Chad K. Klauser, MD
Daniel H. Saltzman, MD
HYPEREMESIS GRAVIDARUM
ESSENTIALS OF DIAGNOSIS
Hyperemesis gravidarum is defined as unexplained intractable nausea, retching, or vomiting beginning in the first trimester, resulting in dehydration, ketonuria, and typically a weight loss of more than 5% of prepregnancy weight.
Symptoms typically start between 3 and 5 weeks of pregnancy and 80% resolve by 20 weeks.
Treatment frequently includes avoidance of noxious stimuli, medications to relieve nausea and vomiting, hydration, and possibly hospitalization.
Pathogenesis
Hyperemesis gravidarum (HEG) affects 0.3–2% of pregnant women. The pathogenesis is largely unknown, with possible contributing factors being increased levels of human chorionic gonadotropin (hCG), estradiol, and possible progesterone. It is more common among younger mothers and those with a history of motion sickness, migraines, and nausea and vomiting associated with oral contraceptives. It is more commonly seen in women carrying multiple gestations, and patients with siblings or a mother with HEG are more likely to be affected.
Clinical Findings
A. Symptoms & Signs
HEG is associated with severe nausea and vomiting that may result in dehydration, weight loss, and frequently social isolation and negative impacts on relationships with family and friends. Patients with HEG, rather than nausea and vomiting of pregnancy, tend to have an earlier onset and longer duration. Excess salivation (ptyalism) may also be seen in a subset of women with HEG.
B. Laboratory Findings
Suppressed thyroid-stimulating hormone/elevated free thyroxine and elevated liver enzymes, bilirubin, amylase, and lipase may all be noted in patients with severe nausea and vomiting; these are transiently abnormal and resolve with improvement of HEG.
C. Imaging Studies
No imaging studies are needed for the diagnosis of hyperemesis; however, they can be used to exclude other conditions such as pancreatitis, cholecystitis, or intracranial lesions.
Differential Diagnosis
Other medical conditions should be suspected if the onset of severe nausea and vomiting is after 9 weeks of gestational age. The differential diagnosis for late HEG should include gastroenteritis, gastroparesis, biliary tract disease, hepatitis, peptic ulcer disease, pancreatitis, appendicitis, pyelonephritis, ovarian torsion, diabetic ketoacidosis, migraines, drug toxicity or withdrawal, psychological conditions, acute fatty liver of pregnancy, and preeclampsia.
Complications
Maternal complications of HEG can include Wernicke’s encephalopathy, acute tubular necrosis, central pontine myelinolysis, Mallory-Weiss tear of the esophagus, pneumomediastinum, and splenic avulsion. Additionally, significant psychological burden of the disease has been reported, with depression, anxiety, and lost work frequently seen among those with persistent or severe HEG. Fortunately, no clear fetal complications have been associated with HEG. One study did show that women with HEG who gain <7 kg during the entire pregnancy have a slightly higher risk of low birth weight and preterm birth. However, there are no congenital anomalies or increased risk of miscarriage or stillbirth noted.
Treatment
Treatment of HEG begins with supportive measures including hydration and vitamin supplementation (in particular thiamine to prevent Wernicke’s encephalopathy). Nonpharmacologic measures such as acupuncture, hypnotherapy, avoidance of defined nausea triggers, herbal teas, vitamin B6, and ginger may help alleviate nausea and vomiting in a subset of patients. Antihistamines as a class have been shown to be efficacious and have a long history of safety during pregnancy. Other antiemetics can be used in an algorithm that balances safety and efficacy (Table 29–1). Patients have also been shown to benefit from frequent contact with the health care provider or from an outpatient nursing services program. If weight loss persists despite therapy, nutritional supplementation by enteral tube feeding or parenteral feeding is necessary. If a patient requires hospitalization, it usually occurs prior to 8 weeks.
Table 29–1. Safe and effective use of antiemetics.
Prognosis
More than 50% of women have resolution of symptoms by 16 weeks of gestational age and 80% by 20 weeks. However, approximately 10% will be affected to some degree with severe nausea and vomiting for the duration of the pregnancy. HEG has been shown to recur in up to 80% of subsequent pregnancies, although earlier aggressive medical therapy prior to significant symptoms has been demonstrated to reduce both the severity and recurrence rate overall in future pregnancies.
