crohn’s disease, ulcerative colitis and pregnancy - dr. falk ...2007/09/05 · 9th edition 2007...

Crohn’s Disease, Ulcerative Colitis and Pregnancy

The informed patient

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Author’s address

Prof. Dr. Axel DignassInnere Medizin IMarkus-KrankenhausWilhelm-Epstein-Str. 260431 Frankfurt / MainGermany

Tel.: ++49-69/95 33-22 01Fax: ++49-69/95 33-22 91E-mail: [email protected]

© 2007 Falk Foundation e.V.All rights reserved.

FALK FOUNDATION e.V.

Publisher

Leinenweberstr. 5Postfach 652979041 FreiburgGermany


9th edition 2007

Crohn’s Disease,Ulcerative Colitisand Pregnancy

Author: A. Dignass, Frankfurt / Main, Germany

The informed patient


Contents

Page

Introduction 4

Can women and men with inflammatory bowel diseases become parents? 6

How do inflammatory bowel diseases affectfemale and male fertility and chances forsuccessful pregnancy? 8

How do inflammatory bowel diseases affect the course of pregnancy and the baby’s health? 12

Which medical examinations are important prior to a planned pregnancy? 16

How does bowel surgery for treatment of inflammatory bowel disease affect a pregnancy? 18

Does pregnancy have an impact on the natural course of inflammatory bowel disease? 20

Can inflammatory bowel disease first appearduring pregnancy? 24

Can drugs for the treatment of inflammatorybowel diseases be taken during pregnancy? 26

Does the standard drug treatment of inflam-matory bowel diseases harm the baby? 28

Can oral contraceptives cause or aggravateinflammatory bowel diseases? 32

Can the immunomodulating drugs azathio-prine or 6-mercaptopurine be taken before or during pregnancy? 34

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Contents

Page

Is the use of cortisone safe during late pregnancy and nursing? 36

Should 5-ASA therapy be interrupted prior to delivery? 38

Are there medical reasons requiring termi-nation of pregnancy in women with inflam-matory bowel diseases? 40

Which diagnostic methods are considered to be safe during pregnancy? 42

What special considerations are necessaryduring delivery? 44

Is a special diet during pregnancy benefi-cial in women with inflammatory boweldiseases? 46

How high is the risk of later developing aninflammatory bowel disease in children whose parent(s) suffer from Crohn’s disease or ulcerative colitis? 48

Should women with inflammatory boweldiseases nurse? 50

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Introduction

4

Inflammatory bowel diseases (IBD), such asCrohn’s disease and ulcerative colitis, frequentlyoccur in younger patients who are concernedabout planning a family and related questions.Women and men suffering from IBD – as wellas their partners – are often unsure of theeffects of diagnostic and therapeutic measureson the outcome of their pregnancy. They mayhave questions about such issues as endoscopicexaminations of the gastrointestinal tract, radio-logic examinations, not to mention the possibleneed for surgery and/or the use of various drugs.

Patients may also have questions on how preg-nancy may affect the course of their boweldisease and whether any special precautions(such as the method of delivery) have to be con-sidered. Does pregnancy lead to a worsening of pre-existing inflammatory bowel diseases orcause an acute episode?

Patients are frequently unsure whether their fer-tility is reduced by inflammatory bowel diseasesand whether pregnancy may be even possible.Patients and their families may also have ques-tions relating to the probable hereditary predis-position involved in the development of inflam-matory bowel diseases.

It is important for patients affected with inflam-matory bowel diseases together with theirspouses and families to be adequately counseledbefore, during and after pregnancy. This will helpto reduce unreasonable fears regarding pregnan-cy and to recognize as soon as possible anydangers or complications for mother or baby.

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Introduction

5

The purpose of this brochure is to offer answersto commonly asked questions. Current know-ledge is explained on the basis of the latestscientific studies.

At the same time, we remind our readers thatthis brochure does not provide the only validanswer to the many controversial questionsinvolved in the context of pregnancy and inflam-matory bowel diseases. It also cannot replacethe trust you place in your personal physicianand the value of personal discussions relating toyour care. Finally, no brochure can address all of the many individual situations that can affectboth your pregnancy and your inflammatorybowel disease.

Prof. Dr. Axel Dignass

051854_Falk_S82e 29.07.2005 9:32 Uhr Seite 9

”Can women and men with

inflammatory bowel diseases

become parents

Can women and men with


become parents?

6

?

