|The Merck Manual of Medical Information--Home Edition
|Section 22. Women's Health Issues
Drug Use During Pregnancy
Most pregnant women take drugs of some kind. The Centers for Disease Control and Prevention and the World Health Organization estimate that more than 90 percent of pregnant women take prescription or nonprescription (over-the-counter) drugs, social drugs such as tobacco and alcohol, or illicit drugs. Drugs cause 2 to 3 percent of all birth defects; most of the others result from hereditary, environmental, or unknown causes. (see page 1223 in Chapter 254, Birth Defects)
Drugs move from the mother to the fetus primarily through the placenta, the same route taken by nutrients for the fetus' growth and development. In the placenta, drugs and nutrients in the mother's blood cross a thin membrane, which separates the mother's blood from the fetus' blood.
Federal Food and Drug Administration Categories of Drug Safety During Pregnancy
|A||Human studies have shown no risk.|
|B||Animal studies have shown no risk but no human studies are available, or animal studies have shown risk but human studies have not.|
|C||No human or animal studies are available, or animal studies have shown risk but no human studies are available.|
|D||Human studies have shown risk, but use may be justified in some cases (life-threatening situation or serious disease for which there is no safer drug).|
|X||The drug should never be taken during pregnancy; known human risk outweighs any benefit.|
Drugs that a woman takes during pregnancy can affect the fetus in several ways:
- By acting directly on the fetus, causing damage, abnormal development, or death
- By altering the function of the placenta, usually by constricting blood vessels and reducing the exchange of oxygen and nutrients between the fetus and the mother
- By causing the muscles of the uterus to contract forcefully, indirectly injuring the fetus by reducing its blood supply
How a drug affects a fetus depends on the fetus' stage of development and the potency and dose of the drug. Certain drugs taken early in pregnancy--before the 17th day after fertilization--may act in an all-or-nothing fashion, either killing the fetus or not affecting it at all. During this stage, the fetus is highly resistant to birth defects. However, the fetus is particularly vulnerable to birth defects between days 17 and 57 after fertilization, when its organs are developing. Drugs reaching the fetus during this stage may cause a miscarriage, an obvious birth defect, or a permanent but subtle defect noticed later in life, or they may have no noticeable effect. Drugs taken after organ development is complete are unlikely to cause obvious birth defects, but they may alter the growth and function of normally formed organs and tissues.
Because the fetus' tissues are growing quickly, their rapidly multiplying cells are very vulnerable to anticancer drugs. Many such drugs are teratogens, which are drugs that cause such birth defects as stunted growth in the uterus (intrauterine growth retardation), underdevelopment of the lower jaw, cleft palate, abnormal development of the skull bones, spinal defects, ear defects, clubfoot, and mental retardation. Some anticancer drugs cause birth defects in animals but haven't been shown to do so in humans.
This drug is no longer prescribed to pregnant women because it causes major birth defects. The drug was first introduced in 1956 in Europe as a remedy for influenza and as a sedative. In 1962, thalidomide taken by pregnant women when the fetus' organs were developing was found to cause birth defects, including severely underdeveloped arms and legs and defects of the intestine, heart, and blood vessels.
Isotretinoin, used to treat severe acne, psoriasis, and other skin disorders, causes major birth defects. Among the most significant are heart defects, small ears, and hydrocephalus--sometimes called water on the brain. The risk of birth defects is about 25 percent. Etretinate, another drug used to treat skin disorders, also causes birth defects in humans. Because this drug is stored in fat beneath the skin and released slowly, it can continue to cause birth defects for 6 months or longer after a woman stops taking it. Therefore, women who use this drug are advised to wait at least 1 year before becoming pregnant.
Androgenic (masculinizing) hormones, used to treat various blood disorders, and synthetic progestins taken during the first 12 weeks after fertilization may masculinize a female fetus' genitals. The clitoris, a small protrusion analogous to the penis in the male, may be enlarged--a condition that is permanent unless corrected with surgery--and the labia minora, which surround the openings to the vagina and urethra, may be fused together. Oral contraceptives don't contain enough progestin to produce such effects.
Diethylstilbestrol (DES), a synthetic estrogen, can cause vaginal cancer in adolescent girls whose mothers took this drug during pregnancy. These girls may later suffer from an abnormal uterine cavity, menstrual problems, a weakened (incompetent) cervix that can cause miscarriages, and an increased risk of having an ectopic pregnancy or having a baby who dies shortly before or after birth. Boys exposed to diethylstilbestrol as fetuses may have penis abnormalities.
Meclizine, frequently taken for motion sickness, nausea, and vomiting, causes birth defects in animals, but the same effects haven't been seen in humans.
