Download Pregnancy - Multidisciplinary Inflammatory Bowel Disease Clinic

Inflammatory Bowel Disease and Pregnancy
Inflammatory bowel disease (IBD) frequently affects young people in their
reproduc ve years, and can have a major impact on pa ents’ family planning
decisions. The majority of women with IBD can have healthy pregnancies and
healthy babies. One of the most important factors for having a healthy pregnancy
is to ensure that your IBD is well controlled both prior to becoming pregnant, as
well as throughout your pregnancy. It is important to discuss your plans for star ng
a family with your IBD doctor and team. The following informa on sheet will
answer some of the most commonly asked ques ons about pregnancy and IBD.
How does IBD affect Fer lity?
Many pa ents with IBD are concerned about how their disease can affect fer lity. An Australian study found that
43% of women with IBD were worried about infer lity.1 Fortunately, women with inac ve IBD, both Crohn’s disease
(CD) and ulcera ve coli s (UC), have fer lity rates similar to the general popula on. However, some women with
ac ve IBD, especially CD, can have decreased fer lity.
Does surgery have an impact on ferƟlity?
Women with UC who have had their colon removed and
had a pouch created (colectomy and ileal pouch‐anal
anastomosis (IPAA)) may have reduced fer lity.2,3 See the
pictogram to the right to see the risk of infer lity for the
general popula on, medically treated IBD, and a er IPAA.
If possible, women who are planning on having children
may want to consider alterna ve surgical procedures,
such as colectomy and the forma on of an ileostomy,
which does not affect fer lity, and wait un l a er child‐
birth to have the pouch surgery. Similarly, women with
CD that have had significant surgery in the pelvic region
may also have reduced fer lity. Women with IBD who are
having problems with infer lity should ask about a refer‐
ral to a fer lity specialist.
1
Do IBD medicaƟons have an impact on ferƟlity?
To date, IBD medica ons do not appear to impact fer lity in women.1 Men with IBD may have decreased fer lity
when taking sulfasalazine. Fer lity returns to normal within 3 months of stopping the medica ons and good alter‐
na ves, such as mesalazine, can be taken instead.4 Methotrexate can affect sperm produc on and quality, and
should be stopped 3‐6 months prior to concep on.5 Methotrexate should also be stopped in women considering
pregnancy due to an increased risk of birth defects.
What are the chances of my child having IBD?
Pa ents with IBD are slightly more likely to have a child with
IBD compared to parents without IBD, although the overall
risk is s ll quite low. If one parent has UC, the risk of their
child having IBD is 1.6%. If one parent has CD, the risk of
their child having IBD is 5.2%.6 Or, to put this in other terms,
less than 2 out of 100 children born to a parent with UC or 5
out of 100 children born to a parent with CD, will get IBD. If
both parents have IBD, the risk of their child developing IBD
in 36 out of 100, or 36%.7
How does pregnancy affect IBD?
The most important factor in predic ng how ac ve your IBD will be throughout pregnancy appears to be how
ac ve your disease is when you become pregnant. If you conceive during remission, rates of flare are similar to
rates for non‐pregnant pa ents. However, if you become pregnant when your disease is ac ve, your disease is
more likely to remain ac ve or get worse.8
Interes ngly, it appears that pregnancy may have a beneficial effect on the course of IBD, with a lower rate of
flares in the years a er pregnancy, compared to the years before pregnancy.8,9
What if I have a flare during pregnancy?
Most of the medica ons used to treat IBD are safe to use in pregnancy, but some are not. It is therefore very
important that you discuss your plans to become pregnant with your IBD team, and let them know as soon as
possible once you become pregnant. More details on the most common IBD drugs are given in the next sec on.
If you start to have symptoms of IBD during your pregnancy, let your IBD team know as soon as possible. Inves ‐
ga ons may need to be done to determine what is happening. Endoscopic procedures such as flexible sig‐
moidoscopy and colonoscopy are considered safe in pregnancy, but should only be done if clearly necessary, and
in the second trimester if possible. Elec ve procedures should be delayed un l a er delivery. MRI and ultra‐
sound are also considered safe, but other radiology tests that involve radia on, such as x‐rays, CT scans, and bari‐
um tests, should be avoided.10
2
How does IBD affect pregnancy?
