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SUMmARY Data from the Finnish Register of Congenital Malformations for the years 1965-73 were used in a search for associations between environmental influences and defects of the central nervous system (CNS). The material consisted of 710 cases of CNS defects and their matched-pair controls. Moreover, an 'internal' control group of 259 cases of polydactyly and their matched-pair controls were used. The first report gives information on variations in time and space, sex distribution, and parental age. A higher incidence of anencephaly was noted in the eastern part of the country, but no significant secular or seasonal variations were found. The sex ratio (M/F) was lower than expected in the groups of anencephaly and CNS defects as a whole. High parental age turned out to be a risk factor in the group of all CNS defects, mainly owing to the subgroup of hydrocephaly. The dangers of observational studies due to confounding factors are discussed.Defects of the central nervous system (CNS) constitute an important medical as well as a social problem which like most congenital defects are likely to be caused by an interaction of both genetic and environmental factors. The purpose of this study is to test some hypotheses concerning the association of environmental factors with CNS defects. This first report gives a description of the material, with information on incidence, seasonal and yearly variations, sex distribution, and parental age. Subsequent reports will deal more specifically with various maternal and exogenous factors associated with CNS defects. Material and methodsThis epidemiological study is based on material from the Finnish Register of Congenital Malformations. Reporting of all congenital malformations detected during the first year of life was made compulsory in Finland in 1963, the year in which the register was founded. The group of CNS defects is one of the 'detector' defects, for which extensive information is collected through the maternity welfare centres. The control for each case is the mother whose delivery preceded that of the study mother in the same maternity welfare district. The information on both the study and the control cases is collected by interviews with the mothers and from the records of the welfare centres obtained during pregnancy. Thus the information is prospective as well as retrospective. Full details of the organisation of the register have been published elsewhere (Sax6n et al., 1974

Seven hundred and ten cases with defects of the central nervous system (CNS) reported to the Finnish Register of Congenital Malformations in 1965-73 were analysed with regard to possible etiological factors. A time-area matched birth for every case, 259 cases of polydactyly, and official statistics for the entire country were used as controls. High birth order turned out to be a risk factor especially for the group of hydrocephaly, maternal age not taken into account. When this confounding factor had been ruled out, it was found that high birth order was associated with anencephaly and high maternal age with hydrocephaly. However, a combination of both these factors gave the most striking association in both groups of defects. Higher rates of abortions and stillbirths in previous pregnancies, previous live births with CNS defects or any kind of defects were significantly associated with the birth of children with CNS defects. The rate of twinning was found to be higher in the study group than in the general population, and in the great majority of twin births the CNS defective child was the later born partner. Parental profession did not seem to be associated with the outcome of pregnancy. The significance of the socio-economic status and other confounding factors are discussed in connection with the concept of the marital status of mothers.

Background: We assessed the performance and validity of cytology in the Finnish screening program by considering high-grade neoplasia and cervical cancer (CIN3+) rates as detected in the program and by reevaluating cases observed after a negative screening test.Methods: This retrospective study included 915 screen-detected CIN3+ cases and 421 cases observed after a negative screen. Randomized and blinded reevaluation of potential false-negative screening tests covered 345 archival case smears from women without a referral to colposcopy, as well as 689 control smears for estimating performance and validity measures.Results: The false-negative rate at the cutoff of low-grade squamous intraepithelial lesion or worse was 35% (95% confidence interval, 30-40%). In the subpopulation with original screening result of Pap I, the false-negative rate was 23% (18-28%). Sensitivity of screening laboratory rereading for detecting low-grade lesions or worse as atypical was 75% (67-82%) and specificity 93% (91-94%). Reproducibility of specific cytologic diagnoses was only fair. False negatives constituted 11% of all CIN3+ diagnoses in the screened population; those false negatives with an original Pap I screening result constituted 5%.Conclusions: Although screen failures in the form of diagnostic false negatives occur within the Finnish screening program, their effect on cancer incidence is fairly small and cannot be readily decreased without sacrificing the high specificity of screening or without high incremental costs. Feedback for the screening laboratories is needed, however, to improve the reproducibility of cytologic diagnoses to optimize the burden of intensified follow-up and treatment of precancerous lesions. Cancer Epidemiol Biomarkers Prev; 19(2); 381-7. ©2010