The irritable bowel syndrome during pregnancy

Gastrointestinal motor abnormalities 

Gastrointestinal motor abnormalities are common in IBS. Patients with IBS exhibit pronounced colonic responses to meal ingestion lasting up to three hours [9]. Patients with constipation-predominant IBS exhibit increases in the electric activity that produces segmenting colonic contractions that retard stool transit, whereas diarrhea-predominant patients exhibit reductions in this activity. Diarrhea-predominant patients with IBS have increased high-amplitude–propagated colonic contractions, the complexes that precede defecation. In the small intestine, fasting contractile amplitude is blunted in constipation-predominant patients, whereas the duration of the stereotypic fasting pattern, the migrating motor complex (MMC), is shortened in diarrhea-predominant patients with IBS. In both constipation- and diarrhea-predominant patients with IBS, the duration of the fed intestinal motor pattern is shorter than in healthy volunteers. Small intestinal transit is delayed in constipation-predominant patients, but is accelerated in diarrhea-predominant patients. Sporadic motor patterns, including retrograde duodenal contractions, discrete clustered contractions, and prolonged ileal contractions, may occur more often in IBS than in healthy volunteers, but these are nonspecific findings. Extraintestinal smooth muscle may exhibit motor dysfunction. In IBS, the lower esophageal sphincter pressure is decreased, esophageal body peristalsis may be abnormal, gastric emptying of solids may be delayed, and tachygastria or bradygastria may occur. Gallbladder emptying and sphincter of Oddi function may be abnormal. Other smooth muscle abnormalities include detrusor instability of the bladder and airway hyperreactivity to methacholine.

Visceral sensory abnormalities 

Abdominal sensation is mediated by afferent pathways activated by stimuli acting on chemoreceptors (which sense osmolarity, temperature, and pH), mechanoreceptors (which detect changes in tension), and mesenteric nociceptors. IBS is postulated to result from sensitization of visceral afferents so that physiologic events, not normally perceived by healthy individuals, induce pain in IBS. Indeed, patients with IBS can perceive physiologic small intestinal muscular contractions or experience pain during passage of food residue from the ileum to the cecum. Patients with IBS perceive exaggerated pain from colonic balloon inflation [10]. Patients with IBS experience heightened sensitivity to mucosal electric stimuli and to intestinal lipid perfusion; they also experience abnormal pain referral patterns during gut distention in that they can experience pain diffusely in the abdomen, back, shoulders, or chest. Patients with IBS who have hypersensitivity to rectal distention show heightened analgesic responses to the μ-opioid agent fentanyl, suggesting central opioid receptor dysfunction [11]. Whether or not the sensory dysfunction is generalized or limited to gut afferents is unknown. Some studies have reported similar responses to electric and thermal cutaneous stimulation in patients with IBS and healthy controls, but others have reported increased perception of cutaneous thermal pain in patients with IBS and heightened generalized somatic sensation in patients with IBS who have fibromyalgia.

Central nervous system dysfunction 

IBS may be a primary gut disturbance with inappropriate CNS input or a primary CNS disorder with centrally directed changes in gut motor and sensory function. Evoked potential recordings in patients with IBS exhibit decreased waveform latencies and increased amplitudes [12]. Using positron emission tomography (PET), patients with IBS demonstrate abnormal activation of regions of the brain, which mediate the affective components of pain perception and the supervision of visceral sensation, suggesting a primary central disturbance in processing of gut sensory information [13]. The presence of a pathogenic CNS defect is supported by the increased frequency of psychiatric abnormalities in IBS: the lifetime incidence of major depression, somatization disorder, generalized anxiety disorder, panic disorder, and phobias are higher in patients with IBS than in healthy controls. Increases in neuroticism, hostility, hypochondriasis, body preoccupation, interpersonal sensitivity, concealed aggression, and introversion also are reported [14]. Psychiatric symptoms usually predate or occur simultaneously with the onset of bowel symptoms, indicating that emotional illness is not a result of IBS. Recent or remote emotional stress often triggers IBS symptoms. Sleep disturbances, including nocturnal awakening and awakening in the morning feeling unrested, occur in 72% of patients with IBS. Rates of severe lifetime sexual trauma, severe childhood sexual abuse, and any lifetime sexual victimization are significantly higher in patients with IBS than in individuals with inflammatory bowel disease [15].

