Pregnancy Not Linked to Worse Disease in Women With HAE: Study

Treatment for HAE attacks during pregnancy found safe and effective

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by Andrea Lobo |

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A pregnant woman holding a teddy bear in one hand cradles her belly with the other hand.

Women with hereditary angioedema (HAE) who have been pregnant multiple times did not experience outcomes of significant disease worsening during pregnancy, a study in Turkey found.

A majority did report a greater frequency of HAE attacks during pregnancy, but this was not statistically significant, according to researchers.

In patients who did experience HAE attacks during pregnancy — including those affecting the larynx, which can impact breathing — treatment with plasma-derived C1 inhibitors was safe and effective.

The researchers recommended that preventive “[plasma-derived C1 inhibitors] should be administered before cesarean delivery,” adding that such treatment also may “be advised during pregnancy, particularly in women who are experiencing an increase in the number of attacks.”

The findings were described in “Clinical outcomes of Hereditary Angioedema on multiparous women,” a study published in the Journal of Cosmetic Dermatology.

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Pregnancy outcomes in HAE

HAE is a rare disorder characterized by unpredictable recurrent swelling attacks in the deeper layers of the skin. In severe cases, it can become life-threatening and require immediate medical attention.

The disease is caused by genetic mutations in the SERPING1 gene, which carries instructions to produce the C1 inhibitor (C1-INH) protein. These mutations can lower the production of C1-INH (HAE type 1) or result in the production of a less effective form of the protein (HAE type 2).

Mutations in the F12 gene, which contains instructions to make coagulation factor 12, also may cause HAE.

Women are usually more severely affected by HAE due to increased estrogen levels and hormonal fluctuations. The impact of pregnancy on the disease is unpredictable, however — and thus may dictate varying disease progression and treatment options to ensure positive outcomes.

According to guidelines, treatment with plasma-derived C1-INH products, such as Berinert, can be used to prevent and treat acute attacks in pregnant women.

To learn more, a team of researchers in Turkey evaluated the impact of HAE in 15 women who had been pregnant multiple times. Their median age was 36, and the median age at HAE symptom onset was 18. The time elapsed between the onset of symptoms and diagnosis was a median of 10 years.

In total, the researchers analyzed data from 88 pregnancies. Two women were pregnant 10 times, two nine times, and another two eight times. The remaining women had seven or fewer pregnancies.

From all the pregnancies studied, 72 healthy babies were born, without congenital problems. Of the 16 other pregnancies, 12 ended in spontaneous abortions or miscarriages, three resulted in a stillbirth, and one in neonatal death. Most babies — 57 infants or 75% — were born vaginally, while 19 (25%) were delivered by cesarean section.

The spontaneous abortion rate seen in this study (13.6%) was similar to the estimated rate for all clinically recognized pregnancies (10–20%), and none of the miscarriages were related to an HAE attack.

“Our study raises the possibility that the genetic abnormalities or impaired control of the contact system seen in HAE may not be associated with increased spontaneous abortions,” the team wrote.

However, these findings might be limited by the study’s small population size, so they must “be interpreted with caution,” according to the researchers.

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Treatments for HAE attacks

Regarding stillbirths, two of the three registered in this study occurred in the same woman, who was older than age 35 during both pregnancies. Thus, the findings indicate a possible relationship with advanced maternal age — a common risk factor for stillbirth.

For disease outcomes, 10 patients or two-thirds of the women reported an increase in the frequency of HAE attacks during pregnancy. These attacks rose from a mean of two per month to three — an effect that was not considered statically significant. Three patients described an amelioration of their symptoms, and two did not have HAE attacks while pregnant.

Most patients described a frequency of HAE attacks similar to that seen in their previous pregnancies, and affecting the same body regions. Nearly all patients (93%) reported at least one abdominal attack.

None of the women had been diagnosed with HAE prior to their first pregnancy. After diagnosis, HAE attacks were effectively treated with plasma-derived C1-INH in eight patients, including those occurring in the larynx. There were no reports of adverse events associated with treatment.

A total of 64 pregnancies occurred before patients received an HAE diagnosis. From these, the majority — 59 pregnancies, or about 92% — resulted in the birth of healthy babies. Six women, with a combined total of 34 pregnancies, were only diagnosed after their last pregnancy.

In seven of 11 cesarean sections performed after the disease was diagnosed, patients received short-term preventive treatment, which was not used in women who had vaginal deliveries. This procedure follows “the latest guidelines on HAE [that] now recommend [short-term prevention] with C1-INH before a cesarean section,” the researchers wrote.

Long-term preventive therapy with C1-INH was not used in any of the women who participated in this study. The team noted, however, that recent studies indicate that such treatment may be safely used during pregnancy and that it could be particularly useful in women experiencing a higher number of HAE attacks.

More than half of the women (60%) stated they experienced fewer HAE attacks while breastfeeding than they did during pregnancy. Two stopped breastfeeding due to frequent severe attacks.

“This work contributes to existing knowledge by providing data about [women with several pregnancies] with HAE,” the researchers wrote. “More research is needed to determine this issue.”