IBD and Pregnancy

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Introduction

Intestinal inflammatory diseases [irritable bowel disease (IBD)], including ulcerous rectocolitis [ulcerative colitis (UC)] and Crohn’s Disease (CD), are pathologies primarily affecting young adults during the reproductive age, often causing a decrease of the patients’ quality of life [1] because of the psychosocial impact caused by the chronic nature of the disease and consequently the therapy and clinical problems connected with complex and sometimes dis- abling symptomatological patterns, which can negatively affect both social and emotional living [2].

Patients of both genders suffering from such diseases must frequently face problems concerning sex life, fertility and, for woman, pregnancy [3]. Patients of child-bearing age often express doubts about their ability to have children because of psychological consequences of their disease in relation to interpersonal relationships and qualms about harmful effects to the foetus caused by relapse of disease activity stages and the drugs they have to take to prevent and/or treat them during pregnancy [4].

Fertility and IBD

One frequently asked question by young patients suffering from IBD concerns its possible impact on fertility [5, 6]. Generally, the infertility rate is similar to that in the healthy population, which is more or less 8–10%. However, epidemiologic studies show that these patients deliver fewer children than the general population. This fact might be ascribable to reduced fertility due to physical damage caused by the disease and by a decision not to have children because of dif- ficulty developing interpersonal relationships due to poor self-image of their body and their sexuality and fears regarding pregnancy.

Prospective studies revealed that in patients suffering from UC, fertility is not affected except in cases in which the patient has undergone surgery [7]. This topic will be discussed later in the chapter. For

women suffering from CD, fertility is reduced exclusively during the stages of the disease activity, probably due to inflammation and accretions involving tubes and ovaries. Control of disease recrudescences usually restores reproductive ability.

As for male patients, there is no certain evidence [8] that CD may cause infertility even if malnutrition and stages of disease activity are negative influences.

As for the influence of the drugs prescribed for patients with IBD, there is considerable proof of the negative but temporary impact caused by the phar- macologic therapy [9], by sulfasalazine, in particular, which causes dose-related anomalies of seminal fluid and fertility in about 60% of men. The effect may be potentially reversible 2 months following interruption of therapy [10]. When sulfasalazine is replaced with another drug belonging to the 5-aminosalicylates group, fertility improves.

In both men and women, psychological attitude towards the disease is important as, even more so than the physical condition, it affects the sex life and, consequently, the ability to conceive.

Sexuality and IBD

Regarding the effect of IBD on interpersonal relationships and sexuality, it must be emphasised that, especially at a young age, patients are considerably affected psychologically, not only because their disease is chronic but because of some peculiar aspects of the disease. Direct and indirect effects of IBD, such as asthenia, diarrhoea, faecal incontinence, consequences of surgery and drug side effects generally cause a psychophysical condition of discomfort, making interpersonal relationships difficult both publicly and privately. In the light of these remarks, recent research pointed out the importance of not only clinical but also psychosocial patient evaluation, creating the basis for a multidisciplinary management of the disease that could considerably improve the patient’s quality of life.

Young women suffering from IBD in particular

IBD and Pregnancy

Gianluca Colucci, Gian Gaetano Delaini, Filippo Nifosì

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must be carefully examined in regard to physical problems, difficulties relating to their sex life and the possibility of pregnancy [11]. Women with UC usually do not present a higher incidence of gynaecological diseases, except those who have undergone ileal pouch anal anastomosis (IPAA) and presenting a higher incidence of dyspareunia. In women with CD, approximately 25% develop organic and functional gynaecological complications such as menstrual irregularity, amenorrhoea, inflammatory pelvic masses, abscesses and fistulae that, in the case of failure of medical therapy, require surgery, which is psychologically invalidating and greatly affect their quality of life and sexuality, especially if associated with laparotomies and creation of stomas.

Heredity

Another problem that often affects the reproductive and affective environment of patients with IBD is the fear that their children may inherit the same disease [12]. There is a 10.5% risk that the children of a par- ent with IBD may develop the disease, and 10% of patients have a first-degree relative with the disease, attesting to the role of heredity and genetic susceptibility to these morbid conditions in which multifac- torial pathogenesis requires triggering factors of an environmental origin.

