by Kari Swanson

In the interest of full disclosure: I am the survivor of two pregnancies with Hyperemesis Gravidarum during which I was given Zofran and/or ondansetron. Both of my children, currently ages 9 and 4, are developmentally normal, with no health problems attributable to my use of ondansetron.

A recent headline in the Toronto Star proclaims in bold face “Birth defects blamed on unapproved morning sickness treatment.” The lengthy piece about the drug ondanestron, which is sometimes prescribed off-label to women with Hyperemesis Gravidarum (HG), is written as an exposé of drug companies and physicians gone wrong, the result of which is “vulnerable” pregnant women being prescribed a harmful drug that causes their babies to be born with extraordinary birth defects as a result. This would be horrifying if it was true, of course, but, it’s not. This article is not a scientific article. It is not a scientific literature review. It is pseudo-scientific sensationalism. One might think the goal of such an article would be to protect women and children, but like most pseudo-science involving medicine it presents very real public health risks.

According to the Hyperemesis Education & Research Foundation web site, HG is

“…a severe form of nausea and vomiting in pregnancy. It is generally described as unrelenting, excessive pregnancy-related nausea and/or vomiting that prevents adequate intake of food and fluids. If severe and/or inadequately treated, it is typically associated with:

• loss of greater than 5% of pre-pregnancy body weight (usually over 10%)
• dehydration and production of ketones
• nutritional deficiencies
• metabolic imbalances
• difficulty with daily activities”

HG is not morning sickness. HG is just plain sickness. In my first pregnancy there were many days when I vomited in excess of once an hour. I lived with constant nausea. I vomited before getting out of bed when I woke up in the morning. I vomited in the shower. I vomited on the side of the road while driving to work. I vomited in my flower garden while weeding. I believe my record was 38 times in one day. I vomited so violently and so frequently at one point that tiny blood vessels broke in my face and eyes. It certainly wasn’t the pregnancy glow I had envisioned.

I tried all of the remedies that everyone, including my obstetricians, suggested: crackers, sips of water, lemon, ginger ale, ginger tea, ginger snaps, candied ginger, extra vitamin B, extra sleep. Nothing worked. I lost weight. At 3 months pregnant I weighed about 11% less than I did before my pregnancy. I had several visits to the ER for IV hydration. More than half way through my pregnancy, after an all-night stay in the ER for IV fluids, my OB finally prescribed Zofran. For me it was a miracle drug, because it meant that I was able to keep at least one meal down every day. It didn’t completely eliminate the symptoms, but it did make them much more manageable. When I became pregnant again 5 ½ years later and started vomiting numerous times every day at 5 weeks pregnant I asked for Zofran. I still experienced nausea and vomiting throughout my second pregnancy, but nothing like I experienced the first time. I only required IV hydration in the ER once the second time around.

HG presents serious risks to a woman’s health. Complications of HG include: dehydration, malnutrition, damage to tooth enamel, renal failure, jaundice, ruptured esophagus, and deconditioning of the heart muscle, just to name some. Some of these complications can be and have been fatal. In addition, HG can cause long term health effects. Some women experience PTSD. Others, like me, develop complications of their complications: prolonged dehydration caused me to develop kidney stones.

HG also presents risks to the child. Fetal complications of HG include: premature birth, low birth weight, neural tube defects, and congenital heart defects, among others. Also, according to the Hyperemesis Education & Research Foundation, “…prolonged stress, malnutrition and dehydration in the mother can potentially put an unborn child at risk for chronic disease (e.g. diabetes, heart disease) in later life.” And, HG can also cause fetal or neonatal death.

Clearly Hyperemesis Gravidarum is a serious health condition. It is not something that can be or should be ignored or treated lightly. Women die. Babies die. When considering treatment options, women and their healthcare providers must weigh the benefits and risks of particular treatments. The decision is not about a minor inconvenience. It is very often a matter of mitigating potential harmful or life-threatening effects.

The Toronto Star article cites data recorded in the US Food & Drug Administration (FDA) Adverse Event Reporting System (FAERS). The reporters cite this data as if it presents irrefutable proof that ondanestron is a dangerous drug that caused harmful effects to babies. But, the truth of the matter is it does no such thing. The FDA states on the FAERS site:

FAERS data do have limitations. First, there is no certainty that the reported event (adverse event or medication error) was actually due to the product. FDA does not require that a causal relationship between a product and event be proven, and reports do not always contain enough detail to properly evaluate an event. Further, FDA does not receive reports for every adverse event or medication error that occurs with a product. Many factors can influence whether or not an event will be reported, such as the time a product has been marketed and publicity about an event. Therefore, FAERS data cannot be used to calculate the incidence of an adverse event or medication error in the U.S. population.

