User login
While many gastroenterologists may be comfortable with inflammatory bowel disease (IBD), most are not experts in women’s concerns about pregnancy. One study found that, although women with IBD may have concerns about the interplay of their disease and reproductive health, many have not had extensive conversations with their gastroenterologist about it. In fact, that same study found most women expect their gastroenterologist to initiate these conversations.
In this roundtable discussion, Uma Mahadevan, MD, professor of medicine and the director of the Colitis and Crohn’s Disease Center at the University of California, San Francisco; Marla C. Dubinsky, MD, professor of medicine at the Icahn School of Medicine at Mount Sinai, New York; and Sunanda V. Kane, MD, professor of medicine at Mayo Clinic in Rochester, Minn., share how they respond to these questions in their clinical practice.
What should a woman with IBD who is interested in having biological children in the future be thinking about now?
Dr. Mahadevan: Because active disease is associated with lower rates of conception and higher rates of pregnancy loss, women with IBD should first ensure they are in remission. I like to document endoscopic healing with a colonoscopy or sigmoidoscopy, but, if this has been done recently, a fecal calprotectin test can be helpful.
Women with IBD, particularly those with small bowel disease, are at risk for nutritional deficiencies, so prior to conception, I also check vitamin B-12, vitamin D, and iron, and repeat as needed. Zinc and folate can be considered. Those who are underweight should work with a nutritionist to ensure adequate caloric intake.
Dr. Dubinsky: I think it’s also important to stress the importance of taking their IBD medications because they can help patients achieve and maintain disease remission. Uncontrolled inflammation is a key risk factor for spontaneous abortion in the first trimester. Medication we would use in pregnancy is not putting them at risk for spontaneous abortion or congenital anomalies, which is what mothers to be are understandably most concerned about.
I am very honest and transparent with my patients: “About the only thing I need to take care of is you. If you are good, the baby is good.”
Dr. Kane: As Dr. Mahadevan mentioned, women with IBD are at higher risk for vitamin deficiencies, so those need to be corrected before conception. If they smoke, they should stop before conceiving.
There is no increased risk of infertility unless there has been a history of abdominal surgery.
Also, if women are not actively planning on getting pregnant, that would be important to share because some gastroenterologists will avoid certain effective medications if pregnancy is a possibility.
If a woman has had surgery for her IBD, could that make it harder for her to get pregnant?
Dr. Kane: Yes, it can because scar tissue may develop within the pelvis. However, if surgery is indicated to manage a patient’s IBD, then talk to the surgeon about ways that they might be able to reduce the risk of scar tissue formation.
Dr. Dubinsky: One thing to note is that almost all the data of infertility risk and scarring are based on open surgical techniques that involve dissection of the rectum. On the other hand, we don’t yet have enough prospective data on the impact of the modern era of laparoscopic surgery to suggest whether it affects fertility. More data is needed because providers may be giving women old information that is no longer relevant in the modern era.
If a woman is experiencing IBD symptoms, should she attempt to conceive?
Dr. Kane: Gastrointestinal symptoms in patients with IBD could be from active disease but also other things, so it’s important to have a thorough check-up to assess if there is active disease or not. Active disease can (but does not always) lead to a more complicated pregnancy, and conception is not recommended while a patient has active IBD.
Dr. Dubinsky: Although some patients feel an urgency to conceive regardless of disease activity, we need to do our due diligence and explain that we need to focus on getting them into the deepest remission possible, including endoscopic findings, biomarkers, and symptoms.
The most important gift you can give your future moms is to optimize the therapy they’re on before they conceive.
Is it important for someone who’s working with a gastroenterologist and an obstetrician to also work with a maternal-fetal medicine (MFM) specialist?
Dr. Kane: Having a diagnosis of IBD makes a woman’s pregnancy “high risk” because just having the diagnosis is associated with a higher risk of prematurity and small for gestational age – but importantly, not birth defects. A woman whose IBD is in remission should still have a discussion with an MFM specialist, just so everyone is on the same page.
Dr. Dubinsky: I refer to care with MFM specialists as “tighter monitoring.” I tell my patients that MFM specialists have managed many complex pregnancies and feel confident around the safety of their medications, understand the impact of when the baby may be exposed to certain medications, and will focus on following them more closely.