The modality of transmission of the genes that may cause the development of IBD is complex and cannot be explained with a mere Mendelian pattern. Studies on twins revealed that, in the case of MC, consistency is 44–50% in monozygotic twins and 0–3% in zygotic twins whereas in the case of UC, consistency is lower, at 6–14% in monozygotic twins and 0-5% in heterozy- gotic twins [12]. Some studies revealed that there is a stronger familial tendency in CD, attesting to the importance of the genetic arrangement in determining the tendency to develop the disease [12]. Recent researches [13] began to detect the chromosome regions that are probably involved in order to deter- mine susceptibility to the disease. Some of these regions seem to be specific in CD and UC whereas oth- ers have a lower specificity. These discoveries are rele- vant in light of the possibility, from studying the geno- type of a certain patient, of anticipating phenotypical features of the disease, distinguishing – for example, in the case of CD – types with a higher risk of fistulisation from those with a predominant tendency to form stenosis. Knowledge of a patient’s genetic arrangement could help in the evaluation of risk of extraintestinal manifestations and the probability of response to medical and surgical therapy. For example, a gene was detected, called CARD 15, situated on chromosome 16, which codifies for a protein involved in the primary

immune response to infections through the activation of the NF-kB. In patients with MC, mutations of this gene seem to be associated with a tendency to ileal localisation, an earlier age of onset and a higher tendency to stenosis. In the light of these considerations, it is reasonable to think that, in a more or less remote future, physicians may be able to anticipate features of the evolutive course of the disease in each patient by targeted genetic studies, optimising management by individualising medical–surgical therapy [13].

Effect of IBD on Pregnancy

As for the progress of pregnancy during IBD, many studies show that pregnant patients may have an ordinary gestational course during the stages of disease quiescence even if there still is, for reasons not yet explained, a risk that is about twice as high compared with healthy women to have complications such as delay of foetal intrauterine growth, prematu- rity and low birth weight. Therefore, strict obstetrical follow-up, particularly during the third trimester, is necessary [14, 15].

There is much evidence that any relapse of the disease, especially CD, increases considerably the risk of adverse events such as foetal malformations, premature delivery and miscarriage, emphasising the importance of planning for conception during the quiescence stage and the use of all diagnostic and therapeutical tools available to prevent or intensively treat any relapse of the activity stage during the entire course of pregnancy [16].

As for UC, any activity stage during pregnancy often determines a state of weakness for the expectant mother that frequently affects foetal growth negatively, causing low birth weight and premature delivery.

This fact emphasises the importance of thorough and early nutritional therapy and intensive support of the overall conditions of the expectant mother. A recent study revealed the likely association between UC relapse during pregnancy and an increased tendency of foetal malformations [17]. The percentage of miscarriage–premature delivery associated with CU in the active non-fulminating stage is 18–40%, with values up to 60% in the case of fulminating relapses.

Effect of Pregnancy on IBD Course

Many studies have been conducted on the effect of pregnancy on the course of intestinal inflammatory diseases [18–20]. From available meta-analytical data, we found that the probability of relapse of disease activity stages did not increase considerably during pregnancy or during puerperium. A study of

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over 500 pregnancies in patients suffering from UC in a quiescent stage revealed that the percentage of patient at risk for relapse of the active stage is 34%, similar to the rate of recrudescence of patients suffering from UC who are not pregnant [20]. Most relapses take place during the first trimester, partly because of the high frequency of therapy interruption during the pregnancy period.

In the abcence of therapy, UC in the active stage at the moment of conception shows a further worsening during pregnancy in 45% of patients; in 26%, it remains unchanged. In a small percentage of women, pregnancy causes improvement or remission during the disease activity stage, mostly during the first trimester. If conception occurs during the active stage, it is likely that the latter does not change during the entire course of pregnancy in about two thirds of patients. It may happen that the first acute onset of UC coincides with the beginning of pregnancy; in this case, its disease course tends to be particularly aggressive. Moreover, in some patients, the disease stays subclinical in the extra-pregnancy periods and becomes symptomatic only during pregnancy.

The course of CD during pregnancy is similar to UC. The patient with quiescent disease at the time of conception usually does not present a higher risk of a relapse during pregnancy whereas the patient con- ceiving during the activity stage presents a further worsening in one third of cases, and in one third they show no change at all [21]. There are no definitive data regarding desirable optimal duration of remission prior conception in order to assure a high probability of a favourable pregnancy course for both the expectant mother and the foetus; however, the longer the quiescence stage, the better the outcome.