Taken during pregnancy by a woman who is epileptic, some anticonvulsant drugs may cause the baby to have a cleft palate and abnormally developed heart, face and skull, hands, or abdominal organs. The baby may also be mentally retarded. Two anticonvulsants are particularly likely to cause birth defects; the risk is about 70 percent with trimethadione and about 1 percent with valproic acid. Carbamazepine, another anticonvulsant, is thought to cause a significant number of minor birth defects. The anticonvulsant phenytoin was previously blamed for a variety of birth defects, but similar defects occurred in babies of epileptic women who didn't take anticonvulsants.
Newborns exposed to phenytoin and phenobarbital (a barbiturate as well as an anticonvulsant) before birth may bleed easily because these drugs can cause a deficiency of vitamin K, which is needed for clotting. This side effect can be prevented if a pregnant woman takes vitamin K by mouth every day for a month before delivery or if the newborn is given an injection of vitamin K soon after birth. During pregnancy, women who have epilepsy are given the smallest effective dose of anticonvulsants and are closely monitored.
Women who have epilepsy, even if they don't take anticonvulsants during pregnancy, are more likely to have babies with birth defects than women who don't have epilepsy. The risk is greater in those who have frequent, severe convulsions or complications of pregnancy and in those in low socioeconomic groups, who tend to receive inadequate health care.
Except under special circumstances, vaccines made with a live virus aren't given to women who are or might be pregnant. Rubella vaccine, a live-virus vaccine, can cause infection of both the placenta and the developing fetus. Live-virus vaccines--such as those for measles, mumps, polio, chickenpox, and yellow fever--and other vaccines--such as those for cholera, hepatitis A and B, influenza, plague, rabies, tetanus, diphtheria, and typhoid--are given to a pregnant woman only if she is at substantial risk of becoming infected with one of those microorganisms.
Radioactive iodine given to a pregnant woman to treat an overactive thyroid gland (hyperthyroidism) can cross the placenta and destroy the fetus' thyroid gland or cause severe underactivity of the thyroid gland (hypothyroidism). Propylthiouracil and methimazole, drugs also used to treat an overactive thyroid gland, cross the placenta and can cause the fetus' thyroid gland to become abnormally enlarged; when needed, propylthiouracil is usually used because it's tolerated better by both the woman and fetus.
Oral Hypoglycemic Drugs
Oral hypoglycemic drugs are given to lower blood sugar (glucose) levels in people who have diabetes, but they often fail to control diabetes in pregnant women and may cause newborns to have very low blood glucose levels (hypoglycemia). Therefore, insulin is preferred for treating diabetes in pregnant women.
Narcotics and Nonsteroidal Anti-inflammatory Drugs
Narcotics and nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin, can reach the fetus in significant amounts if taken by a pregnant woman. Babies of women who are narcotic addicts can become addicted before birth and may show withdrawal symptoms 6 hours to 8 days after birth. Taking large doses of aspirin or other NSAIDs during pregnancy may delay the start of labor and may also cause the connection (ductus arteriosus) (see illustration, page 1227) between the aorta (the large artery that carries blood to the body) and the pulmonary artery (the artery that carries blood to the lungs) in the fetus to close before birth. This connection normally closes immediately after birth. Closure before birth forces blood to flow through the lungs, which haven't expanded yet, overloading the fetus' circulatory system.
When used late in pregnancy, nonsteroidal anti-inflammatory drugs may reduce the amount of amniotic fluid (the liquid surrounding the developing fetus, contained in the amniotic sac)--a potentially dangerous effect. Taking large doses of aspirin may cause bleeding problems in the mother or the newborn. Aspirin or other salicylates may increase bilirubin levels in the fetus' blood, causing jaundice and occasionally brain damage.
Antianxiety Drugs and Antidepressants
Antianxiety drugs may cause birth defects when taken during the first 3 months of pregnancy, although this effect hasn't been proven. Most antidepressants appear to be relatively safe when used during pregnancy, but lithium can cause birth defects--mainly of the heart. Barbiturates, such as phenobarbital, taken by a pregnant woman tend to reduce the slight jaundice newborns commonly have.
When taken during pregnancy, antibiotics can cause problems. Tetracycline antibiotics cross the placenta and are stored in the fetus' bones and teeth, where they combine with calcium. As a result, bone growth may be slow, the baby's teeth may be permanently yellow, and the tooth enamel may be soft and abnormally susceptible to cavities. The risk of tooth abnormalities is greatest from the middle to the end of pregnancy. Because several safe alternative antibiotics are available, tetracyclines are avoided during pregnancy.
