Atrioventricular Septal Defect: Zofran And Heart Conditions

Soon after its approval in 1991, the anti-nausea drug Zofran rocketed to true blockbuster status. By 2006, it was outselling every other pharmaceutical prescribed for morning sickness by 200%. Today, an estimated 1 in 4 American women take Zofran to relieve their early-pregnancy nausea. But there’s a major problem.

Zofran has never been approved for use during pregnancy, and now medical researchers say it may increase the risk for heart defects.

Does Zofran Cause Atrioventricular Septal Defect In Babies?

That’s the troubling conclusion suggested by at least two major studies conducted between 2013 and 2014.

In Denmark and Sweden, researchers reviewed millions of birth and prescription records to learn whether or not Zofran was linked to a harmful effect on unborn babies. Ultimately, they found that it was. Women who took Zofran during early pregnancy were between 2 and 4 times more likely to have children with “hole in the heart” defects.

Baby In Mother's Hands

Known to the medical community as “cardiac septal defects,” these abnormalities involve literal holes in heart tissue. Zofran has been linked to three specific septal defects of the heart, but the drug’s risks seem to be highest in relation to atrioventricular septal defect (AVSD).

Scientists at Copenhagen University looked at every birth record logged in Denmark between 1997 and 2010. Eventually, their study included more than 900,000 pregnancies. When women took Zofran in the first trimester, they were 480% more likely to deliver a child with atrioventricular septal defect.

One year later, a team from Sweden discovered very similar results. Reviewing over 1 million Swedish pregnancies, the researchers found that women prescribed Zofran in pregnancy were at a two-fold increased risk to have babies with a cardial septal defect. Unfortunately, their results didn’t specify which hole in the heart defects were most likely.

What Is An Atrioventricular Septal Defect?

Heart defects are extremely unique. While the exact characteristics of a defect will differ widely from child to child, even the broadest definition of AVSD begins with at least one hole in a heart wall.

Atrioventricular septal defects begin to develop between the third and fourth weeks of pregnancy, when the heart is just starting to form. At this point, the organ is little more than a tube. Over the next two or three weeks, however, it will swell out in four directions, creating the four distinct heart chambers that pump blood throughout the body.

At the center of all this change are the endocardial cushions, a collection of cells that eventually come to form barriers separating each heart chamber from its neighbors. Medical researchers believe that a problem here, in the development of the endocardial cushions, causes atrioventricular septal defect.

While the mechanism is still unclear, something impedes the growth of the endocardial cushion cells and they fail to create complete barriers between the heart chambers. Usually, the defect is most prominent right at the heart’s center, where the organ’s four walls normally meet.

Is It The Same As Atrioventricular “Canal” Defect?


Endocardial Cushion Formation Diagram

Endocardial cushion cells (yellow) push the AV canal (blue).

As we mentioned earlier, the heart is just a tube of cells in the early stages of fetal development. Soon though, the tube is split at its center by a long cavity, an empty space with bulbous chambers at either end. This is called the atrioventricular canal, and it looks a lot like a dumbbell. Over time, the endocardial cushion cells push in against the center of this dumbbell, squeezing it until it becomes very narrow.

In the end, you have a thin septum, or wall, separating two larger cavities.

You may see AVSD referred to as “atrioventricular canal defect” or just “atrioventricular canal.” All of these terms refer to the same range of heart defects, but as we’ll see in the next section, there are at least two distinct types of AVSD.

Complete Vs. Partial AVSD

Healthy Heart

A healthy human heart.

Healthy humans hearts have four chambers. The two on top are called atria and the two on bottom are called ventricles.

Each side of the heart has one atrium and one ventricle. Blood flows down from the atrium, through a valve and into the ventricle below it. From there, it’s pumped away from the heart, either toward the lungs for oxygen or to nourish the rest of the body with nutrients.

But perhaps most importantly, the atria are separated from one another by a wall called the atrial septum. The ventricles are also separated, by a ventricular septum.

