How Medications Work in Pregnancy and Breast-feeding
To understand how a medication may affect you or your developing or breast-feeding baby, it's important to understand how pregnancy changes your body, how an embryo and a fetus develop, how substances can cause birth defects or other medical problems, and how medications can or cannot pass into breast milk and affect a breast-feeding baby.
HOW PREGNANCY CHANGES YOU AND YOUR RESPONSE TO DRUGS
During pregnancy, a woman's body goes through physiological adaptations that alter how medications are absorbed, distributed, and eliminated by her body. For example, a pregnant woman's stomach empties more slowly and food and medications spend a longer time in the bowel, which changes the rate of absorption of drugs taken by mouth. Blood flow to the lungs increases, and breathing is faster and deeper, which increases the absorption of inhaled drugs (such as asthma medications). And a pregnant woman's blood volume increases by half, which reduces the concentrations of proteins in the blood that help bind and regulate drug distribution and elimination.
All of these changes mean that doses of medications appropriate for nonpregnant women are frequently too low to produce the intended therapeutic effect in pregnancy, or are too high, raising the risk of side effects. Doctors often prescribe lower doses than normal to pregnant women in the mistaken belief this will eliminate any possibility of side effects, but this increases the chance the patient will not get the full benefit of the medication.
HOW MEDICATION CAN AFFECT A DEVELOPING EMBRYO OR FETUS
The possibility of birth defects
A birth defect is a general term for a recognizable anatomical problem in a baby that is present at birth. It may be the result of abnormal development or damage to a structure or organ after it has developed. Nobody likes to talk about it, but in any pregnancy, an average, healthy woman has a 2 to 3 percent chance of delivering a baby who has a major birth defect. That's the everyday risk of bringing a child into this world, and it is beyond anyone's control. For women who have a history of genetic defects or who are living with particular chronic health conditions, that risk can be increased, and taking certain substances, including some medications, can also increase the likelihood of having a baby with a birth defect.
Environmental exposures
The scientific name for a substance (such as a medication) that causes birth defects is teratogen. There is a wide range of known teratogens, including prescription and over-the-counter medications, recreational drugs and alcohol, chemicals, physical agents (such as radiation), and maternal diseases. It is estimated at least 10 percent of major birth defects are due to environmental exposures (such as medications and chemicals or nutritional shortages) and therefore they are, to some extent, preventable. In addition, there are substances that are not known to cause birth defects but may increase the risk of adverse outcomes such as miscarriage, stillbirth, preterm delivery (delivery before 37 weeks), low birth weight, and behavioral or mental deficits.
Obviously, this is one of the reasons doctors are so careful about what medications they prescribe during a pregnancy. The purpose of this book is to give you information on the possible effect drugs may have on a developing embryo or fetus. The purpose of this chapter is to help explain how substances can do that, what time periods of development are more sensitive than others, how the dose of a medication can change its effect, and other factors that play a role in deciding if a medication can be taken with relative safety during pregnancy.
Six factors that influence whether a substance will cause a birth defect
1. Whether it crosses the placenta
The first line of defense for a developing embryo and fetus is the placenta. The placenta provides the baby with oxygen, nutrients, and hormones. Some drugs cross the placenta and reach the developing fetus and some do not. If a drug does not cross the placenta, it cannot have a direct effect on the fetus. Drugs that cross the placenta poorly will typically have less of an effect than those that pass efficiently.
2. Genetic susceptibility and other exposures
Environmental exposures (such as medications, chemicals, nutritional deficits, and viruses) can affect different species and even different members of one species in different ways. That is why a drug that causes birth defects in animals may not cause them in humans, and vice versa, and why one human embryo might be affected by a substance when another one isn't. This is why animal studies are not necessarily accurate indicators of how a drug will behave in humans. It can also explain in great part why medications that are known to cause birth defects, such as thalidomide and isotretinoin (Accutane), affect less than half of the embryos and fetuses exposed to them. The chance that a substance will cause a birth defect can be increased when it is combined with another substance and it can be decreased if a mother takes other medicines (such as certain vitamins). As a result of all of these variables, there are few hard-and-fast rules about whether something will definitely cause a birth defect.
3. Timing
Whether something can cause an anatomical defect in a developing embryo also depends on when in pregnancy the exposure occurs. In order for a teratogen (again, a substance that is known to cause birth defects) to affect a developing embryo or fetus it has to be taken at the time when the particular structure it can affect is developing. For instance, the antiseizure medication carbamazepine is known to increase the risk of neural tube defects such as spina bifida. Since the closure of the spine occurs around three weeks after conception (or three to five weeks after the last menstrual period), the medication cannot cause that defect if it is taken after that period of time. This is why certain medications may be safe to take at certain times in a pregnancy and not at others. In addition, some medications can affect multiple areas of an embryo or fetus depending on when they are taken. For example, certain blood thinners (coumarin-derivative anticoagulants such as warfarin) taken in the first trimester, can cause a group of birth defects known as fetal warfarin syndrome, which includes abnormalities in the skeleton, an underdeveloped spine and thigh and heel bones, low birth weight, and developmental difficulties. Second- and third-trimester use can cause central nervous system disorders such as spasticity and seizures due to fetal bleeding. For that reason, it is never considered safe to take these kinds of medications during pregnancy, although some medical conditions require their use.
