Abdominal Pain During Pregnancy

PREGNANCY AND GASTROINTESTINAL DISORDERS 0889-8553/98 $8.00 + .OO

ABDOMINAL PAIN DURING PREGNANCY

Ira E. Mayer, MD, and Hamid Hussain, MD

Abdominal pain is one of the most common symptoms with which patients present to physicans. Primary care physicians, gastroenterologists, gynecologists, surgeons, and emergency physicians evaluate and treat patients with abdominal pain of varying severity on a daily basis. The pregnant patient with abdomhal pain presents unique challenges to the physician. First, the diagnosis of pregnancy may not be established or suspected at the time of patient presentation. Second, the anatomic and physiologic changes that normally occur during pregnancy alter the physical findings and laboratory values that are often used to determine the cause of abdominal pain. Third, several abdominal disorders that occur solely during pregnancy can produce significant morbidity and mortality if not promptly identified and treated. Fourth, the physician is constrained in the use of certain diagnostic procedures because of possible teratogenicity. Fi- nally, the physician is treating two patients simultaneously, the mother and fetus, and must be aware of the potential effect of therapy on both patients at all times. This article reviews the mechanisms of abdominal pain and discusses the causes of abdominal pain in the pregnant patient.

PERCEPTION OF ABDOMINAL PAIN

The sensation of pain is a complex process that is initiated by the stimulation of nociceptor~.7~, 80, 132, These neuroreceptors are located at the free ends of A- delta and C nerve fibers. Nociceptors are activated by mechanical, thermal, or chemical stimuli. Within the gastrointestinal tract, mechanical receptors are located predominately within the walls and supporting structures, whereas chemoreceptors are located predominately within the mucosa. Chemoreceptors are responsive to chemical, pH, and osmotic changes; tissue hormones or inflamma-

From the Division of Gastroenterology, Maimonides Medical Center (IEM, HH); and the Department of Medicine, New York State Health Science Center, Brooklyn (IEM), Brooklyn, New York

GASTROENTEROLOGY CLINICS OF NORTH AMERICA

VOLUME 27 * NUMBER 1 - MARCH 1998 1

2 MAYER & HUSSAIN

tory mediators such as histamine may also directly stimulate receptors or lower the threshold of receptors to other stimuli.

After receptor stimulation occurs, impulses are transmitted to the spinal cord by the A-delta and C nerve fibers. A-delta fibers are larger in diameter, thinly myelinated, and more quickly conducting. Their distribution is predomi- nantly to skin and muscle, and they convey impulses denoting acute, well- localized injury. C fibers are smaller in diameter, nonmyelinated, and slowly conducting, and they convey a nonspecific, nonlocalized sensation of pain. Visceral afferent fibers from the gastrointestinal tract travel with sympathetic nerves to the spinal cord except for visceral afferents from the appendix, left colon and rectum, and pelvic organs, which travel with parasympathetic nerves.

These afferent neurons have their cell bodies in the dorsal root ganglion of the corresponding spinal cord segment. These dorsal horn cells also receive sensory input from afferent fibers supplying skin, subcutaneous tissue, and muscle, accounting for the sensation of referred pain. These neurons interact with other spinal cord neurons as well as transmit impulses to higher centers via second-order neurons, which cross through the anterior commissure to the contralateral side and ascend in the lateral spinothalamic and spinoreticulotha- lamic tracts. These neurons terminate in the reticular area of the brain stem, hypothalamus, or thalamus. Third-order neurons then convey impulses to the limbic system and sensory cortex, where pain is perceived.

Abdominal pain is divided into visceral pain, parietal (somatic) pain, and referred pain. Visceral pain arises from stimulation of nociceptors in abdominal or thoracic viscera, by the mechanisms elaborated previously. The pain is usually dull or varying in intensity, poorly localized, and usually felt in the midline because most viscera have multisegmental innervation and receive afferents from both sides of the spinal cord. This pain may be accompanied by autonomic disturbances, such as nausea, sweating, and pallor, and the patient may move about to attempt to relieve the discomfort.

Parietal pain arises from stimulation of nociceptors in the parietal peritoneum or abdominal wall. This pain is more acute, intense, and sustained than visceral pain. It tends to be well localized to the anatomic site of the lesion. Parietal pain is usually exacerbated by motion, and patients tend to lie still. Referred pain is felt in remote areas supplied by the same neural segment as the diseased organ. It tends to be well localized and is often associated with cutane- ous or muscular hyperesthesia.

To evaluate the cause of abdominal pain, it is helpful to determine the relation of the pain to other activities or physiologic functions, particularly with regard to exacerbation or alleviation of the pain. These activities and functions include eating, sleeping, specific physical activities, bowel movements, micturi- tion, and the menstrual cycle. The association of other symptoms, such as nausea, vomiting, fever, chills, dizziness, diaphoresis, shortness of breath, me- lena, rectal bleeding, hematemesis, or hematuria, may aid in identifying the cause of the patient's symptoms. The location of the abdominal pain often helps narrow the differential diagnosis (Table 1).

OBSTETRIC DISORDERS

Ectopic Pregnancy

An ectopic pregnancy occurs when the fertilized ovum implants in a loca- The number of ectopic pregnancies in the tion other than the

ABDOMINAL PAIN DURING PREGNANCY 3

Table 1. DIFFERENTIAL DIAGNOSIS OF ABDOMINAL PAIN BY LOCATION

Right Upper Quadrant or Epigastrium Gastroesophageal reflux Peptic ulcer disease Acute pancreatitis Acute appendicitis (third trimester) Cholelithiasis/choledocholithiasis Acute cholecystitis Preeclampsia/eclampsia HELLP syndrome Acute fatty liver of pregnancy Viral hepatitis Herpes simplex hepatitis Hepatic hematoma Budd-Chiari syndrome Hepatic adenoma Hepatocellular carcinoma Choledochal cyst Cholangiocarcinoma Liver abscess Hydatid cyst Pyelonephritis Pneumonia Pulmonary infarction Empyema Pneumothorax Myocardial infarction Pericarditis Endocarditis Congestive heart failure Herpes zoster Radiculopathy Discitis Flank Hydronephrosis of pregnancy Pyelonephritis Urolithiasis Acute appendicitis (third trimester)

Lower quadrant Acute appendicitis (first and second

Ectopic pregnancy Abortion: threatened, incomplete, complete Acute salpingitis Tubo-ovarian abscess Ruptured corpus luteum Adnexal mass/ovarian cyst Adnexal torsion Endometriosis Pyelonephritis Ureteral colic Cystitis Cervical cancer

Lower Abdomen

Abruptio placentae Placenta percreta Premature labor Uterine leiomyoma Colonic obstruction Inflammatory bowel disease Irritable bowel syndrome Cystitis Pyelonephritis Urolithiasis

Nonlocalized Abdominal Pain Acute appendicitis (early phase) Intestinal obstruction Acute intermittent porphyria Diabetes mellitus Periarteritis nodosa Sickle hemoglobinopathies Drugs and toxins Miliary tuberculosis Malaria

trimesters)

United States reported to the Centers for Disease Control (CDC) has risen from 17,800 in 1970 to 88,000 in 1987, representing an increase in incidence from 4.5 to 16.8 per 1000 p~egnancies.~~ The maternal mortality of ectopic pregnancy in 1986 was 0.05%0.'~~ This condition represents a significant cause of maternal morbidity and mortality, accounting for 6% of all maternal deaths, usually from hemorrhage and shock owing to rupture.87 The clinical presentation of ectopic pregnancy ranges from asymptomatic instances in which the ectopic pregnancy may be reabsorbed and go ~ndetected:~ to vague abdominal symptoms, and, in the extreme, to an acute abdomen.3O Because of the wide variability in presentation, estimates of errors or delays in diagnosis are as high as 40%0.~, 194, 197 For these reasons, an understanding of ectopic pregnancy is essential in the evaluation of the female patient with abdominal pain.

The average age of patients with ectopic pregnancies was 28 (range 15 to 47) years, and the average gravidity (excluding the current ectopic pregnancy)

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Table 2. RISK FACTORS FOR ECTOPIC PREGNANCY

Previous fallopian tube infection Previous fallopian tube surgery Postcoital estrogens

Tuba1 ligation Progesterone minipill Previous ectopic pregnancy Infertility

Congenital fallopian tube abnormalities Diethylstilbestrol exposure in utero

Previous abortion Gamete intrafallopian transfer Use of intrauterine device

Hormonally altered tuba1 transport

Ovulation induction In-vitro fertilization

Data from references 82, 87, 182, and 194.

was three in one series of 200 cases reported by Chez and Moore.3O African- American patients30, 197 and socially disadvantaged patientss7 have a higher incidence of ectopic pregnancies.

The most common location for an ectopic pregnancy is the fallopian tube, accounting for 95% of casess7, Is2; 70% occur within the ampulla, 20% within the isthmus, and 5% within the fimbria.=! 82, a7, ’a2, 194 Other locations, including the interstitial portion of the uterine wall, cornual end of the fallopian tube, uterine cervix, abdominal wall, ovary, and uterine ligaments, account for the remaining instancess7 Abnormal implantation is believed to be due to mechanical interfer- ence with passage of the fertilized ovum. Risk factors that predispose to the development of ectopic pregnancy are listed in Table 2; however, risk factors are identified in only half of patients with documented ectopic ~regnancies.’~~

Abdominal pain is the most common symptom. The patient may complain of vague abdominal or pelvic pain early during the ectopic pregnancy, at 4 to 6 weeks of gestation, caused by distention of the fallopian tubea2; later during the pregnancy, the patient may complain of sharp pain, which may be sudden and severe.l5, 30, 87 The pain usually localizes to the side of the ectopic pregnancy but may initially occur on the contralateral side secondary to a leaking corpus l ~ t e u m . ~ ~ In a review of more than 1000 patients published between 1959 and 1984, HockbergeP reported the incidence of abdominal pain to be 80% to 100%. In a series of 161 patients published in 1990, Stovall and colleagues197 reported abdominal pain in 30% of patients with unruptured ectopic pregnancy and 100% of patients with ruptured ectopic pregnancy. The pain radiates to the shoulder in 20% of patients, associated with hernoperitoneum ranging from 50 mL to 3500 mL.30

Amenorrhea is present in 85% of patients, and abnormal vaginal bleeding is present in 70% of patients.30, 197 The mean duration of amenorrhea before the onset of vaginal bleeding was 5.5 The classic triad of abdominal pain, amenorrhea, and vaginal bleeding is present in 70% of Nausea and vomiting occur in up to 33% of patients, usually associated with abdominal pain or syncopem; dizziness or syncope may occur in about 25% of patients.8z

Physical findings include abdominal tenderness in 90% of patients, adnexal tenderness in 80%, the presence of blood on vaginal examination in up to 6O%, an adnexal mass in 50%, cul-de-sac fullness in 60%, and uterine enlargement in

and in Chez and Moore’s series,3O 20% of patients presented in shock. Following rupture of an ectopic pregnancy, signs of peritoneal irritation are often present: guarding, rebound tenderness, and hypoactive bowel sounds.82

Misdiagnosis or delay in diagnosis historically has been common in ectopic pregnancy. Ectopic pregnancy may be misdiagnosed as acute salpingitis, gastro-

82 Orthostatic hypotension is present in 10% of


enteritis, threatened or incomplete abortion, ruptured corpus luteum cyst, acute appendicitis, tubo-ovarian abscess, dysfunctional uterine bleeding, torsion of the fallopian tube, and endometriosis.82 Other reports have included diagnoses such as cystitis,197 pyelonephritis, ureteral colic, and cervical cancer (see Table l).30 The accuracy of diagnosis has improved through the development and refinement of hormonal assays, including pregnancy testing, and ultrasonography.

