Pregnancy & Multiple Sclerosis

• Getting Pregnant
  by: Jenna Brooks

• Thyroid Disease During Pregnancy
  by: James Norman, M.D., F.A.C.S.

Objective
To present our experience with management of parturients with Multiple Sclerosis and to examine the role of IntraVenous ImmunoGlobulin (IVIg) in the prevention of postpartum exacerbations of the disease.

Methods
Fifteen patients with Multiple Sclerosis with a Relapsing/Remitting course were followed during pregnancy and 6 months postpartum. To prevent postpartum exacerbations, 14 of the patients had received IVIg after delivery.

Results
None of the patients who received postpartum IVIg relapsed during the 6 months after delivery.

None of the observed obstetric complications nor the operative deliveries could be related to the coexistence of Multiple Sclerosis.

Conclusion
Postpartum IVIg treatment is beneficial in preventing acute childbirth-associated exacerbations in patients with Relapsing/Remitting Multiple Sclerosis.

Furthermore, this disease does not seem to increase obstetric complications.

Background & Methods
Multiple Sclerosis often occurs in young women, and the effect of pregnancy on the disease is poorly understood.

We studied 254 women with Multiple Sclerosis during 269 pregnancies in 12 European countries.

The women were followed during their pregnancies and for up to 12 months after delivery to determine the rate of relapse per trimester and the score on the Kurtzke Expanded Disability Status Scale (range, 0 to 10, with higher scores indicating more severe disability).

The relapse rate in each trimester was compared with the rate during the year before the pregnancy.

The effects of Epidural Analgesia and breast-feeding on the frequency of relapse during the first three months post partum and the disability score at 12 months post partum were also determined.

Results
The mean (+/-SD) rate of relapse was 0.7+/-0.9 per woman per year in the year before pregnancy; it was 0.5+/-1.3 during the first trimester (P=0.03 for the comparison with the rate before pregnancy), 0.6+/-1.6 during the second trimester (P=0.17), and 0.2+/-1.0 during the third (P<0.001).

The rate increased to 1.2+/-2.0 during the first three months post partum (P<0.001) and then returned to the prepregnancy rate. The mean Kurtzke disability score worsened by 0.7 point during 33 months of follow-up, with no apparent acceleration during the post-partum period.

Neither breast-feeding nor Epidural Analgesia had an adverse effect on the rate of relapse or on the progression of disability in Multiple Sclerosis.

Conclusions
In women with Multiple Sclerosis, the rate of relapse declines during pregnancy, especially in the third trimester, and increases during the first three months post partum before returning to the prepregnancy rate.

• Comment in: N Engl J Med 1998 Jul 30;339(5):339-40

Eight women with Multiple Sclerosis were followed up through pregnancy. Clinical conditions, T-Cell subsets, and levels of ImmunoActive pregnancy-associated proteins were measured twice during the pregnancy and twice during the first postpartum year.

None of the women's conditions worsened during pregnancy, although one woman reported a slight increase of symptoms. Six of the eight women experienced relapses within the first 7 weeks after delivery.

The number and percent of CD8 Suppressor T-Cells were lower, and the CD4 Helper-CD8 Suppressor T-Cell ratio was higher in the pregnant patients with Multiple Sclerosis compared with pregnant control women throughout pregnancy and the first 6 months post partum.

There was no evident relationship between these parameters and clinical disease activity.

Levels of -FetoProtein, 2-pregnancy-associated GlycoProtein, and pregnancy-associated Plasma protein A, all ImmunoSuppressive proteins associated with pregnancy, were not significantly different in pregnant patients with Multiple Sclerosis and pregnant controls without Multiple Sclerosis.

The study suggested that the risk of clinical relapse after delivery may be higher than has been reported previously. Furthermore, although there were differences in Suppressor T-Cells, they were not predictably linked to changes in clinical disease activity.

This case history discussed Multiple Sclerosis that began during pregnancy, in a patient with a history of Juvenile Rheumatoid Arthritis.

The Etiology, Epidemiology, PathoPhysiology, Diagnosis, clinical course, and management of MS are reviewed from the point of view of an Obstetrician, with emphasis on the interaction between MS and pregnancy.

The similarities and differences between MS and Rheumatoid Arthritis, with respect to the effect of pregnancy on these diseases, is discussed.

Because of the generally beneficial effect of pregnancy on MS and Rheumatoid Arthritis, and the frequent exacerbations of both diseases seen in the postpartum period, further studies of the relationship between pregnancy and these diseases may provide clues to the Immunology and treatment of Multiple Sclerosis and other AutoImmune Diseases.

