One Allergy, Two Paths: Navigating Penicillin Evaluation in Pregnant Patients Direct Challenges vs Penicillin Skin Testing in Pregnancy: A Controversies in Allergy Review

Contributing Author:

J Allergy Clin Immunol Pract. 2025 Nov 28:S2213-2198(25)01135-3. doi: 10.1016/j.jaip.2025.11.030. Online ahead of print.

ABSTRACT

Unverified penicillin allergy labels are common and can result in preventable maternal and neonatal adverse outcomes. The American College of Obstetricians and Gynecologists recommends evaluation of penicillin allergies in pregnancy to aid in preventing neonatal morbidity and mortality from Group B streptococcal disease. Historically, the standard-of-care procedure has been penicillin skin testing (PST) followed by penicillin challenge. However, direct oral challenge (DOC) is becoming increasingly accepted as the standard of care for patients with low-risk reaction histories. This narrative review presents a pro-con discussion regarding the use of DOCs during pregnancy. We highlight the large body of data supporting the use of PST followed by penicillin challenge in both pregnant and non-pregnant patients, noting that skin testing has captured sensitization to penicillin, potentially averting severe allergic reactions that could have occurred upon penicillin administration. On the other side of the debate, we underscore evidence from observational studies, randomized clinical trials, and meta-analyses in support of DOCs, especially in patients who have been appropriately risk-stratified, including studies focused on pregnant patients. We emphasize how DOCs may aid in addressing disparities in delabeling. Finally, we emphasize the importance of shared decision-making and other evidence-based approaches to enhance first-line antibiotic use during pregnancy.

PMID:41319903 | DOI:10.1016/j.jaip.2025.11.030