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INTRODUCTION — Inflammatory bowel disease (IBD) can affect women in their childbearing years and therefore has implications on fertility, pregnancy, and nursing.
This topic will review issues related to fertility in patients with IBD and the diagnosis and management of IBD in pregnant and nursing women. The medical management of IBD in the general population is discussed in detail separately. (See "Management of mild to moderate ulcerative colitis in adults" and "Management of severe ulcerative colitis in adults" and "Approach to adults with steroid-refractory and steroid-dependent ulcerative colitis" and "Overview of the medical management of mild to moderate Crohn disease in adults".)
FERTILITY — Patients with quiescent inflammatory bowel disease (IBD) do not have decreased fertility as compared with the age-matched general population [1-5]. Low birth rates among women with IBD are often due to patient choice rather than disease-related infertility [1,4]. (See "Overview of infertility".)
However, IBD can cause infertility in the following circumstances:
●Active inflammation in women with Crohn disease may result in infertility due to inflammation involving the fallopian tubes and ovaries . Perianal disease can also cause dyspareunia. (See "Causes of female infertility", section on 'Fallopian tube abnormalities/pelvic adhesions'.)
●Medications may decrease fertility in men. As examples, methotrexate and sulfasalazine can cause reversible oligospermia. In addition, sulfasalazine is also associated with reduced sperm motility and abnormal sperm morphology [6-8].
●Surgery may impact fertility in patients with IBD. Proctocolectomy in men may lead to impotence or ejaculatory difficulties . Restorative proctocolectomy with ileoanal anastomosis has been associated with dyspareunia and a reduction in fertility due to scarring and formation of adnexal adhesions [2,10,11]. (See "Operative management of Crohn disease of the small bowel, colon, and rectum", section on 'Choosing a procedure' and "Surgical management of ulcerative colitis", section on 'Surgical options'.) Female IBD patients with infertility may seek assisted reproductive technology (ART) treatment. A cohort study based on Danish health registries evaluated the chance of live birth in women with IBD who underwent ART treatments . Women with ulcerative colitis had lower rates of successful pregnancy compared to non-IBD infertile women (OR 0.73, 95% CI, 0.58-0.92). Women who had surgery for Crohn disease were also less likely to have live birth following ART (adjusted OR 0.51, 95% CI, 0.29-0.91).
PRECONCEPTION COUNSELING — Preconception counseling offers an opportunity for the clinician to address specific patient concerns regarding the risk of transmission of inflammatory bowel disease (IBD) or other diseases to their offspring, to optimize control of disease activity and nutritional status, avoid inappropriate medication cessation, and discontinue medications that may adversely affect pregnancy. (See "The preconception office visit".)
IBD risk in offspring — Although IBD follows a non-Mendelian pattern of inheritance, genetically determined factors contribute to IBD susceptibility. First-degree relatives of patients with IBD are approximately 3 to 20 times more likely to develop IBD as compared with the general population [13-16]. In a large national, registry-based cohort study with a median follow up of 10 years, the risk of developing IBD was increased in offspring born to mothers with ulcerative colitis (HR 4.6, 95%CI 3.5-6.2) and mothers with Crohn disease (HR 7.7, 95% CI 5.7-10.5) compared with mothers without IBD; the impact of paternal IBD was not evaluated .
Clinical features of the disease also demonstrate a heritable pattern with concordance in disease location (eg, ileal versus colonic Crohn disease) and type (eg, fibrostenotic Crohn disease, fistulas) [18-23]. Subsequent generations may demonstrate "genetic anticipation" with the development of earlier onset of IBD and more severe disease as compared with their parents [16,24].
The role of genetic factors that increase susceptibility to IBD and genetic syndromes associated with IBD is discussed in detail separately. (See "Genetic factors in inflammatory bowel disease".)
