Ondansetron - Medication and Pregnancy KB

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 (general population or NOS) 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 (general population or NOS) 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 (general population or NOS) 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 (general population or NOS) All infants of the cohort.	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 (general population or NOS) 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 (general population or NOS) 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 (general population or NOS) 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 (general population or NOS) 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).
Kerr, 2018	USA and Canada 1993 - 2015	Infants with microcephaly alone (“isolated”) and microcephaly that included other major birth defects (“non-isolated”),	Nonmalformed live-born infants.	166 / 12059	Authors analyzed separately “isolated” microcephaly and “non-isolated” microcephaly. Only isolated microcephaly are indexed in MetaPreg.
Lind, 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 liveborn 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).	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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