Pregnancy in mastocytosis

There has long been a suspicion that mast cells are involved in regulating the female reproductive cycle.  There are direct correlations between the contraction of uterine wall and serum histamine during pregnancy, as well as correlations to other mast cell mediators.  Mast cell activation and degranulation in the endometrium occurs immediately before and during menses.  Many allergic conditions, including asthma and angioedema, are exascerbated during menses, which is thought to be due to mast cell activation.

Throughout pregnancy, sex hormone levels change.  Sex hormones, such as estrogen, can directly influence mast cell activation and degranulation.  Mastocytosis patients often discontinue antihistamine and antimediator medications during pregnancy due to safety concerns.  In 2011, a study was published examining the effect of pregnancy on mastocytosis patients and of mastocytosis on pregnancy and delivery.

During pregnancy, 45% had itching; 40% had flushing; 24% had GI symptoms; and 9% had anaphylaxis.  22% of patients reported worsening symptoms throughout the pregnancy.  2% felt their symptoms were more frequent, while 18% developed new symptoms, and 2% had both new and more frequent symptoms.  New symptoms generally appeared in the first trimester, occasionally in the third.  Worsening of symptoms occurred in 3/6 women with CM and 7/35 with ISM with skin involvement.  One woman developed skin lesions during the third trimester and was diagnosed with ISM via bone marrow biopsy after delivery.

33% of women reported their symptoms had improved during pregnancy.  15% had complete resolution of symptoms, 15% had at least one symptom disappear and 3% had at least one symptom disappear but others worsen.  All resolutions occurred during the first trimester and lasted throughout the pregnancy with the exception of one patient.  In patients who had idiopathic anaphylaxis before pregnancy, 50% of them had no anaphylaxis while pregnant.  In those women who did have anaphylaxis during pregnancy, it was resolved without the use of epinephrine and did not cause early labor or complications.

Complete resolution of symptoms occurred in a patient with well differentiated SM (WDSM), ½ patients with ISM and no skin involvement, 9% of patients with ISM with skin involvement and 17% of patients with CM.  Partial resolution occurred in ½ patients with ISM and no skin involvement, 11% of patients with ISM with skin involvement and 17% of patients with CM.  In 6% of patients with ISM with skin involvement, at least one symptom disappeared while others worsened. 

45% had no change in symptoms during pregnancy (19/35 ISM with skin involvement patients, 1/6 CM patients.)  One patient experienced significant improvement of skin lesions in the first trimester. 

For women who worsened during pregnancy, mast cell symptoms continued to be worse after delivery for 50% of them.  Symptom resolution observed during pregnancy continued after delivery for 4/7 cases that had complete resolution and 3/6 cases that had partial resolution.  Complete resolution of symptoms occurred in two patients that had partial resolution during pregnancy.  There were five cases of worsening skin lesions after delivery. 

78% of infants were delivered vaginally and 22% by Caesarean.  Nine deliveries were induced with oxytocin (8/9) or dinoprostone (1.)  In 38% of cases, the patient took mast cell pre-meds at the onset of labor.  Anesthesia was used in 82% of cases, including epidural (32 cases), local (3) and general (2.)  11% of patients had mast cell attacks during or immediately after labor.  Anesthesia and medications used for labor seemed to be safe.  Only three women had mast cell reactions to epidural; of these, two had not take pre-meds.  Premedication at the initiation of labor is recommended.

3 out of 45 newborns were born premature and 4 out of 45 had low birth weights.  One had Down Syndrome; one had respiratory distress; one had jaundice; and one had heart rhythm abnormalities before birth.  There was no correlation between mother’s symptoms and outcome.  There was no correlation between anaphylaxis and outcome.  None of the children had skin lesions at birth, but one developed CM at the age of 5. 

The frequency of spontaneous pregnancy loss during first trimester (10-15), birth by Caesarean section (25%), prematurity (7.6%) and low birth weight (3-5.8%) were comparable to the rates in the general population.  Nonaggressive forms of mastocytosis did not appear to impact pregnancy outcome.

Reference:

Matito, A., et al.  Clinical Impact of Pregnancy in Mastocytosis: A Study of the Spanish Network on Mastocytosis (REMA) in 45 Cases.  Int Arch Allergy Immunol 2011;156:104-111.