What are the risks of IBD medications during pregnancy and while breastfeeding? Should women stop their medications during pregnancy and breastfeeding?
Dr. Dubinsky: Organogenesis occurs in the first 10 weeks, so any medicines that cross the placenta during that time are up for discussion and debate. Methotrexate and the newer small molecules, such as Janus kinase (JAK) inhibitors and S1P receptor modulators, do cross the placenta during the first trimester and need to be discontinued before conception, sometimes as early as 3 months before conception.
However, biologics are very large proteins and do not cross the placenta until closer to week 27. We are not advocating stopping biologics in advance of conception, or during pregnancy, or during breastfeeding. There is more risk to stopping than continuing.
Dr. Mahadevan: Methotrexate should be stopped at least 3 months prior to conception and should not be taken during pregnancy.
There are limited antibiotic safety data in pregnancy for the longer periods of time used in IBD. I generally prefer amoxicillin/clavulanic acid over ciprofloxacin or metronidazole, but short term (less than 2 weeks) use of any of those three are not contraindicated.
Mesalamine agents and thiopurine monotherapy can be continued through pregnancy and breastfeeding.
Biologic agents, such as anti–tumor necrosis factor, anti-interleukin 23, anti-integrin, and biosimilars, can be continued through pregnancy and during breastfeeding. Given limited exposure in the first trimester, there is no evidence of increased risk of birth defects. As Dr. Dubinsky pointed out, there is active transfer, particularly in the third trimester and minimal transfer in breast milk, but this has not been associated with harm.
Lastly, small molecules, such as the JAK inhibitors tofacitinib and upadacitinib, as well as ozanimod, have virtually no human safety data during pregnancy, and animal data show harm. The use of these agents in pregnancy is not recommended.
Dr. Kane: As Dr. Dubinsky stated, most of the medications our patients take are low risk to continue through pregnancy if the patients are in remission. Although a woman “in remission” on steroids is not really in remission and should not get pregnant until she is on something else.
As far as breastfeeding goes, that should be stopped if the patient is on methotrexate, cyclosporine, or certain antibiotics. If she is on more than 20 mg of prednisone, this can pass to the infant, and a mother should not breastfeed.
Women should avoid fenugreek as a lactation aid, as that contains a compound that can promote bleeding. Lactation cookies are ok.
Otherwise, there are lots of potential benefits to breastfeeding, and I encourage it.
How is a flare treated if it occurs during pregnancy?
Dr. Dubinsky: A flare during pregnancy is treated the same as a flare outside of pregnancy. We want to use noninvasive ways to confirm it, but I think we don’t need to overly investigate in most of our women. If they’re already on a biologic, you may consider changing.
Some women may need corticosteroids. It’s not our favorite move, but there is an urgency to getting a flare under control during pregnancy because of possible complications.
Dr. Mahadevan: Some of this is contingent on when during pregnancy the flare occurs. A patient who has a flare at 38 weeks’ gestation will likely proceed with delivery and the flare will be dealt with separately. Someone at 8 weeks’ gestation is at high risk for pregnancy loss, so treatment should be quick and effective.
As does Dr. Dubinsky, I do try to avoid steroids if possible. For example, I would rather start an effective biologic right away than drag out steroids to see if they will respond.
Dr. Kane: I would add that, if a mother is losing weight, she might need to be hospitalized for additional nutritional support. If surgery is necessary, we usually try to time it for the second or third trimester.
What needs to be taken into consideration regarding mode of delivery? Also, if a woman has undergone prior surgeries, do they increase the risk of delivery complications?
For ulcerative colitis, mode of delivery is based on obstetric, not gastrointestinal, variables. For Crohn’s disease, if there is evidence of perianal disease, then a cesarean is appropriate.
If there is no history of perianal disease, then delivery is based on obstetric variables.
For a woman who has a J pouch, if possible, the surgeon who created it should be contacted to ask about the technical aspects of the pouch and how it lies in the pelvis.
What’s the risk of a postpartum flare if a woman’s IBD remains in clinical remission during pregnancy?
Dr. Mahadevan: There is no increased risk of postpartum flare if a woman continues her IBD medications after delivery. Many of the reports of flare are from stopping medications (mistakenly often) to breastfeed.
