Narcolepsy 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.
Retrospective 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.
Vaccination 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).
Pandemrix 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.
•Maternal and paternal perinatal depressive symptom trajectories seem stable.•This suggests chronic nature of perinatal depressive symptoms for many.•Mothers’ and fathers’ perinatal depressive ...symptom trajectories are correlated.•The strongest predictors are common to both mothers’ and fathers’ trajectories.
This study investigated trajectories of mothers’ and fathers’ depressive symptoms from prenatal to 24 months postpartum. Prenatal correlates of the trajectories were also examined.
Mothers (N = 1670) and fathers (N = 1604) from the Finnish CHILD-SLEEP birth cohort, reported depressive symptoms at 32nd pregnancy week and 3, 8, and 24 months postpartum using the Center for Epidemiologic Studies Depression Scale (CES-D, 10-item). Profile analysis was used to group participants according to their longitudinal patterns of depressive symptoms. Prenatal predictors (sociodemographic, health, substance use, sleep, and stress related factors, family atmosphere) of depressive symptom trajectories as well as association between parents’ trajectories were analyzed using multinomial logistic regression.
For both mothers and fathers, a solution with three stable depressive symptom trajectories (low: 63.1% mothers and 74.9% fathers; moderate: 28.1% and 22.6%; high: 8.8% and 2.6%) was considered the best fitting and most informative. Insomnia, earlier depression, anxiousness, stressfulness, and poor family atmosphere predicted the moderate and high (compared to low) depressive symptom trajectories among both mothers and fathers in multivariate analyses. Mother's higher depressive symptom trajectory was significantly associated with father's higher symptom trajectory (p < 0.001).
Number of cases in the high depressive symptom trajectory group among fathers was low.
Maternal and paternal depressive symptom trajectories from prenatal period up to two years postpartum seem stable, indicating the chronic nature of perinatal depressive symptoms. Mothers’ and fathers’ trajectories are associated with each other and their strongest predictors are common to both.
Aim
No studies have described long‐term paediatric home respiratory support in Nordic countries. We examined the clinical characteristics and long‐term outcomes of paediatric patients who received ...continuous positive airway pressure, non‐invasive‐positive‐pressure ventilation and invasive ventilation from a multidisciplinary home respiratory support team.
Methods
Retrospective tertiary‐level data were collected between 1 January 2010 and 31 December 2020 in Tampere University Hospital. These comprised patient demographics, treatment course and polysomnography‐confirmed sleep‐disordered breathing (SDB).
Results
There were 93 patients (63.4% boys). The median age at treatment initiation was 8.4 (range 0.11–16.9) years. The patients had: neuromuscular disease (16.1%), central nervous system disease (14.0%), developmental disabilities and congenital syndrome (29.0%), lung‐airway conditions (11.8%), craniofacial syndrome (15.1%) and severe obesity (14.0%). More than two‐thirds had severe SDB (66.7%) and the most common one was obstructive sleep apnoea in 66.7%. We found that 92.5% received long‐term therapy for more than 3 months and the mean treatment duration was 3.3 ± 2.7 years. A non‐invasive mask interface was used in 94.7% of cases and 5.3% needed tracheostomy ventilation. More than a quarter (26.7%) achieved disease resolution during the study period.
Conclusion
Most children who needed long‐term home respiratory support had complex conditions and severe, persistent SDB.
Aim
We assessed psychosocial burdens in children who developed narcolepsy after receiving the Pandemrix H1N1 vaccine during the 2009–2010 pandemic. Parental quality of life was also assessed.
Methods
...This multicentre study covered four of the five Finnish University Hospital Districts, which dealt with about 90% of the paediatric narcolepsy cases after the Pandemrix vaccination. The medical records of children diagnosed from 2010 to 2014 were reviewed. The questionnaires included the Youth Self‐Report (YSR), Children's Depression Inventory (CDI), the Child Behaviour Checklist (CBCL) and questions on parental resources, stress and quality of life.
Results
We obtained the medical records of 94 children who were aged 5–17 years at the time of their narcolepsy diagnosis and questionnaire data for 73 of those children. Most children had strong narcolepsy symptoms, and 25% had CDI scores that suggested depression. In addition, 41% had total CBCL problem scores above the clinically significant limit and 48% were anxious, withdrawn and had somatic complaints. Sleep latency was weakly associated with the CBCL total problem score. Half of the children needed psychiatric interventions and parental stress was common.
Conclusion
Depression and behavioural problems were common in children with narcolepsy after the Pandemrix vaccination and their parents frequently reported feeling stressed.
Narcolepsy 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.
All 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.
Altogether 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.
A 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.
Aim
This study evaluated early speech and language development at 18 and 24 months, and associated factors, based on parental reports.
Method
We followed up the CHILD‐SLEEP birth cohort of 1667 ...Finnish‐speaking families, who were randomly recruited in 2011–2013 during routine visits to maternity clinics in the Pirkanmaa Hospital District of Finland. The women were approximately 32 weeks’ pregnant at enrolment. Parents reported the size of their child's expressive vocabulary, word combinations, intelligibility, finger‐pointing and adherence to instructions. A subsample was studied using the Expressive Language subscale of the Bayley Scales of Infant and Toddler Development, Third Edition.