Disease control — Women with IBD should attempt conception at a time when the disease is in remission. Women who have active disease at conception are more likely to have active disease during pregnancy . Emerging data suggest that women with ulcerative colitis are more likely to have disease activity during pregnancy than women with Crohn disease [26,27]. This may reflect the cytokine production of the placenta and its impact on ulcerative colitis. Having active disease is associated with a significant increase in the rate of preterm birth . The risk of disease activity in the untreated patient should be discussed alongside the potential risk of any medications used during pregnancy to maintain remission. (See "Incidence and mortality of the preterm infant".)
Medications — Medications that may affect fertility or adversely affect pregnancy should be discontinued, when possible, in women planning pregnancy. The risks and benefits of fetal drug exposure versus discontinuation of medications and its attendant risk of flare should be specifically discussed. These risks and benefits are discussed in detail below. (See 'Medications during pregnancy and lactation' below.)
Sulfasalazine causes reversible oligospermia that resolves within discontinuation of therapy. Oligospermia is not associated with 5-aminosalicylic acid (5-ASA) medications (eg, mesalamine). Men on sulfasalazine should therefore be transitioned to 5-ASAs four months prior to conception (table 1) [29,30]. (See 'Sulfasalazine and 5-aminosalicylic acid' below.)
Methotrexate is associated with oligospermia and in women is an abortifacient and potent teratogen. However, there have been no data linking male methotrexate use and birth defects. Men should discontinue methotrexate and use contraception for at least four months prior to conception. (See "Use of antiinflammatory and immunosuppressive drugs in rheumatic diseases during pregnancy and lactation", section on 'Methotrexate' and 'Medications during pregnancy and lactation' below.)
Cyclosporine does not appear to reduce male fertility or to have a demonstrable effect on sperm . (See "Use of antiinflammatory and immunosuppressive drugs in rheumatic diseases during pregnancy and lactation", section on 'Cyclosporine' and 'Cyclosporine' below.)
Data on the risk of fetal teratogenicity with paternal azathioprine and mercaptopurine use are limited and studies have had variable results [32-37]. In a 2012 meta-analysis, exposure to thiopurines in men at the time of conception was not associated with congenital abnormalities . We therefore do not routinely recommend that men on azathioprine and mercaptopurine discontinue treatment unless the couple has a history of infertility or miscarriages that is otherwise unexplained. In such cases, we advise the prospective father to discontinue azathioprine/mercaptopurine four months prior to conception. (See "Azathioprine and 6-mercaptopurine in inflammatory bowel disease" and 'Azathioprine and mercaptopurine' below.)
Nutrition and supplements — Consultation with a nutritionist should be considered to offer advice on eating a well-balanced, healthy diet. Folic acid is important for neural tube development during pregnancy. Folate supplementation (2 mg daily) should be recommended in patients with IBD on low residue diets, with ileal involvement, and patients on medications that interfere with folic acid metabolism (eg, sulfasalazine [5,39]). (See "Folic acid supplementation in pregnancy".)
Patients with IBD are at risk for iron and vitamin B12 deficiency. Furthermore, iron requirements increase during pregnancy. Iron and B12 levels should therefore be checked in the first trimester and supplementation should be provided as needed. (See "Nutrient deficiencies in inflammatory bowel disease" and "Nutrition in pregnancy".)
PREGNANCY AND LACTATION — Women with inflammatory bowel disease (IBD) are at an increased risk for worse obstetric and medical outcomes as compared with the age-matched general population [40-42].
Effect of pregnancy on IBD — For patients with quiescent IBD at conception, the course of IBD is approximately the same as in nonpregnant patients. Patients with Crohn disease have a similar disease course during pregnancy and the postpartum as nonpregnant women with IBD. However, for patients with ulcerative colitis, there is greater disease activity during pregnancy and the postpartum than the nonpregnant patient. The reason for this is unclear and may be associated with smoking cessation, and cytokines secreted by the placenta or undertreatment of ulcerative colitis patients prior to pregnancy .
Approximately one-third of women with quiescent disease at conception relapse during the pregnancy, similar to the general IBD population . Relapses are more common during the first trimester. However, remission achieved during pregnancy is likely to be sustained throughout the remainder of the pregnancy.
