The objective was to evaluate HLA DR/DQ alleles and their risk factor for type 1 diabetes in the Abruzzo region (central Italy). Sixty incident cases from the Abruzzo region were studied together with 120 unrelated control subjects living in the same administrative areas. The relative risk of diabetes associated with the alleles under study was calculated by deriving the odds ratio (OR) maximum likelihood estimates and their 95% confidence intervals (CI) by the exponentiation of the logistic regression beta-parameter. The combination DRB1*03/DQA1*0501/DQB1*0201 was found in 20.0% of patients and 7.1% of the control subjects, conferring an OR of 4.04 and a CI of 1.97-8.49. The combination DRB1*04/DQA1*0301/DQB1*0302 was found in 23.3% of diabetic patients and 6.7% of controls, giving an OR of 5.69 and a CI of 2.77-12.05. DRB1*11/DQA1*0505/DQB1*0301 and DQA1*0505/DQB1*0301 were negatively associated with type 1 diabetes (OR=0.27, CI 0.11-0.57; OR=0.07, CI 0.02-0.19). The DQA1 genotype at risk was found to be DQA1*0301/DQA1*0501: OR=23.80, CI 2.97-190.89, as it occurred with the highest frequency in the patient group. The DQB1 genotype at risk was found to be DQB1*0201/DQB1*0302, which occurred in 13.3% of patients but in only 1.1% of the control group (OR=29.75, CI 5.36-549.25). Our results shed further light on the risk of development of this disease during a specific time period in an area where the overall incidence of type 1 diabetes is known.
Background
After a primary maternal CMV infection during pregnancy infants are at risk for disease.
Methods
Factors predictive of infant outcome were analyzed in a database of 304 pregnant women with a primary infection. These were enrolled between 2010 and 2017 and delivered 281 infants, of whom 108 were CMV infected. Long term follow-up occurred for 173 uninfected and 106 infected infants at age 4 years (range 1 to 8 years). 157 women were treated with an average of 2 doses (range 1 to 6) of high dose hyperimmune globulin (HIG: 200 mg/kg/infusion). We used a regression model to define predictors of fetal infection, symptoms at birth, and long-term sequelae. 31 covariates were tested.
Results
Four factors predicted fetal infection: a 1.8 fold increase (30% vs. 56%) in the rate of congenital infection without HIG (P<0.0001, adjusted odd ratio (AOR) =5.2), a 1.8 fold increase (32% vs. 56%) associated with maternal viral DNAemia prior to HIG administration (P=0.002, AOR=3.0), abnormal ultrasounds (P=0.0002, AOR=54.2), and diagnosis of maternal infection via seroconversion rather than avidity (P=0.007, AOR=3.3). Lack of HIG and abnormal ultrasounds also predicted symptoms (P=0.001). Long term sequelae were predicted by not receiving HIG (P=0.001, AOR=13.2), maternal infection in early gestation (P=0.017, OR = 0.9), and abnormal ultrasounds (P<0.003, OR =7.6). Prevalence and copy/number of DNAemia declined after HIG.
Conclusions
Maternal viremia predicts fetal infection and neonatal outcome. This may help patient counseling. High-dose HIG may prevent fetal infection and disease, and is associated with the resolution of DNAemia.
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