriglyceridemic pancreatitis. In pancreatitis, preterm delivery is increased (18%–32%) but maternal and fetal mortality is low (less than 1% and 4%, respectively).

Image What potential causes of pancreatitis may be exacerbated during pregnancy?

Gallstones, hypertriglyceridemia, and hypercalcemia due to hyperparathyroidism which may first become manifest during pregnancy.

Image What features distinguish hyperemesis gravidarum from uncomplicated nausea and vomiting of pregnancy?

Nausea and vomiting are common in early pregnancy (incidence of 50%), usually peaking at 9-week gestation. The majority of cases (91%) resolve by 20-week gestation. Outcomes are favorable as infants born to mothers who lost weight early in pregnancy have lower birth weights, but the rate of miscarriage is lower than that of women without nausea and vomiting.

Hyperemesis gravidarum occurs in 0.3%–1% of pregnancies, and is characterized by persistent vomiting associated with weight loss of over 5%, ketonuria, hypokalemia, and dehydration. Potential complications of hyperemesis gravidarum include peripheral neuropathy due to deficiency of vitamin B6 or B12, and Wernicke’s encephalopathy due to deficiency of vitamin B1 (thiamine). With appropriate treatment, there is no increased risk of pregnancy loss, low birth weight, or congenital malformation compared with the general population.

Image What conditions are associated with an increased incidence of hyperemesis gravidarum?

Multiple pregnancies and hydatidiform mole.

Image What is the significance of new onset nausea and vomiting in the third trimester of pregnancy?

Nausea and vomiting with onset after 8-week gestation are rare in pregnancy and suggest a more serious condition than uncomplicated nausea and vomiting of pregnancy.

Image Describe laboratory changes in pregnancy that may render the diagnosis of illness more difficult.

Mild leukocytosis is normal in pregnancy. Hemodilution decreases measured hemoglobin, hematocrit, and albumin levels. Iron deficiency may occur in the absence of GI bleeding. Alkaline phosphatase rises (2–4 times normal) due to production of this enzyme by the placenta. Serum alanine aminotranserferase (ALT) and serum aspartate aminotransferase (AST) remain within normal limits. Serum bilirubin levels remain normal. Prothrombin time is unchanged.

Image Describe the normal physiologic changes in GI motility during pregnancy.

Lower esophageal sphincter tone is reduced. Nonpropulsive esophageal motor activity is increased, while esophageal contraction wave amplitude and velocity is decreased. Transit through the stomach, small bowel, and colon is prolonged. Intervals between the interdigestive phase III complexes of the migrating motor complex are prolonged. Gallbladder contractility is reduced with slowed gallbladder emptying. Intraabdominal pressure is increased due to gravid uterus.

Image What medications used for gastroesophageal reflux disease (GERD) are safe for use in pregnancy?

All proton pump inhibitors (PPIs) are FDA category B except omeprazole (category C). Meta-analyses and case control studies have not demonstrated a significant increase in spontaneous abortion, preterm delivery, or congenital birth defects in humans exposed to PPIs. Published guidelines suggest PPIs as first-line therapy for GERD in pregnancy. H2 blockers are less effective than PPIs in managing symptoms of reflux in pregnancy but are safe (all are category B). Other medications for GERD that are safe in pregnancy include antacids and sucralfate.

Image What imaging modality is recommended to evaluate acute right lower quadrant pain in pregnancy?

MRI without gadolinium is the imaging test of choice. MRI without contrast has been determined to be safe in pregnancy. Gadolinium-based contrast is pregnancy category C and should not be used routinely. MRI has a high sensitivity (98%–100%) for diagnosing appendicitis, and a high negative predictive value (94%–100%) to rule out the diagnosis throughout pregnancy. CT should be avoided in pregnancy, except in instances where ultrasound (US) is indeterminate and MRI is not feasible. In comparison, US is safe for use in pregnancy and is accurate in the evaluation of the appendix in the first and second trimesters; however, US is technically difficult in the third trimester due to displacement of the appendix by the gravid uterus.

Image What imaging modalities can be considered in the evaluation of suspected biliary pathology in pregnancy?

Magnetic resonance cholangiopancreatography (MRCP) is recommended in pregnant patients with suspected biliary pathology. US has a sensitivity of 95% for detection of cholelithiasis but is limited in the evaluation of the common bile duct (CBD) and the pancreas. In cases where US identifies biliary dilation or there is a suspicion of CBD stones, MRCP has an accuracy of 100% in determining the cause and location of biliary obstruction, and can evaluate pancreatic disease as well. Patients with choledocholithiasis may then be referred for urgent endoscopic retrograde cholangiopancreatography (ERCP), with shielding of the uterus and minimizing fluoroscopy time to limit fetal radiation exposure.

Image What liver diseases are unique to pregnancy?

• Hyperemesis gravidarum (HG): first trimester—intractable nausea and vomiting with transaminase elevation (50%).

• Intrahepatic cholestasis of pregnancy (ICP): second or third trimester—pruritus (severe) with transaminase elevation and elevated serum bile acids (pathognomonic). Jaundice is uncommon (10%–25%) and should trigger evaluation for biliary obstruction.

• Preeclampsia: second or third trimester—hypertension, right upper quadrant (RUQ) pain, and transaminase elevation.