In contrast, approximately 70 percent of patients with active disease at conception are likely to have continued or worsening symptoms during pregnancy [44,45]. (See "Clinical manifestations, diagnosis, and prognosis of ulcerative colitis in adults", section on 'Acute complications'.)
The events occurring during one pregnancy do not correlate with the course in subsequent pregnancies . However, pregnancy may be protective in the long term, as suggested by lower relapse rates up to ten years following pregnancy as compared with rates prior to pregnancy [47,48]. As parity increases, the risk for surgery to treat IBD also decreases, though this may simply be because healthier women are more likely to have multiple pregnancies .
Effect of IBD on pregnancy — Pregnant women with IBD may be at increased risk for antepartum hemorrhage, low birth weight infants, and premature delivery [40,42,49-52]. However, the risk of congenital abnormalities does not appear to be increased [40,53,54].
The degree of disease activity may account, in part, for the poor pregnancy-related outcomes [53,55]. The risk of poor pregnancy outcomes in women with IBD is greatest in those who have active disease at the time of conception, and in whom remission may be difficult to achieve during pregnancy [3,53,55-59]. As an example, in a Danish cohort study, the risk of preterm birth increased if the mother was hospitalized during pregnancy (odds ratio [OR] 1.4), and if the first hospitalization for ulcerative colitis occurred during pregnancy (OR 3.4) .
Women with IBD should be followed as high-risk obstetric patients, particularly in the third trimester, and if the disease is active. (See "Overview of antepartum fetal surveillance" and "Preterm birth: Risk factors and interventions for risk reduction", section on 'Chronic medical disorders'.)
Effect of lactation on IBD — Breastfeeding does not independently affect the course of disease in IBD after adjusting for an increase in disease activity due to cessation of IBD medications. However, 56 percent of women with IBD do not breastfeed their children either because of a clinician recommendation, fear of medication interactions, or personal choice . It is therefore important to discuss the benefits of breastfeeding as well as the compatibility of several antiinflammatory and immunosuppressive medications with breastfeeding as discussed below. (See "Infant benefits of breastfeeding" and 'Medications during pregnancy and lactation' below and "Breastfeeding: Parental education and support".)
SAFETY OF DIAGNOSTIC EVALUATION DURING PREGNANCY AND LACTATION — Endoscopy or imaging studies may be indicated during pregnancy for the diagnosis of suspected inflammatory bowel disease (IBD) or for the assessment of disease severity, or diagnosis and management of complications in patients with established IBD. However, it is important to consider the risks, benefits, and optimal timing of such a diagnostic evaluation in pregnant or nursing women. (See "Clinical manifestations, diagnosis, and prognosis of ulcerative colitis in adults", section on 'Diagnosis' and "Clinical manifestations, diagnosis and prognosis of Crohn disease in adults", section on 'Diagnosis' and "Management of severe ulcerative colitis in adults", section on 'Pretreatment evaluation'.)
The safety and efficacy of endoscopic procedures during pregnancy have not been extensively studied. Endoscopy should be performed during pregnancy only if there is a strong indication (eg, significant bleeding) or if the information is critical for making treatment decisions (eg, establish the diagnosis of IBD in a pregnant patient with chronic diarrhea or stage disease if new therapies are needed). When possible, endoscopy should be postponed until the second trimester . Flexible sigmoidoscopy, which can be performed without sedation or colonic preparation, are low risk in pregnancy in any trimester . While there are several reports of colonoscopies being performed during pregnancy without complications, experience is relatively limited compared with sigmoidoscopy [62,63]. Obstetrical staff should be closely involved and the degree of maternal and fetal monitoring should be individualized. Recommendations for procedural sedation for endoscopy in pregnant and nursing women are discussed in detail separately. (See "Overview of procedural sedation for gastrointestinal endoscopy", section on 'Pregnancy and lactation'.)