Let me reiterate: the FDA does not require that a causal relationship between a product and event be proven. This means that random, purely coincidental health conditions may be reported as side effects of a drug. FAERS data are useful for looking for trends or potential side effects that might have been caused by a drug, but they are not proof that a side effect is caused by a drug. FAERS data should be used for further study. They should not be construed as concrete evidence of a causal relationship.

The use of ondansetron in pregnancy has been studied. The Toronto Star article sites some of the research, but a news article is not a scientific literature review. The reporters do not present the totality of research on the subject, and what they do present is presented in a manner that shows bias in favor of their own assertion: that ondansetron causes birth defects. There are, however, numerous other scientific studies that indicate otherwise. Anyone can easily research the topic for herself (or himself) by utilizing the freely available medical research database PubMed.

Although it has been studied, the use ofondansetron in pregnancy is considered an off-label use. It is unfortunate that the Toronto Star article presents off-label use of medications so negatively. Off-label prescribing is common and sometimes is the best or only treatment option for certain conditions. While it is true that sometimes off-label use of a medication might later be proven (by research) to be of no therapeutic value, or worse: harmful, sometimes off-label use later becomes an FDA approved use after further research supports it. According to WebMD certain beta-blockers once only used for the treatment of high blood pressure and used off-label to treat heart failure later became approved prescription treatments for heart failure.

Despite the fact that use of ondansetron to treat HG is off-label, the prescribing information for Zofran (ondansetron from GlaxoSmithKline) states:

Pregnancy Category B. Reproduction studies have been performed in pregnant rats and rabbits at daily oral doses up to 15 and 30 mg/kg/day, respectively, and have revealed no evidence of impaired fertility or harm to the fetus due to ondansetron.

Pregnancy Category B is defined by the FDA as follows: “Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women.”  The safety and categorization of drugs varies from country to country. For example, acetaminophen is US FDA Pregnancy Category C (less safe to use in pregnant women than ondansetron!), but in Australia acetaminophen is Australian Pregnancy Category A, which means Australia considers acetaminophen to be safer for pregnant women than the US FDA does.

Ondansetron is not entirely without risks or side effects.   The FDA, like Health Canada, issued warnings about potential heart risks, specifically a heart rhythm problem called QT prolongation. However, those risks very clearly apply to people with Long QT syndrome, those with underlying cardiac defects, those with low potassium or magnesium, and people taking other medications that can cause QT prolongation. They did not withdraw the drug from the market. Many thousands of people have taken ondansetron with no apparent harm to their hearts.

Furthermore, many women, including those who have not taken ondansetron or any other drug, give birth to babies with birth defects every year. According to the US Centers for Disease Control and Prevention (CDC), “Birth defects occur in about 3% of all live births.” Recent CDC data on the prevalence of birth defects in the US between the years 2004 and 2006 show an estimated prevalence of 4.71 in 10,000 babies born with atrioventricular septal defect, for example. HG is associated with an increased risk for fetal cardiac defects, but women without HG and who have not taken ondansetron also give birth to babies with heart defects. According to the National Heart, Lung and Blood Institute, “doctors often don’t know why congenital heart defects occur.” Leaping to the conclusion that the heart defect of one infant reported in FAERS was caused by ondansetron is wildly inappropriate.

I do not speak for all women who have experienced HG, but I and more than one of my “HG sisters” found the Toronto Star article disturbing. It is sensationalist journalism that has the potential to cause women or their healthcare providers to delay or avoid effective treatment at the risk of their/their patients’ own or their babies’ immediate or long-term health or even at the risk of their lives.

For another look at the safety of odansetron during pregnancy, see this Huffington Post piece breaking down a Danish study of 1,970 births where the drug was used during pregnancy.

Kari Swanson, MLS, is a daughter, sister, wife, mother of two, member of Generation X and an admin for The Leaky B@@b Facebook page. She has been an academic librarian for 15 years. She blogs occasionally over at Thoughts from BookishMama.