Manufactured by international pharmaceutical giant GlaxoSmithKline, Zofran is now America’s leading morning sickness treatment. Recent estimates suggest that more than 1 million prescriptions for the powerful anti-nausea drug are written to pregnant women every year, despite the fact that Zofran has never been approved for use during pregnancy.
In fact, GlaxoSmithKline has never even studied the drug’s effects in clinical trials involving pregnant women.
Studies Link Zofran To Congenital Heart Defects
Now that millions of women around the world have been exposed to Zofran during pregnancy, teams of independent researchers are beginning to investigate the drug’s effects on fetal development. So far, their findings have been troubling, including a more than 200% increase in the risk for cleft palate.
But in two major epidemiological studies, researchers in Denmark and Sweden have also identified an increased risk for congenital heart defects among babies exposed to Zofran’s active ingredient in utero.
Danish Researchers Identify Increased Risk For Cardiac Septal Defects
A team at Copenhagen University Hospital reviewed every birth record filed in Denmark between 1997 and 2010. Ultimately, their study included a total of 903,207 pregnancies. Of those women, the researchers identified 1,368 who had redeemed prescriptions for ondansetron, Zofran’s active ingredient, during the first trimester. Then they compared the fetal health records of women who had been prescribed ondansetron to those in which ondansetron had not been prescribed.
Women who had taken Zofran were found to be 60% more likely to deliver children with congenital heart defects. Drilling down, the researchers identified even higher risks associated with a category of heart defects known as “cardiac septal defects.” Babies exposed to ondansetron during the first trimester were:
- 2.1 times more likely to be born with an atrial septal defect
- 2.3 times more likely to be born with a ventricular septal defect
- 4.8 times more likely to be born with an atrioventricular septal defect
The team presented their findings in August of 2013 at the International Conference on Pharmacoepidemiology and Therapeutic Risk Management in Montreal. The paper was subsequently published in the peer-reviewed journal Pharmacoepidemiology and Drug Safety.
You can find an abstract of the Danish study on page 13 of this .PDF.
Swedish Team Finds Similar Congenital Heart Defect Risks
One year later, Swedish researchers would use a similar methodology – and come to similar results.
Analyzing every birth record logged in Sweden between 1998 and 2012, the team identified 1,349 infants who had been exposed to ondansetron during early fetal development, the time at which heart abnormalities are most likely to form. The study eventually included an astounding 1.5 million births.
Next, the researchers compared the rate of fetal malformations among babies exposed to ondansetron and babies not exposed. Women who had ingested Zofran’s active ingredient during early pregnancy were:
- 62% more likely to deliver babies with a cardiovascular defect
- 2.05 times more likely to deliver babies with a cardiac septal defect, predominantly atrial and ventricular septal defects
The paper was published under the title “Use of ondansetron during pregnancy and congenital malformations in the infant” in the December 2014 edition of Reproductive Toxicology, a peer-reviewed journal.
You can find a full text of the Swedish findings here.
What Are Cardiac Septal Defects?
In essence, children born with cardiac septal defects have holes in their septum, the barriers that usually separate each heart chamber from its neighbors. But to properly understand this category of congenital heart defects, we need to understand the way a healthy human heart works first.
Human hearts are made up of four chambers: two on top, the atrium, and two on the bottom, the ventricles. In early fetal development, barriers form to separate these chambers from one another; these walls, which maintain blood pressure and proper blood flow, are called septum.
After nourishing cells and body tissues with oxygen, blood flows back into the heart through its right atrium. It travels downward through a valve and enters the right ventricle, which contracts to push the fluid out through the pulmonary artery and enters the lungs. Here blood picks up oxygen; you may also see this process referred to as “oxygenation.” After being oxygenated in the lungs, blood flows back to the heart, but this time, it enters on the left side, filling the left atrium. Contraction brings the blood down into the left ventricle, and another pump sends the oxygenated blood out toward the rest of the body, through a large artery called the aorta. The entire process is repeated, on average around 108,000 times every day.
Now that we understand healthy blood flow, we can turn to what happens when the structures of the heart develop improperly during pregnancy.
