PIANO

PURPOSE

This national prospective registry study is conducted to determine whether the rates of birth defects, miscarriages, premature births and other outcomes in women with inflammatory bowel disease (IBD) taking azathioprine/6MP or biologic therapy (Remicade, Humira, Cimzia, Tysabri, Stelara, Simponi, Entyvio, or Xeljanz) are different from those among IBD-affected women not taking these medications.

What are we measuring:

  1. Whether the level of biologic drug transferred across the placenta to the infant by the time of birth predicts the risk of infection or other adverse outcomes
  2. Whether the achievement of developmental milestones is affected by medication exposure
  3. Whether the rates of birth defects, adverse pregnancy outcomes and complications of labor and delivery are affected by IBD medications
  4. Whether second trimester drug levels can be used to adjust drug and minimize transfer across the placenta to the baby

Little is known about the effects of azathioprine/6MP or biologic therapy (Remicade, Humira, Cimzia, Tysabri, Stelara, Simponi, Entyvio, or Xeljanz) on pregnancy women and their babies.  As many women receive these during their prime reproductive years, the information from PIANO will be valuable in guiding therapy of women with CD or UC who wish to have children while receiving this therapy for their illness.

Please see below for our current results and outcomes.  If you are interested in enrolling please call 415-885-3734 or email [email protected] 

 

WHAT THE STUDY ENTAILS

The PIANO study mainly gathers information through questionnaires.  We ask that you complete a questionnaire at each trimester of your pregnancy, at the end of your pregnancy, 4, 9, and 12 months post-delivery, and once a year up to the age of 15 years of age. 

We also ask for blood work and a fecal calprotectin test at your 2nd trimester as well as blood work from you, your umbilical cord, and your newborn at delivery.  Depending on the results of your newborn’s blood work at delivery we also ask for blood work form your newborn at 3 and 6 months post-delivery. 

All materials that are needed will be sent to you via FedEx so you will not have to worry about finding material or having to provide it on your own.

 

OPTIONAL TESTS

Subjects taking part in this study have the option of checking response to vaccines (Haemophilus influenza, tetanus toxoid) when their child is 7 months or older.  This is part of the standard of care to ensure that your infant had an appropriate response to vaccines.  If you choose to take part in this part of the study, a blood sample will be taken from your child by placing a needle in his/her vein.  Approximately 2 mL or ½ of teaspoon of blood will be obtained.  You can choose not to give your infant’s blood sample for this test and still take part in this study. 

Subjects taking part in this study have the option of checking their infant’s blood at month 12 to determine if development of T and B cells is affected by the drug which they are taking.  The development of T and B cells is very important for keeping your child healthy and preventing injections.  If you choose to participate in this part of the study, a blood collection kit will be sent to you prior to the blood draw.  This blood draw can be done at a local commercial lab or pediatrician’s office.  The blood sample will be taken from your child by placing a needle in their vein.  Approximately 2 mL or ½ of a teaspoon of blood will be obtained.  You can choose not to give your infant’s blood sample for this test and still take part in this study.

Both of these tests try to measure whether exposure to IBD drugs during pregnancy had a more long term impact on your child’s immune system.  So far results have been reassuring, but the more data we have the better we can determine this.

Subjects taking part in this study have the option of submitting their infant’s meconium and stool sample at birth, months 3, 6, and 9, and annually between ages 1-15 for analysis.  A stool collection kit will be sent to you if you choose to take part in this optional study.  The kit will include instructions for obtaining your infant’s first bowel movement of the day as well as instructions for packaging and shipping.  All postage will be prepaid.

This test can help predict whether your child will go on to develop atopy and asthma based on the microbial genes present in your 1 month old newborn’s stool sample.  We are also able to discover if your newborn has early-life microbial-derived products that promote immune dysfunction just by your infant’s stool samples.

