Zofran is a powerful anti-nausea drug approved to treat cancer patients and individuals undergoing surgical procedures. But Zofran, along with generic versions of its active ingredient ondansetron, has also become America’s leading treatment for morning sickness, the nausea and vomiting experienced by as many as 90% of all pregnant women during the first trimester.
While physicians usually restrict the drug’s use to cases of hyperemesis gravidarum, an extremely severe form of morning sickness, a growing body of scientific research has raised significant concerns over Zofran’s safety during pregnancy.
In at least four, peer-reviewed studies, separate teams of researchers from Australia, the US, Sweden and Denmark have begun to establish an association between Zofran taken during the first trimester and severe birth defects.
In a study funded by the US Centers for Disease Control (CDC), researchers concluded that orofacial clefts, including cleft palate and cleft lip, were 2.37 times more likely in babies born to mothers who took Zofran. But the strongest association has been found in relation to congenital heart defects.
Which Congenital Heart Defects Have Been Associated With Zofran?
In this article, we’ll cover the three types of heart defect that have been linked to Zofran. But to understand how a congenital defect can change the heart’s function, we have to understand the heart itself in more detail.
How Does The Heart Work?
The heart is a pump made of muscles, designed to carry blood from your lungs to the rest of your body. It looks like this:
This image is reversed, so on the left side of the picture we actually see the heart’s right side. In essence, the heart is composed of four chambers. On top, we have the “atrium,” labeled “RA” on the right and “LA” on the left. On bottom are the “ventricles,” labeled “RV” and “LV.”
Note that the atria and ventricles are separated from one another by a large barrier called a “septum.” Valves, labeled “TV” and “MV” allow blood to flow from above to below through each side. This is crucial to the heart’s function: blood can flow from an atrium to a ventricle, but not side to side, from one atrium to the other, or one ventricle to the other.
How Does Blood Flow?
Blood enters the heart from above, reaching first the right atrium. From here, it flows downward, into the right ventricle. Then it’s pushed up through the pulmonary valve (labeled “PV”) into a large blood vessel called the pulmonary artery. This artery leads to the lungs, where blood picks up oxygen.
Before coursing through the body, the oxygen-rich blood has to come back to the heart. This time, it enters on the left side and fills the left atrium. Flowing down, it reaches the left ventricle and is then pumped into the aorta (labeled “Ao”), another large blood vessel.
The aorta leads away from the heart, branching in different directions and bringing oxygen-rich blood through the rest of the body. After releasing this oxygen, which nourishes every organ and tissue, blood flows back to the right atrium for more.
Now that we have an understanding of the heart in individuals born without birth defects, we can turn to the congenital anomalies that have been associated with Zofran.
1. Atrial Septal Defects
Researchers in Denmark reviewed every Danish birth record filed between 1997 and 2010. In the end, their study included 903,207 pregnancies. While only 1,368 of these women were prescribed Zofran or a generic equivalent during the first trimester, the study’s authors concluded that women who ingested ondansetron were 2.1 times more likely to deliver babies with an atrial septal defect (ASD).
ASD occurs when the heart’s tissues fail to form properly during fetal development. Instead of a continuous barrier to separate the top two chambers, babies with an ASD have a hole in their atrial septum.
How Does An ASD Change Blood Flow?
Because the left atrium is slightly higher than the right, gravity can pull blood from one side to the other through an atrial septal defect. Remember that blood on the heart’s left side has already been filled with oxygen. If it’s drawn over to the right atrium, it will mix with the oxygen-poor blood normally found in that chamber, and then return to the lungs.
In effect, the heart is pumping a mixture of blood to the lungs, but only a portion of the mixture needs to be there. Some of the blood has already been saturated by oxygen. When it returns to the heart, and is pumped out to the body, organs and tissues are only receiving a fraction of the oxygen that they require.
What Are The Risks Of An ASD?
Over time, the heart is forced to work harder to adequately nourish the body, which puts a strain on arteries and blood vessels that are now filled with more blood, at higher pressures, than they were designed to withstand.
This extra work can cause a wide range of problems over the course of many years, including:
- pulmonary hypertension – high blood pressure in the lungs
- arrhythmia – abnormal heart rhythms
- stroke – the lungs normally filter blood for small clots, making sure that they don’t reach arteries or veins within the body. But in people with an ASD, it’s possible for clots to pass immediately from the right atrium to the left, bypassing the lungs entirely. If a clot reaches blood vessels that feed the brain, it can block blood flow and eventually cause a stroke.
