Fertility, Pregnancy and Nursingin Inflammatory Bowel Disease

Several questions arise in the care of patients with inflammatory bowel disease (IBD) who want to have children. The effect of the disease and its treatment on fertility and pregnancy and the safety of medications or diagnostic tests for pregnant or nursing women with IBD will review in this article.

 

Fertility

Most studies have demonstrated that men and women with IBD disease do not have decreased fertility compared to the general population. There was a reduction in birth weight among women with IBD observed in some studies which is likely secondary to patient choice rather than a consequence of disease-related infertility. However, infertility is observed in some circumstances.

 

Men have become impotent following proctocolectomy (an uncommon complication).

Men taking sulfasalazine, can reduce sperm motility, and cause abnormal shape of the sperm in more than 80 percent of patients that may affect fertility. Most of these effects are reversible within two months of discontinuing therapy. They do not occur with other 5-ASA drugs, such as Asacol, Pentasa, Dipentum, and Colazaal.

 

Decreased fertility has been reported in women with IBD who have undergone surgery (colectomy). Therefore, if a woman wishes to have children, we usually wait until the child-bearing age is complete before considering a colectomy.

 

Pregnancy and Obstetrical Complications

Ulcerative colitis: There are two main questions that need to be addressed in a pregnant woman with ulcerative colitis:

  1. Does pregnancy affect the activity of the disease?
  2. Does ulcerative colitis affect the outcome of pregnancy?

 

Effect on ulcerative colitis - The course of ulcerative colitis during pregnancy appears to be determined in part by the activity of the disease at conception. Patients in remission at the time of conception are likely to remain in remission during pregnancy. Approximately one-third of women relapse during the pregnancy (more common during the first trimester), which is similar to the rate observed over a nine-month period in non-pregnant women. Furthermore, remission achieved during pregnancy is likely to be sustained throughout the remainder of the pregnancy.

 

In contrast, disease that is active at the time of conception is likely to remain active during pregnancy and may worsen. As a result, women with ulcerative colitis who wish to be pregnant should try to conceive at a time when the disease is in remission.

 

Complications during pregnancy in women whose disease is active are similar to those in non-pregnant patients with ulcerative colitis. Fulminate colitis can be treated with a colectomy with subsequent delivery of a healthy infant, however, surgery may be associated with premature labor or spontaneous abortion.

 

In the postpartum period the course of ulcerative colitis is no different from that of other times.

 

Effect on the Pregnancy

In many studies the rate of delivery of healthy offspring in women with ulcerative colitis has been similar to the general population. However, there has also been reported a greater incidence of low-birth weight infants (less than 2,500 grams) was observed in mothers with ulcerative colitis than in controlled population in a large maternity facility. The risks of congenital abnormalities or stillbirth does not appear to be increased.

 

Crohn’s Disease

The same issues are important in Crohn’s disease (i.e. effect on the disease activity and effect on pregnancy).

 

Effect on Crohn’s Disease

Similar to ulcerative colitis, Crohn’s disease that is active at the time of conception is likely to remain active, and, conversely, disease that is quiescent or in remission is likely to remain quiescent. Complications related to Crohn’s disease occurring during pregnancy are similar to those in the non-pregnant patient. For example, fistulas may occur as well as abscess formation and obstruction.

 

A concern in patients with active perianal Crohn’s disease has been that vaginal delivery could worsen disease activity. Considering all of the available data and clinical experience, many obstetricians avoid creating an episiotomy and prefer a C-section in patients with active perianal disease because of the concern that a fistula will arise from the incision. In patients with quiescent disease, the mode of the delivery should be dictated by the obstetrical concerns.

 

Similar to ulcerative colitis the outcome of pregnancy patients with Crohn’s disease does not predict events during subsequent pregnancies.

 

Effect on the Pregnancy

Women with Crohn’s disease are at an increased risk for low-birth weight infants and premature delivery. The effect of Crohn’s disease on birth weight in these studies is similar to that observed in children whose mothers smoke moderately.

 

Although not specifically addressed, other studies have found that the risk of an abnormal pregnancy outcome in women with Crohn’s disease is greatest in those who have active disease at the time of conception, in whom remission may difficult to achieve during pregnancy.

 

Careful monitoring of fetal growth is advisable in women with Crohn’s disease who have become pregnant, particularly if the disease is active. Furthermore, conception should be attempted at the time when the disease is in remission if possible.

