It's hard enough to adequately weigh the risks and benefits of taking certain medications while pregnant. But the bigger problem is when women and doctors simply don't know the risks.
A review article that considered much of the research available and published in April says just that: too little is known about the ways prescription drugs taken by a pregnant mother may affect the developing baby.
This is true even for the drugs used to treat chronic conditions, such as asthma, high blood pressure and mental health disorders.
"Avoid any unnecessary medication during pregnancy."
An article by Melanie Chan, a Core Medical Trainee at the University College London Institute of Child Health, and two colleagues, reviewed the research available regarding prescription drugs and pregnancy and found there simply isn't a significant amount of reliable evidence about the risks.
In fact, for over 80 percent of 468 drugs approved by the Food and Drug Administration in the past 20 years, doctors do not have enough evidence to clearly know the risks to the baby of a woman taking these drugs while pregnant.
According to Chan and colleagues, approximately 2 percent of all babies born have some kind of birth defect, and researchers estimate that about 1 percent of these - or half of all congenital defects - are due to the use of prescription drugs during pregnancy.
Barriers to Knowledge
One problem, Chan and the other authors found in the literature, is that a pregnant woman's body may change in ways that might affect how the drug physically acts. It's also not known what all drugs necessarily can cross into the placenta and what effect they may have on a developing baby.
"The maternal physiological changes that occur during pregnancy can alter what the body does to the drug in some cases," said Jason Waugh, editor in chief of the journal The Obstetrician & Gynaecologist, where Chan's review appeared April 27. "More research is needed into the fetal effects of some drugs as there are big gaps in our knowledge."
A primary reason for these knowledge gaps is that pregnant women very rarely are participants in clinical trials of drugs during which adverse events or side effects are discovered.
"Many pregnant women use prescription drugs, however, the risk to the fetus remains unknown," said review co-author Alastair Sutcliffe, of the University College London's Institute of Child Health. "Pregnant women are excluded from clinical trials, which means when new drugs are released there is almost no information on their safety and efficacy in pregnancy."
This exclusion of pregnant women from drug trials is done for good reason - it would be unwise and likely unethical to test a drug on a pregnant woman without knowing whether it might harm the baby.
Those who remember the use of the medication thalidomide in the late 1950's will recall the horrific images of severely disfigured children that resulted from this drug. From 1957 to 1961, women took thalidomide to counter the effects of morning sickness until it became clear that the drug was responsible for children being born without limbs or with other severely handicapped limbs or birth defects.
While excluding women from clinical trials serves the obvious purpose of protecting babies from other such pharmaceutical disasters, it also largely leaves women and doctors in the dark about what drugs might be safe for a baby to be exposed to in the womb if they serve an important benefit to the mother.
What We (Sort of) Know
The most intensely studied medications in pregnancy are a class of anti-epileptic drugs, which includes anti-seizure medications. About 1 in every 250 pregnancies involve exposure to the baby of an anti-epileptic drug.
Data pulled from the U.K. Epilepsy and Pregnancy Register found that 3.7 percent of 2,598 babies were born with birth defects to mothers taking one anti-epileptic drug, also called anticonvulsants. In a group of 770 babies whose mothers were taking two more or more of these drugs, the rate almost doubled to 6 percent of the children having birth defects.
One type of birth defect sometimes seen with anticonvulsants - though evidence does not show that the anticonvulsants cause this defect - is a neural tube that does not fully close, something usually promoted by a pregnant woman's intake of folic acid in the months before pregnancy and the first four weeks of pregnancy.
If a baby's neural tube - what becomes the backbone - does not fully close, the child could be born with spina bifida or other debilitating or paralyzing conditions.
Not all anti-epileptic drugs are used to treat epilepsy though. Some anti-seizure medications are used to treat other conditions, such as mental health conditions.
A significant number of these anti-seizure drugs appear to act like mood stabilizers and are therefore being prescribed for bipolar disorder, such as Depakote (divalproex sodium) and Lamictal (lamotrigine).
If you are pregnant and taking one of these drugs, however, that does not mean you should stop. A person taking any kind of psychiatric medication, or any prescription drug at all, should always consult their doctor before stopping the drug or changing the way they take it.
In many cases, the benefits of taking the drug - preventing seizures or reducing the psychosis of a woman with a serious mental health condition - are significant enough to outweigh the possible risks to the baby, especially if the baby could be harmed by the condition that requires the drugs if it goes untreated.
Antidepressants During Pregnancy
More commonly used drugs for mental disorders are selective serotonin reuptake inhibitors (SSRIs), prescribed for depression and anxiety. A little over half of the 4 percent of women who take an antidepressant during pregnancy take SSRIs.
The data on SSRI exposure to a fetus is also still sketchy. Chan's review mentions that one birth defect registry study did not discover any links between heart defects and a mother's use of SSRIs while pregnant.
Other studies, however, have found associations between taking antidepressants late in pregnancy and complications at birth including premature birth, feeding problems, respiratory distress syndrome, temperature regulation problems and disorders of the endocrine system.
Yet overall, simply not enough evidence exists for researchers to make recommendations or even to adequately comment on potential risks of SSRIs or anticonvulsants.
How Are Drugs Currently Classified
The U.S. Food and Drug Administration uses a 5-category classification system to guide women on the safety of medications, but a large number of the drugs are in the middle at Category C, which means there is insufficient evidence to say it is safe or unsafe for pregnant women to take.
The categories, verbatim from the FDA, are as follows:
Category A - Adequate and well-controlled studies have failed to demonstrate a risk to the fetus in the first trimester of pregnancy (and there is no evidence of risk in later trimesters).
Category B - Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women.
Category C - Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.
Category D - There is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.
Category X - Studies in animals or humans have demonstrated fetal abnormalities and/or there is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience, and the risks involved in use of the drug in pregnant women clearly outweigh potential benefits.
What's Definitely Dangerous
There are drugs in that category X which are known to cause serious problems to the fetus, such as thalidomide mentioned earlier. Other drugs that are known to cause problems are tetracyclines, a class of antibiotics, and the drug Accutane (isotretinoin), used to treat acne.
Another common drug that should never be taken during pregnancy is fluconazole, or Diflucan, an anti-fungal used to treat conditions such as yeast infections. ACE inhibitors, used to treat blood pressure, are also on the list of medications that cause known serious risks to a developing baby.
In some cases, even vitamins or minerals that do not require FDA approval can cause problems for a baby. Very high doses of vitamin A, for example, while not a guarantee to cause birth defects, have been linked to serious problems in babies whose mothers take lots of vitamin A. This provides additional reason for pregnant women to consult a doctor on any supplement, medical or "natural," before taking it.
A more complete list of all the drugs that are known to cause minor or significant birth defects or complications can be found on the FDA website. The term to search for is "teratogen," which is the term used to describe a substance that is known to cause problems for babies when they are exposed in the womb to it.
Risk vs. Benefit in a World of Doubt
Ultimately, the decision about whether a woman should take a medication is a decision based on the benefits the medication can offer a woman to treat a specific condition versus the possible risks to the baby. For categories B and C medications, this determination is often made by taking into consideration whether the woman's condition, if untreated by the medication, could pose its own dangers to the baby.
This is also the calculation used for category D medications, but the benefit must generally be substantial to the mother and child to risk the potential negative effects to the baby.
Chan and her co-authors said that more research should be done to provide pregnant women with better guidance in what medications to consider taking or not taking and how to better weigh the benefits and risks of certain prescriptions.
Until better information is available, women will have to engage in honest, direct conversations with their doctors to determine together what medications they will choose to take during pregnancy.