To skip directly to a specific congenital heart defect, click one of the links below:
An atrial septal defect (ASD) is a hole in the barrier that normally separates the heart’s two uppermost chambers, the atria. As a result, blood can flow between the two chambers, rather than directly down into the lower ventricles. Oxygenated blood mixes with deoxygenated blood in the right atrium and is then sent back out to the lungs. But some of the blood has already picked up oxygen, which means that the fluid eventually pumped out to the rest of the body isn’t able to provide as much of the vital nutrient as it should.
Over time, the heart is forced to work harder than normal, placing strain on both cardiac tissues and the arteries that lead to the lungs.
As with all cardiac septal defects, ASDs can be large or small, mild or severe. In some cases, patients live with small holes in their atrial barrier for years, never experiencing any side effects. This may explain why a paper published in Circulation: Journal of the American Heart Association concluded that atrial septal defect was the most commonly diagnosed congenital heart defect among adults. In fact, around 50% of all ASDs close of their own accord over time.
But over time, even minor ASDs can place undue strain on the heart’s operation and lead to significant symptoms, including heart palpitations and respiratory problems.
At birth, large atrial septal defects may become immediately apparent. Potential symptoms include:
- Difficult, labored breathing
- A bluish shade to skin and lips called cyanosis, caused by insufficient amounts of oxygen reaching the child’s extremities
- A “heart murmur,” the characteristic sound of blood flowing improperly within the heart. Heart murmurs are often described as a “whooshing” sound.
In particularly severe cases, physicians may even be able to diagnose an atrial septal defect prior to delivery. Using a form of ultrasound called “fetal echocardiogram,” physicians send high-frequency sound waves through a mother’s belly. The waves bounce off the baby’s internal organs, and a special computer program “translates” the way they bounce to create a picture of what’s going on inside. In some cases, this picture may reveal evidence of structural anomalies.
Most newborns born with an ASD do not suffer from complications immediately after birth. Rather, symptoms appear later in life, after years or even decades of abnormal blood flow.
In the absence of adequate treatment, an atrial septal defect can lead to:
- Arrhythmia, an abnormal heart rhythm caused by damage to the organ’s natural “pacemaker,” a complex system of electrical impulses that trigger contractions.
- Stroke, in which a blood clot blocks a vessel transporting blood to the brain. Lungs often “filter out” blood clots before they reach the heart’s left atrium and are pumped out to the rest of the body. But in patients with an atrial septal defect, blood is allowed to enter the left atrium, without first passing through the lungs. Blood clots can be missed, forming in the heart’s right atrium, and then passing directly out to the blood vessels that nourish the body, and ultimately the brain.
- Pulmonary hypertension, a form of high blood pressure affecting blood vessels that branch through the lungs. Over the course of years, high blood pressure can actually “thicken” these vessels, forcing the heart to pump even harder to adequately nourish the body.
- Right heart failure, in which the heart’s right side loses the ability to pump adequately.
Can It Be Treated?
Absolutely. In fact, an open-heart procedure has become so effective in repairing holes in the atrial septum that a full recovery is expected in nearly 100% of cases.
Not all atrial septal defects require open-heart surgery. As we’ve already mentioned, many close on their own eventually. In the meantime, there are several medications used to reduce the risk of complications, including beta blockers, which can prevent arrhythmias, and anticoagulants, which help prevent blood clots from forming in the first place.
In recent decades, procedures less invasive than open-heart surgery, which usually requires the use of a cardio-bypass machine, have become standard in the repair of ASDs. Using a long catheter, surgeons can thread a small patch through blood vessels in the patient’s groin. Once the catheter has reached the heart, the patch can be placed to cover the hole, and new cardiac tissue will eventually grow to cover the patch.
A ventricular septal defect (VSD) is a hole in the wall that normally separates the heart’s bottom chambers or ventricles. Because the left ventricle is slightly higher than the right, gravity draws oxygenated blood downward into the right ventricle, which usually only holds deoxygenated blood about to be sent through the lungs.
