The pregnancy letter categories were retired in 2015

If you were told a medication was "Category C in pregnancy", you were told something that no longer exists in United States prescription labelling. The letters were removed by a rule that took effect on 30 June 2015, and the reason the agency gave was not that the drugs got safer. It was that the letters were being read as a ranking.

Significant findings

The Pregnancy and Lactation Labeling Rule was published as a final rule in the Federal Register on 4 December 2014 (79 FR 72064, docket FDA-2006-N-0515) and took effect on 30 June 2015. In the rule's own words, the categories had been "heavily relied upon by clinicians but misinterpreted, misunderstood, and erroneously used as a grading system where fetal risk increased from A to X", and they "gave the incorrect impression that drugs in the same category carried the same risk".

Three things about the change are easy to get wrong. It covers prescription drugs and biological products only - over-the-counter labelling never used the letters and is unaffected. The removal was phased: some labels had to drop the letter by 30 June 2018, others by 2019, and the outer bound was 30 June 2020, so "the letters were gone in 2015" is not quite true either. And what replaced them is prose, not a grade: subsection 8.1 Pregnancy, 8.2 Lactation, and a new 8.3 Females and Males of Reproductive Potential, with a required statement pointing to a pregnancy exposure registry where a scientifically acceptable one exists.

Whether the prose is better read than the letters is a fair question, and the honest answer is that it is measured only in part. Comparing the American, Australian and Swedish letter systems, Addis and colleagues found that only 61 of 236 drugs common to all three landed in the same category (Drug Saf 2000, doi:10.2165/00002018-200023030-00006) - the clearest evidence the letter was never a property of the drug. Five years after the rule, an AAAAI survey co-authored by FDA staff found 46% of responding clinicians knew the letters had been replaced, and 95% said they still used the letter system when prescribing (J Allergy Clin Immunol Pract 2020, doi:10.1016/j.jaip.2020.01.056). And a review of 290 products found the new Pregnancy subsections carried animal data in 89.7% of cases and human data in 10.7% (JAMA Netw Open 2020, doi:10.1001/jamanetworkopen.2020.15094). The label got longer; the underlying human evidence did not.

Worth asking

Nothing here is a reason to change anything you take. If a letter is still in your head for one of your medications, the concrete questions are: what does the current label's Pregnancy subsection actually say, is there a pregnancy exposure registry for this drug, and what is known from human data rather than animal data? Your prescriber, your obstetrician and your pharmacist can each answer part of that, and the label itself is public.