Effect seen through six months, but not after

Exclusive breast feeding in the first 2 months postpartum was associated with lower risk of relapse in women with relatively mild multiple sclerosis (MS), a prospective registry study found.

Breastfeeding without any supplementation for 2 months or more following delivery, seen in 36% of participants, reduced the risk of relapse in the first 6 months postpartum (adjusted HR 0.37, P=0.009).

The association did not persist beyond 6 months, and no increase in relapse rate was seen in the first 3 months postpartum in the entire cohort, including those with sub-optimally controlled disease before pregnancy.

Markers of disease severity increased the risk, but resuming disease modifying therapy (DMT) — most moderately effective — had no effect on relapse rate.

“Most women diagnosed with MS today can have children without incurring an increased risk of relapses,” wrote Annette Langer-Gould, MD, PhD, of the Southern California Permanente Medical Group in Los Angeles, and coauthors in Neurology. “Women with suboptimal disease control before pregnancy may benefit from highly effective DMTs that are compatible with pregnancy and lactation. Women with MS should be encouraged to breastfeed exclusively.”

In an accompanying editorial, Ruth Dobson, MRCP, PhD, of the Queen Mary University of London, and Ellen Mowry, MD, of Johns Hopkins University in Baltimore, noted that nearly half the women did not have an MS relapse in the 2 years before pregnancy. “The current study provides increasing evidence that among women without features of very active MS before pregnancy or who are using no DMT or injectable therapies before conception, most will not have a postpartum relapse, and exclusive breastfeeding early in the postpartum period is associated with a reduced risk of relapse in the first 6 months,” they wrote.

Previous studies have shown mixed results and been limited by sample size and indication, referral, and selection bias. Breastfeeding exclusively for 2 or more months was associated with a reduced risk of postpartum relapses in a German registry study of 201 women which concluded, “exclusive breastfeeding is a modestly effective MS treatment with a natural end date.” Another study in Italy with data on 423 pregnancies found that postpartum relapses were predicted only by relapses before and during pregnancy, and speculated that “the reported association between breastfeeding and a lower risk of postpartum relapses may simply reflect different patient behavior, biased by the disease activity.”

Some evidence has also suggested that resuming DMTs during the postpartum year produced no relapse benefit.

Langer-Gould and colleagues took on the question of postpartum relapse, DMT, and breastfeeding by analyzing data from the electronic health records of Kaiser Permanente Southern and Northern California. They included 466 pregnancies in 375 women with MS (mean age 32) who gave birth between January 2008 and April 2016, including all women who met 2010 McDonald criteria for MS, of any subtype (or clinically isolated syndrome, CIS) at the onset of or during pregnancy.

Most women (84%) had RRMS, with CIS in 15%. No relapse within the last 2 years before pregnancy was seen in 45%, while 40% had MS-related disability, and 67% had sub-optimally controlled disease at pregnancy onset.

Overall, the average annualized relapse rate (ARR) declined during pregnancy, compared with the 2 years before conception and returned to pre-pregnancy rates 4–6 months postpartum. Nearly three-fourths (74%) of pregnancies were followed by a relapse-free postpartum year, with 1 relapse in 22%.

DMT treatment at any time since diagnosis was found in 70%; almost half (48%) had discontinued treatment a year or more before pregnancy. Of pregnancies exposed to any DMT in the year before pregnancy, 94% used IFN-beta or glatiramer acetate; 13 women were treated with highly effective DMTs.

Predictors of postpartum relapse in the first postpartum year included MS-related disability on examination before pregnancy (adjusted HR 1.79, 95% CI 1.22-2.60, P=0.0026). A high relapse frequency preceding pregnancy was also associated with relapse throughout the postpartum year (adjusted HR 1.64, 95% CI1.07-2.51, P=0.0227).

“Although markers of more severe disease in the year before pregnancy (increased relapse frequency and MS-related disability) and relapses during pregnancy were associated with an increased risk of postpartum relapse, the associations were modest,” the editorialists wrote.

Most (87%) women breastfed; 36% breastfed exclusively for 2 or more months. Women who breastfed exclusively had fewer relapses (n=15, 9%) in the first 6 months postpartum compared with those who breastfed nonexclusively (n=41, 17%) or not at all (n=15, 25%, P= 0.0054).

During the second half of the postpartum year, the proportion of women who had their first postpartum relapse was very similar among women who breastfed exclusively for at least the first 2 months postpartum (n=17, 10.2%), those who breastfed nonexclusively (n=29, 12.1%), and those who did not breastfeed (n=6, 10.2%).

DMT use during the postpartum year had no effect on the risk of postpartum relapses during the entire postpartum year (adjusted HR 0.89, 95% CI 0.56-1.43, P=0.63).

“Resumption of DMT in the postpartum period did not seem to be meaningfully associated with the risk of postpartum relapse, although notably, the median time to restarting DMT was 88 days,” the editorialists observed.

Limitations include lack of imaging and subclinical disease activity may have been missed. Also, registry study design precludes cause and effect inferences. Many participants had mild MS and it is possible that those with more active disease or using higher-efficacy therapies were less likely to become pregnant.

“Whether the influence of pregnancy, the postpartum period, or exclusive breastfeeding on relapse risk is similar in those individuals with more active MS or among those using higher-efficacy therapies before pregnancy remains unknown,” the editorialists noted.

  1. Exclusive breast feeding in the first 2 months postpartum was associated with lower risk of relapse in women with relatively mild multiple sclerosis (MS) during the first 6 months postpartum.

  2. The association did not persist beyond 6 months, and no increase in relapse rate was seen in the first 3 months postpartum in the entire cohort.

Paul Smyth, MD, Contributing Writer, BreakingMED™

This study was supported by the National Multiple Sclerosis Society.

Langer-Gould has received grant support and awards from the NIH, the Patient-Centered Outcomes Research Institute, and the National MS Society.

Dobson has received honoraria and/or support for speaking or other educational activities from Biogen, Merck, Teva, and Sanofi Genzyme. She has received honoraria for serving on advisory boards from Merck and Biogen. She has research support from Biogen, Merck, and Celgene for investigator-initiated research. Mowry reports serving as site principal investigator (PI) for clinical trials or studies sponsored by Biogen. She has research support from Sanofi Genzyme and Biogen for investigator-initiated trials, and she receives free medication for a clinical trial, of which she is PI, from Teva Neuroscience. She receives royalties for editorial duties from UpToDate.

Cat ID: 36

Topic ID: 82,36,730,36,41,192