Parental IBD and Long-term Health Outcomes in the Offspring.

For decades, the research on reproductive consequences in women with inflammatory bowel disease (IBD) has focused on short-term outcomes, including adverse pregnancy outcomes (eg, abruptio placenta, placenta previa, preeclampsia/eclampsia) and adverse birth outcomes (eg, small for gestational age, preterm birth, and congenital malformations). The long-term health outcomes of the children of parents with IBD have been studied to a much lesser extent, and there is a critical research gap in understanding the influence of parental IBD on long-term outcomes. In this review, we propose the reasons for this lack of evidence and highlight the weakest areas of the research on the impact of parental IBD on offspring health. We will focus on health outcomes in children of parents with IBD from an age of 1 year through childhood, adolescence, and adulthood.

[1]  M. Fraenkel,et al.  Maternal Hypothyroidism during Pregnancy and the Risk of Pediatric Endocrine Morbidity in the Offspring , 2018, American Journal of Perinatology.

[2]  M. Lukáš,et al.  Safety of Anti-TNF-Alpha Therapy During Pregnancy on Long-term Outcome of Exposed Children: A Controlled, Multicenter Observation. , 2018, Inflammatory bowel diseases.

[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]  T. Yorifuji,et al.  Genetic basis of early‐onset, maturity‐onset diabetes of the young‐like diabetes in Japan and features of patients without mutations in the major MODY genes: Dominance of maternal inheritance , 2018, Pediatric diabetes.

[5]  G. Veerappan Continuing Medical Education Questions: March 2018: 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.

[6]  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.

[7]  B. Nørgård,et al.  Birth outcomes after preconception paternal exposure to methotrexate: A nationwide cohort study. , 2017, Reproductive toxicology.

[8]  B. Nørgård,et al.  Paternal use of azathioprine/6-mercaptopurine or methotrexate within 3 months before conception and long-term health outcomes in the offspring-A nationwide cohort study. , 2017, Reproductive toxicology.

[9]  Å. Lernmark,et al.  Are Perinatal Events Risk Factors for Childhood Thyroid Autoimmunity , 2017, European Thyroid Journal.

[10]  B. Nørgård,et al.  The Association Between Maternal Chronic Inflammatory Bowel Disease and Long-term Health Outcomes in Children—A Nationwide Cohort Study , 2017, Inflammatory bowel diseases.

[11]  B. Nørgård,et al.  The Effect of Disease Activity on Birth Outcomes in a Nationwide Cohort of Women with Moderate to Severe Inflammatory Bowel Disease , 2017, Inflammatory bowel diseases.

[12]  B. Nørgård,et al.  Birth Outcomes in Children Fathered by Men Treated with Anti-TNF-α Agents Before Conception , 2016, The American Journal of Gastroenterology.

[13]  B. Nørgård,et al.  Reassuring results on birth outcomes in children fathered by men treated with azathioprine/6-mercaptopurine within 3 months before conception: a nationwide cohort study , 2016, Gut.

[14]  D. Landau,et al.  Maternal Inflammatory Bowel Disease During Pregnancy is Not a Risk Factor for Long-term Morbidity of the Offspring. , 2016, Journal of Crohn's & colitis.

[15]  H. Sørensen,et al.  Low Risk of Birth Defects for Infants Whose Mothers Are Treated With Anti-Tumor Necrosis Factor Agents During Pregnancy. , 2016, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[16]  D. Greenwald,et al.  Review article: the safety of therapeutic drugs in male inflammatory bowel disease patients wishing to conceive , 2015, Alimentary pharmacology & therapeutics.

[17]  Vibeke Andersen,et al.  Familial Risk of Inflammatory Bowel Disease: A Population-Based Cohort Study 1977–2011 , 2015, The American Journal of Gastroenterology.

[18]  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.

[19]  H. Sørensen,et al.  Autism spectrum disorders in children of parents with inflammatory bowel disease – a nationwide cohort study in Denmark , 2014, Clinical and experimental gastroenterology.