Gestation is a period of decreased risk for a relapse of MS, whereas the 3 months postpartum is a period of high risk. Taken together, the pregnancy year may also be a period of higher risk for relapse than non-pregnancy periods.

However, the lifetime risk rate does not appear to change because of pregnancy, and on the basis of current retrospective studies, long-term disability is not higher in pregnant women or even women experiencing relapses during the pregnancy year.

MS has little or no effect on the course of pregnancy or delivery, although patients with severe MS may have difficulty fully caring for their newborns.

The decision to become pregnant should be made by the patient and her husband after they are appropriately informed about the risks involved.

Multiple Sclerosis (MS), the most common acquired Neurological Disorder of young adults, often strikes young women in their childbearing years.

Despite the overlap of MS onset with the childbearing years of women, little is known about how women with MS make decisions about pregnancy and childbearing.

In an effort to understand the process of decision making in these women, an exploratory descriptive qualitative study was undertaken; 15 pregnant women with MS were interviewed about their decisions to become pregnant and the factors that entered into their decision-making processes.

Content analysis was used to identify and describe the fears and concerns of women with MS around the process of making decisions and about how the presence of MS had influenced that process.

The unpredictability of MS and the effect that pregnancy might have on MS was a strong theme that emerged from the analysis.

Although participants in this study had proceeded to become pregnant despite their fears related to the effect of pregnancy on the course of their MS, they continued to perceive their decision as risky.

The diagnosis of MS affected their previous plans for number of children as well as spacing of pregnancies.

Problem
Women with three or more unexplained miscarriages have a 60% chance of a subsequent live birth. IntraVenous ImmunoGlobulin (IVIG) has not been conclusively shown to improve this prognosis.

This study assessed the effect of IVIG in patients expected to have a poor outcome if untreated, i.e. women with five or more abortions, who have aborted after paternal Leukocyte immunization or who continue to abort despite expressing AntiPaternal Complement Dependent AntiBody.

Methods
Seventy-six women received IVIG in a dose of 400 mg/kg body weight, in one day (total 30-45 g) in the follicular phase of a cycle in which pregnancy was planned.

A booster dose was administered when pregnancy was diagnosed. Their results were compared to an untreated control group of 74 women.

Results
Thirty-five (49%) pregnancies in treated women have resulted in live births or passed their previous stages of abortion compared to 23 (31%) in control patients (P = 0.04).

Conclusions
These figures indicate that IVIG may prevent further miscarriages in this poor prognosis population.

These figures are especially significant considering the doubt concerning the efficacy of IVIG in patients with three miscarriages and therefore a relatively good prognosis.

The influence of pregnancy in Multiple Sclerosis has been a matter of controversy for a long time.

The Pregnancy in Multiple Sclerosis (PRIMS) study was the first large prospective study which aimed to assess the possible influence of pregnancy and delivery on the clinical course of Multiple Sclerosis.

We report here the 2-year post-partum follow-up and an analysis of clinical factors which might predict the likelihood of a relapse in the 3 months after delivery.

The relapse rate in each trimester up to the end of the second year post-partum was compared with that in the pre-pregnancy year. Clinical predictors of the presence or absence of a post-partum relapse were analysed by logistic regression analysis.

Using the best multivariate model, women were classified as having or not having a post-partum relapse predicted, and this was compared with the observed outcome.

The results showed that, compared with the pre-pregnancy year, there was a reduction in the relapse rate during pregnancy, most marked in the third trimester, and a marked increase in the first 3 months after delivery.

Thereafter, from the second trimester onwards and for the following 21 months, the annualized relapse rate fell slightly but did not differ significantly from the relapse rate recorded in the pre-pregnancy year.

Despite the increased risk for the 3 months post-partum, 72% of the women did not experience any relapse during this period. Confirmed disability continued to progress steadily during the study period.

Three indices, an increased relapse rate in the pre-pregnancy year, an increased relapse rate during pregnancy and a higher DSS (Kurtzke's Disability Status Scale) score at pregnancy onset, significantly correlated with the occurrence of a post-partum relapse.

Neither Epidural analgesia nor breast-feeding was predictive. When comparing the predicted and observed status, however, only 72% of the women were correctly classified by the multivariate model.

In conclusion, the results for the second year post-partum confirm that the relapse rate remains similar to that of the pre-pregnancy year, after an increase in the first trimester following delivery.

