Table 2 Outcome measures and main results of studies on folic acid

Brown 1984 [21]

Psychological: Stanford-Binet, Peabody Picture Vocabulary Test Revised (PPVTR) Leither International Performance Scale of non-verbal performance. Scoring by researchers and parents for eye contact, appropriate social smiling, communicative speech and hyperventilating.

Stanford Binet IQ scores did not change significantly. PPVT-R scores appeared unrelated to folic acid treatment. Leither test of non-verbal performance showed improvement in one subject, from 3.0 to 5.6, but not in the other (no more details in article). Statistical testing not presented.

Safety: no side effects.

Brown 1986 [22]

Leiter or Wechsler IQ tests. Autistic Descriptors Checklist (ADC): parental reporting rating checklist. Alpern-Ball test.

Changes of performance ratings not correlated with treatment. Pooled data not provided, only person by person. Statistical testing not presented.

Safety: nothing reported.

Carpenter 1983 [23]

Psychological, speech and language, and psychiatric evaluations but not specified.

No measurable improvement in speech, language or intellectual abilities were found during therapy. Numeric data not provided. Statistical testing not presented.

Safety: nothing reported.

Note: Data from abstract.

Fisch 1988 [24]

Autistic Descriptors Checklist (ADC). Vineland Adaptative Behaviour Scale (VABS).

No statistically significant improvements in periods of folic acid treatment, neither in prepubescent nor in adolescent patients. Pooled data not provided, only person by person.

Safety: nothing reported.

Froster-Iskenius 1986 [29]

Coloured Progressive Matrices test (CPM). Test for fine motor co-ordination, concentration and comprehension.

No improvement in concentration, fine motor co-ordination or comprehension in adults, but may have some effect in children. Pooled data not provided, only person by person. Statistical testing not presented.

Safety: nothing reported.

Gillberg 1986 [30]

Autism Behaviour Checklist (ABC) and other checklist questionnaires pertaining to autism developed by authors. Parents "unstructured" diaries on child overall behaviour and language skills.

Mean ABC scores did not differ in a statistically significant way between placebo and folic acid periods. Numerical detailed information not provided.

Safety: nothing reported.

Hagerman 1986 [25]

Speech and language testing: Peabody Picture Vocabulary Test (PPVT), Test of Language Development (TOLD) and an apraxia battery. Psychological testing: Yale Revised Developmental Schedules, Stanford-Binet, Leiter International Scale. Behavioural assessments: Autism Behavior Checklist (ABC) of the Autism Screening Instrument for Educational Planning (ASIEP) and the Childhood Autism Rating Scale (CARS).

No statistical differences (Wilcoson Rank Sum Test) between placebo and folic acid in: change in IQ, language (PPVT, TOLD, apraxia battery) behavioural areas, CARS, ABC.

Psychological testing: IQ scores statistically significant improvement in prepuberal males while being treated with folic acid (one tailed p = 0.014; two tailed p = 0.028).

Safety: nothing reported.

Madison 1986 [26]

Memory skills: Automated Device for the Assessment of Memory (ADAM); Verbal recall of objects and number series. Compliance and behavioural appropriateness.

No evident change in memory skills, compliance and behavioural appropriateness during treatment phase. Pooled data not provided, only person by person. Statistical testing not presented.

Safety: nothing reported.

Rosenblatt 1985 [28]

Wechsler Intelligence Scale for Children-Revised (WISC-R) Peabody Picture Vocabulary Test Form M (PPVT), Goodenough-Harris Drawing Test (G-H), Rey Children's Word List, Token Test of Auditory Comprehension, Producing Names on Confrontation (test 8 of Clinical Evaluation of Language functioning (CELF), Boston Naming Test, Developmental Test of Visual-Motor integration (DTVMI), Wide Range Achievement Test (WRAT), reading Comprehension (Barnell Loft Multiple Skills Series Al) and Domino Pattern Counting Task. Parent's Questionnaire, Teacher Behavior Checklist and a Checklist of Problem Behaviors.

Strom 1992 [27]

Cognitive function and behavioural level: Vineland Adaptive Behavioral Scales, Peabody Picture Vocabulary Test-Revised (PPVT-R), Conners' Parent and Teaching Rating Scales, the ADD-H: Comprehensive Teacher's Rating Scales (ACTeRS), and a questionnaire designed by the researchers

No statistically significant differences between the folic acid and placebo phases of the study in any outcome measurement instrument: Vineland (51.0 vs 50.9); PPVT-R (55.4 vs 59.2), Conners' (15.5 vs 13.4).

Safety: minor side effects (transient problems with diarrhea, sleep delays, mood swings.