It is generally agreed that exposure to substances during the first two weeks after conception poses very little risk of birth defects in part because the placenta (which is how substances reach the embryo) is not yet developed, and in part because at that point the embryo is primarily made up of stem cells, which have the ability to develop into many different kinds of cells (for instance they could become bone, blood, nerves, or connective tissue). So if some are damaged for any reason, other cells may be able to assume their roles and enable development to continue normally. Or if the damage is too great, the result may be a miscarriage, which can happen before a woman even knows she is pregnant. This is why the first two weeks after conception are called the "all-or-nothing" period of development.
Virtually all of a fetus's physical structures, with the exception of the brain, develop in the first ten weeks after the last normal menstrual period, and most birth defects, if they are going to occur, happen during that time. Brain development continues throughout pregnancy and after birth, which means that the brain is susceptible to environmental exposures throughout pregnancy. Some birth defects can happen after a fetus's structural development is complete because of events such as fetal blood clots, abnormal bleeding or heart rates, low blood pressure, and viral infections. In addition, exposure to certain substances at any time in pregnancy can increase the rate for other adverse outcomes such as low birth weight or preterm delivery (before 37 weeks).
4. Dose
Some substances that cause birth defects will do so only if the dose is high enough, or they will cause more severe birth defects with higher doses. For instance, the anticonvulsant valproic acid increases the risk of neural tube defects such as spina bifida when it is taken around three weeks after conception (or five weeks after the last normal menstrual period), but this birth defect has been seen when women took very high doses of the medication. Women taking significantly lower doses at the same period of time typically delivered normal, healthy babies.
5. How the medicine is taken
Whether a medication is taken by mouth, through an IV, or applied topically affects how much of it enters a pregnant woman's bloodstream and therefore how much can reach the placenta. For example, retinoid medications (often used to treat severe acne) have been proved to be teratogens. One of them, isotretinoin (Accutane), is a very powerful teratogen when it is taken by mouth (which is why women taking Accutane should use effective birth control and receive monthly pregnancy tests), while topical retinoids (such as Retin-A) when used sparingly are not associated with an increase in the same birth defects. This does not rule out the possibility that topical retinoids could cause birth defects (and so they are not recommended during pregnancy), but it suggests that the amount of topical medication that typically reaches the bloodstream of a pregnant woman is too low to increase the rate of birth defects in a way that is detectable by scientific study.
6. Spectrum of outcomes
"Spectrum of outcomes" is a scientific term for the idea that certain substances, such as alcohol, can cause a range of adverse outcomes in a pregnancy depending on both how much of the substance is taken, how often, and when. Those outcomes can include miscarriage, stillbirth, birth defects, slowed growth (also called growth restriction), low birth weight, preterm delivery (before 37 weeks), and mental deficits or learning disabilities. In the case of alcohol, moderate to heavy use during pregnancy, particularly if it's consumed in a binge pattern, increases the risk for miscarriage, stillbirth, and fetal alcohol syndrome—a characteristic pattern of minor face and skull abnormalities, heart defects, cleft mouth and palate, growth deficiency, and deficits in IQ and learning disabilities. Animal and human studies have shown that these outcomes are not all found in any one pregnancy and that they depend on how much a woman drinks and the pattern of her drinking. The risk is also affected by genetic susceptibility and other factors such as the pregnant woman's nutritional status.
Your doctor should use all of these factors as well as the latest research on medications to determine whether taking a particular medication could present a risk to your health or the health of your developing baby and to decide which medication is the best choice for both of you.
HOW MEDICATIONS CAN AFFECT A BREAST-FEEDING CHILD
It is much easier to study how drugs pass into breast milk than to study them during pregnancy, and most experts in the field agree that most medications are compatible with breast-feeding. That said, a lot of physicians are still not comfortable prescribing medications you need while you are breast-feeding. Here's what you need to know.
Similar to the developing fetus, the amount of a medication that a breast-feeding baby is exposed to varies. In order for a drug you take to affect your breast-feeding baby, it has to be absorbed into your bloodstream in large enough amounts to then be transmitted into your breast milk. If it does reach your milk, it then goes into your baby's stomach and, in order to be absorbed into your baby's bloodstream, it has to not be destroyed by the baby's stomach acid and be easily absorbed out of the gut. Assuming it passes all those hurdles, the resulting amount in your baby must be high enough relative to his or her weight to have an effect. In addition, it is possible to lower the amount of a medication your baby receives in your milk by feeding him or her when the medication is at its lowest concentration in your system. All of these factors mean that many medications can be safely taken by a breast-feeding mom without causing any harm to or side effects in her baby.
More often than not, if you are taking a medication that is necessary and beneficial to your health, there will be a way for you to safely take it while you are breast-feeding, or there will be another medication you can switch to during that time. It is important that you talk with your pediatrician rather than your general physician (who may not be experienced with how medications affect a breast-feeding baby), ask him or her to consult the most recent information, and then make an informed choice together.
Copyright © 2013 by Carl P. Weiner, M.D., and Kate Rope
