Pregnancy and Multiple Sclerosis: Predictors of Postpartum-Relapse

Abstract & Commentary

Synopsis: These studies provide additional data about the higher risk of relapse, and the greater potential for progression of disability following childbirth.

Sources: Vukusic S, et al. Pregnancy and Multiple Sclerosis (The PRIMS Study): Clinical Predictors of Post-Partum Relapse. Brain. 2004;127:1353-1360; Salemi G, et al. The Relapse Rate of Multiple Sclerosis Changes During Pregnancy: A Cohort Study. Acta Neurol Scand. 2004;110:23-26.

Vukusic and colleagues prospectively studied 227 patients who had multiple sclerosis (MS) for at least 1 year, and then had a full-term delivery. They reported a 2 year postpartum follow-up. Compared with the pre-pregnancy year, there was a reduction in the annualized relapse rate during pregnancy, most apparent in the third trimester (0.7 down to 0.2). This was followed by a marked increase in the first 3 months after delivery,1.2 and gradually returning to the pre-pregnancy rate over 9 to 12 months. A postpartum attack, in the first 3 months, was experienced by 28% of patients. Also of concern, the mean confirmed disability score of the total population progressed significantly from 1.3 pre-pregnancy, to 1.6 in the first 3 months postpartum, but then continued to increase to 1.8 at year 1, and 2.0 at year 2. There were 3 clinical variables that correlated with the occurrence of a postpartum attack: An increased relapse rate in the pre-pregnancy year, an increased relapse rate during pregnancy, and a higher disability score at pregnancy onset. Neither breast-feeding nor epidural anesthesia had an effect on relapses and disability.

In a second study by Salemi and colleagues, the investigators examined the mean yearly relapse-rate in 70 MS patients, for a total of 98 pregnancies. They confirmed that the mean annual relapse rate of 0.72, decreased significantly to 0.48 in the third trimester, and then increased to 0.84 in the puerperium period. The calculated relative risk of relapse was 0.63 during pregnancy, rebounding to 1.36 during puerperium.

Commentary

MS is a neurological disorder predominantly affecting young women of child-bearing age. There are recognized environmental determinants for disease pathogenesis, including complex hormonal effects on the immune system, which are poorly understood. For example, prior studies have shown a higher incidence of relapse and gadolinium-enhancing activity on brain MRI in women during their menstrual period. This may result from the drop in estrogen, which then leads to an increase in pro-inflammatory cytokines (such as IL-1 and IL-2) and T-cell activation. Similar hormonal effects may be related to postpartum flares of disease. During pregnancy, there may also be placental secretion of cytokines such as IL-10 and alpha-fetoprotein, that may downregulate the immune response. Autoimmune disorders, such as MS and rheumatoid arthritis, are ameliorated during pregnancy, but often worsen in the postpartum period. Many patients will have their initial presentation of disease during this vulnerable phase, although no clear statistics exist for patients who are diagnosed in puerperium.

The above studies provide additional data about the higher risk of relapse, and the greater potential for progression of disability following childbirth. The study by Vukusic et al provides helpful 2-year follow-up data, which details the significant worsening of disease postpartum. Physicians should counsel their patients that they may have increased symptoms following delivery, and additional support may desirable in caring for their newborn. Further, patients may need to interrupt breastfeeding for urgent drug intervention with MS relapses. Clinicians may choose to identify those patients at higher risk for relapse and disease progression, and treat aggressively with immuno-modulatory agents prior to the obvious onset of postpartum symptoms. — Brian R. Apatoff

Dr. Apatoff, Associate Professor of Neurology, New York Presbyterian Hospital- Cornell Campus, is Assistant Editor of Neurology Alert.