[20]  M. Lukáš,et al.  Impact of Anti–Tumor Necrosis Factor Alpha Antibodies Administered to Pregnant Women With Inflammatory Bowel Disease on Long-term Outcome of Exposed Children , 2014, Inflammatory bowel diseases.

[21]  Diana Anderson,et al.  Male-mediated developmental toxicity , 2013, Asian journal of andrology.

[22]  S. Reif,et al.  Maternal inflammatory bowel disease has short and long-term effects on the health of their offspring: a multicenter study in Israel. , 2013, Journal of Crohn's & colitis.

[23]  H. Sørensen,et al.  Parental Inflammatory Bowel Disease and Risk of Asthma in Offspring: A Nationwide Cohort Study in Denmark , 2013, Clinical and Translational Gastroenterology.

[24]  C. Kneepkens,et al.  Long‐term follow‐up of children exposed intrauterine to maternal thiopurine therapy during pregnancy in females with inflammatory bowel disease , 2013, Alimentary pharmacology & therapeutics.

[25]  A. Hubalewska-Dydejczyk,et al.  How Far Are We from Understanding the Genetic Basis of Hashimoto's Thyroiditis? , 2013, International reviews of immunology.

[26]  A. Engeland,et al.  Outcomes after anti-rheumatic drug use before and during pregnancy: a cohort study among 150 000 pregnant women and expectant fathers , 2012, Scandinavian journal of rheumatology.

[27]  I S Kohane,et al.  Identification of autoimmune gene signatures in autism , 2011, Translational Psychiatry.

[28]  T. Tomson,et al.  Dose-dependent risk of malformations with antiepileptic drugs: an analysis of data from the EURAP epilepsy and pregnancy registry , 2011, The Lancet Neurology.

[29]  W. Reinisch,et al.  Long-term follow-up of babies exposed to azathioprine in utero and via breastfeeding. , 2011, Journal of Crohn's & colitis.

[30]  F. Granath,et al.  Congenital abnormalities and other birth outcomes in children born to women with ulcerative colitis in Denmark and Sweden , 2011, Inflammatory bowel diseases.

[31]  J. Barrett,et al.  New IBD genetics: common pathways with other diseases , 2011, Gut.

[32]  L. Mackillop,et al.  European evidenced-based consensus on reproduction in inflammatory bowel disease. , 2010, Journal of Crohn's & colitis.

[33]  P. Sparén,et al.  Parental Autoimmune Diseases Associated With Autism Spectrum Disorders in Offspring , 2010, Epidemiology.

[34]  H. Sørensen,et al.  Crohn's disease is a risk factor for preterm birth. , 2010, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[35]  K. Hemminki,et al.  Familial Association of Inflammatory Bowel Diseases With Other Autoimmune and Related Diseases , 2010, The American Journal of Gastroenterology.

[36]  C. Lees,et al.  Genetics of inflammatory bowel disease: implications for disease pathogenesis and natural history , 2009, Expert review of gastroenterology & hepatology.

[37]  P. Mortensen,et al.  Association of Family History of Autoimmune Diseases and Autism Spectrum Disorders , 2009, Pediatrics.

[38]  D. Corley,et al.  Pregnancy outcomes in women with inflammatory bowel disease: a large community-based study from Northern California. , 2007, Gastroenterology.

[39]  B. Nørgård,et al.  Disease Activity in Pregnant Women With Crohn's Disease and Birth Outcomes: A Regional Danish Cohort Study , 2007, The American Journal of Gastroenterology.

[40]  L. Herrinton,et al.  Clustering of Inflammatory Bowel Disease With Immune Mediated Diseases Among Members of a Northern California-Managed Care Organization , 2007, The American Journal of Gastroenterology.

[41]  S. E. Mouridsen,et al.  Autoimmune diseases in parents of children with infantile autism: a case—control study , 2007, Developmental medicine and child neurology.

[42]  P. Tekkis,et al.  A meta-analysis on the influence of inflammatory bowel disease on pregnancy , 2006, Gut.

[43]  P. Ashwood,et al.  The immune response in autism: a new frontier for autism research , 2006, Journal of leukocyte biology.