The effect IBD has on pregnancy depends on whether the disease is ac ve or in remission. Current evidence indi‐
cates that well controlled disease has minimal impact on the course and outcome of pregnancy.11,12 However, it ap‐
pears that if a woman with ac ve IBD becomes pregnant, or if the disease flares in pregnancy, the risk for adverse
outcomes is higher. Several studies have shown that there is an increased risk of preterm delivery and low birth
weight babies in women with IBD, par cularly in pa ents who have had ac ve disease either at concep on, or
throughout their pregnancy.11‐13 The risk of congenital malforma ons may be slightly higher in children of mothers
with UC, although a number of other studies did not show any increased risk.12,14 As ac ve disease is associated
with increased risk of adverse outcomes in pregnancy, we therefore recommend, if possible, that women with IBD
who are considering becoming pregnant wait un l their disease is in remission.
Does IBD influence the route of delivery?
Women with IBD are more likely to have caesarean (C) sec ons compared to the general popula on.15,16 There are
only 2 situa ons where your gastroenterologist might recommend a C‐sec on: ac ve perianal disease (inac ve peri‐
anal disease does not require a C‐sec on), and in pa ents who have a pouch (IPAA). Although the route of delivery
was not found to influence whether there were complica ons with the pouch, the recommenda on is based on the
theore cal increased risk of incon nence from damage to the anal sphincter with a vaginal delivery.17
How do IBD medica ons affect pregnancy?
The decision whether to con nue taking medica ons for IBD during
pregnancy can be a difficult one. Most of the medica ons that are
used to treat IBD are considered safe in pregnancy. As complica ons
and adverse outcomes in pregnancy are usually associated with ac ve
disease, the benefits of keeping IBD in remission usually outweigh the
poten al risks. However, some medica ons should not be used in
pregnancy. It is therefore very important to review your medica ons
with your IBD team if you are pregnant, or if you are considering preg‐
nancy. Table 1 describes the Category System used by the Food and
Drug Administra on for drug safety during pregnancy. Details on the
most common IBD medica ons are given below and are summarized
in Table 2.
3
Table 1. US Food and Drug Administra on categories for drug safety during
FDA Category
Descrip on
A
Controlled human studies show no risk. Controlled studies in animals and women have shown no
risk to the fetus during the first trimester of pregnancy (and there is no evidence of risk in later
trimesters)
B
No evidence of risk in studies. Either animal studies have not demonstrated a fetal risk but there
are no controlled studies in pregnant women, OR, animal studies have shown an adverse effect
that was not confirmed in controlled studies in women in the first trimester (and there is no evi‐
dence of a risk in later trimesters)
C
Risk cannot be ruled out. Either there are no animal or human studies OR animal studies have
shown an adverse effect and there are no well controlled studies in humans AND the benefit from
the use of the drug in pregnant women may be acceptable despite its poten al risks
D
Posi ve evidence of risk. Posi ve evidence of human fetal risk, but the poten al benefits from the
use of the drug in pregnant women may be acceptable despite its poten al risks
X
Contraindicated in pregnancy. Studies in animals or humans have demonstrated fetal abnormali‐
es. The risk of the use of the drug in pregnant women clearly outweighs any possible benefit
Aminosalicylates (5‐ASAs)
5‐ASA medica ons are generally considered safe to use in pregnancy. All 5‐ASA formula ons available in
Canada are FDA category B drugs, except Asacol, which is a category C drug. The coa ng of Asacol contains
dibutyl phthalate (DBP). In animal studies, DBP was associated with abnormali es of the kidneys and genital
organs when given in doses greater than 80 mes the human dose. Your IBD team may therefore recommend
switching to a different 5‐ASA medica on if you are planning on becoming pregnant.
Sulfasalazine, is safe to use in pregnancy. However, it interferes with folate synthesis so increased supplemen‐
ta on with 2‐5 mg of folate per day is therefore recommended.
An bio cs
Metronidazole (Flagyl®), ciprofloxacin (Cipro®), and amoxicillin‐clavulanic acid (Clavulin®), are some of the an bi‐
o cs most frequently used in the treatment of IBD. Metronidazole and amoxicillin‐clavulanate are category B
medica ons and can be used during pregnancy. However, an bio cs use should be limited to short‐term use.
Ciprofloxacin is a category C drug. Although the overall risk is limited, animal studies have shown an increased
risk of musculoskeletal abnormali es, so use should be avoided during pregnancy.
