16 Genitourinary Assessment and Renal Disease in Pregnancy

Katherine Ikard Stewart

Robert M. Ehsanipoor

KIDNEY AND URINARY TRACT DISORDERS

Renal Physiology in Pregnancy

• The renal system undergoes many physiologic changes during a normal pregnancy.

• Structural changes: During pregnancy, the kidneys increase 1 to 1.5 cm in length and 30% in volume. The collecting system expands more than 80%, with greater dilation on the right side.

• Mild right-sided physiologic hydronephrosis is seen as early as 6 weeks of gestation. Renal volume returns to normal within the first week postpartum, but hydronephrosis and hydroureter may not normalize until 3 to 4 months after delivery. Elective pyelography should, therefore, be deferred until at least 12 weeks postpartum.

• These structural changes increase the risk of pyelonephritis in the setting of asymptomatic bacteriuria or urinary tract infections.

• Renal filtration: Blood volume expansion during pregnancy increases renal plasma flow by 50% to 80%, which in turn results in an increased glomerular filtration rate (GFR). Increased GFR can be seen within 1 month after conception, peaking at 40% to 50% above prepregnancy levels by the end of the first trimester.

• Elevated GFR increases creatinine clearance, so formulas for GFR based on age, height, and weight do not apply; creatinine clearance must be calculated with a 24-hour urine collection in pregnancy.

• Increased GFR results in lower mean serum blood urea nitrogen (BUN) and serum creatinine during pregnancy (8.5 and 0.46 mg/dL, respectively). A serum creatinine which may be considered normal outside of pregnancy may suggest renal insufficiency in pregnancy.

• Renal tubular function: Decreased tubular resorption in pregnancy increases urinary excretion of electrolytes, glucose, amino acids, and protein.

• Increased calcium clearance is balanced by increased gastrointestinal (GI) tract absorption. Ionized calcium remains stable despite decreased total serum calcium because of the lower serum albumin concentration.

• Physiologic hyponatremia occurs, with plasma sodium concentration falling by 5 mEq/L during pregnancy. Sodium levels return to baseline by 1 to 2 months postpartum.

• Urinary excretion of glucose increases 10- to 100-fold, and glucosuria is observed routinely in normal pregnancy. Increased urinary glucose increases the risk of bacteriuria and urinary tract infections.

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• Renal resorption of bicarbonate decreases to compensate for the respiratory alkalosis of pregnancy, lowering serum bicarbonate by about 5 mEq/L in pregnancy.

• Routine assessment of renal function: Proteinuria should be assessed at every prenatal visit. A urine dipstick value > 1 + should prompt further evaluation by clean-catch urine sample for culture and microscopy.

If proteinuria persists despite negative culture, further evaluation is warranted and may include either a 24ญhour urine protein collection or a random protein to creatinine ratio. A 24-hour total urine protein exceeding 150 mg is abnormal.

• Patients with chronic hypertension, diabetes, preexisting renal disease, or other diseases may have abnormal levels of proteinuria prior to pregnancy and should undergo a baseline 24-hour urine protein collection early in pregnancy.

• Serum creatinine persistently >0.9 mg/dL should prompt investigation for intrinsic renal disease. The presence of comorbidities should be assessed and further evaluation should be considered. Renal biopsy during pregnancy should be considered when the results will change management before delivery.

Urinary Tract Disorders in Pregnancy

Urinary Tract Infection

• Urinary tract infections (UTIs) are common in pregnancy. Urinary stasis secondary to hydroureter and hydronephrosis, bladder trauma due to compression or edema, vesicoureteral reflux, and increased glucosuria may all contribute to the increased risk of infection.

• Asymptomatic bacteriuria (ASB) is the presence of bacteria within the urinary tract, excluding the distal urethra, without signs or symptoms of infection. ASB is associated with low-birth-weight infants and preterm delivery, and its treatment in pregnancy is indicated. The prevalence of ASB during pregnancy ranges from 2% to 7%. If left untreated, 20% to 30% of ASB in pregnant women progresses to pyelonephritis; treatment reduces this to 3%. Screening for bacteriuria with a urine culture is recommended at the first prenatal visit. Women with sickle cell trait have a twofold increased risk of ASB and can be screened every trimester.

