Association of Maternal Immune Activation With Pruritic Urticarial Papules and Plaques of Pregnancy: A Population‐Based Cohort Study

ABSTRACT Background Pruritic urticarial papules and plaques of pregnancy (PUPPP) is a common dermatosis of pregnancy, but its etiology remains poorly understood. This study aimed to identify whether maternal immune activation (MIA) is associated with PUPPP. Methods We conducted a retrospective cohort study of pregnant patients using a population‐based administrative cohort of all live births in California from 2016 to 2021. Patients with PUPPP were identified using ICD‐10 code O26.86. MIA was defined by ICD‐10 diagnoses of infection, autoimmune disease, or atopic disease during pregnancy. Poisson log‐linear regression was used to estimate crude and adjusted risk ratios (RR, aRR) for associations between PUPPP and MIA. Results Among 2,275,929 pregnancies, there were 3286 (0.14%) patients with PUPPP. Compared with patients without PUPPP, patients with PUPPP had higher rates of gestational hypertension (6.2% vs. 4.0%, p < 0.0001) and preeclampsia (10.9% vs. 5.2%, p < 0.0001). Atopy was associated with increased risk of PUPPP (aRR 1.7, 95% confidence interval [95% CI] 1.6–1.9), as was autoimmunity (aRR 1.6, 95% CI 1.2–2.1) and maternal infection (aRR 1.6, 95% CI 1.4–1.7). Patients with PUPPP were less likely to have a pre‐pregnancy body mass index (BMI) ≥ 30 kg/m 2 (21.2% vs. 25.4%, p < 0.0001) but more likely to exceed recommended gestational weight gain (64.3% vs. 52.4%, p < 0.0001). Conclusion MIA during pregnancy, including atopy, autoimmunity, and infection, was independently associated with increased risk of PUPPP. These findings suggest immune dysregulation may contribute to PUPPP pathogenesis. The association with excessive gestational weight gain further supports a potential role for inflammation secondary to connective tissue injury from abdominal distension. image