Prescription Drugs & Orofacial Clefts

In searching for the causes of orofacial clefts, the health community has identified two complex areas of research.

The first, genetics, investigates the link between cleft lip, cleft palate and hereditary abnormalities. Genes are passed down from parent to child and instruct body tissues how to form during fetal development. Mistakes in genes are believed to contribute to the development of many orofacial clefts.

The second area of research involves “environmental factors,” things ingested by a mother that come to affect her unborn baby. As a category, these harmful substances are called teratogens.

Many chemicals, like alcohol and nicotine, have been found to increase the risk for delivering a baby with birth defects. Pesticides, lead and other industrial materials have a harmful effect on growing babies, too.

Medications & Pregnancy: Measuring Risks vs. Benefits

Prescription medications are a major concern as well, and many mothers attempt to avoid all drugs out of a fear that something might affect their child’s development. That fear is not unfounded and, in an ideal world, expectant mothers would take no prescriptions during pregnancy at all.

But this isn’t an ideal world, and many women require medications for their own health. Since all prescriptions can present risks to a growing baby, and most drugs are never tested on pregnant women, physicians rely on the information we have (like studies performed on pregnant animals) to make risk versus benefit analyses.

In this guide, we’ll cover a wide array of medications that have been associated with birth defects. We’ll also discuss drugs that were thought to pose risks, but have recently been found safe for use during pregnancy.

If you’re currently taking a drug on our list, and considering pregnancy or already pregnant, do not discontinue its use before speaking with your physician. Trust your doctor to make the right choice for you, and your baby’s health.

Ondansetron (Zofran)

Marketed as Zofran, ondansetron is an anti-nausea drug used for the treatment of patients with severe nausea after cancer treatments and surgical anesthesia. Ondansetron is also widely prescribed to pregnant women for the treatment of morning sickness, generally during the first trimester.

Several recent studies have begun to establish a link between Zofran and birth defects, including cleft palate and congenital heart defects. While these results are far from conclusive evidence that ondansetron causes congenital abnormalities, pregnant women should speak with their doctors about the potential risks of Zofran.

Learn More About Zofran Litigation

Benzodiazepines

In 1994, researchers estimated that anywhere from 30% to 40% of pregnant women were prescribed medications for anxiety.

Chief among these drugs are benzodiazepines, a category of drugs used to treat anxiety, depression, insomnia, nausea and vomiting, panic attacks and seizures. Initially, these medications were linked to increased risks of cleft lip and / or palate.

Studies conducted in the 1970s found a slightly increased incidence of orofacial clefts in babies born to women prescribed benzodiazepines during early pregnancy. But as researchers from St. Thomas’ Hospital in London were right to point out, many of the women included in these studies were already at an increased risk. Some suffered from epilepsy, others from diabetes; both conditions have been associated with birth defects.

In more recent years, at least 7 different studies have attempted to determine evidence of increased fetal harm in women who take benzodiazepines during pregnancy. No risks were found.

Common benzodiazepines include:

  • Valium (diazepam)
  • Xanax (alprazolam)
  • Ativan (lorazepam)
  • Klonopin (clonazepam)

Speak with your doctor if you have concerns about taking benzodiazepines during your pregnancy. Never stop using a drug until first consulting your physician.

Dilantin

Sold as Dilantin, the drug phenytoin is used to treat patients with epilepsy.

Dilantin has been associated with a two to three-fold increase in the risk of cleft lip and cleft palate, as well as congenital heart defects.

Phenytoin also acts differently in pregnant women than it does in women who are not pregnant. Some studies have found that phenytoin may actually increase the severity or number of seizures when taken during pregnancy. There is a possibility that these convulsions could harm a fetus.

Other brand names for phenytoin:

  • Phenytek
  • Dilantin-215

If you are currently taking phenytoin, speak with your physician about the relative benefits and risks of continuing treatment.

Barbiturates

Barbiturates like phenobarbital, sold in America as Luminal, are another class of epilepsy medications.

Barbiturates have been found to increase the incidence of birth defects. They are also a fairly common drug of abuse, and women taking them are around twice as likely to deliver a baby with cleft lip and / or cleft palate.

Again, talk to your doctor about taking barbiturates during pregnancy before you stop using them.

