Intrauterine exposure and pharmacology of conventional thiopurine therapy in pregnant patients with inflammatory bowel disease

Jharap, Bindia; Boer, Nanne K. H. de; Stokkers, Pieter; Hommes, Daniël W.; Oldenburg, Bas; Dijkstra, Gerard; Woude, C. Janneke van der; Jong, Dirk J. de; Mulder, Chris J.; Elburg, Ruurd M. van; Bodegraven, Adriaan A. van; Crohn, Dutch Initiative on; Colitis,

doi:10.1136/gutjnl-2012-303615

Cited by 126 publications

(125 citation statements)

References 28 publications

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“…In this fetus, the normalization of the pancytopenia was concurrent with the improvement of the T-cell counts with gradual steady improvement postpartum, raising the question of potential stressors on the fetal bone marrow that were absent or minimized after delivery. In utero exposure to azathioprine has been associated with fetal anemia [11] but not to the degree as seen in this case, and not with the significant pancytopenia with T-cell abnormalities. The unaffected co-twin raises the question of whether there may have been a differential response to an external exposure which then recovered with removal of the exposure.…”

Section: Discussionmentioning

confidence: 71%

Fetal Hydrops Secondary to in utero Pancytopenia

2018

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Nonimmune hydrops remains a challenge in the prenatal setting with many cases not having a clear etiology determined prior to birth. We present an unusual case of one fetus of a dichorionic twin pair presenting at 24 weeks’ gestation with hydrops and fetal pancytopenia with complete absence of white cells of unknown etiology, as revealed by cordocentesis. Serial red blood cell transfusions resulted in resolution of hydrops and continuation of the pregnancy until 35 weeks’ gestation. Pancytopenia was noted throughout gestation and persisted in the newborn period. Moreover, the T-cell receptor excision circle (TREC) assay, a newborn screening test for severe T-cell deficiency, was abnormal at birth. Further evaluation revealed detectable TRECs and normal response to lymphocyte mitogens indicating some preserved thymic and lymphocyte function. The affected child had spontaneous resolution of the pancytopenia, including her severe T-cell deficiency, by 10 weeks of life. There has been no recurrence as of 24 months of age. The self-resolving nature of the pancytopenia is an important feature of this case of nonimmune hydrops. The abnormal TREC assay at birth in the affected infant may help explain the discordant prenatal findings.

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Section: Discussionmentioning

confidence: 71%

Fetal Hydrops Secondary to in utero Pancytopenia

2018

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“…Another study from France describing 86 pregnant IBD patients, underlined the general notion that thiopurine use during pregnancy is not associated with congenital abnormalities [10]. More recently, a prospective study in 30 female IBD patients giving birth to 31 infants during steadystate thiopurine therapy confirmed the general opinion that AZA and MP could be prescribed safely to pregnant women with IBD [11].…”

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confidence: 57%

“…A recent pharmacological study in thiopurine using pregnant females with IBD confirmed that the unborn child is exposed in utero to the pharmacologically active thiopurine metabolites 6-thioguanine nucleotides (6-TGNs). More importantly, almost two out of three neonates was born with (mild) anemia and in two newborns a thrombocytopenia was detected directly after birth [11], however not leading to apparent clinical problems. Leukopenia and anemia may occur as adverse events during AZA or MP use in non-pregnant IBD patients [12], this may be largely explained by elevated 6-TGNs levels.…”

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confidence: 99%

Thiopurines during pregnancy in inflammatory bowel disease: is there a risk for the (unborn) child?

Boer

Meij

Bodegraven

2013

Expert Review of Gastroenterology & Hepatology

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“…There are good safety data for hydroxychloroquine, sulfalazine, mesalazine and azathioprine, none of which are associated with any increase in congenital malformation rates or pregnancy loss. Although azathioprine was, in one study, 21 associated with neonatal anaemia, this was a small uncontrolled study and the results were not significant after adjustment for gestational age. 22 A prospective study is currently underway to further evaluate this.…”

Section: Immunomodulators and Immunosuppressantsmentioning

confidence: 73%

Medical problems in pregnancy

Narayan

Nelson‐Piercy

2017

Clinical Medicine

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The prevalence of medical problems in pregnancy is increasing because of a complex interplay between demographic and lifestyle factors, and developments in modern medicine. Maternal mortality and morbidity resulting from treatable medical conditions, such as venous thromboembolism, epilepsy and autoimmune disease, have not decreased in recent years. This is despite a marked decrease in overall maternal mortality. It is vital that all physicians acquire a basic knowledge and understanding of medical problems in pregnancy. This includes prepregnancy measures such as counselling and optimisation of medical therapy, as well as multidisciplinary management throughout pregnancy and the postpartum period. Prompt recognition and treatment of acute and chronic illness is of clear benefit, and most drugs and many radiological investigations may be used in pregnancy.

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Intrauterine exposure and pharmacology of conventional thiopurine therapy in pregnant patients with inflammatory bowel disease

Abstract: Pregnancy has a major effect on maternal thiopurine metabolism. In utero the unborn child is exposed to 6-TGN, but not to 6-MMP. Sixty per cent of the infants were born with anaemia, which raises the question whether infants should be tested for possible anaemia immediately after birth.

Cited by 126 publications

References 28 publications

Fetal Hydrops Secondary to in utero Pancytopenia

Fetal Hydrops Secondary to in utero Pancytopenia

Thiopurines during pregnancy in inflammatory bowel disease: is there a risk for the (unborn) child?

Medical problems in pregnancy

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