Plant-based diet for pregnant women with inflammatory bowel disease: case series

Introduction

Inflammatory bowel disease (IBD) was initially a disease seen primarily in western countries, but it became a global one since around the turning of the 21st century (1,2). It occurs in genetically susceptible individuals due to an environmental factor(s). But there has not been a widely appreciated ubiquitous environmental factor. Our prior research has suggested a strong association between a westernized diet and IBD (3). A westernized diet is characterized by increased consumption of animal fat, animal protein, and sugar with decreased consumption of carbohydrates (3). Therefore, we advise all newly diagnosed patients to be admitted and to experience a plant-based diet (PBD) (lacto-ovo-vegetarian diet) to counter omnivorous western diets (4). Outcomes of our modality incorporating PBD surpassed current standards in both ulcerative colitis (UC) and Crohn’s disease (CD) in both the induction and quiescent phases (4-9). Based on our outcomes together with recent findings in epidemiology, nutrition, microbiology, immunology, and multi-omics studies, we were the first to recommend PBD for IBD in the literature (6-9).

Because the peak incidence of IBD coincides with the reproductive years, specific attention has been paid to pregnancy. Pregnancy per se does not increase the relapse rate in IBD. In UC, the relapse rate per year in patients with and without pregnancy was 34% and 32%, respectively (10). Pregnancy-related adverse events (still birth, preterm birth, small for gestational age, low birth weight, congenital abnormalities, cesarean section) are found more often in pregnancy with IBD than in pregnancy without IBD (11). Activity of IBD increases the risk of maternal and fetal complications such as spontaneous abortion, prematurity, developmental defects, and still birth (12). Because conception in the active phase of IBD causes a significantly higher risk of adverse events of pregnancy than that in remission (13), conception in the quiescent phase is recommended (14,15).

As for diet, a well-balanced, healthy diet is described (15). Even balanced meals could not prevent relapse of CD (4,7-9). To our knowledge, there are no other reports in the literature of pregnant women with IBD treated with a modality incorporating PBD. Therefore, this is the first report focusing on the effect of PBD in pregnant women with IBD. We present this article in accordance with the AME Case Series reporting checklist (available at https://tgh.amegroups.com/article/view/10.21037/tgh-23-67/rc).

Case presentation

Protocol of this study was approved by the Ethical Committee of Nakadori General Hospital and by the Ethical Committee of Akita City Hospital (Protocol number: 19-2003, 12-2013, 15-2015). All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patients for the publication of this case series and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Cases were prospectively studied. There were eight consecutive pregnant cases with IBD (UC =7 and CD =1) provided with PBD between 2004 and 2020 in Akita City Hospital and Nakadori General Hospital. There were 10 pregnancies in these cases. Patients with mild UC or UC in remission who did not need immediate treatment were advised to be admitted at a convenient time, e.g., seasonal holidays. We call this educational hospitalization (9). All inpatients including conventional hospitalization, were provided with educational material on lifestyle diseases, pathogenesis of IBD, healthy lifestyle habits (16), and PBD. At the end of the hospitalization, a qualified dietitian gave dietary guidance to the patient. Patients were advised to continue with the PBD after discharge. Patients were followed up as long as possible.

PBD was a lacto-ovo-vegetarian diet that allowed consumption of fish once a week and meat every other week (4). The details of PBD were previously described (4). Using a food-frequency questionnaire, we developed a simple way to evaluate adherence to the PBD for Japanese patients with IBD (17). A higher PBD score (PBDS) indicates a greater adherence to PBD. The score of PBD during hospitalization was 35. The PBDS was evaluated on admission (baseline PBDS) and again within and beyond 2 years after discharge, referred to as short-term and long-term PBDS, respectively (5,9).

