Final analysis of 379 pregnancy outcomes after exposure to dimethyl fumarate in a prospective international registry.

BACKGROUND: Dimethyl fumarate (DMF) has a favorable benefit-risk profile treating people with multiple sclerosis and should be used in pregnant women only if the potential benefits outweigh potential risks to the fetus. OBJECTIVE: Assess pregnancy outcomes in a completed international registry (TecGistry) of women with MS exposed to DMF. METHODS: TecGistry included pregnant women with MS exposed to DMF, with data collected at enrollment, 6-7 months gestation, 4 weeks after estimated due date, and at postpartum weeks 4, 12, and 52. Outcomes included live births, gestational size, pregnancy loss, ectopic/molar pregnancies, birth defects, and infant/maternal death. RESULTS: Of 397 enrolled, median (range) age was 32 years (19-43). Median (range) gestational week at enrollment was 10 (0-39) and at first DMF exposure was 1 (0-13). Median (range) duration of gestational DMF exposure was 5 weeks (0-40). Fifteen (3.8%) spontaneous abortions occurred. Of 360 (89.1%) live births, 323 were full term and 37 were premature. One neonatal death and no maternal deaths occurred. Adjudicator-confirmed EUROCAT birth defects were found in 2.2%. CONCLUSION: DMF exposure during pregnancy did not adversely affect pregnancy outcomes; birth defects, preterm birth, and spontaneous abortion were in line with rates from the general population.

Interim Analysis of Pregnancy Outcomes After Exposure to Dimethyl Fumarate in a Prospective International Registry.

BACKGROUND AND OBJECTIVES: Oral delayed-release dimethyl fumarate (DMF) is not recommended during pregnancy and should only be used if the potential benefit justifies the potential fetal risk. Although DMF was well tolerated in clinical trials with consistent safety results in postmarketing surveillance, data are limited in pregnant women. The objective was to provide pregnancy outcomes and DMF exposure information from an interim analysis from a prospective, international registry (TecGistry; NCT01911767). METHODS: Women exposed to DMF from the first day of their last menstrual period before conception or during pregnancy were evaluated. Data were obtained at enrollment; 6-7 months' gestation; 4 weeks after estimated due date; and 4, 12, and 52 weeks after birth. Outcomes included live births, gestational size, pregnancy loss, birth defects, and infant or maternal death after delivery. Outcomes were analyzed cumulatively from October 30, 2013 (the start of TecGistry), to April 8, 2020. RESULTS: Of 345 enrolled patients, median (range) age was 32 (20-43) years. The mean (SD) duration of gestational weeks of DMF exposure was 4.9 (3.8). Most infants were full-term at birth (n = 249/274; 91%) and of average gestational size (n = 190/232; 82%). Of 351 outcomes, 277 were live births; 17 (5%) spontaneous abortions (95% confidence interval [CI] 2.6%-7.1%), including 1 (<1%) molar and 1 (<1%) ectopic pregnancy, were reported. There were 8 (2.9% [95% CI 1.3%-5.6%]) adjudicator-confirmed birth defects among the 277 live births. DISCUSSION: Interim results from this large registry indicate that early DMF exposure was not significantly associated with adverse pregnancy outcomes. Outcomes are consistent with previous smaller reports and with the general population. TRIAL REGISTRATION INFORMATION: TecGistry; clinical trial registration number: NCT01911767.

Diagnosed cataracts in patients with cystic fibrosis in a United States administrative database.

BACKGROUND: We estimated the incidence and prevalence of diagnosed cataracts among patients with cystic fibrosis (CF) versus the general population (GP). METHODS: Using a large US health insurance claims database, we identified a CF cohort and a GP cohort matched with respect to age, gender, and calendar year. The prevalence and incidence of diagnosed cataract (primary outcome) for both cohorts were calculated, as well as the incidence rate ratios (IRRs). RESULTS: The prevalence of diagnosed cataracts among patients with CF alive and enrolled in the health plan on August 31, 2012 was 4.8% versus 2.8% in the GP. The incidence in the CF cohort was higher than in the GP and increased with age in both cohorts. The adjusted IRR comparing the CF and GP cohorts was 1.5 (95% CI: 1.2-1.8). CONCLUSIONS: The study suggests that the risk of developing cataract was higher among patients with CF than among the GP.

Social and behavioral risk marker clustering associated with biological risk factors for coronary heart disease: NHANES 2001-2004.

BACKGROUND: Social and behavioral risk markers (e.g., physical activity, diet, smoking, and socioeconomic position) cluster; however, little is known whether clustering is associated with coronary heart disease (CHD) risk. Objectives were to determine if sociobehavioral clustering is associated with biological CHD risk factors (total cholesterol, HDL cholesterol, systolic blood pressure, body mass index, waist circumference, and diabetes) and whether associations are independent of individual clustering components. METHODS: Participants included 4,305 males and 4,673 females aged ≥ 20 years from NHANES 2001-2004. Sociobehavioral Risk Marker Index (SRI) included a summary score of physical activity, fruit/vegetable consumption, smoking, and educational attainment. Regression analyses evaluated associations of SRI with aforementioned biological CHD risk factors. Receiver operator curve analyses assessed independent predictive ability of SRI. RESULTS: Healthful clustering (SRI = 0) was associated with improved biological CHD risk factor levels in 5 of 6 risk factors in females and 2 of 6 risk factors in males. Adding SRI to models containing age, race, and individual SRI components did not improve C-statistics. CONCLUSIONS: Findings suggest that healthful sociobehavioral risk marker clustering is associated with favorable CHD risk factor levels, particularly in females. These findings should inform social ecological interventions that consider health impacts of addressing social and behavioral risk factors.

Implementation of permutation testing to determine clustering of social and behavioral risk factors for coronary heart disease, National Health and Nutrition Examination Survey 2001-2004.

PURPOSE: To determine whether social and behavioral risk factors for coronary heart disease, including education, physical activity, fruit/vegetable intake, and smoking, cluster (i.e., co-occur more than expected as the result of chance) in U.S. adults. METHODS: The study included 4305 male and 4673 female subjects aged ≥20 years from the National Health and Nutrition Examination Survey. Risk factors included: ≤high school diploma/general educational development certificate; <150 minutes of moderate/vigorous physical activity per week; <3 or <2 servings of vegetables and fruit, respectively, per day; and smoking cigarettes. Indicator variables were summed into a sociobehavioral risk index (SRI, range 0 [no risk factors] to 4 [all risk factors]). Ratios of observed-to-expected prevalence (under the assumption of independence) of the SRI were assessed. Statistical significance was evaluated by the use of randomly permuted average observed-to-expected SRI ratios and 95% confidence intervals (95% CIs). RESULTS: In male subjects, the ratio of observed-to-expected prevalence of SRI = 0 was 1.70 (permuted ratio = 1.00; 95% CI: 0.92-1.08), and SRI = 4 was 2.10 (permuted ratio = 1.00, 95% CI: 0.86-1.14), demonstrating significant clustering. In females, the ratio of observed-to-expected prevalence of SRI = 0 was 1.67 (permuted ratio = 1.00, 95% CI: 0.92-1.08), and SRI = 4 was 1.86 (permuted ratio = 1.00, 95% CI: 0.85-1.15). CONCLUSIONS: Social and behavioral risk factors for coronary heart disease cluster in this sample of U.S. adults.