4
Cor costeroids
Steroids (for example Prednisone®, Budesonide®) are category C
medica ons. Cor costeroid use in the first trimester has been
associated with a small increase in the risk of oral cle s (3.35
mes more likely).18 The magnitude of this risk is shown in the
adjacent pictogram. As the risk of steroid use is very small, and
the poten al benefits of trea ng a significant flare are great, ster‐
oids may be recommended to treat IBD flares throughout preg‐
nancy. If steroids are used near the me of delivery, your baby
will be monitored to make sure their adrenal glands (which make
natural steroid) are working properly. Much less is known regard‐
ing the safety of budesonide in pregnancy. Very small case series
have not shown any adverse events.19
Thiopurines
Thiopurines (Azathioprine/Imuran®, 6‐mercaptopurine) are category D medica ons. This designa on is from the
1960s when animal studies using extremely high doses of these medica ons showed adverse effects. However,
mul ple studies of IBD pa ents treated with thiopurines throughout pregnancy have not shown any increased risk
of congenital anomalies.20 Also, the risk of relapse is high when azathioprine is stopped, even in pa ents who are in
remission.21 For these reasons, 9 out of 10 experts recommend con nuing azathioprine throughout pregnancy.22
We do not recommend star ng thiopurines for the first me in pregnancy due to the delay in the onset of ac on,
and the risk of pancrea
s, which can be more serious in pregnancy.
Methotrexate
Methotrexate is contraindicated during pregnancy—category X. Methotrexate can remain in the body even a er it
is stopped. It should therefore be stopped 3‐6 months prior to a emp ng concep on.
Biologics
Infliximab (Remicade®) and adalimumab (Humira®) are category B medica ons. Both of these medica ons are an ‐
bodies, which are unlikely to cross the placenta in the first trimester, but very efficiently cross the placenta in the
late second and third trimesters.23 Two large safety studies have not shown any increased risk of fetal malfor‐
ma ons or neonatal complica ons with infliximab use in pregnancy compared to the general popula on.24,25 Less
data is available for adalimumab. However, small case series show that rates of congenital malforma ons and ad‐
verse pregnancy outcomes are similar in pa ents treated with adalimumab compared to IBD pa ents not receiving
adalimumab and the general popula on.26
We therefore recommend, that if possible (you are well, with no symptoms of ac ve disease), infliximab and ada‐
limumab be stopped in the late 2nd or early 3rd trimester. However, if there is evidence of ongoing ac ve disease,
it may be safer to con nue with an ‐TNF medica ons as ac ve IBD carries risks of adverse pregnancy outcomes.
These decisions can be difficult to make, and must be discussed in detail with you IBD team. Babies exposed to an ‐
TNFs during pregnancy should not receive any live vaccines (common ones are measles, mumps, rubella (MMR),
rotavirus, varicella zoster), un l at least 6 months of age.27
5
Table 2. IBD Medica ons and Risks During Pregnancy
Drug
Example
Safety
Recommenda ons
Sulfalazine
Low risk
Increase folate supplementa on to 2‐5mg
per day
Mesalamine
Low risk
Class B apart from Asacol® (Class C) ‐can
consider switching to different 5‐ASA
Metronidazole
Low risk
Safe for short term use
Amoxicillin‐
Clavulanic acid
Low risk
Safe for short term use
Ciprofloxacin
Avoid
Should be avoided (Class C)—poten al in‐
creased risk of joint problems (arthropathy)
Cor costeroids
Prednisone®,
Budesonide®
Low risk
Class C—very small increased risk of oral
cle with 1st trimester use. However, use
in trea ng IBD flare has significant benefits.
Thiopurines
Azathioprine,
6‐mercaptopurine
Low risk
Class D based on animal studies and human
studies for treatment of cancer. Studies in
IBD pa ents suggest low risk.
Methotrexate
Methotrexate
Contraindicated
Biological agents
Infliximab
low risk
Class
Aminosalicylates
An bio cs
Stop 3‐6 months prior to concep on
If possible, last dose in late 2nd or early 3rd
trimester
No live vaccines to infants un l a er 6
months of age
Adalimumab
low risk
Similar to infliximab
6
What are the recommenda ons for breas eeding and IBD?
In 2009‐2010, 87.3% of Canadian women who had a live birth ini ated
breas eeding, and 25.9% of women exclusively breas ed for 6 months.28
Although one large study found that women with IBD were less likely to
breas eed than women in the general popula on, a recent study from the
University of Manitoba showed similar rates in their IBD pa ents compared
to the general popula on.29,30 Breas eeding has many benefits for both
mother and child, and is recommended as the primary form of nutri on for
the first six months by Health Canada, the Canadian Paediatric Society, Die ‐
cians of Canada, and the Breas eeding Commi ee for Canada.31 For exam‐
ple, breast milk can help keep your infant healthy by protec ng them from
illness and it also promotes op mal brain development. In addi on,
breas eeding helps to develop and strengthen the bond between mother
and child. Breas eeding may also decrease the risk of developing IBD later
in life.32 Only certain IBD medica ons are absolutely contraindicated in
breas eeding (see Table 3).
