Researchers Find Zofran® Increases Risk of Cleft Palate

In this study, researchers at the Sloan Epidemiology Center at Boston University and the Harvard School of Public Health studied nausea and vomiting during pregnancy (NVP) and the medications used to treat it. They wanted to know whether NVP or the medications used to treat it are associated with non-cardiac birth defects, including cleft lip with or without cleft palate (CL/P), cleft palate alone (CP), neural tube defects (defects of the brain, spine, or spinal cord), and hypospadias (in which the opening of the urethra is on the underside of the penis, not at the tip). The research did not address possible cardiovascular defects.

Medications studied included antihistamine, antiemetics, phenothiazines, prokinetics, Emetrol or coke syrup, antacids, proton pump inhibitors, steroids, herbal and natural products, and Zofran (ondansetron) and other drugs in its class (5-HT3 receptor antagonists. 5-HT stands for 5-hydroxytryptamine, the chemical name for the neurotransmitter serotonin.)

NVP itself was not found to be associated with cleft palate or neural tube defects. NVP was found to be negatively associated with CL/P and hypospadias, i.e., women with NVP were less likely to have children with those defects.

The main comparison in this study was between women with nausea and vomiting who took some type of medication during the first trimester of their pregnancies and women with NVP who did not take any medication. Three significant associations were found between drugs taken during the first trimester and birth defects:

  • Proton pump inhibitors were associated with a four-fold increase in the risk of hypospadias.
  • Steroids were associated with a nearly three-fold increase in the risk of hypospadias.
  • Taking ondansetron during the first trimester increased the risk of cleft palate alone by nearly two-and-a-half times (2.4 times). Ondansetron and drugs in its class were the only drugs associated with cleft palate.

Findings were adjusted to account for the possible effect of several factors known to be linked to birth defects, such as maternal age, smoking and obesity.

Summary Information

Medications Used to Treat Nausea and Vomiting of Pregnancy and the Risk of Selected Birth Defects

Marlene Anderka 1; Allen A. Mitchell 2; Carol Louik 2; Martha M. Werler2; Sonia Hernandez-Diaz2,3; Sonja A. Rasmussen4

  1. Center for Birth Defects Research and Prevention at the Massachusetts Department of Public Health, Boston, Massachusetts
  2. Slone Epidemiology Center at Boston University, Boston, Massachusetts
  3. Harvard School of Public Health, Boston, Massachusetts
  4. The National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Georgia

Birth Defects Research (Part A): Clinical and Molecular Teratology (94):22-30, January 2012. Published online November 19, 2011

This study was supported by a grant from the Center s for Disease Control and Prevention (U50/CCU 113247), b y a New Investigator in MCH Research Dissertation Award from MCHB, HHS (1 R03 MC 00004); and by a grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (RO1 HD 046595).