Antibiotics

Aminoglycosides

Ototoxicity (eg, damage to fetal labyrinth), resulting in deafness

—

Gray baby syndrome

In women or fetuses with G6PD deficiency, hemolysis

—

Fluoroquinolones

Possibly arthralgia; theoretically, musculoskeletal defects (eg, impaired bone growth), but no proof of this effect

—

In women or fetuses with G6PD deficiency, hemolysis

Contraindicated during the first trimester, at term (38 to 42 weeks), during labor and delivery, and just before onset of labor

In women or fetuses with G6PD deficiency, hemolysis

—

Ototoxicity

—

Sulfonamides

When given after about 34 weeks gestation, neonatal jaundice and, without treatment, kernicterus

In women or fetuses with G6PD deficiency, hemolysis

—

Slowed bone growth, enamel hypoplasia, permanent yellowing of the teeth, and increased susceptibility to cavities in offspring

Occasionally, liver failure in pregnant women

—

Increased risk of neural tube defects due to folate antagonism

Should be avoided during the first trimester

Anticoagulants

Thrombocytopenia and maternal bleeding

Compatible with pregnancy; does not cross placenta

Thrombocytopenia and maternal bleeding

Inadequate human data; possible harm to the fetus because these drugs appear to cross the placenta

No antidote for reversal; to be avoided during pregnancy

When given during the first trimester, fetal warfarin syndrome (eg, nasal hypoplasia, bone stippling, bilateral optic atrophy, various degrees of intellectual disability)

When given during the second or third trimester, optic atrophy, cataracts, intellectual disability, microcephaly, microphthalmia, and fetal and maternal hemorrhage

Absolutely contraindicated during first trimester of pregnancy

Antiseizure drugs†

Hemorrhagic disease of the newborn

Risk of congenital malformations including neural tube defects

—

No appreciable increased risk with dosage up to 600 mg/day

Compatible with pregnancy

No adequate data available on fetal risks associated with use in pregnant women [1]

Caution is advised, with consideration of whether the benefits outweigh the potential risks and of alternative treatment options

Minor skeletal malformations in animal studies, but no appreciable increased risk in humans

Compatible with pregnancy

Hemorrhagic disease of the newborn

Risk of congenital malformations

—

Congenital malformations (eg, cleft lip, genitourinary defects such as hypospadias, cardiovascular defects

Hemorrhagic disease of the newborn

Trimethadione

High risk of congenital malformations (eg, cleft palate; cardiac, craniofacial, hand, and abdominal defects) and risk of spontaneous abortion

Almost always contraindicated during pregnancy

Valproate

Major congenital malformations (eg, neural tube defects such as meningomyelocele; cardiac, craniofacial, and limb defects)

Antidepressants

Conflicting data on risk of congenital malformations from first trimester exposure

Dosing affected by hepatic or renal impairment

When given during the first trimester, increased risk of congenital malformations (particularly cardiac)

When given during the third trimester, discontinuation syndrome and persistent pulmonary hypertension of the newborn

Consideration of dose tapering during the third trimester in consultation with a mental health professional

When given during the third trimester, discontinuation syndrome and persistent pulmonary hypertension of the newborn

Consideration of dose tapering during the third trimester in consultation with a mental health professional

When given during the third trimester, discontinuation syndrome and persistent pulmonary hypertension of the newborn

Long half-life; drug-drug interactions possibly occurring for weeks after the drug is stopped

Consideration of dose tapering during the third trimester in consultation with a mental health professional

When given during the first trimester, increased risk of congenital malformations (particularly cardiac)

When given during the third trimester, discontinuation syndrome and persistent pulmonary hypertension of the newborn

Use during pregnancy not recommended by some experts*

Consideration of dose tapering during the third trimester in consultation with a mental health professional

When given during the third trimester, discontinuation syndrome and persistent pulmonary hypertension of the newborn

Consideration of dose tapering during the third trimester in consultation with a mental health professional

When given during the third trimester, discontinuation syndrome

Dosing greatly affected by hepatic or renal impairment

Consideration of dose tapering during the third trimester in consultation with a mental health professional

Antiemetics

No evidence of increased risk of congenital malformations

—

Abnormal muscle movements (extrapyramidal symptoms) or methemoglobinemia may potentially occur in neonates exposed during the third trimester and/or delivery [2]

Caution is advised, with consideration of whether the benefits outweigh the potential risks and of alternative treatment options

No significant teratogenic risk in animal studies

When given during the first trimester, possible risk of congenital heart disease (evidence is weak)