051854_Falk_S82e 29.07.2005 9:32 Uhr Seite 10

7

In general, the answer to this question is “yes”.There are, however, a number of fundamentalissues that must be addressed when planning apregnancy. As we will discuss in more detailbelow, it is particularly important to plan a preg-nancy during a period when your disease isinactive. At such times, your fertility is not dimin-ished and your pregnancy will not differ signifi-cantly from that in healthy women and men.

In some cases, inactive disease may be due tothe use of drugs, which may be harmful duringpregnancy. In these cases, it is very important todiscuss your desire for pregnancy with the phy-sicians involved in your care.

051854_Falk_S82e 29.07.2005 9:32 Uhr Seite 11

”How do inflammatory bowel

diseases affect female and

male fertility and chances for

successful pregnancy

8

How do inflammatory bowel

diseases affect female and

male fertility and chances for

successful pregnancy?

?

051854_Falk_S82e 29.07.2005 9:32 Uhr Seite 12

9

■ Fertility in women with inflammatory bowel diseases

Women with ulcerative colitis are usually as fer-tile as healthy women. An exception is thetemporary reduction in fertility associated withextensive abdominal surgery, such as the partialor complete removal of the large intestine (colec-tomy), the creation of a pouch for the smallintestine with anastomosis of the small intestineto the rectum (ileo-anal pouch), or creation of anartificial intestinal orifice (ileostomy). The decreas-ed fertility seen in these women is usually tem-porary and normalizes within weeks or months,although statistically the overall fertility of womenwho have undergone these types of surgery mayremain slightly reduced.

The question of female fertility is not so clear-cutin Crohn’s disease. While it appears that fertilityis not affected during periods of quiescent dis-ease, a temporary reduction in fertility duringacute disease phases and following extensivesurgery can be frequently observed. This mayresult in a missed menstrual period (amenorrhea,i.e. absence of menstruation), a symptom fre-quently observed following significant weightloss caused by active disease.

Reduced fertility during phases of increasedinflammatory activity would also seem to makesense biologically: pregnancy is postponed untilthe best possible conditions for its successfuloutcome can be assured, while, at the sametime, additional stresses are avoided for the pa-tient.

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10

Following complete surgical wound healing andstabilization of disease activity, female fertilitydoes not appear to be significantly affected,though studies do suggest a slight reduction infertility in surgically treated patients. It should beremembered that the failure of pregnancy tooccur cannot always be blamed on inflammatorybowel diseases: even in healthy women expe-riencing regular, unprotected intercourse, onlyabout 90% become pregnant.

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11

■ Fertility in men with inflammatory bowel diseases

Male fertility is usually not affected in inflamma-tory bowel diseases. Abscesses and fistulas inthe pelvis and anal region may, however, causedisturbances in erection and ejaculation. Similardisturbances can also occur in patients who haveundergone extensive surgery, particularly fol-lowing ileo-anal pouch operation. They are, how-ever, very rare.

A particular situation may arise in connection withthe use of salazosulfapyridine or sulfasalazine.These drugs can cause temporary infertility inmen, which normalizes about two months afterdiscontinuing the drugs or switching to puremesalazine or 5-aminosalicylic acid (5-ASA) pre-parations.

The reasons for this temporary infertility include adecreased sperm count, a reduced amount ofseminal fluid and abnormalities in the structureand motility of the sperm cells. These changesoccur in about 80% of men treated with thesedrugs.

051854_Falk_S82e 29.07.2005 9:32 Uhr Seite 15

”

12


diseases affect the course

of pregnancy and the baby’s

health


diseases affect the course

of pregnancy and the baby’s

health?

?

051854_Falk_S82e 29.07.2005 9:32 Uhr Seite 16

13

Numerous studies have investigated the effect ofthe inflammatory bowel diseases Crohn’s diseaseand ulcerative colitis on the outcome of pregnan-cy and the health of the child. Results of thesestudies have generally shown that about 85% ofwomen with Crohn’s disease or ulcerative colitisexperience normal, uncomplicated pregnancies.Congenital malformations in infants born towomen with Crohn’s disease or ulcerative colitisoccur in only about 1%. The risk of miscarriagealso does not, in general, appear to be increased.These rates correspond to those observed inhealthy women. Here again, one should not for-get that pregnancies, even in healthy women, donot progress normally in all cases: in fact, prob-lems or complications relating to the pregnancyor affecting the baby’s health occur in about 15%of cases.

Although pregnancies in women with inflamma-tory bowel diseases usually progress in a mannercomparable to healthy women, various studieshave shown that, in both Crohn’s disease andulcerative colitis, increased inflammatory activityat the time of conception may unfavorably affectthe pregnancy and is associated with a signifi-cantly higher rate of complications (table 1).