From here, this new mixture of blood is pumped out to the lungs, but some has already picked up its own load of oxygen. When it eventually reaches tissues and cells throughout the rest of the body, the blood is only carrying a portion of the oxygen that those structures require.
To compensate, the heart is forced to work extremely hard, pumping larger volumes of blood with each contraction. Eventually, this strain can damage both the heart and lungs.
Depending on the size and severity of a VSD, some children won’t experience any side effects at all. In fact, many ventricular septal defects close up themselves, without any treatment.
Larger holes, on the other hand, can present symptoms directly after birth:
- Chronic lung infections
- Accelerated heart rate
- Difficulty breathing
- Pale or ashen skin
- Sweating during feedings
All of these symptoms are side effects of congestive heart failure, a condition in which the heart isn’t able to pump as vigorously as it would in perfect health. Heart failure does not mean that the heart ceases beating completely.
Congestive heart failure in newborns is generally measured according to weight gain. Babies born with a VSD may “fail to thrive,” because their bodies aren’t receiving sufficient amounts of oxygen to properly process the calories they ingest.
VSD can often be diagnosed based on a “heart murmur” alone. This characteristic “whooshing” sound is created as blood flows along abnormal pathways within the heart. According to Cincinnati Children’s Hospital Medical Center, the heart murmur created by ventricular septal defects is so specific that “a cardiologist may be able to pinpoint the
Babies born with small VSDs are at risk for two primary complications:
- Leaking aortic valve – the aortic valve lies right between the heart’s left ventricle and the aorta, an artery that transports blood out to the rest of the body. The valve’s main function is to prevent blood from leaking back into the ventricle after it’s been pumped out to the aorta. But because hearts with a VSD are forced to pump higher volumes of blood harder, the aortic valve can become weak and ineffective.
- Infective endocarditis – untreated, this infection of heart tissue can be fatal.
The potential long-term complications of a ventricular septal defect relate to pulmonary hypertension, high blood pressure in the lung’s blood vessels. Over time, hypertension actually forces the walls of these vessels to thicken and narrow, making it even harder for the heart to pump adequate amounts of blood through the lungs. In fact, blood can actually “back up” here, and not even reach the lungs. Instead, excess fluid will be forced through the VSD over to the heart’s left side, allowing deoxygenated blood to travel directly out to the body.
After years of stress, young adults with undiagnosed VSDs can develop Eisenmenger’s syndrome, in which the skin takes on a bluish tint due to lack of oxygen. Eisenmenger’s syndrome can result in a host of adverse side effects, including chest pain, fatigue, difficulty breathing, and stroke.
How Are VSDs Treated?
Babies born with small ventricular septal defects may not require any treatment; some holes close on their own over time. Several medications can be administered to reduce the risk of serious complications, including diuretics that promote urination to lower fluid levels traveling through the lungs.
If congestive heart failure occurs, a surgical procedure may be necessary to cover the hole. For large VSDs, open-heart surgery is generally indicated, but smaller defects may be repaired via cardiac catheterization. Catheters, thin tubes, can be inserted through a vessel in the child’s groin, then thread upwards toward the heart. Upon reaching the VSD, a small patch affixed to the end of the catheter can be placed to close the defect.
99% of children who undergo either procedure never experience complications afterward, according to Cincinnati Children’s Hospital.
During early fetal development, the heart begins as a tube. But by around 8 weeks of pregnancy, the organ will have separated into four distinct chambers. As for the barriers between these chambers, they begin as a collection of cells called endocardial cushions. From the endocardial cushions, two valves will also develop one allowing blood flow between the ventricles and another between the atrium.
In children born with an atrioventricular septal defect (AVSD), these endocardial cushion cells failed to develop properly. AVSDs are highly individual and may vary widely from child to child. But in all cases, the heart’s chambers are inadequately divided. For some children, there appears to be a large hole directly in the heart’s center, where all four chambers meet. Children born with an AVSD may also have only one “common” valve, rather than two.