Dr. Kane: As Dr. Mahadevan said, the risk of a flare is usually because a woman stops taking her medications because she thinks that medication will be passed to the infant through breastfeeding, which in most cases is not true.
Otherwise, there is not an increased risk of a flare in a 12-month period. However, it is important to monitor for symptoms after delivery; the risk of a flare is not zero.
What symptoms should women watch out for after delivery that may indicate an uptick in disease activity?
Dr. Kane: The same symptoms as before they were pregnant. Diarrhea, abdominal pain, and rectal bleeding are not normal after delivery and should be considered signs of returning disease.
As a gastroenterologist, is there any additional advice you’d offer about conception, fertility, and pregnancy when treating women with IBD?
Dr. Mahadevan: Women with IBD should, when feasible, have a planned pregnancy when in documented remission and under the care of their gastroenterologists, obstetrician, and an MFM specialist. Life happens, and this is not always possible. That said, a woman with IBD has the same chance of getting pregnant as a woman of the same age without IBD, unless she has active disease or a history of pelvic surgery. Women with IBD in remission will generally have healthy pregnancies if they continue appropriate medications.
Dr. Kane: Agreed. The majority of women with IBD will have normal, healthy pregnancies. It is important for them to not stop their IBD therapy without talking to their gastroenterologist first. Well-intentioned but ignorant obstetricians or midwives may recommend stopping, but then panic when disease flares and the mother’s health is at risk. Active inflammation is the worst enemy to a pregnancy, not active therapy.
Dr. Dubinsky: One additional thing to consider is: How do we help women with IBD who have delivered meet the needs of their family and continue to stay on their meds and be in good inflammatory control?
For example, we can give the biologic in the hospital after they’ve had a cesarean or a vaginal delivery and before they leave. We know that that is safe, giving that to them before they leave the hospital is a huge value added.
Another thing is possibly changing their infusions to home infusions. That would be helpful for the moms as well.
Dr. Mahadevan reports being a consultant for AbbVie, Janssen, Pfizer, Gilead, Bristol-Myers Squibb, Takeda, Protagonist, Prometheus, and Boehringer Ingelheim. Dr. Dubinsky is a consultant for AbbVie, Arena, Bristol-Myers Squibb, Janssen, Eli Lilly, Takeda, and Prometheus BioSciences. She is a shareholder and CEO of a publicly traded company, Trellis Health. Dr. Kane is a consultant for Bristol-Myers Squibb, Boehringer Ingelheim, Gilead, Janssen, Takeda, Seres Therapeutics, TechLab, United Healthcare, Predicta-Med, and InveniAI, and is the editor for the IBD section of UptoDate.
AGA Resource
Planning for a family can be challenging, and if your patient has IBD, there are additional factors to consider. The AGA IBD Parenthood Project is the “go-to” resource for everything patients need to know about IBD and pregnancy throughout all stages of family planning.
While many gastroenterologists may be comfortable with inflammatory bowel disease (IBD), most are not experts in women’s concerns about pregnancy. One study found that, although women with IBD may have concerns about the interplay of their disease and reproductive health, many have not had extensive conversations with their gastroenterologist about it. In fact, that same study found most women expect their gastroenterologist to initiate these conversations.
In this roundtable discussion, Uma Mahadevan, MD, professor of medicine and the director of the Colitis and Crohn’s Disease Center at the University of California, San Francisco; Marla C. Dubinsky, MD, professor of medicine at the Icahn School of Medicine at Mount Sinai, New York; and Sunanda V. Kane, MD, professor of medicine at Mayo Clinic in Rochester, Minn., share how they respond to these questions in their clinical practice.
What should a woman with IBD who is interested in having biological children in the future be thinking about now?
Dr. Mahadevan: Because active disease is associated with lower rates of conception and higher rates of pregnancy loss, women with IBD should first ensure they are in remission. I like to document endoscopic healing with a colonoscopy or sigmoidoscopy, but, if this has been done recently, a fecal calprotectin test can be helpful.
Women with IBD, particularly those with small bowel disease, are at risk for nutritional deficiencies, so prior to conception, I also check vitamin B-12, vitamin D, and iron, and repeat as needed. Zinc and folate can be considered. Those who are underweight should work with a nutritionist to ensure adequate caloric intake.
