Crying babay being checked up by the doctor
14 April 2015

Teratogens: Chemicals & Prescription Drugs Linked To Birth Defects

The scientific community agrees that congenital abnormalities, or “birth defects,” are most likely the result of two potential factors: genetic mutations and harmful, “external” substances.

The former category includes hereditary conditions, in which anomalous genetic information is passed from parents to child at conception, and mutations that occur as a result of the extensive cell copying process that makes fetal development possible. For a thorough explanation of genetic factors that may contribute to birth defects, click here.

In this article, we’ll turn to the second potential cause of congenital malformations: harmful substances. Crying babay being checked up by the doctor

What Are Teratogens?

Non-genetic factors that have been found to adversely affect fetal development are known as teratogens. The category of teratogens includes some viruses and preexisting medical conditions that, when present in a mother, have been found to increase the risk of birth defects.

For example, several studies have found that women diagnosed with diabetes before pregnancy are as many as 8 times more likely to deliver babies with multiple birth defects.

Many common chemicals have also been identified as possible teratogens. When ingested by a mother, these substances can enter her bloodstream and then pass through the placenta into the body of her unborn child.

Natural & Synthetic Chemicals That Can Result In Birth Defects

Some of these chemical teratogens exist around us. This is especially true in industrialized nations, where synthetically-produced (“man made”) chemicals are ubiquitous and, in many cases, allowed to contaminate the environment.

While there is little reason to fear contamination in the US, where the EPA strictly regulates potential environmental toxins, there are many areas of the world in which teratogens like mercury and lead have been found at dangerous concentrations in the air and drinking water.

In Kazakhstan, for example, nearly 50% of a tested population was found to have significant genetic abnormalities. That is a staggering proportion, and researchers have attributed the region’s overwhelming birth defect incidence to the Soviet Union’s unregulated industrial practices, which gave no thought to pollution or environmental contamination.

Some naturally-occurring chemicals may have teratogenic effects, too. In the Rocky Mountains, a type of skunk cabbage on which sheep routinely graze has been found to cause severe neurological defects in their offspring. Note that the effects of a teratogen in pregnant animals are never assumed to entail the same effects in humans.

For more details on potential “environmental” causes of congenital anomalies, check out the chapter on “Environmental Disruption of Normal Development” in this Developmental Biology textbook.

Are There Prescription Drugs That May Cause Birth Defects?

Yes.

Several medications marketed in the US have been associated with an increased incidence of birth defects. Below, we’ll cover three of these drugs, and discuss the scientific research that has established their associations with congenital abnormalities.

As with all medical decisions, never stop or start taking a drug during pregnancy without the guidance of your own physician. Even during pregnancy, leaving a serious medical condition untreated may present its own significant risks. Your doctor will weigh that risk against the potential risks posed by a drug to make an informed decision for your unique circumstances.

1. Anti-Epileptic Medications

According to England’s National Health Service, researchers have suspected since the 1960s that anti-epileptics, a class of drugs used to treat seizure disorders, along with certain mood disorders and migraine headaches, may increase the risk of birth defects. Over the past 50 years, a wealth of epidemiological research has found those early suspicions warranted.

A study published by The Lancet Neurology in 2011 represents the climax of this decades-long search for the truth about anti-epileptics and birth defects.

In collaboration with physicians from 42 different countries, researchers monitored a total of 3,909 pregnancies during which mothers took seizure medications. Eventually, the study’s records spanned eleven years.

The study included pregnant women who took four “old generation” seizure medications:

  • carbamazepine (brand names include Tegretol and Equetro)
  • lamotrigine (sold as Lamictal)
  • valproic acid (brand names include Depakote and Stavzor)
  • phenobarbital (sold as Luminal)

Pregnancies that resulted in babies who were diagnosed with hereditary genetic anomalies upon birth were excluded, since the team was only looking to isolate birth defects potentially caused by the drugs under investigation.

In total, 6% of the pregnant women taking one of the anti-epileptics delivered a baby with a major congenital malformation, a proportion significantly higher than that found among the general population. The birth defect risk increased as dosages increased, irrespective of which medication was being administered.

Lamotrigine was found to present the least severe risk, while valproic acid and phenobarbital presented the most risk.

Do Both New & Old Seizure Medications Pose A Risk?

While this increased risk of birth defects among women taking “old generation” anti-seizure drugs is well established in the medical literature, several “new generation” epilepsy medications also exist.

One of these drugs, topiramate (sold as Topamax), has been linked to an increased risk of orofacial clefts, a category of birth defects that includes cleft lip and cleft palate. In March of 2011, the FDA placed Topamax in Pregnancy Category D, indicating that positive evidence of human fetal risk had been found.

Other “new generation” seizure drugs, like gabapentin (Neurontin) and oxcarbazepine (Trileptal), have been subjected to rigorous scrutiny, as well. Other than topiramate, none of these newer medications have yet been associated with an increased risk of major birth defects. With that being said, most have been placed in Pregnancy Category C, which indicates that an increased risk of birth defects cannot be ruled out.

2. Retinoids: Drugs For Severe Acne

Retinoids, a wide range of chemicals closely related to Vitamin A, work as the active ingredients in many common acne medications. Chief among these drugs is isotretinoin, the active ingredient in Accutane, a medication used to treat a severe form of acne called cystic or nodular acne.

Isotretinoin’s potential to cause a host of congenital defects has been well known for decades. The drug has been associated with an increased risk of:

  • Orofacial clefts including cleft lip and cleft palate
  • Hydrocephalus, an abnormally high volume of fluid around the brain
  • Hearing loss
  • Congenital heart defects

After isotretinoin’s severe teratogenicity was established, Accutane’s manufacturer was only allowed to market the drug after setting up an FDA-approved program called iPLEDGE.

Any physician who intends to prescribe an isotretinoin product must first register with iPLEDGE. Female patients have to register with iPLEDGE, too, and agree to use two forms of birth control simultaneously while taking isotretinoin. They’re also required to take monthly pregnancy tests, administered by an approved lab. The results of these tests must be submitted to iPLEDGE, and only if they are negative can isotretinoin be prescribed. Male patients are required to visit their doctor for each prescription as well.

3. Ondansetron: A Drug For Severe Nausea & Vomiting

Sold in the US under the brand name Zofran, ondansetron is an anti-nausea drug approved for use in patients being treated for cancer, along with certain individuals undergoing surgical procedures. For two decades, physicians have also been prescribing it for an unapproved use: to alleviate the nausea and vomiting common during early pregnancy.

Due to this increase in “off-label” prescription, several research teams have conducted studies to investigate ondansetron’s potential effects on fetal development.

In 2012, a team funded by the US Centers for Disease Control reviewed the birth records of more than 10,000 pregnant women. While only 15.4% had been prescribed any medication for morning sickness during the first trimester, those women who took Zofran or a generic equivalent were found to be more than twice as likely to deliver babies with a cleft palate.

A subsequent study performed by researchers in Western Australia found an increased incidence of kidney malformations, while teams in Denmark and Sweden both found evidence linking ondansetron to congenital heart defects.

You can find more information on these studies here.