Radiographic studies involving ionizing radiation (eg, computed tomography enterography, abdominal x-rays, small bowel follow-through) should be avoided in pregnancy if possible. These studies can be performed if they are necessary for maternal management and if there is no alternative imaging modality available. Several techniques can be used to minimize fetal radiation exposure. Magnetic resonance (MR) enterography is the preferred diagnostic modality in the absence of institutional expertise with ultrasound for IBD because it avoids the ionizing radiation of computed tomography. While MR enterography can be done in any trimester, intravenous gadolinium crosses the placenta . The theoretical risk to the patient needs to be weighed against the additional imaging benefit of using gadolinium. However, oral contrast is routinely used. (See "Diagnostic imaging procedures during pregnancy".)
MEDICATIONS DURING PREGNANCY AND LACTATION — The choice of antiinflammatory and immunosuppressive use during pregnancy and lactation should be based upon their relative safety and indications as well as the risk of relapse of inflammatory bowel disease (IBD) if the medications are discontinued.
Active IBD itself is associated with poor pregnancy outcomes, and therefore the risks associated with discontinuing some medications (eg, azathioprine, anti-tumor necrosis factor [anti-TNF] agents) are higher than the known risks of the medications themselves. (See "Use of antiinflammatory and immunosuppressive drugs in rheumatic diseases during pregnancy and lactation".)
The recommendations on lactation are consistent with the Drugs and Lactation Database of the US National Library of Medicine (LactMed) unless noted otherwise. LactMed is a free, online resource for information on maternal and infant levels of drugs, possible effects on breastfed infants and on lactation.
Antibiotics — Antibiotics, metronidazole and ciprofloxacin, are frequently used in the management of patients with inflammatory bowel disease. (See "Antibiotics for treatment of inflammatory bowel diseases".)
The use of metronidazole should be limited to short courses. A number of studies have suggested that metronidazole is not associated with an increased risk of birth defects or cancer [65,66]. However, long-term use in pregnancy remains controversial because it is carcinogenic in rodents and mutagenic in bacteria [67,68]. In a study of 922 women exposed to metronidazole in pregnancy, there was no association with congenital anomalies, preterm birth, or low birth weight .
Metronidazole is excreted into breast milk and is a possible mutagen. Breastfeeding should be avoided for 12 to 24 hours after a single oral dose. . Ciprofloxacin is not recommended in pregnant women and in children under age 18 as it affects growing cartilage and can cause arthropathy. However, among 200 pregnancies exposed to fluoroquinolones (including ciprofloxacin), the incidence of adverse events were similar to controls .
Amoxicillin-clavulanic acid has a favorable safety profile and is considered acceptable for use during pregnancy and lactation . Rifaximin has no published safety data in human pregnancy or lactation. Per their label, animal studies have revealed evidence of teratogenicity at doses about 0.9 to 5 times (rats) and 0.7 to 33 times (rabbits) the recommended human doses of 600 to 1650 mg/day . It should be avoided in pregnancy. There are no published pregnancy safety data for probiotics in IBD. However, there are several large ongoing trials regarding the use of specific probiotics in all pregnancies to improve outcomes including preterm birth and infant infections and allergies .
Sulfasalazine and 5-aminosalicylic acid — Sulfasalazine and 5-aminosalicylic acid (5-ASA) drugs can be used during pregnancy and lactation.
The incidence of decreased birth weight, prematurity, spontaneous abortion, stillbirths, or birth defects is similar in children born to mothers taking sulfasalazine as compared with the general population . Sulfasalazine and its sulfapyridine metabolite can be found in umbilical cord blood at similar concentrations to maternal blood. However, these concentrations do not cause significant displacement of bilirubin from albumin [76,77]. As a result, sulfasalazine does not have to be discontinued during pregnancy.
