# Management of pregnancy, delivery and breast-feeding in hereditary angioedema: an analysis of 15 pregnancies with conventional treatment approaches and a case of Lanadelumab use

## TL;DR

This study examines how hereditary angioedema (HAE) affects pregnancy and finds that treatment with plasma-derived C1-inhibitor is safe, with a first documented case of Lanadelumab also showing positive outcomes.

## Contribution

The first documented use of Lanadelumab during pregnancy in HAE patients is reported, showing good tolerability and effectiveness.

## Key findings

- Plasma-derived C1-inhibitor was the most commonly used treatment and was well-tolerated during pregnancy.
- Lanadelumab use during pregnancy was well-tolerated and resulted in a healthy newborn with no complications.
- HAE symptoms varied during pregnancy, emphasizing the need for personalized treatment plans.

## Abstract

The course of hereditary angioedema (HAE) during pregnancy varies greatly. Limited treatment options complicate the management of HAE in this period. This study aimed to examine the clinical progression of HAE throughout the perinatal period in relation to management strategies. Additionally, we reported the first documented case of Lanadelumab (Takhzyro) therapy during pregnancy in a patient with HAE.

We performed an observational study at the University Hospital Zurich (a tertiary treatment center), in which we included 7 HAE female HAE patients. We analyzed 15 pregnancies of these women. The average maternal age at delivery was 33 years (range: 21–41), and the average gestational age was 40 + 3/7 weeks. Fourteen deliveries were spontaneous, with one requiring vacuum extraction. There were no miscarriages during the study period. Maternal C1-INH levels averaged 0.09 g/l (range: 0.04–0.16), and functional activity averaged 28% (range: 17–42%). Of the 15 newborns, 8 were HAE-positive. Their mean birth weight was 3170 g (±546), compared to 3618 g (±225) in HAE-negative children. No significant complications or adverse outcomes were observed in either group. Attack frequency during pregnancy increased in 4 cases, decreased in 7, and remained unchanged in 4. Most women (60%) received plasma-derived C1-inhibitor (Berinert) for acute management; 27% used it prophylactically during pregnancy. One patient received combination therapy with Lanadelumab/Takhzyro® and Berinert®, showing good tolerability and effectiveness. The pregnancy proceeded without complications and the child was born healthy at term with normal birth weight.

The variable evolution of HAE symptoms during pregnancy highlights the need for flexible and personalized treatment plans. Plasma-derived C1-inhibitor remains the recommended treatment during pregnancy due to its favorable therapeutic and safety profile. The first documented use of Lanadelumab during pregnancy was well tolerated and linked to positive outcomes for both mother and newborn. Although these findings are promising, further research is necessary to confirm the safety and effectiveness of Lanadelumab in this setting.