Pregnancy tests measure the presence of human chorionic gonadotropin (hCG) in serum or urine!*, Currently available assays provide quantitative measurement of the P subunit of hCG by radioimmunoassay (RIA) or enzyme- linked immunosorbent assay (ELISA). These tests are highly sensitive and specific in diagnosing pregnancy:172, 221 A single determination, however, may not differentiate between viable intrauterine pregnancy, nonviable intrauterine pregnancy, and ectopic pregnancy.221 Kadar and R ~ m e r o ~ ~ demonstrated that the p- hCG level doubles every 1.9 days in normal intrauterine pregnancies, whereas doubling times were slower in 76% of ectopic pregnancies. Pittaway and W e n t ~ ' ~ ~ demonstrated that the doubling time of P-hCG in normal pregnancies varies from 1.6 days in early pregnancy to 3.4 days in the seventh week.

Pelvic ultrasonography should be used in conjunction with hCG determinations to evaluate the patient with suspected ectopic pregnancy. The earliest signs of intrauterine gestation detected by transabdominal ultrasound are the presence of an enlarged uterus and the double-decidual sac sign (produced by the ability to distinguish between the decidua Vera and decidua capsularis), which is usually present by the fourth or fifth gestational week,s2 although it can be detected as early as the second The presence of a gestational sac with a fetal heartbeat is usually not detectable until the seventh to eighth week of gestation.82 Kadar and associatesg1 defined the discriminatory P-hCG zone as the minimal level of P-hCG associated with ultrasonographic demonstration of an intrauterine gestational sac. Using a value of 6500 mIU/mL for transabdominal ultrasonography, absence of a gestational sac had a sensitivity of loo%, specificity of 9670, and positive predictive value of 86% in identifying ectopic pregnancy. Using higher-resolution equipment, Nyberg and demonstrated a lower discriminatory zone with transabdominal ultrasonography; a gestational sac greater than 5 mm in diameter was demonstrable in all patients with normal pregnancies and P-hCG levels above 1800 mIU/mL. Nyberg and colleagues14F also demonstrated that using transvaginal ultrasonography the discriminatory zone was reduced to 1000 mIU/mL. Transvaginal ultrasonography can detect gestational sacs as small as 2 mm in diameter.'% In addition to identification, or lack thereof, of intrauterine gestation, sonography, either transabdominal or transvaginal, may demonstrate an adnexal mass, fluid in the cul-de-sac, or an extrauterine gestational sacs2, 148, 17*, 221

Serum progesterone levels were also investigated as aids in the diagnosis of ectopic pregnancy or nonviable intrauterine gestations. Several studies showed that the mean progesterone levels are lower in patients with abnormal pregnancies2*, 60! 127, 135, lS2 , 197, 198 but frequently overlap with the range of values in normal pregnancies. Although ectopic pregnancy is rarely associated with progesterone levels greater than 20 ~~g / rnL ,*~ 6o up to 10% of normal pregnancies have progesterone levels less than 15 ng/mL.198 Moreover, patients with ectopic pregnancy who underwent ovulation induction had levels greater than 20 ng/ mL.60 Therefore, progesterone levels may be useful adjuncts in stable patients in whom P-hCG levels and sonography are inconclusive but are not diagnostic by themselves.

Invasive tests for the diagnosis of ectopic pregnancy include culdocentesis and laparoscopy. Although culdocentesis had previously been performed in

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most patients with suspected ectopic pregnancy,3O the availability of P-hCG determination and sonography has decreased the need for this procedure?21 Culdocentesis still has a role, particularly in the patient with peritoneal signs and suspected ectopic pregnancys7 or in early pregnancy.1so Aspiration of non- clotting blood is considered evidence of ectopic pregnancy with rupture.

The management of the patient with suspected ectopic pregnancy must be tailored to the specific situation. The patient presenting with hemodynamic instability or signs of peritoneal irritation requires hematocrit and p-hCG determinations, vigorous fluid resuscitation (two large-bore intravenous lines), type and crossmatch, and emergency gynecologic consultation. Culdocentesis is useful to determine rapidly the presence or absence of intraperitoneal blood; sonography may be helpful if it can be rapidly obtained in the emergency department.8z

Stable patients with suspected ectopic pregnancy should undergo j3-hCG determination and transabdominal ultrasonography; transvaginal ultrasonography is useful if the transabdominal study is equivocal. If these studies reveal a normal intrauterine gestational sac, the patient should be evaluated for other causes of abdominal pain. If an intrauterine gestational sac is not identified, and P-hCG levels are above the discriminatory zone, further investigation with laparoscopy or culdocentesis should be performed. If the P-hCG level is below the discriminatory zone, the patient can be monitored closely, with serial P-hCG levels every 2 days. The patient should be instructed to return if she experiences dizziness, syncope, or increasing abdominal pain. If the PhCG level rises by at least 66% every 2 days, sonography should be repeated when the level reaches the discriminatory zone. If no gestational sac is identified or if the p-hCG fails to rise as expected, laparoscopy or culdocentesis should be performed.s2

Definitive therapy consists of surgical excision of the ectopic pregnancy. Although in the past salpingectomy was generally performed, conservative surgery with salpingostomy is currently preferred when feasible to preserve fertility.s7, 194 This can often be accomplished laparoscopically, resulting in decreased morbidity, length of stay, and Oral, intravenous, or intramuscular methotrexate has also been used to treat unruptured ectopic pregnancie~.~~

Abdominal Pregnancy

Abdominal pregnancy is a form of ectopic pregnancy in which the implantation occurs within the peritoneal cavity, unattached to the fallopian tubes, uterus, ovaries, or broad ligaments. Its incidence is 10.8 per 100,000 live births in the United States.lz4 The most common symptom is abdominal pain.41,113, lz4, Other symptoms include malaise, nausea, vomiting, and painful fetal movements.124, I 6 l

Because of the fragility of the implantation site, patients are at high risk for intraperitoneal hemorrhage.lZ4 As with other forms of ectopic pregnancy, the condition is frequently misdiagnosed.I6' Sonography and magnetic resonance imaging may aid in the diagnosis.Iz4 Management is surgical, but there is significant postoperative morbidity related to incomplete placental removal.'", Ma- ternal mortality ranges from 0 to 3 0 O / 0 , ' ~ ~ and fetal mortality in advanced abdominal pregnancy ranges from 40% to 80°/0.124,

Splenic pregnancy is a rare form of ectopic pregnancy, with a few cases reported in the literature. These patients generally present with a history of upper abdominal pain and signs of a ruptured ectopic pregnancy.222


Heterotopic Pregnancy

Heterotopic pregnancy refers to the coexistence of both intrauterine and ectopic pregnancies. The incidence is reported to be about 1 in 5000 pregnancies:z*87 whereas in the past the incidence was estimated to be 1 in 30,000 pregnancie~.~~ The increased incidence is attributed to sexually transmitted diseases, intrauterine devices, previous tuba1 surgery, and use of ovulation induction agent^!^,'^^ The incidence of heterotopic pregnancy is as high as 1 in 100 in in vitro fertilization pr0grams.8~ Therefore, the demonstration of a normal intrauterine gestation and the presence of normal P-hCG levels does not completely exclude the possibility of a concurrent ectopic gestation in high-risk individuals, and further evaluation may be necessary because the correct preoperative diagnosis is made in only 10% of patients."'

Abortion

Lower abdominal pain in the first trimester associated with vaginal bleeding may herald threatened, incomplete, or complete abortion. The pain in this setting tends to be crampy or colicky in nature, whereas the pain in ectopic pregnancy tends to be sharp, severe, and often ~ni la te ra l . '~ , '~~

Placental Disorders

Placental abruption (abruptio placentae) refers to premature placental sepa- ration. It occurs with a frequency of l in 80 deliveries and may occur in the second or third trime~ter."~ Predisposing factors include previous abruption, hypertension, trauma, multiple gestations, uterine leiomyomata, and tobacco or cocaine The classic symptoms are lower abdominal pain and vaginal bleeding. The pain is described as sharp, tearing, or burning and may be

pain, however, may be absent, even with total abruption."' Bleeding ranging from mild to massive occurs in 78% of patient^."^ Complications include disseminated intravascular coagulation, hemorrhagic shock, and renal failure, and fetal loss may be as high as 35Y0.l'~

Placenta previa is a disorder in which the placenta partially or completely obstructs the cervical 0s. Although this disorder classically presents as painless vaginal bleeding in the third trimester, bleeding may occur in the second trimester, and uterine contractions that accompany the bleeding may be painf~l ."~

An abnormally adherent placenta exists in three forms: placenta accreta, in which the villi are attached to myometrium; placenta increta, in which the villi invade the myometrium; and placenta percreta, in which the villi penetrate to the uterine serosa. Although these conditions generally cause postpartum hemorrhage, placenta accreta can be associated with uterine rupture before delivery, and placenta percreta can be associated with antepartum abdominal pain and h e m a t ~ r i a . ~ ~ ~

Preterm Labor

Preterm labor, the premature onset of uterine contractions, may be accompanied by a change in vaginal discharge or vaginal spotting. Although the contractions are frequently painless, the patient may complain of lower abdominal pain,

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back pain, or suprapubic or vaginal pressure. The diagnosis may be made by external monitoring of uterine contractions, along with cervical examination.219 Preterm labor should be managed by the obstetrician.

GYNECOLOGIC DISORDERS

Adnexal Pathology

Adnexal pathology occurs in approximately 1 in 600 de1i~eries.I'~ It may present as an acute surgical emergency secondary to adnexal torsion or ovarian cyst rupturess,115 or as an asymptomatic adnexal mass discovered on physical examination or ~ltrasonography.~~~

Adnexal Torsion

Adnexal torsion can involve the ovary, fallopian tube, or broad ligament. About 15% of cases occur during pregnancy, most commonly between the 6th and 14th weeks of ge~tati0n.l'~ Torsion is most commonly associated with an ovarian cyst, although torsion of a normal ovary and fallopian tube may occur.115 The cysts are most often benign cystic teratomas, and torsion more commonly involves the right ovary than the left.Iz9 Johnson and WoodruffE8 reported that the incidence of adnexal torsion at Johns Hopkins (1 in 1832 deliveries) approxi- mates the incidence of acute appendicitis during pregnancy (1 in 1603 deliveries).

