Management of Pregnancy and Delivery in Patients With Hereditary Angioedema Due to C1 Inhibitor Deficiency

Abstract

Background and Objective: There is little information on pregnancy and delivery in patients with hereditary angioedema due to C1 inhibitor deficiency (C1INH-HAE). The aim of this study was to describe the effect of pregnancy and deliveries on symptoms of C1INH-HAE and review the need for and safety of treatments available during the study period. Methods: Retrospective review using a purpose-designed questionnaire of 61 C1INH-HAE patients from 5 hospitals specialized in the management of HAE in Spain. The outcomes measured were number of pregnancies, changes in symptoms during pregnancy and delivery, mode of delivery, type of anesthesia during delivery, treatments received, and tolerance of treatments. Results: We reviewed 125 full-term pregnancies (89 without a prior diagnosis of C1INH-HAE), 14 miscarriages, and 4 induced abortions. Patients reported an increased frequency of C1INH-HAE symptoms in 59.2% of pregnancies (74/125) and the presence of symptoms throughout pregnancy in 40% (50/125). Prophylactic C1INH-HAE therapy was used during 9 (7.2%) of the 125 pregnancies. Nine patients-in 11 pregnancies (8.8 %)-received treatment for acute attacks. Most deliveries (n=110, 88%) were vaginal. A cesarean section was necessary in 15 cases (12%). Short-term prophylaxis with pdhC1INH was administered before 14 deliveries (11.2 %); 111 deliveries (88.8 %) were performed without premedication and were well tolerated. Anesthesia was used in 51 deliveries (40.8%). Conclusions: Pregnancy has a variable influence on the clinical expression of C1INH-HAE. Attacks tend to occur more frequently but not to increase in severity. Vaginal delivery was mostly well tolerated. pdhC1INH prophylaxis should be administered prior to cesarean delivery and is also recommended before vaginal delivery if there are additional risk factors. pdhC1INH should always be available in the delivery room.

The international WAO/EAACI guideline for the management of hereditary angioedema—The 2017 revision and update

“…Infrequently, the manifestations of HAE‐1/2 first occur during pregnancy . Attack frequency observed during previous pregnancies is only in part predictive of that in subsequent pregnancies . Pregnant HAE‐1/2 patients require vigilant care and meticulous monitoring by an HAE expert.…”

“…Although contraindicated by label, there are isolated case reports about the administration of icatibant during pregnancy with no maternal or fetal adverse effects reported . SDP may be used when C1‐INH concentrate is not available and fresh frozen plasma when SDP is not available We recommend C1‐INH as the preferred therapy for HAE attacks during pregnancy and lactation.Evidence grade: D, strength of recommendation: strong, 100% agreement.…”

“…It is recommended to manage childbirth in the hospital setting, unless robust measures for prompt treatment HAE attacks are available. Although mechanical trauma and stress are known to trigger attacks, few women have developed angioedema during labor and delivery . Therefore, routine administration of preprocedural prophylaxis before uncomplicated natural delivery is not mandatory, but C1‐INH concentrate should be immediately available for on‐demand use.…”

Pregnancy and Postpartum in Hereditary Angioedema With C1 Inhibitor Deficit in Women Who Have No Access to Therapy

“…pdC1-INH should be administered prior to cesarean delivery and is also highly recommended for vaginal delivery in patients with additional risk factors or severe C1INH-HAE symptoms during pregnancy or previous deliveries. Therefore, therapy should always be available on demand in the delivery room and during hospitalization [11].…”

Hereditary Angioedema

“…Cinryze ® was approved in 2011 in Europe and in 2008 in the US for the use of long-term prophylaxis and its recommended dose for adolescents and adults is 1000 U every 3-4 days [48]. Recombinant human C1-inh, which is used in the treatment of atacks, was shown to be efective for long-term prophylaxis in preliminary data [62]. A possible side efect of long-term and high dose of C1-inh therapy is the undesirable immunization with this protein [48].…”