Table 1 shows five active cases during pregnancy, and Table 2 shows the other five cases who experienced the diet before pregnancy, and then conceived after an interval from 9 months to 8 years. Two cases were duplicates. Both tables show the demographics of cases including ages, phenotypes and severity of IBD (18), treatment (19) and outcome of IBD, and outcomes of pregnancy. Five of the eight cases (Cases 3, 4, and 6–8) were included in previous interventional studies without reproductive matters (7,9). Two cases (Cases 2 and 5) developed UC during pregnancy and in the postpartum period, respectively, namely pregnancy-onset UC (PO-UC) (20). These two cases were separately reported as case reports (21,22).

In this case series, there were five cases of educational hospitalization (Tables 1,2). Apart from patients already on medication prescribed by their previous doctor (Cases 5–7), PBD was provided without medication during an educational hospitalization in Cases 1 and 2. The PBD without medication induced remission in these two mild cases. In this case series, remission was defined as the disappearance of active symptoms in both diseases (7,9). Infliximab and the PBD induced remission in a relapse case of CD (Case 4) (Table 1). There were six conceptions during remission without medication in four cases of UC. No cases relapsed during pregnancy in these cases (Table 2). Vaginal, cesarean, and vacuum extraction delivery were performed in four, four, and two deliveries, respectively. Three pregnancies in two cases were preterm delivery (Table 2). There were 10 live births in the eight cases. Two new-born babies from a mother (Case 7) had neonatal jaundice (Table 2).

In the median follow-up period of 71 months after the 1st hospitalization experiencing PBD, all eight cases were in the quiescent phase (Table 3). Five cases were free of medication. One case was on mesalamine. One case was on betamethasone suppository as needed. One patient with CD received scheduled infliximab infusion. The mean short-term PBDS [standard deviation (SD)] was 28.4 (9.4) at a median follow-up period of 6 months, which was higher than the 12.0 (7.7) at baseline (P=0.0061 by paired t-test). The mean long-term PBDS (SD) was 21.4 (6.8) at a median follow-up period of 47 months, which was higher than the 14.4 (10.9) at baseline (P=0.10) (Table 3).

Additional notes of cases were in the followings.

Case 1

Four days after being admitted for educational hospitalization, blood on defecation was not observed. The result of a fecal immunochemical test (FIT) (reference <100 ng/mL) on discharge was <50 ng/mL. The time course indicated that the conception preceded the symptom of proctitis (bloody stool).

Case 2

This was a case of PO-UC and was reported (21). The follow-up study beyond the case report showed that her short- and long-term PBDSs were 36 and 12, respectively (Table 3, Figure 1).

Figure 1 Change in plant-based diet scores over time in PO-UC patients (Case 2 and Case 5). m, month; ms, months; PO-UC, pregnancy-onset ulcerative colitis.

Case 3

In 2008, she affected with severe UC was referred to us. Total parenteral nutrition was undertaken. Intravenous prednisolone 60 mg/day, the standard first choice for severe colitis (19), was ineffective. Granulocyte apheresis twice a week (19) was added, resulting in improvement. PBD (800 kcal/day) was then initiated and gradually increased to 1,700 kcal/day. She was weaned off prednisolone in the outpatient department. She had a cesarean section due to fetal distress. Severe colitis recurred soon after the delivery. The same strategy as the one taken during pregnancy induced remission. Azathioprine was added this time. Maintenance of remission for 3 years allowed withdrawal of medication (azathioprine and mesalamine). Remission was maintained without medication for 1 year. She was lost to follow-up after deciding to stop visits.

Case 4

Infliximab and PBD as first-line (IPF) therapy (7,9) induced remission in CD (Table 2). She took 2.0 g/d of mesalamine. Nine months later she became pregnant in the quiescent phase (Table 1). She was admitted to the obstetric ward at gestation (G) 26 w due to threatened preterm labor and relapse of CD. Infliximab (5 mg/kg body weight) was infused at G 27 w and 29 w, which inducted remission. Mother and new-born were sound (Table 1). Cord blood infliximab concentration was 6.21 µg/mL. At aged 179th day, infliximab concentration was 0.01 µg/mL, which was below the active biologic concentration (>0.5 µg/mL). The baby then received BCG vaccine. At 6 weeks postpartum, she relapsed. Therefore, scheduled infliximab maintenance therapy was initiated. The maintenance therapy on an inpatient basis was continued up to the final visit: 52 infusions of infliximab over a 74 months period (Table 3). She had four PBD meals during the 2 days of hospitalization for each infusion. In the meantime, the stricture of the terminal ileum was surgically removed.

