OBJECTIVE: to assess pregnancy and fetal outcomes after father's exposure to DMD (Disease Modifying Drugs), using the previously collected Italian Pregnancy Dataset (Amato et al., Neurology 2010). BACKGROUND: there is a dearth of information on the role of paternal exposure to DMD for multiple sclerosis (MS) on pregnancy and fetal outcomes. METHODS: we recruited MS male patients, prospectively followed-up in 21 Italian MS Centres, whose partners were pregnant in the period 2002-2008. Patients were divided into two groups: drug-exposed patients (EP: suspension of the drug less than 4 weeks from conception) and non-exposed patients (NEP: suspension of the drug at least 4 weeks from conception or never treated). All the subjects were administered a structured interview which gathered detailed information on pregnancy course and outcomes, as well as on possible confounders. Multivariate logistic and linear models were used for group comparisons. RESULTS: data on 78 pregnancies were collected (six exposed to glatiramer acetate (GA), 36 to beta-interferons (BIFN), 36 non-exposed). We observed 75 full-term deliveries, 41 in couples with exposed and 34 with non-exposed fathers. Paternal DMD exposure was not significantly associated with an increased risk of spontaneous abortion (p >0.351). Mean birth-weight and length were not significantly different for paternal exposure or non-exposure to DMD (p>0.781). There was also no difference in terms of frequency of preterm delivery (EP: 7 out of 41 patients, 17,1%; NEP: 3 out of 34 patients, 8.8%; p=0.240). Caesarean delivery was the only predictor of preterm delivery. These findings were confirmed in the multivariate analysis. The proportion of spontaneous abortion and caesarean delivery in case of paternal exposure to DMD fell within the estimates for the general population. We did not observe any major pregnancy or delivery complications or baby malformations after paternal DMD exposure. CONCLUSIONS: Data in our cohort show that father's exposure to GA and BIFN is safe, so that MS fathers can continue taking these therapies at conception.
Background: There is emerging evidence that intrathecal IgM synthesis (ITMS) is a risk factor for conversion to clinically defined multiple sclerosis (CDMS) in clinically isolated syndrome (CIS) patients. Objectives: The objective of this study is to verify the prognostic role of ITMS as a risk factor for the second clinical attack in patients after the first demyelinating event. Methods: Monocentric observational study performed on prospectively acquired clinical data and retrospective evaluation of magnetic resonance imaging (MRI) data. ITMS was assessed according to Reiber’s non-linear function. We compared time to the second attack by using Kaplan–Meier curves and performed adjustment by Cox regression analysis. Results: Demographics and clinical data were collected prospectively in a cohort of 68 patients. ITMS occurred in 40% (27/68) of patients who had a higher T1-hypointense lesion load at brain MRI ( p = 0.041). In multivariate Cox regression analysis (adjusted for age, sex, baseline Expanded Disability Status Scale, IgG oligoclonal bands and disease-modifying treatment exposure), relapsing-remitting multiple sclerosis (MS) patients with ITMS were at higher risk to experience a second clinical attack (adjusted hazard ratio (aHR) = 6.3, 95% confidence interval (CI) = 2.1–18.4, p = 0.001). Conclusion: Together with previous studies, our findings support the role of ITMS as a prognostic biomarker in MS.
Abstract Background Health, as defined by the WHO, is a multidimensional concept that includes different aspects. Interest in the health conditions of the oldest-old has increased as a consequence of the phenomenon of population aging. This study investigates whether (1) it is possible to identify health profiles among the oldest-old, taking into account physical, emotional and psychological information about health, and (2) there are demographic and socioeconomic differences among the health profiles. Methods Latent Class Analysis with covariates was applied to the Mugello Study data to identify health profiles among the 504 nonagenarians residing in the Mugello district (Tuscany, Italy) and to evaluate the association between socioeconomic characteristics and the health profiles resulting from the analysis. Results This study highlights four groups labeled according to the posterior probability of determining a certain health characteristic: “healthy”, “physically healthy with cognitive impairment”, “unhealthy”, and “severely unhealthy”. Some demographic and socioeconomic characteristics were found to be associated with the final groups: older nonagenarians are more likely to be in worse health conditions; men are in general healthier than women; more educated individuals are less likely to be in extremely poor health conditions, while the lowest-educated are more likely to be cognitively impaired; and office or intellectual workers are less likely to be in poor health conditions than are farmers. Conclusions Considering multiple dimensions of health to determine health profiles among the oldest-old could help to better evaluate their care needs according to their health status.
Objective: to investigate the fetal safety of NTZ exposure during the first trimester of pregnancy.
Background: Safety data on in utero exposure to natalizumab (NTZ) in patients with multiple sclerosis (MS) are scarce.
Methods: we recruited NTZ-exposed pregnancies in MS patients followed-up in 21 Italian Centres. Exposure to NTZ was defined as suspension < ten weeks prior to conception. Results were compared with data from the Italian dataset on interferon-beta (IFNB) exposed and non-exposed pregnancies (Amato et al., 2010). All the patients were administered a structured interview on pregnancy and possible confounders. We used the χ2 test, analysis of variance, mixed factorial design, multivariate and propensity-score adjusted analyses.