Acute abdominal pain and tenderness are uniformly present.88, I l 5 The pain characteristically begins abruptly, is severe, is unilateral, and may be continuous or colicky; the pain may be accompanied by pallor, sweating, and ~0miting.l~ Up to one half of patients may have had prior episodes of pain.Iz9

If torsion is complete and goes untreated, necrosis of the affected ovary and peritonitis may ensue; urgent surgery is, therefore, indi~ated."~ The correct diagnosis of torsion is often not made before surgery1z9; the most common suspected diagnoses are ruptured ectopic pregnancy and acute appendicitis.8E Other diagnoses that should be considered are listed in Table 1. Treatment historically has been salpingo-oophorectomy, but laparotomy with detorsion or laparoscopy with detorsion is becoming widely ac~epted."~

Adnexal Masses

Adnexal masses occur in from 1 in 81 to 1 in 2500 de l i~e r i e s .~~ , "~ This wide range is related to the use of routine ultrasound, which has increased the detection of adnexal masses too small to be detected by physical examination. The masses are less than 5 cm in 5070, 5 to 10 cm in 25%, and greater than 10 cm in 25%.n Ninety-five percent are ~n i l a t e ra l .~~ Most adnexal masses in pregnancy are benign. In one large series, the most common histologic diagnoses were benign teratoma and cystadenoma (23% each), leiomyoma (17%), corpus luteum cyst (12%), and follicle cyst Malignancies account for about 4% of adnexal masses in pregnan~y,~, n, lls, lz9 correlating with an incidence of about 1 in 10,000 live birthsn Approximately one third are low-grade malignancies, one third are invasive epithelial cancers, and one third are gonadal stromal or germ cell tum0rs.6~

Most benign adnexal masses (65%) are asymptomatic at diagnosis.77 The remainder may be associated with vague abdominal discomforP9 or abdominal pain,115 and 12% of adnexal masses result in tor~ion"~ (see earlier). Ovarian


carcinomas discovered during pregnancy are usually a~ymptornatic."~~ Iz9 One series, however, reported abdominal pain in 65% of patients with ovarian carcinoma identified during pregnancy.45

Ninety-four percent of adnexal masses less than 6 cm in diameter detected during the first trimester and not removed surgically resolved spontaneously by the sixth week postpartum, whereas only 25% of masses persisting into the second trimester resolved spontaneously by the sixth week postpartum." Struyk and TreffersZo0 recommended that patients in whom adnexal masses were detected during the first trimester who did not require emergency surgery be observed until the 16th week of gestation. Masses persisting beyond the 16th week should be removed electively, to avoid the risks of hemorrhage, torsion, infarction, or obstruction of labor and to avoid delay in the diagnosis of malignancy. If a mass is discovered during the third trimester and emergency surgery is not required, observation is recommended until the fetus matures, at which time cesarean delivery and excision of the mass can be performed.z00 Elective resection during the second trimester is associated with minimal fetal and maternal morbidity, whereas spontaneous abortion is more likely when surgery is performed during the first trimestec", "

The treatment for ovarian cancer is the same as that in nonpregnant patient~.~], 69, '15, lz9 As in nonpregnant patients, prognosis depends on the histologic grade of the tumor and stage at diagnosis.31, 45, 69, There have been rare reports of colonic perforation secondary to ovarian carcinoma during pregnancy as well as ovarian metastases from perforated colonic carcinoma.44

Endometriosis

Endometriosis is infrequently associated with pregnancy because the incidence of infertility in patients with endometriosis is 40% to 70?'0.~' Nevertheless, endometrioid cysts account for 4% of adnexal masses during pregnancy.31, 77

Rupture of an endometrioid cyst may present as an acute surgical emergency.88

Uterine Leiomyomas

Uterine leiomyomas are present in 20% of reproductive-age women.97 They are detected by ultrasound in 2.5% of p regnanc ie~ .~~ ,~~ , lbi Only 40% are detected by pelvic examination; one fourth of leiomyomas less than 5 cm in size and one half of leiomyomas greater than 5 cm in size are detected.'" Leiomyomas less than 3 cm in size are usually not clinically significant. About 20% of leiomyomas in pregnant patients cause symptoms or complications; complications occur in approximately 1 in 500 ~regnancies.9~

The most common complication is the syndrome of painful myomas of pregnancy, also called red degeneration or hemorrhagic infar~tion.9~ This syndrome typically occurs in the second or early third trimester97 and is more likely when the leiomyoma is greater than 5 cm in diameter.'" Classic descriptions of this syndrome include persistent, unremitting abdominal pain accompanied by malaise, nausea and vomiting, fever, and leukocyt~sis.~~ In a series of 41 patients with this syndrome, only one patient had nausea or vomiting, and no patient had fever, leukocytosis, or rebound tenderne~s.9~ This syndrome has been attributed to bleeding within the leiomyoma, edema, or infarction owing to rapid growth or intramyomal vascular Pain correlated with heterogeneous echo patterns within the leiomyoma on ultrasonography suggests infarction or

10 MAYER & HUSSAIN

degenerati~n.~~. y7 Treatment includes bed rest, nonsteroidal anti-inflammatory drugs such as ibuprofen, and narcotic analgesics, but prostaglandin synthetase inhibitors may not be used beyond the 34th week of gestation because these inhibitors can affect the normal sequence of labor.y7, Other complications of leiomyomas in pregancy include abruptio placentae, premature labor, premature rupture of membranes, fetal malpresentation, retained placenta and postpartum hemorrhage, and puerperal sepsis.53, 97,

ACUTE APPENDICITIS

Acute appendicitis is the most common nonobstetric indication for abdominal surgery during pregnancy, with an average incidence of 1 in 1500 deli~eries.~, 128,203 Although the distribution among trimesters was reported to be equal in the older 215 recent studies have shown a preponderance in the second trimester, with approximately 30% of cases occurring during the first trimester; 45% during the second trimester; and 25% during the third trimester, labor, or puerperium?, 3y, lz8, 203

The pathophysiologic process of acute appendicitis is initiated by obstruction of the appendiceal lumen, which is followed by distention of the appendix. The patient experiences visceral pain, usually periumbilical or epigastric, poorly localized, and associated with anorexia or nausea, with or without vomiting.4z, 47

The distention may lead to increased intestinal peristalsis, with crampy abdominal ~ a i n . 4 ~ Persistent distention leads to mural edema, inflammation, and bacterial invasion, causing acute somatic pain localized to the right lower quadrant in the nonpregnant patient.4z, 47 With increasing inflammation, the parietal peritoneum becomes irritated, causing abdominal guarding and rebound tenderne~s.4~ If untreated, infarction and perforation may occur, leading to diffuse peritonitis. The degree of peritonitis is determined by the ability of the omentum to wall- off the inflammatory process."

The normal anatomic and physiologic changes during pregnancy alter the symptoms and signs of acute appendicitis?, 3y, 42, 47, 184, 215 In 1932, Baer and co- workers7 analyzed the changes in the position of the appendix during different stages of gestation by barium enema. The enlarging gravid uterus causes progressive upward displacement of the appendix, so that by the end of the third month, the tip of the appendix is located above McBurney's point.184, 215 The appendix rises and rotates counterclockwise until the eighth month of gestation;I5 so that by term the tip may drape over the right k idne~ .~ The early visceral pain experienced by the patient may be unaffected by pregnancy, but the localization of somatic pain is determined by the appendiceal In the second and third trimesters, this pain may be located in the right flank, right upper quadrant, or other areas.5, 3y, lffi As the appendix changes position, it may lose contact with the parietal peritoneum, leading to absence of peritoneal irritation and potential delay in diagnosis.'2, 215 Anorexia, nausea, and vomiting, which are common symptoms of appendicitis, are also common symptoms in early pregnancy and are often not helpful in diagnosing acute appendicitis during the first trimestee2; however, nausea and vomiting during the second or third trimesters require careful eval~ation.~, 215

On physical examination, direct abdominal tenderness is present in 90% of patients?, 3y Rebound tenderness is present in 60% of patients, more commonly in early gestations?, 3y, *03 Guarding is a less reliable sign in later pregnancy because of laxity of the abdominal wall muscles.3y Significant fever is present in about 25% of patients? 3y, 203 and significant tachycardia is present in about 15%


of patients5, 203 Rectal or pelvic tenderness is present in less than 50% of patients,lz6, 203 but it is a valuable finding when present, particularly in the first trimester.39 Psoas, obturator, or Rovsing’s sign is present in only one third of patientsza3

Laboratory values may not be helpful in diagnosing acute appendicitis because of the physiologic leukocytosis in pregnancy, an increase in the leukocyte count to 12,500 to 16,00O/mL; the erythrocyte sedimentation rate may be elevated in normal pregnancy as 215 Leukocytosis greater than 15,00O/mL is present in only about 30% of pregnant patients with acute appendicitis.5, 126,203

A neutrophil percentage of greater than 80% in the leukocyte differential may be s ignif i~ant .~,’~~ Pyuria is present in about 15% of pregnant patients with acute appendi~itis?~, lz6, 203 The differential diagnosis of acute appendicitis in pregnancy includes obstetric, gynecologic, gastrointestinal, and urologic disorders (Table

The treatment of acute appendicitis is surgical. Preoperative diagnostic accuracy was classically approximately 70% but may be increasing because of the widespread availability of noninvasive imaging techniques.5, 128, 203 The routine use of antibiotics in all cases of uncomplicated acute appendicitis is controversial, but most authors agree that postoperative antibiotics should be continued in patients with perforation, peritonitis, or absce~ses.~, 39, 203, 215 Antibiotic regimens that can be used during pregnancy include ampicillin, cephalosporins, and clindamycin, in combination with gentamicinZ2”, 215; clindamycin is preferable to metronidazole for anaerobic coverage during pregnancy.22a Maternal mortality is now rare5, Iz6, 184, 203 and is estimated to be 0.1% in nonperforated appendicitis and 4% in perforated appendicitis.“ Fetal mortality is approximately 1.5% in nonperforated appendicitis5, lz6 but is up to 36% in perforated appendicitis? For these reasons, the statement by Babler6 in 1908 that ”the mortality of appendicitis complicating pregnancy is the mortality of delay” is still true. A negative laparotomy rate of 20% to 35% is considered acceptable,’@ and if acute appendicitis is suspected, laparotomy or laparoscopy is justified; in the absence of findings of acute appendicitis at laparotomy, elective appendectomy should be

3).5, 42, 184

performed.5,39, 126,203. 215

Table 3. DIFFERENTIAL DIAGNOSIS OF ACUTE APPENDICITIS IN PREGNANCY

Obstetric Disorders Ectopic pregnancy Ruptured corpus luteum Abruptio placentae Preterm labor Chorioamnionitis Postabortal peritonitis Gynecologic Disorders Pelvic inflammatory disease Ruptured ovarian cyst Adnexal torsion Infarction of normal ovary Degenerating myoma Endometriosis Round ligament syndrome

Gastrointestinal Disorders Acute cholecystitis Cholelithiasis Pancreatitis Gastroenteritis Intestinal obstruction Colonic carcinoma Mesenteric adenitis Hernia Urologic Disorders Pyelonephritis Urolithiasis

~~

Data from references 5, 42, and 184.

