BackgroundNarcolepsy is a chronic sleep disorder with strong genetic predisposition causing excessive daytime sleepiness and cataplexy. A sudden increase in childhood narcolepsy was observed in Finland soon after pandemic influenza epidemic and vaccination with ASO3-adjuvanted Pandemrix. No increase was observed in other age groups.MethodsRetrospective cohort study. From January 1, 2009 to December 31, 2010 we retrospectively followed the cohort of all children living in Finland and born from January 1991 through December 2005. Vaccination data of the whole population was obtained from primary health care databases. All new cases with assigned ICD-10 code of narcolepsy were identified and the medical records reviewed by two experts to classify the diagnosis of narcolepsy according to the Brighton collaboration criteria. Onset of narcolepsy was defined as the first documented contact to health care because of excessive daytime sleepiness. The primary follow-up period was restricted to August 15, 2010, the day before media attention on post-vaccination narcolepsy started.FindingsVaccination coverage in the cohort was 75%. Of the 67 confirmed cases of narcolepsy, 46 vaccinated and 7 unvaccinated were included in the primary analysis. The incidence of narcolepsy was 9.0 in the vaccinated as compared to 0.7/100,000 person years in the unvaccinated individuals, the rate ratio being 12.7 (95% confidence interval 6.1–30.8). The vaccine-attributable risk of developing narcolepsy was 1∶16,000 vaccinated 4 to 19-year-olds (95% confidence interval 1∶13,000–1∶21,000).ConclusionsPandemrix vaccine contributed to the onset of narcolepsy among those 4 to 19 years old during the pandemic influenza in 2009–2010 in Finland. Further studies are needed to determine whether this observation exists in other populations and to elucidate potential underlying immunological mechanism. The role of the adjuvant in particular warrants further research before drawing conclusions about the use of adjuvanted pandemic vaccines in the future.

BackgroundNarcolepsy is a rare neurological sleep disorder especially in children who are younger than 10 years. In the beginning of 2010, an exceptionally large number of Finnish children suffered from an abrupt onset of excessive daytime sleepiness (EDS) and cataplexy. Therefore, we carried out a systematic analysis of the incidence of narcolepsy in Finland between the years 2002–2010.MethodsAll Finnish hospitals and sleep clinics were contacted to find out the incidence of narcolepsy in 2010. The national hospital discharge register from 2002 to 2009 was used as a reference.FindingsAltogether 335 cases (all ages) of narcolepsy were diagnosed in Finland during 2002–2009 giving an annual incidence of 0.79 per 100 000 inhabitants (95% confidence interval 0.62–0.96). The average annual incidence among subjects under 17 years of age was 0.31 (0.12–0.51) per 100 000 inhabitants. In 2010, 54 children under age 17 were diagnosed with narcolepsy (5.3/100 000; 17-fold increase). Among adults ≥20 years of age the incidence rate in 2010 was 0.87/100 000, which equals that in 2002–2009. Thirty-four of the 54 children were HLA-typed, and they were all positive for narcolepsy risk allele DQB1*0602/DRB1*15. 50/54 children had received Pandemrix vaccination 0 to 242 days (median 42) before onset. All 50 had EDS with abnormal multiple sleep latency test (sleep latency <8 min and ≥2 sleep onset REM periods). The symptoms started abruptly. Forty-seven (94%) had cataplexy, which started at the same time or soon after the onset of EDS. Psychiatric symptoms were common. Otherwise the clinical picture was similar to that described in childhood narcolepsy.InterpretationA sudden increase in the incidence of abrupt childhood narcolepsy was observed in Finland in 2010. We consider it likely that Pandemrix vaccination contributed, perhaps together with other environmental factors, to this increase in genetically susceptible children.

Only one fourth of the ELBW infants were classified as normally developed at age 5. The high rate of cognitive dysfunction suggests an increased risk for learning difficulties that needs to be evaluated at a later age. Extended follow-up should be the rule in outcome studies of ELBW infant cohorts to elucidate the impact of immaturity on school achievement and social behavior later in life.

The authors followed two cohorts of children born in northern Finland in 1966 (n = 12,058) and 1985-1986 (n = 9,432) to examine whether associations between maternal sociodemographic factors assessed during pregnancy and intellectual disability in the offspring changed over a 20-year interval. Both of the cohorts were followed up to the age of 11.5 years using similar methods and definitions of intellectual disability. Data on sociodemographic factors were based on comparable questionnaires returned by the mothers during the 25th week of gestation. Despite an interval of 20 years between the cohorts, the main indicators of socioeconomic disadvantage and maternal multiparity remained as having the largest impact on the incidence of intellectual disability, while single factors such as older maternal age at delivery, being single, and living in a remote area lost their association with intellectual disability. Over 20 years, prepregnancy maternal obesity (body mass index > or =30) became a newly associated factor (adjusted odds ratio = 2.8, 95% confidence interval: 1.5, 5.3). A future challenge is to explore the mediating mechanisms between intellectual disability and its associated preventable intergenerational environmental or lifestyle factors.

The prevalence of periventricular leukomalacia and its association with clinical neurological signs in school-age preterm children are unknown. We matched 42 eight-year-old children who were born before term with birth weights lower than 1,750 gm (mean, 1,410 gm; gestational age, 31 weeks) with 42 children who were born at term and of normal birth weight, to compare clinical neurological status and magnetic resonance imaging findings. Of the children born prematurely, 9.5% had cerebral palsy and 31% had minor neurological dysfunction whereas 9% of the children born at term had minor neurological dysfunction and none had cerebral palsy. Deviations in tongue movements, heel walking. Fogs test results, and finger opposition, as well as behavioral disturbances, differentiated the preterm from the full-teem group. The prevalence of periventricular leukomalacia among all children born prematurely was 32%. It was observed in all children with cerebral palsy, in 25% with minor neurological dysfunction, and in 25% of the clinically healthy preterm children. None of the children born at term had evidence of periventricular leukomalacia. Children with periventricular leukomalacia especially demonstrated poor performance on heel walking and Fogs test. Though commonly found in preterm children, periventricular leukomalacia is not uniformly associated with abnormal neurological findings. A thorough neurological examination is a better predictor of later developmental problems than is magnetic resonance imaging.