In addition to disease activity state at the time of conception, according to two recent studies [22], a previous pregnancy might affect the overall course of IBD. In particular, in patients with UC, it seems that the more the parity increases, the lower the need for surgery. Moreover, patients with a history of multiple pregnancies would present, in comparison with non- parous patients, a need for a lower number of intestinal resections and a higher interval among the var- ious surgeries besides a reduction of the rate of disease. These remarks should partly be explained by the effect of pregnancy on the immune system [22].

Diagnostic Tools Usable During Pregnancy in Patients Suffering from IBD

Laboratory

Regarding possible diagnostic means to monitor the disease and for early recognition of recrudescences,

the role of laboratory parameters is limited, as they are undermined by poor reliability of values during pregnancy. Constant physiological modification, connected with hemodilution, is necessary for some parameters that do not present suitable specificity to monitor pregnant women with IBD. These physiological changes include reduction of haemoglobin of about 1 g/dl, reduction of blood iron level, a two- to three-fold increase in erythrocyte sedimentation rate (ESR), reduction of about 1 g/dl of blood albumin and an increase of alkaline phosphatase of about 1.5% . As these parameters may be analogously mod- ified even during the early stages of IBD relapse, they should not be used as diagnostic tools during pregnancy to avoid false positivities, or at least they should always be set in a wider clinical evaluation.

For example, if a pregnant patient with CD shows good health conditions but her hematocrit decreased and her ESR increased, she probably is in a quiescent stage of the disease and does not need further examination. On the contrary, a pregnant patient showing ingravescent diarrhoea, abdominal pain and highly altered laboratory parameters does require further diagnostic examination, possibly including an endoscopic evaluation.

Radiology

During pregnancy, it would be best to avoid whenev- er possible the use of ionising radiation and all exam- inations emitting them, such as abdominal-X-ray, barium meal, barium follow-through or computed tomography, given their likely teratogenic, genotoxic and carcinogenic effect [19], particularly during the first trimester. According to the American Radiology Society, exposition to a radiation dose lower than 5 rads does not considerably increase the risk of foetal damage. For this reason, if a certain radiologic procedure is highly suggested, it should be performed after a careful discussion with the patient regarding cost/benefit ratios and after exclusion of any additional diagnostic procedures that are safer but equally effective.

Gastrointestinal Endoscopy

Many studies have found that flexible colonoscopy frequently necessary to examine pregnant patients with IBD is relative safe, with no considerable risk of complications for the expectant mother or the foetus [19]. The main indications for endoscopy during pregnancy and IBD are the need to confirm clinical suspicion of disease relapse and for management of complications such as gastrointestinal bleeding and

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biliary obstructions. Indications for flexible colonoscopy include haematochezia, chronic diarrhoea and abdominal and rectal pain. Moreover, this procedure is necessary in patients in the active disease stage who do not respond to medical therapy. Also, it may help those with atypical symptoms. As to colonoscopy during pregnancy, few data are available because of the limited casuistics although generally it should be reserved exclusively for patients where the diagnostic benefit is higher than the risk.

Endoscopic examination of the superior intestinal tract is usually used less frequently than other procedures even although many studies emphasise good tolerability both for the expectant mother and the foetus as well as its high diagnostic value in the case of gastrointestinal bleeding.

Pharmacological Therapeutical Management of IBDs During Pregnancy

As for therapeutic management of IBD during pregnancy, recent studies have shown that pregnant patients should continue pharmacological therapy for the duration of the pregnancy, with the primary aim being to prevent disease relapse given the high risk of negative effects on the foetus. It is necessary that the physician perform a careful preliminary evaluation of the risk/benefit ratio associated with therapy during pregnancy, comparing any harmful effect on the foetus and the expectant mother caused by drugs on one hand and by disease relapse in the absence of pharmacological treatment on the other hand. The results of many studies [23] suggest that it would be best to continue therapy during the disease quiescent stage, treating intensively any recrudescences given the higher danger of the latter in comparison with most available drugs [24].

For patients with IBD, the 5-aminosalicylate (5- ASA) group (mesalamine, sulfasalazine, balsalazide), which have become the mainstay of pharmacological therapy of intestinal inflammatory diseases, may be used on pregnant patients to induce and maintain remission, as there is significant evidence regarding their safety during pregnancy. Many patients may be treated with aminosalicylates only [25–27].

