Gestational age at birth and type 1 diabetes in childhood and young adulthood: a nationwide register study in Finland, Norway and Sweden.

AIMS/HYPOTHESIS: Children and adults born preterm have an increased risk of type 1 diabetes. However, there is limited information on risk patterns across the full range of gestational ages, especially after extremely preterm birth (23-27 weeks of gestation). We investigated the risk of type 1 diabetes in childhood and young adulthood across the full range of length of gestation at birth. METHODS: Data were obtained from national registers in Finland, Norway and Sweden. In each country, information on study participants and gestational age was collected from the Medical Birth Registers, information on type 1 diabetes diagnoses was collected from the National Patient Registers, and information on education, emigration and death was collected from the respective national register sources. Individual-level data were linked using unique personal identity codes. The study population included all individuals born alive between 1987 and 2016 to mothers whose country of birth was the respective Nordic country. Individuals were followed until diagnosis of type 1 diabetes, death, emigration or end of follow-up (31 December 2016 in Finland, 31 December 2017 in Norway and Sweden). Gestational age was categorised as extremely preterm (23-27 completed weeks), very preterm (28-31 weeks), moderately preterm (32-33 weeks), late preterm (34-36 weeks), early term (37-38 weeks), full term (39-41 weeks; reference) and post term (42-45 weeks). HRs and 95% CIs from country-specific covariate-adjusted Cox regression models were combined in a meta-analysis using a common-effect inverse-variance model. RESULTS: Among 5,501,276 individuals, 0.2% were born extremely preterm, 0.5% very preterm, 0.7% moderately preterm, 4.2% late preterm, 17.7% early term, 69.9% full term, and 6.7% post term. A type 1 diabetes diagnosis was recorded in 12,326 (0.8%), 6364 (0.5%) and 16,856 (0.7%) individuals at a median age of 8.2, 13.0 and 10.5 years in Finland, Norway and Sweden, respectively. Individuals born late preterm or early term had an increased risk of type 1 diabetes compared with their full-term-born peers (pooled, multiple confounder-adjusted HR 1.12, 95% CI 1.07, 1.18; and 1.15, 95% CI 1.11, 1.18, respectively). However, those born extremely preterm or very preterm had a decreased risk of type 1 diabetes (adjusted HR 0.63, 95% CI 0.45, 0.88; and 0.78, 95% CI 0.67, 0.92, respectively). These associations were similar across all three countries. CONCLUSIONS/INTERPRETATION: Individuals born late preterm and early term have an increased risk of type 1 diabetes while individuals born extremely preterm or very preterm have a decreased risk of type 1 diabetes compared with those born full term.

Goal management training for improving fatigue in children and adolescents with acquired brain injuries: A 2-year follow-up of a randomised controlled trial.

To explore the long-term effectiveness of a paediatric adaptation of Goal Management Training (pGMT), relative to a psychoeducative program (pBHW), in reducing fatigue after pABI 2 years post-intervention. Thirty-eight youths and their parents completed the Paediatric Quality of Life - Multidimensional Fatigue Scale. Primary outcome measures were Total Fatigue Score, General fatigue, Cognitive fatigue, and Sleep/rest fatigue (parent-report). No significant differences in fatigue symptoms by the parental report was observed between the intervention groups at the 2-year follow-up (total score: F = .16, p = .69; general fatigue: F = .36, p = .55; sleep/rest: F = .48, p = .49; and cognitive fatigue: F = .09, p = .76), nor any time*group interactions (total score: F = .25, p = .86; general fatigue: F = .39, p = .76; sleep/rest: F = .20, p = .89; and cognitive fatigue: F = .08, p = .97). In total, 45% of the participants in the pGMT group and 25% in the pBHW group demonstrated a reliable positive clinical change. The significant improvements in fatigue symptoms that were demonstrated 6 months post-intervention could not be confirmed in this 2-year follow-up study. However, a continued positive tendency on most dimensions of fatigue for the participants in the pGMT group could be observed, suggesting that cognitive rehabilitation may help reduce fatigue.

Paternal and maternal psychiatric history and risk of preterm and early term birth: A nationwide study using Swedish registers.

