Drug Use During Pregnancy

More than 90% of pregnant women take prescription or nonprescription (over-the-counter) drugs or use social drugs, such as tobacco and alcohol, or illicit drugs at some time during pregnancy. In general, drugs, unless absolutely necessary, should not be used during pregnancy, because many can harm the fetus. About 2 to 3% of all birth defects result from the use of drugs.
However, drugs are sometimes essential for the health of the pregnant woman and the fetus. In such cases, a woman should talk with her doctor or other health care practitioner about the risks and benefits of taking the drugs. Before taking any drug (including nonprescription drugs) or dietary supplement (including medicinal herbs), a pregnant woman should consult her health care practitioner. A health care practitioner may recommend that a woman take certain vitamins and minerals during pregnancy.
Drugs taken by a pregnant woman reach the fetus primarily by crossing the placenta, the same route taken by oxygen and nutrients, which are needed for the fetus's growth and development. Drugs that a pregnant woman takes during pregnancy can affect the fetus in several ways:
They can act directly on the fetus, causing damage, abnormal development (leading to birth defects), or death. They can alter the function of the placenta, usually by constricting blood
vessels and reducing the supply of oxygen and nutrients to the fetus from the mother and thus sometimes resulting in a baby that is underweight and underdeveloped.
They can cause the muscles of the uterus to contract forcefully, indirectly injuring the fetus by reducing its blood supply or triggering preterm labor and delivery.
How a drug affects a fetus depends on the fetus's stage of development and the strength and dose of the drug. Certain drugs taken early in pregnancy (before the 20th day after fertilization) may act in an all-or-nothing fashion, killing the fetus or not affecting it at all. During this early
stage, the fetus is highly resistant to birth defects. However, the fetus is particularly vulnerable to birth defects between the 3rd and the 8th week 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 that is noticed later in life. 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.
The Food and Drug Administration (FDA) classifies drugs according to the degree of risk they pose for the fetus if they are used during pregnancy. Some drugs are highly toxic and should never be used by pregnant women because they cause severe birth defects. One example is thalidomide. Several decades ago, this drug caused extreme underdevelopment of arms and legs and defects of the intestine, heart, and blood vessels in the babies of women who took the drug during pregnancy. Some drugs cause birth defects in animals, but the same effects have not been seen in people. One example is meclizine, frequently taken for motion sickness, nausea, and vomiting. Often, a safer drug can be substituted for one that is likely to cause harm during pregnancy. For example, doctors prefer to use insulin rather than oral hypoglycemic drugs, for treatment of diabetes in pregnant women. Insulin cannot cross the placenta and controls diabetes better. Oral hypoglycemic drugs can cross the placenta, sometimes resulting in a very low blood sugar level in the newborn. For an overactive thyroid gland, propylthiouracil is usually preferred. For prevention of blood clots, the anticoagulant heparin is preferred. For anxiety disorders, meprobamate and chlordiazepoxide, which do not appear to cause birth defects or brain damage, are preferred. Several safe antibiotics, such as penicillin, are available.
Some drugs can cause effects after they are discontinued. For example, etretinate, a drug used to treat skin disorders, is stored in fat beneath the skin and is released slowly. Etretinate can cause birth defects 6 months or longer after women discontinue it. Therefore, women are advised to wait at least 1 year after discontinuing the drug before they become pregnant. Unless unavoidable, vaccines made with a live virus are not given to women who are or might be pregnant. Other vaccines (such as those for cholera, hepatitis A and B, plague, rabies, tetanus, diphtheria, and typhoid) are given to pregnant women only if they are at substantial risk of developing that particular infection. However, all pregnant women should be vaccinated against the influenza virus during the influenza (flu) season.
Drugs to lower high blood pressure (antihypertensives) may be needed by pregnant women who have had high blood pressure or who develop it during pregnancy (a complication called preeclampsia. Antihypertensives commonly used to treat preeclampsia can markedly reduce blood flow to the placenta if they lower blood pressure too rapidly in pregnant women. So pregnant women who have to take these drugs are closely monitored. Angiotensin- converting enzyme (ACE) inhibitors and thiazide diuretics are usually not given to pregnant women because these drugs can cause serious problems in the fetus. Digoxin, used to treat heart failure and some abnormal heart rhythms, readily crosses the placenta. But it typically has little effect on the baby before or after birth. Most antidepressants appear to be relatively safe when used during pregnancy.

How Drugs Cross the Placenta
Some of the fetus's blood vessels are contained in tiny hairlike projections (villi) of the placenta that extend into the wall of the uterus. The mother's blood passes through the space surrounding the villi (intervillous space). Only a thin membrane (placental membrane) separates the mother's blood in the intervillous space from the fetus's blood in the villi. Drugs in the mother's blood can cross this membrane into blood vessels in the villi and pass through the umbilical cord to the fetus.

