Ondansetron

Exposed non-exposed studies (cohort)

Study Country
Study period
Population source Exposure definition Non-exposure definition Sample size Rmk
Andersen, 2013 Denmark
1997 - 2010
All women giving birth in Denmark between 1997 and 2010 First trimester users of ondansetron unexposed (not otherwise specified)
Non-users of ondansetron
1248 / 895770 Probable Typographic mistake (it should be considered OR = 2.0 (95% CI: 1.3–3.1) instead of OR = 2.0 (95% CI: 0.3–3.1) as mentioned in Danielsson 2014 and an other abstract of Andersen 2013 available in internet.
Bérard, 2019 Canada
1998 - 2015
All pregnancies covered by the Quebec Prescription Drug Insurance Plan administered by the Régie de l’assurance maladie du Quebec (RAMQ) Exposure was defined as having filled at least one prescription for ondansetron within the first trimester of pregnancy. unexposed (not otherwise specified)
Pregnancies without prescription for doxylamine-pyridoxine, metoclopramide, or ondansetron within the first trimester of pregnancy.
31 / 179106 EXPOSURE: 45,623 pregnancies exposed to doxylamine-pyridoxine; 958 to metoclopramide; 31 to ondansetron. TOTAL: 45770.
Colvin, 2013 Australia
2002 - 2005
All pregnancies resulting in a birth in Western Australian (WA) during the study period All births in Western Australian (WA) where the mother was dispensed ondansetron under the Australian Pharmaceutical Benefits Scheme (PBS). unexposed (not otherwise specified)
All other births during the same period
263 / 98062
Danielsson, 2014 Sweden
1998 - 2012
Nearly all births in Sweden Infants exposed in early pregnancy for ondansetron unexposed (not otherwise specified)
Expected number of malformed infants
1349 / 1501434 The remaining malformations were called ”relatively severe” but may contain a few minor or poorly specified conditions. This concept broadly corresponds to major malformations.
Einarson (Control exposed to other antiemetics), 2004 Canada and Australia
A two year period
All pregnant women that called Teratogen Information Services during the study period Women who called either service, were taking ondansetron and were less than three months pregnant at the time of call (most were between 5 and 9 weeks of gestation) exposed to other treatment, sick
Women who called either service and who also suffered from NVP but were not exposed to ondansetron, they had used other anti-emetics, which included Diclectin, metoclopramide, phenothiazines and ginger.
176 / 176
Einarson (Unexposed control), 2004 Canada and Australia
A two year period
All pregnant women that called Teratogen Information Services during the study period Women who called either service, were taking ondansetron and were less than three months pregnant at the time of call (most were between 5 and 9 weeks of gestation) unexposed, disease free
Women who called either service and were exposed to other drugs considered safe to use in pregnancy or those who had not used any medication.
176 / 176
Fejzo (Mainly exposed to other treatements, sick), 2016 USA
2007 - 2014
Women with a diagnosis of Hyperemesis Gravidarum (HG) in a singleton pregnancy and treatment with IV fluids and/or total parenteral nutrition/nasogastric feeding tube and women that that recruited Women with a history of HG whose pregnancies were treated with ondansetron (O ) exposed to other treatment, sick
Women with a history of HG whose pregnancies were not treated with ondansetron (68.2% treated (iv/metoclopramide/promethazine))
1070 / 771
Fejzo (Unexposed control, disease free), 2016 USA
2007 - 2014
Women with a diagnosis of Hyperemesis Gravidarum (HG) in a singleton pregnancy and treatment with IV fluids and/or total parenteral nutrition/nasogastric feeding tube and women that that recruited Women with a history of HG whose pregnancies were treated with ondansetron (O ) unexposed, disease free
Women with no history of HG whose pregnancies were not treated with ondansetron (nor any medication/treatment for nausea/vomiting of pregnancy)
1070 / 1555
Huybrechts, 2019 USA
2000 - 2014
Women aged 12 through 55 years were required to have Medicaid coverage from 3 months before the date of the last menstrual period to 1 month after delivery. (As described previously in Huybrechts, 2018) Women were considered exposed if a claim for Healthcare Common Procedure Coding System code J2405 indicating ondansetron injection was recorded during the first trimester of pregnancy. unexposed (not otherwise specified)
Women without exposure to either oral or intravenous ondansetron from 3 months before the start of pregnancy through the end of the first trimester.
