What are the FDA pregnancy categories?

FDA Pregnancy Categories

The FDA pregnancy letter categories (A, B, C, D, X) were officially discontinued in June 2015 and replaced with the Pregnancy and Lactation Labeling Rule (PLLR), which uses narrative summaries instead of letter grades. 1, 2, 3

Historical FDA Letter Categories (Pre-2015)

While these categories are no longer used for new drug approvals, understanding them remains relevant since many clinicians still reference them and older medications retain this classification system. 4 The original categories were:

Category A

• Controlled studies in pregnant women demonstrated no fetal risk in any trimester 1
• The safest designation, though very few drugs achieved this rating 1

Category B

• Either animal studies showed no fetal risk but human studies are lacking, OR animal studies showed adverse effects that were not confirmed in controlled human studies 1
• Examples include brimonidine 1

Category C

• Animal studies revealed adverse fetal effects and no controlled human studies exist, OR studies in both women and animals are unavailable 1
• Drugs should only be given if potential benefits justify potential fetal risks 1
• Most commonly assigned category; includes beta-blockers, prostaglandin analogs, carbonic anhydrase inhibitors, and parasympathomimetics 1

Category D

• Positive evidence of human fetal risk exists, but benefits from use in pregnant women may be acceptable despite the risk (e.g., life-threatening conditions or serious diseases where safer alternatives are ineffective) 1
• Examples include valsartan, which causes serious fetal risks including renal dysplasia, oligohydramnios, and growth retardation 5

Category X

• Studies in animals or humans demonstrated fetal abnormalities, OR evidence of fetal risk based on human experience exists, and the risk clearly outweighs any possible benefit 1
• Contraindicated in women who are or may become pregnant 1
• Avoid FDA category X medications and most category D medications unless potential maternal benefits outweigh fetal risks 1

Current FDA System (2015-Present)

The PLLR replaced letter categories with three narrative sections providing detailed risk-benefit information rather than oversimplified letter grades. 2, 3 The new format includes:

• Pregnancy subsection: Describes risks to the developing fetus, clinical considerations for labor and delivery, and background data 3
• Lactation subsection: Addresses risks to the breastfed infant 3
• Females and males of reproductive potential: Covers pregnancy testing, contraception, and infertility 3

Clinical Reality and Pitfalls

Despite the FDA's 2015 change, 95% of clinicians continue using the old letter category system to make prescribing decisions, largely due to lack of awareness of the new system. 4 Only 46% of surveyed prescribers were aware the letter categories had been replaced. 4

Common Pitfalls to Avoid

• Do not interpret letter categories as a grading system (A = best, X = worst) - this oversimplifies complex risk-benefit decisions 2, 4, 6
• Category C does not mean "unsafe" - it simply reflects insufficient human data, which applies to most medications 6
• Category D medications are not absolutely contraindicated - they may be appropriate when maternal benefits outweigh fetal risks in serious conditions 1
• In emergency or life-threatening maternal conditions, do not withhold necessary medications even if pregnancy safety data are incomplete 1, 5

Alternative Resources

When the FDA labeling is insufficient, consult specialized databases that provide more nuanced risk assessments based on primary literature rather than regulatory classifications:

• www.embryotox.de - combines scientific sources, expert opinions, and observational data 1
• www.safefetus.com - similar evidence-based approach 1
• Motherisk Program - creates peer-reviewed statements examining fetal outcomes and maternal risk-benefit profiles 6