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Table 1

Course of pregnancy in healthy women and in patients with inflammatory bowel diseases in relation to diseaseactivity (%).(Mean percentages from European and American studies)

Normal Malfor- Premature Abor-mations births tions

General population 83 2 6 9

Crohn’s disease in remission 82 1 7 10

Crohn’s disease in active phase 54 1 25 20

Ulcerative colitis in remission 84 1 6 9

Ulcerative colitis in active phase 65 2 12 21

14

These findings indicate that pregnancies conceiv-ed during inactive disease or during a phase ofmild inflammatory activity progress normally andwithout an increased risk of complications. There-fore, pregnancies should, if possible, be plannedduring phases of inactive disease or mild inflam-matory activity. If conception occurs in a period ofincreased disease activity, the rate of abortions,premature births and other pregnancy complica-tions increases significantly. If possible, activedisease should be treated and the necessity oftherapeutic intervention should be clarified priorto beginning a pregnancy. For example, if it isknown that surgery will be necessary in the nearfuture (for example, to treat stenoses caused byscarring), the operation should occur prior to aplanned pregnancy.

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15

Ultrasound profile of the face of ahealthy female fetus in the 25thweek of pregnancy.

051854_Falk_S82e 29.07.2005 9:32 Uhr Seite 19

”Which medical examinations

are important prior to a planned

pregnancy

16

Which medical examinations

are important prior to a planned

pregnancy?

?

051854_Falk_S82e 29.07.2005 9:32 Uhr Seite 20

d

17

No general plan can be offered here. This is amatter to be discussed individually with your doc-tor. Invasive procedures such as endoscopies orradiologic examinations are not required in allcases.

A detailed discussion with your doctor regardingyour medical history and actual condition andlaboratory tests to determine the activity of thedisease and to exclude any dietary deficienciesseem advisable prior to a planned pregnancy. Anultrasound examination of the abdomen and theintestine performed by an experienced examinercan also provide valuable information.

Individual patients may require more extensiveexaminations including endoscopic and radiologicstudies of the bowel. Results of these tests mayindicate the need for anti-inflammatory therapy oradditional supplementation of certain vitaminsand minerals (e.g., vitamin B12, folic acid, iron).Taking folic acid during early pregnancy is advis-able in all women, since it helps to prevent theoccurrence of rare neural tube defects in thedeveloping fetus. It is possible that the uptakeand metabolism of folic acid is decreased duringtreatment with sulfasalazine or sulfapyridine.

051854_Falk_S82e 29.07.2005 9:32 Uhr Seite 21

”How does bowel surgery

for treatment of inflam-

matory bowel disease affect

a pregnancy

18

How does bowel surgery

for treatment of inflammatory

bowel disease affect

a pregnancy?

?

051854_Falk_S82e 29.07.2005 9:32 Uhr Seite 22

19

Past abdominal operations for treatment of in-flammatory bowel diseases do not in general ap-pear to have a negative impact on the course ofpregnancy. Pregnancies without complicationsare seen even after extensive intestinal surgeryincluding colectomy or creation of an ileostomy.Here, it is important that a sufficient interval pass-es between the operation and the time of con-ception, so that surgical wounds have healed andthere is no significant disease activity.

Following an extensive surgical procedure, it isusually advisable to wait a year before becomingpregnant. This is true regardless of whether anartificial intestinal orifice has been created or thepatient has undergone continence-preserving sur-gery. Occasionally, complications relating to theileostomy (e.g., prolapse, occlusion) may occurduring pregnancy. It has been suggested that therate of premature births may also increase fol-lowing total colectomy and ileostomy.

In certain cases, surgical intervention may be-come necessary during an existing pregnancy.This may in a few, generally rare cases result inpremature birth or in spontaneous abortion (mis-carriage). On the other hand, uncomplicated preg-nancies have been documented even after exten-sive surgery, including total colectomy in patientswhose ulcerative colitis has failed to respond tomedical treatment.

051854_Falk_S82e 29.07.2005 9:32 Uhr Seite 23

”Does pregnancy have an

impact on the natural course

of inflammatory bowel

disease

Does pregnancy have an

impact on the natural course


disease?

20

?

051854_Falk_S82e 29.07.2005 9:32 Uhr Seite 24

Table 2

Effect of pregnancy on disease activity in Crohn’s disease following conception during remission

Remission maintained ~85 %

Beginning of an acute episode: ~15 %

• during the first trimester ~13 %

• during the second trimester <1 %

• during the third trimester <1 %

• during puerperium (childbed) ~2 %

21

In the large majority of cases pregnancy has noeffect on the activity or maintenance of remissionof inflammatory bowel diseases. In individual cases, however, a dramatic improvement orworsening of symptoms of inflammatory boweldiseases can be observed (tables 2 and 3).