Bottomley C, Bourne T. Management strategies for hyperemesis. Best Pract Res Clin Obstet Gynaecol 2009;23(4):549–564. PMID: 19261546.
Goodwin TM. Hyperemesis gravidarum. Obstet Gynecol Clin North Am 2008;35:401–417. PMID: 18760227.
Niebyl JR. Nausea and vomiting in pregnancy. N Engl J Med 2010;363:1544–1550. PMID: 20942670.
PEPTIC ULCER DISEASE
ESSENTIALS OF DIAGNOSIS
Epigastric pain, anorexia, postprandial nausea and vomiting, or abdominal fullness.
The incidence and severity of peptic ulcer disease (PUD) decrease during pregnancy, whereas symptoms of dyspepsia may be increased among this group.
Esophagogastroduodenoscopy is generally considered as safe during pregnancy and is recommended for the evaluation of PUD when symptoms are severe and nonresponsive to medical therapy.
Pathogenesis
Peptic ulcers represent an erosion of the gastrointestinal mucosa, extending through the muscularis mucosae. The majority are caused by Helicobacter pylori infection or the use of nonsteroidal anti-inflammatory drugs (NSAIDs). These exposures affect the gastric mucosal function and repair through alterations in gastric acid secretion, gastric metaplasia, and immune responses. The incidence of PUD during pregnancy is approximately 1 in 4500 pregnancies, compared with approximately 1 per 1000 of the general population. This finding may be related to the fact that many of the risk factors/exacerbating factors for PUD are less common during pregnancy, including cigarette use, NSAID use, and alcohol intake. Ulcers are 5 times more common in the duodenum than in the stomach.
Prevention
Although PUD is multifactorial, in the absence of H pylori, abstaining from cigarette use and limiting the use of aspirin, NSAIDs, and alcoholic beverages may decrease both the incidence of primary occurrence and recurrence.
Clinical Findings
The classic signs of gastric or duodenal ulcer are related to a burning epigastric pain that is relieved by meals or antacids. PUD must be differentiated from reflex esophagitis or simple heartburn, which commonly occurs during pregnancy. Patients with a gastric or duodenal ulcer most often report discomfort rather than pain and describe the feeling as “acid,” burning, or indigestion. Pain from a duodenal ulcer occurs several hours postprandially during the day, occurs nocturnally, and is relieved by eating food. Pregnant patients tend to have milder symptoms than nonpregnant patients.
Most commonly, the diagnosis is confirmed by endoscopic visualization of the ulcer crater in the stomach or duodenum. Upper gastrointestinal x-ray films with barium studies usually are avoided during pregnancy because of radiation exposure and because endoscopy is a more direct diagnostic method. The presence of H pylori can be confirmed based on biopsy histology, culture, or urease test.
Differential Diagnosis
PUD should be distinguished from other common gastrointestinal problems during pregnancy such as gastroesophageal reflux disease (GERD), nausea and vomiting of pregnancy, HEG, pancreatitis, acute cholecystitis, viral hepatitis, appendicitis, acute fatty liver of pregnancy, and irritable bowel syndrome. GERD is extremely common in pregnancy and may be partially distinguished from PUD by the findings of pain radiating to the neck, pain exacerbated by drinking acidic drinks, and recumbency. Other symptoms more commonly seen with GERD include nocturnal asthma, hoarseness, laryngitis, or periodontal disease. Pancreatitis is marked with pain exacerbated with eating, pain radiating to the back, and presence of leukocytosis or pyrexia. Additionally, serum amylase and lipase levels are generally increased with pancreatitis. Acute cholecystitis is also associated with exacerbation after ingestion of fatty meals, right upper quadrant pain, fever, and leukocytosis. Acute hepatitis is diagnosed serologically, whereas appendicitis typically has an acute onset of abdominal pain, rebound tenderness, pyrexia, leukocytosis, and anorexia.
Complications
Complications of PUD occur in pregnancy much less frequently than in the general population. Case reports have documented complications such as hematemesis, perforation, and gastrointestinal obstruction during pregnancy. The fetus generally is not adversely affected unless significant maternal compromise occurs. One retrospective study proposed a small increased risk of low birthweight and preterm delivery in women diagnosed with PUD when compared to pregnant patients without PUD.
