SummaryPrevious data suggests that infliximab is safe in pregnancy. In the past few years, infliximab has started to be used as rescue therapy for acute severe colitis, and the results are comparable to those of ciclosporin, but there are presently no reports of its use in this context during pregnancy. We report the case of a woman with a severe colitis flare during pregnancy which was treated with the anti-TNF-alpha inhibitor infliximab.
History and examinationA 35-year-old woman, with a 2-year history of left-sided ulcerative colitis (UC), was admitted with an acute severe exacerbation of colitis in the 25th week of pregnancy.
She had been admitted for 3 days earlier in her pregnancy (14/40), had responded well to intravenous steroids and was discharged for outpatient follow up on a reducing course of oral prednisolone and steroid enemas. In view of her improvement, other immunomodulators were not commenced at this point. Before the pregnancy her disease had been quiescent and she was on no other concomitant treatment as she had previously been intolerant of topical and systemic 5-ASAs.
On readmission the patient was opening her bowels 10 times per day with bloody diarrhoea. Her pulse rate was 100/min and she was apyrexial. There was no other obvious source of sepsis.
InvestigationsBlood results revealed CRP 42mg/l, Hb 9.6g/dl and platelets 416 x 109/l. Limited flexible sigmoidoscopy revealed moderately active UC and abdominal ultrasound showed a thickened bowel wall from the splenic flexure distally. Obstetric review and cardio-tocography indicated a viable, normally developing, fetus at this point.
Management and outcomeAfter 7 days there was little clinical response to intravenous hydrocortisone 100mg q.d.s. and her inflammatory markers remained elevated (CRP 39 mg/l).
Options for further management were hence discussed in detail with the patient and her partner including ciclosporin, surgery and infliximab. She favored infliximab and following further discussion also with the obstetrician, hospital pharmacy, and in agreement with the Local Ethics committee, she was given 3 infliximab infusions (5mg/kg) at 0, 2 and 6 weeks and was also started on azathioprine (2mg/kg).
Her symptoms improved gradually over the following 6 weeks and her bowel frequency dropped to 1-2/day, but her inflammatory markers remained elevated (CRP 69 mg/l, platelets 518 x 109/l at week 31/40). A repeat ultrasound continued to show moderate thickening in the bowel wall from the proximal transverse colon to the distal sigmoid, and power Doppler showed ongoing moderate to marked increase in vascularity in this area. Full examination and a septic screen were negative, although a high vaginal swab grew β-hemolytic Streptococcus which was thought to be insignificant as this is a common part of the normal flora of the female genital tract. Ultrasound at 29/40 revealed a normally developing fetus with no evidence of in utero growth retardation. Cardio-tocography and obstetric assessments at 29/40 and 32/40 were normal.
Sadly, at 34/40 she was admitted with contractions and a scan revealed intrauterine death. Significant growth retardation of the fetus since the previous ultrasound scan had occurred. The patient declined post-mortem. The cause of foetal death was considered to be either placental abruption, based on histological assessment of the placenta, or intrauterine infection.
DiscussionThe evidence thus far suggests that infliximab poses a low risk in pregnancy in patients with inflammatory bowel disease. TREAT (Crohn's Therapy, Resource, Evaluation, Assessment Tool) is a prospective registry of Crohn's patients, in which 66 pregnancies were reported, with 36 exposed to infliximab . No significant difference in the rates of miscarriage, neonatal complications or foetal malformation were observed between the infliximab-treated and non-treated group.
The Infliximab Safety Database contains retrospective data on 96 women with exposure to infliximab before or during pregnancy and the outcomes among these women were similar to those expected for the general population .
A recent small retrospective study also looked at the effects of infliximab on foetal outcome in ten women with Crohn's disease treated during pregnancy . Three infants were premature and one had low birth weight but there were no cases of IUGR or IUD.
In the past few years, infliximab has started to be used as rescue therapy for acute colitis, and the results are comparable to those of ciclosporin [4, 5], but there are presently no reports of its use in this context during pregnancy.
Clearly, in this case, the exact cause of intrauterine death is uncertain, but high-dose steroids are known to cause premature rupture of the membranes  and acute severe disease in itself may be associated with fetal growth retardation [7, 8].
If the cause of fetal demise was related to intrauterine infection, then probably all of the immunosuppressive agents used in this case may have played a part. The role of infliximab in the fetal death is unclear, but, in view of the limited data currently available, we advise thoughtful consideration before using infliximab for acute colitis in pregnancy.
This article was first published on GastroHep.com on 8 June 2008.
AuthorsR B Palmer
SpR Gastroenterology, Dept of Gastroenterology, St Georges Hospital, London SW17 0QT, UK
A P Poullis
Consultant Gastroenterologist, St Georges Hospital, London SW17 0QT, UK
R C G Pollok Consultant Gastroenterologist, St George's Hospital, London SW17 0QT. UK
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