12 MAYER & HUSSAIN

GASTROESOPHAGEAL REFLUX AND PEPTIC ULCER DISEASE

Gastroesophageal reflux is common during pregnancy, occurring in 30% to 50% of pregnant patients.", 52, 138 Typical symptoms include burning epigastric or substernal pain, nausea, vomiting, or Symptoms tend to be more pronounced in later pregnancy; symptoms are worse after meals and in the recumbent position.11, 52

The incidence of peptic ulcer disease is difficult to determine, in part because of the overlap of symptoms with gastroesophageal reflux disease and in part because of the reluctance of physicians to perform diagnostic studies on pregnant patients with upper gastrointestinal symptoms, particularly those who respond to symptomatic therapy.25, 134 Clark32 reported that symptoms improved or resolved in 90% of patients with peptic ulcer disease during pregnancy. The incidence and risk of recurrence appears to be neither increased nor decreased during pregnancy.138

Epigastric pain or discomfort occurs in 70% of patients; the pain may radiate to the back and may be either exacerbated or alleviated by f00d.I~~ Nausea, vomiting, heartburn, and indigestion may occur. Management of patients with both gastroesophageal reflux and peptic ulcer symptoms includes physical and dietary measures to prevent reflux and minimize gastric retention. Fatty foods, caffeine, alcohol, chocolate, and nicotine should be a ~ 0 i d e d . I ~ ~ Antacids are the first-line drugs for symptoms during pregnancy.25, Sucralfate appears to be safe during pregnancy.11z, 134 Cimetidine and ranitidine have been used in the second and third trimesters; ranitidine is preferable because it lacks the antian- drogenic properties of cimetidine.llz* *W 138

Complications of peptic ulcer disease such as hemorrhage and perforation are rare in pregnancy138; the treatment of these complications, however, is the same as in the nonpregnant patient. Upper gastrointestinal endoscopy is the diagnostic procedure of choice in evaluating patients with upper gastrointestinal hemorrhage or symptoms refractory to medical therapy.z6, 27, Endoscopy appears to be well tolerated by both mother and fetus, has a diagnostic accuracy approaching 95% in upper gastrointestinal hemorrhage, and has the therapeutic capabilities of controlling hemorrhage and preventing rebleeding.z6, 27, For a detailed discussion of gastroesophageal reflux disease and peptic ulcer disease during pregnancy, the reader is referred to the articles in this issue by CastellZ9 and Garcia and Ca~pell.5~

INTESTINAL OBSTRUCTION

Intestinal obstruction is the second most common indication, after acute appendicitis, for nonobstetric surgery during In 1940, Smith and BartletP reported an incidence of about 1 in 66,000 pregnancies. Meyerson and co-worker~'~~ reported an incidence of about 1 in 17,000 deliveries. Other reviews have estimated the incidence at about 1 in 3000 de1iveries.Q 52, 184 The increasing incidence has been attributed to the increased number of surgical procedures that women of childbearing age have undergone, along with the increased incidence of pelvic inflammatory d i ~ e a s e . ~ ~ , ~ ~ , 133

Intestinal obstruction is most likely during the fourth and fifth months of gestation, when the gravid uterus becomes an abdominal organ; during the eighth or ninth months, when the fetal head descends into the pelvis; or during the puerperium, when uterine size rapidly decreases.40~ 133 Maternal age and

ABDOMINAL PAIN DUIUNG PREGNANCY 13

parity are not significant risk factors in the development of intestinal obstruction.l3

Adhesions are the most common cause of intestinal obstruction in both pregnant and nonpregnant individuals, accounting for approximately 60% of cases during pregnancys1, 133, 151 Adhesions are secondary to surgery in most cases; the most common prior operations undergone by these patients are appendectomy and gynecologic surgerym, l5I Adhesions are secondary to inflammatory disease in 18% of patients and congenital in Volvulus is the cause of obstruction in 25% of pregnant ~atients.9~. ls1, lS7, 217 Although incarcerated inguinal and femoral hernias are the second most common cause of obstruction in the general population, these hernias account for less than 5% of cases during pregnancy because the enlarging gravid uterus displaces bowel upward and out of the pelvis.m, 81, 133 Other causes of obstruction during pregnancy include intussusception,'sl which is most commonly caused by Meckel's diverticulum but may be caused by neoplasmm; carcinoma74, 15'; malrotation'"; and complications of Crohn's disease.'42 Diaphragmatic hernia is a rare cause of intestinal obstruction during pregnancy, with 18 cases reported in the literature through 1988. It may be acquired, congenital, or traumatic.'06

Abdominal pain, nausea, vomiting, and obstipation are the most common symptoms in both pregnant and nonpregnant 142, Abdominal pain is present in 90% of patients?O, 15' The pain may be constant, unremitting, and poorly localized, or the pain may be intermittent?0,81 The period of time between bouts of pain is typically 4 to 5 minutes in small bowel obstruction and 10 to 15 minutes in colonic obstruction.m, 81 The pain may radiate to the back or flank, mimicking pyelonephritis.81 Colonic obstruction may cause lower abdominal or perineal pain.'% Vomiting occurs in 82% of patients.15' Although nausea and vomiting are common symptoms of pregnancy, the onset of vomiting after the first trimester should alert the clinician to-the possibility of other causes, including intestinal obstruction.81 Although constipation is also common in pregnancy, obstipation is characteristic of prolonged obstr~ction'~~ and is found in 30% of patient^.'^' Patients with malrotation may present with vague, chronic symptoms of crampy abdominal pain or nonbilious vomiting.173

Physical findings in pregnant patients with intestinal obstruction include abdominal tenderness in 71% and abnormal bowel sounds in 55% of patient^.'^^ Abdominal distention, a common finding in nonpregnant patients with obstruction, may be difficult to assess during pregnancy because of the overlying gravid uterus.52,81 Occasionally a dilated cecum or loop of sigmoid may be palpable in cases of colonic obstruction, or a sausage-shaped mass may be detected in cases of intussusception.m Leukocytosis may be present, but the leukocyte count may not exceed the normal physiologically increased level during pregnancy.151 Other laboratory tests provide information regarding electrolyte balance and renal

In late stages of untreated obstruction, fever, tachypnea, oliguria, hypotension, and shock may result from massive third-spacing of fluid, meta- bolic acidosis, and superimposed sepsis.m

When intestinal obstruction is suspected, supine and upright abdominal radiographs should be obtained.81 Perdue and associate^'^^ reported finding typical patterns of obstruction in 91% of patients with these studies. Radiographs may be nondiagnostic in early obstruction; serial radiographs, recommended at 4- to 6-hour intervals, may demonstrate progressive dilation of bowel loops and air-fluid levels.4°, 133 Abdominal radiographs in patients with colonic volvulus often demonstrate a grossly dilated bowel loop.4O, 70, A plain abdominal radio- graph exposes the fetus to 275 mrad?*fs6 Exposure of the fetus to 1 rad is associated with a 0.1% risk of congenital malformation,2°, *l which is considerably

14 MAYER & HUSSAIN

less than the risk of spontaneous abortion, malformation, or congenital disease?O, 2s, 133 Concern regarding fetal exposure to ionizing radiation must be weighed

against the morbidity and mortality from a missed or delayed 133,142,184

If obstruction is still suspected in the absence of typical findings on plain abdominal radiographs, contrast studies may be obtained by the administration of contrast material orally or by enema.4o, 151, 184

The management of intestinal obstruction is the same in pregnant and nonpregnant patients.'% Treatment consists of fluid and electrolyte replacement, bowel decompression, and prompt surgical intervention when decompression is unsuccessful.40, 142, 15' Fluid resuscitation must be aggressive to maintain adequate uterine perfusion and fetal ~iabi1ity.l~' Meyerson and colleagues133 advo- cate surgical intervention in all instances of small bowel obstruction, with nasogastric tube decompression as preparation for surgery rather than as an attempt at definitive therapy. The nature of the surgery is determined by the intraopera- tive findings.'33 Bowel viability must be carefully assessed intra~peratively.'~~ Sigmoid volvulus may occasionally be successfully managed by sigmoidoscopic or tube decompression?0, lx6, Broad-spectrum antibiotics should be instituted preoperatively in patients with intestinal ob~truction~~, 15* and prophylactically in patients with volvulus, before endoscopic or surgical intervention.Il6 Combina- tions employing ampicillin, cephalosporins, clindamycin, and gentamicin may be used during pregnancy."a

The morbidity and mortality of intestinal obstruction during pregnancy are related to delay in diagnosis. In the series published by Perdue and colleague^,'^^ the median length of time from onset of symptoms to hospitalization was 48 hours, and the median length of time from hospitalization to laparotomy was another 48 hours; 32% of patients in this series were hospitalized for more than 72 hours before undergoing surgery. In this study, maternal mortality was 6%, and fetal mortality was 26%. Meyerson and reported no maternal mortality but a fetal mortality of 37.5%. Other reviews estimate a maternal mortality of 15% and fetal mortality of 40%."O For volvulus, maternal mortality has been reported to be 13% and fetal mortality to be 2070.'~~

The mortality from obstruction caused by diaphragmatic hernias during pregnancy is high, with 8 maternal deaths and 6 fetal deaths among the 18 cases reviewed by Kurzel and associates.'06 They recommend repair in patients presenting in the first or second trimester; asymptomatic patients in the third trimester may be observed closely until fetal viability is documented.'" If symptoms of obstruction develop, immediate surgical repair should be attempted. Vaginal delivery should not be attempted because of the increased intra-abdominal pressures during labor.1o6

INTESTINAL PSEUDO-OBSTRUCTION

Intestinal pseudo-obstruction, or adynamic ileus of the colon, is characterized by gaseous distention of the colon without mechanical obstruction. This may occur after vaginal delivery or cesarean section and usually develops during a 2- to 3-day period.40,'M The most common symptoms are nausea and constipation. The diagnosis may be made on abdominal radiographs; the more proximal colon is usually more distended?" The critical colonic diameter at which colonic perforation may occur has been estimated to be about 12 c ~ . ~ O

The mortality from postpartum intestinal pseudo-obstruction has been reported to be 8% in patients with impending perforation and 70% in patients with cecal perforation.1M Treatment consists of intravenous fluid replacement, nasogastric

ABDOMINAL PAIN DUIUNG PREGNANCY 15

suction, and rectal tube decompression. Colonoscopy has been used diagnosti- cally and therapeutically.’@ If there is no improvement with medical or endoscopic management, or if radiographs indicate the cecum has reached a critical diameter, surgical therapy, using cecostomy, is indicated.40, I@

INFLAMMATORY BOWEL DISEASE

Inflammatory bowel disease (IBD) includes ulcerative colitis and Crohn’s disease, both of which are characterized by inflammation of the colon or small intestine. The cause is unknown, but the inflammatory process is immunologi- cally mediated. The incidence of IBD in the United States is estimated to be 25,000 new cases per Because the disorder is common in young adults, it is estimated that 1 in 1000 women of childbearing age are affe~ted.9~ Common symptoms include abdominal pain, diarrhea (often bloody diarrhea in ulcerative colitis), anorexia, and nausea.

