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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., (Copyright © 2019. Published by Elsevier Inc.)

An objective and validated index of nausea and vomiting such as the Pregnancy-Unique Quantification of Emesis (PUQE) and HyperEmesis Level Prediction (HELP) tools can be used to classify the severity of NVP and HG. [Grade C] Ketonuria is not an indicator of dehydration and should not be used to assess severity. [Grade A] There are safety and efficacy data for first line antiemetics such as anti (H1) histamines, phenothiazines and doxylamine/pyridoxine (Xonvea®) and they should be prescribed initially when required for NVP and HG (Appendix III). [Grade A] There is evidence that ondansetron is safe and effective. Its use as a second line antiemetic should not be discouraged if first line antiemetics are ineffective. Women can be reassured regarding a very small increase in the absolute risk of orofacial clefting with ondansetron use in the first trimester, which should be balanced with the risks of poorly managed HG. [Grade B] Metoclopramide is safe and effective and can be used alone or in combination with other antiemetics. [Grade B] Because of the risk of extrapyramidal effects metoclopramide should be used as second-line therapy. Intravenous doses should be administered by slow bolus injection over at least 3 minutes to help minimise these. [Grade C] Women should be asked about previous adverse reactions to antiemetic therapies. If adverse reactions occur, there should be prompt cessation of the medications. [GPP] Normal saline (0.9% NaCl) with additional potassium chloride in each bag, with administration guided by daily monitoring of electrolytes, is the most appropriate intravenous hydration. [Grade C] Combinations of different drugs should be used in women who do not respond to a single antiemetic. Suggested antiemetics for UK use are given in Appendix III. [GPP] Thiamine supplementation (either oral 100 mg tds or intravenous as part of vitamin B complex (Pabrinex®)) should be given to all women admitted with vomiting, or severely reduced dietary intake, especially before administration of dextrose or parenteral nutrition. [Grade D] All therapeutic measures should have been tried before considering termination of pregnancy. [Grade C]., (© 2024 John Wiley & Sons Ltd.)

Background: In France, few data are available on the prescription patterns of antiemetic medications in pregnant women., Objectives: The purpose of this study was to describe antiemetic medication prescriptions and trends over time. Can we observe significant changes in pregnant woman prescriptions in recent years?, Methods: We conducted a drug utilization study among pregnant women using data from the EFEMERIS database, including 135 574 pregnant women who had a pregnancy outcome between 2004 and 2017 in Haute-Garonne (France)., Results: During the study period, 40 028 women (29.5%) received at least one antiemetic prescription during pregnancy. Metoclopramide (56.6%), domperidone (34.9%), and metopimazine (28.5%) were the most commonly prescribed antiemetics, whatever the trimester of pregnancy. Prescriptions of ondansetron only concerned 53 women (0.1%). The prevalence of women who received at least one prescription for an antiemetic decreased from 32.5% in 2010 to 21.6% in 2017. This decline mainly concerned domperidone prescriptions (from 13.1% in 2010 to 1.2% in 2017). Metoclopramide prescriptions also decreased slightly (18.3% in 2010 and 14.0% in 2017). Metopimazine prescriptions increased lowly (8.0% in 2010 and 9.0% in 2017)., Conclusion: This study showed a decrease of antiemetic prescriptions between 2010 and 2017, linked to the sharp decrease in domperidone use from 2011, probably related to warnings about the risk of cardiovascular adverse effects following exposure to domperidone. We could not observe real switches to other antiemetic medications. No switches to ondansetron could be noted either, with only rare exposure during pregnancy, contrary to other countries, like the United States., (© 2021 Société Française de Pharmacologie et de Thérapeutique.)

