mercaptopurine and Premature-Birth

Inflammatory bowel disease (IBD) affects people during their prime reproductive years. The thiopurines (6-mercaptopurine and azathioprine), commonly used for induction and maintenance of remission, are U.S. Food and Drug Administration (FDA) pregnancy category D, raising concern for fetal risk. We performed a systematic review and meta-analysis to evaluate the effects of thiopurine exposure during pregnancy or at the time of conception on three measures of fetal risk in women and men with IBD.. A systematic search of PubMed and Web of Science using a combination of Mesh and text terms was performed to identify studies reporting birth outcomes from IBD women and men exposed to thiopurines within 3 months of conception and/or during pregnancy. A meta-analysis was performed using the random effects model to pool estimates and report odds ratio (OR) for three outcomes in women: low birth weight (LBW), preterm birth, and congenital abnormalities and one in men: congenital abnormalities.. In women with IBD exposed to thiopurines, the pooled ORs for LBW, preterm birth, and congenital abnormalities were 1.01 (95% confidence interval [CI] 0.96, 1.06), 1.67 (95% CI 1.26, 2.20), and 1.45 (95% CI 0.99, 2.13), respectively. In men, the pooled OR for congenital abnormality was 1.87 (95% CI 0.67, 5.25).. Thiopurine exposure in women with IBD was not associated with LBW or congenital abnormalities, but was associated with preterm birth. Exposure in men at the time of conception was not associated with congenital abnormalities.

Topics: Azathioprine; Congenital Abnormalities; Female; Humans; Immunosuppressive Agents; Infant, Low Birth Weight; Infant, Newborn; Inflammatory Bowel Diseases; Male; Mercaptopurine; Meta-Analysis as Topic; Odds Ratio; Pregnancy; Pregnancy Complications; Premature Birth; Prognosis

Maintaining remission of inflammatory bowel disease (IBD) during pregnancy is critical for positive pregnancy outcomes. Conflicting data exist regarding the association between thiopurine use for IBD treatment in pregnancy and adverse pregnancy outcomes and this meta-analysis aims to clarify this association. A meta-analysis was performed of all original human studies reporting outcomes in pregnancy in patients receiving thiopurines. Nine studies satisfied the inclusion criteria and a total of 494 patients with IBD and 2,782 IBD controls were reported. When compared with healthy women, those receiving thiopurines had an increased risk for congenital malformations (RR 1.45; 95% CI 1.07-1.96; p = 0.02); however, when compared with IBD controls, there was no increased risk (RR 1.37; 95% CI 0.92-2.05; p = 0.1). These data provide support for thiopurines having a minimal risk, if any, to the fetus.

Topics: Abnormalities, Drug-Induced; Abortion, Spontaneous; Animals; Azathioprine; Birth Weight; Case-Control Studies; Female; Humans; Immunosuppressive Agents; Inflammatory Bowel Diseases; Mercaptopurine; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Premature Birth

The aim of this study was to describe the long-term health outcomes of children born to mothers with inflammatory bowel disease (IBD) and to assess the impact of maternal IBD medication use on these outcomes.. We performed a multicentre retrospective study in The Netherlands. Women with IBD who gave birth between 1999 and 2018 were enrolled from 20 participating hospitals. Information regarding disease characteristics, medication use, lifestyle, pregnancy outcomes and long-term health outcomes of children was retrieved from mothers and medical charts. After consent of both parents, outcomes until 5 years were also collected from general practitioners. Our primary aim was to assess infection rate and our secondary aims were to assess adverse reactions to vaccinations, growth, autoimmune diseases and malignancies.. We included 1000 children born to 626 mothers (381 (61%) Crohn's disease, 225 (36%) ulcerative colitis and 20 (3%) IBD unclassified). In total, 196 (20%) had intrauterine exposure to anti-tumour necrosis factor-α (anti-TNF-α) (60 with concomitant thiopurine) and 240 (24%) were exposed to thiopurine monotherapy. The 564 children (56%) not exposed to anti-TNF-α and/or thiopurine served as control group. There was no association between adverse long-term health outcomes and in utero exposure to IBD treatment. We did find an increased rate of intrahepatic cholestasis of pregnancy (ICP) in case thiopurine was used during the pregnancy without affecting birth outcomes and long-term health outcomes of children. All outcomes correspond with the general age-adjusted population.. In our study, we found no association between in utero exposure to anti-TNF-α and/or thiopurine and the long-term outcomes antibiotic-treated infections, severe infections needing hospital admission, adverse reactions to vaccinations, growth failure, autoimmune diseases and malignancies.

Topics: Adalimumab; Adult; Anti-Bacterial Agents; Autoimmune Diseases; Cesarean Section; Child Development; Child, Preschool; Congenital Abnormalities; Drug Prescriptions; Drug Therapy, Combination; Female; Gastrointestinal Agents; Humans; Infant; Infant, Newborn; Infant, Small for Gestational Age; Infections; Inflammatory Bowel Diseases; Infliximab; Mercaptopurine; Neoplasms; Netherlands; Patient Admission; Pregnancy; Pregnancy Complications; Premature Birth; Prenatal Exposure Delayed Effects; Retrospective Studies; Tumor Necrosis Factor Inhibitors; Vaccines

