Abstract
Objectives
The aim of the study was to quantify the risk of major congenital malformations (MCM)
associated with first-trimester exposure to antiemetics.
Study Design and Setting
Using the Quebec Pregnancy Cohort (1998–2015), first-trimester doxylamine–pyridoxine,
metoclopramide, and ondansetron exposures were assessed for their association with
MCM. Generalized estimating equations were used to estimate odds ratios (OR), adjusting
for potential confounders (aOR).
Results
Within 17 years of follow-up, the prevalence of antiemetic use during pregnancy increased
by 76%. Within our cohort, 45,623 pregnancies were exposed to doxylamine–pyridoxine,
958 to metoclopramide, and 31 to ondansetron. Doxylamine–pyridoxine and metoclopramide
use were associated with an increased risk of overall MCM (aOR 1.07, 95% confidence
interval [CI]: 1.03–1.11; 3,945 exposed cases) and (aOR 1.27, 95% CI: 1.03–1.57; 105
exposed cases), respectively. Doxylamine–pyridoxine exposure was associated with increased
risks of spina bifida (aOR 1.87, 95% CI: 1.11–3.14; 23 exposed cases), nervous system
(aOR 1.25, 95% CI: 1.06–1.47; 225 exposed cases), and musculoskeletal system defects
(aOR 1.08, 95% CI: 1.02–1.14; 1,735 exposed cases). Metoclopramide exposure was associated
with an increased risk of genital organ defects (aOR 2.26, 95% CI: 1.14–4.48; 10 exposed
cases). No statistically significant association was found between ondansetron exposure
and the risk of overall MCM.
Conclusion
First-trimester doxylamine–pyridoxine and metoclopramide exposure was associated with
a significantly increased risk of overall and specific MCM.
Keywords
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Article info
Publication history
Published online: July 25, 2019
Accepted:
July 20,
2019
Footnotes
Funding: This study was funded by the Canadian Institutes of Health Research—Drug Safety, and Effectiveness Network (DSEN), Canada; Fonds de la Recherche du Québec Santé (FRQS), Canada, grant number 30962 to A.B.
The funders had no role in the study design; collection, analysis, and interpretation of data; writing of the report; and in the decision to submit the article for publication.
Declarations of interest: none.
Ethics approval and consent to participate: The study was approved by the Sainte-Justine's Hospital Ethics Committee. The Quebec “Commission d'accès à l'information” authorized database linkages.
Availability of data and material: Diagnoses, medication, and procedure codes used in the present study are available from the corresponding author on request.
Competing interests: The authors declare that they have no competing interests.
Identification
Copyright
© 2019 Published by Elsevier Inc.