However, for nonresponsive patients or for those allergic to 5-ASA and/or suffering from a more extended disease, corticosteroids are frequently prescribed [28]. Corticosteroids are particularly indicated during the stages of moderate–serious activity analogous to cases of the disease outside the pregnancy period. Many study attest to sufficient tolerability of these drugs and their poor effect on the risk of foetal malformations; despite their ability to cross the placental barrier, they are rapidly transformed by

placental 11-hydroxigenasis in less active metabolites with a consequent reduction of their levels in placental blood, especially in the case of some types of steroids, such as prednisone. For this reason, sup- pression of the hypothalamus-hypophysis- suprarenal axis of the foetus is rare. Among the latest steroidal compounds, Budesonide – a synthetic glu- cocorticoid selectively released in the small bowel and therefore particularly indicated in the case of ileal localisation of CD – falls into classification cate- gory C of drugs that may be used during pregnancy, as a teratogenic effect was found in animals but not in humans.

Another likely therapeutic option in non-responsive patients or in patients allergic to first-choice drugs is represented by immunosuppressant drugs [30]. Rationale for their use is based on the recog- nised immunomediated pathogenesis of IBDs, including azathioprine, 6-mercaptopurine, cyclosporine, methotrexate and infliximab. Azathio- prine and 6-mercaptopurine [29], taken in the usual doses, showed no negative effect on gametogenesis or evidence of a likely teratogen effect. However, given the poor number of studies investigating their use in pregnant patients with IBD, it would be best not to begin therapy with these agents during pregnancy.

Cyclosporine is not associated with an increased risk of teratogenesis [29], but given the high incidence of hepatic and kidney toxicity in the expectant mother, it must be exclusively used in pregnant women suffering from fulminating colitis who are non-responsive to steroids in order to avoid an urgent proctocolectomy, which is associated with a high risk of losing the foetus.

Methotrexate [31] is an antimetabolite drug and antagonist of folic acid. It is a teratogen and mutagen and therefore is contraindicated during pregnancy in those planning a pregnancy. Guinea pigs in utero exposed to methotrexate develop craniofacial and cardiovascular malformations and flaws of the neural tube caused by this drug’s antagonism of folic acid.

For these reasons, patients with IBD beginning therapy with methotrexate should use effective contra- ceptive methodologies. If conception takes place and interruption of pregnancy is not considered, high doses of folic acid should be administered during the entire course of pregnancy.

Recently, monoclonal antibodies (infliximab) against tumour necrosis factor (TNF) [32] were introduced as therapy for CD. In guinea pigs, these molecules, belonging to the class of biologic drugs, were not associated with a high risk of toxicity, embryotoxicity or teratogenic effect, and from data presently available, there is no definite evidence on the outcome of a woman’s pregnancy. As rare cases

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of foetal death secondary to cerebral and/or pul- monary haemorrhage were found, as well as cardiac malformations such as Fallot’s tetralogy and premature delivery, and given the small amount of studies regarding the effect of these drugs during pregnancy, their use is contraindicated in pregnant patients with CD and those planning to become pregnant.

In patients with IBD, some antibiotics, such as metronidazole and the fluoroquinolones, are sometimes used [33] not only to treat intervening infections but as primary therapy to treat CD. However, little data exists regarding the safety of antibiotics during pregnancy. In particular, metronidazole is the teratogen, foetotoxin and carcinogen in the mouse but these effects were not found in humans. For this reason short cycles of therapy with metronidazole may be used relatively safely to treat vaginal candi- dosis during pregnancy.

Regarding fluoroquinolones such as ciprofloxacin, there is no evidence of possible harmful effect on the foetus although available data are still limited.

In addition to the above-mentioned drugs, many studies show that the quality of life of pregnant patients may be incredibly improved by aspecific symptomatic drugs active on more frequently reported symptoms, such as abdominal pain, nausea and diarrhoea [34]. Among these drugs, metoclopramide (Plasil) may be used as an antiemetic without risk of foetal damage. On the contrary, given the small quantity of available data, loperamide, an antihemor- rhoidal drug frequently used by patients with IBD, must be taken cautiously and exclusively by patients where probable benefits are higher than the risks. An alternative to loperamide, kaolin with pectin or cholestyramine may be used, the latter being suggested especially in ileal localisation of CD or in patients with gravidic cholestasis.

Musculoskeletal and some other forms of abdominal pain may be treated safely with acetaminophen whereas non-steroidal anti-inflammatory drugs (NSAIDs), such as aspirin, are contraindicated because of the risk of premature delivery, extended labour and extended postpartum haemorrhage [35].