[44]  J. Lewis,et al.  Increased risk for demyelinating diseases in patients with inflammatory bowel disease. , 2005, Gastroenterology.

[45]  C. Bernstein,et al.  The clustering of other chronic inflammatory diseases in inflammatory bowel disease: a population-based study. , 2005, Gastroenterology.

[46]  A. Scialli,et al.  The transport of chemicals in semen. , 2005, Birth defects research. Part B, Developmental and reproductive toxicology.

[47]  B. Nørgård,et al.  The risk of congenital abnormalities in children fathered by men treated with azathioprine or mercaptopurine before conception , 2004, Alimentary pharmacology & therapeutics.

[48]  A. Ekbom The Epidemiology of IBD: A Lot of Data but Little Knowledge. How Shall We Proceed? , 2004, Inflammatory bowel diseases.

[49]  E. Lindberg,et al.  Inflammatory bowel disease in a Swedish twin cohort: a long-term follow-up of concordance and clinical characteristics. , 2003, Gastroenterology.

[50]  W. Webster,et al.  Prescription drugs and pregnancy , 2003, Expert opinion on pharmacotherapy.

[51]  G. Koren,et al.  Effect of methotrexate on male fertility. , 2003, Canadian family physician Medecin de famille canadien.

[52]  E. Boyko,et al.  Outcomes of infants born to mothers with inflammatory bowel disease: a population-based cohort study , 2002, American Journal of Gastroenterology.

[53]  C. Mittermaier,et al.  Azathioprine treatment and male fertility in inflammatory bowel disease. , 2001, Gastroenterology.

[54]  W. Webster,et al.  Is this drug safe in pregnancy? , 2001, Reproductive toxicology.

[55]  H. Sørensen,et al.  Birth outcomes of women with ulcerative colitis: a nationwide Danish cohort study , 2000, American Journal of Gastroenterology.

[56]  M. Orholm, V. Binder, T. I. A. Sørensen, L. P. Ras Concordance of Inflammatory Bowel Disease among Danish Twins: Results of a Nationwide Study , 2000 .

[57]  J. Trasler,et al.  Teratogen update: paternal exposures-reproductive risks. , 1999, Teratology.

[58]  H. Sørensen,et al.  Pregnancy outcome for women with Crohn's disease: a follow-up study based on linkage between national registries , 1998, American Journal of Gastroenterology.

[59]  B. Korelitz,et al.  Outcome of pregnancies when fathers are treated with 6-mercaptopurine for inflammatory bowel disease , 1998, American Journal of Gastroenterology.

[60]  S. Cnattingius,et al.  Pregnancy outcomes in women with inflammatory bowel disease--a population-based cohort study. , 1997, American journal of obstetrics and gynecology.

[61]  R. Pounder,et al.  Genetics versus environment in inflammatory bowel disease: results of a British twin study , 1996, BMJ.

[62]  D. Anderson,et al.  Malformed foetuses and karyotype abnormalities in the offspring of cyclophosphamide and allyl alcohol-treated male rats. , 1990, Mutation research.

[63]  Sumner J. Yaffe,et al.  Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 8th Edition , 1986 .

[64]  A. Levi,et al.  MALE INFERTILITY DUE TO SULPHASALAZINE , 1979, The Lancet.

[65]  Davis Jg Letter: Curious curd. , 1975 .

[66]  C. Chambers,et al.  Drug Safety and Risk of Adverse Outcomes for Pregnant Patients With Inflammatory Bowel Disease. , 2017, Gastroenterology.

[67]  Subrata Ghosh,et al.  Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. , 2012, Gastroenterology.

[68]  Yulian Zhao,et al.  Effects of Pharmaceutical Medications on Male Fertility , 2012, Journal of reproduction & infertility.

[69]  Kevin G Becker,et al.  Autism, asthma, inflammation, and the hygiene hypothesis. , 2007, Medical hypotheses.

[70]  James L. Schardein,et al.  Chemically Induced Birth Defects , 1985 .