HAE attack number, severity higher during pregnancy, breastfeeding
Normal vaginal delivery without anesthesia associated with a lower attack rate
Women with hereditary angioedema (HAE) see an increase in the number and severity of disease attacks during pregnancy and while breastfeeding, according to a study in Turkey.
A normal vaginal delivery without anesthesia was associated with a lower attack rate, leading researchers to argue that in the absence of “special indications for [cesarean section], clinicians should recommend vaginal delivery.” They also noted that short-term preventive therapy with plasma-derived C1 inhibitors “could be beneficial prior to cesarean delivery and vaginal delivery in case of severe symptoms during pregnancy.”
HAE is a rare genetic disease that features unpredictable recurrent swelling attacks in the deeper layers of the skin. Mutations in the SERPING1 gene, which carries instructions to produce the C1 inhibitor (C1-INH) protein, are the underlying cause of HAE types 1 and 2, and people with it have low levels or a defective C1-inhibitor protein, causing bradykinin to build up. Bradykinin is the signaling molecule that drives HAE swelling.
Women with HAE who are pregnant are more susceptible to episodes of disease worsening, called exacerbations. Treatment with plasma-derived C1-INH products can act as a first-line strategy to prevent attacks during pregnancy.
HAE with pregnancy, delivery, and breastfeeding
In this study, a team led by researchers at Istanbul University analyzed data from 48 HAE women who were followed between 1999 and 2021 at an outpatient clinic to better understand “the course of HAE during pregnancy, delivery, and breastfeeding.” The women were divided into two groups, depending on the timing of their HAE diagnosis. Those in the first group were diagnosed before becoming pregnant. Those in group 2 were diagnosed after becoming pregnant. The analysis included 88 full-term pregnancies, 21 miscarriages and six induced abortions, as well as three fetal deaths.
HAE type 1 was diagnosed in 43 women and HAE type 2 in five women. In most cases (54 pregnancies, 61.8%), the pregnancies occurred before an HAE diagnosis. Twelve women were under long-term preventive treatment with danazol, but 11 of them stopped taking the medication at least three months before conceiving. One woman continued treatment until the 20th week of pregnancy, when she became aware she was pregnant.
No miscarriages occurred during an HAE attack or due to danazol. There was an increase in the number of attacks during pregnancy in 33.3% of the miscarriages, however.
An analysis of all the patients showed that in 67% of the cases, patients reported an increase in the frequency of attacks, while 21.6% saw a reduction in attack rate. The severity of attacks worsened over time in 28 pregnancies. In 14, the attacks occurred more frequently in the first three months.
Diagnosis before, after pregnancy
In group 1, the median number of attacks increased significantly during pregnancy compared with the period preceding pregnancy (39 vs. 17). This number dropped again during the breastfeeding period, but was still significantly higher than immediately before pregnancy (24 vs. 17).
The first trimester was the period with the highest number of attacks (median, 15.5).
The attack severity was significantly higher during pregnancy than before pregnancy, as measured by a 10-point Visual Analogue Scale (VAS), where higher scores indicate increased severity (mean, 8.33 vs. 6.59). Mean VAS scores dropped in the breastfeeding period (7.32) and continued dropping after that (6.95), but remained higher than before pregnancy.
Most attacks that occurred during pregnancy affected the extremities (76.5%), abdomen (70.6%), and face (29.4%). Some attacks occurred in the larynx (8.8%) and genitalia (5.9%).
Attacks were successfully resolved in 22 pregnancies with plasma-derived C1-INH products and in three patients with fresh frozen plasma.
In group 2, there was an increase in the number of attacks in 32 pregnancies (59.3%), while in 13 (24.1%) the number decreased. No changes in attack rate were seen in nine pregnancies. The attacks’ severity was higher during pregnancy in 63% of the cases (34 pregnancies). It eased in nine cases.
A total of 47 women had a normal vaginal delivery, with no anesthesia in 39 cases and with spinal anesthesia in eight. A total of 41 deliveries occurred via cesarean section, with 20 conducted under general anesthesia and 21 under spinal anesthesia.
Among the 39 women who received no anesthesia during normal vaginal delivery, 34 didn’t receive any preventive treatment with plasma-derived C1-INH products. The women in this group had a lower attack rate compared with the five women who received preventive plasma-derived C1-INH.
The mother’s age, the number of pregnancies, and course of pregnancy weren’t associated with an increased risk of HAE attacks during delivery.
The findings show that normal vaginal delivery “is related to fewer HAE attacks and prophylaxis [preventive treatment] with C1-INH during [normal vaginal delivery] is not necessary to prevent a HAE attack,” the researchers wrote. “We believe that obstetricians should recommend [normal vaginal delivery] as a first choice in HAE.”