Q&A: In utero exposure to Bendectin linked to increased risk for CRC in adult offspring
Click Here to Manage Email Alerts
Prenatal exposure in the 1960s and ’70s to dicyclomine, a component of the anti-nausea drug Bendectin, increased the risk for colorectal cancer in adult offspring, according to data reported in JNCI Cancer Spectrum.
“In the 1960s, Bendectin (doxylamine/pyridoxine/dicyclomine) was frequently prescribed to pregnant women to manage nausea and vomiting. Bendectin was initially approved in 1956 and quickly became the most common treatment for nausea or vomiting of pregnancy in the U.S as its use grew in the 1960s and ’70s,” Caitlin C. Murphy, PhD, MPH, associate professor at UTHealth Houston School of Public Health, and colleagues wrote. “After reports of birth defects and concerns in the wake of the thalidomide tragedy, in 1976, the manufacturer removed dicyclomine from the three-part formulation.”
To examine the association between in utero Bendectin exposure and risk for CRC, Murphy and colleagues evaluated data from 14,507 mothers and 18,751 liveborn offspring enrolled in the Child Health and Development Studies in California between 1959 and 1966. Researchers reviewed prescribed medications in mothers’ medical records and determined that 5.4% of offspring were exposed in utero to Bendectin.
After more than 50 years of follow-up, 83 offspring had CRC in adulthood, 34 of whom were diagnosed younger than 50 years. The majority had tumors in the distal colon (40.7%) or rectum (32.1%). Compared with offspring who were not exposed to Bendectin, exposed offspring had a higher risk for CRC (adjusted HR = 3.38; 95% CI, 1.69-6.77) with incidence rates of 10.1 per 100,000 (95% CI, 7.9-12.8) and 30.8 per 100,000 (95% CI, 15.9-53.7), respectively.
“We have been very motivated, like many people, to understand the increasing rates of colorectal cancer in young people and, even more recently, the increasing rates of colorectal cancer in people in their 50s,” Murphy told Healio. “This is no longer an epidemic of people under the age of 50 but seems to be affecting people of all ages. We have been curious to identify the causes of these trends.”
In a Healio interview exclusive, Murphy expanded on these results and highlighted the significance for patient care.
What were the key takeaways?
Murphy: First, and perhaps most important, is that part of our study was driven by some evidence showing that things events and exposures in early periods of life are important for risk for colorectal cancer. From this particular cohort that forms the basis of this study, we have previously shown that in utero exposure to certain antibiotics, as well as maternal obesity, may be important risk factors for colorectal cancer. We wanted to continue to study the prenatal period and identify other risk factors and exposures that may be relevant.
Sure enough, we see that same story with Bendectin exposure in early periods of life, even in the womb, seem to be important determinants for risk for colorectal cancer many decades later.
How do these results inform patient care going forward?
Murphy: I do not think we can yet make, for example, different recommendations for screening or surveillance based on prior exposure to Bendectin. Anyone exposed to this drug in utero through 1978 is already of the age to begin average-risk screening. I want to instead emphasize that what we see in this study, and together with some of the other studies that we have conducted, is that many of the risk factors we have long thought to be related to colorectal cancer, like obesity, may play only a small part in the epidemic. Rather, risk factors, the things that we never once thought were possible to be associated with colorectal cancer seem to be playing a really important role.
The reasons a patient may have colorectal cancer today are different than the reasons many years ago. We need to think outside the box and start to identify other risk factors that may explain increasing rates.
What additional research is needed?
Murphy: It is important that we continue to understand the use of pharmaceuticals during pregnancy, for example, by identifying other medications that were used in the ’60s and may also be related to colorectal cancer. There are likely other medications responsible for the increasing incidence rates. It will also be important to confirm these findings in experimental studies.
What guidance exists for the use of this drug or others in pregnant patients with GI conditions?
Murphy: The three-part formulation of Bendectin that we studied is no longer manufactured. However, dicyclomine was included in the three-part formulation and continues to be used to treat irritable bowel syndrome, including in pregnant persons. The FDA designates dicyclomine as Pregnancy Category B. That means, at this time, we do not have enough evidence from studies conducted in humans to determine whether this particular drug has harmful effects to the fetus. I think it remains an individual choice, and one that weighs the potential risks and benefits for each pregnant person. That is true for dicyclomine and any drug that you might consider taking during pregnancy.
Is there anything else our audience should know about this topic?
Murphy: We are identifying things that we never thought could be related to colorectal cancer, and I think it is really important that researchers especially change the way that we have been thinking about this particular cancer. That will help us open up the possibility of discovering other risk factors that may be important to preventing cancer in the future.
Reference:
Collapse
Read more about
Click Here to Manage Email Alerts