Case 5

This was a case of PO-UC and was reported (22). The follow-up study beyond the case report showed that her short- and long-term PBDSs were 40 and 27, respectively (Table 3, Figure 1). She had a second baby 19 months after the educational hospitalization. She took mesalamine for mild relapse at 37 months after the educational hospitalization. At the final visit, she was G 11 w and UC was quiescent without medication.

Case 6

Onset of UC was at the age of 28 in 1998. She was hospitalized twice (in 1999 and 2003) for relapses before visiting us in 2004. She underwent educational hospitalization. Positive fecal occult blood became negative during the hospitalization: FIT from 533 to 95 ng/mL (Table 2). Eight years later, she became pregnant in S0 (quiescent phase) (18) without medication and delivered the baby in 2012.

Case 7

Faint blood attached to stool was unchanged during educational hospitalization. Therefore, betamethasone sodium phosphate suppository was added. Her symptom subsequently disappeared, resulting in withdrawal of mesalamine. She then used betamethasone suppository as needed. She became pregnant twice (4 and 6 years later).

Case 8

UC was diagnosed by her previous gastroenterologist in 2009, after which she was referred to us. Remission was achieved during hospitalization. She was weaned off prednisolone (20 mg/day) (Table 2).

Discussion

We herein reported eight cases of pregnant women with IBD who were provided with PBD. As expected from our previous series of IBD patients provided with PBD (4-7,9), the outcomes of PBD in pregnant women seemed favorable in general. PBD without medication induced remission in two mild cases of UC. IPF therapy induced remission in a relapsed case of CD. There were six conceptions during remission without medication in four cases of UC. No patients relapsed during pregnancy in these cases. There were 10 live births in the eight cases. In the median follow-up period of 71 months, all eight cases were in the quiescent phase, and five of them were without medication. PBDS during the follow-up period exceeded baseline PBDS.

PBDs are recommended to the public, including pregnant women, as a healthy diet to prevent common chronic diseases such as metabolic syndrome, diabetes mellitus, coronary heart disease, and stroke (23). In addition, PBDs are more environmentally sustainable than meat-based diets and correspond to UN Sustainable Development Goals (23). PBDs are known to be associated with reduced risk of gestational hypertension and gestational diabetes mellitus (24).

There are recent reports focusing on cases in which IBD occurred during pregnancy or postpartum. It was referred to as PO-IBD (20). Unfavorable long-term outcomes were shown to be a feature of PO-UC: lower frequency of long-term remission and more hospitalizations than non-PO-UC (20,25). No concern was shown for dietary factors on relapse or onset of IBD during pregnancy and postpartum (26). Focusing on diet, we reported onset or relapse of UC during a change in dietary habits toward unhealthy diets: during a low-carbohydrate weight-loss diet and during a busy life, respectively (7,9). Our two cases of PO-UC were typical illustrative cases. The patients were aware that they changed their diets towards unhealthy ones due to emesis or a feeling of being freed from pregnancy and childbirth (21,22). We just pointed out their risky dietary changes, and then they recognized the importance of diet. This seemed to result in them paying greater attention to their diet and its contribution toward relapse prevention (Figure 1). Case 2 had been in remission for more than 5 years, and Case 5 had her 2nd child and was going to have a 3rd child. We do not feel that the clinical course of PO-UC is poor compared to non-PO-UC. Onset and relapse of IBD occur more frequently in the first and second trimesters than the third trimester (14,20). The reason for this is not known. Morning sickness is quite common in the first trimester, and it often extends to the second trimester. An investigation on whether dietary change toward an unhealthy one due to morning sickness is related to onset and relapse of IBD is eagerly awaited.