Valproic Acid

Valproic acid, marketed as Depakote, Depakene, Stavzor and Depacon, is prescribed for the treatment of epilepsy and bipolar disorder.

This study, published in the New England Journal of Medicine, found that women taking valproic acid during pregnancy were 5.2 times more likely to deliver a baby with cleft palate.

But the potential of having a seizure also poses significant dangers for both fetus and mother, and women taking valproic acid should speak with their doctors before discontinuing use of this drug.

Download our informational brochure on Depakote.

 Carbamazepine

Another treatment for conditions that cause seizures, along with bipolar disorder and severe neurological pain, carbamazepine is sold as Tegretol, Carbatrol, Equitro and Epitol.

This large meta-analysis (a study that looks at similarities and differences between other studies) concluded that carbamazepine use during pregnancy was associated with increased rates of cleft palate, as well as neural tube defects and congenital heart defects.

Among anti-epileptic drugs, carbamazepine carries one of the lowest risks of birth defects, although its potential danger has been well-established in the medical literature. Speak with your doctor to discuss an ongoing plan of treatment.

Trimethadione

Sold under the brand name Tridione, trimethadione is an epilepsy medication usually prescribed after other treatment options have been found ineffective.

When administered to pregnant women, trimethadione poses extremely high risks to a developing baby. In 1997, the American Journal of Diseases of Children reported that almost 9 out of 10 pregnancies exposed to Tridione would result in fetal loss or major congenital malformations.

The drug has even been linked to its own syndrome: fetal trimethadione syndrome. Characteristics include:

  • Craniofacial abnormalities, including cleft palate
  • Absent kidney
  • Developmental delay
  • Spina bifida

It is extremely rare that pregnant women are prescribed trimethadione anymore. If you are considering becoming pregnant, inform your doctor immediately and discuss a new form of treatment.

Corticosteroids

Corticosteroids are a class of chemicals that closely mimic cortisol, a hormone naturally produced in the body. These drugs are in wide-spread use, and include:

  • Cortisone
  • Prednisone
  • Hydrocortisone
  • Fluticasone

As a category, corticosteroids work by reducing inflammation and inhibiting immune system response. They are usually prescribed to treat skin rashes, asthma and rheumatoid arthritis, although their indications contain numerous conditions.

The medical literature on corticosteroids and birth defects is contradictory. Some studies have found increased risks, including a significant rise in the incidence of orofacial clefts after expectant mothers had taken prednisone. But later trials, including a Danish study that reviewed over 800,000 births, excluded the possibility of at least moderate to severe risks.

In short, corticosteroids may pose a small danger to fetal development, but this risk should be weighed against the drug’s benefits with the help of a healthcare professional.

Download our Hydrocodone informational brochure here.

Fluconazole

Sold as Diflucan, fluconazole is a drug used to treat fungal infections, most commonly yeast infections. For years, fluconazole has been linked to several birth defects, including cleft palate and cleft lip.

Researchers in Denmark recently published a study that contradicted most of these fears, finding that women prescribed smaller dosages of fluconazole during pregnancy were at higher risk of only one birth defect: a rare heart abnormality called “tetralogy of Fallot.” The studies that found an increase in other birth defects generally included women who had been prescribed uncommonly large dosages of Diflucan.

Still, the health community is unanimous in recommending that women with yeast infections should first be prescribed topical treatments, and then given fluconazole only if other methods don’t work.

Download our informational brochure on Fluconazole here.

Mycophenolate Mofetil

Marketed as CellCept, mycophenolate mofetil is used to lower the chance of organ rejection after kidney, liver and heart transplants.

The drug has been found to increase the chances of fetal death and birth defects, including orofacial clefts. Women who are about to take mycophenolate mofetil, or currently take it, are required to use some form of birth control to rule out the possibility of pregnancy.

Retinoids

Retinoids are a class of chemicals derived from Vitamin A that regulate skin growth. Forms of the chemical are sold as acne and psoriasis treatments, including:

  • Accutane
  • Claravis
  • Sotret
  • Amnesteem
  • Myorisan
  • Tegison

Numerous clinical studies have established a marked association between retinoids and birth defects. Orofacial clefts are common, as are heart defects and brain abnormalities.

