The PIANO is the largest prospective study of the safety of biologic therapies and thiopurines among pregnant women with inflammatory bowel disease (IBD). This research project began in 2007. Kerri Glassner, DO, from Houston Methodist Hospital in Houston, Texas, gave a presentation on the PIANO study at the Advances in Inflammatory Bowel Diseases (AIBD) virtual regional meeting June 19, and afterward answered a few questions for Gastroenterology Learning Network.

GLN: The PIANO study is now in its 14^th year.  Can you tell us about the original objectives of this study and whether they have changed over the years?

Dr Glassner: The PIANO study was designed to determine the rates of miscarriage, birth defects, or premature births among women with IBD treated with biologics or thiopurines while pregnant. As the study has continued over the years additional therapies have been approved for IBD and evaluated in the study outcomes.

GLN: One objective of the PIANO study is to determine whether the level of biologic drug transferred through the placenta predicts risks of infection or other adverse outcomes for the infant. What has been found so far?

Dr Glassner: In the PIANO study, there was not an increased risk of infection during the first year of life in infants born to mothers on biologic or immunomodulator therapy. In addition, there has not been any difference in achievement of developmental milestones or increased risk of congenital malformations.

GLN: The PIANO study also sought to find out if second-trimester drug levels can be used to adjust drug and minimize transfer across the placenta to the fetus. What have you discovered about this aspect of the study? Is the transfer of IBD medications to the fetus dangerous? Are certain medications safer than others?

Dr Glassner: The PIANO study showed that there is placental transfer of biologics, but there was no increased risk of neonatal infections or any difference in the achievement of developmental milestones in infants born to women who were exposed to biologics in the third trimester. Previous studies,  however, have shown an increased risk of disease flare when biologics are stopped in the second trimester. Therefore, there is no strong rationale to withhold biologic therapy in any pregnant patient with IBD, and drug levels are not routinely checked in the second trimester.  

GLN: Have any preliminary conclusions been reached about whether fetal exposure to these IBD therapies affects the continuing development of babies after birth?

Dr Glassner: Data from the PIANO study suggests that fetal exposure to biologic and thiopurine therapy does not affect the achievement of developmental milestones. In fact, many of the infants did better than the general population and the children of IBD moms not exposed to these medications.

GLN: The PIANO study focuses particularly on biologics and thiopurines. What do we know about corticosteroids and other therapies for IBD, and their impacts on developing fetuses?

Dr Glassner: Corticosteroids have been associated with an increased risk for gestational diabetes, preterm birth, and low birth weight, and some data suggest there is an increased risk of birth defects with use of these drugs during the first trimester. Our goal is to help our patients achieve remission prior to conception and maintain remission throughout pregnancy avoiding the use of corticosteroids.  Methotrexate is absolutely contraindicated during pregnancy due to its teratogenic and abortifacient effects. We don’t have enough data yet on tofacitinib to recommend use during pregnancy. Dibutyl phthalate is no longer in any of the mesalamine formulations, so they are all low-risk to continue during pregnancy. 

GLN: Overall, how does the risk of poorly controlled IBD among pregnant women compare to the risks of therapies that treat IBD, in terms of such outcomes as premature birth, low birth weight, complications, or birth defects?

Dr Glassner: The risk of poorly controlled IBD at the time of conception and during pregnancy is a much greater risk to both mom and baby than the risk of IBD therapy. We saw in the PIANO study that active disease was associated with an increased risk for spontaneous abortion. Previous studies have also shown an increased risk of spontaneous abortion, low birth weight, preterm birth, and stillbirth with active disease during pregnancy. The PIANO study also found preterm birth to be associated with an increased risk of infection in the first year of the infant’s life, further emphasizing the importance of controlling disease activity to decrease the risk of preterm birth. The use of biologics and thiopurines was not found to be associated with premature birth, low birth weight, or birth defects.