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Fourteen years of newborn screening in Massachusetts for congenital toxoplasmosis infection identified subpopulations that appeared to have higher rates of infection. Elaborating an epidemiologic profile and risk correlates might aid implementing targeted prenatal education and newborn screening strategies with the goal of early postnatal treatment to prevent morbidity.To describe the epidemiology of congenital toxoplasmosis in Massachusetts and risk correlates of infection using birth certificate data.A case-control study was conducted based on Massachusetts birth certificate data. Cases were all infants with congenital toxoplasmosis identified by statewide universal newborn screening from 1988 to 1999. Controls were all children born on the same day as those infants in Massachusetts.Factors that strongly predicted congenital toxoplasmosis infection were mother’s country of birth outside the US (especially the southeast Asian refugee origin countries of Cambodia and Laos), mother’s educational level and higher gravidity.More extensive, culturally and linguistically appropriate, prenatal education is needed for pregnant women, regardless of a mother’s educational level, especially for non-US-born mothers, and not focused only on primiparous women. Other states may be able to use their state-specific birth certificate data to compare risk profiles with those of Massachusetts to guide a toxoplasmosis screening policy on the basis of population similarities and differences.