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Retinochoroiditis is the main complication of congenital toxoplasmosis. Its risk factors have rarely been investigated and were the object of this study.A retrospective study was conducted on 300 infants with congenital toxoplasmosis born between July 1, 1996 and December 31, 2002 and treated with pyrimethamine and sulfonamide for at least 12 months. Results of eye tests were collected up to 24 months. Risk factors associated with first retinochoroiditis were identified by univariate then multivariate analyses (Cox model).One hundred forty-nine boys and 151 girls were included. Maternal infection dated from the first trimester in 34 cases, the second in 97 cases, and the last in 169 cases. At birth, 22 infants had cerebral calcifications. During the first 2 years of life, first retinochoroiditis was diagnosed in 36 infants (12%).In multivariate analysis, 3 factors were significantly associated with first retinochoroiditis before the age of 2 years: a delay of >8 weeks between maternal seroconversion and first treatment [hazard ratio, 2.54; 95% confidence interval (CI), 1.14–5.65], female gender (hazard ratio, 2.02; 95% CI, 1.01–4.1), and cerebral calcifications at birth (hazard ratio, 4.3; 95% CI, 1.9–10). There was no correlation between gestational age at the time of maternal infection and risk for retinochoroiditis.A delay of >8 weeks between maternal seroconversion and the beginning of treatment, female gender, and especially cerebral calcifications are risk factors for retinochoroiditis during the first 2 years of life in infants treated for congenital toxoplasmosis.