Abstract
The IBD frequently affect women and men of childbearing age. Genetics seem to play a role in the development of IBD (CD more than UC). IBD does not affect fertility, however, infertility is higher after surgery due to adhesions and tubal block. Pregnancy should be planned during remission phase. Most medications used to treat active IBD are safe. The risks of not treating are greater than the risks of treating.
Ulcerative colitis (UC) and Crohn’s
disease (CD), collectively known as inflammatory bowel disease (IBD) demonstrate a bimodal age distribution with the first peak between the ages of 15 and 25 (childbearing age) and the second peak between ages 50 and 80. To advise the patient effectively, following factors should be considered:
- Inheritance pattern of IBD for counselling and family planning.
- Effect of active IBD, medications, surgery on fertility.
- The effect of pregnancy on the course of IBD.
- The effects and potential risks of active IBD, diagnostic tests, medical and surgical treatments on the developing foetus.
- Approach to delivery.
- The risk of breastfeeding while receiving treatment for IBD.
Inheritance
Twin studies have demonstrated very high concordance rate. The risk for UC and CD among offspring of patient with IBD is 2 to 13 times higher than that for the general population. IBD is more common among jews. Knowing the patients genotype may help predict the disease phenotype (structuring, perforating or fistulising, locations); the presence of extraintestinal manifastations; response to treatment and susceptibility to drug toxicity. Genetics does increase the susceptibility of developing IBD when exposed to the environmental triggers.
Fertility
In general, infertility rate in patients with IBD are similar to that of the general population, approximately 8% to 10%.
CD does not seem to affect fertility when the disease is inactive; however active disease does affect female fertility.
Medications used to treat IBD for the most part have no effect on fertility except for the well described effect of sulphasalazine on male fertility. Of 60% of men receiving sulphasalazine develop reversible, dose related decrease in sperm count and motility. When sulphasalazine is substituted by another 5ASA, sperm function improves in 2 month's time.
The effects of pregnancy on the course of IBD
The course of UC and CD during pregnancy tends to be similar to that in the non pregnant population if conception occurs at a time of disease inactivity.
About one third relapses during the pregnancy or puerperium. Relapse is more likely to occur in the first trimester. If the disease is active at the time of conception, two third, activity may persist or worsen. Physician strongly advise a couple to plan pregnancy during remission phase. The course of disease is aggressive in patients developing UC first time during pregnancy.
Nwokolo et al have shown that in CD, as parity increases, the need for surgical intervention decreases. Patients with history of pregnancy required fewer resections and interval between surgeries tend to be longer. Castiglione et al demonstrated lower relapse rates for both UC and CD after pregnancy when compared with that before pregnancy.
The effect of IBD on the course and outcome of pregnancy
UC and CD when inactive has little effect on the course of pregnancy. Poor course definitely leads to poor maternal health, premature labour and low birth weight. Active, non fulminant UC carries a combined abortion-still birth rate of 18% to 40%, whereas fulminant disease requiring surgery carries a corresponding rate of 60%. The risks seems to be related to disease activity rather than the medications used to treat the disease.
Diagnostic studies used to assess the pregnancy patient with IBD
Radiology studies
It is best to avoid ionizing radiation like plain films, barium and CT studies during pregnancy. Foetal risks of anomalies, growth retardation or abortion does not increase when the radiation exposure is less than 5 rads. There are no detrimental foetal effect of MRI. MRI should not be used during first trimester.
Gastrointestinal endoscopy
It is a good idea to refrain from endoscopic procedures during pregnancy, if there are clearly indicated or emergent, they should be performed.
Flexible sigmoidoscopy is safe. Upper GI endoscopy is also safe during pregnancy.
The effect of medications
It is best to achieve and maintain disease remission before conceiving.
Aminosalicylates
No detrimental effects are seen during pregnancy or nursing.
Antibiotics
The use of antibiotics in IBD is becoming increasingly more frequent not only for the treatment of recurrent infections, but also as first line therapy for CD. Metronidazole can be safely given for a short period. Quinolones, especially Ciprofloxacin is probably safe for sue during pregnancy, and is unlikely to pose a substantial teratogenic risk.
Other antibiotics used for management of CD like penicillins, cephalosporins and erythromycin can be safely used. Tetracyclines and sulphonamides should be avoided during pregnancy.
Corticosteroids
Corticosteroids are indicated for treatment of moderate to severe IBD. During pregnancy, corticosteroids cross the placental barrier but are rapidly converted to less active metabolites by placenta resulting in lower foetal blood levels. Rectal preparations can be used until the third trimester unless premature delivery is a concern.
There is no studies evaluating oral budesonide during pregnancy. It should theoretically be safer than other corticosteroids given the high first -pass effect.
Commonly used corticosteroids like prednisone and prednisolon result in very low breast milk concentration and are very safe for use during nursing. To minimize neonatal exposure, some advocate at least a 4-hour delay after oral dosing.
Azathioprine and 6-mercaptopurine
Azathioprine and 6-MP seem safe for use in pregnancy. Patients should not stop their medications before conception.
There is insufficient safety data on the use of 6MP and azathioprine during nursing.
Cyclosporine
Cyclosporine is indicated for moderate to severe UC as either a steroid sparing agent or as a means of avoiding surgery in severe steroid refractory cases. It is also effective in treating fistulising CD. The indications in pregnant patients are no different.
There is insufficient safety data on the use during nursing.
Tacrolimus
Data on the safety of this drug during pregnancy are very limited. Although it is rated as pregnancy category C by the FDA (risk can not be ruled out), the transplant literature shows that it seems to be safe.
Methotrexate
Methotrexate is contraindicated for use during pregnancy. If a couple is planning pregnancy, the prospective father should remain off methotrexate for at least 3 months and the prospective mother for at least 1 month.
Infliximab
Post marketing survey shows of 35 pregnancies (74.3%), 26 live birth; 5 (14.3%) miscarriages, 4 (11.4%) therapeutic termination. The FDA rates Remicade as pregnancy category B (no evidence of risk in humans).
Non specific symptomatic agents
For nausea of pregnancy, metoclopramide, Vitamin B6, ondensetron can be used safely. Antacids, H2 receptor antagonists, sucralfate and PPI are safe for use during pregnancy.
Musculoskeletal pain can be managed by paracetamol. Aspirin is better avoided for 10 days after delivery, as it can cause maternal and neonatal haemostatic abnormalities. Aspirin during pregnancy can cause prolonged gestations, prematurity, prolong labour and greater blood loss during labour.
Safest medications to control diarrhoea are those which are not absorbed like kaolin and pectin and bulking agent. Loperamide should be used cautiously. Diphenoxylate with atropine produces teratogenic effects.
The effect of IBD surgery on pregnancy
Performing surgery for IBD during pregnancy has about 50% rate of spontaneous abortions and still births. It is better to treat flares medically. Surgery should be reserved for emergent situations like fulminant colitis, toxic megacolon, perforation, obstruction or haemorrhage.
Approach to delivery
Patients with UC can expect normal vaginal delivery. Patients who have undergone surgery can also deliver vaginally.
Patients with active CD and perianal involvement should undergo elective caesarean. It is preferable to avoid episiotomy.
Sterling Hospital, Ahmedabad.
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