Information on the safety of paternal use of azathioprine (AZA) and 6-mercaptopurine (6-MP) prior to conception is limited. Based on nationwide data from the Danish health registries, we examined the association between paternal use of AZA/6-MP within 3 months before conception and adverse birth outcomes.. This nationwide cohort study is based on data from all singletons born in Denmark from 1 January 1997 through 2013. Children fathered by men who used AZA/6-MP within 3 months before conception constituted the exposed cohort (N=699), and children fathered by men who did not use AZA/6-MP 3 months prior to conception constituted the unexposed cohort (N=1 012 624). The outcomes were congenital abnormalities (CAs), preterm birth and small for gestational age (SGA). We adjusted for multiple covariates and performed a restricted analysis of men with IBD.. There were no significantly increased risks of CAs, preterm birth or SGA in exposed versus unexposed cohorts of children. The adjusted ORs were 0.82 (95% CI 0.53 to 1.28) for CAs, 1.17 (95% CI 0.72 to 1.92) for preterm birth and 1.38 (95% CI 0.76 to 2.51) for SGA. Restricting our analysis to fathers with IBD showed similar results with no significantly increased risk of adverse birth outcomes.. This nationwide study is the largest to date, examining the effect of preconceptual paternal use of AZA/6-MP on birth outcomes in live born singletons. The results of no significantly increased risks of adverse birth outcomes are reassuring and support the continuation of paternal AZA/6-MP treatment during conception.

Topics: Adult; Azathioprine; Case-Control Studies; Cohort Studies; Congenital Abnormalities; Denmark; Female; Humans; Immunosuppressive Agents; Infant, Small for Gestational Age; Inflammatory Bowel Diseases; Male; Mercaptopurine; Paternal Exposure; Pregnancy; Pregnancy Outcome; Premature Birth; Young Adult

Previous data on inflammatory bowel disease (IBD) relapse during pregnancy mainly originate from retrospective studies. The aim of this study was therefore (i) to evaluate the effect of active disease at conception and IBD disease type on disease relapse during pregnancy and (ii) to study the effects of disease relapse during pregnancy on birth outcomes in a prospective cohort with adequate representation of current treatments.. From 2008 to 2014, IBD women were recruited from an ongoing prospective clinical cohort. All patients with confirmed IBD diagnosis with a pregnancy wish or pregnancy were prospectively followed-up until pregnancy and delivery. Disease relapse was measured at each visit. Birth outcomes were recorded from the obstetrician.. A total of 298 pregnancies were observed in 229 IBD patients (157 Crohn's disease (CD), 66 ulcerative colitis (UC), and 6 IBD unclassified), resulting in 226 live births. Active disease at conception was strongly associated with disease relapse during pregnancy (aOR=7.66, 95% confidence interval (CI): 3.77-15.54). UC patients experienced relapse during pregnancy more often than CD patients, independent of maternal age, smoking, periconceptional disease activity, previous IBD surgery, and the use of immunosuppressives or anti-tumor necrosis factor (TNF) (aOR=3.71, 95% CI:1.86-7.40). Disease relapse was not associated with adverse birth outcomes such as spontaneous abortion, low-birth weight, or preterm birth.. This study confirms that active disease around conception increases the risk of disease relapse during pregnancy. In addition, UC patients relapse more often during pregnancy than CD patients. Birth outcomes were excellent, reflecting the stringent follow-up and treatment of this group of patients.

Topics: Abortion, Spontaneous; Adult; Anti-Inflammatory Agents, Non-Steroidal; Cohort Studies; Colitis, Ulcerative; Crohn Disease; Female; Glucocorticoids; Humans; Immunosuppressive Agents; Infant, Low Birth Weight; Infant, Newborn; Inflammatory Bowel Diseases; Maintenance Chemotherapy; Mercaptopurine; Mesalamine; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Premature Birth; Prospective Studies; Recurrence; Tumor Necrosis Factor-alpha

To investigate the effects of azathioprine/6-mercaptopurine (AZA/6-MP) on birth outcomes in women with inflammatory bowel disease (IBD).. Details of pregnant women with IBD were obtained through an ObstetriX Database in 3 major teaching hospitals in Sydney from 1996 to 2006. Medical records were reviewed. Birth outcomes of interest were single live births, low birth weight (LBW) at term (<2500 g), preterm births (<37 weeks gestation), neonatal adverse outcomes, and congenital anomaly. Placental blood flow during third trimester of pregnancy was measured using arterial Doppler ultrasonography, where available.. All women had IBD diagnosed before pregnancy. 19 births were exposed to AZA/6-MP. 74 births that were never exposed to AZA/6-MP were selected as controls. Preterm birth was seen in 26.3% of the exposed group as compared to 13.5% of controls (p<0.001). However, in univariate analysis, preterm birth was not associated with AZA/6-MP (OR=2.28; CI: 0.67-7.73). There was 1 neonatal adverse outcome in the exposed group as compared to 4 in controls (5.3% vs 5.4%, p=0.97). One congenital anomaly was seen in each group (p=0.27). No LBW at term was seen in either group. Placental blood flow in 4 women exposed to AZA/6-MP was normal.. The use of AZA/6-MP during pregnancy in IBD women was not associated with an increased risk of preterm birth, LBW at term, neonatal adverse outcomes and congenital anomalies.

Topics: Adult; Azathioprine; Female; Gestational Age; Humans; Immunosuppressive Agents; Infant, Low Birth Weight; Infant, Newborn; Inflammatory Bowel Diseases; Live Birth; Mercaptopurine; Placental Circulation; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Premature Birth