BACKGROUND: Women with psychiatric diagnoses are at increased risk of preterm birth (PTB), with potential life-long impact on offspring health. Less is known about the risk of PTB in offspring of fathers with psychiatric diagnoses, and for couples where both parents were diagnosed. In a nationwide birth cohort, we examined the association between psychiatric history in fathers, mothers, and both parents and gestational age. METHODS AND FINDINGS: We included all infants live-born to Nordic parents in 1997 to 2016 in Sweden. Psychiatric diagnoses were obtained from the National Patient Register. Data on gestational age were retrieved from the Medical Birth Register. Associations between parental psychiatric history and PTB were quantified by relative risk (RR) and two-sided 95% confidence intervals (CIs) from log-binomial regressions, by psychiatric disorders overall and by diagnostic categories. We extended the analysis beyond PTB by calculating risks over the whole distribution of gestational age, including "early term" (37 to 38 weeks). Among the 1,488,920 infants born throughout the study period, 1,268,507 were born to parents without a psychiatric diagnosis, of whom 73,094 (5.8%) were born preterm. 4,597 of 73,500 (6.3%) infants were born preterm to fathers with a psychiatric diagnosis, 8,917 of 122,611 (7.3%) infants were born preterm to mothers with a pscyhiatric diagnosis, and 2,026 of 24,302 (8.3%) infants were born preterm to both parents with a pscyhiatric diagnosis. We observed a shift towards earlier gestational age in offspring of parents with psychiatric history. The risks of PTB associated with paternal and maternal psychiatric diagnoses were similar for different psychiatric disorders. The risks for PTB were estimated at RR 1.12 (95% CI [1.08, 1.15] p < 0.001) for paternal diagnoses, at RR 1.31 (95% CI [1.28, 1.34] p < 0.001) for maternal diagnoses, and at RR 1.52 (95% CI [1.46, 1.59] p < 0.001) when both parents were diagnosed with any psychiatric disorder, compared to when neither parent had a psychiatric diagnosis. Stress-related disorders were associated with the highest risks of PTB with corresponding RRs estimated at 1.23 (95% CI [1.16, 1.31] p < 0.001) for a psychiatry history in fathers, at 1.47 (95% CI [1.42, 1.53] p < 0.001) for mothers, and at 1.90 (95% CI [1.64, 2.20] p < 0.001) for both parents. The risks for early term were similar to PTB. Co-occurring diagnoses from different diagnostic categories increased risk; for fathers: RR 1.10 (95% CI [1.07, 1.13] p < 0.001), 1.15 (95% CI [1.09, 1.21] p < 0.001), and 1.33 (95% CI [1.23, 1.43] p < 0.001), for diagnoses in 1, 2, and ≥3 categories; for mothers: RR 1.25 (95% CI [1.22, 1.28] p < 0.001), 1.39 (95% CI [1.34, 1.44] p < 0.001) and 1.65 (95% CI [1.56, 1.74] p < 0.001). Despite the large sample size, statistical precision was limited in subgroups, mainly where both parents had specific psychiatric subtypes. Pathophysiology and genetics underlying different psychiatric diagnoses can be heterogeneous. CONCLUSIONS: Paternal and maternal psychiatric history were associated with a shift to earlier gestational age and increased risk of births before full term. The risk consistently increased when fathers had a positive history of different psychiatric disorders, increased further when mothers were diagnosed and was highest when both parents were diagnosed.

Preterm birth and asthma and COPD in adulthood: a nationwide register study from two Nordic countries.

BACKGROUND: Preterm birth affects lungs in several ways but few studies have follow-up until adulthood. We investigated the association of the entire spectrum of gestational ages with specialist care episodes for obstructive airway disease (asthma and chronic obstructive pulmonary disease (COPD)) at age 18-50 years. METHODS: We used nationwide registry data on 706 717 people born 1987-1998 in Finland (4.8% preterm) and 1 669 528 born 1967-1999 in Norway (5.0% preterm). Care episodes of asthma and COPD were obtained from specialised healthcare registers, available in Finland for 2005-2016 and in Norway for 2008-2017. We used logistic regression to estimate odds ratios (ORs) for having a care episode with either disease outcome. RESULTS: Odds of any obstructive airway disease in adulthood for those born at <28 or 28-31 completed weeks were 2-3-fold of those born full term (39-41 completed weeks), persisting after adjustments. For individuals born at 32-33, 34-36 or 37-38 weeks, the odds were 1.1- to 1.5-fold. Associations were similar in the Finnish and the Norwegian data and among people aged 18-29 and 30-50 years. For COPD at age 30-50 years, the OR was 7.44 (95% CI 3.49-15.85) for those born at <28 weeks, 3.18 (95% CI 2.23-4.54) for those born at 28-31 weeks and 2.32 (95% CI 1.72-3.12) for those born at 32-33 weeks. Bronchopulmonary dysplasia in infancy increased the odds further for those born at <28 and 28-31 weeks. CONCLUSION: Preterm birth is a risk factor for asthma and COPD in adulthood. The high odds of COPD call for diagnostic vigilance when adults born very preterm present with respiratory symptoms.

