Azoles (local routes only) - Medication and Pregnancy KB

Azoles (local routes only)

Exposed non-exposed studies (cohort)

Study	Country Study period	Population source	Exposure definition	Non-exposure definition	Sample size	Rmk
Araujo - Sertaconazole (Topical), 2022	France 2004 - 2018	Pregnant women in the Haute-Garonne region whose pregnancy ended between July 2004 and December 2018.	Pregnant women exposed to sertaconazole at least once during pregnancy.	unexposed (general population or NOS) Pregnant women not exposed to sertaconazole at least once during pregnancy.	16222 / 91976
Daniel - Clotrimazole and/or miconazole (Vaginal), 2018	Israel 2003 - 2009	All clinically apparent pregnancies to women 15-45 years of age registered with Clalit Health Services (CHS) maintenance organization who were admitted for birth or diagnosed with spontaneous abortion at Soroka Medical Center (SMC).	Dispensation of vaginal clotrimazole and/or miconazole from the first day of the last menstrual period until the date of admission to the hospital for pregnancies that resulted in spontaneous abortion or until 20 weeks of pregnancy for pregnancies that ended with birth.	unexposed (general population or NOS) No dispensation of anti-mycotic medication (vaginal or oral).	3246 / 62137	Vaginal exposure.
Jick - Azole (Topical route), 1999	United Kingdom Not specified	Not specified	Pregnant women who received a prescription for topical azole in the first trimester of pregnancy.	unexposed (general population or NOS) Pregnant women not exposed to fluconazole or other azole.	492 / 1629
Molgaard-Nielsen - Clotrimazole/miconazole (Vaginal) (Controls exposed to pivmecillinam), 2016	Denmark 1997 - 2013	All pregnancies ending with a singleton live birth, stillbirth, spontaneous abortion, and other abortive outcomes (including ectopic pregnancy, hydatidiform mole, other abnormal products of gestation, or induced abortion) in Denmark.	Exposure to vaginal azole antifungals (intravaginal clotrimazole or miconazole) during the specific time windows: gestational week 7 to 22 and week 7 to birth for spontaneous abortion and stillbirth, respectively.	exposed to other treatment, sick Exposure to pivmecillinam during the specific time windows: gestational week 7 to 22 and week 7 to birth for spontaneous abortion and stillbirth, respectively.	4301 / 4357
Molgaard-Nielsen - Clotrimazole/miconazole (Vaginal) (Controls unexposed, NOS), 2016	Denmark 1997 - 2013	All pregnancies ending with a singleton live birth, stillbirth, spontaneous abortion, and other abortive outcomes (including ectopic pregnancy, hydatidiform mole, other abnormal products of gestation, or induced abortion) in Denmark.	Exposure to vaginal azole antifungals (intravaginal clotrimazole or miconazole) during the specific time windows: gestational week 7 to 22 and week 7 to birth for spontaneous abortion and stillbirth, respectively.	unexposed (general population or NOS) No exposure to fluconazole during the specific time windows: gestational week 7 to 22 and week 7 to birth for spontaneous abortion and stillbirth, respectively.	4301 / 1400113
Rotem - Clotrimazole (Vaginal), 2018	Israel 1999 - 2009	All women who gave birth or underwent a pregnancy termination at Soroka Medical Center, Beer-Sheva, Israel.	Women who were dispensed with clotrimazole vaginal tables during the first trimester of pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study).	unexposed (general population or NOS) Pregnancies that were not exposed to either drug from the azoles family (e.g. vaginal, systemic or topical formulation).	1993 / 95781	Vaginal exposure
Zhu - Azoles (Local routes), 2020	USA 2000 - 2014	Pregnant women aged 12-55 who were continuously enrolled in Medicaid from three or more months before the last menstrual period to one or more months after delivery, and liveborn infants.	Pregnant women who filled one or more prescriptions for topical/vaginal azoles during the first trimester and had no dispensing for other oral antifungal agents between 90 days before the LMP and the end of the 1st trimester. (This is a subgroup of exposure among the whole exposed group).	unexposed (general population or NOS) Pregnant women with no prescriptions for oral antifungal agents during the baseline and first trimester periods.	82090 / 1875257	'Exclusions were pregnancies with a chromosomal abnormality or exposure to a known teratogenic drug during the first trimester...'.