Other pathogenic factors 

Other contributing factors have been proposed. In a controversial recent study, 78% of patients had bacterial overgrowth based on hydrogen breath test responses to lactulose [16]. Some patients relate having gastrointestinal infection before developing IBS. Abnormal bowel function persists for more than six months after culture-proven bacterial gastroenteritis in approximately 25% of patients [17]. These patients have increased ileocecal mast cells, colonic mucosal enterochromaffin cells, CD3 lamina propria lymphocytes, and intraepithelial lymphocytes, which suggest a subtle inflammatory disorder in some cases of IBS. Some patients with IBS show a partial response to dietary exclusion of lactose, fructose, or sorbitol. True food intolerance is exceedingly rare. Several recent double-blind, placebo-challenge studies, however, identified offending foods in 6% to 58% of IBS cases, especially with diarrhea predominance [18].

Investigators have reported cholinergic dysfunction in constipation-predominant patients, adrenergic dysfunction in diarrhea-predominant patients, and abnormal release of various peptide hormones in selected patients. Serotonin (5-hydroxytryptamine, 5-HT) may play a pivotal pathogenic role. Diarrhea-predominant patients with IBS have increased postprandial plasma serotonin levels and increased numbers of serotonin-containing colonic epithelial cells [19]. Family members of patients with IBS often report bowel disturbances, suggesting a possible genetic component to the disorder. In one study, 4.8% of same-sex twins, including 186 monozygotic and 157 dizygotic pairs, shared a functional bowel disorder [20]. Mathematic modeling indicated that 56.9% of the variance was attributable to genetic factors and 43.1% was attributable to environmental factors.

Irritable bowel syndrome pathogenesis in pregnancy 

Pathogenic factors of IBS have not been studied rigorously in pregnancy. Hormonal and nonhormonal changes, however, during pregnancy modify gastrointestinal function.

Gut function in pregnancy 

Analysis of human gut function in pregnancy is restricted by the invasiveness of diagnostic tests; many tests employ ionizing radiation, which is teratogenic. Nevertheless, physiologic studies in humans and animal models have provided insight into gastrointestinal motor function during pregnancy. Using hydrogen breath test measurements after ingestion of nonabsorbable sugars, investigators have observed prolonged orocecal transit in women in the third trimester of pregnancy compared with the postpartum period (Fig. 1) [43], [44]. In rats, small intestinal transit is retarded selectively in association with loss of the periodicity of fasting myoelectric complexes [45], [46]. Studies of gastric emptying in human pregnancy, as measured by acetaminophen absorption, have been contradictory: one study showed delays in the first trimester, but other studies showed no changes [47], [48], [49]. Slowed gastric emptying in pregnant guinea pigs is not associated with impaired smooth muscle responsiveness to acetylcholine, indicating that this effect of pregnancy does not result from impaired muscle contractility [50]. Retarded colonic transit in pregnant rats, however, parallels increases in nitric oxide synthase levels and production of cyclic guanosine monophosphate (GMP) in smooth muscle tissues, indicating that nitrergic nerve function increases during pregnancy [51].

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Fig. 1. Median values (horizontal bar) and 5th and 95th percentiles (open circles) of the orocecal transit time (OCTT) in the first trimester, third trimester, and postpartum period in 11 pregnant women are shown. OCTT increased significantly during the third trimester (P<0.05), but returned to normal postpartum (From Chiloiro M, Carconza G, Piccioli E, et al. Gastric emptying and orocecal transit time in pregnancy. J Gastroenterol 2001;36:538–43; with permission.)

Sex hormone effects on gut function 

Pregnancy is associated with increased production of several hormones that affect gastrointestinal motor, myoelectric, and sensory function. Estrogen and progesterone increase throughout normal pregnancy. Administration of progesterone markedly increases gastrointestinal complaints in patients with functional bowel disorders [52]. Progesterone reduces the contractile force of smooth muscle in the canine colon and the murine jejunum [53], [54]. The effects of progesterone on the stomach are controversial: some animal studies show acceleration of gastric emptying and others show delay; human studies show disruption of the gastric slow wave rhythm [55], [56], [57]. The effects of estrogen similarly are inconsistent: some animal studies show inhibition of gastric emptying; human studies show no effect on gastric function. Estrogen and progesterone synergistically cause degeneration of the gastric slow wave rhythm and delay colonic transit in rats [57], [58]. These motor effects of estrogen and progesterone might increase the symptoms of IBS. Conversely, these hormones have analgesic properties that might reduce the pain of IBS. In rats, estrogen and progesterone administered in amounts that achieve the serum levels present in pregnancy produce opioid antinociception, antagonized by κ-opiate–receptor antagonists [59]. LH, produced midway through the menstrual cycle, and human chorionic gonadotropin (hCG), produced most prominently in the first trimester of pregnancy, bind to the same receptor. In rat small intestine, LH and hCG promote fragmentation and prolongation of the cycle length of the MMC [60]. Relaxin, a hormone produced after the tenth gestational week, produces relaxation of the cervix and symphysis pubis, increases ileal expression of nitric oxide synthases, and reduces ileal smooth muscle contractions in mice via increased nitrergic nerve activity (Fig. 2) [61].

