Thrombocytosis and Transaminitis in Infants Born to Women With Inflammatory Bowel Disease Is Associated With Exposure to Maternal Inflammation In Utero

被引:0
作者
Prentice, Ralley [1 ,2 ,3 ,8 ]
Flanagan, Emma [2 ,4 ]
Wright, Emily [2 ,4 ]
Hardikar, Winita [4 ,5 ]
Ross, Alyson [2 ]
Burns, Megan [1 ]
Prideaux, Lani [1 ]
Connell, William [2 ,4 ]
Sparrow, Miles [3 ,6 ]
De Cruz, Peter [3 ,7 ]
Lust, Mark [2 ]
Goldberg, Rimma [1 ,3 ]
Vogrin, Sara [4 ]
Greeve, Tessa [1 ]
Bell, Sally [1 ,3 ,4 ]
机构
[1] Monash Hlth, Gastroenterol Dept, Melbourne, Australia
[2] St Vincents Hosp Melbourne, Gastroenterol Dept, Melbourne, Australia
[3] Monash Univ, Fac Med Nursing & Hlth Sci, Melbourne, Australia
[4] Univ Melbourne, Fac Med Dent & Hlth Sci, Melbourne, Vic, Australia
[5] Royal Childrens Hosp, Gastroenterol Dept, Melbourne, Australia
[6] Alfred Hlth, Gastroenterol Dept, Melbourne, Australia
[7] Austin Hlth, Gastroenterol Dept, Melbourne, Australia
[8] Monash Hlth, Dept Gastroenterol, 246 Clayton Rd, Clayton, Vic 3146, Australia
基金
英国医学研究理事会;
关键词
pregnancy; inflammatory bowel disease; thiopurines; inflammation; TRANSIENT HYPERPHOSPHATASEMIA; REFERENCE RANGES; INTERLEUKIN-6; THERAPY; AZATHIOPRINE; NEUTROPENIA; THIOPURINES; SECONDARY; OUTCOMES; ANEMIA;
D O I
10.1093/ibd/izae008
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background Despite reassuring clinical safety data, thrombocytosis, anemia, lymphopenia, and liver function derangements have been observed in infants born to women with inflammatory bowel disease (IBD) treated with thiopurines and biologics. We aimed to define the prevalence, course, associations, and clinical impact of hematological and biochemical abnormalities in such infants.Methods This multicenter prospective cohort study assessed clinical, hematologic, and biochemical outcomes of infants exposed to thiopurines or biologics in utero for management of maternal IBD. Liver transaminases, full blood examination, and infant thiopurine metabolites (where exposed) were taken at delivery and 6 weeks of age. Abnormal results were repeated until normalization. Infants were followed clinically by a pediatric gastroenterologist up to 2 years of age.Results A total of 130 infants were included. Thrombocytosis and elevated alanine transaminase (ALT) were seen in over half of infants up to 6 months of age with no significant clinical impact. Elevated ALT was associated with increasing maternal C-reactive protein in second trimester, while thrombocytosis was associated with increasing maternal C-reactive protein and fecal calprotectin in third trimester. Preceding infection and vaccination were associated with an increased risk of elevated alkaline phosphatase at 3 months. In those exposed to thiopurines, increasing maternal 6-methylmercaptopurine at delivery was associated with increased ALT to 6 months.Conclusions Infants born to women with IBD commonly developed thrombocytosis, elevated alkaline phosphatase, and elevated ALT. These findings were associated with exposure to maternal inflammation, elevated 6-methylmercaptopurine at delivery, and infant vaccinations and infections, and had minimal clinical consequence. Hematological and biochemical abnormalities have been observed in infants born to women with inflammatory bowel disease. This prospective study shows that thrombocytosis and elevated alanine transaminase are common in infants to 6 months of age and are associated with maternal inflammation, rather than with in utero medication exposures.
引用
收藏
页码:2323 / 2334
页数:12
相关论文
共 48 条
[1]   The fetal response to maternal inflammation is dependent upon maternal IL-6 in a murine model [J].
Bermick, Jennifer ;
Watson, Sarah ;
Lueschow, Shiloh ;
McElroy, Steven J. .
CYTOKINE, 2023, 167
[2]   Fetal hemolytic anemia associated with maternal sulfasalazine therapy during pregnancy [J].
Bokström, H ;
Holst, RM ;
Hafström, O ;
Swolin, B ;
Johansson, ML ;
Brunlöf, G ;
Hedner, T .
ACTA OBSTETRICIA ET GYNECOLOGICA SCANDINAVICA, 2006, 85 (01) :118-121
[3]   Birth Outcomes in Women with Inflammatory Bowel Disease: Effects of Disease Activity and Drug Exposure [J].
Broms, Gabriella ;
Granath, Fredrik ;
Linder, Marie ;
Stephansson, Olof ;
Elmberg, Maria ;
Kieler, Helle .
INFLAMMATORY BOWEL DISEASES, 2014, 20 (06) :1091-1098
[4]   Elucidating the Mechanism of 6-mercaptopurine Induced Hepatotoxicity and How Combination with Allopurinol Eliminates the Hepatotoxicity [J].
Cunningham, Bethany ;
Krishnamurthy, Jayasree ;
Deutsch, Jennifer ;
Flora, Michael ;
Lieuw, Kenneth .
PEDIATRICS, 2018, 141
[5]   Interleukin-6 in the maternal circulation reaches the rat fetus in mid-gestation [J].
Dahlgren, Jovanna ;
Samuelsson, Anne-Maj ;
Jansson, Thomas ;
Holmang, Agneta .
PEDIATRIC RESEARCH, 2006, 60 (02) :147-151
[6]   Primary and secondary thrombocytosis in childhood [J].
Dame, C ;
Sutor, AH .
BRITISH JOURNAL OF HAEMATOLOGY, 2005, 129 (02) :165-177
[7]   Systemic inflammation as fuel for acute liver injury in COVID-19 [J].
Effenberger, Maria ;
Grander, Christoph ;
Grabherr, Felix ;
Griesmacher, Andrea ;
Ploner, Thomas ;
Hartig, Frank ;
Bellmann-Weiler, Rosa ;
Joannidis, Michael ;
Zoller, Heinz ;
Weiss, Guenter ;
Adolph, Timon Erik ;
Tilg, Herbert .
DIGESTIVE AND LIVER DISEASE, 2021, 53 (02) :158-165
[8]   Mesalazine as a cause of fetal anemia and hydrops fetalis A case report [J].
Ek, Sverker ;
Rosenborg, Staffan .
MEDICINE, 2017, 96 (50)
[9]   Age- and Sex-related Reference Ranges of Alanine Aminotransferase Levels in Children: European Paediatric HCV Network [J].
England, Kirsty ;
Thorne, Claire ;
Pembrey, Lucy ;
Tovo, Pier-Angelo ;
Newell, Marie-Louise .
JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION, 2009, 49 (01) :71-77
[10]   Maternal thiopurine metabolism during pregnancy in inflammatory bowel disease and clearance of thiopurine metabolites and outcomes in exposed neonates [J].
Flanagan, Emma ;
Wright, Emily K. ;
Hardikar, Winita ;
Sparrow, Miles P. ;
Connell, William R. ;
Kamm, Michael A. ;
De Cruz, Peter ;
Brown, Steven J. ;
Thompson, Alexander ;
Greenway, Anthea ;
Westley, Ian ;
Barclay, Murray ;
Ross, Alyson L. ;
Kiburg, Katerina V. ;
Bell, Sally J. .
ALIMENTARY PHARMACOLOGY & THERAPEUTICS, 2021, 53 (07) :810-820