Table 3

Effect of pregnancy on disease activity in Crohn’s disease following conception in a phase of acute disease

achieving remission 15 %

improved 20 %

no change in disease activity 30 %

worsening during pregnancy 25 %

worsening during puerperium (childbed) 10 %

051854_Falk_S82e 29.07.2005 9:32 Uhr Seite 25

22

Only about 15% of women with Crohn’s diseasewho conceived during a remission phase experi-ence an acute disease episode during their preg-nancy. This rate approximates the normal clinicalcourse of Crohn’s disease. If an increased dis-ease activity is already present at the beginningof pregnancy, this increased activity remainsmore or less constant throughout pregnancy inabout one-third of patients (table 3). Episodes ofacute disease occur more frequently during pa-tients’ first trimester of pregnancy and during thepuerperium (childbed).

Pregnancy also does not seem to exert a majoreffect on disease activity in patients with ulcera-tive colitis. About one-third of women with ulcer-ative colitis who conceived during a phase of re-mission experience an episode of acute diseaseduring pregnancy (table 4). This corresponds tothe normal course of the disease in women whoare not pregnant.

Table 4

Effect of pregnancy on disease activity of ulcerative colitis following conception during remission

Remission maintained ~70 %

Beginning of an acute episode: ~30 %

• during the first trimester ~20 %

• during the second trimester ~7 %

• during the third trimester <1 %

• during puerperium (childbed) ~3 %

051854_Falk_S82e 29.07.2005 9:32 Uhr Seite 26

Table 5

Effect of pregnancy on disease activity in ulcerative colitis following conception in a phase of acute disease

achieving remission 19 %

improved 18 %

no change in disease activity 32 %

worsening of disease activity 31 %

23

Episodes of acute disease occur more frequentlyduring the first six months of pregnancy andduring the puerperium (childbed). As in Crohn’sdisease, the majority of women who conceiveduring an active disease phase usually continueto have active disease throughout pregnancy(table 5).

Generally, the natural course of inflammatorybowel diseases can be improved by drug therapyeven during pregnancy. Drugs may induce remis-sion or decreased disease activity, which canthen be maintained for the remainder of the preg-nancy. In addition, worsening of symptoms ininflammatory bowel diseases during one preg-nancy does not automatically implicate that thismay occur in subsequent pregnancies.

051854_Falk_S82e 29.07.2005 9:32 Uhr Seite 27

”Can inflammatory bowel

disease first appear during

pregnancy

Can inflammatory bowel

disease first appear during

pregnancy?

24

?

051854_Falk_S82e 29.07.2005 9:32 Uhr Seite 28

25

Both Crohn’s disease and ulcerative colitis canshow their first symptoms during pregnancy. Ingeneral, the course of inflammatory bowel dis-eases in these patients is not more severe thanin patients who are not pregnant.

A significant problem that may delay the definitediagnosis is the understandable fear of under-going diagnostic procedures, such as endoscopyor radiologic examinations, at this time (see alsopage 42).

051854_Falk_S82e 29.07.2005 9:32 Uhr Seite 29

”Can drugs for the treatment


diseases be taken during

pregnancy

Can drugs for the treatment


diseases be taken during

pregnancy?

Everyone knows the importance of avoidingmedications during and even prior to a plannedpregnancy in order to protect the unborn childfrom unnecessary risks. The use of drugs in treat-ing inflammatory bowel diseases represents aspecial problem. It is only natural that patientsand their families may be unsure and have manyquestions relating to this issue. These concernsare reinforced by the package inserts of a greatmajority of medications, which advise patients touse them during pregnancy only on the advice ofa doctor and for a strictly defined indication. Thedecision to treat a pregnant woman with any drug

26

?

051854_Falk_S82e 29.07.2005 9:32 Uhr Seite 30

must be made for each patient individually, ifnecessary after consultation of the proper specia-lists. This advice is based on the requirement forthe highest possible degree of safety. Even in thecase of drugs for which no adverse effects havebeen reported to date for either mother or baby,there is always a remaining risk, which, though itmay be ever so slight, cannot be totally excluded.

Therefore, the general rule during pregnancy is totake only those medications that are absolutelynecessary. However, we should not forget thatmany diseases, if inadequately treated, also posea serious threat to the well-being of the motherand her child.

In this context, it is important to repeat, what wesaid above: even in healthy women, only about85% of pregnancies develop without any compli-cations.

