Perinatal Management and Clinical Outcomes of Hereditary Angioedema in Japan: A Case Series and Comprehensive Literature Review.

Hereditary angioedema (HAE) is a rare autosomal dominant disorder caused by C1-inhibitor (C1-INH) deficiency or dysfunction, leading to recurrent, nonpruritic edema of the skin, gastrointestinal tract, and airways. Estrogen fluctuations during pregnancy can exacerbate attacks; however, standardized perinatal management protocols remain underdeveloped in Japan. We report two cases of vaginal delivery in type I HAE and review 14 Japanese reports encompassing 19 pregnancies to clarify clinical characteristics, maternal-fetal outcomes, and evolving treatment strategies. Case 1 involved a primigravida with a marked increase in abdominal attacks during pregnancy (23 episodes), all treated with plasma-derived C1-INH (pdC1-INH). Short-term prophylaxis (STP) was administered before forceps-assisted delivery, which was completed without an attack; however, she experienced weekly postpartum attacks. Case 2, diagnosed via family screening, underwent three vaginal deliveries-one with forceps-over 7 years. Long-term prophylaxis was available in later pregnancies but not initiated due to low attack frequency and patient preference. STP with pdC1-INH was given at all deliveries, with only one mild lip swelling 3 years after the first birth and no postpartum attacks after the latter two. Among 17 Japanese pregnancies with available data, 9 (52.9%) showed increased attack frequency during gestation, particularly in early and late trimesters. Since 2013, STP at delivery-regardless of mode-was performed in 12 of 15 documented cases (80.0%). Postpartum attacks occurred in 6 of 16 cases (37.5%), warranting close monitoring. In Japan, since 2017, pdC1-INH has been the only approved agent for STP at delivery, recommended in guidelines for its proven safety and efficacy. Our findings support individualized, multidisciplinary perinatal care, with STP using pdC1-INH as a cornerstone for enhancing maternal safety and providing substantial psychological reassurance.