๎ A clean-catch urine culture with > 100,000 colonies/mL or catheterized urine culture with >100 colonies/mL warrants treatment.

๎ Escherichia coli accounts for 75% to 90% of infections. Klebsiella, Proteus, Pseudomonas, Enterobacter, and coagulase-negative Staphylococcus are other common pathogens.

๎ Initial therapy is usually empiric and may be altered based on urine culture sensitivities. Repeat urine culture is obtained 1 to 2 weeks after treatment and again each trimester. If bacteriuria persists after two or more treatment courses, suppressive therapy should be considered for the remainder of the pregnancy.

• Acute cystitis occurs in approximately 1 % to 3% of pregnant women. Symptoms include urinary frequency, urgency, dysuria, hematuria, and/or suprapubic discomfort. Empiric treatment regimens are the same as for ASB. If possible, a urine culture should be sent prior to initiating antibiotic therapy.

• Urethritis is usually caused by Chlamydia trachomatis, and it should be suspected in patients with symptoms of acute cystitis and a negative urine culture. Mucopurulent cervicitis may also be present. The treatment of choice is azithromycin 1 g as a single oral dose for both the patient and her partner.

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Pyelonephritis

• Acute pyelonephritis occurs in approximately 1 % to 2% of all pregnancies and is the leading cause of septic shock in pregnancy. Complications include preterm labor, preterm premature rupture of membranes (PPROM), bacteremia, sepsis, acute respiratory distress syndrome, and hemolytic anemia. Prompt diagnosis and treatment of pyelonephritis in pregnancy are crucial.

• Symptoms include fever, chills, flank pain, nausea, and vomiting. Frequency, urgency, and dysuria are variably present.

• Pyelonephritis is a clinical diagnosis. Urine culture, complete blood count (CBC), serum creatinine, and electrolytes should be obtained at admission. Blood cultures need not be routinely performed in pyelonephritis and can be reserved for severely ill patients.

• Treatment includes administration of intravenous (IV) broad-spectrum antibiotics, hydration, and antipyretics. Cefazolin or ceftriaxone are commonly used and are equivalent to ampicillin plus gentamicin. For penicillin allergy, clindamycin plus gentamicin is appropriate. Fluoroquinolones are generally avoided during pregnancy.

• Pregnant women with pyelonephritis are at significant risk for developing acute respiratory distress syndrome. They should be closely monitored for evidence of respiratory symptomatology with provision of respiratory support as needed.

• T ransition to an oral regimen is appropriate after an afebrile period of greater than 48 hours. Antibiotic regimen should be chosen based on urine culture sensitivities. Oral therapy is continued to complete a 14ญday antibiotic course. Daily suppressive therapy (T able 16-1) is then initiated for the remainder of pregnancy due to the recurrence risk of approximately 20%.

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• If there is no response to antibiotic treatment within 48 hours, review antibiotic dosing and sensitivities, send repeat urine culture, and obtain renal ultrasonography to evaluate for anatomic anomalies, nephrolithiasis, and intrarenal or perinephric abscess.

TABLE 16-1 Antimicrobial Agents for Treatment of Urinary Tract Infection and Asymptomatic Bacteriuria

Single dose

Amoxicillin, 3 g

Ampicillin, 2 g

Cephalexin, 2 g

Nitrofurantoin, 200 mg

Sulfisoxazole, 2 g

Trimethoprim-sulfamethoxazole, 320/1,600 mg

Short course (3-7 days)

Amoxicillin, 250-500 mg tid

Ampicillin, 250 mg qid

Cephalexin, 250-500 mg qid

Nitrofurantoin, 100 mg bid

Sulfisoxazole, 1 g then 500 mg qid

Trimethoprim-Sulfamethoxazole, 320/1,600 mg bid

Suppression therapy

Nitrofurantoin, 100 mg qhs

Ampicillin, 250 mg po qd

Trimethoprim-Sulfamethoxazole, 160/800 mg qd

tid, three times a day; qid, four times a day; bid, twice a day; qhs, at bedtime; po, by mouth; qd, every day.

