Medicines that can be used in pregnancy

The most commonly used drugs during pregnancy include antiemetics, antacids, antihistamines, analgesics, antimicrobials, tranquilizers, hypnotics, diuretics, and social and illicit drugs. The U.S. Food and Drug Administration (FDA) classifies drugs into 5 safety categories for use during pregnancy. Well-controlled studies have been conducted with some therapeutic drugs in pregnancy. Most information on drug safety during pregnancy comes from experimental studies and uncontrolled studies in humans (eg, postmarketing recalls). Drugs are used during pregnancy to treat specific disorders. Despite widespread acceptance of drug safety, drug use, excluding alcohol, accounts for only 2% to 3% of birth defects in fetuses; most birth defects have genetic, environmental, or unknown causes.

FDA Pregnancy Drug Safety Categories

Category	Description
A	Clinical studies have not revealed any harmful effects on the embryo; these drugs are the safest
IN	Animal studies suggest no risk to the fetus, but no human clinical studies have been conducted; experimental animal studies suggest risk to the fetus, but no controlled human studies have been conducted.
WITH	Adequate studies in animals or humans have not been conducted; or adverse effects on the fetus were noted in animal studies, but human studies are not available
D	There is a fetal risk, but in certain situations the benefits may outweigh the risk (eg, life-threatening disorders, serious disorders for which safer drugs cannot be used or are ineffective)
X	The proven risks of the effect on the fetus outweigh the positive effect of the drug

Not all drugs taken by the mother cross the placenta to the fetus. Drugs may have a direct toxic or teratogenic effect (for known and suspected teratogenic factors). Those drugs that do not cross the placenta may harm the fetus in the following ways: spasm the placental vessels and as a result lead to a disruption of gas and nutrient metabolism; cause severe uterine hypertonicity, leading to anoxic injury; change the physiology of the mother (for example, causing hypotension).

Known or suspected teratogenic factors

ACE inhibitors	Azotretinoin
Alcohol	Lithium
Aminopterin	Metamizole sodium
Androgens	Methotrexate
Carbamazepine	Phenytoin
Coumarins	Radioactive iodine
Danazol	Tetracycline
Diethylstilbestrol	Trimethadone
Etretinate	Valproic acid

Drugs cross the placenta in a manner similar to that by which they cross other epithelial barriers. Whether and how quickly a drug crosses the placenta depends on its molecular weight, whether it is bound to another substance (e.g., a carrier protein), whether it is readily available for intervillous exchange, and the amount of drug metabolized by the placenta. Most drugs with a molecular weight of less than 500 Da are able to cross the placenta and enter the fetal circulation. High-molecular-weight drugs (e.g., those bound to a carrier protein) generally do not cross the placenta. An exception is immunoglobulin G, which is sometimes used to treat disorders such as fetal alloimmune thrombocytopenia. In general, equilibration between maternal blood and fetal tissues takes at least 40 min.

The effect of a drug on the fetus is determined largely by the fetal age at release, the potency, and the dosage of the drug. Drugs administered within 20 days of fertilization may have an uncompromising effect, causing harm to the embryo or leaving it unharmed. Teratogenesis is unlikely at this stage, but is more likely during organogenesis (between days 14 and 56 after fertilization). Drugs that reach the embryo during this period may cause abortion, sublethal anatomical defects (true teratogenic effect), or latent embryopathies (permanent metabolic or functional defects that may manifest later in life), or may have no effect. Drugs administered after organogenesis (in the 2nd and 3rd trimesters) are rarely teratogenic, but they may alter the growth and function of normally formed fetal organs and tissues.

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Vaccines and pregnancy

Immunization is as effective in pregnant women as in non-pregnant women. Influenza vaccination is recommended for all pregnant women in the 2nd or 3rd trimester during influenza epidemics. Other vaccines should be used in situations where the risk of infection is high for the woman and fetus, but the risk of adverse effects from the vaccine is low. Vaccines against cholera, hepatitis A and B, measles, mumps, plague, polio, rabies, diphtheria, tetanus, typhoid, and yellow fever can be used during pregnancy when the risk of infection is significant. Live virus vaccines are not given to pregnant women. Rubella vaccine, an attenuated live virus vaccine, can cause subclinical placental and intrauterine infection. However, no birth defects associated with rubella vaccination have been identified. Patients who were accidentally vaccinated early in pregnancy should not be advised to terminate their pregnancy based solely on the theoretical risk of vaccination. Chickenpox is an attenuated live virus vaccine that can potentially infect the fetus; the greatest risk is between the 13th and 22nd weeks of gestation. This vaccine is contraindicated during pregnancy.

Vitamin A and Pregnancy

Vitamin A at 5,000 IU/day, as found in prenatal vitamins, is not teratogenic. However, doses greater than 10,000 IU/day during early pregnancy may increase the risk of birth defects.

Social and illegal means

Smoking cigarettes and using alcohol or cocaine during pregnancy can cause significant problems in the fetus and newborn. Although the main metabolite of marijuana can cross the placenta, regional use of this substance does not increase the risk of congenital malformations, does not limit fetal growth, and does not cause postpartum neurobehavioral disorders. Many mothers of children with congenital heart defects stop using amphetamines during pregnancy, suspecting a possible teratogenic effect.

The effect of high caffeine intake on the risk of perinatal complications is unclear. Low levels of caffeine (eg, 1 cup of coffee per day) do not pose a risk to the fetus, but some data, which did not account for tobacco or alcohol consumption, suggest that high levels (>7 cups of coffee per day) increase the risk of stillbirth, preterm birth, low birth weight, and spontaneous abortion. Decaffeinated beverages theoretically reduce fetal risk. The use of the dietary sugar substitute aspartame during pregnancy has been controversial. The most common metabolite of aspartame, phenylalanine, is transferred to the fetus by active placental transport; toxic levels may cause mental retardation. However, when aspartame is consumed within the normal range, fetal phenylalanine levels are far from toxic. Moderate use of aspartame during pregnancy probably reduces the risk of fetal toxicity. However, pregnant women with phenylketonuria are prohibited from consuming aspartame (and thus phenylalanine).