Aust NZ J Obstet Cynaecol 1992; 32: 1: 40
Inflammatory Bowel Disease Presenting in Pregnancy Mark R. Morton', FRACP Royal Adelaide Hospital, Adelaide, South Australia EDITORIAL COMMENT: We accepted this paper for publication because it reports an unusual case of ulcerative colitis occurring for the first time during pregnancy. In the discussion the author reviews the literature on ulcerative colitis and Crohn disease in pregnancy, these being the 2 important examples of inflammatory bowel disease encountered in pregnant women.
Summary: A case of inflammatory bowel disease (IBD) presenting in pregnancy is described. Despite previous reports of severe fulminating disease in this type of patient, this woman did well with an uncomplicated course; she responded to standard medical therapy and there were no fetal complications. IBD should not be a contraindication to pregnancy unless the disease is poorly controlled. Pregnancy does not increase the risk of relapse of IBD, but should this occur it is more likely in the first trimester or in the postpartum period. Treatment of IBD in pregnancy should be much the same as in the nonpregnant woman. Corticosteroids and sulphasalazine are safe in pregnancy and are the mainstays of medical treatment. Surgery should proceed for the usual indications of toxic megacolon and perforation. In the group requiring surgery fetal mortality is considerable but the maternal outcome is improving. Patients presenting with IBD in pregnancy may have more severe disease but recent reports suggest that the outcome for mother and infant in this group is improving. Inflammatory bowel disease (IBD) presenting in pregnancy is an unusual event (1). It is more common for the diagnosis of IBD to be known prior to the commencement of pregnancy. In the literature there is an impression that the onset of IBD in pregnancy is associated with a poor outcome for mother and fetus (2-7). Here is described a case of IBD presenting in pregnancy, treated with conventional medical therapy, with a good fetal and maternal outcome. The current literature on IBD in pregnancy is also reviewed.
Case report A 25-year-old woman was admitted to the Royal Adelaide Hospital in July, 1989, in the 18th week of pregnancy. She was a nonsmoker and had consumed no alcohol since becoming pregnant. She had a past history of a Caesarean section in 1988 for a breech presentation and a small pelvis. She took no regular medication. She presented with a 3-month history of colicky abdominal pain associated with small bowel actions. She subsequently developed 3 weeks of frequent bloody bowel actions, up to 10 per day. She had been anorexic with 3 kg of weight loss over 2 weeks. 1. Medical Registrar. Address for correspondence: Mark R. Morton, FRACP, Consultant Physician, Modbury Hospital, Smart Road, Modbury, South Australia.
Examination revealed a flushed unwell woman with a tachycardia of 120 beats per minute and a blood pressure of 110170. She was febrile with a temperature of 37.8 "C. Abdominal examination revealed generalized tenderness which was more marked in the left upper quadrant. There was an 18-week-sizeduterus palpable. Rectal examination revealed blood and mucus. Investigations revealed a haemoglobin value of 10.6g/dl, a white cell count of 12,20O/ul with 85% neutrophils and an ESR of 66mm/hr. Biochemical analysis showed an albumin of 28 g/l with normal liver enzymes and electrolytes. Several faecal specimens showed numerous inflammatory cells and no pathogenic organisms on culture. Clostridium deficile toxin was not detected. Sigmoidoscopy revealed a granular friable oedematous mucosa with mucopus. A rectal biopsy demonstrated a florid chronic colitis with expansion of the lamina propria by mononuclear inflammatory cells, loss of goblet cell populations, patchy neutrophilic cryptitis and several crypt abscesses. There were no granulomas demonstrated. The patient was initially commenced on intravenous hydrocortisone. There was a considerable improvement over the initial 24 hours with reduction of abdominal cramps and normalization of temperature. On the fourth hospital day she was changed to oral prednisolone. However, she continued to have 3 to 4 bloody bowel actions per day. On the eighth hospital day there was an increase in the number of bowel motions and
MARKR.MORTON