Studies suggest that 5-ASA agents by themselves are safe during pregnancy [78-81]. Enteric coating of mesalamine with dibutyl phthalate (DBP) has been associated with skeletal malformations and adverse effects on the male reproductive system in fetal animal models exposed to high doses of DBP . Patients on 5-ASAs containing DBP (eg, Asacol and Asacol HD) should therefore be switched to another 5-ASA (table 1). (See "Sulfasalazine and 5-aminosalicylates in the treatment of inflammatory bowel disease" and "Overview of occupational and environmental risks to reproduction in females", section on 'Phthalates'.)
Sulfasalazine and 5-ASAs are excreted in breast milk in low concentrations. Infants whose mothers are on sulfasalazine and 5-ASAs should be monitored for the development of diarrhea, a rare complication of breastfeeding [70,83,84].
Glucocorticoids — Glucocorticoids are considered low risk in pregnancy and should be administered for the same indications as a nonpregnant patient with IBD. The lowest possible dose of systemic glucocorticoids should be used and they should not be considered an alternative to standard maintenance therapy. (See "Use of antiinflammatory and immunosuppressive drugs in rheumatic diseases during pregnancy and lactation", section on 'Glucocorticoids' and "Preterm birth: Risk factors and interventions for risk reduction".)
Although older studies have demonstrated a threefold increase in the risk of cleft palate after maternal exposure to glucocorticoids, the absolute risk is low (0.2 to 0.4 percent)  and multiple other studies have not confirmed that risk . In addition, as palatal closure is usually complete by the 12th week of pregnancy, the risk is limited to administration during the first trimester. (See "Etiology, prenatal diagnosis, obstetrical management, and recurrence of orofacial clefts".)
Fetal adrenal insufficiency and low birth weight have also been associated with glucocorticoids . However, adrenal insufficiency of the fetus following maternal administration of glucocorticoids is rare as rapid maternal metabolism of prednisolone, binding to serum proteins, and conversion to inactive metabolites by placental 11 beta-hydroxysteroid dehydrogenase results in relatively low fetal concentrations [88,89]. However, long-term administration of high doses of glucocorticoids (>20 mg) is associated with adrenal insufficiency and warrants close neonatal monitoring. (See "Overview of antepartum fetal surveillance".)
Glucocorticoids have the potential for exacerbating pregnancy-induced hypertension, gestational diabetes, and preterm delivery from premature rupture of membranes . Therefore, pregnant women on glucocorticoids should be appropriately monitored for these complications [85,91]. (See "Gestational hypertension" and "Gestational diabetes mellitus: Glycemic control and maternal prognosis" and "Gestational diabetes mellitus: Obstetrical issues and management" and "Preterm premature (prelabor) rupture of membranes".)
Although low levels of prednisone and its metabolite, prednisolone, can be measured in breast milk, these are unlikely to be clinically significant. In one study, following a dose of prednisolone 50 mg IV, an average of 0.025 percent was recovered from breast milk .
Azathioprine and mercaptopurine — Thiopurines, azathioprine and mercaptopurine, should be continued during pregnancy if the IBD cannot be managed with other medications [32,93]. In a 2012 meta-analysis of 3045 women with IBD, thiopurine exposure was associated with preterm birth (odds ratio [OR] 1.7, 95% CI 1.3-2.2), but not with congenital abnormalities or low birth weight . In addition, discontinuing azathioprine and mercaptopurine is associated with a high rate of relapse and active IBD is itself associated with an increased risk of low birth weight [32,94-100].
Azathioprine and mercaptopurine are detectable in breast milk but studies have demonstrated that levels in breast milk are low and metabolites are undetectable in breastfed neonates [101,102]. Although data are limited, these studies suggest that breastfeeding is safe. Breastfeeding can be continued while on azathioprine and mercaptopurine after a detailed discussion of the risks and benefits of breastfeeding . (See "Use of antiinflammatory and immunosuppressive drugs in rheumatic diseases during pregnancy and lactation", section on 'Azathioprine and 6-MP'.)
Cyclosporine — Cyclosporine is effective at inducing remission in patients with severe steroid refractory ulcerative colitis during pregnancy . When the administration of cyclosporine is necessary during pregnancy, the minimum dose should be used. (See "Approach to adults with steroid-refractory and steroid-dependent ulcerative colitis", section on 'Cyclosporine'.)