Treatment
Documented PUD is treated symptomatically during pregnancy by avoiding symptom-provoking foods and using antacids and sucralfate. Supportive advice can be given regarding cessation of smoking, bed rest, and avoidance of stress. For persistent symptoms, an H2 antagonist such as cimetidine or ranitidine can be given. With continued symptoms, a proton pump inhibitor such as lansoprazole can be added to the drug regimen. Eradication of H pylori is 90% successful with an antibiotic such as amoxicillin or clarithromycin, a bismuth compound, and a proton pump inhibitor. Both the H2 antagonists and proton pump inhibitors have been extensively studied for teratogenic effects, and no significant abnormal findings have been associated with their use during pregnancy.
Chen Y, Lin HC, Lou HY. Increased risk of low birthweight, infants small for gestational age, and preterm delivery for women with peptic ulcer. Am J Obstet Gynecol 2010;202:164. PMID: 20113692.
Engemise S, Oshowo A, Kyei-Mensah A. Perforated duodenal ulcer in the puerperium. Arch Gynecol Obstet 2009;279:407–410. PMID: 18642012.
Parikh N, Howden CW. The safety of drugs used in acid-related disorders and functional gastrointestinal disorders. Gastroenterol Clin North Am 2010;39:529–542. PMID: 20951916.
INFLAMMATORY BOWEL DISEASE
ESSENTIALS OF DIAGNOSIS
Crohn’s disease is one subcategory of inflammatory bowel disease (IBD), characterized by insidious onset, episodes of low-grade fever, diarrhea, right lower quadrant pain, and perianal disease with abscess and fistulas formed. Radiographic evidence includes ulceration, stricturing, or fistulas of the small intestine or colon. It may involve any segment of the gastrointestinal tract from the mouth to the anus.
Ulcerative colitis is the other subcategory of IBD manifesting with bloody diarrhea, lower abdominal cramps, fecal urgency, anemia, and low serum albumin. It is diagnosed with sigmoidoscopy and only involves the colon.
Pathogenesis
Inflammatory bowel disease (IBD) affects approximately 500,000 individuals in the United States at present. There are 2 major categories of IBD: Crohn’s disease and ulcerative colitis. Ulcerative colitis is characterized by recurrent episodes of inflammation affecting the mucosal layer of the colon. Lesions are seen to affect the colon in a continuous fashion. In contrast, Crohn’s disease is characterized by inflammation affecting the full thickness of the bowel wall and is associated with “skip lesions” in the bowel, lesions separated by unaffected areas. Crohn’s disease can affect any area of the gastrointestinal tract from the mouth to the anus, but the most commonly affected site is the distal ileum.
Although the cause of the inflammatory lesions is poorly understood, risk factors have been identified. Most cases of IBD initially present between the ages of 15 and 40 years. Both types of IBD are more common in individuals of Jewish descent. The disease may also have a hereditary component because a family history of IBD increases one’s risk of developing IBD.
Clinical Findings
A. Symptoms & Signs
Both Crohn’s disease and ulcerative colitis often affect women during their reproductive years and have similar risks in pregnancy as well as with similar treatments. In these conditions, cramping, lower abdominal pain, and diarrhea are the main complaints. Weight loss and anorexia may occur, as well as electrolyte imbalance with severe diarrhea.
B. Diagnostic Studies
Flexible sigmoidoscopy is considered safe during pregnancy and preferred to colonoscopy unless it is felt to be critical for making treatment decisions. The diagnosis is established by finding characteristic intestinal ulcerations and excluding alternative diagnoses.
Differential Diagnosis
The differential diagnosis for IBD includes enteric infection, bowel ischemia, diverticulitis, amyloidosis, diarrhea of acquired immunodeficiency syndrome, celiac sprue, and NSAID-induced changes.
Complications
Poor maternal weight gain, bowel perforation, toxic megacolon, and obstruction are rare complications of IBD during pregnancy. Fertility rates for both ulcerative colitis and Crohn’s disease are similar to baseline. Additionally, women with IBD are as likely to flare during pregnancy (34% chance per year) as when not pregnant (32% chance per year).