How to Approach Delivery in Patients with IBD

On the basis of data given in the literature, patients with RCU may expect ordinary labour and a transvaginal delivery unless there are contraindications connected with concomitant morbid conditions. This consideration is generally valid also for patients who underwent IPAA, as transvaginal delivery does not seem to considerably compromise the integrity of anastomosis [36]. However, as will be discussed later, there is still no consensus regarding this subject.

Differently from pregnant women with UC, most patients with CD, especially those with active perineal involvement, should have a caesarean deliver. If transvaginal delivery cannot be avoided, episiotomy should be avoided [37]. If unavoidable, a mediolater- al episiotomy is preferable in order to avoid anal sphincter damage. According to recent studies, development of new perineal complications after transvaginal delivery, usually associated with episiotomy, in patients without previous perineal disease is 17.9%. Moreover, while planning how to perform the delivery, the obstetrician should take into account the specific features of each patient.

Restorative Proctocolectomy with Ileal Pouch Anal Anastomosis and Women’s Health

The restorative proctocolectomy with IPAA (RP- IPAA) is now a standard operation proposed for the treatment of UC. It is a complex operation requiring an expert surgical team. Despite the fact that it is generally performed in third-level centres only, complication rate is extremely high, varying in the studies reported in the literature between 13% and 64%

[37–39]. Indications for this procedure are different in emergency or elective surgery: toxic megacolon, perforation or massive bleeding (in emergency surgery] or failure of medical therapy and rectal dyspha- sia/cancer (in elective surgery]. The operation greatly modifies the anatomy of the pelvic space because, after resection of the entire colon and rectum, an ileal reservoir (pouch] is engaged in the top of the anal canal. Since 1978, the year of the first formal descrip- tion of the operation, many women of child-bearing age have undergone this operation. In the last 20 years, many studies have been published attempting to analyse two aspects: how this operation may influence female reproductive health and whether pregnancy affects functionality of the ileal pouch.

RP-IPAA and Menses

In the literature, four major works analyse this aspect [40–43]. These studies found that most patients noted no change in menses or that initial cycle irregularity eventually disappeared.

IPAA and Pelvic Anatomy

As we will soon see, most studies show a reduction in fertility after RP-IPAA. One hypothesis to explain this phenomenon is the presence of postoperative adhesions. Oresland [41] observed that, even if 20/21

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women who underwent RP-IPAA had a normal physical examination, a hysterosalpingography showed some anomalies in 67% of subjects (14/21). Finding such as tubes adhered to the pelvis (48%) or bilateral tubal occlusion (10%) may certainly explain the decreased fertility, as recently emphasised by Dia- mond [44]. An important bias in this work, however, is the lack of performance of an examination before surgery, making the comparison between the pre- and postoperative situation impossible. Also, a study by Sjogren [45] showed an altered endopelvic status with reduced uterine mobility in 47% of women after RP-IPAA or the presence of adnexal tenderness in 13%.

Female Sexual Function After RP-IPAA

Many studies examined sexual function after RP- IPAA and particularly sexual satisfaction, desire, ability to experience orgasm and coital frequency [40, 43, 45, 46]. Results were satisfactory, as most of these aspects are influenced very little by surgery.

However, a percentage of patients, ranging from 3%

to 18%, were afraid of having stool leaks during intercourse. In contrast, especially in those with postoperatively unchanged or increased coital frequency from 82% to 100%, the appearance of dyspareunia was a rather frequent complication. Inci- dence varied considerably, from 0% to 38% [41, 42], stabilising in most works at 25%. Moreover, Farouk found that the incidence of this complication after surgery seems to increase over time [47].

RP-IPAA and Fertility

The desire to have a child is one of the primary instincts of the woman. This may explain why many women, despite the sequelae of such a serious surgery, decide to have a child. As already seen, UC in itself does not seem to influence fertility [6]. Almost all studies present in the literature agree on ascribing the serious negative effect of RP-IPAA on fertility [40, 41, 43, 45]. However, these works contained important methodologic bias or included a small number of participants. Three recent publications stand out, being points of reference on this topic.

Johnson et al. [48] compared 153 patients who underwent RP-IPAA with 60 patients with UC but treated with medical therapy. In this study, we come to two essential conclusions:

1. Women who underwent surgery had an infertility rate significantly higher in comparison with women who did not undergo surgery (28.1% vs 13.3%).