Women with greater disease activity in the year before pregnancy and during pregnancy have a higher risk of relapse in the post- partum 3 months.

This is, however, not sufficient to identify in advance women with Multiple Sclerosis who are more likely to relapse, especially for planning therapeutic trials aiming to prevent post-partum relapses.

Acute exacerbations may complicate the course of pregnancy and the postpartum period in patients with Relapsing/Remitting Multiple Sclerosis (RRMS).

To evaluate relapse rate and the effect of immunomodulatory treatment with IntraVenous ImmunoGlobulin (IVIg) during pregnancy and the postpartum period we retrospectively analyzed the data of 108 pregnant RRMS patients.

Group I patients were not treated,

Group II patients were treated with IVIg 0.4 g/kg body weight/day for 5 consecutive days within the first week after delivery with additional booster doses of 0.4 g/kg body weight/day at 6 and 12 weeks postpartum (defined as 12 weeks after labor),

and Group III patients were treated continuously with IVIg during gestation and the postpartum period

(0.4 g/kg body weight/day for 5 consecutive days within the 6-8 weeks of gestation with additional booster doses of 0.4 g/kg body weight/day once every 6 weeks until 12 weeks postpartum).

All patients underwent antenatal care and fetal UltrasonoGraphic surveillance examinations. Relapse rate per woman per year during the pregnancy and the postpartum period as well as neonatal outcome data and IVIg related adverse events were analyzed.

Relapse rate per woman per year for patients treated with IVIg for the whole pregnancy and postpartum period (Group III, N = 28) compared with the untreated Group I patients (N = 39) were as follows:

first trimester 0.43 vs. 0.72, second trimester 0.15 vs. 0.61, third trimester 0.0 vs. 0.41, and postpartum period 0.28 vs.1.33 (p < 0.05).

Patients treated with IVIg only during the postpartum period (Group II, N = 41) also showed a decrease in relapse rate compared with untreated Group I patients, 0.58 vs. 1.33 (p = 0.012).

The mean maternal age, disease duration, gestational age at delivery and fetal delivery weight did not significantly differ between the three groups.

Mode of delivery, Obstetrical complications, the use of Epidural analgesia and breast-feeding, did not affect postpartum relapse rate.

No severe adverse events were associated with IVIg treatment either during the pregnancy or postpartum period for the patients and newborns.

We conclude that in RRMS patients IVIg treatment could be considered as an optional treatment to reduce the incidence of pregnancy and postpartum-related relapses. Further randomized double-blind studies are needed to confirm our findings.

Objective
To estimate the national occurrence of pregnancies in women with Multiple Sclerosis (MS) and Epilepsy and to compare these pregnancy outcomes cross-sectionally with those in women with pregestational Diabetes Mellitus (DM) and the general obstetric population.

Methods
We studied the 2003-2006 Nationwide Inpatient Sample, of the Healthcare Cost and Utilization Project, to estimate the number of deliveries in women with MS, Epilepsy, DM, and the general obstetric population.

Pregnancy outcomes included length of hospital stay, Hypertensive Disorders including Preeclampsia (HTN), Premature Rupture Of Membranes (PROM), Intrauterine Growth Restriction (IUGR), and cesarean delivery.

Multivariable regression analyses used maternal age and race/ethnicity as covariates.

Results
Of an estimated 18.8 million deliveries, 10,055 occurred in women with MS, 4,730 with Epilepsy, and 187,239 with DM.

MS was associated with mildly increased odds of antenatal hospitalization (odds ratio [OR] 1.3, 95% confidence interval [CI] 1.2-1.5),

IUGR (OR 1.7, 95% CI 1.2-2.4), and cesarean delivery (OR 1.3, 95% CI 1.1-1.4).

Similarly, Epilepsy was associated with increased rates of antenatal hospitalization (OR 3.0, 95% CI 2.6-3.5), IUGR (OR 1.9, 95% CI 1.2-3.3), and cesarean delivery (OR 1.5, 95% CI 1.3-1.9).

HTN and PROM were not increased in either group. DM was associated with an increased risk of all adverse outcomes. Length of stay was modestly increased in all groups compared with controls.

Conclusion
In this large national database study of pregnancy outcomes in women with Multiple Sclerosis and Epilepsy.

Rates of intrauterine growth restriction and cesarean delivery were only marginally higher than the general obstetric population without increases in other adverse outcomes.