 

ABOUT DR. UMA MAHADEVAN

Uma Mahadevan

 

 

 

 

Uma Mahadevan, MD

Professor of Medicine
University of California, San Francisco
Co-Director
UCSF Center for Colitis and Crohn's Disease
San Francisco, California

Uma Mahadevan completed a medical degree at the State University of New York in Brooklyn. She completed a residency in internal medicine at Mount Sinai Medical Center in New York, a fellowship in gastroenterology at the University of California, San Francisco (UCSF) and a fellowship in inflammatory bowel disease (IBD) at the Mayo Clinic in Rochester, Minnesota. Dr. Mahadevan currently serves as Professor of Medicine at UCSF, Clinical Services Chief for Gastroenterology, and Co-Director of the UCSF Center for Colitis and Crohn’s Disease and Director of the IBD Fellowship.

Certified by the American Board of Internal Medicine as a Diplomate in internal medicine and gastroenterology, Dr. Mahadevan is a fellow of the American Gastroenterological Association, for whom she is a Chair for the Clinical Immunology, Microbiology and Inflammatory Bowel Disease (IMIBD) Section and Chair of the AGA National IBD Parenthood initiative. She is a Fellow of the American College of Gastroenterology and serves on the Educational Affairs Committee and as a member of the Advanced IBD Fellow Curriculum Committee.  She is currently Chair of the Crohns Colitis Foundation Clinical Research Grants committee and a member of their National Scientific Advisory Committee and Taskforce on Women in IBD.

Dr. Mahadevan is a special section editor for the journal Gastroenterology and an editorial board member and reviewer for several journals. Dr. Mahadevan has published original articles, abstracts, editorials, and invited reviews in such peer-reviewed journals as Gastroenterology, American Journal of Gastroenterology, Inflammatory Bowel Diseases, and Gut along with several book chapters. 

Dr. Mahadevan specializes in the treatment of ulcerative colitis, Crohn’s disease, and pouchitis. She has a particular interest in pregnancy and fertility in IBD, as well as in clinical trials of experimental therapy for both ulcerative colitis and Crohn’s disease. Her current projects include a national prospective registry of pregnancy outcomes and drug safety in women with IBD on immunosuppressive and biologic medications (PIANO), clinical trials in biologic therapy for IBD, and the impact of nutritional interventions in the management of IBD.

HOW TO ENROLL

It is completely up to you if you would like to enroll in our study.  Please take the time to read over our consent form with family members and/or your doctor to see if this study is the best fit for you.

If you are interested in enrolling in our study or have any questions about the study please contact our clinical research coordinator at [email protected] or 415-885-3734.

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 11th year and is continuing to enroll patients. Below is a short summary of the results and outcomes we have so far. If you would like more detailed results and outcomes, please read Drug Safety and Risk of Adverse Outcomes for Pregnant Patients With Inflammatory Bowel Disease authored by Dr. Uma Mahadevan (principal investigator of PIANO), Dr. Ryan A. McConnell, and Dr. Christina D. Chambers.

In general, it was found corticosteroid use was associated with gestational diabetes, preterm birth, and low birth weight and there was no significant increase in infant infections in the first 4 months of life.

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. However, when using thiopurine as combination therapy with a biologic (adalimumab, certolizumab, golimumab, infliximab, ustekinumab, vedolizumab) there is a likely increased risk of infant infection at 1 year of age.

Biologics as monotherapy 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 stopped between 36-37 gestation weeks, golimumab is stopped between 34-36 gestation weeks, infliximab is stopped between 30-32 gestation weeks, natalizumab is stopped between 34-36 gestation weeks, ustekinumab is stopped between 30-32 gestation weeks, and vedolizumab is stopped between 30-32 gestation weeks. Certolizumab is excluded from this list because it does not actively cross the placenta. Therefore, no adjustment is needed for certolizumab.

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 Drug Safety and Risk of Adverse Outcomes for Pregnant Patients With Inflammatory Bowel Disease authored by Dr. Uma Mahadevan (principal investigator of PIANO), Dr. Ryan A. McConnell, and Dr. Christina D. Chambers and discuss with your doctor.

FUTURE RESEARCH

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

DONATE

If you would like to donate to the PIANO study, please click the "MAKE A GIFT" button below.  Any amount of contribution will be greatly appreciated and will help further our understanding of pregnancy and IBD.

MAKE A GIFT

RESOURCES

Published Articles:

  1. 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
  2. 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
  3. 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
  4. 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]
  5. 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: ClinicalTrials.gov

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

Download Files
PIANO Consent Form