Pregnancy and fetal outcomes after interferon-β exposure in multiple sclerosis

Amato, Maria Pia; Portaccio, Emilio; Ghezzi, Angelo; Hakiki, Bahia; Zipoli, Valentina; Martinelli, Vittorio; Moiola, Lucia; Patti, Francesco; Mantia, L. La; Mancardi, Gianluigi; Solaro, Claudio; Tola, Maria Rosaria; Pozzilli, Carlo; Giglio, Laura De; Totaro, Rocco; Lugaresi, Alessandra; Tommaso, V. Di; Paolicelli, Damiano; Marrosu, Maria Giovanna; Comı, Gıancarlo; Pellegrini, Fabio; Trojano, María

doi:10.1212/wnl.0b013e3181fd62bb

Cited by 145 publications

(164 citation statements)

References 28 publications

Supporting

Mentioning

150

Contrasting

Unclassified

Order By: Relevance

“…However, the significant differences between the control and experimental groups in terms of yolk sac diameter, crown-rump length and head length parameters revealed that embryos growing in IFNb-1a and IFNb-1b added medium had lower body size. When evaluated in this respect, our results were consistent with previous studies investigating the relationship between the use of IFNb and its teratogenicity during pregnancy [2,4]. They determined that using IFNb during the first 3 months of pregnancy caused low birth weight and short stature compared to the healthy control group.…”

Section: Discussionsupporting

confidence: 91%

“…Studies in humans, Amato et al [2] demonstrated that IFNb use during pregnancy did not increase the risk of spontaneous miscarriage; however, it was related to low birth weight and short birth length. Boskovic et al [4] showed that the usage of IFNb in the first 3 months of pregnancy caused foetal loss and low birth weight when compared to healthy pregnant control group and unexposed pregnant women with MS. On the contrary, Hellwig et al [17] stated that congenital anomalies were in the normal rate in pregnant women used IFNb and concluded the drug not to have any teratogenic risk.…”

Section: Discussionmentioning

confidence: 99%

“…Several studies showed that using IFNb during the first 3 months of pregnancy increased the risk of stillbirth and low birth weight [2,4]. However, there are limited studies investigating their teratogenic effects during pregnancy, thus IFNb-1a, IFNb-1b have received category C by FDA [12].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The potential teratogenic effects of interferon beta-1a and interferon beta-1b on in vitro embryonic development

et al. 2016

View full text Add to dashboard Cite

show abstract

Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

The potential teratogenic effects of interferon beta-1a and interferon beta-1b on in vitro embryonic development

et al. 2016

View full text Add to dashboard Cite

show abstract

“…This finding may be explained by subclinical levels of circulating AQP4-IgG, which may be present years before clinical presentation. 24,25 The miscarriage rate of 42.9% is outside the 95% CI that would be expected if the true miscarriage rate post-NMOSD was equal to reported rates in multiple sclerosis (expected 95% CI 1.29%-40.9%) 26,27 and just within the expected range calculated from published rates in systemic lupus erythematosus (expected 95% CI 2.56%-45.5%). 28 This suggests that the miscarriage rate in patients with NMOSD is higher than in patients with multiple sclerosis, although larger prospective studies with adequate control groups are needed to test this hypothesis.…”

mentioning

confidence: 54%

Pregnancy outcomes in aquaporin-4–positive neuromyelitis optica spectrum disorder

et al. 2016

View full text Add to dashboard Cite

Objective: To investigate the association between neuromyelitis optica spectrum disorder (NMOSD) and pregnancy outcome.Methods: An international cohort of women with aquaporin-4 antibody-positive NMOSD and $1 pregnancy was studied retrospectively. Multivariate logistic regression was used to investigate whether pregnancy after NMOSD onset was associated with an increased risk of miscarriage (cohort of 40 women) or preeclampsia (cohort of 57 women).Results: Miscarriage rate was higher in pregnancies after NMOSD onset (42.9% [95% confidence interval 17.7%-71.1%] vs 7.04% [2.33%-15.7%]). Pregnancies conceived after, or up to 3 years before, NMOSD onset had an increased odds ratio of miscarriage (7.28 [1.03-51.6] and 11.6 [1. , respectively), independent of maternal age or history of miscarriage. Pregnancies after, or up to 1 year before, NMOSD onset ending in miscarriage were associated with increased disease activity from 9 months before conception to the end of pregnancy, compared to viable pregnancies (mean annualized relapse rate 0.707 vs 0.100). The preeclampsia rate (11.5% [6.27%-18.9%]) was significantly higher than reported in population studies. The odds of preeclampsia were greater in women with multiple other autoimmune disorders or miscarriage in the most recent previous pregnancy, but NMOSD onset was not a risk factor.Conclusions: Pregnancy after NMOSD onset is an independent risk factor for miscarriage, and pregnancies conceived at times of high disease activity may be at increased risk of miscarriage. Women who develop NMOSD and have multiple other autoimmune disorders have greater odds of preeclampsia, independent of NMOSD onset timing. Neurology ® 2016;86:79-87 GLOSSARY AQP4 5 aquaporin-4; ARR 5 annualized relapse rate; CI 5 confidence interval; IgG 5 immunoglobulin G; NMO 5 neuromyelitis optica; NMOSD 5 neuromyelitis optica spectrum disorder; ON 5 optic neuritis; OR 5 odds ratio.Neuromyelitis optica spectrum disorder (NMOSD) is a severe recurrent antibody-mediated inflammatory disorder of the CNS, mainly characterized by optic neuritis (ON) and longitudinally extensive transverse myelitis, 1 but also affecting other areas in the CNS (e.g., brainstem and hypothalamus). The presence of immunoglobulin G (IgG) that binds to aquaporin-4 (AQP4), 2,3 known to be key in the pathogenic process of this disorder, distinguishes NMOSD from other CNS inflammatory disorders.1 NMOSD is up to 8 times more prevalent in women, 4 many of whom have active disease during childbearing years. [5][6][7] Recently, experimental and clinical reports have demonstrated the presence of AQP4 in human and animal placenta, and have linked AQP4-mediated placental inflammation to fetal death. [8][9][10] It is clear that the annualized relapse rate (ARR) of NMOSD is significantly increased in the 0-to 3-month postpartum period, 11-13 but there is a lack of information on the influence of NMOSD on the course of pregnancy.We investigated the effect of NMOSD on miscarriage and preeclampsia rates using multivariate logistic regre...

show abstract

“…Although safety data on exposure for newer drugs like natalizumab and fingolimod are still lacking 9 , there seems to be strong data on the safety of glatiramer acetate 10,11 and interferon beta 11,12 exposure during pregnancy. Is it time to rethink our recommendations?…”

mentioning

confidence: 99%

Is it correct for a woman with multiple sclerosis to forgo medication because she may become pregnant?

Fragoso¹

2013

Arq. Neuro-Psiquiatr.

View full text Add to dashboard Cite

Pregnancy and fetal outcomes after interferon-β exposure in multiple sclerosis

Abstract: Our findings point to the relative safety of IFNβ exposure times of up to 4 weeks and can assist neurologists facing therapeutic decisions in women with MS with a pregnancy plan.

Cited by 145 publications

References 28 publications

The potential teratogenic effects of interferon beta-1a and interferon beta-1b on in vitro embryonic development

The potential teratogenic effects of interferon beta-1a and interferon beta-1b on in vitro embryonic development

Pregnancy outcomes in aquaporin-4–positive neuromyelitis optica spectrum disorder

Is it correct for a woman with multiple sclerosis to forgo medication because she may become pregnant?

Contact Info

Product

Resources

About