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Fig. 2. Representative recordings of the force of spontaneous ileal muscular contractions, in grams of weight, versus time, in minutes, are shown in (A) control mice and (B) mice treated for 18 hours with relaxin. Relaxin markedly reduced ileal contractions (From Bani D, Baccari MC, Quattrone S, et al. Relaxin depresses small bowel motility through a nitric oxide-mediated mechanism. Studies in mice. Biol Reproduction 2002;66:778–84; with permission.)

History and physical examination 

Because IBS is a chronic disorder, many women already have an established diagnosis before conception. In these individuals, no further diagnostic testing is indicated during pregnancy, unless their symptoms drastically change or alarm symptoms, such as bleeding, weight loss, or pyrexia, occur. When symptoms begin during pregnancy, IBS usually is reliably diagnosed by recognition of characteristic symptom profiles. In a questionnaire survey of nonpregnant individuals, Manning and colleagues identified the following symptoms as significantly more common in IBS than in organic disease: relief of abdominal pain upon defecation, looser stools with pain onset, more frequent stools with pain onset, and abdominal distention [62]. Ninety-one percent of patients with IBS had two or more of these symptoms versus 30% of those with organic disease. Kruis and coworkers found that absence of organic disease was predicted by (1) the combination of pain, flatulence, and irregular defecation; (2) symptoms persisting for more than two years; (3) pain described as burning, cutting, very strong, or terrible; (4) diarrhea alternating with constipation; (5) pencil-like or pellet-like stools; and (6) passage of mucus in stool [63]. More recently, the Rome I and II criteria have categorized more precisely the symptomatic patterns of IBS [1]. The accuracy of these symptomatic criteria has been assessed only in nonpregnant individuals. The Manning criteria have a sensitivity ranging from 58% to 90% and specificity of 74% to 87%, whereas the Kruis system has a sensitivity of 81% and specificity of 97%. In a prospective study, the positive predictive value of the Rome I criteria, in the absence of alarm findings, was 98% [64].

Physical examination of the pregnant woman with IBS usually is normal, except for the presence of the enlarged gravid uterus. Abdominal compression may elicit vague and poorly localized tenderness. Tender bowel loops may be palpated. Abdominal masses, hepatosplenomegaly, lymphadenopathy, ascites, blood in the stool, or autonomic or peripheral neuropathy are suggestive of organic disease and warrant further investigation.

Laboratory and structural findings in irritable bowel syndrome 

Minimal laboratory evaluation and diagnostic testing are recommended for presumed new-onset case of IBS during pregnancy. Basic testing includes a complete blood count to assess for anemia, leukocytosis, or leukopenia; serum electrolytes; stool analysis for ova and parasites, bacterial pathogens, or Giardia antigen in the diarrhea-prone patient; an erythrocyte sedimentation rate as an indicator of inflammation; and thyroid chemistries to exclude thyroid dysfunction [65]. Recent studies suggest a possibly increased prevalence of celiac sprue in IBS; thus, determination of endomysial or tissue transglutaminase antibody status can be considered [66]. For diarrhea-predominant individuals, hydrogen breath testing, to exclude lactase deficiency, is recommended or an empiric dietary trial of lactose restriction if breath testing is unavailable. Sigmoidoscopy has been recommended for nonpregnant patients younger than 50 years old to exclude distal obstruction in patients with constipation and to exclude inflammatory diseases in patients with diarrhea [65]. In diarrhea-predominant patients, random colonic biopsies have been advocated to exclude microscopic colitis. The utility of many of these diagnostic tests in nonpregnant patients has been questioned. A study of patients satisfying the Rome I criteria found no diagnostic yield from the sedimentation rate, thyroid profile, and stool examination for ova and parasites in the absence of specific historical or examination findings. In two multicenter trials, lactose intolerance was diagnosed in 23% of patients, structural abnormalities were found in 2%, abnormal thyroid tests were observed in 6%, and ova and parasites were detected in feces in 2% [67]. The advisability of performing sigmoidoscopy in pregnancy to facilitate diagnosis of IBS is questionable. In a multicenter retrospective report of 48 sigmoidoscopies in 46 pregnant patients, sigmoidoscopy caused no complications, did not induce labor, and did not lead to fetal anomalies [68]. The indications for sigmoidoscopy, however, in this investigation included hematochezia in 29 patients, and the findings of sigmoidoscopy included ulcerative colitis in 12, Crohn's colitis in 8, pseudomembranous colitis in 1, and anastomotic ulcers in 1. This study population exhibited clinical presentations much more worrisome for organic disease than most individuals with presumed IBS. Even though diagnostic testing, including sigmoidoscopy, is generally is safe in pregnancy, the clinician should weigh any potential benefits against the discomfort and anxiety such an evaluation produces. In many instances, testing can be deferred until postpartum.