Overall, the treatment of inflammatory boweldiseases in pregnant women is, in most of itscomponents, based on the same general princi-ples as are applied to patients who are not preg-nant. Optimal care, however, depends on closeand regular interaction between the gastroenter-ologist and the gynecologist and should considersome important differences and exceptions withregard to determining the individual medical treat-ment of a single patient.

27

051854_Falk_S82e 29.07.2005 9:32 Uhr Seite 31

”Does the standard drug

treatment of inflammatory

bowel diseases harm

the baby

Does the standard drug

treatment of inflammatory

bowel diseases harm

the baby?

Unfortunately, it is impossible to give a generallyvalid answer to this question. The care of eachindividual patient should be one of cooperationbetween the gynecologist and the specialist ininternal medicine or gastroenterology. The variouscortisone (prednisone, prednisolone, hydrocorti-sone) and mesalazine or 5-ASA preparations in thecustomary doses generally prescribed for thetreatment of inflammatory bowel diseases do not appear to represent an increased risk to theunborn fetus based on current evidence. Never-theless, the package inserts for all of these drugsdo urge caution and strict determination of indi-cation during the first trimester of pregnancy. Patients who depend on 5-ASA- or corticosteroid-(cortisone) preparations for maintaining remis-

28

?

051854_Falk_S82e 29.07.2005 9:32 Uhr Seite 32

29

sion, should continue this therapy even after preg-nancy is confirmed: an increase in the inflamma-tory activity of the disease is a much greater riskfor the fetus. If an acute episode of an inflamma-tory bowel disease should occur during pregnan-cy, these drugs should be taken in adequate dos-ages in order to control disease activity as quicklyas possible. Inadequately treated, inflammatorybowel diseases harm both the baby and itsmother more than the drug therapy.

The conventional therapy of inflammatory boweldiseases with pure 5-ASA- or corticosteroid-pre-parations in fathers does not have any adverseeffects on the outcome of a pregnancy based onour current knowledge. Only the above describedtemporary reduction in fertility caused by salazo-sulfapyridine or sulfasalazine should lead to sub-stitution of pure 5-ASA- or mesalazine-prepara-tions in males who wish to start a family.

To date, there has not been sufficient clinicalexperience with budesonide to permit generallyvalid statements with regard to its use in preg-nancy. Our own limited experience with the use ofbudesonide in pregnancy has not shown any evi-dence for increased risk to mother or baby, butuse of the drug should be adequately discussedwith the patient and her doctor prior to startingtherapy with budesonide.

The use of other drugs such as antibiotics orimmunomodulators such as azathioprine or 6-mercaptopurine requires a very strict determina-tion of indication and should only be consideredafter careful consultation with an experiencedspecialist (see also page 34 of this brochure).

051854_Falk_S82e 29.07.2005 9:32 Uhr Seite 33

30

The use of the other immunomodulating drugs,such as methotrexate (MTX), cyclosporine, tacroli-mus and mycophenolate-mofetil, must be careful-ly discussed in each individual case. In general,these drugs should not be used during pregnancysince evidence from animal experiments providessome evidence for adverse outcomes duringpregnancy. This is particularly true for methotrex-ate, which, in large doses, can be used for induc-ing termination of a pregnancy. Experience withcyclosporine and tacrolimus in many patients withinflammatory bowel diseases and also followingorgan transplantations has shown uncomplicatedpregnancies despite use of these drugs. There-fore, current knowledge does not support ageneral indication for pregnancy termination incases of unplanned pregnancy while the mothersare taking cyclosporine or tacrolimus.

No clear-cut data are available regarding the use ofinfliximab during pregnancy. Therefore, use ofinfliximab during pregnancy is not recommendedand, as is generally recommended for the use ofazathioprine, patients taking infliximab shouldpractice adequate contraception for at least threemonths after discontinuing infliximab. On theother hand, a number of healthy babies have beenborn to mothers taking infliximab during pregnan-cy, so that current evidence does not support adefinite indication for pregnancy termination inmothers taking infliximab.

The use of antibiotics such as metronidazole orciprofloxacin during pregnancy requires a strictindication; their long-term use is generally contra-indicated. Since both of these drugs are lesseffective than the standard therapy with cortico-

051854_Falk_S82e 29.07.2005 9:32 Uhr Seite 34

31

steroids or 5-ASA-preparations and are reservedto cases, in which these standard drugs havebeen proven ineffective, therapy with either corti-costeroids or 5-ASA should be tried before con-sidering treatment with these antibiotics.

Pregnant women with inflammatory bowel dis-eases should also exercise caution when usingcertain antidiarrheal drugs such as loperamide ordiphenoxylate/atropine, since individual cases ofcongenital defects suggest a certain risk for fetalmalformations.