Taking antibiotics such as streptomycin or kanamycin during pregnancy may damage the fetus' inner ear, possibly resulting in deafness. Chloramphenicol doesn't harm the fetus but can cause a serious illness in the newborn called gray baby syndrome. Ciprofloxacin should not be taken during pregnancy because it has been shown to cause joint abnormalities in animals. Penicillins appear to be safe.
Most sulfonamide antibiotics taken late in pregnancy may cause the newborn to develop jaundice, which can result in brain damage. However, one sulfonamide antibiotic, sulfasalazine, is much less likely to cause this problem.
The developing fetus is highly sensitive to warfarin, an anticlotting drug (anticoagulant). Significant birth defects occur in up to one fourth of babies exposed to the drug during the first 3 months of pregnancy. Also, abnormal bleeding may occur in both the woman and fetus. If a pregnant woman is at risk of developing blood clots, heparin is a much safer alternative. However, prolonged use during pregnancy may result in a low platelet count in the mother (platelets are cell-like particles that help blood clot) or in bone thinning (osteoporosis).
Drugs for Heart or Blood Vessel Disorders
Some women need these drugs during pregnancy for disorders that are chronic or that develop during pregnancy, such as preeclampsia (high blood pressure, protein in the urine, and fluid accumulation during pregnancy) and eclampsia (seizures resulting from preeclampsia). Drugs to lower high blood pressure, frequently given to pregnant women with preeclampsia or eclampsia, affect the functioning of the placenta and are used with great care to avoid causing problems in the fetus. (see page 1161 in Chapter 246, Diseases That Can Complicate Pregnancy) In general, these problems result from lowering the mother's blood pressure too rapidly, which markedly reduces blood flow to the placenta. Angiotensin converting enzyme inhibitors and thiazide diuretics usually are avoided during pregnancy because they can cause serious problems in the fetus. Digoxin, used to treat heart failure and some heart rhythm abnormalities, readily crosses the placenta but typically has little effect on the baby before or after birth.
Some drugs, such as nitrofurantoin, vitamin K, sulfonamides, and chloramphenicol, may cause the breakdown of red blood cells in pregnant women and fetuses who have glucose-6-phosphate dehydrogenase (G6PD) deficiency, a hereditary disorder that affects red blood cell membranes. Therefore, these drugs aren't given to women who have this disorder.
Drugs Used During Labor and Delivery
Local anesthetics, narcotics, and other analgesics usually cross the placenta and can affect the newborn--for example, by weakening its urge to breathe. (see page 1175 in Chapter 248, Labor and Delivery) Therefore, if drugs are needed during labor, they are given in the smallest effective doses and preferably as late as possible so that they are less likely to reach the fetus before birth.
Social and Illicit Drugs
Smoking during pregnancy can be harmful. (see page 1149 in Chapter 244, High-Risk Pregnancy) The average birth weight of babies born to women who smoke during pregnancy is 6 ounces less than that of babies born to women who don't smoke. Miscarriages, stillbirths, premature births, and sudden infant death syndrome (SIDS) are more common among babies of women who smoke during pregnancy.
Drinking alcohol during pregnancy can cause birth defects. Babies of women who drink excessive amounts of alcohol during pregnancy may have fetal alcohol syndrome. (see page 1214 in Chapter 252, Problems in Newborns and Infants) Such babies are small, often with small heads (microcephaly), facial abnormalities, and borderline mental deficiency. Less commonly, they have joint abnormalities and heart defects. They don't thrive and are more likely to die soon after birth. Because the amount of alcohol required to cause this syndrome is unknown, pregnant women are advised to abstain from drinking alcohol.
Whether caffeine harms the fetus has been debated. Several studies have suggested that drinking more than seven or eight cups of coffee a day may increase the risk of having a stillbirth, premature birth, low-birth-weight baby, or miscarriage. However, these studies were flawed because many of the coffee drinkers also smoked cigarettes. A later study, which accounted for cigarette smoking, concluded that the problems were caused by tobacco, not caffeine. Whether heavy coffee drinking during pregnancy affects the newborn is unclear.
Aspartame, an artificial sweetener, appears to be safe during pregnancy when it's consumed in amounts used for dietary sweetening.
Cocaine use during pregnancy increases the risk of miscarriage; early detachment of the placenta from the uterus (abruptio placentae); birth defects of the brain, kidneys, and genital organs; and less interactive behavior in newborns. (see page 1214 in Chapter 252, Problems in Newborns and Infants)
No conclusive evidence that marijuana causes birth defects or interferes with fetal growth and development has been found. However, studies suggest that heavy use of marijuana during pregnancy may lead to abnormal behavior in newborns.