The research was conducted as a single-center retrospective cohort study. We reviewed the medical records of all female patients with IBD who had been treated and followed up by the Kyoto University Hospital between May 2005 and May 2015. A total of 170 female patients with IBD (46 with CD and 124 with UC) were enrolled. Of the 170 female IBD patients, we identified 19 patients (five with CD and 14 with UC) who had become pregnant with a total of 23 pregnancies over the study period. Of the 19 patients, 18 had become pregnant after being diagnosed with IBD and were treated with probiotics, 5-ASA, or infliximab (IFX) when the pregnancy was confirmed. Only one patient had developed UC newly after pregnancy. Moreover, all the patients were treated with probiotics, 5-ASA, prednisolone (PSL), cytapheresis, or IFX throughout the gestation. This retrospective single-center study was conducted in accordance with the principles of the Declaration of Helsinki, and was reviewed and approved by the Institutional Review Board of Kyoto University Hospital.

The following data were collected: (1) the maternal variables, (2) the IBD treatment type, (3) the disease activity, (4) the pregnancy outcome, and (5) the mode of delivery. The maternal variables included the age at conception, the number of previous pregnancies, and details of the underlying IBD. The therapeutic regimen and disease activity were recorded at conception and every third month thereafter. To evaluate the disease activity, the Simple Clinical Colitis Activity Index (SCCAI)5 was used for UC patients, and Harvey & Bradshaw's activity index (HBI)6 was used for CD patients. Each trimester, we classified the disease activity into two categories: remission (SCCAI ≤3 and HBI ≤5) or active disease.7

We identified 23 pregnancies in 19 patients with IBD (four patients experienced two pregnancies) between May 2005 and May 2015. All the patients had become pregnant during clinical remission (CR). The maternal variables are shown in Table 1. The mean age of the 23 patients at pregnancy was 32.9 years (range, 27–43 years). Among the 14 patients with UC, five had pancolitis, seven had left-sided colitis, one had proctitis, and one had proctosigmoiditis. Of the five patients with CD, two presented small bowel involvement, and three presented small bowel and colon involvement. Four CD cases and one UC case had a history of intestinal surgery before becoming pregnant. Four UC cases and four CD cases had a history of one previous delivery.

The mean gestation at delivery was 38.8 weeks (range, 30–41 weeks). Case 10 required an emergency Caesarean section due to placental dysfunction caused by gestational hypertension, and delivered preterm despite maintaining CR throughout the pregnancy. Although a very low-birth-weight infant was born as a result, no congenital malformations were found. Five other cases also required Caesarean sections for the following reasons: a history of uterine myomectomy in case 1, breech presentation in cases 9 and 13, fetal distress in case 16, and a history of previous Caesarean section in case 17. The remaining 17 cases gave birth by spontaneous vaginal delivery. Although case 20 had a history of anal lesion treated with a seton placement, she was able to give birth by spontaneous vaginal delivery. The median neonatal birth weight was 2,992 g (range, 1,174–3,790 g). All of the infants, except for those in cases 10 and 16, were over 2,500 g. Although the disease activity in the mother had been well controlled with 3,000 mg 5-ASA/day, and despite being full-term, the infant in case 16 was under 2,500 g. No congenital malformation was observed in any of the infants. Moreover, none of the patients followed throughout the observational period had a miscarriage (Table 2).

In the first trimester, 22 of the 23 cases maintained CR. The remaining case (case 15) developed UC newly during the first trimester and showed mild disease activity. Of the 23 cases, 12 were treated with 5-ASA, four with 5-ASA and IFX, one with IFX, and six with probiotics. The strain of probiotics used in the three UC cases (cases 7, 13, and 15) was Bifidobacterium bifidum (Biofermin tablets). Among the three cases that received probiotics as a maintenance therapy, cases 7 and 13 had been treated with thiopurines in addition to probiotics before pregnancy, as they were allergic to 5-ASA. However, they stopped taking thiopurines after finding out about their pregnancy, as they feared the drug's potential side effects on the fetus. Therefore, they received probiotics alone throughout the pregnancy. Despite her mild disease activity, case 15 was treated with probiotics due to her allergy to 5-ASA. As patient 19 had undergone bowel resection in 2003, before immunomodulators and anti-tumor necrosis factor (anti-TNF) agents had been approved for the treatment of CD in Japan, she had been treated with an elemental diet, 5-ASA, and probiotics after the surgery. She had remained in remission without either immunomodulators or anti-TNF agents. Fortunately, remission was maintained with probiotics alone after she stopped her elemental diet and the 5-ASA, and she experienced two pregnancies without trouble.

In the second trimester, the disease flared up in four of the 23 cases (1, 9, 11, and 15), calling for intensification of the patients' treatments. CR was achieved by weekly cytapheresis in case 1. In case 9, both cytapheresis and 20 mg PSL/day were used. CR was achieved with an escalating dose of 5-ASA from 2,000 mg/day to 4,000 mg/day in case 11, and by induction treatment with 25 mg PSL/day in case 15.

In the third trimester, case 8 experienced a flare-up. An increased dose of IFX from 7.5 mg/kg to 10 mg/kg every 4 weeks improved her symptoms, resulting in the delivery of a healthy baby. In all cases except for those in which the disease flared up, the therapeutic regimen was not changed throughout the pregnancy. For the cases treated with 5-ASA, the mean dose of 5-ASA was 2,769 mg/day (range, 2,000–4,000 mg/day). None of the pregnant patients was treated with thiopurine or calcineurin inhibitors (Table 3).