The use of psyllium seed shells (Plantago ovata,ispaghula husks) is often useful in cases of diar-rhea.

051854_Falk_S82e 29.07.2005 9:32 Uhr Seite 35

”Can oral contraceptives cause

or aggravate inflammatory

bowel diseases

Can oral contraceptives cause

or aggravate inflammatory

bowel diseases?

32

?

051854_Falk_S82e 29.07.2005 9:32 Uhr Seite 36

33

In the past, several investigators have presentedevidence suggesting that women taking oral con-traceptives have a slightly higher incidence ofCrohn’s disease and suffer from acute episodesof the diseases more frequently. Other investiga-tors, however, have been unable to confirm thesefindings. To date, no evidence has suggested anunfavorable connection between oral contracep-tives and ulcerative colitis.

In general, our experience has shown that the riskof developing inflammatory bowel diseases or ofa worsening of symptoms due to the use of oralcontraceptives is quite low. Thus, we see no con-traindication for the use of oral contraceptives inwomen with inflammatory bowel diseases.

It is important to remember, however, that thesevere diarrhea accompanying inflammatorybowel diseases in individual cases may disturbuptake of the contraceptive hormones in thebowel and thus compromise the efficacy of themethod. Patients using contraceptive medicationwith low amounts of hormone (such as the so-called “minipills”) should be particularly aware of this possible reduction in contraceptive pro-tection. Discussion of this issue with your gyne-cologist is advisable.

051854_Falk_S82e 29.07.2005 9:32 Uhr Seite 37

”Can the immunomodulating

drugs azathioprine or 6-mer-

captopurine be taken before or

during pregnancy

Can the immunomodulating

drugs azathioprine or 6-mer-

captopurine be taken before or

during pregnancy?

The immunomodulating drugs azathioprine or 6-mercaptopurine should, if possible, be discon-tinued at least three months prior to planned con-ception because of the very uncertain state of ourcurrent knowledge of their risks in pregnancy. If,however, a patient taking either of these drugsshould become pregnant, there is no general indi-cation for pregnancy termination since there areno data suggesting an increased risk of malforma-tions or stillbirths in humans.

More recent data, particularly from studies intransplant patients and rheumatology, suggestthat uncomplicated pregnancies are possible inwomen taking azathioprine or 6-mercaptopurine.

The decision to discontinue azathioprine therapyafter pregnancy is confirmed or whether concep-

34

?

051854_Falk_S82e 29.07.2005 9:32 Uhr Seite 38

35

tion is possible during ongoing therapy with thedrug requires careful consideration of the ad-vantages and disadvantages together with appro-priate counseling of the parents. This decisionrequires a high degree of responsibility andshould include a joint discussion with the parentsand their respective primary care physician, gyne-cologist and specialist in gastroenterology.

The effect of azathioprine or 6-mercaptopurine onthe outcome of pregnancies when taken by fa-thers prior to conception, is controversial. Whilemany physicians and scientists do not see anincreased risk of pregnancy complications, anAmerican research group has recently reportedan increased risk of miscarriages and congenitalmalformations in cases, in which the male part-ner took these drugs in the last three months pri-or to conception. Until this issue remains contro-versial, it is advisable for men to discontinueazathioprine at least three months prior to a plan-ned pregnancy. This is based on the presumptionthat azathioprine may cause damage to geneticmaterial in sperm cells and the fact that the pro-duction of a new generation of sperm cells takesabout 90 days.

Current knowledge, based on experience fromtransplant patients and rheumatology, does not,in our opinion, justify a general indication for preg-nancy termination in women taking azathioprineor 6-mercaptopurine. In certain special cases,therapy with azathioprine can even be continuedbased on careful consideration of the benefitsand risks involved for mother and baby.

051854_Falk_S82e 29.07.2005 9:32 Uhr Seite 39

”Is the use of cortisone safe

during late pregnancy and

nursing

36

Is the use of cortisone safe

during late pregnancy and

nursing?

It is generally accepted that the dosages of corti-costeroid preparations (e.g. prednisone, predniso-lone, hydrocortisone) usually prescribed for thetreatment of inflammatory bowel diseases arenot associated with an increased risk of miscar-riage or fetal malformations. It is theoreticallypossible that very high doses of corticosteroidstaken during the final phases of pregnancy mightcause reduced corticosteroid production in thenewborn’s adrenal gland resulting in low levels ofcirculating cortisone after birth, together withapathy and reduced activity. Therefore, infantsborn to mothers taking high corticosteroid doses

?