In a meta-analysis, cyclosporine was not associated with an increase in risk of congenital malformations but was associated with increased rates of prematurity . A higher incidence of small for gestational age infants has also been reported. However, it is unclear if fetal growth restriction and prematurity were due to cyclosporine or due to the mother’s underlying disease.
Cyclosporine is excreted in breast milk, and therapeutic levels have been reported in breastfed infants [104,105]. However, as the amount of transfer is minimal, cyclosporine can be used in the breastfeeding mother and infant levels of drug can be monitored if concern for toxicity. (See "Use of antiinflammatory and immunosuppressive drugs in rheumatic diseases during pregnancy and lactation", section on 'Cyclosporine'.)
Methotrexate — Methotrexate is contraindicated in pregnancy as it is a potent abortifacient, and its use during pregnancy is associated with multiple skeletal abnormalities. Women who plan to conceive should therefore discontinue methotrexate and use contraception for at least three months, and ideally six months, prior to conception.
The rate of congenital malformations due to maternal methotrexate use is estimated to be 9 to 17 percent [106,107]. The risk of methotrexate-induced developmental toxicity is highest at 8 to 10 weeks of gestation and with doses ≥10 mg/week.
Breastfeeding is contraindicated in women on methotrexate as it is excreted into breast milk and can accumulate in neonatal tissues [5,108]. (See "Use of antiinflammatory and immunosuppressive drugs in rheumatic diseases during pregnancy and lactation", section on 'Methotrexate'.)
Anti-tumor necrosis factor agents — Experience with anti-tumor necrosis factor (anti-TNF) therapy agents used to treat IBD during pregnancy is limited but reassuring [109,110]. The Toronto Consensus on Management of IBD in pregnancy recommended that pregnant women on anti-TNF monotherapy for maintenance should continue therapy throughout pregnancy . Discontinuation of anti-TNF therapy or switching from combination biologic and azathioprine/mercaptopurine therapy to monotherapy may be considered in very select low-risk patients. Low-risk patients are those in sustained deep remission prior to pregnancy (symptomatic remission off of corticosteroids with evidence of endoscopic healing for at least three months duration) and no history of multiple medication failures, significant perianal disease, or multiple surgeries.
Anti-TNF-alpha agents alone given during pregnancy have not been associated with an increased risk of birth defects or adverse pregnancy outcomes [112-114]. In an interim analysis of data from a prospective cohort (Pregnancy in IBD and Neonatal Outcomes Registry [PIANO]) of 1232 pregnant women (329 unexposed, 242 exposed to azathioprine, 357 exposed to biologic therapy, and 109 on combination biologic therapy and azathioprine during pregnancy), the use of thiopurines was not associated with an increase in pregnancy complications or birth defects . Among pregnant women on biologics (264 on infliximab, 151 on adalimumab, 67 on certolizumab pegol, and 29 on more than one biologic during pregnancy), there was no increase in the rate of birth defects, achievement of developmental milestones at one year, infection at one year, or height and weight based on drug exposure. However, there was an increase in any complication (OR 1.7, 1.0-2.2) and preterm birth (OR 2.4, 1.3-4.3) in the combination therapy group compared with the unexposed. Patients with Crohn disease did not have any differences in outcome based on drug exposure, but patients with ulcerative colitis (UC) had higher rates of preterm birth, low birth weight, NICU stay, and any complication in the combination therapy group as compared with those unexposed. Patients with UC tended to have higher rates of disease activity compared with patients with Crohn disease. (See "Use of antiinflammatory and immunosuppressive drugs in rheumatic diseases during pregnancy and lactation" and "Anti-tumor necrosis factor therapy in ulcerative colitis" and "Infliximab in Crohn disease".)
Rates of live births, miscarriages, and therapeutic terminations do not appear to be significantly different in women exposed to infliximab during pregnancy as compared with the general population [113,115,116].