Ondansetron is increasingly used off label to treat nausea and vomiting during pregnancy. The main objective of this study was to evaluate the risk of major congenital malformations (MCM), cardiac defects and orofacial clefts associated with first trimester exposure to ondansetron using a meta-analytic approach. MEDLINE, ClinicalTrials.gov and Scopus were searched until November 2019. All comparative cohort and case-control studies on MCM, cardiac or orofacial defects and use of ondansetron during pregnancy were included. A team of paired reviewers independently extracted data using a proprietary collaborative WEB-based meta-analysis platform (metaPreg.org). Pooled odd ratios with corresponding 95% CIs were calculated using random effects models. From 214 records initially retrieved, 12 studies were included. Using all available information to date, first trimester exposure to ondansetron was found to be associated with an increased risk of (a) ventricular septal defects (VSD) (OR 1.11, 95% CI 1.00-1.23; p < .05; n = 6 studies; I 2 = 0%) and (b) oral clefts (OR 1.22, 95% CI 1.00-1.49; p < .05; n = 4 studies; I 2 = 0%). No significant association was observed for the risk of cleft palate but, when excluding the study that contributed to the study heterogeneity, we found an OR of 1.48 (95% CI 1.19-1.84; p < .01; n = 5 studies; I 2 = 0%). No statistically significant association was found for MCM, overall cardiac malformations, atrial septal defects and cleft lip with or without cleft palate. Exploratory investigations of other malformations showed an increased risk of diaphragmatic hernia, hypoplastic left heart and "respiratory system anomalies.", (© 2020 Wiley Periodicals, Inc.)

Objective: To compare patterns in use of different antiemetics during pregnancy in Canada, the United Kingdom, and the United States, between 2002 and 2014. Methods: We constructed population-based cohorts of pregnant women using administrative healthcare data from five Canadian provinces (Alberta, British Columbia, Manitoba, Ontario, and Saskatchewan), the Clinical Practice Research Datalink from the United Kingdom, and the IBM MarketScan Research Databases from the United States. We included pregnancies ending in live births, stillbirth, spontaneous abortion, or induced abortion. We determined maternal use of antiemetics from pharmacy claims in Canada and the United States and from prescriptions in the United Kingdom. Results: The most common outcome of 3 848 734 included pregnancies (started 2002–2014) was live birth (66.7% of all pregnancies) followed by spontaneous abortion (20.2%). Use of antiemetics during pregnancy increased over time in all three countries. Canada had the highest prevalence of use of prescription antiemetics during pregnancy (17.7% of pregnancies overall, 13.2% of pregnancies in 2002, and 18.9% in 2014), followed by the United States (14.0% overall, 8.9% in 2007, and 18.1% in 2014), and the United Kingdom (5.0% overall, 4.2% in 2002, and 6.5% in 2014). Besides use of antiemetic drugs being considerably lower in the United Kingdom, the increase in its use over time was more modest. The most commonly used antiemetic was combination doxylamine/pyridoxine in Canada (95.2% of pregnancies treated with antiemetics), ondansetron in the United States (72.2%), and prochlorperazine in the United Kingdom (63.5%). Conclusions: In this large cohort study, we observed an overall increase in antiemetic use during pregnancy, and patterns of use varied across jurisdictions. Continued monitoring of antiemetic use and further research are warranted to better understand the reasons for differences in use of these medications and to assess their benefit-risk profile in this population. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the risk of major congenital malformations (MCMs) associated with first‐trimester exposure to propulsives with a special focus on domperidone using a large administrative database in Japan. Methods: A large claims database was used from January 2005 to August 2016. The dates of pregnancy onset and delivery were estimated using the developed algorithms. MCMs were defined according to the International Classification of Diseases, 10th revision codes. We compared the infants' risk of overall MCMs between women with or without first‐trimester prescriptions of propulsives and estimated the odds ratios (ORs) with unadjusted and adjusted analyses. We also compared the risk of overall MCMs between women with domperidone prescriptions and those with other propulsive prescriptions during the first trimester. Results: Among 38 270 women, propulsives were prescribed to 3197 women (8.4%) in the first trimester, including domperidone to 371 women (1.0%). Propulsive prescriptions in the first trimester were not significantly associated with an increased risk of overall MCMs (adjusted OR [aOR] 1.030, 95% confidence interval [CI] 0.843–1.257). Compared to the prescription of other propulsives in the first trimester, the prescription of domperidone in the first trimester was not associated with an increased risk of overall MCMs (aOR 0.724, 95% CI 0.363–1.447). Conclusions: The first‐trimester prescription of propulsives, including domperidone, was not associated with an increased risk of overall MCMs. [ABSTRACT FROM AUTHOR]

Prescription fills of medications used for nausea and vomiting of pregnancy were summarized in treatment pathways to determine drug utilization patterns. During the third pregnancy, antiemetic prescriptions were filled by 53.5% of women who filled a prescription for antiemetics in the previous two pregnancies and decreased to 5.5% for women without a history of antiemetic medication prescription fills. Treatment Pathways Among the women who filled prescriptions for antiemetic medication during pregnancy, we determined the gestational week of initiating treatment, the number of prescription fills, and the total number of DDDs dispensed. [Extracted from the article]