Table 3. IBD Medica ons and Recommenda ons for Breas eeding
Medica on
Aminosalicylates
An bio cs
Recommenda on in Breas eeding
Compa ble. Reports of infant diarrhea.
Metronidazole—not recommended
Ciprofloxacin—probably compa ble
Amoxicillin/clavulanic acid—compa ble
Cor costeroids
Thiopurines
Methotrexate
An ‐TNFs
Compa ble
Low levels found in breast milk (<1% of maternal dose) and majority excret‐
ed in first 4 hours a er taking medica on.33,34 Breast feeding probably safe.
Can wait 4 hours between taking medica on and breas eeding to be safe.
Contraindicated
Limited human data, probably compa ble
7
What else should I do to prepare for pregnancy?
All women who are considering becoming pregnant should:

Avoid alcohol and smoking as they nega vely affect infant development.

Proper nutri on is a very important part of a healthy pregnancy.

Follow EaƟng Well with Canada’s Food Guide.

Take a maternal mul vitamin.

Limi ng caffeine to a maximum of 200 mg per day (about 1 cup of coffee).

In addi on, for women with IBD, supplementa on with 2‐5 mg of folic acid per day both
before and during pregnancy is recommended to help prevent neural tube defects.
Your IBD team can provide you with addi onal nutri onal advice for before, during and a er pregnancy.
References
1.
Moun field, R., Bampton, P., Prosser, R., Muller, K., & Andrews, J.M. Fear and Fer lity in inflammatory
bowel disease: a mismatch of percep on and reality affects family planning decisions. Inflamm Bowel Dis
2009;15:720‐725.
2.
Olsen, K.O., Joelsson, M., Laurberg, S., & Oresland, T. (1999). Fer lity a er ileal pouch‐anal anastomosis in
women with ulcera ve coli s. BriƟsh Journal of Surgery, 86, 493‐495.
3.
Cornish JA, Tan E, Teare J, et al. (2007). The effect of restora ve proctocolectomy on sexual func on, uri‐
nary func on, fer lity, pregnancy and delivery: a systema c review. Dis Colon Rectum, 50(8):1128‐38.
4.
Riley SA, Lecarpen er J, Mani V, et al. Sulphasalzaine induced seminal abnormali es in ulcera ve coli s:
results of a sesalazine subs tu on. Gut 1987;28:1008‐12.
5.
French AE, Koren G, Motherisk Team. Effect of methotrexate on male fer lity. Can Fam Physician
2003;49:577‐8.
6.
Yang H, McElree C, Roth M‐P, et al. Familial empirical risks for inflammatory bowel disease: differences be‐
tween Jews and non‐Jews. Gut 1993;34:517‐524.
7.
Bennet RA, Rubin PH, and Present DH. Frequency of inflammatory bowel disease in offspring of couples
both presen ng with inflammatory bowel disease. Gastroenterology 1991;100(6):1638‐43.
8.
Riis L, Vind I, Poli P, et al. A study in a European cohort of pa ents with inflammatory bowel disease. Am J
Gastroenterol 2006;101:1539‐45.
9.
Cas glione F, Pignata S, Morace F, et al. Effect of pregnancy on the clinical course of a cohort of women
with inflammatory bowel disease. Ital J Gastroenterol 1996;28:199‐204.
10.
Habal, F.M., & Huang, V.W. (2012). Review ar cle: a decision‐making algorithm for the management of
pregnancy in the inflammatory bowel disease pa ent. Alimentary Pharmacology and TherapeuƟcs, 35:
501‐515.
11.
Norgard B, Hundborg HH, Jacobsen BA, et al. Disease ac vity in pregnant women with Crohn’s disease and
birth outcomes: a regional Danish cohort study. Am J Gastroenterol 2007;102:1947‐54.
8
12.
Cornish J, Tan E, Teare J, et al. A meta‐analysis on the influence of inflammatory bowel disease on pregnan‐
cy. Gut 2007;56:830‐7.
13.
Morales M, Berney T, Jenny A, et al. Crohn’s disease as a risk factor for the outcome of pregnancy. Hepato‐
gastroenterology 2000;47:1595‐8.
14.
Vermeire S, Carbonnel F, Coulie P, et al. Management of inflammatory bowel disease in pregnancy. Journal
of Crohn’s and Coli s 2012;6:811‐823.
15.
Iinyckyji A, Blanchard JF, Rawsthorne P, Bernstein CN. Perianal Crohn’s disease and pregnancy: role of the
mode of delivery. Am J Gastroenterol 1999;94:3274‐8.
16.