Complete AVSD

In babies with complete atrioventricular septal defect, holes in both of these walls create a much larger hole at the center of the heart. The heart’s valves are also affected; rather than having two distinct valves on either side of the organ, children with complete AVSD have one valve near the heart’s center. Usually, this valve is malformed and can’t open or close properly.

Complete Atrioventricular Septal Defect

In the picture above, courtesy of the US Centers for Disease Control, we can see how these abnormalities change the heart’s structure.

We can also see how an atrioventricular septal defect alters blood flow. Rather than staying on one side of the organ and being transported to its proper destination, blood can flow right through the holes. This allows blood that’s already picked up oxygen in the lungs to mix with blood that hasn’t yet reached the lungs, literally starving the body of oxygen.

Partial AVSD

In children with partial atrioventricular septal defect, there may be a hole in the atrial septum, or in the ventricular septum, or both, but usually they don’t combine to create a large hole in the center of the heart. Most babies who are diagnosed with partial AVSD have two separate valves, although usually the mitral valve on the heart’s left side is malformed.

The effect on blood flow is very similar to that in complete AVSD, although children with complete forms of the defect are generally considered at a higher risk of complications. In fact, Medscape reports that patients with partial AVSD “rarely require medical therapy.”

Sometimes partial AVSD is referred to as “incomplete atrioventricular septal defect.”

AVSD Signs & Symptoms

Very large atrioventricular septal defects are medical emergencies, and some children will require immediate intervention to prevent life-threatening complications. But many smaller AVSDs only begin to cause noticeable symptoms weeks or months after a child’s birth:

  • Cyanosis – a blue tinge to the lips and skin caused by inadequate oxygen
  • Wheezing or other breathing difficulties
  • Sluggishness, fatigue
  • Rapid heart rate
  • Chronic chest infection
  • Lack of appetite
  • Failure to thrive
  • Swollen legs and feet
  • Congestive heart failure

Most of these signs and symptoms are caused by the heart’s inability to pump adequate amounts of oxygen-rich blood from the lungs to the body.

AVSD can also be diagnosed before birth by ultrasound.

Possible Complications

People with a partial AVSD might not even have symptoms until they reach early adulthood. Over time, the defect can have a significant impact on cardiovascular health, leading to:

  • high blood pressure – especially pulmonary hypertension, a high blood pressure specifically in the lungs
  • arrhythmia – an abnormal heart rhythm
  • breathing problems
  • heart failure

Heart failure doesn’t mean your heart stops working, it means your heart isn’t working as well as it could be. When blood flows through the body slowly, it increases pressure in the heart. To compensate, heart chambers can stretch to get larger or the walls of the heart can thicken. Both of these changes will increase blood flow in the short term, but over longer stretches of time, the heart becomes strained and can suffer even worse damage.

Can AVSD Be Repaired?

Yes, but for many children the treatment process is long and difficult. Under any circumstances, how and when a medical team decides to repair an AVSD will depend entirely on individual considerations.

Some babies with AVSD are first given medicines to reduce their risk for congestive heart failure, until they become old enough to withstand an operation. But unlike other septal defects of the heart, the standard treatment for patients with AVSD is complete surgical repair. This is traditionally an open-heart surgery using a cardiopulmonary bypass machine, which artificially breathes and pumps blood for the child during the operation.

For children with complete AVSD, surgery is usually indicated between 3 and 6 months, while babies with partial defects generally undergo an operation by their 18th month.

In surgery, a team of pediatric specialists will attempt to patch up the holes in the heart and then construct a second valve to control blood flow through the heart’s chambers. Surgeons will also take into account whether or not a child’s atrioventricular septal defect is “unbalanced.” In a balanced AVSD, both sides of the heart are affected to a similar degree, which means the pressure holds somewhat stable of its own accord.

Living With A Heart Defect

Most children born with AVSD will grow up to life healthy lives, but they’ll also need regular attention from a cardiac specialist to help them meet any challenges that come up.

After repair, one of the most common complications involves the valve that was artificially constructed out of existing heart tissue. In many patients, this valve can become leaky over time, and some people will need to have their valves repaired or replaced.


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