Social Drugs
Cigarette Smoking: Although cigarette smoking harms both pregnant women and the fetus, only about 20% of women who smoke quit during pregnancy. The most consistent effect of smoking on the fetus during pregnancy is a reduction in birth weight: The more a woman smokes during pregnancy, the less the baby is likely to weigh. 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 do not smoke. The reduction in birth weight seems to be greater among the babies of older smokers.
Birth defects of the heart, brain, and face are more common among babies of smokers than among those of nonsmokers. Also, the risk of sudden infant death syndrome (SIDS) may be increased. A mislocated placenta (placenta previa), premature detachment of the placenta (placental abruption), premature rupture of the membranes, preterm labor, uterine infections, miscarriages, stillbirths, and premature births are also more likely. In addition, children of women who smoke have slight but measurable deficiencies in physical growth and in intellectual and behavioral development. These effects are thought to be caused by carbon monoxide and
nicotine. Carbon monoxide may reduce the oxygen supply to the body's tissues. Nicotine stimulates the release of hormones that constrict the vessels supplying blood to the uterus and placenta, so that less oxygen and fewer nutrients reach the fetus.
Pregnant women should avoid exposure to secondhand smoke because it may similarly harm the fetus.

Alcohol: Drinking alcohol during pregnancy is the leading known cause of birth defects. Because the amount of alcohol required to cause fetal alcohol syndrome is unknown, pregnant women are advised to abstain from drinking alcohol altogether. The range of effects of drinking during pregnancy is great.
The risk of miscarriage almost doubles for women who drink alcohol in any form during pregnancy, especially if they drink heavily. Often, the birth weight of babies born to women who drink during pregnancy is substantially below normal. The average birth weight is about 4 pounds for babies exposed to significant amounts of alcohol, compared with 7 pounds for all babies. Newborns of women who drank during pregnancy may not trive and are more likely to die soon after birth. Fetal alcohol syndrome is one of the most serious consequences of drinking during pregnancy. It occurs in about 2 of 1,000 live births. This syndrome includes inadequate growth before or after birth, facial defects, a small head (probably caused by inadequate growth of the brain), mental retardation, and abnormal behavioral development. Less commonly, the position and function of the joints are abnormal and heart defects are present.
Babies or developing children of women who drank alcohol during pregnancy may have severe behavioral problems, such as antisocial behavior and attention deficit disorder. These problems can occur even when the baby has no obvious physical birth defects.

Caffeine: Whether consuming caffeine during pregnancy harms the fetus is unclear. Evidence seems to suggest that consuming caffeine in moderation during pregnancy poses little or no risk to the fetus. Caffeine, which is contained in coffee, tea, some sodas, chocolate, and some drugs, is a stimulant that readily crosses the placenta to the fetus. Thus, it may stimulate the fetus, increasing the heart and breathing rates. Caffeine also may decrease blood flow across the placenta and decreases the absorption of iron (possibly increasing the risk of anemia. Whether drinking more than seven or eight cups of coffee a day increases the risk of having a stillbirth, premature birth, low-birth-weight baby, or miscarriage is also unclear. Some experts recommend limiting coffee consumption to two or three cups a day and drinking decaffeinated beverages when possible.

Aspartame: Aspartame, an artificial sweetener, appears to be safe during pregnancy when it is consumed in small amounts, such as in amounts used in artificially sweetened foods and beverages.