Both ulcerative colitis and Crohn’s disease are associated with an increased risk of first-trimester miscarriage, preterm birth, and small for gestational age infants, as well as an increased caesarean delivery rate. Women who experienced increased disease activity at conception have experienced the most significant increase in these poor obstetrical outcomes. Contradictory findings have been found in regard to congenital anomalies, with some showing an increased risk with ulcerative colitis but not Crohn’s disease. These findings are not consistent and may be associated with medications used during the pregnancy.
Treatment
Treatment of IBD typically consists of both dietary changes and medications. Total parenteral nutrition may be required in extreme cases for a period of time during a pregnancy. Sulfasalazine is a frequently used first-line medication that does cross the placenta but has not been associated with an increased risk of birth defects or pregnancy loss. Supplemental folic acid should be given as an adjunct to sulfasalazine. Steroids are also frequently used for moderate to severe cases of IBD, with possible association with low-birth-weight infants and increased risk of oral clefts (when given <10 weeks and at high dose). Immunosuppressive medications such as azathioprine and 6-mercaptopurine can be used in refractory cases, although there are concerns for potential fetal myelotoxicity, as well as miscarriage and preterm birth. Cyclosporine should only be used in those women not responsive to steroids to avoid emergency colectomy; it may be associated with an increased risk of preterm birth and intrauterine growth restriction. Methotrexate is contraindicated in pregnancy secondary to its mutagenic and teratogenic effects. Select antibiotics may be used, especially with Crohn’s disease.
In terms of obstetrical management, serial growth ultrasounds and monitoring for preterm labor should be considered in women affected by IBD. Caesarean delivery is generally reserved for obstetrical indications, with the exception of active perianal disease or the presence of an ileoanal pouch.
Prognosis
Symptoms of active IBD during pregnancy are similar to those in the nonpregnant state: abdominal pain, cramping, and rectal bleeding. Pregnancy is not contraindicated with IBD, but when possible, the disorder should be controlled by surgery or medication prior to conception. Pregnancy does not exert an adverse effect on IBD. In most patients, pregnancy and delivery proceed smoothly.
Correia LM, Bonilha DQ, Ramos JD, et al. Treatment of inflammatory bowel disease and pregnancy: A review of the literature. Arq Gastroenterol 2010;47:197–201. PMID: 20721468.
Ferguson C, Mahsud-Dornan S, Patterson RN. Inflammatory bowel disease in pregnancy. BMJ 2008;337:427. PMID: 18599468.
Habal F, Ravindran NC. Management of inflammatory bowel disease in the pregnant patient. World J Gastroenterol 2008;14:1326–1332. PMID: 18322943.
Mahadevan U. Pregnancy and inflammatory bowel disease. Gastroenterol Clin North Am 2009;38:629–649. PMID: 19913206.
Reddy D, Murphy SJ, Kane SV, et al. Relapses of inflammatory bowel disease during pregnancy: In-hospital management and birth outcomes. Am J Gastroenterol 2008;103:1203–1209. PMID: 18422816.
ACUTE FATTY LIVER OF PREGNANCY
ESSENTIALS OF DIAGNOSIS
Acute fatty liver of pregnancy (AFLP) is a rare complication of the third trimester of pregnancy involving acute hepatic failure (average gestational age at onset of 36 weeks).
Symptoms of AFLP include malaise, anorexia, nausea, vomiting, epigastric pain, headache, or jaundice.
Laboratory abnormalities include thrombocytopenia, elevated transaminases, hyperuricemia, and elevated creatinine. Additionally, hyperbilirubinemia, hypoglycemia, and hyperammonemia are found.
Other findings may include hypertension, low-grade fever, bleeding from coagulopathy, agitation, or confusion of the patient.
Pathogenesis
Acute fatty liver of pregnancy (AFLP) occurs in approximately 1:10,000 pregnancies and is associated with microvesicular fatty infiltration of the liver and possibly kidney, leading to fatty liver and renal insufficiency. Although it has been diagnosed as early as 23 weeks’ gestational age and as late as 1–2 weeks postpartum, it typically occurs in the third trimester, with an average age at diagnosis of 36 weeks. Approximately 50% of patients with AFLP have associated preeclampsia and/or HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome. Additionally, it is more common in first pregnancies, multiple gestations, and a male fetus. AFLP has been associated with an inherited defect in mitochondrial beta-oxidation of fatty acids, long-chain 3-hydroxyacyl coenzyme A dehydrogenase deficiency (LCHAD). Both fetal possession and maternal possession of the defect have been linked to a significantly increased risk of developing AFLP, with many women having recurrences in subsequent pregnancies.
