Research and Resources

Results/Outcomes

In the A Multicenter National Prospective Study of Pregnancy and Neonatal Outcomes in Women with Inflammatory Bowel Disease (PIANO) Study, we have enrolled over 1600 patients at 30 Crohn’s & Colitis Foundation Clinical Alliance (CCF) sites. This study is in its 14th year and is continuing to enroll patients. Below is a short summary of the results and outcomes we have so far. In general, it was found that:

  1. Disease activity had a negative impact on pregnancy outcome including preterm birth and miscarriage
  2. Corticosteroid use was associated with gestational diabetes, preterm birth, birth defects and infant infections
  3. The uses of immunomodulators have varying results.
    • Methotrexate is contraindicated during conception with risks of congenital limb and craniofacial anomalies and developmental delay with intrauterine exposure. Women should stop methotrexate 3-6 months before attempting conception.
    • There is low risk of thiopurines (azathiopurine, 6-mercaptopurine) on their own.
  4. Biologics were not associated with an increased in adverse pregnancy outcomes. During pregnancy, it is recommended the medication is continued throughout, but that dosing schedules be adjusted so that: adalimumab is last given between 37-38 weeks gestation, golimumab between 36-38 gestation weeks, infliximab, ustekinumab, and vedolizumab between 32-36 weeks gestation. Certolizumab is excluded from this list because it does not actively cross the placenta. Therefore, no adjustment is needed for certolizumab.
  5. There is little data on safety of small molecules like tofacitinib, ozanimod and upadacitinib in pregnancy
    • Many questions are brought up about breastfeeding while on biologics. In a sub-study within PIANO, it was found that there is no increased infection risk and no delayed developmental milestone achievement when breastfeeding while on a biologic and the amount of transfer is very little.
    • For a more detailed explanation on results and outcomes from the PIANO study, please read  Pregnancy and Neonatal Outcomes After Fetal Exposure to Biologics and Thiopurines Among Women With Inflammatory Bowel Disease. Mahadevan U, Long MD, Kane SV, Roy A, Dubinsky MC, Sands BE, Cohen RD, Chambers CD, Sandborn WJ; Crohn’s Colitis Foundation Clinical Research Alliance.Gastroenterology. 2021 Mar;160(4):1131-1139. doi: 10.1053/j.gastro.2020.11.038 and discuss with your doctor.

Future Research

  1. Transfer of protective COVID antibodies from mother to baby
  2. Does IBD Medication Exposure effect immune system development as measured by T and B cells at 1 year
  3. What is the long-term impact of drug exposure in children exposed to biologic therapy during pregnancy
  4. What is the impact of nutrition in early childhood on outcomes in children

Resources

  1. Inflammatory Bowel Disease in Pregnancy Clinical Care Pathway: A Report From the American Gastroenterological Association IBD Parenthood Project Working Group. Mahadevan U, Robinson C, Bernasko N, Boland B, Chambers C, Dubinsky M, Friedman S, Kane S, Manthey J, Sauberan J, Stone J, Jain R.Gastroenterology. 2019 Apr;156(5):1508-1524. doi: 10.1053/j.gastro.2018.12.022
  2. Pregnancy and Neonatal Outcomes After Fetal Exposure to Biologics and Thiopurines Among Women With Inflammatory Bowel Disease. Mahadevan U, Long MD, Kane SV, Roy A, Dubinsky MC, Sands BE, Cohen RD, Chambers CD, Sandborn WJ; Crohn’s Colitis Foundation Clinical Research Alliance.Gastroenterology. 2021 Mar;160(4):1131-1139. doi: 10.1053/j.gastro.2020.11.038.
  3. Exposure Concentrations of Infants Breastfed by Women Receiving Biologic Therapies for Inflammatory Bowel Diseases and Effects of Breastfeeding on Infections and Development. Matro R, Martin CF, Wolf D, Shah SA, Mahadevan U.Gastroenterology. 2018 Sep;155(3):696-704. doi: 10.1053/j.gastro.2018.05.040. Epub 2018 May 30.
  4. Drug Safety and Risk of Adverse Outcomes for Pregnant Patients With Inflammatory Bowel Disease. Mahadevan U, McConnell RA, Chambers CD. Gastroenterology. 2017 Feb;152(2):451-462
  5. Vertical Transmission of Histoplasmosis Associated With Anti-Tumor Necrosis Factor Therapy. Carlucci JG, Halasa N, Creech CB, Dulek DE, Gómez-Duarte OG, Nelson GE, Talbot HK, Scalise ML, Scott PL, Mahadevan U, Beaulieu DB
  6. Inadequate gestational weight gain predicts adverse pregnancy outcomes in mothers with inflammatory bowel disease: Results from a prospective US pregnancy cohort. May-Bente Bengtson, PhD a,b, Christopher F. Martin, PhD c, Geir Aamodt, PhD d, Morten. H.Vatn, PhD, Uma Mahadevan, MD, Digestive Diseases and Sciences, in press
  7. Use of Biologic Therapy by Pregnant Women with Inflammatory Bowel Disease Does Not Affect Infant Response to Vaccines. Beaulieu DB, Ananthakrishnan AN, Martin C, Cohen RD, Kane SV, Mahadevan U. Clin Gastroenterol Hepatol. 2017 Sep 1. pii: S1542-3565(17)31049-2.doi: 10.1016/j.cgh.2017.08.041. [Epub ahead of print]
  8. Anti-TNF and thiopurine therapy in pregnant IBD patients does not significantly alter a panel of B and T cell subsets in one-year-old infants. Michael G. Kattah, Jeffrey Milush, Trevor Burt, Robert P. McCabe Jr, Michael Whang, Averil Ma, Uma Mahadevan Clinical and Translational Gastroenterology. 2018.  In press

For more details, visit ClinicalTrials.gov.

Should I stop biologic agents among patients who are pregnant with IBD?:  https://youtu.be/3QpN8n9kW_k