Benjamin Koslowsky1, Chen Sadeh2, Sorina Grisaru-Granovsky3, Hagit Miskin4, Eran Goldin2, Ariella Bar-Gil Shitrit2. 1. Digestive Diseases Institute, Shaare Zedek Medical Center, 12 Bayit St., 91031, Jerusalem, Israel. binyaminkos@szmc.org.il. 2. Digestive Diseases Institute, Shaare Zedek Medical Center, 12 Bayit St., 91031, Jerusalem, Israel. 3. Fetal-Maternal Medicine, Shaare Zedek Medical Center, Jerusalem, Israel. 4. Pediatric Hematology Unit, Shaare Zedek Medical Center, Jerusalem, Israel.
Abstract
INTRODUCTION: Thiopurine exposure throughout pregnancy in patients with inflammatory bowel diseases (IBD) is common and teratogenically safe. Late consequences of in utero exposure to thiopurines and its metabolite, 6-thioguanine nucleotides (6-TGN), such as neonatal and infant anemia are still disputed. AIM: To evaluate whether 6-TGN exposure during pregnancy influences anemia in infants at 1 year of life. METHODS: A comparative observational study was performed between 2009 and 2015 at a multidisciplinary IBD clinic dedicated to pregnant women. The hemoglobin level and signs of anemia between 9 and 15 months after birth of infants born to women exposed to thiopurines throughout the entire pregnancy was compared to infants of women with no thiopurine exposure during pregnancy. RESULTS: Altogether, 34 patients, 21 in the study group and 13 in the control group, were included. The median duration of maternal thiopurine exposure prior to pregnancy was 24 months (range 12-72 months), and median dosage was 100 mg (range 50-175 mg). Maternal IBD activity, infants' iron supplementation, and iron deficiency diagnoses were similar between both groups. The infants' mean hemoglobin level (gr/dL) in the thiopurine-exposed women versus the control group was 11.48 ± 0.8 versus 11.54 ± 0.6, respectively, p = 0.81. The composite risk of any sign of infant anemia was numerically higher in the thiopurine-exposed women, 10 (47%), compared to non-exposed women, 3 (23%), p = 0.17. The mean corpuscular volume, red cell distribution width, white blood cell, and platelet counts were similar among groups. CONCLUSIONS: Thiopurine therapy during pregnancy in women with IBD is safe for long-term neonatal outcomes; still large-scale confirmatory studies are required.
INTRODUCTION:Thiopurine exposure throughout pregnancy in patients with inflammatory bowel diseases (IBD) is common and teratogenically safe. Late consequences of in utero exposure to thiopurines and its metabolite, 6-thioguanine nucleotides (6-TGN), such as neonatal and infantanemia are still disputed. AIM: To evaluate whether 6-TGN exposure during pregnancy influences anemia in infants at 1 year of life. METHODS: A comparative observational study was performed between 2009 and 2015 at a multidisciplinary IBD clinic dedicated to pregnant women. The hemoglobin level and signs of anemia between 9 and 15 months after birth of infants born to women exposed to thiopurines throughout the entire pregnancy was compared to infants of women with no thiopurine exposure during pregnancy. RESULTS: Altogether, 34 patients, 21 in the study group and 13 in the control group, were included. The median duration of maternal thiopurine exposure prior to pregnancy was 24 months (range 12-72 months), and median dosage was 100 mg (range 50-175 mg). Maternal IBD activity, infants' iron supplementation, and iron deficiency diagnoses were similar between both groups. The infants' mean hemoglobin level (gr/dL) in the thiopurine-exposed women versus the control group was 11.48 ± 0.8 versus 11.54 ± 0.6, respectively, p = 0.81. The composite risk of any sign of infantanemia was numerically higher in the thiopurine-exposed women, 10 (47%), compared to non-exposed women, 3 (23%), p = 0.17. The mean corpuscular volume, red cell distribution width, white blood cell, and platelet counts were similar among groups. CONCLUSIONS:Thiopurine therapy during pregnancy in women with IBD is safe for long-term neonatal outcomes; still large-scale confirmatory studies are required.
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