Dr. Dubinsky: I think it’s also important to stress the importance of taking their IBD medications because they can help patients achieve and maintain disease remission. Uncontrolled inflammation is a key risk factor for spontaneous abortion in the first trimester. Medication we would use in pregnancy is not putting them at risk for spontaneous abortion or congenital anomalies, which is what mothers to be are understandably most concerned about.
I am very honest and transparent with my patients: “About the only thing I need to take care of is you. If you are good, the baby is good.”
Dr. Kane: As Dr. Mahadevan mentioned, women with IBD are at higher risk for vitamin deficiencies, so those need to be corrected before conception. If they smoke, they should stop before conceiving.
There is no increased risk of infertility unless there has been a history of abdominal surgery.
Also, if women are not actively planning on getting pregnant, that would be important to share because some gastroenterologists will avoid certain effective medications if pregnancy is a possibility.
If a woman has had surgery for her IBD, could that make it harder for her to get pregnant?
Dr. Kane: Yes, it can because scar tissue may develop within the pelvis. However, if surgery is indicated to manage a patient’s IBD, then talk to the surgeon about ways that they might be able to reduce the risk of scar tissue formation.
Dr. Dubinsky: One thing to note is that almost all the data of infertility risk and scarring are based on open surgical techniques that involve dissection of the rectum. On the other hand, we don’t yet have enough prospective data on the impact of the modern era of laparoscopic surgery to suggest whether it affects fertility. More data is needed because providers may be giving women old information that is no longer relevant in the modern era.
If a woman is experiencing IBD symptoms, should she attempt to conceive?
Dr. Kane: Gastrointestinal symptoms in patients with IBD could be from active disease but also other things, so it’s important to have a thorough check-up to assess if there is active disease or not. Active disease can (but does not always) lead to a more complicated pregnancy, and conception is not recommended while a patient has active IBD.
Dr. Dubinsky: Although some patients feel an urgency to conceive regardless of disease activity, we need to do our due diligence and explain that we need to focus on getting them into the deepest remission possible, including endoscopic findings, biomarkers, and symptoms.
The most important gift you can give your future moms is to optimize the therapy they’re on before they conceive.
Is it important for someone who’s working with a gastroenterologist and an obstetrician to also work with a maternal-fetal medicine (MFM) specialist?
Dr. Kane: Having a diagnosis of IBD makes a woman’s pregnancy “high risk” because just having the diagnosis is associated with a higher risk of prematurity and small for gestational age – but importantly, not birth defects. A woman whose IBD is in remission should still have a discussion with an MFM specialist, just so everyone is on the same page.
Dr. Dubinsky: I refer to care with MFM specialists as “tighter monitoring.” I tell my patients that MFM specialists have managed many complex pregnancies and feel confident around the safety of their medications, understand the impact of when the baby may be exposed to certain medications, and will focus on following them more closely.
What are the risks of IBD medications during pregnancy and while breastfeeding? Should women stop their medications during pregnancy and breastfeeding?
Dr. Dubinsky: Organogenesis occurs in the first 10 weeks, so any medicines that cross the placenta during that time are up for discussion and debate. Methotrexate and the newer small molecules, such as Janus kinase (JAK) inhibitors and S1P receptor modulators, do cross the placenta during the first trimester and need to be discontinued before conception, sometimes as early as 3 months before conception.
However, biologics are very large proteins and do not cross the placenta until closer to week 27. We are not advocating stopping biologics in advance of conception, or during pregnancy, or during breastfeeding. There is more risk to stopping than continuing.
Dr. Mahadevan: Methotrexate should be stopped at least 3 months prior to conception and should not be taken during pregnancy.
There are limited antibiotic safety data in pregnancy for the longer periods of time used in IBD. I generally prefer amoxicillin/clavulanic acid over ciprofloxacin or metronidazole, but short term (less than 2 weeks) use of any of those three are not contraindicated.
Mesalamine agents and thiopurine monotherapy can be continued through pregnancy and breastfeeding.
Biologic agents, such as anti–tumor necrosis factor, anti-interleukin 23, anti-integrin, and biosimilars, can be continued through pregnancy and during breastfeeding. Given limited exposure in the first trimester, there is no evidence of increased risk of birth defects. As Dr. Dubinsky pointed out, there is active transfer, particularly in the third trimester and minimal transfer in breast milk, but this has not been associated with harm.