she was recommenced on intravenous hydrocortisone. Oral intake was ceased and she was commenced on total parenteral nutrition via a central venous catheter. The possibility of surgical intervention was raised but the patient remained systemically well with only a mild fever and no tachycardia. The patient continued to improve with only one bowel action per day. A flexible sigmoidoscopy was performed on the 13th hospital day which showed a major improvement. There was an erythematous mucosa but no blood or pus. Two days later the total parenteral nutrition was ceased and oral prednisolone introduced. She was discharged on the 18th hospital day on 60 mg of prednisolone a day and ‘Fefol’, one b.d. The haemoglobin value on discharge was 8.2 g/dl and ESR was 15 mm/hr. The prednisolone was reduced by 10 mg every 2 weeks and sulphasalazine commenced at 23 weeks’ gestation. An oral glucose tolerance test performed at 28 weeks’ gestation was normal, despite continued oral prednisolone. The prednisolone was ceased at 37 weeks’ gestation and sulphasalazine was continued at a dose of 1 g b.d. The rest of the pregnancy was uncomplicated. At 38 weeks’ gestation she had a spontaneous onset of labour with ruptured membranes. She had a normal vaginal delivery of a live female infant weighing 2,580 g (Just above the 10th percentile for gestational age). Apgar scores at 1 and 5 minutes were 7 and 9 respectively. The patient was given intravenous hydrocortisone during labour. She had an uneventful postpartum course and was discharged 6 days after delivery on sulphasalazine. DISCUSSION Abramson (2) proposed the following classification for inflammatory bowel disease (IBD) in pregnancy: Group 1 - IBD inactive at conception; Group 2 - IBD active at conception; Group 3 - IBD arising during gestation; Group 4 - IBD arising during the puerperium. This case would be classified into group 3. The number of cases in groups 3 and 4 is small, so definite conclusions are difficult to make.
Inflammatory Bowel Disease Presenting in Pregnancy It has been suggested that IBD presenting in pregnancy (Group 3) is more severe with a worse outcome for the fetus. Early reports suggested that patients were likely to be seriously ill when ulcerative colitis had its onset in pregnancy (2,4-7), with a maternal mortality rate in the region of 15% (7). The early series by Abramson (2) described 5 patients in group 3, and all had fulminant colitis with a mortality of 80%. This compared to a 0% mortality in groups 1 and 2. This was before the use of steroids in treatment. Martimbeau et a1 (3) reported 2 cases of Crohn disease presenting in pregnancy, and found 8 other cases in the literature to 1974. Eight of the 10 mothers required surgery and 6 of the 11 infants died. However, since that time there have been 6 cases reported of IBD presenting
41
in pregnancy (5,7-9). There were no perinatal or maternal deaths, but 4 mothers required surgery. This suggests that there have been improvements in medical and surgical therapy. The patient presented here had moderately severe disease at presentation but the diagnosis had been delayed many weeks. Despite this she eventually responded to conventional medical therapy and had an uncomplicated pregnancy and delivery. It seems that those patients presenting in pregnancy have more severe disease, often requiring surgery, although the numbers in the literature are small.
Effect of Inflammatory Bowel Disease on pregnancy Miller (1) reviewed the outcome of 1308 pregnancies in women with ulcerative colitis from 10 major series. The overall figures were similar to the general population with the average ulcerative colitis patient having an 85% chance of delivering a normal infant. Group 2 patients (disease active at conception) are more likely to have a spontaneous abortion or premature delivery than those in group 1. In 748 pregnancies with Crohn disease reviewed by Miller (1) the chances of a normal infant (83%) were again similar to the normal population. However, the presence of active IBD at the time of conception (group 2) doubled the chance of a spontaneous abortion (6). Two recent retrospective controlled studies of pregnancy complicated by IBD (10,ll) found statistically significant higher preterm delivery rates. In one of these studies (11) the risk of preterm delivery was higher in patients with Crohn disease. Exacerbations of IBD increased the risk of preterm delivery and the delivery of small for gestational age infants. The infant in this case was not (quite!) small for gestational age. The outlook for pregnancy in women with IBD is very favourable provided the disease is controlled and conception occurs when the IBD is quiescent. Fertility It is generally accepted that ulcerative colitis does not substantially alter fertility (1,4,6,12). In Crohn disease, however, fertility may be impaired. The frequency of pregnancy may be as low as 40 to 65% (6), although one group reported that only 11% of their patients with Crohn disease were involuntarily fertile (1). Factors contributing to subfertilitymay include tuba1 occlusion, nutritional deficiencies and the presence of active disease. Effect of pregnancy on Inflammatory Bowel Disease Approximately 30% of women whose ulcerative colitis is quiescent at the onset of pregnancy will have a relapse of their disease during the 9 months of pregnancy and the 3 months after delivery (1,6,12). This is similar to the risk of relapse in the nonpregnant population. Recurrence of disease tends to occur more frequently in the first trimester and the postpartum period (L4,W).