Accutane and Tegison, two of the more commonly prescribed retinoids, currently bear warnings that “pregnancy should be ruled out before treatment begins.”

Penicillamine

Used to treat rheumatoid arthritis and a rare congenital disorder called Wilson’s disease, penicillamine is marketed as Depen.

Reports of birth defects, including cutis laxa, a disorder of the soft tissues, have been reported after fetal exposure to penicillamine.

Depen’s use as a treatment for rheumatoid arthritis is contraindicated for women during pregnancy (a “contraindication” is an accepted reason to not prescribe a drug). Women with Wilson’s Disease, on the other hand, are generally continued on penicillamine treatment, even after becoming pregnant. Interrupting the treatment for this condition poses its own substantial dangers for both mothers and their developing babies.

Selective Serotonin Reuptake Inhibitors (SSRI)

Commonly prescribed to treat major depressive and anxiety disorders, SSRIs include:

  • Paxil
  • Zoloft
  • Celexa
  • Prozac

Concerns have long been raised about SSRI use during pregnancy, especially since up to 7% of all pregnant women take one of these medications. But their effects on fetal development are far from certain.

There is evidence that antidepressants increase the risk of “persistent pulmonary hypertension,” a rare lung condition, but claims that SSRIs may increase the incidence of autism remain largely unsubstantiated. Further, depression itself may be associated with congenital disorders. Women suffering from untreated depression have been found more likely to deliver babies with autism spectrum disorders, and chronic maternal stress certainly has an effect on fetal development.

With these conclusions in mind, antidepressant use during pregnancy is a clear example of weighing benefits versus risks. While SSRIs may increase the risk for certain birth defects, so can clinical forms of depression.

A reasoned approach, taking individual factors into account, is the only way to make the best decision on whether or not you should take antidepressants during pregnancy. Speak with your primary care physician, as well as your psychiatrist, about the benefits and risks in your own case.

Download our informational brochure on SSRIs.

Antineoplastics

Antineoplastics are cancer drugs, used in chemotherapy. These powerful chemicals enter cells, degrade their DNA and essentially force cancer cells to self-destruct. But they also affect normal cells, which is why cancer treatment is often debilitating.

For obvious reasons, antineoplastics in maternal blood are extremely dangerous for fetal development.

Pregnant women working in clinical oncology settings should be extremely careful handling chemotherapy drugs.

On our sister site, we’ve created a series of guides that go into more depth on many of the drugs we mentioned above. You can find them by clicking here.

Should I Stop Taking These Drugs?

No.

Every decision to begin or discontinue the use of a prescription medication should be thoroughly discussed with your preferred healthcare professional.

Again, any drug can pose risks to the development of a growing baby. But so can many of the conditions that those drugs are meant to treat. Weighing the potential risks against the possible benefits is the only way to make an informed decision for yourself and your baby. These decisions should always be made with the guidance of your physician.

FDA Pregnancy Categories

As of December 3, 2014, the US Food & Drug Administration (FDA) has changed the way it labels medications for risks during pregnancy and breastfeeding.

Before the change, drugs were put into one of five “catch-all” categories: A, B, C, D and X.

  • Drugs in A had been found safe for women to take during the first and subsequent trimesters (the risk of developing a birth defect is highest during the first trimester).
  • Drugs in B had been found safe in tests on pregnant animals, but there were no adequate studies performed on pregnant women.
  • Drugs in C had been found to pose risks for fetuses in pregnant animals, but there were no adequate studies performed on pregnant women.
  • Drugs in D had been found to pose fetal risks in humans, although the benefits of use may have still outweighed the potential for adverse outcomes.
  • Drugs in X had been found to pose fetal risks in humans, and those risks clearly outweighed any potential benefits.

But after widespread agreement that the “Category” scheme was overly simplistic, the FDA decided to dispense with the letters and adopt a new system. New warning labels will include three sections:

  1. Pregnancy
  2. Lactation
  3. Females & Males of Reproductive Potential

These new descriptions will summarize the particular risks that each medication can pose, along with an explanation of the actual studies that have demonstrated those risks. The labels will conclude by supplying specific recommendations to help prescribing physicians make better decisions.