Lastly, small molecules, such as the JAK inhibitors tofacitinib and upadacitinib, as well as ozanimod, have virtually no human safety data during pregnancy, and animal data show harm. The use of these agents in pregnancy is not recommended.
Dr. Kane: As Dr. Dubinsky stated, most of the medications our patients take are low risk to continue through pregnancy if the patients are in remission. Although a woman “in remission” on steroids is not really in remission and should not get pregnant until she is on something else.
As far as breastfeeding goes, that should be stopped if the patient is on methotrexate, cyclosporine, or certain antibiotics. If she is on more than 20 mg of prednisone, this can pass to the infant, and a mother should not breastfeed.
Women should avoid fenugreek as a lactation aid, as that contains a compound that can promote bleeding. Lactation cookies are ok.
Otherwise, there are lots of potential benefits to breastfeeding, and I encourage it.
How is a flare treated if it occurs during pregnancy?
Dr. Dubinsky: A flare during pregnancy is treated the same as a flare outside of pregnancy. We want to use noninvasive ways to confirm it, but I think we don’t need to overly investigate in most of our women. If they’re already on a biologic, you may consider changing.
Some women may need corticosteroids. It’s not our favorite move, but there is an urgency to getting a flare under control during pregnancy because of possible complications.
Dr. Mahadevan: Some of this is contingent on when during pregnancy the flare occurs. A patient who has a flare at 38 weeks’ gestation will likely proceed with delivery and the flare will be dealt with separately. Someone at 8 weeks’ gestation is at high risk for pregnancy loss, so treatment should be quick and effective.
As does Dr. Dubinsky, I do try to avoid steroids if possible. For example, I would rather start an effective biologic right away than drag out steroids to see if they will respond.
Dr. Kane: I would add that, if a mother is losing weight, she might need to be hospitalized for additional nutritional support. If surgery is necessary, we usually try to time it for the second or third trimester.
What needs to be taken into consideration regarding mode of delivery? Also, if a woman has undergone prior surgeries, do they increase the risk of delivery complications?
For ulcerative colitis, mode of delivery is based on obstetric, not gastrointestinal, variables. For Crohn’s disease, if there is evidence of perianal disease, then a cesarean is appropriate.
If there is no history of perianal disease, then delivery is based on obstetric variables.
For a woman who has a J pouch, if possible, the surgeon who created it should be contacted to ask about the technical aspects of the pouch and how it lies in the pelvis.
What’s the risk of a postpartum flare if a woman’s IBD remains in clinical remission during pregnancy?
Dr. Mahadevan: There is no increased risk of postpartum flare if a woman continues her IBD medications after delivery. Many of the reports of flare are from stopping medications (mistakenly often) to breastfeed.
Dr. Kane: As Dr. Mahadevan said, the risk of a flare is usually because a woman stops taking her medications because she thinks that medication will be passed to the infant through breastfeeding, which in most cases is not true.
Otherwise, there is not an increased risk of a flare in a 12-month period. However, it is important to monitor for symptoms after delivery; the risk of a flare is not zero.
What symptoms should women watch out for after delivery that may indicate an uptick in disease activity?
Dr. Kane: The same symptoms as before they were pregnant. Diarrhea, abdominal pain, and rectal bleeding are not normal after delivery and should be considered signs of returning disease.
As a gastroenterologist, is there any additional advice you’d offer about conception, fertility, and pregnancy when treating women with IBD?
Dr. Mahadevan: Women with IBD should, when feasible, have a planned pregnancy when in documented remission and under the care of their gastroenterologists, obstetrician, and an MFM specialist. Life happens, and this is not always possible. That said, a woman with IBD has the same chance of getting pregnant as a woman of the same age without IBD, unless she has active disease or a history of pelvic surgery. Women with IBD in remission will generally have healthy pregnancies if they continue appropriate medications.
Dr. Kane: Agreed. The majority of women with IBD will have normal, healthy pregnancies. It is important for them to not stop their IBD therapy without talking to their gastroenterologist first. Well-intentioned but ignorant obstetricians or midwives may recommend stopping, but then panic when disease flares and the mother’s health is at risk. Active inflammation is the worst enemy to a pregnancy, not active therapy.