Taking Drugs While Breastfeeding
When new mothers who are breastfeeding have to take a drug, they wonder whether they should stop breastfeeding. The answer depends on how much of the drug appears in the milk, whether the drug is absorbed by the baby, how the drug affects the baby, and how much milk the baby consumes. How much milk the baby consumes depends on the baby's age and the amount of other foods and liquids in the baby's diet. Some drugs, such as epinephrine, heparin, and insulin, do not appear in breast milk and are thus safe to take. Most drugs appear in breast milk but usually in tiny amounts. However, even in tiny amounts, some drugs can harm the baby. Some drugs appear in breast milk, but the baby usually absorbs so little of them that they do not affect the baby. Examples are the antibiotics gentamicin, kanamycin, streptomycin, and tetracycline. Drugs that are considered safe include most nonprescription (over-the-counter) drugs. Exceptions are antihistamines (commonly contained in cough and cold remedies, allergy drugs, motion sickness drugs, and sleep aids) and, if taken in large amounts for a long time, aspirin and other salicylates. Acetaminophen and ibuprofen, taken in usual doses, appear to be safe. Drugs that are applied to the skin, eyes, or nose or that are inhaled are usually safe. Most antihypertensive drugs do not cause significant problems in breastfed babies. Warfarin is considered compatible with breastfeeding a full-term, healthy baby. Caffeine and theophylline do not harm breastfed babies but may make them irritable. Even though some drugs are reportedly safe for breastfed babies, women who are breastfeeding should consult a health care practitioner before taking any drug, even a nonprescription drug, or a medicinal herb. Drug labels should be checked because they contain warnings against use during breastfeeding, if applicable. Some drugs require a doctor's supervision during their use. Taking them safely while breastfeeding may require adjusting the dose, limiting the length of time the drug is used, or timing when the drug is taken in relation to breastfeeding. Most antianxiety drugs, antidepressants, and antipsychotic drugs require a doctor's supervision, even though they are unlikely to cause significant problems in the baby. However, these drugs stay in the body a long time. During the first few months of life, babies may have difficulty eliminating the drugs, and the drugs may affect the baby's nervous system. For example, the antianxiety drug diazepam (a benzodiazepine) causes lethargy, drowsiness, and weight loss in breastfed babies. Babies eliminate phenobarbital (an anticonvulsant and a barbiturate) slowly, so this drug may cause excessive drowsiness. Because of these effects, doctors reduce the dose of benzodiazepines and barbiturates as well as monitor their use by women who are breastfeeding. Some drugs should not be taken while breastfeeding. They include atropine, chemotherapy drugs (such as doxorubicin and methotrexate) , chloramphenicol, ergotamine, lithium, methimazole, methysergide, radioactive drugs for diagnostic procedures, thiouracil, vaccines, and illicit drugs such as cocaine, heroin, and phencyclidine (PCP). Other drugs should not be taken because they may suppress milk production. They include bromocriptine, estrogen, oral contraceptives that contain high-dose estrogen and a progestin, and levodopa.
If women who are breastfeeding must take a drug that may harm the baby, they must stop breastfeeding. But they can resume breastfeeding after they discontinue the drug. While taking the drug, women can maintain their milk supply by pumping breast milk, which is then discarded.

Illicit Drugs
Use of illicit drugs (particularly cocaine and opioids) during pregnancy can cause complications during pregnancy and serious problems in the developing fetus and the newborn. For pregnant women, injecting illicit drugs also increases the risk of infections that can affect or be transmitted to the fetus. These infections include hepatitis and sexually transmitted diseases (including AIDS). Also, growth of the fetus is more likely to be inadequate, and premature births are more common.

Cocaine: Cocaine readily crosses the placenta and affects the fetus. It constricts blood vessels, possibly reducing blood flow (and the oxygen supply) to the fetus. The reduced blood and oxygen supply to the fetus can slow the growth of the fetus, particularly of the bones and the intestine. Babies are more likely to be small and to have a small head. Rarely, use of cocaine results in birth defects of the brain, eyes, kidneys, and genital organs.
Use of cocaine during pregnancy can also cause complications during pregnancy. Among women who use cocaine throughout pregnancy, about 31% have a preterm delivery and 15% have premature detachment of the placenta (placental abruption). The chances of a miscarriage are also increased. About 19% have a baby who did not grow as much as normally expected before birth. If women stop using cocaine after the first 3 months of pregnancy, the risks of a preterm delivery and premature detachment of the placenta are still increased, but the fetus's growth will probably be normal. Newborns may have withdrawal symptoms. Their behavior is also affected.
Newborns interact less with other people. Babies of cocaine users may be hyperactive, tremble uncontrollably, and have difficulty learning (which may continue through age 5 years or even longer).

Opioids: Opioids, such as heroin, methadone, and morphine, readily cross the placenta. Consequently, the fetus may become addicted to them and may have withdrawal symptoms 6 hours to 8 days after birth. However, use of opioids rarely results in birth defects. Use of opioids during pregnancy increases the risk of complications during pregnancy, such as miscarriage, abnormal presentation of the baby, and preterm delivery. Babies of heroin users are more likely to be small.

Amphetamines: Use of amphetamines during pregnancy may result in birth defects, especially of the heart.

Marijuana: Whether use of marijuana during pregnancy can harm the fetus is unclear. The main ingredient of marijuana, tetrahydrocannabino l, can cross the placenta and thus may affect the fetus. If marijuana is used heavily during pregnancy, newborns may have behavioral problems.

Drugs Used During Labor and Delivery
Local anesthetics, opioids, and other analgesics usually cross the placenta and can affect the newborn. For example, they can weaken the newborn's urge to breathe. Therefore, if these drugs are needed during labor, they are given in the smallest effective doses.
[Merck]