42
AUST. AND N.Z. JOURNAL OF OBSTETRICS
The risk of relapse of Crohn disease in pregnancy and the puerperium is 25 to 40% (1,4,12). Again this is similar to the nonpregnant patient and relapses are more likely in the first trimester and puerperium (1,4,6). In general, pregnancy does not influence the frequency or severity of attacks of IBD. Should relapses occur they are more likely in the first trimester or in the postpartum period.
Medical treatment in pregnancy Recent surveys indicate that the usual regimens of steroid therapy for IBD can be used in pregnancy (6,13). Studies in animals of large doses of steroids given early in pregnancy resulted in an increased incidence of cleft palate, stillbirths and fetal islet cell degeneration. However in humans few, if any, adverse effects have been demonstrated in human fetuses (13). Mogadam et a1 (13) reviewed 184 cases of IBD treated in pregnancy with steroids. No significant complication arose in the treated group when compared to the general pregnant population. Corticosteroids cross the placenta but cortisol is converted to the more inactive cortisone, and prednisolone levels in the fetal circulation are only 10-12% of those in the maternal circulation (1). However, this is sufficient to cause fetal hypothalamic-pituitaryadrenal suppression as is seen almost invariably when urinary oestriol excretion is measured in women after treatment with betamethasone for enhancement of fetal puImonary maturity. Despite this, clinically significant neonatal adrenal collapse is rare when prednisolone is given during pregnancy. Sulphasalazine comprises of 5 amino-salicylic acid (5ASA) linked to sulphapyridine by an azo bond. Sulphonamides have the potential to produce kernicterus by displacing bilirubin from albumin. Although sulphasalazine and sulphapyridine cross the placenta, the levels in cord blood cause negligible displacement of bilirubin (1,4,6,12). Hence, kernicterus is not a clinical problem. No firm evidence of harmful effects to the fetus has arisen (1,4,13) and it should be used for treatment of IBD in pregnancy as it is in the nonpregnant patient. It has been suggested that wathioprine exposure is sufficient reason for termination (12). Animal studies have shown a high incidence of fetal abnormalities and this has resulted in such recommendations. However, normal deliveries of mothers taking steroids and azathioprine have been reported in the renal transplant literature (14). The precise incidence of stillbirth is uncertain but the incidence of congenital abnormality did not exceed 4% (1). Azathioprine is probably best avoided in the pregnant patient with IBD unless other treatments have failed to control the disease. Where conception has occurred on the drug it is reasonable to proceed with the pregnancy. Surgery of Inflammatory Bowel Disease in pregnancy Those patients requiring surgery have severe disease and this is reflected by a worse fetal and maternal
AND
GYNAECOLOGY
outcome. Anderson et a1 (7) found 35 cases in the literature up to 1987. The overall fetal mortality rate was 53% and the maternal mortality rate was 29%. I have found only 1 such case reported since then (15), with a successful outcome for mother and infant. Indeed later reports of surgery for IBD in pregnancy have a much better maternal mortality rate. Of 8 reported cases of surgery for fulminant colitis in pregnancy since 1977 (5,7,8,15) there were no maternal deaths and 6 of the 8 infants survived. It is likely that better medical and surgical therapy has improved the outcome in this group. Certainly the indications for surgery should be the same as in the nonpregnant patient. It has been suggested that the poor fetal outcome may reflect the severity of the disease rather than the effects of the operation (7).