Clinical Findings
A. Symptoms & Signs
The patient typically reports malaise and fatigue for 1–2 weeks prior to presentation, with gradual onset of anorexia, worsening nausea and vomiting, headaches, and epigastric/right upper quadrant pain. On physical exam, jaundice may be noted, as well as a deep yellow-orange–colored urine.
B. Laboratory Findings
Laboratory studies typically reveal some degree of thrombocytopenia, as well as low serum glucose and elevated transaminases, bilirubin, creatinine, and ammonia levels. Additionally, varying degrees of coagulopathy can also be found.
C. Imaging Studies
Imaging studies are most useful to exclude other diagnoses such as intrahepatic hemorrhage or hepatic infarct, although changes consistent with nonspecific fatty infiltrations can be seen on computed tomography scan or hepatic ultrasound.
D. Special Tests
Liver biopsy is usually diagnostic, but frequently, coagulation abnormalities preclude this from being done. Moreover, the clinical presentation and laboratory values often lead to a certain diagnosis. Screening both the patient and the neonate after delivery for the LCHAD mutation can greatly assist in the diagnosis and counseling for future pregnancy.
Differential Diagnosis
AFLP is frequently confused with thrombotic thrombocytopenic purpura (TTP), hemolytic-uremic syndrome (HUS), sepsis, HELLP syndrome, or severe preeclampsia. TTP does not typically have significant elevation of liver transaminases, and there is usually a more severe thrombocytopenia present. HUS has an earlier and more severe renal involvement with less hepatic laboratory abnormalities. Hypertensive diseases (preeclampsia/HELLP) may overlap the diagnosis of AFLP frequently; however, increased ammonia levels and a more significant elevation in aspartate transaminase (AST)/alanine transaminase (ALT) and bilirubin are found in AFLP.
Treatment
Patients suspected to have AFLP should be hospitalized in either a labor and delivery unit or intensive care unit, based on maternal/fetal stability. Hypoglycemia should be corrected, and a patient should receive replacement of blood products or coagulation factors as needed. Once the mother is stabilized, delivery should be achieved; induction of labor can be attempted, based on the gestational age, maternal response to resuscitation, and fetal condition since caesarean section may be associated with an increased risk of complications due to maternal coagulopathy. Caesarean section should be performed under general anesthesia, a midline vertical incision should be considered (less dissection, more avascular planes), and placement of a subfascial and subcutaneous drain upon closing the abdomen may be beneficial to track bleeding and decrease hematoma formation. Supportive therapy should be continued in the postpartum period, with special attention to maintaining adequate perfusion to liver, kidneys, and other organs. Pancreatitis can be a lethal complication of AFLP, requiring close monitoring in the postpartum period. Initial improvement is generally is seen within 3–5 days after delivery, with hospitalization of up to 15–20 days not being unusual. Plasmapheresis has been proposed for patients that have worsening hepatic and renal function despite delivery, although the benefit of this is uncertain.
Prognosis
The maternal mortality rate from AFLP and associated complications (eg, infection, disseminated intravascular coagulation) is approximately 10%, which is significantly improved from a historical rate of 70%. Fetal/neonatal mortality is 23%, largely secondary to indicated preterm birth. Liver transplant is a rare but occasionally life-saving procedure for women progressing to fulminant liver failure. As mentioned earlier, the patient, father, and neonate should be screened for the LCHAD mutation. The risk of recurrence in future pregnancies is significant, especially among families with LCHAD deficiency, ranging from 15–70%.
Cappell MS. Hepatic disorders severely affected by pregnancy: Medical and obstetric management. Med Clin North Am 2008;92:739–760. PMID: 18570941.
Rajasri AG, Srestha R, Mitchell J. Acute fatty liver of pregnancy (AFLP): An overview. J Obstet Gynaecol 2007;27:237–240. PMID: 17664801.
Sibai BM. Imitators of severe pre-eclampsia. Semin Perinatol 2009;33:196–205. PMID: 19464511.
