As in the case of all birth defects, the causes of orofacial clefts are often complex, with many potential factors to be considered, including genetics, medications that are ingested by the mother, prenatal nutrition and other “environmental” factors. With that being said, the scientific community is unanimous in its belief that most, if not all, birth defects can be reduced to the effects of two factors crucial to fetal development.
In this article, we’ll provide an overview of these two areas of research with an eye to specific factors that may predispose children to developing orofacial clefts.
What Causes Orofacial Clefts?
During early fetal development, both lips and palate (roof of the mouth) form in much the same way. Mouth and lip tissues begin growing from the sides, eventually meet in the middle and fuse together to create a continuous surface. The small groove beneath your nose, or “philtrum,” is evidence of this process. Those two lines that define your philtrum’s borders are where lip tissues met and joined together.
In children born with cleft lip and / or palate, something impeded this fusing process: there was an insufficient amount of lip or mouth tissue, and the joining was inhibited for some reason.
As a result, babies born with orofacial clefts have splits (which can be large or small) that separate their upper lips and / or the roof of their mouths.
Now that we’ve covered what happens during clefting, we can turn to potential causes.
Genetic mutations very likely play a role in most individual cases of orofacial clefting.
Genetic material, passed from parents to growing baby, contain information essential to the development of a human child. You can think of genes as a set of instructions, telling cells to produce certain things in certain quantities. And among their many functions, genes instruct lip and mouth tissues to develop in a certain way.
But in order to be passed on to a child, genetic information must be copied. Babies themselves begin as one cell, which then copies itself over and over, about 26 million times before birth. That’s a lot of copies, and sometimes, cells make mistakes during the process. We call these mistakes “mutations,” and abnormal genetic material is probably a contributing factor in some orofacial clefts.
Orofacial clefts are also known to be hereditary, which means that babies are at a higher risk of developing cleft lip and / or palate if their parents, siblings or other family members were born with them. In this case, the genetic mutation is already contained in a parents’ DNA, and is then passed on to their child.
A “syndrome” is a group of physical or developmental characteristics that usually occur alongside one another. Most are the product of mutated genes, but they need not be.
Orofacial clefts have been associated with more than 300 different genetic syndromes, including:
- Van der Woude Syndrome
- Pierre Robin sequence
- Velocardiofacial syndrome
You can learn more about genetic syndromes that include orofacial clefts as a characteristic here.
When a geneticist refers to “environmental factors,” they mean everything that isn’t considered genetic information.
Most scientists believe that individual cases of orofacial clefting are produced by an interplay between genetics and these so called “environmental” causes.
In essence, developing babies inside the womb can be exposed to numerous substances before birth. Many of these chemicals are ingested by a mother, travel into her bloodstream and then enter the body of her developing child through the umbilical cord. Substances that have been associated with an increased risk of fetal harm are called teratogens.
Nicotine, a well-established danger to fetal development ingested by smoking, has been associated with an increased risk of orofacial cleft by at least 19 separate studies conducted between the years of 1979 and 2004.
Have Any Prescription Drugs Been Linked To Orofacial Clefts?
Another primary concern is that of prescription medications. Before we continue, it’s crucial to note that pregnant women should never begin taking or discontinue the use of a drug without first consulting their doctor.
Several commonly-prescribed drugs have been linked to an increased incidence of orofacial cleft, including the topical acne medication Accutane and “vasoactive” drugs like pseudoephedrine and aspirin.
Anticonvulsants, used to treat forms of epilepsy, like topiramate (sold under the brand name Topamax), phenobarbital and dilantin (sold under the brand name Depakote) have also been associated with cleft lip and / or palate, although there is some debate over whether or not maternal epilepsy itself may increase the risk of delivering a child with an orofacial cleft.
Ondansetron’s Potential Link To Orofacial Clefts
Ondansetron, an anti-nausea medication sold as Zofran, has been commonly prescribed “off-label” to pregnant women during the first trimester as a treatment for morning sickness. Prescribing “off-label” is a practice in which physicians prescribe drugs to treat conditions for which they have not been approved.
In 2012, researchers at Harvard University’s School of Public Health and Boston University’s Slone School of Epidemiology compared the birth outcomes of 4,524 pregnant women who had been prescribed ondansetron during the first trimester to those of 5,859 women who had not sought medical treatment for morning sickness. They found that women who had taken ondansetron as a morning sickness treatment were 2.37 times more likely to deliver babies with a cleft palate.
One study may or may not be enough to provide conclusive evidence that a prescription drug has the potential to cause birth defects. But three other large-scale studies have also found an increased incidence of birth defects among babies born to women who were prescribed ondansetron during the first trimester.
It is possible that Zofran’s effects on fetal development deserve further scrutiny from the health community.
The Cleft Lip & Palate Foundation of Smiles has prepared a number of reports on the links between specific prescription drugs and orofacial clefts. You can find more information at CleftSmile.org.