cb‐Mrozek‐Budzyn 2013.

Study characteristics
Methods	Prospective cohort study, Krakow. The aim of the study was to examine the hypothesis that MMR exposure has a negative influence on cognitive development in children.
Participants	The data from an earlier established Krakow birth cohort of children are used (part of collaborative study with Columbia University in New York, on the vulnerability of fetus and child to environmental factors). The enrolment (3 November 2000 to 22 August 2003) included only non‐smoking women, aged 18 to 35 years, with singleton pregnancy without illicit drug use and HIV infection, free from chronic diseases such as diabetes or hypertension and residing in Krakow for at least 1 year prior to pregnancy. The infants were followed up to 8th year of life. Each year mothers were asked to provide information on infants’ health and household characteristics by trained interviewers, who carried out detailed, face‐to‐face standardised interviews.
Interventions	MMR vaccine (and measles vaccine). Data on infants’ vaccination history (date of vaccination and type of vaccine) were extracted from the physician’s records. The vaccination status was based on measles vaccination during the second year of life.
Outcomes	The Fagan Test of Infant Intelligence at 6th month of life. The Bayley Scales of Infants Development, second edition was administered in the 12th, 24th, and 36th months of life. The Mental Scale of that test includes items that assess memory, habituation, problem solving, early number concepts, generalisation, classification, vocalisation, language, and social skills. Test scores are adjusted to child’s age to obtain the Mental Development Index. Test results are in 1 of 4 categories (range 50 to 150): (1) accelerated performance (score > 115); (2) within normal limits (score 85 to 114); (3) mildly delayed performance (score 70 to 84); and (4) significantly delayed (score < 69). The Raven’s Colored Progressive Matrices test was administered twice, in 5th and 8th year of life. The outcomes of the test were measured in terms of centiles. Because the results of this test were generally high, the cut point of poor result category was 74th percentile, which means middle intelligence outcomes. Output scale was presented in centiles standardised to age groups. The Wechsler Intelligence Scale for Children (WISC‐R) was administered in the 6th and 7th years of life, and generated verbal, non‐verbal, and total IQ for evaluated children. Category with IQ < 100 was considered as the poorer outcomes. The outcomes range is from 40 to 160. All neurodevelopment tests were conducted in the Department of Epidemiology and Preventive Medicine by carefully trained examiners who were unaware of the child’s exposure. Bayley Scales as well as Raven test have well‐defined criteria and were considered as fully consent between different examiners. In order to provide fully comparable assessment of WISC‐R test, 1 psychologist rated performed answers for all children.
Funding Source	Government
Notes	Conclusion: the results suggest that there is no relationship between MMR exposure and children’s cognitive development. Furthermore, the safety of triple MMR is the same as the single measles vaccine with respect to cognitive development.
Risk of bias
Bias	Authors' judgement	Support for judgement
PCS/RCS ‐ exposed cohort selection	Low risk	From physician record ‐ drawn from the same community
PCS/RCS ‐ non‐exposed cohort selection	Unclear risk	Krakow (Poland) birth cohort of children ‐ selected group: women aged 18 to 35 singleton pregnancy
PCS/RCS ‐ comparability	Unclear risk	There was insufficient information ‐ probable residual confounding.
PCS/RCS ‐ assessment of outcome	Low risk	Adequate ‐ standardised method
Summary Risk of Bias assessment	Unclear risk	We had concerns regarding at least 1 domain such that some doubt is raised about the results.