Nephrolithiasis

• Nephrolithiasis should be considered in a pregnant patient with acute onset of abdominal or flank pain. The incidence is between 0.3 and 4.0 per 1,000 pregnancies. Increased urinary excretion of calcium, urinary stasis, and dehydration are risk factors associated with development of renal stones in pregnancy.

• Diagnosis is primarily clinical. Classic symptoms include acute onset of colicky flank pain, hematuria, and pyuria. In more than 50% of cases, the stone passes spontaneously after hydration and may be observed directly by filtering the patient's urine. Renal ultrasonography should be performed to rule out obstruction, but pathologic obstruction from a renal stone must be differentiated from physiologic hydronephrosis of pregnancy. If the diagnosis remains uncertain and there is a negative ultrasound, magnetic resonance (MR) urography or noncontrast computed tomography (CT) scan can be considered.

• Initial treatment is administration of IV hydration and analgesia, with the patient lying on her side with the symptomatic side up. This helps reduce the pressure from the gravid uterus on the affected side. Approximately 75% of stones will pass spontaneously. Associated infections must be treated aggressively.

Glomerular Disease

• Glomerular disease is caused by a wide spectrum of diseases, and its clinical presentation can vary from asymptomatic to renal failure. Clinical syndromes are defined to differentiate these patients, with nephritic and nephrotic syndrome being the most common. Definitive diagnosis ultimately requires a renal biopsy. However, with potential risks, renal biopsy should only be pursued in pregnancy if results will change management.

• Acute nephritic syndrome

• Usually presents with hypertension, hematuria, urinary red cell casts, pyuria and mild to moderate proteinuria.

• Causes include poststreptococcal glomerulonephritis, lupus nephritis, immunoglobulin A (IgA) nephropathy, membranoproliferative glomerulonephritis, endocarditis-associated glomerulonephritis, antiglomerular basement membrane disease, Goodpasture syndrome, Wegener syndrome, and Churg-Strauss syndrome.

• Goodpasture, Wegener, Churg-Straus, Henoch-Schonlein purpura, or cryoglobulinemia can also present as a pulmonary renal syndrome with significant hemoptysis along with glomerulonephritis.

• Nephrotic syndrome

• Usually presents with severe proteinuria (>3.5 g/day), hypertension, edema, hyperlipidemia, and minimal hematuria. Minimal cells or casts are present in urine other than fatty casts.

• Causes include minimal change disease, focal segmental glomerulosclerosis often secondary to HIV, membranous glomerulonephritis, diabetic nephropathy, hepatitis C, systemic lupus erythematosus (SLE), and amyloidosis.

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• Complications of glomerular disease in pregnancy include preterm delivery, intrauterine growth restriction (IUGR), stillbirth, maternal hypertension, preeclampsia, and impaired renal function.

Chronic Kidney Disease

• Chronic kidney disease is present in less than 0.2% of all pregnancies. It is defined as impaired renal function or damage for 3 or more months. The most common causes are diabetes, hypertension, glomerulonephritis, and polycystic kidney disease.

• The degree of renal impairment is the major determinant of pregnancy outcome and can be categorized as mild (serum creatinine 3.0 mg/dL). In general, patients with mild renal dysfunction experience little disease progression during pregnancy, whereas patients with moderate to severe renal insufficiency are at high risk for potentially irreversible loss of renal function. Chronic renal disease in the setting of poorly controlled hypertension markedly increases both maternal and fetal risks. Thus, it is very important to optimize blood pressure in addition to other comorbidities such as diabetes or connective tissue disorders that may worsen renal disease.

• Pregnancy complications with chronic renal disease include fetal demise, fetal growth restriction, preeclampsia, eclampsia, and preterm delivery. Maternal and fetal outcomes correlate with severity of baseline renal function and presence of comorbidities.

• Antepartum management includes the following:

• Early pregnancy diagnosis and dating.

• Preconception planning and counseling are encouraged.

• Baseline laboratory studies including serum creatinine, electrolytes, BUN, 24-hour urine protein and creatinine clearance, urinalysis, and urine culture. Serial monitoring of maternal renal function, as clinically indicated.