Williams J, Mozurkewich E, Chilimigras J, et al. Critical care in obstetrics: Pregnancy-specific conditions. Best Pract Res Clin Obstet Gynaecol 2008;22:825–846. PMID: 18775679.
HELLP SYNDROME
ESSENTIALS OF DIAGNOSIS
HELLP syndrome is a disorder in the spectrum of preeclampsia/eclampsia characterized by hemolysis with a microangiopathic blood smear, elevated liver enzymes, and a low platelet count.
Up to 20% of patients with HELLP syndrome will be normotensive and/or lack proteinuria.
Pathogenesis
HELLP syndrome complicates up to 1 in 200 pregnancies and is seen in 10–20% of women with preeclampsia. It generally occurs in the third trimester. HELLP syndrome is a disorder characterized by hemolysis, elevated liver enzymes, and low platelets (hence, the acronym HELLP). It is believed to fall within the spectrum of disorders related to preeclampsia, although the absolute cause is unknown.
Clinical Findings
A. Symptoms & Signs
Patients most commonly present with abdominal/epigastric pain, nausea, vomiting, and malaise. Frequently, this is associated with elevated blood pressure and proteinuria (80%). Jaundice, oliguria, and ascites may be seen less frequently.
B. Laboratory Findings
The diagnosis of HELLP syndrome is dependent on the presence of all of the following laboratory findings: evidence of hemolysis (demonstrated by the presence of schistocytes on peripheral smear, bilirubin ≥1.2 mg/dL, or serum lactate dehydrogenase ≥600 IU/L), platelet count <100,000, and serum 
. Women who have some but not all of these laboratory abnormalities are given a diagnosis of partial HELLP syndrome. Additionally, mild elevation of prothrombin time (PT)/partial thromboplastin time (PTT) and decrease in fibrinogen may be seen in some women.
Differential Diagnosis
The differential diagnosis includes severe preeclampsia; a significant overlap in symptoms and findings may be seen, but HELLP is diagnosed when the previously mentioned laboratory findings are met. AFLP has abnormal PT/PTT more commonly and more significant liver failure. TTP and HUS do not affect hepatic function as frequently as HELLP syndrome.
Complications
Complications can include disseminated intravascular coagulation (21%), placental abruption (16%), acute renal failure (8%), pulmonary edema (6%), and subcapsular liver hematoma (1%). Hepatic rupture in patients with HELLP syndrome, especially with significant thrombocytopenia, has been associated with a 50% mortality rate. Risk factors for rupture include advanced maternal age, multiparity, and preeclampsia. Blood products may be required in up to 50% of affected pregnancies, and maternal mortality may approach 1%. Neonatal loss rate may range from 7 to 25%, based on gestational age at delivery and presence of growth restriction.
Treatment
Management of the patient diagnosed with HELLP syndrome includes stabilization of the patient/fetus, with replacement of blood and coagulation factors as needed; monitoring urine output/renal function; and treatment of hypertensive disease as necessary. Delivery is the primary treatment and is standard in all but special circumstances. Vaginal delivery is preferred unless there is evidence of fetal growth restriction, placental abruption, or early gestational age with rapidly worsening disease. Antenatal corticosteroids can be given for pregnancies <34 weeks, with some benefit conferred during the labor induction process. If caesarean section is required, a vertical midline incision is recommended secondary to fewer wound separations or infections. HELLP syndrome frequently resolves quickly after delivery, although the platelets and transaminases may nadir up to 36 hours after delivery before improving. Intravenous steroids have not been shown to affect long-term outcome, although one trial demonstrated more rapid recovery of the platelet count with steroids.
Prognosis
Complications of HELLP syndrome can be significant for both the mother and the fetus; however, with prompt recognition and delivery, the vast majority of patients rapidly improve. Recurrence rate for HELLP syndrome ranges from 3 to 25%, whereas the incidence of preeclampsia in subsequent pregnancies ranges from 25 to 75%. Additionally, these women may be at increased risk for cardiovascular disease later in life in the nonpregnant state. Low-dose aspirin prophylaxis has been demonstrated to reduce the recurrence rate in future pregnancies.
