Fetal risk in pregnant women with multiple sclerosis treated with natalizumab
StefanoSotgiu, Child Neuropsychiatry, Department of Medical, Surgical and Experimental Sciences, University of Sassari (Italy)
AnnaEusebi, Resident, Child Neuropsychiatry School, University of Sassari (Italy)
ChiaraBegliuomini, Resident, Child Neuropsychiatry School, University of Sassari (Italy)
Franca R.Guerini, Molecular Biology and immunogenetics, Don C. Gnocchi Foundation IRCCS (Milano, Italy)
AlessandraCarta, Child Neuropsychiatrician, PhD Student, Department of Medical, Surgical and Experimental Sciences, University of Sassari (Italy)
Submitted March 06, 2018
Portaccio et al. reported that fetal exposure to natalizumab increases the risk of spontaneous abortions and congenital anomalies. [1] The authors also described one autism spectrum disorder (ASD) and one language disorder case.
We report 5-year-old dizygotic twins with severe ASD who were exposed to natalizumab for nearly 8 weeks of gestation. At the pre-term (33 weeks) cesarean delivery, both had very low weight and congenital anomalies. There were no reports of ASD-related risk factors, except for maternal multiple sclerosis. Results of the extensive clinical, radiological and genetic studies were unremarkable.
In the first 3 gestation months, decidual natural killer (NK)-cells, expressing VLA-4, have fundamental roles in fetal tolerance [2] and in optimizing maternal nourishment of the fetus [3] both through the HLA-G/KIR axis. Natalizumab-driven VLA-4 blockade on uterine NK-cell surface may alter key NK-cell functions [4] possibly leading to miscarriages, [2] ASD-predisposing maternal immune activation, [2,5] and fetal growth impairment with congenital anomalies. [3] To obtain more accurate measures of neurodevelopmental risk in natalizumab-exposed children, we advise pediatric monitoring longer than 22 months.
1. Portaccio E, Annovazzi P, Ghezzi A, et al. Pregnancy decision-making in women with multiple sclerosis treated with natalizumab: I: Fetal risks. Neurology 2018;90:e823-e831.
2. Guerini FR, Bolognesi E, Chiappedi M, et al. HLA-G coding region polymorphism is skewed in autistic spectrum disorders. Brain Behav Immun 2018;67:308-313.
3. Fu B, Zhou Y, Ni X, et al. Natural Killer Cells Promote Fetal Development through the Secretion of Growth-Promoting Factors. Immunity 2017; 47:1100–1113.
4. Gandoglia I, Ivaldi F, Carrega P, et al. In vitro VLA-4 blockade results in an impaired NK cell-mediated immune surveillance against melanoma. Immunol Lett 2017; 181:109-115.
5. Estes ML, McAllister AK. Maternal immune activation: implications for neuropsychiatric disorders. Science 2016; 353:772-777.
Portaccio et al. reported that fetal exposure to natalizumab increases the risk of spontaneous abortions and congenital anomalies. [1] The authors also described one autism spectrum disorder (ASD) and one language disorder case.
We report 5-year-old dizygotic twins with severe ASD who were exposed to natalizumab for nearly 8 weeks of gestation. At the pre-term (33 weeks) cesarean delivery, both had very low weight and congenital anomalies. There were no reports of ASD-related risk factors, except for maternal multiple sclerosis. Results of the extensive clinical, radiological and genetic studies were unremarkable.
In the first 3 gestation months, decidual natural killer (NK)-cells, expressing VLA-4, have fundamental roles in fetal tolerance [2] and in optimizing maternal nourishment of the fetus [3] both through the HLA-G/KIR axis. Natalizumab-driven VLA-4 blockade on uterine NK-cell surface may alter key NK-cell functions [4] possibly leading to miscarriages, [2] ASD-predisposing maternal immune activation, [2,5] and fetal growth impairment with congenital anomalies. [3] To obtain more accurate measures of neurodevelopmental risk in natalizumab-exposed children, we advise pediatric monitoring longer than 22 months.
1. Portaccio E, Annovazzi P, Ghezzi A, et al. Pregnancy decision-making in women with multiple sclerosis treated with natalizumab: I: Fetal risks. Neurology 2018;90:e823-e831.
2. Guerini FR, Bolognesi E, Chiappedi M, et al. HLA-G coding region polymorphism is skewed in autistic spectrum disorders. Brain Behav Immun 2018;67:308-313.
3. Fu B, Zhou Y, Ni X, et al. Natural Killer Cells Promote Fetal Development through the Secretion of Growth-Promoting Factors. Immunity 2017; 47:1100–1113.
4. Gandoglia I, Ivaldi F, Carrega P, et al. In vitro VLA-4 blockade results in an impaired NK cell-mediated immune surveillance against melanoma. Immunol Lett 2017; 181:109-115.
5. Estes ML, McAllister AK. Maternal immune activation: implications for neuropsychiatric disorders. Science 2016; 353:772-777.
For disclosures, please contact the editorial office at journal@neurology.org.