• Consider increased frequency of prenatal visits, depending on disease severity.

• Consider serial ultrasonographic fetal growth examinations.

Consider antepartum fetal testing in the third trimester.

Renal Dialysis

• Conception occurs in approximately 1 % per year of reproductive aged women on dialysis. Between 40% and 75% of these pregnancies result in delivery of a surviving infant. There is a high rate of spontaneous abortion and pregnancy complications. Most infants are born premature usually secondary to severe maternal hypertension or preeclampsia. These patients are also at increased risk of IUGR, polyhydramnios, PPROM, nonreassuring fetal testing, and placental abruption. With significant maternal risks of pregnancies being maintained on dialysis, including severe hypertension, cardiac events, and death, delaying pregnancy until after renal transplantation may be advantageous.

• Neonatal outcomes are improved with maintenance of the BUN Lab abnormalities arise a mean of 3 weeks after the development of pruritus. Serum alkaline phosphatase and transaminase levels are modestly elevated. Serum gamma glutamyl transpeptidase, albumin, and prothrombin time remain normal.

• Treatment is mainly for symptomatic relief until delivery, which is the definitive therapy. Diphenhydramine, topical emollients, and dexamethasone (12 mg/day for 7 days) can relieve pruritus. Ursodeoxycholic acid (8

to 10 mg/kg/day) is the most effective treatment and works by increasing bile flow, thereby decreasing serum bile acid levels and decreasing pruritus. Cholestyramine (8 to 16 g, two to four times per day) decreases intestinal absorption of bile salts and is effective for mild to moderate symptoms but does not improve lab values. Fat-soluble vitamins (A, D, E, and K) and prothrombin time should be checked periodically for patients taking cholestyramine for extended treatment. If the prothrombin time is elevated, 10 mg/day of oral vitamin K should be administered until the coagulation profile normalizes.

• ICP at term is associated with 3% risk of fetal demise. Antepartum fetal testing is recommended, although intrauterine demise may occur despite reassuring testing. Delivery should be performed no later than 38 weeks' gestation. When cholestasis is severe, delivery at 36 weeks with or without fetal lung maturity may be considered.

• Recurrence risk in subsequent pregnancies is approximately 70% and is usually more severe. Estrogen- containing oral contraceptives can cause cholestasis in these patients.

TABLE 17-1 Liver Function Test Changes during Normal Pregnancy

↑, increased or elevated; j, decreased; -→, unchanged. PT, prothrombin time; aPTT, activated partia l thromboplastin time.

Acute Fatty Liver of Pregnancy

• Acute fatty liver of pregnancy (AFLP) is uncommon, occurring in 1 in 10,000 pregnancies. It typically occurs in primigravid women in the third trimester and is associated with multiple gestations, male fetuses, and with a fetal mitochondrial gene mutation causing long chain 3-hydroxylacyl-CoA-dehydrogenase deficiency. Patients present with nausea, vomiting, epigastric pain, anorexia, jaundice, and malaise. Intra-abdominal bleeding or altered mental status may indicate disease progression to disseminated intravascular coagulation (DIC) or hepatic failure. Laboratory tests may reveal hypoglycemia, elevated aminotransferases to 1,000 IU/L, leukocytosis, thrombocytopenia, coagulopathy, markedly reduced antithrombin III, metabolic acidosis, hyperuricemia, and renal failure. Treatment includes maternal stabilization with intensive supportive care and prompt delivery, either with induction of labor with close maternal and fetal surveillance or cesarean delivery. Liver function usually normalizes within 1 week postpartum, and recurrence in subsequent pregnancy is uncommon.

Hepatic Disorders Not Directly Related to Pregnancy

Hepatitis

• Acute and chronic hepatitis—See Chapter 11.

Cirrhosis

• Hepatic cirrhosis leads to metabolic and hormonal derangements that usually induce anovulation, amenorrhea, and infertility. Cirrhosis is associated with 30% to 40% risk of spontaneous abortion, 25% risk of preterm delivery, and up to 18% risk of neonatal mortality. Maternal mortality is estimated at 10% but may be up to 50% in patients with portal hypertension who develop gastrointestinal bleeding during pregnancy. Outcomes are generally poor, but hepatic dysfunction before pregnancy and the presence of portal hypertension correlate with worse maternal/fetal prognosis.