An extensive body of literature has accumulated dealing with IBD in pregnancy. This literature describes the effects of IBD on fertility, the effects of pregnancy on IBD, the effects of IBD on pregnancy, and drug therapy of IBD during pregnancy. The consensus of most studies is that fertility is mostly unaffected and that pregnancy does not adversely affect the course of IBD and IBD does not adversely affect the course of pregnancy in the majority of cases. If IBD is quiescent at the onset of pregnancy, it is likely to remain quiescent; patients with active disease at conception, however, are more likely to experience

Gastrointestinal symptoms during pregnancy in patients with IBD present a challenge to the clinician, who must determine whether symptoms such as abdominal pain, nausea, vomiting, or diarrhea are secondary to pregnancy, IBD, or another illness (see Table l).7* Bloody diarrhea, fever, and weight loss all may implicate the underlying IBD, and abdominal pain associated with recurrent vomiting suggests the possibility of intestinal obstruct i~n.~~ Furthermore, either ulcerative colitis or Crohn’s disease may present initially during pregnancy.48, 99,

125,220 Evaluation of pregnant patients, as in nonpregnant patients, should include complete blood count, appropriate stool cultures to exclude bacterial pathogens, and evaluation of nutritional parameter^.^^ Flexible sigmoidoscopy may be performed in pregnant patients with suspected IBD,72 and colonoscopy may have a role in the evaluation of certain If warranted by the clinical condition, radiographic studies may be performed.72 For a detailed discussion of the cause, presentation, and therapy of IBD during pregnancy, the reader is referred to the article by Korelitz104 in this issue.

continued SymptomS.48,99. 105. 139. 145, 146. 156.220

IRRITABLE BOWEL SYNDROME

Irritable bowel syndrome is a motor disorder with the symptoms of abdominal pain and alteration in bowel habits, without demonstrable organic pathology.In The nature of the pain is variable. It can be bloating, burning, cramping, dull, or sharp; it can be constant or intermittent; it can be diffuse or localized; and it is most often in the lower abdomen, particularly the left lower quadrant.179 The pain is often exacerbated by eating and relieved by defecation?18 Associated bowel disturbances include alterations in stool frequency or consistency; symptoms of bloating or distention are common.‘8, 218

Irritable bowel syndrome is a common gastrointestinal disorder, and female

16 MAYER & HUSSAIN

patients outnumber male patients by 1.5:l to 5.2:l.18, 179 Studies have demonstrated that gastrointestinal transit time is prolonged during the luteal phase of the menstrual cycle, when serum progesterone levels are elevated,2I2 as well as during the second and third trimesters of pregnancy, when serum progesterone levels are also elevated.Iug It is likely that many patients experience symptoms of irritable bowel syndrome during pregnancy; however, no prospective studies have been performed.21s

The diagnosis can often be made by a careful history that documents the duration of the patient's symptoms and pattern of bowel movements. Manage- ment during pregnancy consists of dietary measures, such as avoiding offensive foods and increasing dietary fiber; behavioral therapy and biofeedback may be useful in some instances.z18

ACUTE PANCREATITIS

Acute pancreatitis is uncommon during pregnancy, with a reported incidence ranging from 1 in 1000 pregnancies to 1 in 10,000 pregnancie~?~, 89, I3O

Parity does not appear to influence the i n c i d e n ~ e . ~ ~ Pancreatitis may occur at any stage of pregnancy but is most common during the third trimester and

Early reports of pancreatitis during pregnancy considered the cause often to be idiopathic or secondary to pregnancy.35, 42 Recent studies demonstrated that the most common cause is cholelithia~is.~~~, I4O, 224 Other causes include alcohol- ism, hyperlipidemia, hyperparathyroidism, infections (mumps, infectious mono- nucleosis, viral hepatitis), medications, penetrating peptic ulcer, trauma, and vas~ulitis?~, 42, 56, 84, 202, 214 The frequency of alcohol-induced and drug-induced pancreatitis is lower in pregnant versus nonpregnant

The clinical presentation of acute pancreatitis during pregnancy is similar to that in nonpregnant patients.'", 184 Upper abdominal or epigastric pain, often radiating to the back or flank, and nausea and vomiting are the most common symptom^.^^,^^, 140 The patient often lies on the side with flexed knees, hips, and trunk.'% Fever may be present in up to 66% of Physical findings include abdominal tenderness, abdominal distention, hypoactive bowel sounds, guarding, and rebound tenderne~s.'~~ In severe cases, ascites and flank ecchymo- ses (Grey Turner's sign) may be presentzz4 as well as signs of hypovolemic shock.", 142

The diagnosis of pancreatitis rests on the demonstration of elevated serum levels of pancreatic enzymes. Studies of normal pregnant women have demonstrated that serum amylase levels are 149 or mildly elevated (less than twice the upper limit of normal)'* during pregnancy. Serum lipase levels are normal in a normal pregnancy.149 The amylase-to-creatinine clearance ratio in normal pregnant women is either or lower than that in nonpregnant women.43 Therefore, demonstration of an elevated serum amylase level or an elevated amylase-to-creatinine clearance ratio supports the diagnosis of acute pancreatitis during pregnancy. Hyperamylasemia may also occur in other conditions, such as perforated viscus, bowel obstruction, and holec cyst it is,^^^ but the amylase-to-creatinine clearance ratio is normal in these conditions. Serum lipase levels are more specific for pancreatitis, remain elevated for a longer period of time, and are particularly useful in patients with hypertriglyceridemia because hypertriglyceridemia may mask an elevated serum amylase level but does not affect serum lipase activity.'" Ultrasonography may be useful, particularly for gallstone pan~reatitis.2~. 52,

puerperium.35, 130. 140, 142. 184,224


Most cases respond to conservative therapy with bowel rest, fluid and electrolyte replacement, analgesics, and, in selected cases, nasogastric suction.25,

Intravenous alimentation is useful in certain cases.52 The subject of intravenous alimentation is discussed in another article of this issue. About 85% of patients respond to these measures within 1 142 Severe cases or cases with complications such as pancreatic phlegmon, abscess, or hemorrhagic pancreatitis may require care in an intensive care unit or surgical intervention,l'2, 1M

In uncomplicated pancreatitis, maternal mortality is low, but there is an increased risk of spontaneous abortion in the first trimester and an increased risk of premature labor in late p r e g n a n ~ y . ~ ~ In complicated pancreatitis, maternal mortality is about lo%, and fetal mortality may be as high as 4 o O / 0 ? ~

BlLlARY TRACT DISEASE

Cholelithiasis and Cholecystitis

An association between pregnancy and gallstone formation is widely accepted. Evidence of this association includes the preponderance of female patients with gallstones,'y~ lY2 the frequent history of previous or recent pregnancy in patients undergoing cholecy~tectorny,~~~ 63 the effects of estrogen on bile litho- genicity:2, 93 and abnormalities of gallbladder function during pregnancy that are not duplicated by administration of contraceptive steroids.'y Stauffer and co- w o r k e r ~ ~ ~ ~ studied 338 asymptomatic pregnant women with ultrasonography and detected gallstones in 3.5%. Valdivieso and colleaguesZ1O studied 980 pregnant Chilean women and found gallstones in 12.2%, compared to 1.3% in matched controls. Despite the high rate of cholelithiasis during pregnancy, the incidence of acute cholecystitis during pregnancy is relatively low, ranging from 1 to 8 cases per 10,000 pregnancies? 93, Io7, 131, lW

Symptoms of acute cholecystitis or biliary colic are similar in pregnant and nonpregnant patients and are usually precipitated by cystic duct obstruction.'Q lffl The most common symptom is abdominal pain, which may begin in the right upper quadrant or epigastrium; the pain may later radiate to the back, right scapula, or right shoulder?Z, 142, The pain in biliary colic usually begins abruptly, may be sharp or crampy, and may last for periods ranging from 15 minutes to several The pain is frequently accompanied by nausea and vomiting.52, Iffl In acute cholecystitis, right upper quadrant tenderness is usually present.lo7, 142 Fever and tachycardia may be present.'07, Laboratory findings may include leukocytosis and elevation of serum amylase, alkaline phosphatase, and bilirubin levels.42, 142, Jaundice, however, is unusual in the absence of choledocholithiasis.

The differential diagnosis of acute cholecystitis includes acute appendicitis, peptic ulcer disease, pancreatitis, pyelonephritis, pneumonia, hepatitis, myocardial infarction, and herpes zoster infection (see Table l).42, In addition, the differential diagnosis in pregnant patients with right upper quadrant pain, with or without abnormal liver chemistries, includes preeclampsia, acute fatty liver of pregnancy, and HELLP syndrome (discussed subsequently).'@ Ultrasonogra- phy has a diagnostic accuracy of about 97% in detecting cholelithiasis but a poor diagnostic accuracy in detecting choledocholithiasis.25~ 52, 78, lo7

Medical therapy is favored over surgical therapy as the initial treatment of acute cholecystitis during the first and third trimesters of pregnancy, when there is the greatest risk of spontaneous abortion or preterm labor respec-

52,

18 MAYER & HUSSAIN

tive1y.Q y3, 78, 107, 131, 181 Medical therapy consists of nasogastric suction, intravenous fluids, analgesics, and antibiotics for signs of infection or sepsis.42, 18*, IR4

Ampicillin or a first-generation or second-generation cephalosporin alone is adequate therapy for mild cases because these drugs achieve high biliary concen- trations; for severe cases or cases associated with sepsis, a third-generation cephalosporin or a combination of ampicillin, a cephalosporin, or clindamycin along with gentamicin may be used during pregnancy?2a Surgery is reserved for patients with recurrent attacks, sepsis, or complications.42~ l8I, 184 Dixon and colleagues46 demonstrated that cholecystectomy may be performed safely during the second trimester, with a better outcome than a matched control group treated medically. Many authorities now recommend medical therapy in the first trimester, followed by elective surgery during the second trimester; primary surgical therapy during the second trimester; and medical therapy during the third trimester, followed by surgery 93, 131 Although pregnancy had been considered a contraindication to laparoscopic cholecystectomy, preliminary reports suggest it may be safely performed during pregnancy.5o

Complications of cholelithiasis include pancreatitis (discussed earlier), and choledocholithiasis (discussed subsequently). Gallbladder perforation is a rare complication of gallstone disease during pregnancy or postpartum. The presenting symptoms of abdominal pain, nausea, vomiting, and distention are nonspecific, and patients are frequently misdiagn~sed.’~~ Ultrasonography, magnetic resonance imaging, computed tomography (CT), and ascitic fluid analysis may be helpful in making the diagnosis.15z

Choledocholithiasis

Although the incidence of cholelithiasis during pregnancy has been studied (see earlier),192 the incidence of choledocholithiasis is unknown. It accounts for 7% of cases of jaundice during pregnancyy3 Choledocholithiasis significantly increases maternal morbidity and mortality as well as fetal loss after surgery, presumably from sepsis or pancreatiti~.~~. 93