23877 / 1762018 Women exposed to known teratogenic mediations were excluded from the cohort (ie, warfarin, antineoplastic agents, lithium, isotretinoin, misoprostol, thalidomide).
Huybrechts (Control exposed to other treatment), 2018 USA
2000 - 2013
Women aged 12 through 55 years were required to have Medicaid coverage from 3 months before the date of the last menstrual period to 1 month after delivery Women who filled at least 1 ondansetron prescription during the first 3 months of pregnancy. exposed to other treatment, sick
Women who filled a prescription during the first 90 days of pregnancy for pyridoxine (with or without doxylamine), promethazine, metoclopramide, or any of these alternative pharmacological treatments
88467 / 185876 Exclusion of pregnancies to a known teratogenic medication (ie, warfarin, antineoplastic agents, lithium, isotretinoin, misoprostol, thalidomide) during the first trimester (n = 3562) and with a chromosomal abnormality (n = 3156)
Huybrechts (Unexposed control), 2018 USA
2000 - 2013
Women aged 12 through 55 years were required to have Medicaid coverage from 3 months before the date of the last menstrual period to 1 month after delivery. Women who filled at least 1 ondansetron prescription during the first 3 months of pregnancy. unexposed (not otherwise specified)
Women who did not fill a prescription for ondansetron during the 3 months before the start of pregnancy through the end of the first trimester.
88467 / 1727947 Exclusion of pregnancies to a known teratogenic medication (ie, warfarin, antineoplastic agents, lithium, isotretinoin, misoprostol, thalidomide) during the first trimester (n = 3562) and with a chromosomal abnormality (n = 3156)
Lemon, 2019 USA
2006 - 2014
Liveborn, singleton deliveries at Magee–Womens Hospital of the University of Pittsburgh Medical Center (UPMC). Ondansetron exposure (intravenous and oral) during the first trimester of pregnancy. unexposed (not otherwise specified)
Unexposed to ondansetron.
3733 / 29944 Routes of administration were combined, as route is not expected to impact the association with VSD (n = 3171 oral; n = 1074 intravenous; n = 18 injection).
Marciniak, 2015 Poland
Not specified
Patients undergoing elective Caesarean sections Patients were received 8 mg of intravenous ondansetron. unexposed, sick
Patients were received 10 ml of isotonic sodium chloride.
35 / 34 Birth weight, pH and
Oofuvong, 2018 Thailand
2016 - 2017
Singleton pregnant women at a gestational age of 37–42 weeks who under- went elective cesarean section under spinal anesthesia and had no abnormal signs on electrocardiography. Women receiving intravenously ondansetron 0.05 mg/kg (group O1) or ondansetron 0.1 mg/kg (group O2) (maximal dose of 8 mg). unexposed, sick
Women receiving intravenously either normal saline (group NS)
143 / 72 Results of Apgar scores not reported because they were presented as continuous variables (with Interquartile range).
Ozdemirci, 2014 Turkey
2006 - 2011
Pregnant women who were refractory to oral meclizine dihydrochloride-pyridoxine hydrochloride, unable to tolerate oral nutrition and required hospitalization for treatment of HG were included in the study if treated with either ondansetron or chlorpromazine. Pregnancies less than 13 weeks treated with 8 mg ondansetron once a day intravenously exposed to other treatment, sick
Pregnancies less than 13 weeks treated with 12.5 mg chlorpromazine twice a day intravenously
100 / 85
Pasternak, 2013 Denmark
2004 - 2011
All pregnancies that resulted in a singleton live birth or stillbirth or ended with any abortive outcome Pregnant women who receive ondansetron throughout the exposure time window unexposed (not otherwise specified)
Pregnant women who did not receive ondansetron throughout the exposure time window were categorized as “unexposed.” and propensity-score–matched
-9 / -9 Exposure time windows: the first trimester (through 12 GW) for any major birth defect, any time before 37 GW for preterm delivery, any time during pregnancy for birth weight, week 7 to 22 for spontaneous abortion, and week 7 until birth for stillbirth.
Shahraki, 2016 Iran
2014 - 2015
Primipara singleton pregnant females with pregnancy-related nausea and vomiting who were referred from the state healthcare centers to Amir-Almomenin hospital Ondansetron tablets (4 mg) to take one tablet twice daily, initiated on an average of 4 to 16 weeks gestation exposed to other treatment, sick
Vitamin B6 tablets (40 mg) to take one tablet twice daily, initiated on an average of 4 to 16 weeks gestation.
88 / 100 No differences between the neonates in ondansetron and vita- min B6 groups regarding birth-weight (p = 0.67), height at birth (p = 0.75) and head circumference at birth (p = 0.56).