• Esophageal variceal bleeding is the most common complication, occurring in 18% to 32% of pregnant women with cirrhosis. To reduce portal pressure and the risk of acute bleeding, beta-blockers such as propranolol should be considered. As in nonpregnant patients, endoscopic variceal ligation is the mainstay of therapy for acute episodes of hemorrhage. Portal decompression shunt placement is required when hemorrhage cannot be controlled by endoscopy. If endoscopy is unavailable, balloon tamponade can be employed to control severe bleeding. Other complications include ascites and bacterial peritonitis, splenic artery aneurysm, portal vein thrombosis, portal vein hypertension, hepatic encephalopathy or coma, postpartum uterine hemorrhage, and death.

• Vaginal delivery is preferred over cesarean delivery due to the high rate of intraoperative and postoperative complications. In patients with portal hypertension, however, repetitive Valsalva in the second stage of labor can increase the risk of significant variceal bleeding. A passive second stage with forceps-assisted delivery may be beneficial.

Budd-Chiari Syndrome

• Budd-Chiari syndrome is a veno-occlusive disease of the hepatic vein that increases hepatic sinusoidal pressure and can result in portal hypertension or hepatic necrosis. The disease presents with abdominal pain and the abrupt onset of ascites and hepatomegaly. Cases are often caused by congenital vascular anomalies, myeloproliferative disorders, and thrombophilic disorders. In obstetrics, the disease typically occurs postpartum. Diagnosis is by hepatic Doppler ultrasonography to identify venous occlusion and evaluate the direction and amplitude of blood flow. Acute therapy includes selective thrombolytics and a surgical shunt or transjugular intrahepatic portosystemic shunt (TIPS) for portal hypertension. Chronic Budd-Chiari syndrome is treated with anticoagulation therapy.

Choledochal Cyst

• Choledochal cysts are rare, occurring in 1 in 100,000 people. They generally produce abdominal pain, jaundice, and a palpable abdominal mass. Compression

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by the gravid uterus may lead to cyst rupture, potentially resulting in cholangitis. Surgical management is

generally recommended.

Gallbladder Disorders

Cholelithiasis

• Cholelithiasis occurs in up to 10% of pregnancies and is often clinically silent. Biliary stasis from progesterone-induced smooth muscle relaxation and the prolithogenic effect of elevated estrogen levels in pregnancy may predispose to gallstone formation. Symptomatic patients typically complain of vague intermittent right upper quadrant discomfort that occurs with meals. Asymptomatic cholelithiasis requires no treatment during pregnancy.

• Symptomatic cholelithiasis and acute cholecystitis—See Chapter 22.

Other Gastrointestinal Disorders

Hyperemesis Gravidarum

• Hyperemesis gravidarum is a severe form of nausea and vomiting in pregnancy, characterized by intractable vomiting, dehydration, alkalosis, hypokalemia, and weight loss usually exceeding 5% of prepregnant body weight. It affects 0.3% to 2% of pregnancies and peaks between the 8th and 12th weeks of pregnancy. The etiology may be multifactorial, involving hormonal, neurologic, metabolic, toxic, and psychosocial factors.

• Nausea (with or without vomiting) occurs in up to 90% of pregnancies at any time of day, despite the general term “morning sickness.” Mean onset of symptoms is 5 to 6 weeks' gestation. Although symptoms typically abate by 16 to 18 weeks of gestation, they continue into the third trimester in 15% to 20% of pregnant women and until delivery in 5%.

• With true hyperemesis gravidarum, persistent vomiting leads to plasma volume depletion and elevated hematocrit and metabolic derangements that include increased blood urea nitrogen, hyponatremia, hypokalemia, hypochloremia, and metabolic alkalosis. A complete workup includes pelvic sonogram to identify multiple gestation or molar pregnancy and thyroid function tests to evaluate for hyperthyroidism. Some patients with hyperemesis gravidarum have transient benign hyperthyroidism most likely due to thyroid stimulation by the human chorionic gonadotropin (hCG) molecule, which is structurally similar to thyroidstimulating hormone (TSH) and has been shown in animal studies to be a weak thyrotropin. This usually resolves spontaneously as pregnancy continues.

