Is Zofran safe during pregnancy?

What does the evidence say about Zofran during pregnancy?

1. Most studies following thousands of pregnant women on ondansetron have not found a higher chance of birth defects or miscarriage. 1
2. Ondansetron wasn't tied to a higher rate of miscarriage, stillbirth, major birth defects, or early delivery in a Danish study of more than 600,000 pregnancies, with birth-defect rates landing at almost the same 2.9 percent in exposed and unexposed groups. 2
3. Heart defects weren't more common after first-trimester ondansetron in a US study of over 1.8 million pregnancies, though the same study found a small rise in oral clefts, about 3 extra cases per 10,000 births. 3
4. Overall birth-defect risk from ondansetron looks low across the combined research, and doctors typically reserve it for nausea that hasn't improved with gentler options first. 4
5. Oral clefts and a specific heart-wall defect called a ventricular septal defect showed small upticks with first-trimester ondansetron use when 12 studies were pooled together, but major malformations, general heart defects, and cleft lip alone did not rise overall. 5

Is Zofran safe in each trimester?

• First trimester. Ondansetron is usually started in the first trimester, after ginger, vitamin B6, or a doxylamine-B6 combination hasn't calmed nausea and vomiting enough, the same stepwise pattern most obstetric practices follow. This trimester gets the most research attention because it's when major organs form: the largest cohort found no rise in overall birth defects, while a couple of reviews flagged a modest, still-unsettled signal for oral clefts tied to first-trimester exposure.
• Second trimester. Nausea usually eases by the second trimester, so ondansetron here is typically reserved for people still dealing with severe or persistent symptoms, including hyperemesis-type cases. The reassuring safety data on stillbirth, preterm delivery, and birth weight covers continued use past the first trimester, though the oral-cleft signal from other reviews is tied specifically to first-trimester timing.
• Third trimester. Third-trimester data on ondansetron is thinner than first-trimester data, and nothing in the sources reviewed here points to a late-pregnancy or delivery-specific concern. If nausea is still severe enough this late to need ondansetron, that's worth revisiting with your obstetric provider as you plan for delivery.