Between 2013 and 2014, three separate teams of researchers developed studies to investigate the possible effects of the drug Zofran on early fetal development. Spurred by evidence that Zofran, a potent anti-nausea drug never approved for use during pregnancy, had gained popularity as a treatment for morning sickness, scientists in Denmark and Sweden pored over hundreds of thousands of birth and prescription records. All three teams came to a troubling conclusion: women who had been prescribed Zofran’s active ingredient, ondansetron, were at a significantly increased risk of delivering children with congenital heart defects.
But one year earlier, a collaboration between public health researchers at Harvard and Boston University had already revealed evidence of Zofran’s association with major birth defects.
Researchers Find Link Between Zofran & Increased Risk Of Cleft Palate
Funded by the US Centers for Disease Control & Prevention, the American team reviewed more than 10,000 birth records. Searching back through prescription logs, they identified pregnant women who had been prescribed ondansetron, and then compared their fetal outcomes to women who had not taken the drug.
Babies that had been exposed to ondansetron during the first trimester of fetal growth were 2.37 times more likely to be born with a cleft palate.
Why Is The First Trimester So Important To Fetal Development?
The first trimester of pregnancy is absolutely crucial for organ formation, a process known to the medical community as organogenesis.
Between four and ten weeks of development, a growing embryo’s early stem cells quickly differentiate. According to the dictates of genetic information contained within their nuclei, each cell becomes specialized in both form and function.
Eventually, after around six weeks of startling transformation, the embryo’s cells have arranged themselves into the organs upon which sustained life is based.
As you might expect, this process is extremely delicate. Even among cells without active genetic anomalies, the presence of toxins can interrupt cellular differentiation, multiplication and alignment. If organ development is inhibited, or altered in some way, these abnormalities commonly result in what we call “birth defects.”
It should be noted that the period during which organs develop is also when the majority of pregnant women begin to experience morning sickness. According to the National Library of Medicine, this nausea and vomiting “usually begins during the first month of pregnancy,” right at the beginning of organogenesis. Medical experts have observed that if ondansetron can alter fetal development, its “off label” use as a morning sickness treatment would present the most risk to a growing child.
What Are Cleft Lip & Cleft Palate?
The word “cleft” can be used to describe any split or opening, but in this context, cleft lip and cleft palate are congenital abnormalities in which cells that would have formed the continuous surfaces of an upper lip or roof of the mouth failed to do so for some reason. Together, these conditions are often referred to as “orofacial clefts,” because they result in a split or opening somewhere in the oral region of the face.
While lips form before palates during embryonic development, both organs are created in much the same way. Once stem cells have differentiated, newly-specialized cells crowd together to form sheets of tissue. But the tissues that will come to form lips and palate don’t start growing at the center of a child’s head. Instead, they begin forming on both sides and gradually work their way inward. Ultimately, both sides will meet in the middle and fuse together, unless some factor prevents a sufficient amount of cells from growing or blocks the two sides from fusing properly.
In children born without a cleft lip, the small depression directly under the nose, called the philtrum, is evidence of this process. This horseshoe-shaped groove marks the point at which a sheet of tissue from the left met a sheet of tissue from the right to create a continuous, unbroken surface. But as we’ve mentioned, in children born with orofacial clefts, something stopped the formation of lip or palate from coming to completion.
Types Of Orofacial Clefts
Babies can be born with clefts in their upper lip, clefts in their palate, or both simultaneously. When a child is born with only one of these organs affected by an opening, the condition is considered “isolated.”
In this drawing, courtesy of the Centers for Disease Control & Prevention, we see a baby born with an isolated cleft lip. Technically, this baby is shown with a complete unilateral cleft lip. The split is “complete” because it extends upwards far enough to affect the nose, and it is “unilateral” because the lip is separated only on one side. Children born with bilateral cleft lips have two distinct clefts, one on either side of the nose.
Because it affects the exterior of a child’s face, a cleft lip is simpler (although still difficult) to diagnose before birth than an isolated cleft palate, which exists entirely within a baby’s mouth. Doctors often use ultrasound technology, sending high-frequency sound waves that pass through a mother’s belly and bounce off the bodily structures of her unborn child, to diagnose birth defects of this nature.