• Treatment depends on the severity of symptoms. Usually, intravenous (IV) hydration and antiemetic therapy are sufficient. Patients may require hospitalization for intractable emesis, electrolyte abnormalities, and severe hypovolemia. Thiamine supplementation (100 mg daily intramuscularly [IM] or IV) is given prior to administration of glucose to prevent Wernicke encephalopathy. Oral feeding with a bland diet should be introduced slowly as tolerated. If symptoms are refractory to medical and supportive care, a psychiatry consultation may be considered.

๎ There are no drugs approved specifically for the treatment of nausea and vomiting in pregnancy; however, the following medications have been clinically effective:

๎ Pyridoxine (vitamin B₆) 10 to 25 mg PO three times daily

๎ Doxylamine succinate 12.5 mg PO three times daily taken with pyridoxine 10 to 50 mg. A recent formulation of delayed release tablets of 10 mg of

doxylamine and 10 mg of pyridoxine has recently become available in the United States, which may be taken as needed up to two tablets in the morning and one in the afternoon and evening.

๎ Metoclopramide hydrochloride (Reglan) 5 to 10 mg PO or IV three times daily

๎ Promethazine hydrochloride (Phenergan) 12.5 to 25 mg PO or IV four times daily

๎ Prochlorperazine (Compazine) 10 to 50 mg PO, IV, or IM three or four times daily

๎ Ondansetron hydrochloride (Zofran) 4 to 8 mg PO or IV three times daily

๎ Methylprednisolone (Medrol) 16 mg PO or IV every 8 hours for 3 days may be used for refractory cases after 10 weeks' gestation. There is a theoretical risk of cleft lip and palate when administered in the early to mid-first trimester.

๎ In severe cases requiring prolonged IV hydration, enteral feeds via gastric tube or parenteral nutrition may be initiated. Complications from parenteral nutrition are common and severe. Peripherally inserted catheters (PICC) appear to have a lower complication than centrally inserted catheters, although the complication rate of both is near 50%. Potential complications include pneumothorax, hemothorax, brachial plexus injury, thromboembolism, and catheter sepsis. Risk of line infection can be as common as one in three, with resulting bacteremia or fungemia that can significantly complicate a pregnancy. Vitamin K should be supplemented in addition to the standard parenteral nutrition formula secondary to the risk of fetal intracranial hemorrhage secondary to maternal vitamin K deficiency. Due to these risks, initiation of enteral feeding is strongly recommended preferentially prior to proceeding with parenteral nutrition.

Acid Reflux

• Gastroesophageal reflux disease (GERD) and the resulting symptom of pyrosis (“heartburn”) are common during pregnancy secondary to the altered position of the stomach, decreased lower esophageal sphincter tone (due to elevated progesterone levels), and lower intraesophageal pressures. The incidence is 30% to 50% but may approach 80% in selected populations. Symptoms begin late in the first trimester and become more frequent and severe with increasing gestational age. Risk factors include multiparity and history of GERD before pregnancy.

• Treatment is medical and aimed at neutralizing or decreasing reflux. Lifestyle modification is key in treating mild diseases. Elevating the head of the bed at night, avoiding meals within 3 hours of bedtime, and consuming smaller but more frequent meals can help. Dietary modification is recommended, including reduced consumption of fatty foods, chocolate, and caffeine. Cigarette smoking and alcohol consumption can exacerbate GERD and are discouraged in all patients.

• More persistent symptoms can be treated with over-the-counter antacids (e.g., calcium carbonate) or sucralfate 1 g orally thrice daily. An H₂ blocker, such as ranitidine 150 mg orally twice daily, may be considered. Proton pump inhibitors (e.g., omeprazole) and promotility agents (e.g., metoclopramide) are generally effective and may be used if necessary. Endoscopy is considered if therapeutic measures are unsuccessful and symptoms are severe.