Cappell MS. Hepatic disorders severely affected by pregnancy: Medical and obstetric management. Med Clin North Am 2008;92:739–760. PMID: 18570941.
Joshi D, James A, Quaglia A, et al. Liver disease in pregnancy. Lancet 2010;375:594–605. PMID: 20159293.
Kirkpatrick CA. The HELLP syndrome. Acta Clinica Belgica 2010;65:91–97. PMID: 20491358.
OTHER GASTROINTESTINAL DISORDERS IN PREGNANCY
VIRAL HEPATITIS
Hepatitis A
Hepatitis A may occur sporadically or in epidemics. A generalized viremia occurs with the infection that is predominantly hepatic. Symptoms include nausea, headaches, poor appetite, and weight loss. Additionally, diarrhea, fever, and jaundice can be seen. The primary mode of transmission is the fecal–oral route. Excretion of the virus in stool normally begins approximately 2 weeks prior to the onset of clinical symptoms and is complete within 3 weeks after the onset of clinical symptoms. No known carrier state exists for the virus. Both blood and stool are infectious during the 206-week incubation period. Illness during the third trimester may be associated with an increased risk of preterm labor. Vertical transmission of hepatitis A has not been reported, and breastfeeding is encouraged with attention to appropriate hand washing. The hepatitis A vaccine is safe to receive during pregnancy.
Hepatitis B
This virus is typically transmitted by inoculation of infected blood or blood products or through sexual intercourse. The virus is contained in most body secretions, and infection by parenteral and sexual contact has been documented. Groups at risk for hepatitis B infection are intravenous drug users, men who have sex with men, health care personnel, spouses of hepatitis carriers, those with multiple sexual partners, and Southeast Asian emigrants. Approximately 5–10% of people infected with hepatitis B virus become chronic carriers of the virus. The incubation period is 6 weeks to 6 months. The clinical features of hepatitis A and B are similar, although hepatitis B is more insidious. Fulminant hepatitis is rare with hepatitis A but occurs in approximately 1% of patients infected with hepatitis B.
The hepatitis B surface antigen (HBsAg) is the marker usually measured in blood to document prior exposure. This is the first manifestation of viral infection; it usually appears before clinical evidence of the disease and lasts throughout the infection. Persistence of HBsAg after the acute phase of hepatitis usually is associated with clinical and laboratory evidence of chronic hepatitis. The hepatitis B core antibody (HBcAb) is produced against the core of the viral particle and occurs with acute hepatitis B infection at the onset of clinical illness. Hepatitis B e antigen (HBeAg) is found only when HBsAg is present. Pregnant women who are HBeAg positive in the third trimester frequently transmit this infection to the offspring (80–90%), whereas those who are negative have a much lower transmission rate (10–20%).
Treatment of an acute infection during pregnancy is supportive, and there is no associated increased mortality or teratogenicity. Women with elevated hepatitis B viral loads (>106 copies/mL) or who are HBeAg positive during the third trimester are frequently treated with lamivudine, which has been demonstrated to significantly decrease the risk of vertical transmission. In addition, newborns born to HBsAg-positive mothers should receive hepatitis B immunoglobulin within 12 hours after birth concurrently with the first pediatric dose of the vaccine. Breastfeeding is not contraindicated in patients with hepatitis B (chronic or acute).
Hepatitis C
Up to 85% of infected individuals become chronic carriers. The incubation period usually is 7–8 weeks, but ranges from 3 to 21 weeks. The course of infection is similar to that of hepatitis B. Hepatitis C antibody is present in approximately 90% of patients. However, the antibody may not be detectable for weeks after infection. Acute or chronic hepatitis C does not adversely affect a pregnancy, with similar rates of miscarriage, growth restriction, preterm delivery, or hypertensive disorders among infected patients and controls. Vertical transmission occurs in 5–8% of infected pregnancies and is increased with concomitant HIV infection (36%). The risk of vertical transmission is increased with higher hepatitis C viral loads. The mode of delivery does not appear to influence transmission rate; however, fetal scalp blood sampling or placement of a fetal scalp electrode for fetal heart rate monitoring should be avoided if possible. Prolonged rupture of membranes increases transmission risk, but in the premature fetus, risks of the gestational age must be balanced against the risk of transmission. Breastfeeding is not contraindicated in women infected with hepatitis C.