Acknowledgements I would like to thank Dr J Dent for his helpful comments on the manuscript. References 1. Miller JP. Inflammatory Bowel Disease in Pregnancy: A Review. J R SOCMed 1986; 79: 221-225. 2. Abramson D, Jankelson IR, Milner LR. Pregnancy in Idiopathic Ulcerative Colitis. Am J Obstet Gynecol 1951; 61: 121-128. 3. Martimbeau PW, Welch JS, Weiland LH. Crohn’s Disease and Pregnancy. Am J Obstet Gynecol 1975; 122: 746-749. 4. Vender RJ, Spiro HM. Inflammatory Bowel Disease and Pregnancy. J Clin Gastroenterol 1982; 4: 231-249. 5. Bohe MG, Ekelund GR, Gene11 SN et al. Surgery for Ulcerative Colitis During Pregnancy. Dis Col Rect 1983; 26: 119-122. 6. Donaldson RM. Management of Medical Problems in Pregnancy - Inflammatory Bowel Disease. N Engl J Med 1985; 312: 1616-1619. 7. Anderson JB, Turner OM, Williamson RCN. Fulminant Ulcerative Colitis in Late Pregnancy and The Puerperium. J R SOCMed 1987; 80: 492-494. 8. Cooksey G, Gunn A, Wotherspoon WC. Surgery for Acute Ulcerative Colitis and Toxic Megacolon During Pregnancy. Br J Surg 1985; 72: 547. 9. Porter RJ, Stirrat GM. The Effects of Inflammatory Bowel Disease on Pregnancy: A Case-Controlled RetrospectiveAnalysis. Brit J Obstet Gynaecol 1986; 93: 1124-1131. 10. Fedorkow DM, Persaud D, Nimrod CA. Inflammatory Bowel Disease: A Controlled Study of Late Pregnancy Outcome. Am J Obstet Gynecol 1989; 160: 998-1001. 11. Baird DD, Narendranathan M, Sandler RS. Increased Risk of Preterm Birth for Women with Inflammatory Bowel Disease. Gastroenterol 1990; 99: 987-994. 42. Sorokin JJ, Levine SM. Pregnancy and Inflammatory Bowel Disease: A Review of The Literature. Obstet Gynecol 1983; 62: 247-252. 13. Mogadam M, Dobbins WO, Korelitz BI et al. Pregnancy in Inflammatory Bowel Disease: Effect of Sulfasalazine and Corticosteroids on Fetal Outcome. Gastroenterol 1981; 8 0 72-76. 14. Registration Committee of the European Dialysis and Transplant Association. SuccessfulPregnanciesin Women Treated by Dialysis and Kidney Transplantation. Br J Obstet Gynaecol 1980; 87: 839-845. 15. Watson WJ, Gaines TE. Third-trimester Colectomy for Severe Ulcerative Colitis. A Case Report. J Reprod Med 1987; 32: 869-872.
Inflammatory Bowel Disease Presenting in Pregnancy Mark R. Morton', FRACP Royal Adelaide Hospital, Adelaide, South Australia EDITORIAL COMMENT: We accepted this paper for publication because it reports an unusual case of ulcerative colitis occurring for the first time during pregnancy. In the discussion the author reviews the literature on ulcerative colitis and Crohn disease in pregnancy, these being the 2 important examples of inflammatory bowel disease encountered in pregnant women.
Summary: A case of inflammatory bowel disease (IBD) presenting in pregnancy is described. Despite previous reports of severe fulminating disease in this type of patient, this woman did well with an uncomplicated course; she responded to standard medical therapy and there were no fetal complications. IBD should not be a contraindication to pregnancy unless the disease is poorly controlled. Pregnancy does not increase the risk of relapse of IBD, but should this occur it is more likely in the first trimester or in the postpartum period. Treatment of IBD in pregnancy should be much the same as in the nonpregnant woman. Corticosteroids and sulphasalazine are safe in pregnancy and are the mainstays of medical treatment. Surgery should proceed for the usual indications of toxic megacolon and perforation. In the group requiring surgery fetal mortality is considerable but the maternal outcome is improving. Patients presenting with IBD in pregnancy may have more severe disease but recent reports suggest that the outcome for mother and infant in this group is improving. Inflammatory bowel disease (IBD) presenting in pregnancy is an unusual event (1). It is more common for the diagnosis of IBD to be known prior to the commencement of pregnancy. In the literature there is an impression that the onset of IBD in pregnancy is associated with a poor outcome for mother and fetus (2-7). Here is described a case of IBD presenting in pregnancy, treated with conventional medical therapy, with a good fetal and maternal outcome. The current literature on IBD in pregnancy is also reviewed.