Nonoperative, endoscopic management of choledocholithiasis and biliary pancreatitis is currently an accepted practice in nonpregnant patients. Concern regarding radiation exposure to the fetus, however, has limited its application during pregnancy. Reports have demonstrated that with modifications in tech- nique, such as shielding the lower abdomen and limiting fluoroscopic time, endoscopic retrograde cholangiopancreatography (ERCP) with endoscopic sphincterotomy, stone extraction or stent insertion may be performed safely in pregnant patients3, 8, 85 Radiation exposure in these studies is believed to be within an acceptable limit for the developing fetus?, 8, 20, 21, 85 The subject of ERCP during pregnancy is discussed in greater detail in the article on endoscopy during pregnancy in this issue?6

Spontaneous perforation of the common bile duct is a rare complication of choledocholithiasis, usually presenting as severe abdominal pain with signs of peritonitis. Through 1995, three cases have been reported during pregnancy; two were treated with surgical repair, and one was treated with surgical drainage at the time of cesarean section, followed by endoscopic stent insertion.”’, 205

Choledochal Cysts and Neoplasms

in females, and 70% are diagnosed before age Choledochal cysts are congenital cysts of the biliary tree. About 75% occur

Through 1987, only 20 cases


were reported during pregnancy.16 They may present with the classic triad of right upper quadrant pain, jaundice, and a palpable mass; all three features, however, are present in only approximately 40% of patients, and the mass may be difficult to appreciate during pregnancy.2 The patient who presents in adulthood may have a history of unexplained prior episodes of abdominal pain or jaundice.16

The patient may present during pregnancy with recurrent abdominal pain and jaundice: l6 severe pain and signs of peritonitis secondary to cyst or signs of cyst rupture after delivery?8 Exacerbation during pregnancy has been explained by the enlarging gravid uterus compressing and further obstructing the distal common bile duct2; postpartum enlargement or rupture has been attributed to the strain of labor?* Ultrasonography is useful in diagnosis.

The management of choledochal cysts during pregnancy is not well established. The cyst should be monitored sonographically to detect enlargement; an enlarging cyst may require decompression by cholecystostomy or internal

Cholangitis may respond to antibiotics, but drainage may also be required.I6 Whenever possible, nonoperative management should be attempted until the fetus is viable, at which time the mother should undergo cesarean section to avoid labor. Definitive therapy consists of cyst excision, cholecystectomy, and Roux-en-Y hepaticojejunostomy or choledochojejunostomy.

Choledochal cysts are associated with adenocarcinoma. One patient with choledochal cyst during pregnancy reported by Binstock and colleagues'6 had adenocarcinoma within the cyst identified after postpartum excision; their literature review identified only two other cases of bile duct carcinoma associated with pregnancy through 1987.

LIVER DISEASE DURING PREGNANCY

Liver disease is uncommon during pregnan~y.~, '~~ Severe liver disease occurs in less than 0.1% of pregnan~ies.'~~ Liver disease occurring during pregnancy may be classified into liver disease unique to pregnancy, intercurrent liver disease in the pregnant patient, and preexisting liver disease in pregnancy.lol, 178, 185,211 A detailed discussion of liver diseases in pregnancy is beyond the scope and purpose of this article. Abdominal pain may be a presenting or prominent feature of many hepatic disorders, however, and inasmuch as prompt recognition and therapy are necessary to avert significant morbidity and mortality, hepatic disorders associated with abdominal pain are discussed. Table 1 lists the differential diagnosis of those disorders presenting with right upper quadrant or epigastric pain.

Preeclampsia and Eclampsia

Preeclampsia is a complication of about 5% of all pregnancies, occurring in the late second or third trimester?, 54, Io2 It is characterized by the triad of hypertension, proteinuria, and edema. Hypertension is defined as a blood pressure greater than 140/90 mm Hg or an increase of 30 mm Hg systolic or 15 mm Hg diastolic greater than the blood pressure in the first trimester.', lo2 Severe preeclampsia is defined as a blood pressure greater than 160/110 mm Hg on two determinations at least 6 hours apart and proteinuria greater than 1 g per 24 These patients may also have oliguria and visual or cerebral disturbances.I2 Eclampsia is marked by additionally having seizures.12, 54, lo2 Risk

20 MAYER & HUSSAIN

factors for the development of preeclampsia include preexisting hypertension, nulliparity, extremes of maternal age, multiple gestations, diabetes mellitus, hydatidiform mole, and fetal hydrops.', 12, '02, 178 Although of unknown etiology, preeclampsia is believed to be related to abnormal endothelial reactivity, leading to hypertension and intravascular fibrin deposition, with resultant end-organ darnage.I2, lo2

Epigastric or right upper quadrant pain is the most common symptom of hepatic involvement from preeclampsia.', 9, 12, Io2, 178 Patients may also complain of right subscapular or shoulder pain' and nausea or vomiting.178 Physical examination often reveals right upper quadrant tendernes~.~'~ Serum aminotransferase levels are moderately to markedly elevated (5 to 100 times normal), whereas serum bilirubin levels are only mildly elevated, usually less than 5 mg/ dL.', l2 Thrombocytopenia is present in 20% of patients, but standard coagulation tests are usually normal.Iz Histologically the liver demonstrates periportal hemorrhage and sinusoidal fibrin deposition and occasionally demonstrates periportal hepatocellular necrosis.', 12, 17', 178 Hepatic involvement reflects severe preeclampsia, and prompt recognition and treatment are therefore necessary to prevent hepatic complications, such as hepatic hemorrhage and rupture (discussed subsequently), or progression to eclampsia.', j2, 178

In mild preeclampsia beginning near term, maternal and fetal mortality approaches that of uncomplicated pregnancies.'OZ In severe preeclampsia, perinatal mortality is 13.5%; maternal mortality in experienced centers is 1%.'02, ls7

Central nervous system involvement accounts for 80% of maternal mortality; hepatic involvement accounts for 15% of maternal deaths.102, 178

HELLP Syndrome

The term HELLP syndrome was first used by Weinstein2I6 in 1982 to describe patients with severe preeclampsia who also had hemolysis (H), elevated liver enzymes (EL), and a low platelet count (LP). HELLP syndrome occurs in 0.1% to 0.6% of all pregnancies and in 4% to 12% of patients with preeclampsia.102, 178 Seventy percent of cases occur during the third trimester, and 30% occur postpartum.186 Right upper quadrant or epigastric pain is the presenting symptom in about 75%'02, 178, 216 of patients. Other symptoms include nausea, vomiting, headache, visual changes, bleeding, jaundice, diarrhea, and shoulder or neck pain.'% Severe hypertension is not a constant findingI4 and may be absent in 20% of patients.'02

Laboratory criteria for the diagnosis of HELLP syndrome include an abnormal peripheral smear consistent with microangiopathic hemolysis, elevated serum lactate dehydrogenase (>600 U/L) or bilirubin (>1.2 mg/dL), elevated aspartate aminotransferase (>70 U/L), and thrombocytopenia (<100,000/ rr~n~).'~, lffi Aminotransferase elevations may be mild or severe.54 Liver histology is similar to that described for preeclampsia. The severity of hepatic histologic involvement, however, does not correlate with the degree of aminotransferase elevation or thromb~cytopenia.~~

Maternal complications include disseminated intravascular coagulation, abruptio placentae, acute renal failure, pulmonary edema, and hepatic hematoma or rupture.'02, 178, In addition, the preeclampsia may progress to eclampsia.I4 Abruptio placentae correlates strongly with the development of disseminated intravascular coagulation and renal failure.'86 Maternal mortality in HELLP syndrome is 1% to 4%,'02, 178, 186, and perinatal mortality is approximately 35%.102,178 There is also an increased incidence of prematurity and intrauterine


growth retardat i~n.~~ The differential diagnosis of the HELLP syndrome includes disorders associated with abdominal pain, such as appendicitis, gallbladder disease, gastroenteritis, peptic ulcer disease, nephrolithiasis, and pyelonephritis; hepatic disorders, such as acute fatty liver of pregnancy and viral hepatitis; and disorders associated with thrombocytopenia, such as thrombotic thrombocytopenic purpura, hemolytic-uremic syndrome, and systemic lupus erythemato~us.~~, 54

Management of Preeclampsia, Eclampsia, and HELLP Syndrome

Delivery is the definitive therapy of preeclampsia and HELLP syndrome. Selected cases of mild preeclampsia occurring before the 36th week of gestation may be managed expectantly, with careful monitoring and control of blood pressure and prevention of seizures with magnesium sulfate, until the fetal lung matures.12, Io2 Therapy for severe preeclampsia, eclampsia, or HELLP syndrome should include prompt delivery.12, 14, lU2, lS6, Is7, 216 M anagement of severe preeclampsia or HELLP syndrome occurring before the 34th week of gestation is controversial; in some cases, delivery may be postponed for 24 to 48 hours while corticosteroids are administered to enhance fetal lung maturity.Iz, 14, lo2, 187 If delivery is postponed, the patient should be closely monitored, with control of blood pressure and prevention of seizures. Patients with HELLP syndrome may require considerable supportive care, with transfusion of blood products and management of pulmonary and renal complications.186, 216 These patients should be monitored closely postpartum in an intensive care unit. Most patients begin improving within 48 hours ~ostpartum,'~ and the platelet count should normal- ize within 7 days." Management of HELLP syndrome presenting postpartum is similar except for more aggressive blood pressure control. Exchange plasmapher- esis has been used in patients with HELLP syndrome who have not improved after 72 lo*, lE6

Hepatic Hemorrhage and Rupture

Hepatic hemorrhage with rupture is a rare, frequently lethal complication of pregnancy. The incidence of hepatic hemorrhage with rupture in one large review was about 1 per 45,000 live births.lYu About 90% of cases are associated with pree~lampsia'~, IYo or the HELLP syndr~me.'~, Iy3 In a large series of 442 patients with HELLP syndrome, Sibai and co-workers1s6 reported a 0.9% incidence of subcapsular hematoma. Patients who develop hemorrhage or rupture are more likely to be older and m~ltiparous.~~, 7y, 177 Hemorrhage and rupture has also been reported with benign and malignant hepatic tumors, hemangiomas,

The most common symptom of hepatic hemorrhage is epigastric or right upper quadrant pain, often radiating to the shoulder.17, 76, I z 3 , 144, Iy1 Nelson and colleagues'" described a triad of toxemia, right upper quadrant pain, and sudden unexplained shock with hepatic rupture. Symptoms usually occur in the third trimester but may occur up to several days after delivery.'=,

On physical examination, right upper quadrant tenderness may be present initially; with rupture, abdominal distention, signs of peritoneal irritation, and shock may ensue.17 Laboratory tests are nonspecific. Thrombocytopenia and elevated levels of serum liver enzymes may be present, especially in patients

and abscesses.66.79. 114,143,169

193

22 MAYER & HUSSAIN

with HELLP Is6, 190; leukocytosis and a decreasing hematocrit may also be present.l7. 123

Histologically, hemorrhage is believed to result from the hepatic lesions in preeclampsia, of sinusoidal fibrin deposition and periportal hemorrhage.*, 193

Hemorrhagic areas may extend peripherally and become confluent with similar areas arising from other portal tracts.17' Parenchymal hematomas are more common in the right hepatic lobe.17,79,144,171 As the hematoma expands, it can exceed the capability of Glisson's capsule to distend, and rupture may occur.'93 The role of minor trauma in these patients is uncertain.