Dr. Dubinsky: One additional thing to consider is: How do we help women with IBD who have delivered meet the needs of their family and continue to stay on their meds and be in good inflammatory control?
For example, we can give the biologic in the hospital after they’ve had a cesarean or a vaginal delivery and before they leave. We know that that is safe, giving that to them before they leave the hospital is a huge value added.
Another thing is possibly changing their infusions to home infusions. That would be helpful for the moms as well.
Dr. Mahadevan reports being a consultant for AbbVie, Janssen, Pfizer, Gilead, Bristol-Myers Squibb, Takeda, Protagonist, Prometheus, and Boehringer Ingelheim. Dr. Dubinsky is a consultant for AbbVie, Arena, Bristol-Myers Squibb, Janssen, Eli Lilly, Takeda, and Prometheus BioSciences. She is a shareholder and CEO of a publicly traded company, Trellis Health. Dr. Kane is a consultant for Bristol-Myers Squibb, Boehringer Ingelheim, Gilead, Janssen, Takeda, Seres Therapeutics, TechLab, United Healthcare, Predicta-Med, and InveniAI, and is the editor for the IBD section of UptoDate.
AGA Resource
Planning for a family can be challenging, and if your patient has IBD, there are additional factors to consider. The AGA IBD Parenthood Project is the “go-to” resource for everything patients need to know about IBD and pregnancy throughout all stages of family planning.
While many gastroenterologists may be comfortable with inflammatory bowel disease (IBD), most are not experts in women’s concerns about pregnancy. One study found that, although women with IBD may have concerns about the interplay of their disease and reproductive health, many have not had extensive conversations with their gastroenterologist about it. In fact, that same study found most women expect their gastroenterologist to initiate these conversations.
In this roundtable discussion, Uma Mahadevan, MD, professor of medicine and the director of the Colitis and Crohn’s Disease Center at the University of California, San Francisco; Marla C. Dubinsky, MD, professor of medicine at the Icahn School of Medicine at Mount Sinai, New York; and Sunanda V. Kane, MD, professor of medicine at Mayo Clinic in Rochester, Minn., share how they respond to these questions in their clinical practice.
What should a woman with IBD who is interested in having biological children in the future be thinking about now?
Dr. Mahadevan: Because active disease is associated with lower rates of conception and higher rates of pregnancy loss, women with IBD should first ensure they are in remission. I like to document endoscopic healing with a colonoscopy or sigmoidoscopy, but, if this has been done recently, a fecal calprotectin test can be helpful.
Women with IBD, particularly those with small bowel disease, are at risk for nutritional deficiencies, so prior to conception, I also check vitamin B-12, vitamin D, and iron, and repeat as needed. Zinc and folate can be considered. Those who are underweight should work with a nutritionist to ensure adequate caloric intake.
Dr. Dubinsky: I think it’s also important to stress the importance of taking their IBD medications because they can help patients achieve and maintain disease remission. Uncontrolled inflammation is a key risk factor for spontaneous abortion in the first trimester. Medication we would use in pregnancy is not putting them at risk for spontaneous abortion or congenital anomalies, which is what mothers to be are understandably most concerned about.
I am very honest and transparent with my patients: “About the only thing I need to take care of is you. If you are good, the baby is good.”
Dr. Kane: As Dr. Mahadevan mentioned, women with IBD are at higher risk for vitamin deficiencies, so those need to be corrected before conception. If they smoke, they should stop before conceiving.
There is no increased risk of infertility unless there has been a history of abdominal surgery.
Also, if women are not actively planning on getting pregnant, that would be important to share because some gastroenterologists will avoid certain effective medications if pregnancy is a possibility.
If a woman has had surgery for her IBD, could that make it harder for her to get pregnant?
Dr. Kane: Yes, it can because scar tissue may develop within the pelvis. However, if surgery is indicated to manage a patient’s IBD, then talk to the surgeon about ways that they might be able to reduce the risk of scar tissue formation.
Dr. Dubinsky: One thing to note is that almost all the data of infertility risk and scarring are based on open surgical techniques that involve dissection of the rectum. On the other hand, we don’t yet have enough prospective data on the impact of the modern era of laparoscopic surgery to suggest whether it affects fertility. More data is needed because providers may be giving women old information that is no longer relevant in the modern era.