Lopez M, Coll O. Chronic viral infections and invasive procedures: Risk of vertical transmission and current recommendations. Fetal Diagn Ther 2010;28:1–8. PMID: 20558971.
Panda B, Panda A, Riley LE. Selected viral infections in pregnancy. Obstet Gynecol Clin North Am 2010;37:321–331. PMID: 20685556.
Zhongjie S, Yang Y, Ma L, et al. Lamivudine in late pregnancy to interrupt in utero transmission of hepatitis B virus. Obstet Gynecol 2010;116:147–159. PMID: 20567182.
CHOLECYSTITIS
Cholecystitis occurs rarely during pregnancy (0.3%) secondary to the relaxing effects of progesterone on the smooth muscle of the gallbladder and biliary duct. Acute inflammation during pregnancy is treated with intravenous fluids and limitation of oral intake. If acute cholecystitis does not resolve or if pancreatitis develops, cholecystectomy should be considered. If this operation can be performed in the second trimester, the fetal loss rate is likely not increased. The laparoscopic approach in pregnancy is widely accepted. After 20 weeks’ gestation, it should be performed with special care to avoid injury to the uterus. In the third trimester, surgical intervention can contribute to preterm delivery, and monitoring of uterine contractions should be done after surgery. Additionally, it is generally recommended to have fetal monitoring during the surgical procedure, especially if the pregnancy is past viability. See Chapter 25 (Surgical Disorders in Pregnancy) for an extended review of this topic.
INTRAHEPATIC CHOLESTASIS OF PREGNANCY
Intrahepatic cholestasis of pregnancy is characterized by accumulation of bile acids in the liver with subsequent accumulation in the plasma, causing pruritus and jaundice. It is similar to cholestasis that occasionally occurs during combined oral contraceptive therapy. Estrogens are considered to play a role in its etiology, probably by slowing the enzymes involved in bile transport. Its incidence varies with geographical location and ethnicity (most common in Chile); there is an increased incidence with multiple pregnancies.
The most significant symptom is total-body itching, specifically involving the palms and soles. The differential diagnosis includes hepatitis and biliary tract disease, in addition to AFLP and the HELLP syndrome. Laboratory values show increased levels of alkaline phosphatase, bilirubin, and serum bile acids (chenodeoxycholic acid, deoxycholic acid, cholic acid). AST and ALT levels may be mildly elevated. Patients may be symptomatic weeks before the diagnostic laboratory abnormalities are noted.
Symptomatic treatment of pruritus with antihistamines such as diphenhydramine is useful as an initial therapy. Ursodeoxycholic acid (10–15 mg/kg/d in 2 divided doses) has been shown to inhibit absorption of bile acids and increase their biliary excretion. In doing so, the medication normalizes bile acids, improves liver function tests, and alleviates pruritus. Oral steroids also have been used to relieve symptoms. There is rapid resolution of both laboratory abnormalities and symptoms after delivery.
Intrahepatic cholestasis of pregnancy has been associated with fetal death, spontaneous preterm birth, meconium staining of the amniotic fluid and/or placenta, and postpartum hemorrhage. No specific method of antepartum testing has been demonstrated to prevent fetal demise, although twice-weekly modified biophysical profile testing is suggested by some. Poor obstetrical outcomes seem to be highest in women with total bile acid levels >40 nmol/L. There is no consensus on management of patients with regard to delivery; varying strategies include amniocentesis for fetal lung maturity between 36 and 37 weeks’ gestational age, delivery at 37–38 weeks without fetal lung maturity studies, or allowing spontaneous labor to ensue if bile acids are <40 nmol/L and only intervening earlier if the bile acids are higher than this threshold.
See Chapter 30 (Dermatologic Disorders in Pregnancy) for an extended review of this topic.
Greenes V, Williamson C. Intrahepatic cholestasis of pregnancy. World J Gastroenterol 2009;15:2049–2066. PMID: 19418576.
Mays JK. The active management of intrahepatic cholestasis of pregnancy. Curr Opin Obstet Gynecol 2010;22:100–103. PMID: 20124899.
Pathak B, Sheibani L, Lee RH. Cholestasis of pregnancy. Obstet Gynecol Clin North Am 2010;37:269–282. PMID: 20685553.