Hepatic hematoma is most reliably diagnosed by CT scan."*, Iz3, 143, 178, 193 CT scan may also demonstrate intraperitoneal fluid, suggesting oozing of blood or

143 Ultrasound may also demonstrate subcapsular he ma to ma^^^, lg3 but is generally less sensitive.IZ3 Nuclear scans may demonstrate a hematoma but provide little information regarding anatomic details or the presence of intraperitoneal fluid.'14, 143, 193 Paracentesis is a safe, accurate method of identifying or confirming intraperitoneal hemorrhage.76, 143, 193

Historically the morbidity and mortality of hepatic hemorrhage was high. Bis and WaxmanI7 reviewed 91 cases in 1976 and found a maternal mortality of 59% and a fetal mortality of 62%; no patient survived without surgery. A variety of surgical procedures have been employed; evacuation of the hematoma with packing and drainage is generally performed initially, with other techniques, such as hepatic artery ligation or lobectomy, reserved for patients who do not respond to packing and drainage.76, 193 More recently, transcatheter arterial embolization has been successfully employed in the treatment of hepatic hemorrhage and r~pture."~, Zw Conservative therapy of an intact hepatic hematoma without rupture, consisting of blood pressure control and (usually) cesarean delivery, has also been reported to be successful.'u, Ig3 There has been one report of recurrent hepatic hemorrhage in a subsequent pregnancy.@

Acute Fatty Liver of Pregnancy

Acute fatty liver of pregnancy (AFLP) is a disorder that occurs during the third trimester and is characterized by microvesicular fatty infiltration of the liver."'*, 170 It occurs in approximately 1 in 13,000 deli~eries.~" 'O2, 'I8, 155, 167 It occurs more often in nulliparous women and in twin gestations.%, 96, 'I8, 167, 170

AFLP is a potentially lethal condition; through the 1970s, maternal and fetal mortality was as high as 85Y0.9~ The recent literature reports that maternal mortality is 18%, and the fetal mortality is 23?0?~,

The initial symptoms are nonspecific: headache, fatigue, malaise, nausea, and vomiting.54, 96, 'I8, 209 Abdominal pain is a common symptom and may be localized to the epigastrium, right upper quadrant, or lower right chest.118, 167, zo9

Preeclampsia is present in up to 46% of patients96, I7O, *09; some investigators believe that preeclampsia plays a role in the pathogenesis of AFLP.167 Serum aminotransferase levels range from mild elevations to up to 30 times normal; the mean value of aspartate aminotransferase is 8 times the upper limit of normal, with aspartate aminotransferase usually greater than alanine amino- t ransfera~e .~~~ Jaundice may occur at initial presentation or may occur later during the illness.96, 11*, 167, I7O The leukocyte count is often elevated above 15,000/ mm3, and the platelet count may be depressed. There may be evidence of disseminated intravascular coagulation, with prolonged prothrombin time and partial thromboplastin time, decreased fibrinogen level, and presence of fibrin- split products?" 167 Uric acid levels are usually elevated, blood urea nitrogen

178


and creatinine may be elevated, serum albumin is usually low, and serum ammonia is usually elevated.y6, If untreated, the patient may progress rapidly to fulminant hepatic failure.", 96 Additional complications include pancreatitis, gastrointestinal hemorrhage, renal failure, and adult respiratory distress syndr~rne. '~~, 178

The hepatic histology with AFLP is variable.118 The characteristic abnormal- ity is microvesicular fatty infiltration; this may be panacinar or zonal, affecting Rappaport zone 3 or zones 2 and 3 of the hepatic a~in i .~~ , '~O The fat is best demonstrated using a special stain such as oil red 0.96r170 Other findings include liver cell necrosis, Kupffer 's cell hypertrophy, cholestasis, and mild to moderate inflammation.'68, I7O Riely and associates'% have identified sinusoidal fibrin deposition, but this was not found by Rolfes and Ishak.'"

The differential diagnosis of AFLP includes preeclampsia, HELLP syndrome, intrahepatic cholestasis of pregnancy, viral hepatitis A through E, herpes simplex hepatitis, Budd-Chiari syndrome, acetaminophen overdose, adult-onset Reye's syndrome, acute cholecystitis, choledocholithiasis, cholangitis, thrombotic thrombocytopenic purpura, hemolytic-uremic syndrome, systemic lupus erythe- matosus, and other hepatic diseases with microvesicular steatosis."* Ultrasonog- raphy may show diffusely increased hepatic echogenicity, and CT scanning may show decreased hepatic attenuation, but these studies are neither sufficiently sensitive nor specific for a definitive diagnosis.Io2, 209 Differentiating between AFLP and severe preeclampsia is a common diagnostic problem, but the treatment of both conditions consists of prompt delivery and supportive care.'o2, *I8, Most patients begin to improve 2 to 3 days after delivery,"8 but depending on the severity and complications, full recovery may take weeks to months.'67 A small percentage of cases of AFLP may present after delivery, and AFLP should be considered in the differential diagnosis of postpartum maternal jaundice.'67, I7O

Budd-Chiari Syndrome

Hepatic venous outflow obstruction (Budd-Chiari syndrome) is a rare complication of pregnancy.'" It may occur during late pregnancy or weeks to months after delivery.65, 'O0, lZo, 206 Patients typically present with the triad of abdominal pain, hepatomegaly, and ascites. The pain may be due to hepatic distention from outflow obstruction or abdominal distention from ascites.Iz0 Laboratory values usually reveal normal to mildly elevated serum aminotransferase levels (up to twice normal), normal to mildly elevated bilirubin (usually <5 mg/dL), and alkaline phosphatase levels of 1.5 to 5 times The diagnosis may be made by liver biopsy,lZ0 hepatic venography,'zO or magnetic resonance imagi11g.6~ Therapeutic modalities include thrombolytic therapy, surgical decompression, and hepatic transplantation.'20 Despite these measures, the prognosis is extremely poor, with most patients dying within several months to 3 years from progressive hepatic failure."Q

Hepatic Tumors, Cysts, and Abscesses

Hepatic adenomas may become symptomatic during pregnancy, causing abdominal pain or presenting with rupture.98 They may also present as an asymptomatic mass.'y5 It has been postulated that the elevated serum estrogen levels during pregnancy stimulate the growth and vascularity of these benign

24 MAYER & HUSSAIN

tumors.96, 195 Hepatic hemangiomas have also been reported to become symptomatic during pregnancy, owing to either intratumor hemorrhage or rupture.@j

Hepatocellular carcinoma is rare during pregnancy. Lau and colleagues1o8 reported 5 cases in 1995 and identified 28 reported cases. The tumors may be asymptomatic and detected by the presence of hepatomegaly or an elevated serum a-fetoprotein leve1108; the tumor may cause abdominal pain1os, I6O, 213; or the tumor may rarely present with rupture.lo6, Median survival in patients with hepatocellular carcinoma in pregnancy appears to be shorter than in nonpregnant patients with inoperable hepatocellular carcinoma.lo8 Other rarely reported hepatic causes of abdominal pain during pregnancy include amebic liver abscess,'37 pyogenic liver abscess,'03 and hydatid cysts."

Acute intermittent Porphyria

The porphyrias are inherited disorders of porphyrin metabolism. The most common and severe hepatic form is acute intermittent porphyria (AIP).94, AIP has a prevalence of 3 per 100,000 population.11o It is inherited in an autosomal dominant fashion, but most patients are women, suggesting that hormones may influence disease expres~ion.~~, In AIP, porphobilinogen deaminase activity is reduced; however, the illness remains asymptomatic until hepatic aminolevulinic acid synthetase activity is stimulated, usually by drugs, hormones, or dietary factors. This stimulation leads to excessive production of 6-aminolevulinic acid and porphobilinogen, which are ne~ropathic.~~, Attacks are characterized by abdominal pain, vomiting, neuropsychiatric disturbances, and autonomic dys- functi0n.2~~ Cyclical attacks in women are common, relating to the menstrual cycle.11o

AIP in association with pregnancy is rare. Early studies reported high maternal mortalities and fetal wastage.94 Recent studies report that although 54% of women with AIP have attacks during pregnancy, only 1 maternal death occurred among 50 ~atients.2~ Fetal mortality was 13%, and infants born to mothers who had attacks during pregnancy had lower birth Because attacks of AIP often produce hypertension and autonomic dysfunction, it may be confused with pree~lampsia.9~, Brodie and co-workersZ reported 13 patients in whom the diagnosis was first made during pregnancy; the diagnosis should, therefore, be considered in pregnant patients with unexplained abdominal pain.

URINARY TRACT DISORDERS

During normal pregnancy, renal physiology and urinary tract anatomy are altered. Hydronephrosis and hydroureter occur in up to 90% of pregnancies.153, 162,201 The dilation begins in the second trimester, affects the right side more than the left, occurs only above the pelvic brim, and usually disappears within 1 month after delivery.162 This dilation is due to mechanical ureteral compression by the gravid uterus and by engorged ovarian veins and iliac vessels. The asymmetry is related to relative protection of the left ureter by the sigmoid

*01 Earlier theories of hormone-induced alterations of ureteral pressures were not ~ubstantiated.'~~, Although physiologic hydronephrosis of pregnancy is usually asymptomatic, it may be associated with attacks of pain owing to ureteral obstruction, which may be relieved by lying on the contralateral side in the knee-elbow position.162


Bacteriuria and Cystitis

Symptomatic acute cystitis occurs in 1% to 2% of pregnancies; typical symptoms include suprapubic discomfort, frequency, and urgency.142 Treatment with a 5- to 7-day course of oral antibiotics is recommended for symptomatic cystitis in pregnancy?’, 142 Follow-up cultures should be obtained to exclude recurrent infe~ti0n.l~~

The rate of asymptomatic bacteriuria in pregnancy is 2% to 10%; this rate is similar to that for age-matched nonpregnant women.37, Is3, Bacteriuria, however, is more likely to become symptomatic during pregnancy153 Twenty percent to 25% of pregnant patients with asymptomatic bacteriuria develop serious urinary tract infection^.^^,'^^ For this reason, pregnant patients should be screened and treated for asymptomatic bacter i~r ia .~~ Although most patients respond to antibiotic therapy, up to one third of infections may recur, so close follow-up is needed.37 Ampicillin or amoxicillin, cephalosporins, and nitrofurantoin may be used to treat lower urinary tract infections during pregnancy; sulfonamides may be used during early pregnancy but should be avoided near term; and quino- lones should be avoided during pregnancyza, 153

Pyelonephritis

The incidence of acute pyelonephritis during pregnancy is 1% to 2 7 0 . ~ ~ ~ 142

Common symptoms include fever, chills, nausea and vomiting, and flank pain.62 142