Case report A 25-year-old woman was admitted to the Royal Adelaide Hospital in July, 1989, in the 18th week of pregnancy. She was a nonsmoker and had consumed no alcohol since becoming pregnant. She had a past history of a Caesarean section in 1988 for a breech presentation and a small pelvis. She took no regular medication. She presented with a 3-month history of colicky abdominal pain associated with small bowel actions. She subsequently developed 3 weeks of frequent bloody bowel actions, up to 10 per day. She had been anorexic with 3 kg of weight loss over 2 weeks. 1. Medical Registrar. Address for correspondence: Mark R. Morton, FRACP, Consultant Physician, Modbury Hospital, Smart Road, Modbury, South Australia.
Examination revealed a flushed unwell woman with a tachycardia of 120 beats per minute and a blood pressure of 110170. She was febrile with a temperature of 37.8 "C. Abdominal examination revealed generalized tenderness which was more marked in the left upper quadrant. There was an 18-week-sizeduterus palpable. Rectal examination revealed blood and mucus. Investigations revealed a haemoglobin value of 10.6g/dl, a white cell count of 12,20O/ul with 85% neutrophils and an ESR of 66mm/hr. Biochemical analysis showed an albumin of 28 g/l with normal liver enzymes and electrolytes. Several faecal specimens showed numerous inflammatory cells and no pathogenic organisms on culture. Clostridium deficile toxin was not detected. Sigmoidoscopy revealed a granular friable oedematous mucosa with mucopus. A rectal biopsy demonstrated a florid chronic colitis with expansion of the lamina propria by mononuclear inflammatory cells, loss of goblet cell populations, patchy neutrophilic cryptitis and several crypt abscesses. There were no granulomas demonstrated. The patient was initially commenced on intravenous hydrocortisone. There was a considerable improvement over the initial 24 hours with reduction of abdominal cramps and normalization of temperature. On the fourth hospital day she was changed to oral prednisolone. However, she continued to have 3 to 4 bloody bowel actions per day. On the eighth hospital day there was an increase in the number of bowel motions and
MARKR.MORTON
she was recommenced on intravenous hydrocortisone. Oral intake was ceased and she was commenced on total parenteral nutrition via a central venous catheter. The possibility of surgical intervention was raised but the patient remained systemically well with only a mild fever and no tachycardia. The patient continued to improve with only one bowel action per day. A flexible sigmoidoscopy was performed on the 13th hospital day which showed a major improvement. There was an erythematous mucosa but no blood or pus. Two days later the total parenteral nutrition was ceased and oral prednisolone introduced. She was discharged on the 18th hospital day on 60 mg of prednisolone a day and ‘Fefol’, one b.d. The haemoglobin value on discharge was 8.2 g/dl and ESR was 15 mm/hr. The prednisolone was reduced by 10 mg every 2 weeks and sulphasalazine commenced at 23 weeks’ gestation. An oral glucose tolerance test performed at 28 weeks’ gestation was normal, despite continued oral prednisolone. The prednisolone was ceased at 37 weeks’ gestation and sulphasalazine was continued at a dose of 1 g b.d. The rest of the pregnancy was uncomplicated. At 38 weeks’ gestation she had a spontaneous onset of labour with ruptured membranes. She had a normal vaginal delivery of a live female infant weighing 2,580 g (Just above the 10th percentile for gestational age). Apgar scores at 1 and 5 minutes were 7 and 9 respectively. The patient was given intravenous hydrocortisone during labour. She had an uneventful postpartum course and was discharged 6 days after delivery on sulphasalazine. DISCUSSION Abramson (2) proposed the following classification for inflammatory bowel disease (IBD) in pregnancy: Group 1 - IBD inactive at conception; Group 2 - IBD active at conception; Group 3 - IBD arising during gestation; Group 4 - IBD arising during the puerperium. This case would be classified into group 3. The number of cases in groups 3 and 4 is small, so definite conclusions are difficult to make.
Inflammatory Bowel Disease Presenting in Pregnancy It has been suggested that IBD presenting in pregnancy (Group 3) is more severe with a worse outcome for the fetus. Early reports suggested that patients were likely to be seriously ill when ulcerative colitis had its onset in pregnancy (2,4-7), with a maternal mortality rate in the region of 15% (7). The early series by Abramson (2) described 5 patients in group 3, and all had fulminant colitis with a mortality of 80%. This compared to a 0% mortality in groups 1 and 2. This was before the use of steroids in treatment. Martimbeau et a1 (3) reported 2 cases of Crohn disease presenting in pregnancy, and found 8 other cases in the literature to 1974. Eight of the 10 mothers required surgery and 6 of the 11 infants died. However, since that time there have been 6 cases reported of IBD presenting
41
in pregnancy (5,7-9). There were no perinatal or maternal deaths, but 4 mothers required surgery. This suggests that there have been improvements in medical and surgical therapy. The patient presented here had moderately severe disease at presentation but the diagnosis had been delayed many weeks. Despite this she eventually responded to conventional medical therapy and had an uncomplicated pregnancy and delivery. It seems that those patients presenting in pregnancy have more severe disease, often requiring surgery, although the numbers in the literature are small.