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Peptic Ulcer Disease

• Peptic ulcer disease(PUD) is not common in pregnancy, and the hormonal changes of pregnancy usually decrease PUD severity and symptoms.

• Treatment during pregnancy is similar to treatment for GERD and consists of diet modification, avoiding nonsteroidal anti-inflammatory drugs (NSAIDs), and starting H₂ blockers or proton pump inhibitors. Avoid indomethacin for tocolysis of patients with PUD. Diagnosis of Helicobacter pylori infection is usually reserved for those with active ulcers; treatment regimens for H. pylori without tetracycline are selected.

Inflammatory Bowel Disease

• Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn disease, often presents in reproductive age women. IBD increases the risk for preterm birth, low birth weight, and intrauterine growth restriction. There is no evidence that pregnancy influences disease activity; however, patients with active disease around the time of conception often fail to achieve remission during the pregnancy.

• Treatment is largely pharmacologic, usually with sulfasalazine and corticosteroids. Because sulfasalazine may interfere with folate absorption, supplemental folate should be prescribed. Immunosuppressive agents, such as azathioprine, 6-mercaptopurine, cyclosporine, or infliximab, are used for more severe disease. Limited experience shows that all these medications are safe during pregnancy. Methotrexate and mycophenolate are not used in pregnancy. Antibiotics, particularly metronidazole and cephalosporins, are used for perirectal abscesses/fistulae. There is limited data regarding the safety of antidiarrheal medications such as Kaopectate, Lomotil, and Imodium in pregnancy, but significant teratogenicity is unlikely. Surgical intervention is indicated only for severe complications of IBD.

• The mode of delivery may be affected by IBD depending on disease activity and past surgical history. Vaginal delivery can usually be attempted unless there is severe perineal disease or previous colorectal surgery. In such cases, a colorectal surgery consultation should be obtained. Operative vaginal delivery or episiotomy may be avoided to prevent excessive perineal trauma as possible. Cesarean section should be considered in patients with active perianal disease due to the risk of wound complications and fistulae formation.

Pancreatitis

• Pancreatitis is an uncommon cause of abdominal pain in pregnancy, with an incidence of 1 in 1,000 to 1 in 3,800 pregnancies.

• The presentation is usually midepigastric or left upper quadrant pain with radiation to the back, nausea, vomiting, ileus, and low-grade fever. Cholelithiasis is the most common cause of pancreatitis during pregnancy. Ultrasound is of limited use for acute pancreatitis in pregnancy because of the enlarged uterus and overlying bowel gas.

• Management consists of IV hydration, analgesics, and bowel rest. Most cases of gallstone pancreatitis can be managed medically. See Chapter 22 for surgical management.

Appendicitis

• Appendicitis can be a challenging diagnosis in the gravid patient due to the changes of pregnancy. See Chapter 22.

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SUGGESTED READINGS

Bacq Y, Sentilhes L, Reyes HB, et al. Efficacy of ursodeoxycholic acid in treating intrahepatic cholestasis of pregnancy: a meta-analysis. Gastroenterology 2012;143(6):1492-1501.

Brites D, Rodrigues CM, Oliveira N, et al. Correction of maternal serum bile acid profile during ursodeoxycholic acid therapy in cholestasis of pregnancy. J Hepatol 1998;28(1 ):91-98.

Holmgren C, Aagaard-Tillery KM, Silver RM, et al. Hyperemesis in pregnancy: an evaluation of treatment strategies with maternal and neonatal outcomes. Am J Obstet Gynecol 2008;198(1):56.e1-e4.

Kenyon AP, Piercy CN, Girling J, et al. Obstetric cholestasis, outcome with active management: a series of 70 cases. Br J Obstet Gynaecol 2002;109(3):282-288.

Ogura JM, Francois KE, Perlow JH, et al. Complications associated with peripherally inserted central catheter use during pregnancy. Am J Obstet Gynecol 2003;188(5):1223-1225.

Russo-Stieglitz KE, Levine AB, Wagner BA, et al. Pregnancy outcome in patients requiring parenteral nutrition. J Matern Fetal Med 1999;8(4):164-167.