In developed countries with advanced health systems, these potential complications are extremely rare. In fact, many smaller atrial septal defects close on their own within the first years of life. Most patients should be monitored closely to ensure that the defect does close, but many will never experience any of the associated problems.
At the end of this article, we’ll explain how most congenital heart defects, including ASD, can be effectively treated.
2. Ventricular Septal Defects
In their study of over 900,000 pregnancies, the Danish team found an even higher association between Zofran and ventricular septal defects. Expectant mothers prescribed ondansetron during the first trimester were 2.3 times more likely to deliver a baby with a VSD.
Children with a VSD are born with a hole in the barrier separating the heart’s two lower chambers, the ventricles.
How Does VSD Affect Blood Flow?
Similar to the case of an atrial septal defect, oxygen-rich blood in the left ventricle is allowed to flow over to the right, and mix with blood that has not yet reached the lungs. As a result, the heart is forced to work harder to deliver adequate levels of oxygen throughout the body.
What Complications Are Associated With VSD?
Over time, extra work can damage blood vessels and arteries, as well as the heart itself.
In infants, symptoms of a VSD may include:
- Labored or fast breathing
- Difficulty feeding – VSD puts a strain on the lungs, as well as the heart. This can make it difficult for babies to breath and many infants with a VSD will tire easily, especially during feeding. Although this is rare, some babies may have trouble getting an adequate amount of nutrients, and experience impaired growth.
Doctors are often able to diagnose a VSD shortly after birth by listening to heart murmurs. These sounds, commonly described as a “whooshing” noise, are created when blood flows improperly through the heart. VSDs create a particularly unique heart murmur, and many physicians can actually diagnose the defect’s location and size based on sound alone.
Adults with undiagnosed ventricular septal defects are at a higher risk for many of the same conditions as those with ASD, including pulmonary hypertension and arrhythmia. Infective endocarditis, an infection of cardiac tissue, is also a concern.
3. Atrioventricular Septal Defects
According to the Danish study’s conclusions, the condition whose risk was most increased by taking Zofran was an atrioventricular septal defect. Babies born to mothers who had ingested ondansetron were 4.8 times more likely to deliver a child with AVSD.
Babies with an AVSD are born with a hole at the heart’s center, where the wall separating the atrium from one another meets the wall that separates the ventricles. In most infants, this hole is actually the result of malformed valves.
As we’ve discussed, the top and bottom atria are closed off from one another by a valve, as are the ventricles. But early in embryonic development, these two valves are still connected to one another. Eventually, they separate, migrating to either side and controlling blood flow through the chambers. In children born with AVSD, this single “common” valve failed to divide and remained near the middle of the heart.
What Are The Risks Of AVSD?
Unlike many ASDs and VSDs, atrioventricular septal defects do not close of their own accord. Babies born with the defect will usually present symptoms of congestive heart failure anywhere from one to two months after birth. A large amount of blood is being allowed to flow directly from the heart’s left side to its right, forcing the organ to work extremely hard to nourish the body adequately.
Heart murmur, cyanosis (a blue tinge to the skin and lips) and impaired growth are all potential signs of congestive heart failure.
How Are Congenital Heart Defects Treated?
Babies with an AVSD almost always require open-heart surgery, though the procedure is often delayed for several months to allow the infant to grow.
During this procedure, pediatric cardiac surgeons will attempt to separate the common valve with one or two patches, which may be enough to close the opening between the chambers.
According to the University of Michigan, upwards of 95% of patients “do well without significant complications” after repair of an AVSD.
As for atrial and ventricular septal defects, we’ve already mentioned that many defects close on their own over time. During the wait, several medications can be prescribed to normalize heart rhythms and reduce blood pressure in the lungs.
For larger defects, or those that have been diagnosed in adulthood, open-heart surgery is a possibility. But a less-invasive procedure, cardiac catheterization, is often attempted first. Catheters are thin tubes that can be inserted into a vein (usually near the groin) and then threaded up, through the body, to the heart. By attaching a small patch to the end of a catheter, surgeons may be able to reach the defect and close it through this method.
With adequate monitoring and treatment, these defects can be successfully repaired, and children will continue to live happy, healthy lives.