Case-control studies (cohort)

Study Country
Study period
Case Control Sample size Rmk
Anderka, 2012 USA
1997 - 2004
All infants with any of more than 30 selected birth defects. Controls without birth defects. 4524 / 5859 No superposition of data between Anderka 2012 and Parker 2018, using both the NPBDS dataset: for the 4 defects studied by both, the study periods were 1997-2004 and 2005-2011, respectively.
Clements, 2015 USA
1997 - 2010
Infants who had at least one ICD-9 code of 299 (pervasive developmental disorder) or with ICD-9 code of 314.x (attention-deficit hyperactivity disorder (ADHD)). Infants not having any prior history of Autism Spectrum Disorder (ASD), attention-deficit hyperactivity disorder (ADHD) or intellectual disability (ICD9 of 299, 314 or 317–319). 2243 / 5631 1377 children with ASD matched to 4022 healthy control children and 2243 with ADHD (but no ASD diagnosis) matched to 5631 healthy control children.
Fejzo, 2015 USA
2007 - 2011
Children exposed to hyperemesis gravidarum (HG) with neurodevelopmental delay. Children exposed to hyperemesis gravidarum (HG) with a good outcome. 138 / 174 Main analysis: case control related to the impact of the HG illness (treated or not) on child outcomes. Then impact of 37 medications/treatments (1st and/or 2nd trimester) on child outcome was investigated (none was significantly associated with delay).
Lind (Controls exposed to metoclopramide, sick), 2013 USA
1997 - 2007
Male infants with isolated second- or third-degree hypospadias, defined as the urethral opening at the penile shaft, scrotum, or perineum. Male infants with no major birth defects selected randomly from vital records or birth logs. 1537 / 4314 The National Birth Defects Prevention Study excludes first-degree hypospadias. Arkansas, California, Georgia, Iowa, and Texas also include pregnancies that are diagnosed prenatally.
Lind (Controls unexposed, NOS), 2013 USA
1997 - 2007
Male infants with isolated second- or third-degree hypospadias, defined as the urethral opening at the penile shaft, scrotum, or perineum. Male infants with no major birth defects selected randomly from vital records or birth logs. 1537 / 4314 National Birth Defects Prevention Study excludes first-degree hypospadias. Arkansas, California, Georgia, Iowa, and Texas also include pregnancies that are diagnosed prenatally.
Parker, BDS study, 2018 USA
1997–2014
Live births, stillbirths, and elective terminations with any major birth defects. Liveborn neonates without malformations. 8533 / 5873 1st trimester definition: the 2 weeks before and 98 days after the estimated date of conception.
Parker, NBDPS study, 2018 USA
1997–2011
Infants (live births, stillbirths, and (in selected sites) elective terminations) with one of the more 30 selected major birth defects studied A random sample of liveborn neonates without birth defects identified from birth certificates or birth hospitals in the same geographic regions and time periods as those in the case group 14667 / 6751 No superposition of data between Anderka 2012 and Parker 2018, using both the NPBDS dataset: for the 4 defects studied by both, the study periods were 1997-2004 and 2005-2011, respectively. NBDPS: 1st trimester: first 90 days after the date of conception
Werler, 2014 USA
2007 - 2011
All infants less than 11 months of age with a diagnosis of talipes equinovarus or clubfoot without a known chromosomal anomaly, inherited syndrome, bilateral renal agenesis, Potter syndrome, or neural tube defect, reported to the study data by the birth defect registries. Random samples of children born in the same years as cases but without known malformations. 646 / 2037 Ondansetron is one of the medications studied by authors. 'On the basis of the timing of clubfoot development, the exposure window of interest is lunar months (LMs) 2–4, which is 29–112 days after the first day of the last menstrual period.'
Zambelli-Weiner (Unexposed control, NOS), 2019 USA
2000 - 2014
Infants diagnosed with birth defects (cardiovascular, orofacial clefts, other circulatory defects, diaphragmatic hernia or renal collecting system anomalies) Infants with all birth defects with ICD-9 codes 740.xx-759.xx, excluding the a priori birth defects of interest. -9 / 802253 Nested case-control study. Exclusion of chromosomal anomalies and exposure to known teratogens: infection (toxoplasmosis, syphilis, varicella- rubella, ...), or prescription for thalidomide or isotretinoin in the pre-birth period.
Zambelli-Weiner (Unexposed control, sick), 2019 USA
2000 - 2014
Infants diagnosed with birth defects (cardiovascular, orofacial clefts, other circulatory defects, diaphragmatic hernia or renal collecting system anomalies) Infants with all birth defects with ICD-9 codes 740.xx-759.xx, excluding the a priori birth defects of interest. -9 / 802253 Nested case-control study. Exclusion of chromosomal anomalies and exposure to known teratogens: infection (toxoplasmosis, syphilis, varicella- rubella, ...), or prescription for thalidomide or isotretinoin in the pre-birth period.

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