Dietary measures and fiber supplements in irritable bowel syndrome 

Dietary modifications commonly are recommended in IBS. No controlled investigations of these interventions have, however, been performed during pregnancy. Dietary changes should play a prominent role in treating IBS during pregnancy because they usually are safe. Restriction of fat intake is reasonable because fat potently activates motor reflexes, such as the gastrocolic response. Patients with bloating and diarrhea should restrict intake of poorly digestible sugars, such as fructose and sorbitol. Diets that restrict selected foods according to the amount of gas produced have been advocated for patients with IBS who have bloating and excessive flatus.

Fiber supplements exhibit beneficial properties including enhanced fecal water retention, bulking of stool, formation of gels to provide stool lubrication, and binding potentially harmful bile acids. Bran accelerates colonic transit in healthy volunteers with relatively infrequent defecation, but retards transit in those with relatively frequent defecation. Psyllium reduces the perception of rectal distention, indicating that fiber may also improve visceral afferent function. In a meta-analysis, bran increased fecal weight in 18 of 20 studies and accelerated fecal transit in 16 of the studies [69]. Soluble fiber, such as pectin, psyllium, or oat bran, enhances fecal water retention, whereas insoluble fiber, such as cellulose or lignin, more effectively enhances fecal bulk.

Fiber supplements, including bran, psyllium, processed flea seed husk (ispaghula), and calcium polycarbophil, have been analyzed in placebo-controlled studies in patients with IBS. Many investigators report increases in stool weight, decreases in colonic transit time, and improvement in constipation, but most investigators observe no improvement in patients with diarrhea- or pain-predominant IBS. Different fiber preparations may have different effects on specific symptoms. Bran increases abdominal distention and flatulence, whereas processed preparations, such as psyllium, reduce these symptoms [70].

Pregnant women with constipation do not eat less fiber than pregnant women without constipation [71]. Nevertheless, corn biscuits or wheat bran supplementation increases stool frequency and improves stool consistency in constipated pregnant patients (Fig. 3) [72]. Fiber supplementation thus should be considered a first-line therapy for constipation-predominant IBS during pregnancy.

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Fig. 3. The number of bowel movements per week is shown before (A) and during (B) fiber supplementation with a corn biscuit (Fibermed), bran, or placebo. Both fiber preparations increased stool frequency but the placebo produced no effect (From Anderson AS, Whichelow MJ. Constipation during pregnancy: dietary fiber intake and the effect of fiber supplementation. Human Nutr Appl Nutr 1985;39:202–7; with permission.)

Medications for irritable bowel syndrome 

Drug recommendations for IBS during pregnancy must weigh carefully the expected therapeutic gain versus the fetal risk. Although IBS adversely affects quality of life, it does not produce significant physical debilitation. Thus, the clinician should rely more on reassurance, dietary modification, and psychologic intervention and less on drugs in pregnant than nonpregnant women. Initiation of a new medication during pregnancy should be performed with obstetric consultation.

Prescription drugs are categorized by the Food and Drug Administration (FDA) according to safety during pregnancy. Most agents used to treat IBS are category B—animal studies do not show risks to the fetus and there are no controlled human studies, or animal studies show adverse effects but human studies show no risk to the fetus; category C—animal studies show teratogenic or embryocidal effects but there are no human studies, or there are no animal or human studies in pregnancy; or category D—positive evidence of human fetal risk exists but benefits in certain situations may make the drug acceptable despite the risks. Although imperfect, this classification helps assess the risks versus benefits of medications in the pregnant woman with IBS.

