PEDIATRICS Vol. 95 No. 1 January 1995, pp. 11-20
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Neurologic and Developmental Outcome in Treated Congenital Toxoplasmosis

Nancy Roizen MD1, Charles N. Swisher MD2, Mark A. Stein PhD1, Joyce Hopkins PhD1, Kenneth M. Boyer MD3, Ellen Holfels 4, Marilyn B. Mets MD2, Laszlo Stein PhD2, Dushyant Patel MD4, Paul Meier PhD5, Shawn Withers RN4, Jack Remington MD6, Douglas Mack PhD7, Peter T. Heydemann MD3, Diane Patton 4, and Rima McLeod MD8

1 The Pritzker School of Medicine of the University of Chicago, Chicago, Illinois
2 Children's Memorial Hospital and Northwestern University, Chicago, Illinois
3 Rush Presbyterian-St. Luke's Medical Center and Rush Medical College, Chicago, Illinois
4 Michael Reese Hospital, Chicago, Illinois
5 Columbia University, New York, New York
6 Palo Alto Research Institute and Stanford University School of Medicine, Palo Alto, California
7 Michael Reese Hospital, Chicago, Illinois, The University of Illinois School of Medicine at Chicago, Chicago, Illinois
8 The Pritzker School of Medicine of the University of Chicago, Chicago, Illinois, Michael Reese Hospital, Chicago, Illinois

Background. Earlier studies have shown that infants with untreated congenital toxoplasmosis and generalized or neurologic abnormalities at presentation almost uniformly develop mental retardation, seizures, and spasticity. Children with untreated subclinical disease at birth have developed seizures, significant cognitive and motor deficits, and diminution in cognitive function over time.

Objective. To determine neurologic, cognitive, and motor outcomes for children with congenital toxoplasmosis who were treated for approximately 1 year with pyrimethamine and sulfadiazine.

Design and methods. Systematic, prospective, and longitudinal neurologic, cognitive, and motor evaluations were performed for 36 individuals with congenital toxoplasmosis. These infants were born between December 1981 and January 1991 and were treated with pyrimethamine and sulfadiazine for approximately 1 year beginning in the first months of life. Compliance with medications was documented. These individuals were evaluated in a standardized manner in a single center in the first months of life and at approximately 1, 3.5, 5, 7.5, and 10 years of age. Their cognitive function was compared with the cognitive function of a nearest-age, samesex sibling when such siblings older than 3.5 years were available for study.

Results. Signs of active central nervous system infection (eg, cerebrospinal fluid [CSF] pleiocytosis, hypoglycorrhachia, elevated CSF protein, and, in some instances, seizures and motor abnormalities) resolved during therapy. Six of the 36 children had perinatal seizures. Four had their anticonvulsant therapy discontinued successfully within the first months of life, and two additional children developed new seizures at 3 and 5 years of age. Tone and motor abnormalities resolved by 1 year of age in 12 of 20 infants who exhibited abnormalities of tone and motor function at their initial neonatal evaluation. By February 1992, 29 of the 36 children had been evaluated when they were 1 year old, and 23 (79%) had a mean ± standard deviation Mental Developmental Index (MDI) of 102 ± 22 (range, 59 to 140). Six (21%) had a measure of their cognitive function that was less than 50. Results of sequential IQ tests, performed at 1.5 year intervals or greater, did not differ significantly over time (P .05). Seven children with MDIs greater than 50 were compared with sibling controls; they had scores of 87 ± 11 (range, 68 to 97) and their siblings had scores of 112 ± 15 (range, 85 to 132) (P .008). Seventeen of 18 children without hydrocephalus and six of eight children with obstructive hydrocephalus responsive to shunting had normal or near-normal neurologic and developmental outcomes. Children with hydrocephalus ex vacuo present at birth, with high CSF protein, and with lack of response to shunting have done less well.

Conclusions. Neurologic and developmental outcomes were significantly better for most of these treated children than outcomes reported for untreated children or those treated for only 1 month (P .001). Although the level of cognitive function for treated children was less than for their uninfected siblings (P .008), there was no significant deterioration in neurologic and cognitive function of the treated children tested sequentially. These favorable treatment outcomes justify systematic identification and treatment of pregnant women with acute gestational Toxoplasma infection and young infants with congenital toxoplasmosis.

Submitted on April 11, 1994
Accepted on July 12, 1994


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