051854_Falk_S82e 29.07.2005 9:32 Uhr Seite 40

in late pregnancy should be closely monitored byan experienced neonatologist. If necessary, thebaby can receive cortisone substitution until theadrenal glands are able to produce sufficient cor-tisone.

Since cortisone can pass through breast milk intothe baby, it is conceivable that an infant’s corti-sone intake during nursing could result in a sim-ilar depression of cortisone production in thebaby’s adrenal glands. Again, careful follow-up byan experienced pediatrician is important.

In both instances, however, no permanent harmto the infant is to be expected. Once cortisonetherapy is discontinued, the function of theinfant’s adrenal gland normalizes with adequateproduction of cortisone.

Regarding the use of budesonide during pregnan-cy and lactation, it is still too early to give general-ly valid statements, since experience with thisdrug during pregnancy is quite limited. In theory,the rapid metabolism of budesonide in themother’s liver leads to relatively low circulatinglevels of the drug and thus only a slight transmis-sion to the baby through the milk. Our own expe-rience with budesonide during pregnancy andnursing has been positive and we have notobserved any adverse effects in the infants. Theuse of budesonide sprays for the treatment ofasthma during pregnancy also does not seem tobe associated with an increased risk of fetal mal-formations. Because of the limited experiencewith the drug, however, the use of budesonideduring pregnancy and nursing should includecomprehensive counseling of the mother.

37

051854_Falk_S82e 29.07.2005 9:32 Uhr Seite 41

”Should 5-ASA therapy

be interrupted prior to

delivery

38

Should 5-ASA therapy

be interrupted prior to

delivery?

?

051854_Falk_S82e 29.07.2005 9:32 Uhr Seite 42

39

Unlike acetylsalicylic acid (aspirin), 5-aminosalicy-lic acid (5-ASA, mesalazine) at therapeutic dos-ages does not affect coagulation of the blood orinhibit the aggregation of the platelets, which isimportant for the control of bleeding.

Therefore, interruption of 5-ASA therapy prior todelivery is not generally required, particularlysince blood levels of 5-ASA are very low.

051854_Falk_S82e 29.07.2005 9:32 Uhr Seite 43

”Are there medical reasons

requiring termination

of pregnancy in women

with inflammatory bowel

diseases

Are there medical reasons

requiring termination

of pregnancy in women

with inflammatory bowel

diseases?

40

?

051854_Falk_S82e 29.07.2005 9:32 Uhr Seite 44

41

Termination of pregnancy is very rarely or evennever necessary because of inflammatory boweldiseases in the mother. Instead, there should beadequate therapy of the woman’s inflammatorybowel disease together with comprehensive careby her doctors.

051854_Falk_S82e 29.07.2005 9:32 Uhr Seite 45

”Which diagnostic methods are

considered to be safe during

pregnancy

42

Which diagnostic methods are

considered to be safe during

pregnancy?

?

051854_Falk_S82e 29.07.2005 9:32 Uhr Seite 46

43

Ultrasound examinations of the abdomen andbowel are not harmful to mother or baby and pro-vide important information about the activity andextent of the disease. When performed by anexperienced examiner, there is no reason thatendoscopic examinations of the stomach (gas-troscopy) or bowel (rectoscopy, sigmoidoscopyand even ileo-colonoscopy) cannot be performedsafely in pregnant women.

These invasive methods, however, should only beused when absolutely necessary to determine the most appropriate type of therapy. Magneticresonance imaging (MRI), which is probably alsonot harmful, may be useful in certain cases. Dia-gnostic procedures involving radiation exposureshould be postponed until after delivery and re-served to emergency situations.

051854_Falk_S82e 29.07.2005 9:32 Uhr Seite 47

”What special considerations

are necessary during

delivery

What special considerations

are necessary during

delivery?

44

?

051854_Falk_S82e 29.07.2005 9:32 Uhr Seite 48

45

Vaginal delivery is generally preferred even inwomen with inflammatory bowel diseases. Gen-erally, vaginal delivery is even possible in womenwho have undergone ileostomy, although theincreased intra-abdominal pressure due to con-tractions may cause prolapse of the intestinal ori-fice. In such cases, many obstetricians prefer de-livery by cesarean section. The method of deliveryin patients with ileostomy, therefore, should bediscussed in advance with the patient’s obste-trician.

Another group of patients in whom cesarean sec-tion is preferred and may be useful are thosewomen suffering from extensive formation offistulas in the perianal area and pelvis. This issue,however, must also be decided in consensus be-tween the patient and her obstetrician.