There are actually two structures that make up the palate: a layer of bone, known as the hard palate is covered over by a flexible membrane, the soft palate. The soft palate extends further toward the throat than the hard palate, which ends about midway back in the mouth.
Like cleft lips, cleft palates can be thought of in terms of their extent. With an incomplete cleft palate, only the soft palate is split, and these openings generally occur further back in the mouth. In some children, the cleft in their soft palate extends to the uvula, the teardrop of hanging tissue over the throat’s opening. In an associated condition called bifid uvula, the uvula is cleft as well.
Complete cleft palates, on the other hand, affect both hard and soft palates. We can see an artist’s rendering of this condition on the left, with the bony hard palate, separated itself, protruding from behind a split in the soft palate.
“Submucous” cleft palate occurs when a thin layer of mucous membrane covers clefts in either soft, hard or both palates.
Living With A Cleft Palate Or Lip
To understand the effect that a cleft palate can have on a child’s life, we should first come to an understanding of the palate’s function. When continuous, palates separate the oral cavity from the nasal passages directly above it. This barrier prevents substances in the mouth from entering the sinuses.
During feeding, the soft palate rises upward to completely block the nasal passages, creating a vacuum that draws fluids and solid foods back to the throat. This upward motion is essential to sucking. After drawing foods inward, the soft palate descends to increase pressure and push substances back and down the throat.
While most babies with cleft lips are able to breastfeed adequately, children with cleft palates find it difficult to create enough suction to draw milk from a nipple. Most require specialized bottles and feeding strategies to be properly nourished.
With a cleft in the palate, babies can have difficulty sucking and swallowing adequately. For some, milk or formula will pass through the cleft, entering nasal passages and exiting through the nostrils. This loss of sustenance means that some babies with a cleft palate require additional feedings, or high-calorie formulas, to receive all the nourishment they need.
When fluids or solid foods are allowed to enter nasal passages, the resulting buildup can lead to hearing loss.
Directly behind the eardrum is the “middle ear,” a small gap that holds several interconnected bones. When these bones vibrate, their vibrations tap against a membrane, and the information is “translated” into a nerve impulse that the brain reads as sound. But the gap in which these bones are located is also connected to the nasal passages by a small passageway called the eustachian tube.
Usually, this tube is closed during daily activity, and only opens during times of chewing and swallowing to equalize the ear’s air pressure. When the eustachian tube opens, it also allows fluids to drain from the middle ear.
As we’ve suggested, the palate provides an additional barrier that protects the eustachian tube from filling with fluids. But in children with a cleft palate, no such barrier exists and the eustachian tube can become filled by liquids that are ingested through the mouth, causing inflammation.
Along with this inflammation, which itself can degrade the ear’s structures, influxes of liquid from the nasal passages can transport foreign bacteria into the middle ear. Middle ear infections, or otitis media, are a common result, and while upwards of 70% of all children will experience at least one middle ear infection by the age of three, children with a cleft palate are far more likely to have chronic and severe infections.
In fact, this 1984 study on middle ear infections and cleft palate found that 97% of children with a cleft palate were diagnosed with a more serious form of the infection, otitis media with effusion, which occurs when fluid builds up behind the ear drum but stays there even after an infection. Compounding the problem, children born with a cleft palate generally lack the muscles that open the eustachian tube, and thus fluid build-up is prevented from draining out of the middle ear.
Unfortunately, there is no evidence that palatoplasty, surgical procedures to reconstruct a cleft palate, improve middle ear function. Children born with an isolated cleft lip, on the other hand, have been found at no higher risk for middle ear infections than children without orofacial clefts.
Problems With Speech
Muscles in the soft palate are essential in forming certain speech sounds. But because children with a cleft palate lack many of these muscles, the very process of learning how to form certain speech sounds can be difficult from an early age.
When we speak, the soft palate rises to block the nasal passages, forcing air and words out through the mouth, rather than up through the nose. With an opening between the oral cavity and sinuses, and no structure to close it off, children with a cleft often develop abnormally nasal voices. This condition is called velopharyngeal inadequacy.
In addition, many common speech sounds require the tongue to touch certain portions of the palate that children born with orofacial clefts lack.