The pain in pyelonephritis may radiate to the upper or lower quadrants or to the inguinal and thigh region^.^^,'^^ Most cases of pyelonephritis during pregnancy occur in patients with preexisting bacteri~ria.’~~ The most common organ- isms causing pyelonephritis are members of the Enterobacteria~eae?~ Patients with pyelonephritis should be hospitalized and treated with intravenous fluids and intravenous antibiotics, such as cephalosporins, ampicillin, and gentami-

90% of patients respond within 72 hours. If fever persists beyond 72 hours, the patient should be evaluated for underlying urinary tract ob~truction.~~ Sepsis may develop in up to 10% of patients, and septic shock may occur in up to 3%.37, 16* Other complications include renal dysfunction,62 hematologic

and pulmonary dysfunction, including adult respiratory distress syndrome.37, 38, 207 These complications are believed to be mediated by bacterial endotoxin.% Although most patients respond to antibiotic treatment, 23% may develop recurrent pyelonephritis.6

Urolithiasis

Urolithiasis has been reported to occur during pregnancy with a wide range of frequencies, from about 1 in 90 to 1 in 3800 pregnancies.2O’ Stones occur more frequently in multiparas, usually present in the second and third trimesters, and occur with equal frequency on either side.121,1z2 The majority of stones are calcium stones. Coe and associatesx reported the cause of nephrolithiasis during pregnancy to be idiopathic hypercalciuria in 42%, hyperuricosuria in 13%, struv- ite stones in 13%, primary hyperparathyroidism in lo%, cystine stones in 3%, and idiopathic in 19%.34

Flank pain is the most common symptom in both pregnant and nonpregnant patients.196 The pain varies from intermittent aching to severe unremitting pain, often radiating to the lower quadrant.51 The pain is classically accompanied by

26 MAYER & HUSSAIN

nausea, vomiting, and urinary frequency or urgency.142 The pain is caused by distention of the proximal ureter and renal pelvis by an obstructing calculus.51 Abdominal pain is a frequent symptom but may not be well localized because the gravid uterus may alter pain perception.201 Gross or microscopic hematuria is usually present52,196 but may occur in other conditions as Hendricks and c o - ~ o r k e r s ~ ~ reported that urinary tract infection was a presenting symptom in all 15 patients in their series. Infection was present in 20% of the patients reported by Coe and associates34 and in approximately 45% of patients in other reported series.93 Premature labor may be induced by renal colic and may be the presenting symptom during pregnancy.1z1, lz2, 201

Ultrasonography is the primary diagnostic study in patients with suspected urolithiasis.122 It is noninvasive, inexpensive, and readily available and has no risk of radiation.201 Hendricks and co-w~rkers~~ identified stones by ultrasonography in 10 of 15 patients. About 75% of stones pass spontaneously with conservative management, consisting of bed rest, analgesia, and adequate hydra- tion.z8, 75, 196 In patients with persistent obstruction or infection or in patients in whom the diagnosis is uncertain, modified excretory urography may be safely performed.75, lz2, 201 A study comprised of one kidney, ureter, and bladder film and three additional radiographs exposes the fetus to 0.2 rad; this dosage does not result in a significant increase in fetal malformations after the 17th week of gestation.2o1

Therapeutic options for stones that fail to pass spontaneously include cys- toscopy with ureteral stent placement, ureteroscopy with stone manipulation, percutaneous nephrostomy, and open surgical treatment.75, Iz2, 196, 201 When procedures requiring fluoroscopy are performed, the duration of fluoroscopic exposure to the fetus should be minimized.Zo' Extracorporeal shock wave lithotripsy is contraindicated during pregnancy.75, 201

EXTRA-ABDOMINAL CAUSES OF ABDOMINAL PAIN

Abdominal pain may be a manifestation of thoracic, neurologic, systemic, or toxicologic disorders. Thoracic disorders that may cause abdominal pain by diaphragmatic irritation include pneumonia, pulmonary infarction, empyema, pneumothorax, endocarditis, pericarditis, and myocardial infarction. These disorders may also be associated with nausea and vomiting, which may further complicate the diagnosis.159 Right-sided congestive heart failure with hepatic congestion may cause right upper quadrant pain and tendemess.Is9 The associated symptoms and physical findings should aid in the diagnosis of cardiac and pulmonary disorders. Neurologic disorders include thoracic nerve root dysfunction, which may be secondary to diabetes, herpes zoster, scoliosis, osteo- arthritis, bony metastases, or other diseases of the thoracic spine; discitis; and abdominal rnigraine.l8, 159

Systemic disorders that can cause abdominal pain include diabetes mellitus and ketoacidosis (with or without associated pancreatitis), collagen vascular disorders, and hematologic disorders. Several cases of periarteritis nodosa during pregnancy have been reported. Typical symptoms include fever, malaise, nausea, and abdominal pain, often associated with hypertension and renal dysfunction, thus mimicking preeclampsia.'@ Maternal mortality is extremely high during pregnancy, but the fetus is usually unaffected, and all fetuses of viable gestational age have survived in reported cases.'@

The sickle hemoglobinopathies are the most common hematologic disorders encountered during pregnancy. The major clinically significant sickle hemoglo-


binopathies are sickle cell anemia (Hb SS), hemoglobin SC disease (Hb SC), and hemoglobin S-P-thalassemia (Hb S-thal).l” The prevalence of these disorders in the African-American population is about 1 in 625 for Hb-SS, 1 in 800 for Hb- SC, and 1 in 1700 for Hb S-tha1.I” Patients with sickle hemoglobinopathies are susceptible to vaso-occlusive crises, leading to decreased blood perfusion, vascular stasis, tissue hypoxia, and acidosis; microvascular injury may lead to ischemic necrosis and infarction.’” Vaso-occlusive crises typically produce pain in the long bones, abdomen, chest, or back. Approximately 50% of pregnant patients with Hb SS or Hb S-thal and 30% of pregnant patients with Hb SC experience painful vaso-occlusive crises during pregnancy, and 8% of pregnant patients with sickle hemoglobinopathies experience vaso-occlusive crises during the postpartum period.s3, 189 Cholelithiasis is common in patients with sickle hemoglobinopathies, and acute cholecystitis may occur during pregnancy; cholecystitis is more common with Hb SS than with either Hb SC or Hb S-thal.175 Before 1970, maternal mortality in patients with sickle hemoglobinopathies was 35%, and fetal mortality was as high as 80O/0.’~~ With improved prenatal care and more aggressive treatment of complications, maternal mortality is now less than 1%,’“, lS9

and fetal mortality is 8%?3, la3, lS9 Pregnancies complicated by sickle cell disease are more likely to be associated with premature labor, preeclampsia, and low birth

Abdominal pain may result from ingestion of drugs, toxins, or other substances. Ingested substances can cause corrosive injury (aspirin, iron, mercury, acids, and alkali), obstruction or ileus (anticholinergics, narcotics in “body packers”), or systemic toxicity (lead, arsenic, envenom at ion^).'^^ In addition, some drugs may induce ischemia (cafergot, digitalis, vasoconstrictors) or direct organ damage (drug-induced hepatic injury or pancreatiti~).’~~ Prescribed systemic drugs are generally avoided during pregnancy. Cocaine intoxication has been associated with preeclampsia, eclampsia, and uterine rupture during pregnan~y.’~~, *08 The venom of the black widow spider, Latrodectus mactans, produces severe abdominal pain and abdominal muscle spasm.141 Latrodectus is found in every state except Alaska, and Latrodectus envenomation has been described during pregnancy; treatment is supportive and symptomatic.1n Other rare systemic causes of abdominal pain during pregnancy include miliary tuberc~losis~~ and malaria.158

IDIOPATHIC ABDOMINAL PAIN DURING PREGNANCY

A number of pregnant patients may be evaluated or hospitalized because of abdominal pain for which no cause can be determined. Brewer and colleaguesz2 reported 1000 consecutive patients seen in a university hospital emergency department because of abdominal pain; in 18 patients (l.8%), the diagnosis was pregnancy. Baker and associates1o compared 140 pregnant patients with unexplained abdominal pain with 280 pregnant women without abdominal pain. They found no difference in the outcome of pregnancy between the two groups, but the group with unexplained abdominal pain had a higher proportion of unmarried women, smokers, and women whose partners were unemployed. These findings suggest that socioeconomic factors might play a role in some instances of unexplained abdominal pain during pregnancy.

DIAGNOSTIC IMAGING DURING PREGNANCY

Both patients and physicians are concerned about the safety of diagnostic imaging studies during pregnancy. Ultrasonography is considered safe during

28 MAYER & HUSSAIN

pregnancy2*' and is widely used to evaluate both normal and abnormal pregnancies as well as to evaluate abdominal pain. Magnetic resonance imaging is preferable to CT during pregnancy because of its lack of ionizing radiationF2I

Fetal risk from x-ray examinations depends on the period of gestation when the examination is being performed, fetal proximity to the area being irradiated, and the radiation dosage. Risk of fetal death is greatest during the preimplanta- tion phase (0 to 9 days' postconception), whereas risks of congenital malformations, growth retardation, or mental retardation are greatest during weeks 2 through 14T6, The estimated minimal dose necessary to cause these abnormalities is 10 rad (0.1 Gy)F5, 86, 221 Fetal radiation exposure is 0.06 mrad for a chest film, 50 mrad for an upper gastrointestinal series, 260 mrad for abdominal radiographs, and 820 mrad for a barium enema or standard intravenous pyelo- gram.86

Brent20,21 reported that the risk of fetal malformation from exposure to 1 rad is several orders of magnitude less than the risk of spontaneous abortion, malformation, or genetic disease. Therefore, when x-ray examination is needed for clinical management, the benefit of the x-ray significantly outweighs the potential small risk to the fetus.67 Fetal exposures should be minimized by minimizing fluoroscopy time and using fewer exposures, collimation, and shielding whenever possible.6*, Patients should be informed of the risks whenever possible. When extensive x-ray studies or CT scanning is necessary, radiation dosimetry calculations should be considered for future genetic counseling.z1 Termination of pregnancy should not be recommended because of radiation exposure alone for exposures to less than 5 rad.20,21,61 If the exposure is greater than 15 rad, the risks may be sufficient to consider termination; if the cumulative dose is between 5 and 15 rad, other maternal factors, including age, health, and mental and emotional state, should be considered in the

SUMMARY

In evaluating the .pregnant patient with abdominal pain, the physician is presented with a wide range of diagnostic possibilities, including disorders that can occur in nonpregnant individuals and disorders that are unique to pregnancy. The development of modem laboratory testing methods and diagnostic imaging techniques has led to a decline in the morbidity and mortality from many of these disorders. With an understanding of the physiologic changes occurring during pregnancy, a careful history and physical examination, and judicious use of laboratory tests and imaging studies, the physician should be able to determine the cause of the patient's pain in the great majority of cases and, in the words of Babler; avoid "the mortality of delay."

ACKNOWLEDGMENTS

The authors t ' n d Dr. Joel Mollii and Dr. Perry Gerard for providing several references on the use of radiologic procedures and ultrasound during pregnancy.

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Abdominal Pain During Pregnancy

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