If a woman is experiencing IBD symptoms, should she attempt to conceive?
Dr. Kane: Gastrointestinal symptoms in patients with IBD could be from active disease but also other things, so it’s important to have a thorough check-up to assess if there is active disease or not. Active disease can (but does not always) lead to a more complicated pregnancy, and conception is not recommended while a patient has active IBD.
Dr. Dubinsky: Although some patients feel an urgency to conceive regardless of disease activity, we need to do our due diligence and explain that we need to focus on getting them into the deepest remission possible, including endoscopic findings, biomarkers, and symptoms.
The most important gift you can give your future moms is to optimize the therapy they’re on before they conceive.
Is it important for someone who’s working with a gastroenterologist and an obstetrician to also work with a maternal-fetal medicine (MFM) specialist?
Dr. Kane: Having a diagnosis of IBD makes a woman’s pregnancy “high risk” because just having the diagnosis is associated with a higher risk of prematurity and small for gestational age – but importantly, not birth defects. A woman whose IBD is in remission should still have a discussion with an MFM specialist, just so everyone is on the same page.
Dr. Dubinsky: I refer to care with MFM specialists as “tighter monitoring.” I tell my patients that MFM specialists have managed many complex pregnancies and feel confident around the safety of their medications, understand the impact of when the baby may be exposed to certain medications, and will focus on following them more closely.
What are the risks of IBD medications during pregnancy and while breastfeeding? Should women stop their medications during pregnancy and breastfeeding?
Dr. Dubinsky: Organogenesis occurs in the first 10 weeks, so any medicines that cross the placenta during that time are up for discussion and debate. Methotrexate and the newer small molecules, such as Janus kinase (JAK) inhibitors and S1P receptor modulators, do cross the placenta during the first trimester and need to be discontinued before conception, sometimes as early as 3 months before conception.
However, biologics are very large proteins and do not cross the placenta until closer to week 27. We are not advocating stopping biologics in advance of conception, or during pregnancy, or during breastfeeding. There is more risk to stopping than continuing.
Dr. Mahadevan: Methotrexate should be stopped at least 3 months prior to conception and should not be taken during pregnancy.
There are limited antibiotic safety data in pregnancy for the longer periods of time used in IBD. I generally prefer amoxicillin/clavulanic acid over ciprofloxacin or metronidazole, but short term (less than 2 weeks) use of any of those three are not contraindicated.
Mesalamine agents and thiopurine monotherapy can be continued through pregnancy and breastfeeding.
Biologic agents, such as anti–tumor necrosis factor, anti-interleukin 23, anti-integrin, and biosimilars, can be continued through pregnancy and during breastfeeding. Given limited exposure in the first trimester, there is no evidence of increased risk of birth defects. As Dr. Dubinsky pointed out, there is active transfer, particularly in the third trimester and minimal transfer in breast milk, but this has not been associated with harm.
Lastly, small molecules, such as the JAK inhibitors tofacitinib and upadacitinib, as well as ozanimod, have virtually no human safety data during pregnancy, and animal data show harm. The use of these agents in pregnancy is not recommended.
Dr. Kane: As Dr. Dubinsky stated, most of the medications our patients take are low risk to continue through pregnancy if the patients are in remission. Although a woman “in remission” on steroids is not really in remission and should not get pregnant until she is on something else.
As far as breastfeeding goes, that should be stopped if the patient is on methotrexate, cyclosporine, or certain antibiotics. If she is on more than 20 mg of prednisone, this can pass to the infant, and a mother should not breastfeed.
Women should avoid fenugreek as a lactation aid, as that contains a compound that can promote bleeding. Lactation cookies are ok.
Otherwise, there are lots of potential benefits to breastfeeding, and I encourage it.
How is a flare treated if it occurs during pregnancy?
Dr. Dubinsky: A flare during pregnancy is treated the same as a flare outside of pregnancy. We want to use noninvasive ways to confirm it, but I think we don’t need to overly investigate in most of our women. If they’re already on a biologic, you may consider changing.
Some women may need corticosteroids. It’s not our favorite move, but there is an urgency to getting a flare under control during pregnancy because of possible complications.