Results
The children's vocabulary was smaller than previously reported. At 18 months of age, 68.8% of the 997 children had a vocabulary of 20 words or less and 35.7% used about five words at most. At 24 months, 32.4% of the 822 children had a vocabulary of 50 words or less and 18.4% used about 20 words at most. Longer child and parental exposure to electronic media was negatively associated with the size of the child's expressive vocabulary.
Conclusion
Vocabulary size at 18 and 24 months was smaller than previously reported and negatively associated with exposure to electronic media.
Early microbial colonization has a key impact on infant health through nutritional, immunological, and metabolic programming. The origin of child snoring is multifactorial and complex, and may ...thereby also generate long-term health problems. The link between child snoring and gut microbes remains unclear, although indirect evidence exists regarding this relationship. This study aimed to characterize the connection between gut microbiota and child snoring.
In a prospective, observational CHILD-SLEEP birth cohort study, gut microbiota in a subcohort of 43 of these children at 2 years of life was profiled with 16S ribosomal RNA gene amplicon sequencing.
A higher abundance of the Proteobacteria phylum, the Enterobacteriaceae family, and Erysipelotrichaceae family, as well as a higher ratio of Firmicutes to Bacteroidetes were detected in snorers as compared to controls. Furthermore, snorers showed significantly lower microbial diversity and richness than non-snorers.
The snoring children manifest different gut microbiota as compared with healthy children. Considering that snoring and sleep disorders can be a source of long-term consequences, including cardiovascular, metabolic, immunological, neurocognitive and behavioral consequences, our results proposes early microbiota as a new treatment target.
Aim
This prospective study examined the prevalence of snoring during infancy and the prenatal and postnatal risk factors for this condition.
Methods
The study population comprised 1388 infants from ...the CHILD‐SLEEP birth cohort, who were recruited in the Pirkanmaa Hospital District, Finland, between 2011 and 2013. Sleep and background factor questionnaires were filled out prenatally by parents and when the infant was three and eight months old.
Results
The prevalence of habitual snoring was 3.2% at the age of three months and 3.0% at eight months, and snoring infants had more sleeping difficulties at those ages, with odds ratios (ORs) of 3.11 and 4.63, respectively. At three months, snoring infants slept for a shorter length of time (p = 0.001) and their sleep was more restless (p = 0.004). In ordinal logistic regression models, parental snoring (adjusted OR = 1.65 and 2.60) and maternal smoking (adjusted OR = 2.21 and 2.17) were significantly associated with infant snoring at three and eight months, while formula feeding and dummy use (adjusted OR = 1.48 and 1.56) were only associated with infant snoring at three months.
Conclusion
Parental snoring and maternal smoking increased the risk of snoring. Infants who snored also seemed to suffer more from other sleep difficulties.
Narcolepsy results from immune-mediated destruction of hypocretin secreting neurons in hypothalamus, however the triggers and disease mechanisms are poorly understood. Vaccine-attributable risk of ...narcolepsy reported so far with the AS03 adjuvanted H1N1 vaccination Pandemrix has been manifold compared to the AS03 adjuvanted Arepanrix, which contained differently produced H1N1 viral antigen preparation. Hence, antigenic differences and antibody response to these vaccines were investigated.
Increased circulating IgG-antibody levels to Pandemrix H1N1 antigen were found in 47 children with Pandemrix-associated narcolepsy when compared to 57 healthy children vaccinated with Pandemrix. H1N1 antigen of Arepanrix inhibited poorly these antibodies indicating antigenic difference between Arepanrix and Pandemrix. High-resolution gel electrophoresis quantitation and mass spectrometry identification analyses revealed higher amounts of structurally altered viral nucleoprotein (NP) in Pandemrix. Increased antibody levels to hemagglutinin (HA) and NP, particularly to detergent treated NP, was seen in narcolepsy. Higher levels of antibodies to NP were found in children with DQB1*06:02 risk allele and in DQB1*06:02 transgenic mice immunized with Pandemrix when compared to controls.
This work identified 1) higher amounts of structurally altered viral NP in Pandemrix than in Arepanrix, 2) detergent-induced antigenic changes of viral NP, that are recognized by antibodies from children with narcolepsy, and 3) increased antibody response to NP in association of DQB1*06:02 risk allele of narcolepsy. These findings provide a link between Pandemrix and narcolepsy. Although detailed mechanisms of Pandemrix in narcolepsy remain elusive, our results move the focus from adjuvant(s) onto the H1N1 viral proteins.
We examined several parent-reported prenatal and postnatal factors as potential risk factors for attention-deficit and hyperactivity disorder (ADHD) symptomatology in 5-year-old children. Our study ...is based on the CHILD-SLEEP birth cohort. Several parental questionnaires were collected prenatally (32nd pregnancy week) and postnatally (i.e. child aged 3, 8, and 24 months and at 5 years). At 5 years of age, ADHD symptoms were assessed using questionnaires. Our main results showed that being a boy, parental depressive symptoms, more negative family atmosphere or a child’s shorter sleep duration, and maternal authoritarian parenting style predicted inattentive/hyperactive symptoms. Maternal and paternal authoritative parenting style predicted less inattentive/hyperactive symptoms. Children with several risk factors together had the highest risk for inattentive/hyperactive symptoms. Our findings emphasise the need for early screening and treatment of parental mental health, and early evidence-based targeted parental support, to enable early intervention in those children at a risk of developing ADHD.
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