Antidepressant agents 

Tricyclic antidepressants have clear efficacy in selected nonpregnant patients with IBS. Amitriptyline produces benefits in global well being, abdominal pain, and bowel habits, whereas trimipramine ameliorates vomiting, depression, insomnia, and fecal mucus and sometimes reduces abdominal pain. Desipramine decreases abdominal pain, stool frequency, and depression in diarrhea-prone patients.

The efficacy of other classes of antidepressants is less clear. The selective serotonin reuptake inhibitor (SSRI) paroxetine accelerates orocecal transit, suggesting possible use in constipation-predominant patients. The SSRI citalopram blunts perception of rectal distention and reduces the magnitude of the gastrocolic response in healthy volunteers [90]. In a small placebo-controlled study, citalopram reduced abdominal pain in IBS [91]. A meta-analysis of tricyclic and nontricyclic antidepressants reported an odds ratio for clinical improvement of 4.2 (confidence interval 2.3–7.9) [92]. A meta-analysis of all antidepressant trials in IBS reported an odds ratio for improvement in abdominal pain of 8.0 and for global improvement of 4.4 [93].

The safety of antidepressant drugs during pregnancy has been studied extensively for the treatment of depression but not for the treatment of IBS. In one study, women who became pregnant on tricyclic antidepressants, women who were prescribed tricyclics while pregnant, and women who refused tricyclic antidepressants during pregnancy exhibited no significant differences in the rate of fetal malformations or pregnancy complications, although neonates whose mothers had taken tricyclic antidepressants during pregnancy had short-term neonatal withdrawal symptoms of cyanosis, respiratory distress, irritability, autonomic dysfunction, and hypoactivity [94], [95]. Cases of neonatal heart failure and electrocardiographic abnormalities also have been reported [89]. In one investigation, fluoxetine tended to cause an increased rate of miscarriage, but this finding was not confirmed in a recent meta-analysis [96], [97]. A study of 267 women on newer SSRIs reported no increase in fetal malformations, miscarriage, prematurity, or low-birth-weight infants [98]. Intrauterine SSRI exposure also causes a neonatal withdrawal syndrome consisting of irritability, crying, shivering, increased tonus, difficulty eating, insomnia, and seizures [99]. Maternal use of tricyclics or SSRIs during pregnancy does not affect global intelligence quotients, language, or behavioral development of their children assessed at the preschool level (Table 1) [100]. In women receiving these two classes of antidepressants, symptoms need to be monitored as the dose requirement progressively increases during pregnancy [101], [102]. Tricyclic agents are listed either as FDA category C (desipramine and amitriptyline) or D (nortriptyline and imipramine); whereas SSRIs, such as fluoxetine, paroxetine, sertraline, and citalopram, are FDA category C. These drugs should be considered only for severe gastrointestinal symptoms of IBS during pregnancy.

Table 1. Results of neurobehavioral tests in infants according to exposure in utero to antidepressant drugsa

		Score			Adjusted differences (95% CI)c
	Testb	Tricyclic antidepressant drugs (N=80)	Fluoxetine (N=55)	Control (N=84)	Tricyclic antidepressant drugs vs. control	Fluoxetine vs. control
	Bayley Mental Development Index	118±17	117±17	115±14	2.4 (−4.5 to 9.4)	2.1 (−5.0 to 9.2)
	McCarthy General Cognitive Index	117±10	114±16	114±13	2.7 (−2.3 to 7.6)	4.7 (−4.0 to 13.4)
	Reynell Verbal Comprehension Scale	1.3±0.8	1.2±1.2	1.1±0.9	0.3 (−0.1 to 0.5)	0.3 (−0.1 to 0.6)
	Reynell Expressive Language Scale	0.3±0.9	−0.2±1.0	0.1±1.0	0 (−0.3 to 0.3)	−0.1 (−0.4 to 0.3)

From Nulman I, Rovet J, Stewart DE, et al. Neurodevelopment of children exposed in utero to antidepressent drugs. New Engl J Med 1997;3336:258–62; with permission.

a Plus–minus values are means±SD. c Multiple regression analysis was used after adjustment for children's age; maternal IQ, socioeconomic status, score on the Center for Epidemiologic Studies Depressed Mood Scale, and score on the Global Assessment Scale; and duration of exposure to drug (first trimester vs. entire pregnancy). CI denotes confidence interval. b The children were tested between 16 and 86 months of age (mean, 33±14). The Bayley and McCarthy scores are typical for this age. The normal range for both rests is 100±1 SD. Lower scores mean lower cognitive function. The mean Reynell score in normal children of this age is 0±1 (range of possible scores, −3 to +3).