Effect of Inflammatory Bowel Disease on pregnancy Miller (1) reviewed the outcome of 1308 pregnancies in women with ulcerative colitis from 10 major series. The overall figures were similar to the general population with the average ulcerative colitis patient having an 85% chance of delivering a normal infant. Group 2 patients (disease active at conception) are more likely to have a spontaneous abortion or premature delivery than those in group 1. In 748 pregnancies with Crohn disease reviewed by Miller (1) the chances of a normal infant (83%) were again similar to the normal population. However, the presence of active IBD at the time of conception (group 2) doubled the chance of a spontaneous abortion (6). Two recent retrospective controlled studies of pregnancy complicated by IBD (10,ll) found statistically significant higher preterm delivery rates. In one of these studies (11) the risk of preterm delivery was higher in patients with Crohn disease. Exacerbations of IBD increased the risk of preterm delivery and the delivery of small for gestational age infants. The infant in this case was not (quite!) small for gestational age. The outlook for pregnancy in women with IBD is very favourable provided the disease is controlled and conception occurs when the IBD is quiescent. Fertility It is generally accepted that ulcerative colitis does not substantially alter fertility (1,4,6,12). In Crohn disease, however, fertility may be impaired. The frequency of pregnancy may be as low as 40 to 65% (6), although one group reported that only 11% of their patients with Crohn disease were involuntarily fertile (1). Factors contributing to subfertilitymay include tuba1 occlusion, nutritional deficiencies and the presence of active disease. Effect of pregnancy on Inflammatory Bowel Disease Approximately 30% of women whose ulcerative colitis is quiescent at the onset of pregnancy will have a relapse of their disease during the 9 months of pregnancy and the 3 months after delivery (1,6,12). This is similar to the risk of relapse in the nonpregnant population. Recurrence of disease tends to occur more frequently in the first trimester and the postpartum period (L4,W).
42
AUST. AND N.Z. JOURNAL OF OBSTETRICS
The risk of relapse of Crohn disease in pregnancy and the puerperium is 25 to 40% (1,4,12). Again this is similar to the nonpregnant patient and relapses are more likely in the first trimester and puerperium (1,4,6). In general, pregnancy does not influence the frequency or severity of attacks of IBD. Should relapses occur they are more likely in the first trimester or in the postpartum period.
Medical treatment in pregnancy Recent surveys indicate that the usual regimens of steroid therapy for IBD can be used in pregnancy (6,13). Studies in animals of large doses of steroids given early in pregnancy resulted in an increased incidence of cleft palate, stillbirths and fetal islet cell degeneration. However in humans few, if any, adverse effects have been demonstrated in human fetuses (13). Mogadam et a1 (13) reviewed 184 cases of IBD treated in pregnancy with steroids. No significant complication arose in the treated group when compared to the general pregnant population. Corticosteroids cross the placenta but cortisol is converted to the more inactive cortisone, and prednisolone levels in the fetal circulation are only 10-12% of those in the maternal circulation (1). However, this is sufficient to cause fetal hypothalamic-pituitaryadrenal suppression as is seen almost invariably when urinary oestriol excretion is measured in women after treatment with betamethasone for enhancement of fetal puImonary maturity. Despite this, clinically significant neonatal adrenal collapse is rare when prednisolone is given during pregnancy. Sulphasalazine comprises of 5 amino-salicylic acid (5ASA) linked to sulphapyridine by an azo bond. Sulphonamides have the potential to produce kernicterus by displacing bilirubin from albumin. Although sulphasalazine and sulphapyridine cross the placenta, the levels in cord blood cause negligible displacement