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PIANO Interim Reports – 2012

Report December 2012

PIANO: PREGNANCY IN INFLAMMATORY BOWEL DISEASE AND NEONATAL OUTCOMES

 

II. Overall Objectives and Specific Aims: Unchanged from original Proposal

 

Hypothesis

Women with IBD exposed to azathioprine/6-mp and anti-TNF therapies during pregnancy and conception have different pregnancy outcomes than women with IBD not exposed to these medications.  

 

Primary Objective

  • Determine whether the rates of congenital malformations, spontaneous abortion, preterm birth and small for gestational age (SGA) infants in a prospective national sample of women from the United States with IBD exposed to azathioprine/6MP or anti-TNF therapy are greater than those among IBD-affected women not exposed to these medications
  • Determine 4 year outcomes of infants born to mothers with IBD with respect to developmental delay, infections and other health related complications

 

Secondary Objectives

  • Determine whether the rate of any adverse pregnancy outcomes (defined below) in a prospective national sample of women from the United States with IBD differ with respect to exposure to azathioprine/6MP or anti-TNF therapy
  • Determine factors that predict adverse pregnancy outcomes in a prospective national sample of women from the United States with IBD
  • Determine rates of disease activity during pregnancy and the post-partum in a prospective national sample of women from the United States with IBD
  • Determine whether adverse outcomes are more common when the expectant mother has active IBD than when the expectant mother has quiescent IBD
  • Determine the rate of neonatal complications (defined below) up to one year from birth in a prospective national sample of children born to women from the United States with IBD

 

III. Concise description of the results

  • This project received approval from the CCFA in late January of 2007.  Institutional review board (IRB) approval was obtained from the University of California, San Francisco by July 2007.
  • At this time 31 sites have received IRB approval and have been contracted to participate in this study
  • As of October 26, 2012, 1087 patients have been enrolled in the registry
  • 337 patients have enrolled in the PIANO extension
  • Along with the data monitoring center at the University of North Carolina, case report forms have been continually upgraded as the various sites proceeded through the multiple questionnaires.  A sophisticated website for data entry has been created that can be accessed on-line by each study site.  We have created programs that send automated reminders to each site for when each individual patient questionnaire is due.  We have had excellent compliance with less than 2% of the forms being delinquent
  • Patients who have delivered are eligible for the extension with questionnaires at infant years 1, 2 ,3 and 4.  In addition to maternal and infant health questionnaires, Ages and Stages developmental questionnaires are filled out as well.

 

IV. List of Publications

  1. Abstract presented as an oral presentation at DDW in 2009, 2010, 2012
  2. IMIBD Plenary Session presentation 2012
  3. This study will generate multiple papers. All contributors will be on at least one publication from this.
  4. Paper for PIANO in progress

 

V. 2013 plans

a. Funding requested from CCFA SRA for a 3 year study to measure placental and breastmilk levels of anti-TNF at birth and correlate with infections. Also will capture data on newer medications approved for IBD

b. Funding requested for separate study to analyze B and T cell development based on drug exposure

 

VI. Interim Analysis 5/12

a. 1000 women enrolled, 896 have delivered

b. Group A (azathioprine/6mp) n= 204; Group B (biologics) n = 291; Group AB (both) n= 75; Unexposed (to aza/biologics) n = 326

c. Overall minimal differences between Group A, B, AB and unexposed group, except:

i. Increased risk of preterm birth Group AB: OR 1.83 (1.01-3.31) (1.35-5.00)

ii. No statistical increased risk of complications, infections, congenital anomalies based on medication exposure