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Active maternal inflammatory bowel disease during pregnancy carries a greater risk to the fetus than appropriate treatment. Careful management is essential to achieve good obstetric outcome
Inflammatory bowel disease is a collective term for chronic illnesses characterised by inflammation of the intestinal tract, the most common of which are ulcerative colitis and Crohn’s disease. The natural course of inflammatory bowel disease is marked by periods of relapse followed by periods of remission, and the aims of management are induction and maintenance of remission and avoidance of disease complications.
A 32 year old woman (para 2) presented at week 14 of pregnancy with bleeding from the rectum (clots and overt bleeding mixed with stools) but no change in bowel habit. She did not have haemorrhoids, stool cultures were negative, and she had moderate proctitis on proctoscopy. She was given steroid enemas, but these had no effect, and at 29 weeks’ gestation she was started on a course of oral prednisolone under the close supervision of the obstetricians. She had a good clinical response, but on tapering the dose her symptoms recurred, and at 35 weeks the dose was increased again to control her symptoms. The obstetricians monitored the fetus weekly and she delivered at term. Her steroid dose was again tapered and mesalazine was started. Subsequent colonoscopy showed mild rectosigmoiditis. She remains on maintenance mesalazine, she is breast feeding, and mother and baby are well.
Diagnosis is often made early in life and 50% of patients are diagnosed before 35 years of age. The incidence of ulcerative colitis is estimated at 10.4 per 100000 and that of Crohn’s disease at around 5.6/100000 in Western populations.1 2 About a quarter of female patients with inflammatory bowel disease will conceive after the diagnosis is made, so an understanding of managing the disease during pregnancy is essential for practitioners caring for these patients (see Scenario box).
We searched the PubMed database using the terms “inflammatory bowel disease”, “Crohn’s disease”, “ulcerative colitis”, “pregnancy”, and “congenital malformations”. We assessed the results for relevance and all relevant articles were reviewed where possible. Papers that were referenced in these articles were also reviewed if thought to be relevant.
There is no evidence to suggest that pregnancy causes progression of the disease, and some evidence indicates that it has a favourable effect on disease over time. Two European cohort studies of 634 pregnancies in 303 women showed that pregnancy improves the disease course, with a reduction in flares in subsequent years.3 4 A retrospective study of 111 patients in the United Kingdom also showed that pregnancy has beneficial effects on the disease— increased parity is associated with a reduction in surgical resections.5
The key point is that disease activity at the time of conception strongly influences the course of disease during pregnancy. If the disease is quiescent at the time of conception it will remain so in about two thirds of patients. If the disease is active at the time of conception, two thirds of patients will have ongoing active disease, and the condition will deteriorate in up to 60% of patients and tend to be less responsive to treatment.6
The disease will flare in 20-30% of patients with inactive disease at the time of conception, which is similar to the expected rate of relapse in non-pregnant women.7 8 Such flares tend to respond well to treatment. After birth the risk of a flare is increased if the disease is active at term.6 9
Several studies have looked at the effect of inflammatory bowel disease on the outcome of pregnancy and the baby. Results have been conflicting, perhaps because of the heterogeneity of the condition.
Overall, patients with inactive inflammatory bowel disease have no increased risk of adverse pregnancy outcomes,6 whereas miscarriage can be as high as 35% in patients with active disease.10 A diagnosis of Crohn’s disease, however, increases the risk of low birth weight, preterm delivery, and adverse perinatal outcomes, particularly if the mother has active disease.6
A recent retrospective cohort study from California of 461 pregnant women with inflammatory bowel disease found that, compared with controls, these women were more likely to have an adverse outcome of conception or pregnancy and a complication of pregnancy.11 In this study of patients with mostly mild disease, severity and treatment were not predictive of adverse outcome. Neonatal outcomes were not statistically different between women with inflammatory bowel disease and the control group in this study. Other studies have shown that although preterm delivery rates are higher, adverse perinatal outcomes are not.12
A meta-analysis of 12 studies looking at 3907 patients found higher rates of adverse outcomes of pregnancy in women with inflammatory bowel disease than in controls.13 The rate of caesarean section and prematurity was increased by factors of 1.5 and 1.87, respectively, and the incidence of low birth weight was doubled. The risk of congenital abnormalities was more than doubled in patients with inflammatory bowel disease, but it was unclear what factors increased the risk, and further studies are needed to determine this.13
Rates of caesarean section are higher in women with inflammatory bowel disease.13 14 Although this mode of delivery is recommended for women with active perianal Crohn’s disease, it is not indicated for those with inactive disease, no perianal disease, or previous ileal pouch-anal anastomosis, and it seems to be overused in these groups.14 Caesarean section may be considered in patients with impaired anal continence or those with extensive perineal scarring and loss of skin elasticity, because episiotomy or tear may result in the formation of a fistula. Such procedures should be performed under the supervision of an experienced obstetrician.
Because of the increased risk of adverse outcomes in pregnant women with inflammatory bowel disease, these women should be managed by a multidisciplinary team, which includes a maternal fetal medicine specialist and a gastroenterologist. Patients should have regular clinical assessment along with growth scans and biophysical scans every two to four weeks.