Used during pregnancy only for hyperemesis gravidarum when other treatments are ineffective

No significant teratogenic risk in animal studies

Generally no increased risk of congenital malformations

Possibly decreased platelet aggregation in neonates

—

Antifungals

No significant teratogenic risk in animal studies

Monitoring recommended for systemic toxicities (electrolyte imbalance, renal dysfunction) in the mother

Teratogenic at high doses in animal studies

No apparent increased risk of congenital malformations after a single dose of 150 mg/day

After higher doses (> 400 mg/day) taken for most or all of the first trimester, increased risk of various malformations

—

With oral use, adverse effects in animal studies

When applied to the skin, no significant risk of congenital malformations

Intravaginal use during the first trimester not shown to increase risk of congenital malformations

Adverse effects in animal studies

No significant risk of congenital malformations

Intravaginal use during the first trimester not shown to increase risk of congenital malformations

Antihistamine/anticholinergic drugs

Possible hypospadias (weak association)

—

Teratogenic in rodents, but no proof of this effect in humans

—

Antihyperglycemics (oral)

Chlorpropamide

Neonatal hypoglycemia

—

Neonatal hypoglycemia

Unknown long-term effects on fetus

Crosses the placenta

Neonatal hypoglycemia

Unknown long-term effects on fetus

Crosses the placenta; generally considered safe in pregnancy

Tolbutamide

Neonatal hypoglycemia

—

Antihypertensives

ACE inhibitors

When given during the second or third trimester, fetal hypocalvaria and hypoperfusion (which can cause renal defects), renal failure, and the oligohydramnios sequence (oligohydramnios, craniofacial deformities, limb contractures, and hypoplastic lung development)

—

Aldosterone antagonists

—

Beta-blockers [3]

—

Calcium channel blockers

Considered safe in pregnancy

Thiazide diuretics

Prevention of normal maternal volume expansion, reducing placental perfusion and contributing to fetal growth restriction

Neonatal hyponatremia, hypokalemia, and thrombocytopenia

—

Antineoplastic drugs‡

Actinomycin

Teratogenic in animals, but no proof of this effect in humans

—

Congenital malformations (eg, fetal growth restriction, mandibular hypoplasia, cleft palate, cranial dysostosis, spinal defects, ear defects, clubfoot)

—

—

No increased risk of major birth defects or pregnancy loss has been found with maternal use throughout pregnancy (including first trimester) for familial Mediterranean fever or other rheumatic diseases [6]

—

—

Teratogenic in animals and humans

Potential for dose-dependent cardiac dysfunction

Use during pregnancy not recommended

Effective contraception recommended during pregnancy and for 6 months after treatment of male or female partner

Congenital malformations (eg, fetal growth restriction, mandibular hypoplasia, cleft palate, cranial dysostosis, spinal defects, ear defects, clubfoot)

—

Congenital malformations (eg, fetal growth restriction, mandibular hypoplasia, cleft palate, cranial dysostosis, spinal defects, ear defects, clubfoot)

Contraindicated during pregnancy except for ectopic pregnancy, which requires an initial and a follow-up visit to confirm a diagnosis of ectopic pregnancy to avoid harming the fetus if the pregnancy is intrauterine

Effective contraception recommended for 8 weeks after the last dose

Teratogenic in animals, but no proof of this effect in humans

—

Teratogenic in animals, but no proof of this effect in humans

—

Antipsychotics and mood stabilizers

When given during the third trimester, associated with a risk for abnormal muscle movements (extrapyramidal symptoms) and/or withdrawal symptoms in newborns [7]

Symptoms in the newborn may include agitation, feeding problems, hypertonia, hypotonia, respiratory distress, somnolence, and tremor; these effects may be self-limiting or require hospitalization

Adverse effects in animal studies

When given during the first trimester, possibly limb malformations

When given during the third trimester, increased risk of extrapyramidal symptoms or withdrawal symptoms in the neonate

—

No evidence of adverse effects in animal studies

When given during the third trimester, increased risk of extrapyramidal symptoms or withdrawal symptoms in the neonate

—

Adverse effects in animal studies

When given during the first trimester, teratogenic (cardiac malformations)

When given later in pregnancy, lethargy, hypotonia, poor feeding, hypothyroidism, goiter, and nephrogenic diabetes insipidus in the neonate

—

Adverse effects in animal studies

When given during the third trimester, increased risk of extrapyramidal symptoms or withdrawal symptoms in the neonate