Mahadevan U, Sandborn WJ, Li D‐K, et al. Pregnancy outcomes in women with inflammatory bowel dis‐
ease: a large community‐based study from Northern California. Gastroenterology 2007;133:1106‐12.
17.
Selinger CP, Leong RWL and Lal S. Pregnancy related issues in inflammatory bowel disease: evidence base
and pa ents’ perspec ve. World Journal of Gastroenterology 2012;18(21):2600‐2608.
18.
Park‐Wyllie L, Mazzo a P, Pastuszak A, et al. Birth defects a er maternal exposure to cor costeroids: pro‐
spec ve cohort study and meta‐analysis of epidemiological studies. Teratology 2000;62:385‐92.
19.
Beaulieu DB, Ananthakrishnan AN, Issa M, et al. Budesonide induc on and maintenance therapy for
Crohn’s disease during pregnancy. Inflamm Bowel Dis 2009;15:25‐8.
20.
Cleary BJ, Kallen B. Early pregnancy azathioprine use and pregnancy outcomes. Birth Defects Res A Clin Mol
Teratol 2009;85:647‐54.
21.
Treton X, Bouhnik , Mary J‐Y, et al. Azathioprine Withdrawal in pa ents with Crohn’s disease maintained on
prolonged remission: A high risk of relapse. Clin Gastro Hepatol 2009;7:80‐85.
22.
Peyrin‐Biroulet L, Oussalah A, Roblin X, Sparrow MP. The use of azathioprine in Crohn’s disease during
pregnancy and in the post‐opera ve se ng: a world wide survey of experts. Aliment Pharmacol Ther
2011;33:707‐13.
23.
Simister NE. Placental transport of immunoglobulin G. Vaccine 2003;104:228‐33.
24.
Lichtenstein GR, Feagan BG, Cohen RD, et al. Serious infec ons and mortality in associa on with therapies
for Crohn’s disease: TREAT registry. Clin Gastroenterol Hepatol 2006;4:621‐30.
25.
Katz JA, Antoni C, Keenan GF, et al. Outcome of pregnancy in women receiving infliximab for the treatment
of Crohn’s disease and rheumatoid arthri s. Am J Gastroenterol 2004;99:2385‐92.
26.
Chambers CD, Johnson DL, Jones KL. Adalimumab and pregnancy outcome: the OTIS autoimmune diseases
in pregnancy project. Am J Gastroenterol 2006;101:S421‐S422.
27.
Mahadevan U, Cucchiara S, Hyams JS, et al. The London Posi on Statement of the World Congress of Gas‐
troenterology on Biological therapy for IBD with the European Crohn’s and Coli s Organiza on: Pregnancy
and Pediatrics. Am J Gastroenterol 2011;106:214‐223.
28.
Public Health Agency of Canada. Perinatal Health Indicators for Canada 2011. O awa, 2012.
29.
Kane S, Lemieux N. The role of breas eeding in postpartum disease ac vity in women with inflammatory
bowel disease. Am J Gastroenterol 2005;100:102‐5.
9
30.
Moffat, D.C., Ilnyckyj, A., & Bernstein, C.N. (2009). A Popula on‐based study of breas eeding in inflamma‐
tory bowel disease: ini a on, dura on, and effect on disease in the postpartum period. The American
Journal of Gastroenterology, 104, 2517‐2523.
31.
Health Canada. Nutri on for Healthy Term Infants—A joint statement of Health Canada, Canadian Paediat‐
ric Society, Die cians of Canada and Breas eeding Commi ee for Canada. h p://www.hc‐sc.gc.ca/fn‐an/
nutri on/infant‐nourisson/recom/index‐eng.php (Accessed May 10, 2013).
32.
Klement E, Cohen RV, Boxman J, et al. Breas eeding and risk of inflammatory bowel disease: a systema c
review and meta‐analysis. Am J Clin Nutr 2004;80:1342‐52.
33.
Christensen LA, Dahlerup JF, Nielsen MJ. Azathioprine treatment during lacta on. Aliment Pharmacol Ther
2008;28:1209‐13.
34.
Saha, S & Wald, A. (2012). Safety and efficacy of immunomodulators and biologics during pregnancy and
lacta on for the treatment of inflammatory bowel disease. Expert Opin. Drug. Saf. , 11(6):947‐957.
Handout designed by Sharyle Fowler, MD and Megan Sander, MSc RD,
University of Saskatchewan. Reviewed by: Natasha Haskey MSc RD
and Jennifer Jones, MD, MSc, University of Saskatchewan. Funding
for this project provided by the Interprofessional Health Collabora ve
of Saskatchewan and the Saskatoon Health Region.
10