Infliximab crosses the placenta . The exact timing is unclear but in general, maternal antibodies are actively transported across the placenta by the neonatal Fc receptor (FcRn) beginning in the early to mid-second trimester, with the highest fetal concentration in the third trimester near term. High levels of infliximab have been detected in the cord blood of newborns [117,118]. The clinical significance of this is unclear but it raises concern about an increased risk of infection and a suboptimal response to vaccinations in the newborn . (See "Standard immunizations for children and adolescents: Overview".) Live vaccines should not be given to infants exposed to infliximab, adalimumab, golimumab, or natalizumab, as newborns may have detectable serum levels of drug for up to nine months [111,117,120]. All other vaccinations can be given on schedule.
Discontinuing infliximab early in the third trimester or at the end of the second trimester may help to reduce infliximab transport across the placenta and lower levels of serum infliximab in the newborn. Discontinuation of anti-TNF therapy also appears to be safe for pregnant women with quiescent IBD, though the risk of flare in the post-partum and immunogenicity needs to be strongly considered . Patients should be well-informed and infliximab can be stopped 8 to 10 weeks before the estimated date of delivery in patients with quiescent IBD who prefer to stop therapy. Infliximab can then be resumed immediately after delivery, assuming no infection. IBD flares following discontinuation of infliximab can be treated with resumption of infliximab, unless birth is imminent .
Infliximab is considered compatible with breastfeeding as it is excreted in trace amounts in human milk and is poorly absorbed orally, thus reducing the potential for systemic adverse effects [5,121].
Adalimumab — Adalimumab is considered compatible with use during conception and pregnancy throughout pregnancy . In small observational studies, the incidence of congenital malformations, spontaneous abortion, stillbirth, and preterm delivery was not increased in pregnant women exposed to adalimumab. Adalimumab actively crosses the placenta as well [117,118]. We therefore suggest discontinuing adalimumab four to five weeks prior to the due date.
Limited evidence suggests that adalimumab is compatible with breastfeeding. While it can be detected in breast milk, levels are low and it has not been demonstrated to adversely affect the nursing infant .
Certolizumab — Certolizumab is a PEGylated Fab fragment of a humanized anti-TNF-alpha monoclonal antibody. Unlike infliximab and adalimumab which are actively transferred across the placenta in the third trimester, there is minimal placental transfer of certolizumab to the infant during pregnancy as it does not have an Fc component to bind to the FcRn on the placenta .
Certolizumab can therefore be used through conception and continued throughout pregnancy until delivery. Although there are limited data, certolizumab pegol may also be compatible with breastfeeding as it is minimally excreted into breast milk . There is no need to adjust vaccine schedules in infants exposed to certolizumab in utero.
Natalizumab — There are limited safety data on the use of natalizumab during pregnancy and lactation. The risk of congenital malformations was not increased in 164 pregnancies in patients with Crohn disease or multiple sclerosis on natalizumab during the first trimester .
Vedolizumab — There are limited safety data on the use of vedolizumab during pregnancy. Preliminary data from 25 pregnancies in patients with IBD found no increase in congential anomalies . There are no human data at this time on lactation safety. However, it is the author’s practice to continue medication during breastfeeding given low levels of transfer in other biologic agents and benefit to mother of the agent.
Ustekinumab — There is limited safety data in Crohn disease, but safety registries in psoriasis report a 1.7 percent rate of fetal malformations, similar to what would be expected in the general population . There are limited human data on lactation safety, but again, it is the author’s practice to continue breastfeeding in the healthy term infant.
Antidiarrheal drugs — Antidiarrheal drugs should be avoided, especially early in pregnancy. Antidiarrheals should only be used for severe diarrhea that cannot be controlled with dietary manipulation and bulking agents (eg, kaolin/pectin, Metamucil, psyllium).
Diphenoxylate with atropine and loperamide are not teratogenic in animal studies but there are no controlled studies in humans. Case reports have reported fetal malformations in infants exposed to diphenoxylate with atropine during the first trimester, but it is unclear if this was causal [126,127].