—

Adverse effects in animal studies

Based on limited data, no increased teratogenic risk

When given during the third trimester, increased risk of extrapyramidal symptoms or withdrawal symptoms in the neonate

—

Anxiolytics

Benzodiazepines

When given late in pregnancy, respiratory depression or a neonatal withdrawal syndrome that can cause irritability, tremors, and hyperreflexia

—

Nonsteroidal anti-inflammatory drugs (NSAIDs)

Fetal kernicterus

With high doses, possibly first-trimester spontaneous abortion, delayed onset of labor, premature closing of the fetal ductus arteriosus, jaundice, occasionally maternal (intrapartum and postpartum) and/or neonatal hemorrhage, necrotizing enterocolitis, and oligohydramnios

Use permitted for short durations during the second trimester if the fetus is carefully monitored

Does not appear to cause major malformations

Use in second trimester may increase risk of oligohydramnios

—

Opioids and partial agonists

Adverse effects but no teratogenicity in animal studies

Risk of a neonatal opioid withdrawal syndrome (neonatal abstinence syndrome)

Improved fetal outcomes compared with those when pregnant women use illicit substances

In neonates of women addicted to opioids, withdrawal symptoms possibly occurring 6 hours to 8 days after birth

With high doses given in the hour before delivery, possibly neonatal CNS depression and bradycardia

—

Adverse effects in animal studies

Risk of a neonatal opioid withdrawal syndrome

Improved fetal outcomes compared with those when pregnant women use illicit substances

Possible need for acute short-acting analgesics to supplement maintenance dosing during labor and delivery

Retinoids

High teratogenic risk (eg, multiple congenital malformations), spontaneous abortion, and intellectual disability

Contraindicated during pregnancy and in patients who may become pregnant

Sex hormones

When given during the first 14 weeks, masculinization of a female fetus’s genitals (eg, pseudohermaphroditism)

Contraindicated during pregnancy

Hormonal contraceptives

Exposure to estrogen-progestin contraceptives prior to conception or during pregnancy does not appear to be associated with an increased risk of major birth defects [8, 9]

No indication for use during pregnancy; should be discontinued

When taken in second or third trimester, associated with an increased risk of gestational diabetes (weak association) [12]

Contraindicated during first trimester of pregnancy

Exposure during pregnancy not associated with increased risk of major birth defects [13]

—

Thyroid medications

Preferred treatment of maternal hypothyroidism with established safety profile

—

Fetal goiter, facial dysmorphism,neonatal scalp defects (aplasia cutis), and other potential abnormalities

Contraindicated during first trimester of pregnancy

Fetal goiter and maternal hepatotoxicity and agranulocytosis

Typically used in the first trimester of pregnancy

Radioactive iodine (¹³¹I)

Destruction of the fetal thyroid gland or, when the drug is given near the end of the first trimester, severe fetal hyperthyroidism

Increased risk of childhood cancer

Absolutely contraindicated during pregnancy

Large fetal goiter, which may obstruct breathing in neonates

—

Triiodothyronine

Fetal goiter

Ultrasonography to monitor the fetus for potential goiter

Vaccines [14]

COVID-19 vaccines

No safety concerns for pregnant people, or for fetuses or neonates, found in early data from safety monitoring systems [15]

—

Inactivated influenza vaccine

No safety concerns for pregnant people or for fetuses or neonates [16]

—

Tetanus, reduced diphtheria toxoid, acellular pertussis (Tdap) vaccine

No safety concerns for pregnant people or for fetuses or neonates [17]

—

Live-virus vaccines such as the measles, mumps, and rubella vaccine; polio vaccine; varicella vaccine; and

With rubella and varicella vaccines, potential infection of the placenta and developing fetus

With other live vaccines, potential but unknown risks

Contraindicated in patients who are or may be pregnant

Others

Corticosteroids

When used during the first trimester, possibly orofacial clefts

—

No increased risk at usual doses

May be started in the first trimester for risk reduction

Possible transient increases in maternal aminotransferase levels, peripheral neuropathy

Not to be used with other hepatotoxic drugs

Placental vasoconstriction and possible risk of gastroschisis

—

Use considered for pregnant patients with early mild to moderate COVID-19, particularly for patients with at least one additional risk factor for severe disease

Congenital malformations

In the amount typically present in prenatal vitamins (5000 IU/day), no association with teratogenic risk, but possible risk with doses > 10,000 IU/day during early pregnancy

Vitamin K

In women or fetuses with G6PD deficiency, hemolysis

—