Tacrolimus (all routes) - Medication and Pregnancy KB

Tacrolimus (all routes)

Exposed non-exposed, cohort studies

Study	Country Study period Study design	Data source	Exposure definition	Non-exposure definition	Exposition period	Sample size (exposed/unexposed) Or (case / control)	Remarks	Risk of bias
Al-Otaibi 2019	Kuwait 2004 - 2017 retrospective cohort	The Hamed Alessa Organ Transplant Center of Kuwait	Pregnant women maintained on tacrolimus-based regimen (all patients also maintained on steroids plus azathioprine).	exposed to other treatment, sick Pregnant women maintained on cyclosporin-based regimen (all patients also maintained on steroids plus azathioprine).	throughout pregnancy	33 / 49
Al-Otaibi 2019	Kuwait 2004 - 2017 retrospective cohort	The Hamed Alessa Organ Transplant Center of Kuwait	All pregnancy data were collected from medical records maintained by the institution.		throughout pregnancy	33 / 49
Alvaro 2013	Spain 1986 - 2011 retrospective cohort	Hospital Universitario 12 de Octubre Surgery.	Pregnant women with orthotopic liver transplantation using tacrolimus during pregnancy.	exposed to other treatment, sick Pregnant women with orthotopic liver transplantation using cyclosporine during pregnancy.	throughout pregnancy	15 / 5	No mention of mycophenomate mofetil.
Alvaro 2013	Spain 1986 - 2011 retrospective cohort	Hospital Universitario 12 de Octubre Surgery.	Examination of the records of all women recipients of reproductive age who underwent transplantation from 1986 to 2011.		throughout pregnancy	15 / 5	No mention of mycophenomate mofetil.
Ichinose 2018	Japan 2008 - 2016 retrospective cohort	Nagasaki University Hospital, National Hospital Organization (NHO) Nagasaki Medical Center, and Japan Community Healthcare Organization (JCHO) Isahaya General Hospital.	Mothers with systemic lupus erythematosus treated with tacrolimus during the pregnancy.	unexposed, sick Mothers with systemic lupus erythematosus never treated with tacrolimus during pregnancy.	during pregnancy (anytime or not specified)	15 / 39	The patients for whom tacrolimus treatment was terminated during a pregnancy were excluded.
Ichinose 2018	Japan 2008 - 2016 retrospective cohort		Patients’ medical records were reviewed retrospectively including clinical and laboratory information.		during pregnancy (anytime or not specified)	15 / 39
Kim 2015	Seoul, Korea 1991 - 2012 prospective cohort	Asan Medical Center and Seoul National University Hospital	Deliveries given tacrolimus-based immunosuppressants mostly combined with azathioprine and/or steroids (prednisolone or methylprednisolone).	exposed to other treatment, sick Deliveries given cyclosporine-based immunosuppressants mostly combined with azathioprine and/or steroids (prednisolone or methylprednisolone).	throughout pregnancy	28 / 60	None of the pregnancies were exposed to mycophenolic acid.
Kim 2015	Seoul, Korea 1991 - 2012 prospective cohort	Asan Medical Center and Seoul National University Hospital	Medical records. Whole blood trough drug concentrations of CNI were examined at eight consecutive time points: from 12 months before delivery to 12 months after.		throughout pregnancy	28 / 60	None of the pregnancies were exposed to mycophenolic acid.
Perales-Puchalt 2012	Valencia, Spain 1995 - 2009 retrospective cohort	Hospital Universitario La Fe	Immunosuppressive drugs used was Tacrolimus. All patients used Prednisone as a co-adjuvant therapy. The treatment protocol of the patients remained unchanged during the study period.	exposed to other treatment, sick Immunosuppressive drugs used were Cyclosporine-A and four had a combination with Azathioprine. All patients used Prednisone as a co-adjuvant therapy. The treatment protocol of the patients remained unchanged during the study period.	throughout pregnancy	9 / 11	Cyclosporine-A (CsA) and Azathioprine (AZA) groups could not be add because four pregnancies had a combination of CsA and AZA. Combinations are detailed and no mycophenolate mofetil involved.
Perales-Puchalt 2012	Valencia, Spain 1995 - 2009 retrospective cohort	Hospital Universitario La Fe	Patient information was gathered for clinical records, used to obtain the information for the study in a retrospective manner. The treatment protocol of the patients remained unchanged during the study period.		throughout pregnancy	9 / 11
Thompson 2003	England 1976 - 2001 retrospective cohort	Centre for Nephrology and Department of Obstetrics and Gynaecology, Royal Free and University College School of Medicine, London.	Pregnant transplanted patients under tacrolimus, prednisolone and azathioprine.	exposed to other treatment, sick Pregnant transplanted patients under prednisolone, azathioprine -based regimens, with or without cyclosporine.	throughout pregnancy	4 / 23	No mycophenolate mofetil.
Thompson 2003	England 1976 - 2001 retrospective cohort		Review of the case notes detailed doses of immunosuppression and dose changes made during pregnancy, and other medications.		throughout pregnancy	4 / 23	No mycophenolate mofetil.
Wielgos 2012	Poland 2005 - 2010 retrospective cohort	A retrospective, single-center study conducted in the Department of Obstetrics and Gynecology, Medical University of Warsaw.	Pregnant women who underwent renal or liver transplantation treated with tacrolimus-based regimen (alone or with prednisolone and/or azathioprine).	exposed to other treatment, sick Pregnant women who underwent renal or liver transplantation treated with cyclosporine-based regimen (alone or with prednisolone and/or azathioprine)..	throughout pregnancy	21 / 9	Data of patients treated with tacrolimus who underwent both renal and liver transplantation were added. None of women were treated with mycophenolate mofetil nor sirolimus during the time of pregnancy.
Wielgos 2012	Poland 2005 - 2010 retrospective cohort		Complete data was obtained for doses and regimens of immunosuppressive medication and maternal/fetal outcomes (Not otherwise specified).		throughout pregnancy	21 / 9

Case-control studies

Study	Country Study period Study design	Data source	Case	Control	Exposition	Exposition period	Sample size (exposed/unexposed) Or (case / control)	Remarks	Risk of bias
Sugawara 2019	Japan 2007 - 2016 nested case control	Hokkaido University Hospital in Hokkaido, Japan	Pregnant women with any maternal and/or fetal complications.	Pregnant women without any maternal and/or fetal complications.	Clinical characteristics including history of rheumatic diseases treatment were recorded from medical records.	during pregnancy (anytime or not specified)	34 / 23	Maternal adverse events: 34 cases and 23 controls. Fetal adverse events: 27 cases and 30 controls. Authors made some comparison with general obstetric population in Japan (GOP), but there is no distinction between treatments (results not reported here).
Sugawara 2019	Japan 2007 - 2016 nested case control	Hokkaido University Hospital in Hokkaido, Japan	Data on pregnancy outcomes and maternal complications were collected (Not other specified).			during pregnancy (anytime or not specified)	34 / 23

Risk of bias: : NA; : low; : moderate; : serious; : critical; : unclear;

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