Whether an episiotomy (incision in the perineum)contributes to an increased risk of perianal fistulaformation remains controversial. Most data pub-lished to date do not support an increased risk ofperianal fistula formation following episiotomy.

051854_Falk_S82e 29.07.2005 9:32 Uhr Seite 49

”Is a special diet during

pregnancy beneficial in

women with inflammatory

bowel diseases

Is a special diet during

pregnancy beneficial in

women with inflammatory

bowel diseases?

46

?

051854_Falk_S82e 29.07.2005 9:32 Uhr Seite 50

47

Patients with inflammatory bowel diseases gener-ally do not require a special diet. Patients should,of course, follow the general recommendationsfor a balanced diet with adequate intake of calo-ries, vitamins and minerals during pregnancy.

051854_Falk_S82e 29.07.2005 9:32 Uhr Seite 51

”How high is the risk of later

developing an inflammatory

bowel disease in children

whose parent(s) suffer from

Crohn’s disease or ulcerative

colitis

48

How high is the risk of later

developing an inflammatory

bowel disease in children

whose parent(s) suffer from

Crohn’s disease or ulcerative

colitis?

The risk for the children of parents with inflamma-tory bowel diseases to develop Crohn’s disease orulcerative colitis themselves is relatively small.Inflammatory bowel diseases are not hereditarydiseases in the strict sense. What is passed on toone’s children is a genetic predisposition to devel-op these diseases under certain circumstances. Inindividual cases, there may be an increased pre-valence of inflammatory bowel diseases in certainfamilies.

A person’s individual risk to develop an inflamma-tory bowel disease when another family member

?

051854_Falk_S82e 29.07.2005 9:32 Uhr Seite 52

49

is affected cannot be precisely predicted and canbe estimated only on the basis of empirical ob-servations. Thus, the relative risk of developing aninflammatory bowel disease ranges from zero to36% depending on how closely related the per-son is to the already affected family member(table 6).

Despite the increased risk in children of parentswith inflammatory bowel diseases to develop aninflammatory bowel disease, we do not advisesuch patients to forego being biological parents. Ifdiagnosed early, inflammatory bowel diseases arerelatively well treated by improved medical thera-py. Indeed, the life expectancy of patients withinflammatory bowel diseases does not differ sig-nificantly from that of normal, healthy subjects.

Table 6

Estimated relative risk of developing an inflammatory bowel disease

Risk for children with one affected parent 1 – 7 %

Risk for children with both parents affected up to 36 %

Risk for other siblings, when one child is affected 2 – 6 %

Risk for the parents, when one child is affected 1 – 5 %

051854_Falk_S82e 29.07.2005 9:32 Uhr Seite 53

”Should women with


nurse

50

Should women with


nurse?

?

051854_Falk_S82e 29.07.2005 9:33 Uhr Seite 54

51

The use of cortisone or 5-ASA preparations by themother is not a problem during nursing since onlynegligible amounts of these drugs enter thechild’s organism through the milk and no perma-nent harmful effects on the baby are known. Theuse of cortisone preparations should, however,be reduced as quickly as possible, both in preg-nant and non-pregnant patients. If high doses ofcortisone are required, careful follow-up of theinfant by a pediatrician is important. The use ofbudesonide during lactation has been addressedin this brochure on page 37.

If the use of immunomodulatory agents such asazathioprine, 6-mercaptopurine, methotrexate(MTX), cyclosporine, tacrolimus or infliximab isnecessary, the newborn should not be breast-fedsince the long-term effects and possible harm tothe baby cannot yet be predicted.

051854_Falk_S82e 29.07.2005 9:33 Uhr Seite 55

051854_Falk_S82e 29.07.2005 9:33 Uhr Seite 56

Further information for patients with

inflammatory bowel diseases:

– Ulcerative colitis and Crohn’s disease

An overview of the diseases and their treatment68 pages (S80e)

– Nutrition in inflammatory bowel diseases

55 pages (S84e)

– Crohn’s disease and its associated disorders

40 pages (S85e)

– Corticosteroid therapy in inflammatory bowel

diseases

28 pages (Bu80e)

These brochures can be orderedfree of charge from Falk Foundation e.V.or the local Falk partner.

FALK FOUNDATION e.V.Leinenweberstr. 5Postfach 652979041 FreiburgGermany


Leinenweberstr. 5Postfach 6529

Germany

FALK FOUNDATION e.V.

FOUNDATION e.V.


79041 Freiburg

S82e 9

–5/2

007/

3.00

0 B

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crohn’s disease, ulcerative colitis and pregnancy - dr. falk ...2007/09/05 · 9th edition 2007...

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