• HELLP syndrome (Hemolysis, Elevated Liver tests, and Low Platelet count syndrome): second trimester or third trimester—hypertension, RUQ pain (65%–90%), nausea and vomiting (35%–50%), a flu-like illness (90%), and headache (30%). Labs typically reveal proteinuria (86%), transaminase elevation (10–20 times normal), mild bilirubin elevation, hemolysis, and thrombocytopenia. Severe cases may present with disseminated intravascular coagulation (DIC).

• Acute fatty liver of pregnancy (AFLP): second or third trimester—1–2 weeks of anorexia followed by nausea and vomiting, headache, and RUQ pain. Patients may present with fulminant hepatic failure with encephalopathy.

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Figure 60-1. Onset of cholestatic diseases of pregnancy.

Image True/False: The definitive treatment of ICP, HELLP, and AFLP is early delivery.

True. Corticosteroids may improve maternal and fetal outcomes in HELLP.

Image List the criteria for diagnosing HELLP syndrome.

• Hemolysis (abnormal blood smear, elevated LDH, increased indirect bilirubin, low haptoglobin)

• AST > 70 IU/L

• Platelet count < 100,000

Image What distinguishes AFLP from HELLP syndrome?

Patients with AFLP may present with fulminant liver failure and encephalopathy. Jaundice is also a more common feature in AFLP.

Image What common immunosuppressant used in liver transplant recipients is pregnancy category D?

Most immunosuppression (tacrolimus, cyclosporine, and steroids) should be continued during pregnancy; however, mycophenolate mofetil is associated with an increased risk of birth defects and should be discontinued before a woman attempts to conceive. It is recommended a woman wait at least 1 year after transplant before attempting conception.

Image What poses the greatest risk to the cirrhotic patient who is pregnant?

Portal hypertension with variceal bleeding. Over 25% of women with portal hypertension will have a variceal bleed during pregnancy, and 70% if varices are detected prior to conception. Maternal mortality due to a variceal bleed is high, between 20% and 50%. Onset is usually in the third trimester, when blood volume is greatest. Treatment is the same as with nonpregnant patients. For women with known portal hypertension, endoscopy should be performed early in the second trimester. Beta-blocker prophylaxis should be offered if varices are found.

Image True/False: Most cirrhotic women are anovulatory and infertile.

True.

Image Describe the clinical presentation of a ruptured splenic artery aneurysm.

Rupture of a splenic artery aneurysm complicates up to 2.5% of pregnancies in cirrhotic women and is associated with a high mortality. Typical clinical presentation includes acute onset of abdominal pain, pulsatile mass in the left upper quadrant, and presence of an abdominal bruit.

Image True/False: Endoscopic procedures are safe during pregnancy.

True. Endoscopy is safe in pregnancy and can be performed with or without conventional sedation and analgesia.

Image What interventions are utilized to reduce vertical transmission of hepatitis B virus (HBV) infection?

Infants of mothers with HBV should receive HBV vaccination and hepatitis immunoglobulin within 12 hours of birth to prevent vertical transmission during labor and delivery. Completion of HBV vaccination should occur according to the standard schedule. Antiviral treatment such as lamivudine (FDA pregnancy category C), tenofovir (pregnancy category B), and hepatitis B immunoglobulin have each been used successfully in the third trimester to reduce vertical transmission of HBV.

Image True/False: Antiviral treatment is recommended for pregnant patients with chronic hepatitis C (HCV) and high viral loads.

False. Ribavirin is teratogenic and should not be used during pregnancy. Chemoprophylaxis of pregnant women with HCV to reduce the risk of vertical transmission is not recommended at this time. Vertical transmission of HCV is not as efficient as with HBV, occurring in only 4%–6% of pregnancies.

Image True/False: Budd–Chiari syndrome (BCS) in pregnancy usually occurs during the second trimester.

False. BCS presents with acute onset of RUQ pain, hepatomegaly, and ascites, usually in the third trimester (elevated estrogen levels and decrease in serum antithrombin III late in pregnancy promote thombogenesis).

Image What is the most morbid form of acute viral hepatitis in pregnancy?

Acute hepatitis E virus (HEV) infection is particularly virulent in pregnant patients and can present with fulminant hepatic failure in the third trimester. Mortality is high, 15%–25%. Cases are found primarily in Southeast Asia, Northern Africa, and Mexico, although less virulent strains have been identified in North America.

Image What other virus can cause fulminant liver failure during the third trimester of pregnancy?

Herpes simplex virus (HSV). Typical oral or genital lesions are present in only the minority of cases (30%). Fever and upper respiratory symptoms may be present. Bilirubin level may be normal or near normal at initial presentation. Diagnosis can be made by detection of viremia if no vesicular lesions are present. Treatment with antivirals may reduce mortality.

• • • SUGGESTED READINGS • • •

Carey E, Hay J. Pregnancy and liver disease. In: Talley N, Lindor K, Vargas H, eds. Practical Gastroenterology and Hepatology: Liver and Biliary Disease. Hoboken, NJ: Wiley-Blackwell; 2010:152-163.

Niebyl JR. Clinical practice. Nausea and vomiting in pregnancy. N Engl J Med. 2010;363:1544-1550.

Parangi S, Levine D, Henry A, et al. Surgical gastrointestinal disorders during pregnancy. Am J Surg. 2007;193:223-232.

van der Woude CJ, Kolacek S, Dotan I, et al. European evidenced-based consensus on reproduction in inflammatory bowel disease. J Crohns Colitis. 2010;4:493-510.