Loperamide is compatible with nursing . However, there are no data for diphenoxylate. Diphenoxylate-atropine should therefore be used only in short, infrequent courses, at low doses while breastfeeding an older infant.
SURGERY — Complications associated with IBD that warrant surgery in a pregnant patient include acute refractory colitis, perforation, abscesses, severe hemorrhage, and obstruction . There are limited data pertaining to the risk of surgery in pregnant patients with inflammatory bowel disease (IBD) [128,129]. Surgery has been associated with preterm labor and spontaneous abortions, possibly related to inadvertent uterine manipulation, but complications are rare [5,130,131]. When possible, medical treatment should be intensified prior to considering surgery . (See "Clinical manifestations, diagnosis, and prognosis of ulcerative colitis in adults", section on 'Acute complications' and "Operative management of Crohn disease of the small bowel, colon, and rectum".) Also, a decision for surgery should be made prior to viability, at 24 weeks gestation, if possible.
MODE OF DELIVERY — Patients with active perineal disease or rectal involvement with Crohn disease should undergo cesarean delivery in order to avoid perineal trauma from vaginal birth that can trigger or worsen existing perineal disease [111,133]. The mode of delivery in all other patients with inflammatory bowel disease should be dictated by obstetric necessity. In patients with an ileoanal anastomosis or J pouch, many advocate planned cesarean delivery as well, though data suggest no long-term worsening of pouch function . (See "Perianal complications of Crohn disease".)
Vaginal delivery can be attempted in women with a colostomy, ileostomy, or continent ileostomy and has not been associated with an increased risk of ostomy complications [5,134]. (See "Routine care of patients with an ileostomy or colostomy and management of ostomy complications".)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Ulcerative colitis in adults" and "Society guideline links: Crohn disease in adults".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Beyond the Basics topics (see "Patient education: Inflammatory bowel disease and pregnancy (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●Inflammatory bowel disease (IBD) can affect women in their childbearing years and therefore has implications on fertility, pregnancy, and nursing. (See 'Introduction' above.)
●Patients with quiescent IBD disease do not have decreased fertility compared with the general population. However, fertility in patients with IBD may be affected by active inflammation, medications, and prior surgery. (See 'Fertility' above.)
●The course of IBD during pregnancy is determined in part by the activity of the disease at conception. Patients in remission at the time of conception are likely to remain in remission during pregnancy. In contrast, up to 70 percent of patients with active disease at conception are likely to have continued or worsening symptoms during pregnancy. (See 'Disease control' above.)
●Women with ulcerative colitis have more disease activity during pregnancy than women with Crohn disease. Women with IBD are at an increased risk for worse obstetric and pregnancy related outcomes as compared with the general population even with disease in remission. (See 'Pregnancy and lactation' above.)
●Endoscopy should be performed during pregnancy only if there is a strong indication or if the information is critical for making treatment decisions. An unsedated flexible sigmoidoscopy is considered low risk. Magnetic resonance enterography is the preferred diagnostic modality in pregnant patients with IBD in the absence of institutional expertise with ultrasound for IBD. (See 'Safety of diagnostic evaluation during pregnancy and lactation' above.)
●The choice of antiinflammatory and immunosuppressive medications during pregnancy and lactation should be based upon their relative safety and indications as well as the risk of relapse of IBD if the medications are discontinued. (See 'Medications during pregnancy and lactation' above.)
●Patients with perineal disease or rectal involvement with Crohn disease should undergo a cesarean delivery. The mode of delivery in all other patients with IBD should be dictated by obstetric necessity. (See 'Mode of delivery' above.)
●Complications associated with IBD that warrant surgery in a pregnant patient include acute refractory colitis, perforation, abscesses, severe hemorrhage, and obstruction. Although data are limited, surgery is associated with premature labor or spontaneous abortion, possibly related to inadvertent uterine manipulation. (See 'Surgery' above.)
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