 

Safety of Evaluation During Pregnancy

A flexible sigmoidoscopy is safe during pregnancy. Colonoscopy has been performed during pregnancy without complications. However, experience is relative in women compared to sigmoidoscopy. We feel that a colonoscopy should generally be avoided unless the information is critical for making treatment decisions. X-rays should be avoided unless life-threatening situations justify the use.

 

Safety of Drugs During Pregnancy and Nursing

The choice of drugs used during pregnancy should be based upon their relative safety and indications.

 

Sulfasalazine – several decades of experience suggests that it is safe during pregnancy. Sulfasalazine and its metabolite can be found in the umbilical cord blood at similar concentrations to maternal blood. However, these the concentrations do not cause significant displacement of bilirubin from albumin. As a result sulfasalazine does not have to be stopped during breast feeding to prevent kernicterus.

 

Antibiotics – a number of studies have demonstrated that metronidazole (Flagyl) is not associated with an increased risk of birth defects or cancer in humans. However, long-term use in pregnancy remains controversial because of it is carcinogenic potential. Short-term courses are commonly given. In contrast, ciprofloxacin affects growing cartilage in animals and humans and can cause arthropathy, or joint, problems. As a result it is not recommended in children under age 18 or for pregnant women. Both of these antibiotics are excreted in to breast milk and thus nursing during administration is not recommended.

 

5-ASA drugs – experience with 5-ASA drugs during pregnancy and lactation is much more limited than for sulfasalazine, however, a growing body of information suggests that oral and topical 5-ASA are safe during pregnancy.

 

Corticosteroids – because of their importance in treatment of a variety of inflammatory conditions systemic corticosteroids have been used fairly extensively during pregnancy. The risk of steroids in this study appears to be small and generally agreed that they should not be withheld during pregnancy when they are clinically indicated.

 

Three potential areas of concerns have been raised:

 

Congenital malformations (primarily cleft palate), neonatal adrenal insufficiency, and low-birth weight. It should be noted that palatal closure is usually complete by the 12th week of pregnancy so the potential risk would be limited to administration during the first trimester. Neonatal adrenal insufficiency following maternal administration of steroids is unusual.

 

In a number of studies in women with IBD, there were no adverse affects on fetal outcome in mothers who took corticosteroids during pregnancy. Corticosteroids should be administered to pregnant women with IBD for the same indication as for non-pregnant patients. However, glucocorticoids have the potential for exacerbating pregnancy-induced hypertension, gestational diabetes, and pre-term delivery from premature rupture of membranes. Thus women at risk should be appropriately monitored. It also appears to be safe during breast feeding.

 

6-mercaptopurine and azathioprine – both 6-mercaptopurine and azathioprine cross the placenta and can be detected in cord blood. The largest experience with these drugs in pregnancy has been derived from patients in whom they were given for non-IBD indications such as a solid organ transplantation. These data combined with experience with IBD suggests that it is reasonable to continue these drugs during pregnancy in patient who can not be management with other types of therapy. Reports of teratogenicity with these drugs have occured in fetuses in whom exposure was either the mother or father. A small study suggests that males on 6-mercaptopurine should stop the agent three months before conception to lessen the risk of spontaneous abortion and fetal abnormalities. However, this is not etched in stone as other studies have shown just the opposite. Both of these drugs are detectable at low levels in breast milk. Mothers taking these drugs should be discouraged from nursing although no good data are available regarding the risk to the nursing infant.

 

Cyclcosporin – can be given successfully during pregnancy. Teratogenicity appears to be low but premature labor and small gestational age infants have been reported.

 

Methotrexate – use in pregnancy is associated with multiple skeletal abnormalities. Therefore, one should not use this in pregnancy. A patient should discontinue this drug and use contraception for at least three months prior to conception.

 

Infliximab - experience with infliximab (Remicade) during pregnancy is limited. No maternal toxicity or teratogenicity was observed in a mouse model conducted by the manufacturer. According to the manufacturer’s prescribing information, infliximab should be given to a pregnant woman only if clearly needed. We usually suggest staying off of infliximab six months prior to conception.

 

Antidiarrheal drugs – Lomotil and Imodium do not cause teratogenicity during pregnancy; however, case reports in humans suggest the potential of fetal malformations in infants exposed to Lomotil with atropine during the first trimester. As a result it is probably best to avoid the use, especially during pregnancy unless measures with bulking agents and dietary manipulations fail to control disabling diarrhea. These agents should also probably be avoided in women who are breast feeding since there is little information about the risk to nursing infants. As alternatives, kaopectum and psyllium (Metamucil) are safe during pregnancy

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