Women with inflammatory bowel disease may wish to stop taking their drugs during pregnancy because of the perceived risk of harm to the fetus. However, it is crucial that the disease is controlled, and fears of adverse drug events—which are not always evidence based—should be allayed. The medical management of inflammatory bowel disease is no different in pregnancy, with a few important exceptions.
Assessment of inflammatory bowel disease in pregnancy should rely on clinical factors such as abdominal pain, stool frequency, and rectal bleeding because pregnancy can affect laboratory indices such as haemoglobin concentration, erythrocyte sedimentation rate, and serum albumin. C reactive protein is not normally raised in pregnancy so it is valuable for assessing women with Crohn’s disease and ulcerative colitis. Abdominal radiography should be used if the clinical situation warrants it because the risks to the fetus are minimal. Flexible sigmoidoscopy seems to be safe in pregnancy15;it does not induce labour or congenital abnormalities, but it should be used only when necessary.16
Commonly used drugs in inflammatory bowel disease include aminosalicylates, corticosteroids, immunomodulators such as azathioprine and methotrexate, and newer biological agents such as anti-tumour necrosis factor-α drugs. Pooled analysis of 19 mostly retrospective studies suggests that these drugs do not significantly increase the incidence of stillbirth, ectopic pregnancy, low
birthweight babies, or miscarriage.13 Congenital abnormalities may be higher in patients treated with aminosalicylate, anti-tumour necrosis factor-α, and azathioprine, but this may be related to disease activity rather than the drugs themselves.13
The table table provides details of the safety profiles of drugs commonly used during pregnancy and breast feeding. These data come from the European Crohn’s and Colitis Organisation’s consensus statement on managing Crohn’s disease in pregnancy,16 and the recommendations are based on varying degrees of evidence, graded according to the Oxford Centre for Evidence Based Medicine. Readers should refer to the original article for further information.
Most of the data on aminosalicylates and corticosteroids relate to oral preparations and, although information on topical preparations is limited, such preparations seem to be safe in pregnancy. Methotrexate is contraindicated in pregnancy, and prospective parents should be advised to discontinue this drug at least six weeks before conception.
Other agents including ciclosporin, tacrolimus, and thalidomide can be used in certain circumstances and under specialist supervision in inflammatory bowel disease and are not covered in this article.
Ideally, the patient should discuss problems relating to conception and pregnancy with her gastroenterologist, primary care doctor, and obstetrician in advance. Pregnancy should be planned if possible and disease should be controlled before conception. The importance of adherence to treatment and prevention of relapse during pregnancy should be stressed, and the patient should be monitored as a high risk pregnancy.
Supplementation with folic acid before conception is recommended for all women, and women with inflammatory bowel disease may benefit from higher doses (5 mg daily) because they have a higher rate of vitamin deficiency.
Smoking is more common in patients with Crohn’s disease than in the general population and is associated with more severe disease.17 Pregnant women with Crohn’s disease who smoke have a higher risk of low birth weight and preterm labour, and these women should be encouraged to stop smoking.6
None of the drugs commonly used for inflammatory bowel disease seems to have any long term adverse effects on fertility in men or women. Salazopyrin causes reversible oligospermia and reduced sperm motility in men, so prospective fathers should be switched to an alternative aminosalicylate.
Fertility rates in women with inflammatory bowel disease are similar to those of the general female population, except for women with active Crohn’s disease, who have reduced fertility.7 18 However, the average number of children born to parents with inflammatory bowel disease is lower than in the general population, which suggests an association with voluntary childlessness.19 Infertility rates are increased in some women who have had surgery for inflammatory bowel disease, and a threefold increase has been seen in women with ulcerative colitis after ileal pouch-anal anastomosis.7 20
No other commonly used agents seem to affect male fertility and they should be continued. Methotrexate should be stopped six weeks or more before conception, however, because of the risk of teratogenesis. Male sexual dysfunction may increase after ileal pouch-anal anastomosis, although overall sexual satisfaction is improved.21
The beneficial effects of breast feeding are well documented and include reduced risk of developing inflammatory bowel disease later in life.22 In a retrospective study of 122 women with inflammatory bowel disease, only 44% of patients breast fed their infants and many stopped their drugs before doing so, which caused a flare in the condition. No evidence exists to suggest that breast feeding causes a flare in inflammatory bowel disease after birth.8 Many of the most commonly used drugs are safe for breastfeeding mothers (table), although women are recommended to wait for four hours after taking oral steroids before they breast feed. Rarely, diarrhoea can occur in breastfed infants as a result of maternal use of aminosalicylate, and women should be warned about this possible adverse effect.
Many women with inflammatory bowel disease will hope to become pregnant during the course of their disease. Where possible, pregnancy should be planned to coincide with disease remission and any flare in the disease should be treated aggressively because active disease carries the greatest risk to the fetus. Delivery should be transvaginal unless active perianal disease is present or caesarean section is indicated for obstetric reasons.
This is one of a series of occasional articles about how to manage a pre-existing medical condition during pregnancy
Contributors: CBF searched the literature and drafted the paper. SM-D revised and edited the paper from an obstetric perspective. RNP revised and edited the paper and is guarantor.
Competing interests: None declared.
Provenance and peer review: Not commissioned; externally peer reviewed.
Patient consent not required (patient anonymised, dead, or hypothetical).
Cite this as: BMJ 2008;337:a427