Background
In various countries, metoclopramide is the antiemetic drug of choice in pregnant women, but insufficient information exists regarding its safety in pregnancy.
Methods
We investigated the safety of metoclopramide use during the first trimester of pregnancy by linking a computerized database of medications dispensed between January 1, 1998, and March 31, 2007, to all women registered in the Clalit Health Services, southern district of Israel, with computerized databases containing maternal and infant hospital records from the district hospital during the same period. We assessed associations between the use of metoclopramide in pregnancy and adverse outcomes for the fetus, adjusting for parity, maternal age, ethnic group, presence or absence of maternal diabetes, smoking status, and presence or absence of peripartum fever.
Results
There were 113,612 singleton births during the study period. A total of 81,703 of the infants (71.9%) were born to women registered in Clalit Health Services; 3458 of them (4.2%) were exposed to metoclopramide during the first trimester of pregnancy. Exposure to metoclopramide, as compared with no exposure to the drug, was not associated with significantly increased risks of major congenital malformations (5.3% and 4.9%, respectively; odds ratio, 1.04; 95% confidence interval [CI], 0.89 to 1.21), low birth weight (8.5% and 8.3%; odds ratio, 1.01; 95% CI, 0.89 to 1.14), preterm delivery (6.3% and 5.9%; odds ratio, 1.15; 95% CI, 0.99 to 1.34), or perinatal death (1.5% and 2.2%; odds ratio, 0.87; 95% CI, 0.55 to 1.38). The results were materially unchanged when therapeutic abortions of exposed and unexposed fetuses were included in the analysis.
Conclusions
In this large cohort of infants, exposure to metoclopramide in the first trimester was not associated with significantly increased risks of any of several adverse outcomes. These findings provide reassurance regarding the safety of metoclopramide for the fetus when the drug is given to women to relieve nausea and vomiting during pregnancy.
From NEJM Volume 360:2528-2535 June 11, 2009 Number 24
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In the U.S., treatment of nausea and vomiting during early pregnancy usually involves pyridoxine (vitamin B6) and antihistamines, such as doxylamine succinate, promethazine, or meclizine. If these agents are not effective, clinicians might turn to more-potent antiemetics, such as the dopamine antagonist metoclopramide. To assess the association between metoclopramide use during early pregnancy and risk for congenital malformations, investigators linked administrative records from an Israeli HMO with medical records from the hospital at which the insured women delivered. From 1998 to 2007, 81,703 singleton live births and 998 induced abortions occurred among participants (mean age, 28; two thirds Bedouin Muslim, one third Jewish).
Among women who had singleton births and induced abortions, 4.2% and 3.8%, respectively, received first-trimester metoclopramide. Among women who had singleton births and who were exposed to metoclopramide, the rate of major congenital malformations was 5.3%; among those who were not exposed, the rate was 4.9% (adjusted odds ratio, 1.04; 95% confidence interval, 0.89–1.21). Analyses that included pregnancy terminations yielded similar findings. Early exposure to metoclopramide also was not associated with significantly altered risk for minor or multiple congenital malformations; moreover, metoclopramide showed no dose-response effect.
Comment:
Although metoclopramide is used more widely for treating women with nausea and vomiting during early pregnancy in Israel and some European countries than in the U.S., its use for this indication in the U.S. is not uncommon. Results of previous small studies have suggested that use during pregnancy is not linked to incidence of congenital anomalies. This large, retrospective cohort study provides substantial reassurance that metoclopramide does not cause congenital malformations. However, clinicians should be aware that use of this dopamine antagonist can cause maternal extrapyramidal symptoms (i.e., acute dystonic reactions and tardive dyskinesia).
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Andrew M. Kaunitz, MD
Published in Journal Watch Women's Health June 10, 2009
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Andrew M. Kaunitz, MD
Published in Journal Watch Women's Health June 10, 2009
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