For severe cases of AVSD, symptoms usually present immediately after birth or within the first few weeks of life:
- Trouble feeding which can lead to low weight gain
- Difficulty breathing
- Accelerated heartbeat
- Fatigue or lethargy
- Cyanosis, a bluish tint to the skin and lips caused by low blood oxygen levels
- Swollen legs and abdomen
- A “heart murmur,” a characteristic sound produced by abnormal blood flow
These are symptoms of congestive heart failure, a condition in which excessive strain on cardiac tissue weakens the organ’s pumping ability.
In less-severe cases of AVSD, symptoms may not present for days, weeks, even years. Many congenital heart defects go undiagnosed for decades. But eventually, improper blood flow can lead to pulmonary hypertension, a form of high blood pressure in the lung’s blood vessels, arrhythmia, an abnormal heart rhythm and congestive heart failure.
Pulmonary edema is widely considered the most pressing concern for children born with an AVSD. With blood allowed to flow directly from the heart’s left side to its right, the organ is forced to pump double, even triple the amount of blood normally transported toward the lungs at any one time. The lungs, meanwhile, are being stressed by high volumes of blood pumped at elevated pressures.
As a consequence, the lungs can become engorged with blood. Fluids traveling through the blood vessels are forced out, leaking into spaces normally reserved for air. This is known as pulmonary edema, and it impedes the very movement by which lungs are filled with oxygen.
How Can Atrioventricular Septal Defects Be Treated?
However severe, the majority of AVSDs will be repaired through open-heart surgery. During this procedure, surgeons hope to patch any holes in cardiac tissue and, if necessary, separate a common valve into two distinct valves.
Since newborns are not ideal candidates for open-heart surgery, some physicians will first attempt to control symptoms by administering medications. Then, when the child has matured enough to undergo a complex procedure, surgeons will perform the operation.
With that being said, children born with severe AVSDs are generally operated on between three and six months after birth. Less severe cases can be repaired later, anywhere between six and eighteen months after delivery.
These procedures have become extremely effective in recent decades. In moderate cases of AVSD, almost 100% of children will survive their procedure. Severe AVSDs, however, have around a 97% survival rate.
What Causes Congenital Heart Defects?
In the case of any child’s individual congenital heart defect, it’s unlikely that doctors will be able to point out a precise cause. But there are two potential causal factors upon which the medical community agrees:
- Environmental factors
Congenital heart defects may be caused by abnormalities in genetic information, either one is passed from parent to child as DNA or anomalies that arise spontaneously as an embryo’s cells divide and multiply.
But environment also plays a role. When ingested by a mother, many substances pass through the blood stream, cross what researchers call the “placental barrier” and enter the tissues of her growing child. If these chemicals have the potential to alter fetal development, if they are teratogenic, they will do so by crossing the placental barrier.
Zofran is certainly able to cross the placental barrier. Early animal studies conducted by GlaxoSmithKline prior to the drug’s approval demonstrated this fact, as did a study conducted in human subjects by Chinese researchers in 2006. In fact, several Plaintiffs in Zofran birth defect lawsuits have accused the company of concealing this evidence from the public.
Zofran Birth Defect Lawsuits
Now that major scientific studies have associated prenatal exposure to Zofran with an increased risk for congenital heart defects, families have begun to file lawsuits. While at least two of these claims have been filed in relation to orofacial defects like cleft palate, the vast majority have been brought by parents who say Zofran caused their unborn children to develop heart defects.
These families level a number of serious allegations against GlaxoSmithKline. They say that the company unlawfully promoted Zofran as a “safe and effective” morning sickness treatment. But as we’ve mentioned, GlaxoSmithKline has never even studied the drug’s effects during pregnancy. But perhaps more troubling are their allegations that GlaxoSmithKline has concealed mounting evidence of Zofran’s potential link to major birth defects from the public and physicians across the globe.
Joined by an alliance of experienced plaintiffs’ attorneys, Banville Law’s Zofran birth defect lawyers are currently investigating potential claims against GlaxoSmithKline. If you were prescribed Zofran as an “off label” morning sickness treatment and delivered a child with congenital heart defects, we urge you to contact our attorneys to learn more about your legal options. Your consultation is free and comes with no obligation.