Although Case 4 with CD became pregnant in the quiescent phase, she relapsed during pregnancy and the postpartum. Because infliximab was effective for initial induction, it was natural to use infliximab again for the relapse. Infliximab was used in the late of 2nd trimester (G 26 w) and in the beginning of the 3rd trimester (G 29 w). It has been reported that infliximab and adalimumab cross the placenta, and that their use beyond the second trimester results in neonatal levels of biologics exceeding maternal levels (27). Therefore, we did not provide a third infusion of infliximab based on European Crohn-Colitis Organisation (ECCO) Guidelines (14). The relapse rate in the postpartum in CD according to a recent cohort study was 30% (28). All risk factors for relapse in the postpartum in CD, i.e., stricture type, relapse during pregnancy, and nonuse of infliximab after delivery, applied to her (26). It is of note that the patient in Case 4, who had poor prognostic factors (young onset, late start of treatment due to delayed diagnosis, stricture type), became a mother and was in clinical remission for more than 6 years with infliximab maintenance therapy alone without immunosuppressants or steroids. There is a rapidly growing body of data on maternal and neonatal outcomes by biologic use. Neonatal short- and long-term outcomes have been shown to be the same between biologic use and its non-use (29). Maintaining quiescence via biologics is preferable to relapse due to withdrawal of biologics for maternal and neonatal outcomes. It is now recommended that biologics be used continuously preconception, throughout pregnancy, and postpartum (15,29,30). Live vaccinations of newborns whose mothers are on anti-tumor necrotizing factor (TNF) antibodies are recommended beyond the first 6 months of life (15,27).

Case 3 was a case of severe UC in 2008 when infliximab was not yet approved for UC in Japan. Because prednisolone (intravenous 60 mg/day), the first-line therapy in current guidelines (20), has several disadvantages (5,31), we replaced prednisolone (glucocorticoid) with infliximab in 2010. IPF therapy induced a high remission rate in severe UC (76%) and a low colectomy rate (6%) (5). We now perform IPF therapy for severe cases of UC like Case 3. Although both severe UC and glucocorticoid therapy increase the risk of preterm birth and low birth weight (32,33), Case 3 delivered a healthy new-born at G 39 w 0 d. Relapse is known to decrease in the years following pregnancy in both UC and CD (34). She was well without relapse during 4 years of follow-up.

It is obvious that our small case series without a control diet does not constitute evidence for the superiority of PBD for pregnant patients with IBD over the current westernized diet. This case series, however, certainly implies the efficacy of PBD for pregnant patients with IBD. We hope that large, controlled studies will validate our findings.

Conclusions

In conclusion, contemporary guidelines are available for safe pregnancy and a favorable outcome in women with IBD. Conception in the quiescent phase is desirable. Medication(s) including anti-TNF antibodies, used in the quiescent phase should be continued during pregnancy, with the exception of methotrexate. Appreciation of PBD for a healthy diet will further contribute to favorable maternal and neonatal outcomes.

Acknowledgments

The authors thank Dr. Fumiko Saito, Dr. Akihiro Karube (Division of Obstetrics and Gynecology, Yuri-Kumiai General Hospital, Yurihonjo City, Japan), and Dr. Akira Sato (General Perinatal Medical Center, Akita Red Cross Hospital, Akita City, Japan) for providing information on maternal and fetal outcomes.

Funding: None.

Footnote

Reporting Checklist: The authors have completed the AME Case Series reporting checklist. Available at https://tgh.amegroups.com/article/view/10.21037/tgh-23-67/rc

Peer Review File: Available at https://tgh.amegroups.com/article/view/10.21037/tgh-23-67/prf

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tgh.amegroups.com/article/view/10.21037/tgh-23-67/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Protocol of this study was approved by the Ethical Committee of Nakadori General Hospital and by the Ethical Committee of Akita City Hospital (Protocol number: 19-2003, 12-2013, 15-2015). All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patients for the publication of this case series and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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