Psychologic therapy of irritable bowel syndrome 

Psychologic therapies are reserved for patients with IBS who have psychosocial features that fail to respond to standard therapy. A comprehensive review identified only 14 well-designed, controlled studies of psychologic treatments published between 1966 and 1994 [107]. Eight of the studies reported that psychologic treatment was superior to control treatment, but six reported no benefit. Because of methodologic inadequacies, the efficacy of psychologic therapy in IBS is not established. Promising forms of psychotherapy for IBS include dynamically oriented psychotherapy, group psychotherapy, and psychodrama. Cognitive therapy produces long-term, persistent improvements in bowel symptoms. A recent trial reported superior responses and improved quality of life when a multicomponent program, consisting of IBS education, muscle relaxation, cognitive coping strategies, and assertiveness training, was added to standard therapy, compared with standard therapy alone [108]. Muscle relaxation training and education reduce bowel symptoms, including abdominal pain, flatulence, eructation, and bloating in some studies. Hypnosis decreases abdominal pain, abdominal distention, nausea, and flatulence; regularizes bowel habits; and improves overall well being. These effects are sustained for up to 18 months [109]. The pregnant patient with IBS may be considered for psychologic therapy for severe symptoms because of concern about using drugs during pregnancy.

Alternative medicine in irritable bowel syndrome 

Because of the limited efficacy of prescribed medicines for IBS, some nonpregnant individuals turn to alternative medicines for symptomatic relief. Open trials report benefits from arrowroot and artichoke leaf. Placebo-controlled studies of probiotic therapies, such as lactobacillus and Streptococcus faecium, have yielded variable results ranging from efficacy to no benefit [110]. In a large placebo-controlled, double-blind trial, Fumaria officinalis, Curcuma xanthorrhiza, Ayurvedic, or spagyric remedies did not improve abdominal pain, stool function, or quality of life as compared to placebo. Contrariwise, in a randomized, controlled 16-week trial, traditional Chinese herbal medicine produced improvements in bowel symptoms and global well being, as rated by patients and their gastroenterologists [111]. An uncontrolled study noted reduced bloating and enhanced well being with acupuncture. The safety and efficacy of these alternative treatments in pregnant women with IBS are unknown.

The constipation-predominant patient 

The management of the pregnant patient with IBS who has constipation involves increasing stool water and bulk. Fiber supplements are highly effective for this purpose. They should be introduced gradually to prevent abdominal gas and bloating. Drugs that slow colonic transit should be discontinued. When the response to fiber is inadequate, an osmotic laxative is recommended. Radiographic studies to assess colonic motor function should be deferred until after delivery. Laboratory studies can screen for porphyria or heavy metal toxicity if clinically suspected.

The diarrhea-predominant patient 

The goal of therapy for diarrhea in IBS is to reduce stool frequency and urgency and to improve stool consistency. Kaolin and pectin can be used safely but may be inadequate for symptomatic relief. Loperamide usually is more effective, but should be used judiciously and infrequently. Bile acid–binding agents or antispasmodics reduce postprandial diarrhea, but should be employed with caution. Tricyclic antidepressants should be avoided if possible. Patients not responsive to these therapies may require additional testing. Quantitative analysis of stool volume and fat can exclude secretory diarrhea or malabsorption. Screening tests for laxative abuse are indicated for refractory or atypical symptoms.

Painful irritable bowel syndrome 

Controlling the pain of IBS during pregnancy can be challenging. Narcotics should be avoided because of the risks of tolerance and dependence. As mentioned previously, antispasmodics should be used cautiously and antidepressants should not be given if possible. Investigation of the cause of pain should focus on objective historical findings, physical signs, and routine laboratory tests. Serum biochemical parameters of liver and pancreatic function should be determined if hepatobiliary or pancreatic disease is suspected. Patients occasionally need laboratory testing to exclude lead toxicity or porphyria.