of bilirubin (1,4,6,12). Hence, kernicterus is not a clinical problem. No firm evidence of harmful effects to the fetus has arisen (1,4,13) and it should be used for treatment of IBD in pregnancy as it is in the nonpregnant patient. It has been suggested that wathioprine exposure is sufficient reason for termination (12). Animal studies have shown a high incidence of fetal abnormalities and this has resulted in such recommendations. However, normal deliveries of mothers taking steroids and azathioprine have been reported in the renal transplant literature (14). The precise incidence of stillbirth is uncertain but the incidence of congenital abnormality did not exceed 4% (1). Azathioprine is probably best avoided in the pregnant patient with IBD unless other treatments have failed to control the disease. Where conception has occurred on the drug it is reasonable to proceed with the pregnancy. Surgery of Inflammatory Bowel Disease in pregnancy Those patients requiring surgery have severe disease and this is reflected by a worse fetal and maternal
AND
GYNAECOLOGY
outcome. Anderson et a1 (7) found 35 cases in the literature up to 1987. The overall fetal mortality rate was 53% and the maternal mortality rate was 29%. I have found only 1 such case reported since then (15), with a successful outcome for mother and infant. Indeed later reports of surgery for IBD in pregnancy have a much better maternal mortality rate. Of 8 reported cases of surgery for fulminant colitis in pregnancy since 1977 (5,7,8,15) there were no maternal deaths and 6 of the 8 infants survived. It is likely that better medical and surgical therapy has improved the outcome in this group. Certainly the indications for surgery should be the same as in the nonpregnant patient. It has been suggested that the poor fetal outcome may reflect the severity of the disease rather than the effects of the operation (7).
Acknowledgements I would like to thank Dr J Dent for his helpful comments on the manuscript. References 1. Miller JP. Inflammatory Bowel Disease in Pregnancy: A Review. J R SOCMed 1986; 79: 221-225. 2. Abramson D, Jankelson IR, Milner LR. Pregnancy in Idiopathic Ulcerative Colitis. Am J Obstet Gynecol 1951; 61: 121-128. 3. Martimbeau PW, Welch JS, Weiland LH. Crohn’s Disease and Pregnancy. Am J Obstet Gynecol 1975; 122: 746-749. 4. Vender RJ, Spiro HM. Inflammatory Bowel Disease and Pregnancy. J Clin Gastroenterol 1982; 4: 231-249. 5. Bohe MG, Ekelund GR, Gene11 SN et al. Surgery for Ulcerative Colitis During Pregnancy. Dis Col Rect 1983; 26: 119-122. 6. Donaldson RM. Management of Medical Problems in Pregnancy - Inflammatory Bowel Disease. N Engl J Med 1985; 312: 1616-1619. 7. Anderson JB, Turner OM, Williamson RCN. Fulminant Ulcerative Colitis in Late Pregnancy and The Puerperium. J R SOCMed 1987; 80: 492-494. 8. Cooksey G, Gunn A, Wotherspoon WC. Surgery for Acute Ulcerative Colitis and Toxic Megacolon During Pregnancy. Br J Surg 1985; 72: 547. 9. Porter RJ, Stirrat GM. The Effects of Inflammatory Bowel Disease on Pregnancy: A Case-Controlled RetrospectiveAnalysis. Brit J Obstet Gynaecol 1986; 93: 1124-1131. 10. Fedorkow DM, Persaud D, Nimrod CA. Inflammatory Bowel Disease: A Controlled Study of Late Pregnancy Outcome. Am J Obstet Gynecol 1989; 160: 998-1001. 11. Baird DD, Narendranathan M, Sandler RS. Increased Risk of Preterm Birth for Women with Inflammatory Bowel Disease. Gastroenterol 1990; 99: 987-994. 42. Sorokin JJ, Levine SM. Pregnancy and Inflammatory Bowel Disease: A Review of The Literature. Obstet Gynecol 1983; 62: 247-252. 13. Mogadam M, Dobbins WO, Korelitz BI et al. Pregnancy in Inflammatory Bowel Disease: Effect of Sulfasalazine and Corticosteroids on Fetal Outcome. Gastroenterol 1981; 8 0 72-76. 14. Registration Committee of the European Dialysis and Transplant Association. SuccessfulPregnanciesin Women Treated by Dialysis and Kidney Transplantation. Br J Obstet Gynaecol 1980; 87: 839-845. 15. Watson WJ, Gaines TE. Third-trimester Colectomy for Severe Ulcerative Colitis. A Case Report. J Reprod Med 1987; 32: 869-872.
