Data was collected for 130 pregnancies; (UC: 75/130 [57.7%], CD: 54/130 [41.5%] and IBD-U in one patient). Baseline demographics and IBD characteristics are set out in Table 1. All pregnancies were singleton except for one; this pregnancy resulted in the live birth of one neonate after fetal loss of the twin at eight weeks’ gestation. Mean duration of IBD diagnosis at the time of delivery was 7.1 ± 5.5 years (CD 9.4 ± 5.9; UC 5.3 ± 4.3; p =  < 0.01). Nine women (6.9%) had a previous ileocecal resection and three (2.3%) had a previous hemicolectomy for Crohn’s disease. Four patients had a previous sub-total colectomy (3.1%; 3/54 [5.6%] for CD and 1/75 [1.3%] for UC). There were no patients with ileal pouch-anal anastomosis (IPAA). Five patients (3.8%) had an ileostomy. Disease phenotype in UC was available for 74/75 patients; proctitis/E1 (22 [29.7%]), left-sided/E2 (25 [33.8%]) and extensive/E3 disease (27 [36.5%]). With Crohn’s disease, 16 (29.5%) had isolated colonic disease and 29 (53.7%) had ileo-colonic disease. Most Crohn’s patients (37 [68.5%]) had non-stricturing, non-penetrating disease. Seven women (13%) had perianal CD (Table 1).

There was no statistical association between BMI, age at delivery, smoking status and the outcomes of congenital anomalies (p = 0.5018, p = 0.0819, p = 0.9341), LBW (p = 0.4494, p = 0.3609, p = 0.8633), SGA (p = 0.2365, p = 0.3692, p = 0.6647), neonatal infections (p = 0.1455, p = 0.3910, p = 0.9583), emergency CS (p = 0.4991, p = 0.7949, p = 0.4631) and preterm birth (p = 0.5345, p = 0.5573, p = 0.9316).

The mean BMI at conception was 26.1 ± 5.8 kg/m2 and mean maternal age at delivery was 30.5 ± 4.7 years; comparable for both CD and UC (p = 0.01 and p = 0.87 respectively). Active smoking was more frequent with CD than UC (11/54 [20.4%] vs. 3/75 [4%]) and a past history of smoking was also more frequent with CD (12/54 [22.2%] vs. UC 7/75 [9.3%], p =  < 0.01). Forty-nine women (38%) were nulliparous, 45 (34.9%) were primiparous and 36 (27.9%) were multiparous.

Active follow-up with an IBD specialist was in place at conception in 120/130 (92.3%) and 91/120 patients had been reviewed within six months prior to conception. Prior to conception, a documented discussion had taken place about family planning and optimal disease control for conception in 24/120 patients (20%). All 130 patients were actively under follow-up by IBD team during their pregnancy. During pregnancy, all women were under routine midwife review, in accordance with standard UK antenatal care. Additionally, 92/130 (70.8%) were also under obstetric review. The mean number of reviews by the IBD team during pregnancy was 2.3 (± 1.7). There was documented communication between the obstetric and IBD team in 59/130 cases (45.4%) although the record of clinical assessment is electronically available to clinicians caring for patients across specialities. Advice regarding the importance of inducing and maintaining remission and advice regarding IBD medications in pregnancy was documented in 75/130 cases (57.7%).

IBD activity, stratified by diagnosis and trimester, is summarized in Table 2. Overall, 73/130 (56.2%; CD 34/54, [63%]; UC 39/75, [52%]) were in clinical remission at the time of conception and 49/130 had mild-moderate disease activity at conception, based on physician global assessment (37.8%; CD 19/54 [35.2%]; UC 29/75 [38.7%], IBD-U 1/1). There were no patients with severe disease activity at the time of conception and data was not available for the pre-conception period in 8/130 women. Of patients in clinical remission at the time of conception, 15/73 developed mild-moderate disease activity during pregnancy and one patient, with UC, developed severe disease activity.

Overall, 49/130 (37.7%) patients had mild-moderate disease at the time of conception. There was higher disease activity during pregnancy in this group, with 35/45 (77.8%) continuing to experience mild-moderate disease (CD = 10, UC = 25) and 4/45 (8.9%) with severe activity (CD = 2, UC = 2). Six women (4.6%, UC = 5, CD = 1) had an IBD-related hospital admission during pregnancy. Four of the UC patients were admitted for a flare, one for campylobacter-positive diarrhea and one for PR bleeding, resulting in early CS. The CD patient had two admissions for flares at 10/40 and 13/40.

