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Drug Use During Pregnancy

By Ravindu Gunatilake, MD, Avinash S. Patil, MD

More than 50% 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, and use of drugs during pregnancy is increasing. In general, drugs should not be used during pregnancy unless absolutely necessary because many can harm the fetus. About 2 to 3% of all birth defects result from drugs that are taken to treat a disorder or symptom.

Sometimes drugs are 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 drug. Before taking any drug (including over-the-counter 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 causing blood vessels to narrow (constrict) and thus reducing the supply of oxygen and nutrients to the fetus from the mother. Sometimes the result is 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.

  • They can also affect the fetus indirectly. For example, drugs that lower the mother's blood pressure may reduce blood flow to the placenta and thus reduce the supply of oxygen and nutrients to the fetus.

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.

How a drug affects a fetus depends on the fetus's stage of development and the strength and dose of the drug.

Timing and the Effects of Drugs During Pregnancy

Time Frame

Possible Drug* Effects

Status of the Fetus

Within 20 days after fertilization

An all-or-nothing effect (death of the fetus or no effect at all)

The fetus is highly resistant to birth defects.

3‒8 weeks after fertilization

Possibly no effect

A miscarriage

An obvious birth defect

A permanent but subtle defect that is noticed only later in life

The fetus's organs are developing, making the fetus particularly vulnerable to birth defects.

2nd and 3rd trimesters

Changes in the growth and function of normally formed organs and tissue

Unlikely to cause obvious birth defects Unknown long-term effects

Organ development is complete.

*Only certain drugs are likely to have harmful effects.

Categories of Risk for Drugs During Pregnancy

CATEGORY

DESCRIPTION

A

These drugs are the safest. Well-designed studies in people show no risks to the fetus.

B

Studies in animals show no risk to the fetus, and no well-designed studies in people have been done.

or

Studies in animals show a risk to the fetus, but well-designed studies in people do not.

C

No adequate studies in animals or people have been done.

or

In animal studies, use of the drug resulted in harm to the fetus, but no information about how the drug affects the human fetus is available.

D

Evidence shows a risk to the human fetus, but benefits of the drug may outweigh risks in certain situations. For example, the mother may have a life-threatening disorder or a serious disorder that cannot be treated with safer drugs.

X

Risk to the fetus has been proved to outweigh any possible benefit.

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 prevention of blood clots, the anticoagulant heparin is preferred to warfarin. Several safe antibiotics, such as penicillin, are available to treat infections.

Some drugs can have effects after they are stopped. For example, isotretinoin, a drug used to treat skin disorders, is stored in fat beneath the skin and is released slowly. Isotretinoin can cause birth defects if women become pregnant within 2 weeks after the drug is stopped. Therefore, women are advised to wait at least 3 to 4 weeks after the drug is stopped before they become pregnant.

Some Drugs That Can Cause Problems During Pregnancy *

Type

Examples

Problem

Antianxiety drug

Diazepam

When the drug is taken late in pregnancy, depression, irritability, shaking, and exaggerated reflexes in the newborn

Antibiotics

Fluoroquinolones (such as ciprofloxacin, ofloxacin, levofloxacin, and norfloxacin)

Possibility of bone and joint abnormalities (seen only in animals)

Nitrofurantoin

In women or fetuses with G6PD deficiency, the breakdown of red blood cells

Streptomycin

Damage to the fetus's ear, resulting in deafness

Sulfonamides (such as sulfasalazine and trimethoprim- sulfamethoxazole)

When the drugs are given late in pregnancy, jaundice and possibly brain damage in the newborn

With sulfasalazine, much less risk of problems

In women or fetuses with G6PD deficiency, the breakdown of red blood cells

Tetracycline

Slowed bone growth and permanent yellowing of the teeth

Occasionally, liver failure in the pregnant woman

Trimethoprim

Defects of the brain and spinal cord (neural tube defects), such as spina bifida

Anticoagulants

Heparin

Thrombocytopenia (a decrease in the number of platelets, which help blood clot) in the pregnant woman, possibly resulting in excessive bleeding

Warfarin

Birth defects

Bleeding problems in the fetus and the pregnant woman

Anticonvulsants

Carbamazepine

Some risk of birth defects, including neural tube defects (such as spina bifida)

Bleeding problems in the newborn (hemorrhagic disease of the newborn), which can be prevented if pregnant women take 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

Phenobarbital

Same as those for carbamazepine

Phenytoin

Same as those for carbamazepine

Valproate

Some (1%) risk of birth defects, including a cleft palate, neural tube defects (such as a meningomyelocele), and defects of the heart, face, skull, spine, and limbs

Antihypertensives

Angiotensin-converting enzyme (ACE) inhibitors (see Table: Antihypertensive Drugs.)

