Pregnancy is a sensitive time for women, in particular for those with chronic diseases. The physiologic and hormonal changes that women experience during pregnancy can influence hereditary angioedema (HAE) symptoms in a variety of ways. There are cases of worsening, improvement, or no change at all in HAE clinical course.

“Fortunately, HAE-related complications seem rare; safely and effectively treating or preventing symptoms, anticipating HAE triggers, and avoiding iatrogenic complications during pregnancy is paramount,” said Marc A. Riedl, MD, MS, clinical director of the US HAEA Angioedema Center at UC San Diego.

Although most patients have onset of HAE symptoms in childhood and adolescence, some present for the first time during pregnancy. However, diagnosing HAE during pregnancy and the postpartum period can be challenging, and not uncommonly, pregnancy contributes to delayed or misdiagnosis of HAE.

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Recently, Irene Chair and colleagues have reported such a challenging case in the Canadian Medical Association Journal. “Despite our patient having clear evidence of bowel wall edema on CT [computerized tomography] scans and impressive, asymmetric swelling in the extremities and labia, the edema was never questioned or documented as angioedema, and no trials of therapy were considered.”

Read more about HAE diagnosis

“Our patient is one of the approximately 25% of patients with HAE who do not present with facial swelling during attacks; facial swelling is more easily recognized as angioedema.”

The patient, a 23-year-old female, showed reduced levels of C4 and C1 inhibitor (C1-INH) at 10 and 11 months postpartum. Genetic analysis revealed a likely pathogenic variant of SERPING1, c1475T > C, p.(Met492Thr).

The patient was diagnosed with type 1 HAE, and prophylactic C1-INH therapy and icatibant was initiated. Despite the delay in the diagnosis, she responded well to treatment.

Managing pregnant women with HAE can be challenging as therapeutic options are limited during pregnancy. Therefore, the safety of treatment plans must be carefully considered.

Given the particularities of managing HAE during prepregnancy, pregnancy, delivery, and postpartum, Marc A. Riedl, MD, MS, clinical director of the US HAEA Angioedema Center at UC San Diego, has published several management considerations as presented in the sections that follow.

Read more about HAE treatments

Prepregnancy

  • Discuss pregnancy with every woman of reproductive age who is diagnosed with HAE to anticipate any HAE-related issues and consider treatment options as needed.
  • Explain the HAE inheritance pattern (autosomal-dominant with variable expression) to potential parents so they become aware of the risk of children inheriting the condition.
  • Explain the variable course of HAE symptoms during pregnancy to patients/families.
  • Discuss HAE medication safety data for pregnancy and evidence-based guidelines for optimal safety while using plasma-derived C1-INH (pdC1-INH).
  • Adjust prescribed medications before pregnancy when planned and possible as medications with unknown safety in pregnancy should be avoided, particularly during the first trimester.
  • For assisted reproductive procedures, discuss the risk of exacerbating HAE symptoms with ovulation induction procedures and adjust management plans to include long-term prophylaxis with pdC1-INH, if needed.

Pregnancy

  • Review medication safety data during pregnancy and adjust management plans to maximize safety based on available data.
    • Note that in light of current safety data, pdC1-INH is the preferred medication for HAE treatment during pregnancy.
  • Ensure reliable access to HAE medication and a clear administration plan.
  • Inform patients of the possibility of a change in symptoms during pregnancy and ensure regular communication between patients and HAE clinical care teams to review symptom changes.
  • Adjust HAE treatment plans as needed; consider long-term prophylaxis with pdC1-INH for women who would benefit from it based on individualized care plans and shared-decision making.
  • Recommend short-term prophylactic treatment with pdC1-INH administered intravenously for invasive diagnostic procedures.
  • Monitor weight periodically and adjust dosing of weight-based HAE medication as needed.

Delivery and Postpartum

  • Communicate with patients and obstetrics teams regarding management plans surrounding childbirth to ensure proper planning.
  • Ensure access to acute HAE medication for use as needed during the delivery period.
  • pdC1-INH IV is recommended when forceps or vacuum assistance is required; otherwise, uncomplicated labor and normal spontaneous vaginal delivery rarely triggers HAE symptoms.
  • Short-term prophylaxis with pdC1-INH IV and regional anesthesia (when possible) are recommended for surgical delivery.
  • Monitor for HAE symptoms postpartum because of a potential increased risk of attacks and to ensure access to effective acute treatments.
  • pdC1-INH is recommended during breastfeeding based on current safety data.
  • Discuss the importance of complement system testing in children born to a parent with confirmed HAE at any time after birth (some levels may be difficult to interpret before 12 months of age).

References

Riedl MA. Hereditary angioedema during pregnancy: considerations in management. Immunol Allergy Clin North Am. 2023;43(1):145-157. doi:10.1016/j.iac.2022.05.011

Chair I, Lacuesta G, Nash CM, Cook V. A challenging diagnosis: hereditary angioedema presenting during pregnancy. Can Med Assoc J. 2022;194(37):E1283 LP-E1287. doi:10.1503/cmaj.220604

dermatologists Gastroenterologists gynecologists immunologists obstetricians Physicians