Case-control studies (cohort)

Study	Country Study period	Case	Control	Sample size	Rmk
Abdel-Salam - Clotrimazole, 2000	Hungary 1980 - 1996	Newborn infants (including infant deaths and usual stillborn fetuses) with isolated microcephaly.	Newborn infants (including infant deaths and usual stillborn fetuses) without congenital abnormalities.	109 / 218	Study design completed with other studies published on the Hungarian Case-Control Surveillance of Congenital Abnormalities (HCCSCA).
Carter - Clotrimazole, 2008	USA 1997 - 2003	Cases with selected birth defects (included live births, stillbirths 20 weeks or longer or greater than 500 g, or elective terminations).	Live births without birth defects that were randomly selected from birth certificates or birth hospitals in the geographic regions monitored by the state surveillance systems.	12274 / 4774	Study analyzing several local azoles => to avoid redundancy of cases and controls, only 1 substance was reported here, this one with the most exposed cases.
Czeizel - Clotrimazole, 1999	Hungary 1980 - 1992	Infants (liveborn infants, stillborn infants, and electively aborted fetuses) with congenital abnormalities (CAs) were selected from the Hungarian Congenital Abnormality Registry.	Infants without congenital abnormalities, matched according to sex, birth week, and district of parents' residence selected from the national birth registry of the Central Statistical Office.	18515 / 32804	Overlapping: Abdel-Salam 2000, Vermes 2015 and Medveczky 2004 studied specifically 3 outcomes (Microcephaly; oesophagial atresia; neural tube defects) on the same database and a longer period (1980 - 1996) => these outcomes are not reported here.
Kazy b - Metronidazole (Vaginal), 2005	Hungary 1980 - 1996	Cases with congenital abnormalities (CAs) were selected from the Hungarian Congenital Abnormality Registry.	Controls were extracted from from the National Birth Registry of the Central Statistical Office.	22843 / 38151	Database analyzing several local azoles => to avoid redundancy of cases and controls, only 1 substance reported here, this one with the most exposed cases: Czeizel 1999, except for 2 outcomes: Esophageal atresia/stenosis and Rectal/anal atresia/stenosis.
Medveczky - Clotrimazole, 2004	Hungary 1980 - 1996	Newborn infants (including infant deaths and usual stillborn fetuses) with Neural tube defects with non-syndromic (i.e. isolated anencephaly, spina bifida aperta/cystica, encephalocele).	Newborn infants (including infant deaths and usual stillborn fetuses) without congenital abnormalities.	1202 / 38151	Study design completed with other studies published on the Hungarian Case-Control Surveillance of Congenital Abnormalities (HCCSCA). For metronidazole, data not reported because already included (Kazy 2005b; Czeizel 1998).
Rosa - Clotrimazole, 1987	USA 1980 - 1983	Patients aged zero to four years with suspected birth defect diagnoses, pregnancies ending in spontaneous abortions (ICD9 634-634.9).	Deliveries not linked to birth defects.	6564 / 97775	Study on the efficacy of azole in an obstetrical indication, including the intrauterine deaths and/or late pregnancy and/or neonatal outcomes that are studied as efficacy criteria rather than safety one. => Not reported here.
Ross - Clotrimazole, 2003	USA and Canada 1983 - 1988	Children diagnosed with acute leukemia (i.e., acute myeloid leukemia, AML and acute lymphoblastic leukemia, ALL) in the first 18 months of life.	Children without leukemia identified through random digit dialing.	243 / 393
Zarante - Clotrimazole (Vaginal), 2009	Colombia 2001- 2006	All newborns and stillborns of weight >500 g that presented only one craniofacial malformation, not associated with any other congenital condition.	The next non-malformed same sex child born in the same hospital.	374 / 728
Zarante - Metronidazole (Vaginal), 2009	Colombia 2001- 2006	All newborns and stillborns of weight >500 g that presented only one craniofacial malformation, not associated with any other congenital condition.	The next non-malformed same sex child born in the same hospital.	374 / 728

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