When the drugs are taken late in pregnancy, kidney damage in the fetus, a reduction in the amount of fluid around the developing fetus (amniotic fluid), and defects of the face, limbs, and lungs

Beta-blockers

When some beta-blockers are taken during pregnancy, a slowed heart rate, a low blood sugar level, and possibly slowed growth in the fetus

Low blood pressure in the mother

Calcium channel blockers

Inadequate growth before birth (growth restriction)

Thiazide diuretics

A decrease in the levels of oxygen, sodium, and potassium and in the number of platelets in the fetus's blood

Inadequate growth before birth

Chemotherapy drugs

Actinomycin

Possibility of birth defects (seen only in animals)

Busulfan

Birth defects such as underdevelopment of the lower jaw, cleft palate, abnormal development of the skull bones, spinal defects, ear defects, and clubfoot

Slowed growth

Chlorambucil

Same as those for busulfan

Cyclophosphamide

Same as those for busulfan

Doxorubicin

Heart problems, depending on the dose taken

Possibly birth defects (seen only in animals)

Mercaptopurine

Same as those for busulfan

Methotrexate

Same as those for busulfan

Vinblastine

Possibility of birth defects (seen only in animals)

Vincristine

Possibility of birth defects (seen only in animals)

Mood-stabilizing drug

Lithium

Possibly birth defects (mainly of the heart)

Lethargy, reduced muscle tone, poor feeding, underactivity of the thyroid gland, and nephrogenic diabetes insipidus in the newborn

Nonsteroidal anti-inflammatory drugs (NSAIDs)

Aspirin and other salicylates

Ibuprofen

Naproxen

When the drugs are taken in large doses, possibly miscarriages during the 1st trimester, a delay in the start of labor, premature closing of the connection between the aorta and artery to the lungs (ductus arteriosus), jaundice, necrotizing enterocolitis (damage to the lining of the intestine), and (occasionally) brain damage in the fetus and bleeding problems in the woman during and after delivery and/or in the newborn

When the drugs are taken late in pregnancy, a reduction in the amount of fluid around the developing fetus

Oral antihyperglycemic drugs

Chlorpropamide

Glyburide

Metformin

Tolbutamide

A very low blood sugar level in the newborn

Inadequate control of diabetes in the pregnant woman

When the drug is taken early in pregnancy by a woman with type 2 diabetes, possibility of increased risk of miscarriage

Sex hormones

Danazol

When this drug is taken very early in pregnancy, masculinization of a female fetus’s genitals, sometimes requiring surgery for correction

Diethylstilbestrol (DES)

Abnormalities of the uterus, menstrual problems, and an increased risk of vaginal cancer and complications during pregnancy in daughters

Abnormalities of the penis in sons

Synthetic progestins (but not the low doses used in oral contraceptives)

Same as those for danazol

Skin treatments

Etretinate

Birth defects, such as heart defects, small ears, and hydrocephalus (sometimes called water on the brain)

Isotretinoin

Same as those for etretinate

Intellectual disability

Risk of miscarriage

Thyroid drugs

Methimazole

An enlarged or underactive thyroid gland in the fetus

Scalp defects in the newborn

Propylthiouracil

An enlarged or underactive thyroid gland in the fetus

Radioactive iodine

Destruction of the thyroid gland in the fetus

When the drug is given near the end of the 1st trimester, a very overactive and enlarged thyroid gland in the fetus

Triiodothyronine

An overactive and enlarged thyroid gland in the fetus

Vaccines (live virus)

Vaccine for German measles (rubella) and chickenpox (varicella)

Potential infection of the placenta and developing fetus

Vaccines for measles, mumps, polio, or yellow fever

Potential but unknown risks

Other

Buprenorphine and methadone, which are opioids

Drowsiness in the newborn shortly after birth

Irritability and shaking (symptoms of drug withdrawal) in the newborn because at birth, passage of the opioid from the mother is stopped

Corticosteroids

Possibly a cleft lip when these drugs are taken during the 1st trimester

Pseudoephedrine (a decongestant)

Narrowing of the blood vessels in the placenta, possibly reducing the amount of oxygen and nutrients the fetus receives and thus resulting in inadequate growth before birth

Possible risk of a defect in the wall of the abdomen that allows the intestines to protrude outside the body (called gastroschisis)

Vitamin K

In women or fetuses with G6PD deficiency, destruction of red blood cells (hemolysis)

*Unless medically necessary, drugs should not be used during pregnancy. However, drugs can be essential to maintain the health of the pregnant woman and the fetus. In such cases, a woman should talk with her health care practitioner about the risks and benefits of the prescription drugs she is taking before she stops taking them. She should not stop taking them on her own.

Resources In This Article

Drugs Mentioned In This Article

  • Generic Name
    Select Brand Names
  • ACHROMYCIN V
  • FURADANTIN, MACROBID, MACRODANTIN
  • AZULFIDINE
  • AFRINOL, SUDAFED
  • IQUIX, LEVAQUIN, QUIXIN
  • No US brand name
  • CILOXAN, CIPRO
  • MYLERAN
  • ANTIVERT
  • FLOXIN OTIC
  • PANHEPRIN
  • TEGRETOL
  • OTREXUP
  • MARQIBO KIT
  • VALIUM
  • GLUCOPHAGE
  • COUMADIN
  • DILANTIN
  • BUPRENEX
  • LITHOBID
  • SOTRET
  • NOROXIN
  • DOLOPHINE
  • ADVIL, MOTRIN IB
  • DIABETA, GLYNASE
  • CYTOXAN (LYOPHILIZED)
  • THALOMID
  • ALEVE, NAPROSYN
  • PURINETHOL
  • DIABINESE
  • TAPAZOLE
  • LEUKERAN
  • LANOXIN
  • PAXIL
  • COMMIT, NICORETTE, NICOTROL
  • ADRENALIN
  • ERGOMAR
  • ELIXOPHYLLIN
  • PARLODEL
  • GENOPTIC
  • TYLENOL
  • KETALAR
  • DESOXYN
  • DURAMORPH PF, MS CONTIN