Orofacial clefts may affect a child’s upper gum line, inhibiting proper tooth development, spacing or placement. Particularly deep clefts can even alter the jawbone, making oral surgery a possibility.
How Are Cleft Lip & Cleft Palate Treated?
Because orofacial clefts produce a number of different, yet interconnected, complications, the standard of care for children born with these conditions has turned toward a “team” approach, in which a general practitioner and multiple specialists work together to address the full range of concerns.
Possible Surgical Procedures
Obviously, the treatment for every individual patient will vary significantly depending on the extent and severity of their cleft. With that being said, most children born with orofacial clefts undergo surgery within the first year of life.
Surgery for babies born with an isolated cleft lip is usually indicated between three and six months after birth, according to the Children’s Hospital of Philadelphia (CHOP). For many patients, the lip’s appearance and function can be repaired in one procedure, although two may be necessary, especially if nasal tissues are impacted by the cleft.
Surgery for a cleft palate is usually more extensive. Between nine and twelve months after delivery, a first procedure will close the cleft to improve feeding and adequately prepare the child to develop speech. While several techniques have become widely used, each method seeks to reposition muscles and tissues to close the palate. Some surgeons advocate for a one-stage intervention, while others prefer a series of surgeries spaced out over time.
Additional procedures may be required to promote proper jaw alignment and tooth development. Most children benefit from the expertise of specialized surgeons. An orofacial cleft team can include several different types of surgeon, including a plastic surgeon to perform initial reconstruction procedures and an oral surgeon to reposition segments of the jaw if necessary.
While surgical intervention is generally the first line of treatment, most children born with orofacial clefts will require additional therapies throughout childhood and adolescence. Depending on a child’s unique needs, an orofacial cleft team may include:
- Otolaryngologist (ear, nose and throat doctor, or ENT) to assess hearing problems and develop strategies of treatment
- Speech pathologist to evaluate problems with speech and feeding
- Audiologist to treat conditions that arise from hearing impairment
- Orthodontist to ensure that teeth develop properly, and possibly a prosthodontist, who specializes in creating unique dental appliances
In addition to these specialists, many families benefit from the guidance of a social worker or psychologist. While our society is becoming more accepting of children with orofacial differences, some children experience difficulties adjusting to social life. Parents, too, may need help balancing the stresses of caring for a child with unique needs.
Many families also find great support in meeting with other families affected by orofacial clefts, sharing stories and discussing strategies for improving their child’s care. You can find more information on joining a cleft lip and palate support group in your area on CleftSmile.org, the official website of The Cleft Lip & Palate Foundation of Smiles.
What Causes Cleft Palate?
Some orofacial clefts may have been caused by genetic abnormalities, many of which are passed down from parent to child, which is why some orofacial cleft teams also include a geneticist, who can help families determine the likelihood of having other children with clefts.
But toxic chemical substances ingested by a mother, including some pharmaceutical drugs, are another possible cause of many individual orofacial clefts, especially cases of cleft palate. At the beginning of this article, we mentioned one drug that has been recently associated with an increased risk of cleft palate: Zofran.
Beyond cleft palate, researchers have linked Zofran to a range of major birth defects, including several severe congenital heart defects. American families have even begun to file lawsuits against Zofran’s manufacturer for birth defects they say were caused by the drug.
These parents claim that the company unlawfully promoted Zofran to doctors as a “safe and effective” treatment for morning sickness, without ever studying its effects during pregnancy. They have also alleged that the company behind Zofran has been aware of the drug’s potential to alter fetal development for more than two decades, but has done nothing to warn the public or medical community.
Can My Family File A Zofran Cleft Palate Lawsuit?
If these allegations are true, other parents who were prescribed Zofran as a morning sickness treatment and then delivered a baby with a cleft palate may be eligible to bring a legal claim against Zofran’s manufacturer.
This website is sponsored by an alliance of attorneys dedicated to protecting the rights of families and birth defect survivors. Led by Monheit Law, our coalition is currently offering free consultations to any parent who believes that their child’s cleft palate may have been caused by prenatal exposure to Zofran. For more information on the current litigation, and to learn about your own case eligibility, call 1-877-620-8411 or fill out our contact form.