Zofran Cleft Palate and Cleft Lip malformations

Cleft palate and cleft lip are some of the birth defects associated with the off-label use of Zofran (Ondansetron) during pregnancy. Although they can be treated surgically, these malformations may negatively impact the health and development of the newborns affected by causing speech problems or increasing the risk of infections.

Ondansetron has never been approved for use in expectant mothers, despite GlaxoSmithKline widely marketed it as an off-label treatment for morning sickness and nausea and vomiting during pregnancy (NVP). The Food and Drugs Administration (FDA) only approved this medication as an antiemetic drug in patients who underwent surgical interventions and cancer chemotherapy and radiotherapy. This drug pregnancy category is FDA Category B, meaning that there are no adequate and well-controlled studies that demonstrate its safety in pregnant women. GSK was thus publicly accused of hiding or misrepresenting the results of their animal studies that showed this medication’s risks during pregnancy.

Cleft palate and cleft lip are some of the most common and known congenital abnormalities caused by the drug that forced many babies to end in the operating room. A human study performed by the Center for Birth Defects Research and Prevention (CDC) showed that the risk of cleft lip and palate defects are more than doubled if the mother took Zofran for NVP during the first trimester of gestation. The study examined about 10,000 total patients and found a risk for these two congenital defects of 2.37 (adjusted odds ratio [aOR]) in pregnant women who used ondansetron, compared to a 0.87 aOR for those who took no medications. Other studies and reports showed an association between the antiemetic and birth defects, with an increased risk of roughly 30 percent.


What is a cleft palate malformation?

A cleft palate is a congenital abnormality that comes from the incomplete fusion of bones forming the inner top area of the mouth. A baby with a cleft palate has a “hole” in the upper portion of the roof of the mouth (hard palate) because the bone tissues fail to merge among themselves. Often, even the soft, skinny portion of the palate (soft palate) does not close, leaving a gap between the mouth and nose that makes feeding difficult. A baby with a cleft palate also shows several difficulties in speaking, as air leaks in the nasal cavity during the articulation of words. Complications include recurrent ear infections, hearing impairment, dental problems, and speech retardation. Many children with cleft palate often suffer from hearing loss due to the inability for the ear muscles to function properly without an adequate anchoring.

This abnormality must be treated surgically with a temporary prosthetic device called palatal obturator which is used to fill the gap inside the roof of the mouth. When the baby reaches 6-12 months a series of new surgical interventions is required to permanently correct the malformation. As the child grows in fact, the palate changes its morphology, requiring many new re-interventions until the gap is filled. To improve the hearing ability of the baby, a tympanostomy tube is usually inserted in the eardrum to drain the excess ear fluid discharge that is commonly associated with this condition. Infants affected by cleft palate often require language intervention and speech therapy to correct their speech problems.


What is a cleft lip malformation?

When the gap does not involve the palate but the mouth, the condition is called “cleft lip”. The baby’s two upper lip portions do not fuse themselves, leaving a hole (cleft) that may continue to the nose. Mild forms of this birth defect may leave just a small indentation between the lips, while in more severe forms the gap leaves a hole behind the nostrils that may even affect the muscle tissues. Similarly to cleft palate, babies who suffer from this congenital abnormality often show several dental issues such as cavities, as the lack of protection from external agents increases the quantity of bacteria inside the mouth. Other dental malformations such as extra teeth or missing teeth are also common, and often require additional dental procedures to be corrected.

Babies with cleft lip usually have trouble feeding due to their inability to properly suck milk. As lips are used for suction, mothers need to use specialized equipment to feed their babies, such as special bottles and mouth guards, to provide them with adequate nutrition. Speech problems are also very common, and usually require early speech therapy to be corrected. Corrective surgery needs to be performed to close the lip as early as possible, preferably within the first 2-3 months after birth, although 10 weeks is the preferred age. Surgical procedures vary depending on the type of cleft and often require more than just one intervention. Plastic surgery may help restore the muscles behind the lip and reduce the size of the scarring. Scarred babies may also lead to psychosocial issues such as anxiety, depression and aggressive behaviors during adolescence and adulthood.
Article written by: Dr. Claudio Butticè, Pharm.D.
Published: 2016/08/10
Last Updated: 2016/08/10