Results: we analysed 59 pregnancies in patients exposed to NTZ, 88 exposed to IFNB and 318 non-exposed to disease-modifying drugs. Mean duration of exposure was 1.15+4.10 weeks to NTZ, 4.6+5.8 weeks to IFNB . The rate of spontaneous abortion (SA) was 19[percnt] in NTZ-exposed, 8[percnt] in IFNB-exposed, 6.6[percnt] in non-exposed group (p=0.009). The higher risk of abortion in NTZ-exposed group was confirmed in the multivariate analysis: OR 3.9 (95[percnt]CI 1.7-9.0; p=0.002). This rate, however, was within the limits calculated for the Italian population (4.4[percnt]-21.6[percnt]). The timing of SA was 7.8+3.3 for NTZ, 8.2+ 1.6 for IFNB and 8.4+2.3 weeks for non-exposed pregnancies. Both in the NTZ and IFNB-exposed group mean birth weight of the baby was decreased in comparison with the non-exposed group (NTZ: 2.970+563 gr, IFNB 3.010+513 gr, non-exposed 3.200+510 gr, p 0.013). Reduced mean birth length (48.7+3.4cm) and gestational age (37.8+2.1 weeks) were observed only in the IFNB-exposed compared with non-exposed group (p<0.03). No major malformation of the baby was observed.
Conclusions: Exposure to NTZ in early pregnancy does not appear to increase the risk of malformations, whereas, in our population, it was associated with an increased risk of SA. Disclosure: Dr. Giannini has received personal compensation for activities with Biogen Idec and Almirall. Dr. Portaccio has received personal compensation for activities with Biogen Idec, Bayer, and Merck Serono as a scientific advisory board member. Dr. Portaccio has received research support from Biogen Idec, Bayer, Merck Serono, and Sanofi-Aventis. Dr. Hakiki has received personal compensation for activities with Novartis as a speaker. Dr. Pasto(apos) has received personal compensation for activities with Biogen Idec and Almirall. Dr. Razzolini has nothing to disclose. Dr. Isabella has received personal compensation for activities with Novartis as speaker honoraria. Dr. Tortorella has received personal compensation for activities with Biogen, Sanofi-Aventis, Serono and Bayer-Schering, Teva,Genzyme and Novartis as a speaker. Dr. Trojano has received research support from Biogen Ide., Merck-Serono and Novartis Pharmaceuticals. Dr. Cocco has received personal compensation for activities with Biogen Idec, Teva Neuroscience, Novartis, Sanofi-Aventis, Merck Serono, and Bayer. Dr. Melis has nothing to disclose. Dr. Marrosu has received personal compensation for activities with Biogen, Sanofi-Aventis, TEVA, Novartis, Merck Serono and Bayer Healthcare. Dr. Di Tommaso has nothing to disclose. Dr. Farina has nothing to disclose. Dr. Lugaresi has received personal compensation for activtiies with Bayer Healthcare, Biogen Idec, Genzyme/Sanofi, EMD Serono, Novartis, and Teva CNS. Dr. Lugaresi has received research support from Bayer Healthcare and Biogen. Dr. Annovazzi has received personal compensation for activities with Biogen Idec, Novartis and Teva pharmaceuticals as a consultant, speaker and scientific advisory board forum member. Dr. Ghezzi has received personal compensation for activities with Biogen Idec, Merk-Serono, Novartis, Genzyme, Teva, Serono Symposia Int Found., Novartis, and Almirall. Dr. Gasperini has received personal compensation for activities with Merck Serono, Biogen Idec, Teva, Novartis, Genzyme, and Bayer Schering as a speaker. Dr. Iudice has nothing to disclose. Dr. Fantozzi has nothing to disclose. Dr. Bellantonio has received personal compensation for activities with Bayer Shering Pharma., Biogen Idec., Merck-Serono, Sanofi-Aventis, Novartis Pharmaceuticals as a speaker. Dr. Messina has received personal compensation for activities with Novartis, Biogen, and Almirall as a speaker. Dr. Patti has received personal compensation for activities with Merck-Serono; Bayer Schering, and Dompe Biotec. Dr. Carlotta has nothing to disclose. Dr. Cavalla has nothing to disclose. Dr. Protti has nothing to disclose. Dr. Totaro has received personal compensation for activities with Bayer Shering Pharma, Biogen Idec, Merck Serono, Sanofi-Aventis Pharmaceuticals, Inc., Teva Neuroscience, and Novartis as a speaker and/or consultant. Dr. Pozzilli has received personal compensation for activities with Actelion, Biogen Idec, Genzyme Corporatoin, Merck Serono, Novartis, and Teva Neuroscience as a consultant. Dr. De Giglio has nothing to disclose. Dr. Uccelli has received personal compensation for activities with Biogen Idec, Genzyme Corporation, Merck Serono, Novartis, Roche Diagnostics Corporation, and Teva Neuroscience as a consultant and/or speaker. Dr. Sartori has received personal compensation for activities with Merk Serono as a consultant. Dr. Bosco has nothing to disclose. Dr. Lanzillo has nothing to disclose. Dr. Brescia Morra has nothing to disclose. Dr. Amato has received personal compensation for activities with Biogen Idec, Merk Serono, Bayer, Novartis, Teva, Sanofi, Genzyme, Almirall.