2. Surgery is the key element to explaining this dif- ference. If the infertility rate in women before surgery matched that of patients treated with medical therapy only (odds ratio 0.68, P=0.23), reduction of the fertility rate in the same study group of women evaluated before and after surgery is very high (odd ratio 0.021, P<0,0001).

Moreover, through univariate data analysis, the authors attempted to identify which variables might influence the reduction in fertility. Surprisingly, only the increase of age seemed to have a statistically higher influence on fertility while the history of small-intestinal obstruction, the number of abdominal operations and postoperative pelvic sepsis (three events predisposing the development of adhesions) did not seem to have any influence.

The other two important studies come from the same Scandinavian group. In the first, the fertility rate of a cohort of patients who underwent RP-IPAA was compared with the expected number of births in the general population [49]. Also in this study, the fertility of patients with UC seemed to be slightly reduced in the preoperative stage but is halved after surgery. This reduction reaches the 35% if operated patients who underwent in vitro fertilisation are not included. In the second study, the fecundity rate of 290 women with UC who underwent surgery was compared with 661 healthy women, showing in this case also a reduction of fertility of 80%.

The implications of these studies are very important for preoperative counselling, which must explore the desire for maternity of women waiting to undergo RP-IPAA and, if the clinical situation allows, advise postponement of surgery until after pregnancy.

Ileal Pouch Function, Pregnancy and Delivery

There are at least two theoretical premises regarding a negative effect of pregnancy on pouch function.

The first concerns the volumetric increase of the uterus, with a consequent increase of endoabdominal pressure (besides a direct compression effect on the reservoir). The second concerns the worsening of sphincterial function (it may already have been com- promised after surgery) after vaginal delivery [50].

Surprisingly, most authors emphasise that pregnancy influences pouch functionality in a small way [47, 51–53], limited to a few cases of slight worsening and temporary incontinence, which generally disappears after delivery.

Even though this topic has been discussed for a long time, vaginal delivery is considered safe by most authors. Two large, retrospective, controlled series compare pouch function after vaginal delivery with pouch function in nulliparous [47] or after caesarean

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delivery [52], showing no differences. All authors emphasise, moreover, that episiotomy, especially medial episiotomy, must be avoided. We should con- clude, therefore, considering the risks connected with caesarean delivery, it must be reserved for cases in which there is obstetrical indication.

In 2005, the authoritative group of Fazio [54] published a work that seems to refute what has been so far written. Recognising that the effects of delivery on sphincterial function in the short term are reduced, it emphasises a high incidence of sphincter injuries that can be detected with endorectal ultrasonogra- phy. Using the words from the title of this work, “a word of caution” is essential because, in the long run, functional response to this sphincter damage will need to be assessed. The authors suggested the oppo- site of what thus far appears in the literature, as they advise a planned caesarean delivery. In light of this work, it is necessary to carefully evaluate each patient in an attempt to assess the risk/benefit ratio between the two delivery modalities.

Conclusion

UC and CD are inflammatory diseases of the intes- tine, with a multifactor pathogenesis and the tendency to especially afflict young women of reproductive age, affecting their quality of life as well as their interpersonal relationships. In reference to this aspect, it is important to emphasise the psychological effect of the disease on patients’ sexual life, which can under- mine the opportunity of having children despite the fact that IBD itself does not considerably affect fertility. Moreover, even if pregnant women suffering from IBD require strict monitoring, particularly concerning the nutritional aspect and the need for aggressive treatment of any disease relapses, risk to the foetus or the expectant mother are moderate in suitably controlled disease, and many concerns about pregnancy and its possible consequences are not justified.

Risks increase in insufficiently treated disease, as in this case, relapses are frequent and invariably influence foetal growth negatively, resulting in low birth weight, premature delivery and miscarriage.

For this reason, it is necessary when treating young women with IBD to apply a multidisciplinary approach involving careful evaluation of patients’

psychosocial status and including discussion about medical, psychological and sexual problems, inform- ing and educating them about the peculiar aspects of pregnancy and its management during IBD.

On the basis of the present trend, a patient with IBD that is kept in a quiescent stage thanks to increasingly effective medical therapies, most of

which are well tolerated during pregnancy, may expect pregnancy course and outcome not too different from those expected in young healthy women.

Acknowledgment

The authors thank Dr. Isabella Pichiri for her pre- cious help and assistance.

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