Anti-TNF Therapy in Pregnant Women With Inflammatory Bowel Disease: Effects of Therapeutic Strategies on Disease Behavior and Birth Outcomes.

BACKGROUND Active inflammatory bowel disease (IBD) adversely affects pregnancy outcomes. Little is known about the risk of relapse after stopping anti-tumor necrosis factor (anti-TNF) treatment during pregnancy. We assessed the risk of relapse before delivery in women who discontinued anti-TNF treatment before gestational week (GW) 30, predictors of reduced infant birth weight, a marker associated with long-term adverse outcomes, and rates and satisfaction with counseling. METHODS Pregnant women with IBD receiving anti-TNF treatment were prospectively invited to participate in an electronic questionnaire carried out in 22 hospitals in Denmark, Australia, and New Zealand from 2011 to 2015. Risk estimates were calculated, and birth weight was investigated using t tests and linear regression. RESULTS Of 175 women invited, 153 (87%) responded. In women in remission, the relapse rate did not differ significantly between those who discontinued anti-TNF before GW 30 (1/46, 2%) compared with those who continued treatment (8/74, 11%; relative risk, 0.20; 95% confidence interval [CI], 0.02 to 1.56; P = 0.08). Relapse (P = 0.001) and continuation of anti-TNF therapy after GW 30 (P = 0.007) were independently associated with reduced mean birth weight by 367 g (95% CI, 145 to 589 g; relapse) and 274 g (95% CI, 77 to 471 g; anti-TNF exposure after GW 30). Of 134 (88%) women who received counseling, 116 (87%) were satisfied with the information provided. CONCLUSIONS To minimize fetal exposure in women in remission, discontinuation of anti-TNF before GW 30 seems safe. Relapse and continuation of anti-TNF therapy after GW 30 were each independently associated with lower birth weight, although without an increased risk for birth weight <2500 g. Most women received and were satisfied with counseling.

[1]  M. Dubinsky,et al.  Inflammatory Bowel Disease in Pregnancy Clinical Care Pathway: A Report From the American Gastroenterological Association IBD Parenthood Project Working Group. , 2019, Inflammatory bowel diseases.

[2]  W. Czuber-Dochan,et al.  Systematic review: the consequences of psychosocial effects of inflammatory bowel disease on patients′ reproductive health , 2018, Alimentary pharmacology & therapeutics.

[3]  A. Barkun,et al.  Continuous Anti‐TNF&agr; Use Throughout Pregnancy: Possible Complications For the Mother But Not for the Fetus. A Retrospective Cohort on the French National Health Insurance Database (EVASION) , 2018, The American Journal of Gastroenterology.

[4]  J. Gisbert,et al.  Long-Term Safety of In Utero Exposure to Anti-TNFα Drugs for the Treatment of Inflammatory Bowel Disease: Results from the Multicenter European TEDDY Study , 2018, The American Journal of Gastroenterology.

[5]  B. Nørgård,et al.  Anti–TNF-&agr; Use During the Third Trimester of Pregnancy in Women with Moderate–severe Inflammatory Bowel Disease and the Risk of Preterm Birth and Low Birth Weight , 2017, Inflammatory bowel diseases.

[6]  R. Gearry,et al.  Fecal Calprotectin Is Not Affected by Pregnancy: Clinical Implications for the Management of Pregnant Patients with Inflammatory Bowel Disease , 2017, Inflammatory bowel diseases.

[7]  Christopher F. Martin,et al.  Exposure to Biologic Therapy and Childhood Development among Offspring of Women with Inflammatory Bowel Disease: Results from the Piano Registry , 2017 .

[8]  G. Nguyen,et al.  "Just in Time": When Is It Safe to Administer Live Vaccines to Infants Exposed to Anti-Tumor Necrosis Factor Agents In Utero? , 2016, Gastroenterology.

[9]  C. J. van der Woude,et al.  Preconception Care Reduces Relapse of Inflammatory Bowel Disease During Pregnancy. , 2016, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[10]  Steven J Brown,et al.  Concentrations of Adalimumab and Infliximab in Mothers and Newborns, and Effects on Infection. , 2016, Gastroenterology.

[11]  A. Bitton,et al.  The Toronto Consensus Statements for the Management of Inflammatory Bowel Disease in Pregnancy. , 2016, Gastroenterology.

[12]  D. Kennedy,et al.  Pregnancy outcome after TNF-α inhibitor therapy during the first trimester: a prospective multicentre cohort study. , 2015, British journal of clinical pharmacology.

[13]  C. J. van der Woude,et al.  Tailored anti-TNF therapy during pregnancy in patients with IBD: maternal and fetal safety , 2015, Gut.

[14]  C. J. van der Woude,et al.  The second European evidenced-based consensus on reproduction and pregnancy in inflammatory bowel disease. , 2015, Journal of Crohn's & colitis.

[15]  J. Andrews,et al.  It IS worth the effort: Patient knowledge of reproductive aspects of inflammatory bowel disease improves dramatically after a single group education session. , 2014, Journal of Crohn's & colitis.

[16]  M. Nørgaard,et al.  Self-reported adherence to medical treatment, breastfeeding behaviour, and disease activity during the postpartum period in women with Crohn’s disease , 2014, Scandinavian journal of gastroenterology.

[17]  M. Nørgaard,et al.  Influence of medical treatment, smoking and disease activity on pregnancy outcomes in Crohn's disease , 2014, Scandinavian journal of gastroenterology.

[18]  M. Dubinsky,et al.  Placental transfer of anti-tumor necrosis factor agents in pregnant patients with inflammatory bowel disease. , 2013, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[19]  A. Hokken-Koelega,et al.  Circulating maternal cytokines influence fetal growth in pregnant women with rheumatoid arthritis , 2012, Annals of the rheumatic diseases.

[20]  J. Mclaughlin,et al.  Patients' knowledge of pregnancy‐related issues in inflammatory bowel disease and validation of a novel assessment tool (‘CCPKnow’) , 2012, Alimentary pharmacology & therapeutics.

[21]  M. Nørgaard,et al.  Self‐reported adherence to medical treatment prior to and during pregnancy among women with ulcerative colitis , 2011, Inflammatory bowel diseases.

[22]  M. Nørgaard,et al.  Self‐reported antenatal adherence to medical treatment among pregnant women with Crohn’s disease , 2010, Alimentary pharmacology & therapeutics.

[23]  A. Kornbluth,et al.  Relapses of Inflammatory Bowel Disease During Pregnancy: In-Hospital Management and Birth Outcomes , 2008, The American Journal of Gastroenterology.

[24]  R. Devlieger,et al.  Maternal obesity: pregnancy complications, gestational weight gain and nutrition , 2008, Obesity reviews : an official journal of the International Association for the Study of Obesity.

[25]  J. Bartha,et al.  Inflammatory cytokines in intrauterine growth retardation , 2003, Acta obstetricia et gynecologica Scandinavica.

[26]  D. Barker,et al.  Mothers' pelvic size, fetal growth, and death from stroke and coronary heart disease in men in the UK , 1996, The Lancet.

[27]  D J Barker,et al.  Fetal origins of coronary heart disease , 1995, BMJ.

[28]  D. Barker,et al.  WEIGHT IN INFANCY AND DEATH FROM ISCHAEMIC HEART DISEASE , 1989, The Lancet.

[29]  L. Keefer,et al.  Documentation of reproductive health counseling and contraception in women with inflammatory bowel diseases. , 2014, Patient education and counseling.

[30]  A. Harris,et al.  Carboplatin/cisplatin , 2012, Reactions Weekly.