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Uma Mahadevan, MD, on the PIANO Study of Pregnancy and IBD
The PIANO study was designed to determine the rates of miscarriage, birth defects, or premature births among women treated for IBD with thiopurines or biologics while pregnant. Patients fill out questionnaires at each trimester of pregnancy; at the end of the pregnancy; at 4, 9, and 12 months postpartum; and annually for 18 years. Principal investigator Uma Mahadevan, MD, from the University of California San Francisco, answered some questions for Gastroenterology Learning Network about this landmark prospective study, now in its 14th year.
Gastroenterology Learning Network: 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 have you found so far?
Dr Mahadevan: Biologic therapies do cross the placenta as they are full antibodies, with very efficient transfer in the third trimester. Babies are often born with higher levels of drug on the day of birth than the mother. We found no association between drug of exposure as well as drug level at birth and infections out to 1 year of age.
GLN: Your objectives also include determining whether second trimester drug levels can be used to adjust drug and minimize transfer across the placenta to the baby. Is this particularly important as the pregnancy enters the third trimester?
Dr Mahadevan: We have not fully analyzed that data yet, but it does not seem to be important. Anecdotally, most of the drug levels are in an appropriate range so no changes were made. We would not want to reduce dose and risk a maternal flare of disease. I do not routinely check second trimester levels in practice.
GLN: Have you come to any preliminary conclusions about whether fetal exposure to these IBD therapies affects the achievement of developmental milestones?
Dr Mahadevan: We published our data in the PIANO publication in Gastroenterology1 this year. There was no negative impact on achievement of developmental milestones by drug of exposure. Most of the children did better than the general population (socioeconomic factors play a role) and at least as well, if not better, than children of IBD moms not exposed to these therapies.
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 Mahadevan: We do think mesalamine agents are low-risk, based on prior data from other sources. Within PIANO, we recently looked closely at steroids. We know moms are on steroids because they have active disease. However, first trimester steroid exposure was associated with an increase in birth defects and overall steroid exposure was associated with increased adverse pregnancy and neonatal outcomes.
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 Mahadevan: The data from multiple studies have suggested that active disease during conception is associated with an increased risk of pregnancy loss and difficulty in conception. Active disease during pregnancy is associated with an increased risk of poor weight gain, preterm birth, neonatal infections, and other adverse events. It also makes it challenging for the mother to take care of her baby and produce enough milk to breastfeed should she want to. Healthy mom: Healthy baby.
Reference:
Mahadevan U, Long MD, Kane SV. Pregnancy and neonatal outcomes after fetal exposure to biologics and thiopurines among women with inflammatory bowel disease. Gastroenterology; 160(4): 1131–1139. Published online November 20, 2020.
