Pregnancy Risks Not Likely to Rise With Early DMT Use, Study Finds

The rates of pregnancy complications are not higher in women with multiple sclerosis (MS) who were using disease-modifying therapies (DMTs) in the earliest stages of pregnancy, a study reported.

The study, “Pregnancy outcomes after early fetal exposure to injectable first-line treatments, dimethyl fumarate or natalizumab in Danish women with multiple sclerosis,” was published in the European Journal of Neurology. The work was funded by the Danish Multiple Sclerosis Society.

MS disproportionately affects women, and it most commonly develops between the ages of 20 and 50. As such, many people with MS wanting to become pregnant have to navigate how best to go through pregnancy while also managing their disease.

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Although more than a dozen approved MS therapies are available, most either are known to be toxic in pregnancy, or they have not been rigorously studied in pregnant people and their safety profile is unclear.

The only DMTs generally considered safe in pregnancy are interferon treatments and glatiramer acetate (sold as Copaxone, among others), which are older, injection medicines with well-established safety profiles that are commonly used as first-line treatment in MS.

Interferons, Copaxone commonly taken in early weeks of MS pregnancy

Using the Danish Multiple Sclerosis Registry and other national databases (from Jan. 1, 1997, to Dec. 31, 2018), a neurology team at Copenhagen University Hospital identified data on 1,009 pregnancies among 704 women with MS. In all of these pregnancies, the fetus was exposed to a disease-specific DMT — meaning there was some overlap between DMT use and the pregnancy.

Most of these patients were treated with interferons or Copaxone. The study also included some women using Tecfidera (dimethyl fumarate) or Tysabri (natalizumab).  Median fetal exposure — defined as treatment on or after a last menstrual period — to interferons was 6.8 weeks, 7.7 weeks with Copaxone, 5 weeks for Tecfidera, and 1.9 weeks with Tysabri.

The scientists compared outcomes from these pregnancies with outcomes from 1,073 pregnancies in 709 MS patients who were very similar in age and disease duration, but where there was no fetal DMT exposure. A third group included 91,112 pregnancies to 40,845 women who did not have MS, serving as controls.

In the exposed, unexposed, and control groups, the rates of live birth were comparable: 70.5%, 77.2%, and 70.2, respectively. Rates of spontaneous abortions, stillbirth, and ectopic pregnancies — when a fetus implants outside of the uterus — also were very similar among the three groups.

Other adverse outcomes, such as a fetus being small for its gestational age, congenital malformations, placenta complications, and a newborn requiring medical attention also were not different between exposed and unexposed MS patients and with controls.

However, rates of elective cesarean delivery (C-section) in both MS patient groups were markedly higher than among women without the disease: 17.2% and 16.6% for exposed and unexposed MS patients and 8.6% for controls.

“Possible explanations for the increased rate of elective C-sections among women with MS might include MS-related symptoms such as fatigue and/or neuromuscular perineal weakness which could prompt both the clinician and women to be precautious,” the researchers wrote.

Outcomes for 58 pregnancies with exposure to Tecfidera were highlighted, as animal studies have suggested Tecfidera can harm a developing fetus. The researchers noted that in patients, “data on [Tecfidera] exposed pregnancies are very sparse and only few studies have reported outcomes.”

Among the 58 Tecfidera-exposed pregnancies, 15 ended in elective abortion and nine in miscarriage. All of the remaining 34 pregnancies resulted in birth at term; three of the babies had congenital malformations or were unusually small, but the 31 other infants showed no apparent adverse effects.

Excluding patients age 35 or older in either the exposed or unexposed group, researchers found that among women using this DMT during the first weeks of pregnancy “the prevalence of spontaneous abortion (10.2%) or CM [congenital malformations] (2.4%)” was lower than that reported in previous studies “and in concordance with those of the general population.”

Our study, the scientists concluded, “confirms that newborns exposed to injectable first-line treatments, dimethyl fumarate or natalizumab demonstrate a similar prevalence of stillbirths, spontaneous abortions, placenta complications, SGA [small for gestational age], low Apgar score, preterm birth and CM as the general population.” Apgar scores are used to rate a newborn’s “normality” based on vital signs, muscle tone, and coloration.

The scientists also noted that the rates of elective C-sections were particularly high among MS patients on Tysabri. “This might be due to a higher disease burden in these women hence a more precautious approach regarding their birth plan,” they wrote.