Data on bio-chemical markers were available for a limited number of women during pregnancy. Mean CRP within two months prior to conception was 6.1 ± 9.6 mg/L (n = 59). The mean CRP during the T1, T2, T3 was 7.89 ± 17 mg/L (n = 49), 11.7 ± 21.1 mg/L (n = 48) and 11.4 ± 19.7 mg/L (n = 54), respectively. Mean FC within two months pre-conception was 255 ± 276.9 µg/g (n = 13). Mean FC in the T1, T2, T3 was 635 ± 754.6 µg/g, 442.6 ± 737.3 µg/g and 495.3 ± 528.1 µg/g, respectively.

Table 3 provides an overview of the IBD medications used in each trimester of pregnancy. Over ¾ of the cohort (102/130) were on IBD medication during pregnancy. Seventy-eight women (60%) were on 5-ASA therapy at conception, falling to 73 (56.2%) in T1, based on physician discretion. Twenty-five women were on a thiopurine at conception (azathioprine n = 23, 6-mercaptopurine n = 2) and a majority (18/25) continued a thiopurine throughout pregnancy. Eight patients were taking systemic corticosteroids at conception, while 26 were prescribed ≥ 1 course of corticosteroids (prednisolone n = 23, budesonide n = 3) during pregnancy.

There were 26 patients on no therapy at all at the time of conception (CD = 13; UC = 13). Of the patients with Crohns, seven were in remission at conception and five had mild disease activity. There was insufficient data to allow PGA of disease activity for one patient. Eleven of these patients requires no therapy in pregnancy; two received steroids. A further two patients with mild disease activity on 5-ASA at conception had their 5-ASA stopped at conception and required no IBD therapies in pregnancy, including steroids. Of the 13 patients not requiring any therapy in pregnancy, there was one preterm delivery at 36 weeks’ gestation due to active CD in the setting of past perianal disease, two instances of minor congenital anomalies (camptodactyly and talipes) and one incidence of both SGA and LBW in a single infant. There were four episodes of neonatal infection (three non-serious, one serious) and three women experiencing IBD complications within 30 days post partum.

Of the 13 patients with UC not on therapy at conception, PGA assessment, possible for 10 of these at conception, concluded four had mildly active disease, two moderate and four were in remission. Six patients completed pregnancy without IBD therapy and seven received 5-ASA only during pregnancy. An additional fourwomen elected to stop their 5-ASA after a positive pregnancy test. Of these 10 patients not on therapy throughout the remainder of pregnancy, none required steroids either. There was one pre-term delivery at 35 weeks by elective CS due to a complex surgical history and the wish to avoid sphincteric injury due to planned future IPAA surgery. There was one incidence of LBW and SGA in a term infant, no congenital anomalies, one instance of neonatal infection (non-serious) and two instances of maternal IBD complications within 30 days post partum.

Twenty-four patients (18.4%) were on biologic therapy at conception; 13 (10%) on adalimumab, 10 (7.7%) on infliximab and one (0.8%) on ustekinumab. Five of these patients had UC (infliximab n = 2; adalimumab n = 3) and 19 had CD (infliximab n = 8; adalimumab n = 10; ustekinumab n = 1). One patient commenced infliximab therapy in T2. Eight patients were on a combined biologic and immunomodulator; one patient with UC on infliximab with azathioprine and seven patients with CD on anti-TNF therapy with either azathioprine (n = 6) or mercaptopurine (n = 1). All but one maintained combined therapy throughout pregnancy; this patient chose to stop their azathioprine after a positive pregnancy test. One patient on combined therapy received prednisolone in T2 and T3 for UC; there was otherwise no steroid exposure in these patients.

One patient on ustekinumab at conception was switched to adalimumab in T1 due to non-response. There was documentation of discussion between clinician and patients regarding the risks and benefits of continuing or stopping biologic therapy in T3 in 23/24 patients (95.8%). Seventeen patients discontinued biologic therapy during pregnancy; sixteen on the advice of the IBD team in T3 to limit placental drug transfer and one patient stopped therapy unilaterally in early pregnancy. Statistical analysis and comparison of patients who either continued or stopped anti-TNF therapy in T3 is described in Supplementary Table D.

Table 4 summarizes the data on last dose of biologic administered during pregnancy. There was inadequate data on the timing of the last biologic dose prior to delivery for four patients on adalimumab, possibly due to patient self-administration of drug. All patients continued biologic treatment throughout T1 and T2, except one patient on adalimumab discontinuing the drug early in pregnancy out of personal choice. Last dose of biologic therapy was given at mean gestational age of 28 weeks and biologics were restarted post partum at median 57.5 days.