Dr. Mahadevan: Some of this is contingent on when during pregnancy the flare occurs. A patient who has a flare at 38 weeks’ gestation will likely proceed with delivery and the flare will be dealt with separately. Someone at 8 weeks’ gestation is at high risk for pregnancy loss, so treatment should be quick and effective.
As does Dr. Dubinsky, I do try to avoid steroids if possible. For example, I would rather start an effective biologic right away than drag out steroids to see if they will respond.
Dr. Kane: I would add that, if a mother is losing weight, she might need to be hospitalized for additional nutritional support. If surgery is necessary, we usually try to time it for the second or third trimester.
What needs to be taken into consideration regarding mode of delivery? Also, if a woman has undergone prior surgeries, do they increase the risk of delivery complications?
For ulcerative colitis, mode of delivery is based on obstetric, not gastrointestinal, variables. For Crohn’s disease, if there is evidence of perianal disease, then a cesarean is appropriate.
If there is no history of perianal disease, then delivery is based on obstetric variables.
For a woman who has a J pouch, if possible, the surgeon who created it should be contacted to ask about the technical aspects of the pouch and how it lies in the pelvis.
What’s the risk of a postpartum flare if a woman’s IBD remains in clinical remission during pregnancy?
Dr. Mahadevan: There is no increased risk of postpartum flare if a woman continues her IBD medications after delivery. Many of the reports of flare are from stopping medications (mistakenly often) to breastfeed.
Dr. Kane: As Dr. Mahadevan said, the risk of a flare is usually because a woman stops taking her medications because she thinks that medication will be passed to the infant through breastfeeding, which in most cases is not true.
Otherwise, there is not an increased risk of a flare in a 12-month period. However, it is important to monitor for symptoms after delivery; the risk of a flare is not zero.
What symptoms should women watch out for after delivery that may indicate an uptick in disease activity?
Dr. Kane: The same symptoms as before they were pregnant. Diarrhea, abdominal pain, and rectal bleeding are not normal after delivery and should be considered signs of returning disease.
As a gastroenterologist, is there any additional advice you’d offer about conception, fertility, and pregnancy when treating women with IBD?
Dr. Mahadevan: Women with IBD should, when feasible, have a planned pregnancy when in documented remission and under the care of their gastroenterologists, obstetrician, and an MFM specialist. Life happens, and this is not always possible. That said, a woman with IBD has the same chance of getting pregnant as a woman of the same age without IBD, unless she has active disease or a history of pelvic surgery. Women with IBD in remission will generally have healthy pregnancies if they continue appropriate medications.
Dr. Kane: Agreed. The majority of women with IBD will have normal, healthy pregnancies. It is important for them to not stop their IBD therapy without talking to their gastroenterologist first. Well-intentioned but ignorant obstetricians or midwives may recommend stopping, but then panic when disease flares and the mother’s health is at risk. Active inflammation is the worst enemy to a pregnancy, not active therapy.
Dr. Dubinsky: One additional thing to consider is: How do we help women with IBD who have delivered meet the needs of their family and continue to stay on their meds and be in good inflammatory control?
For example, we can give the biologic in the hospital after they’ve had a cesarean or a vaginal delivery and before they leave. We know that that is safe, giving that to them before they leave the hospital is a huge value added.
Another thing is possibly changing their infusions to home infusions. That would be helpful for the moms as well.
Dr. Mahadevan reports being a consultant for AbbVie, Janssen, Pfizer, Gilead, Bristol-Myers Squibb, Takeda, Protagonist, Prometheus, and Boehringer Ingelheim. Dr. Dubinsky is a consultant for AbbVie, Arena, Bristol-Myers Squibb, Janssen, Eli Lilly, Takeda, and Prometheus BioSciences. She is a shareholder and CEO of a publicly traded company, Trellis Health. Dr. Kane is a consultant for Bristol-Myers Squibb, Boehringer Ingelheim, Gilead, Janssen, Takeda, Seres Therapeutics, TechLab, United Healthcare, Predicta-Med, and InveniAI, and is the editor for the IBD section of UptoDate.
AGA Resource
Planning for a family can be challenging, and if your patient has IBD, there are additional factors to consider. The AGA IBD Parenthood Project is the “go-to” resource for everything patients need to know about IBD and pregnancy throughout all stages of family planning.
