Ondansetron offered to relieve nausea and vomiting in pregnant women throughout the very first trimester is associated along with a reasonable risk for birth defects, and possibly a small improve in the incidence of cardiac malformations in newborns, according to a systematic review published online April 4 in Obstetrics & Gynecology.
On balance, however, Shaun D. Carstairs, MD, from the Division of Medical Toxicology, Department of Emergency Medicine, University of California, San Diego, conclude that ondansetron need to be considered a great option as soon as various other treatments are insufficient.
“If first-line agents for the treatment of nausea and vomiting in pregnancy are not felt to manage a patient’s symptoms adequately, particularly after the very first 10 weeks, good health care providers and patients need to be reassured that ondansetron usage throughout pregnancy is generally safe and is a highly efficient measure for manage of nausea and vomiting in pregnancy, and its usage need to be considered in patients in whom various other means have actually failed,” he writes.
Writing in an accompanying commentary, Lara L. Siminerio, PharmD, from the Department of Epidemiology, Graduate School of Public Health, Department of Obstetrics, Gynecology and Reproductive Sciences, School of Medicine, Magee Womens Hospital of the University of Pittsburgh Medical Center, Pennsylvania, and colleagues endorse that view.
“In the face of recent questioning of the safety of ondansetron usage in pregnancy, it is [our] opinion that current data do not support a reluctance to handle women along with ondansetron in clinical practice. The maternal incentive of treatment for nausea and vomiting of pregnancy and hyperemesis gravidarum along with ondansetron outweighs the risks,” Dr Siminerio and colleagues write.
“Teratogen exposure is relevant throughout the period of organogenesis, yet, in previous studies, the majority of the women began ondansetron after the heart is fully formed at roughly 8 weeks of gestation,” they explain. “Just [one study] tested the effect of limiting the exposure window to 2–8 weeks or 4–10 weeks of gestation and confirmed their null findings.”
Eight Studies Available
Dr Carstairs identified eight studies for their review. To be included, studies called for to be written in English, report the outcomes of original research, report on ondansetron exposure throughout the very first trimester, consist of structural birth defects as an outcome, and consist of a comparison population of patients that were not exposed to ondansetron.
A large cohort study that analyzed data on 608,385 pregnancies discovered no substantial association between ondansetron exposure and the incidence of serious birth defects (odds ratio [OR], 1.12; 95% self-confidence interval [CI], 0.69 – 1.82), small for gestational age (OR, 1.13; 95% CI, 0.89 – 1.44), reasonable birth weight (OR, 0.76; 95% CI, 0.51 – 1.13), or preterm delivery (OR, 0.90; 95% CI, 0.66 – 1.25).
“This was the Just study to account for maternal medical history, including diabetes mellitus of any kind of type, which is known to improve risk of congenital heart defects,” Dr Siminerio and colleagues write in their commentary. “We conclude that the strongest evidence comes from [this study].”
In addition, one study analyzed data from 4524 cases and 5859 controls and viewed no evidence of increased risk for 3 of the four birth defects examined: cleft lip, neural tube defects, or hypospadias. However, the risk for the fourth defect examined, cleft palate, was roughly twofold better in neonates exposed to ondansetron in utero throughout the very first trimester (OR, 2.37; 95% CI, 1.18 – 4.76), along with 11 cleft palate cases among the 55 exposed neonates and 514 cases among the 4479 unexposed neonates.
“The relatively small sample size in this study limits the interpretability of these results, and no various other studies thus far have actually demonstrated the increased risk for cleft palate reported in this study,” Dr Carstairs cautions.
One report that was published in abstract form Just analyzed data from two case-manage studies along with a total of 10,354 women, 354 of whom were exposed to ondansetron throughout their pregnancies. The risk for cleft palate was not significantly increased in one study (OR, 1.5; 95% CI, 0.9 – 2.5), and it was significantly decreased in the various other study (OR, 0.4; 95% CI, 0.2 – 0.8). The risk for renal agenesis or dysplasia was modestly increased in one study (OR, 2.3; 95% CI, 1.3 – 4.0).
Two various other studies discovered a small improve in the risk for cardiac defects. One was a cohort study of 1.5 million births along with 1349 newborns that were exposed to ondansetron in utero. The risks for total malformations (OR, 0.95; 95% CI, 0.72 – 1.26) or “relatively severe” malformations (OR, 1.11; 95% CI, 0.81 – 1.53) were not significantly increased. The risk for cardiac malformations was slightly increased compared along with that for newborns exposed to meclizine in utero (OR, 1.62; 95% CI, 1.04 – 2.14). Many of the cardiac defects in this study were septal defects (17 of 19 total; OR, 2.05; 95% CI, 1.19 – 3.28).
Another study included a total of 897,018 births, 1248 of which ensued in women offered a prescription for ondansetron throughout pregnancy. There were 58 congenital malformations (4.7%) in the ondansetron-exposed group and 31,357 congenital malformations (3.5%) in the nonexposed group. Ondansetron exposure was associated along with a small improve in the risk for serious malformations (OR, 1.3; 95% CI, 1.0 – 1.7). The prevalence of heart defects, which accounted for Many of the increased malformations, was apparently doubled (OR, 2.0; 95% CI, 1.3 – 3.1).
“It is important to note that even though this study is regularly cited, it was published Just as an abstract and never ever as a peer-reviewed article. The abstract lacks important post such as the total variety of heart defects in the study,” Dr Siminerio and colleagues write. “[This study] discovered a significantly increased risk of cardiac malformations, however as a result of this lack of peer review and incomplete information, it is inappropriate to usage these findings in any kind of important assessment of ondansetron.”
A small study that compared the risk for birth defects in 176 women exposed to ondansetron throughout the very first trimester along with two teams of unexposed women showed no substantial differences between the teams in the variety of stillbirths or miscarriages, incidence of serious malformations, gestational age at birth, and mean birth weights. However, the study was underpowered and would certainly have actually detected Just “a fivefold improve in the incidence of serious malformations,” the authors write.
Similarly, there were no malformations in an observational cohort study of 65 women that were exposed to ondansetron throughout the very first trimester.
Finally, a study looked at 263 newborns born to 251 women that were exposed to ondansetron throughout pregnancy (81% throughout the very first trimester). There was a small however insignificant improve in the risk for any kind of serious birth defect in babies that were born to women exposed throughout the very first trimester (OR, 1.2; 95% CI, 0.6 – 2.2). The risk for obstructive renal defects was significantly increased (OR, 6.2; 95% CI, 2.0 – 19.5), however the variety of cases was much less compared to five, and the self-confidence interval was wide.
Benefit Outweighs Risks
“First-line agents such as ginger or pyridoxine and doxylamine are not constantly efficient for treating nausea and vomiting in pregnancy, and the known risks associated along with suboptimally treated nausea and vomiting in pregnancy or hyperemesis gravidarum should be weighed versus the quite small potential risks associated along with ondansetron use,” Dr Carstairs concludes.
Dr Carstairs and the commentators have actually disclosed no relevant financial relationships.
Obstet Gynecol. Published online April 4, 2016. Article abstract, Commentary extract