Validity of the Behavioural Assessment of the Dysexecutive Syndrome for Children (BADS-C) in children and adolescents with pediatric acquired brain injury.

The Behavioural Assessment of the Dysexecutive Syndrome for Children (BADS-C) was developed to address the need for a standardized ecologically valid test of executive function (EF) in the pediatric population. Our study aimed to investigate the discriminant, concurrent, and ecological validity of BADS-C in a sample with pediatric acquired brain injury (pABI). Seventy-four participants with pABI aged 10-17 years were included to a pre-registered randomized controlled trial, and baseline assessment was used for the current study. Controls consisted of 60 participants aged 10-17 years. Participants with pABI were assessed with neuropsychological tests and questionnaires of EF, and measurements of general intellectual ability (IQ). Results showed that all BADS-C subtests discriminated between participants with pABI and controls, except for the Playing Cards Test. Concurrent and ecological validity was demonstrated through associations between BADS-C total score, Key Search Test, and Zoo Map Test 1, and neuropsychological tests and teacher questionnaire ratings of EF. Key Search Test and Zoo Map Test 1 predicted teacher ratings of EF, beyond IQ and other neuropsychological test of EF. These findings provide support for BADS-C as a valid clinical assessment tool that can detect everyday executive dysfunction in the pABI population, and guide rehabilitation and treatment decisions.

Gestational age and cancer risk up to young adulthood in Swedish population born 1974 to 2013: A population-based cohort study.

We examined the association between gestational age and risk of any primary cancer and observed whether the risk patterns differed by sex, birth weight for gestational age categories, cancer site and age of onset. All people live-born in Sweden 1974 to 2013 were prospectively followed up from birth until 2016 using national registers. Gestational age was extracted from the Medical Birth Register and primary malignant cancer diagnoses were from the Swedish cancer register. The adjusted hazard ratios (aHR) for any primary cancer according to weekly gestational age and gestational age categories were determined using cox proportional hazards models adjusted for birth year and parental age. The study included 3 137 691 people; 180 363 (5.8%) born preterm and 254 790 (8.1%) born postterm. They were followed up for 71 691 112 person-years, to a maximum of 43 years and recorded 22 604 new cancers. Although aHRs for the predefined GA categories were only increased for moderate to late preterm delivery (aHR 1.07, 95% CI 1.01-1.14), gestational week-specific aHRs were increased for gestational weeks 30 to 35, with greatest aHR observed for 31 weeks (aHR 1.18, 95% CI 1.05-1.32). Increased cancer risk related to shorter gestational ages were observed particularly for women, those born small for gestational age, childhood cancers and for cancers originating at certain sites (eg, testicular and liver cancer). We provide the first evidence that those born between 30 and 35 weeks gestation may have increased risk of any primary malignant cancer up to young adulthood. Additionally, increasing gestational ages may reduce the risk of testicular and liver cancer.

Rehabilitation of executive function in chronic paediatric brain injury: a randomized controlled trial.

BACKGROUND: Impaired executive functions (EFs, i.e., purposeful, goal-directed behaviour) cause significant disability after paediatric acquired brain injury (pABI) warranting efficient interventions. Goal Management Training (GMT) is a metacognitive protocol proven effective for executive dysfunction in adults. This pre-registered, blinded, parallel-randomized controlled trial evaluated efficacy of a paediatric adaptation (pGMT) compared to a psychoeducative control (paediatric Brain Health Workshop, pBHW) to improve EF. METHODS: Children aged 10 to 17 years with pABI (e.g., traumatic brain injury, brain tumour), ≥ 1 year post-onset or ended treatment, with parent-reported EF complaints were eligible. Participants were randomized (computer-algorithm) to either group-based pGMT (n = 38) or pBHW (n = 38). The active control was tailored to keep non-specific factors constant. Thus, both treatments comprised of 7 sessions at hospitals over 3 consecutive weeks, followed by 4 weeks of telephone counselling of participants, parents, and teachers. Parent-reported daily life EF, assessed by the questionnaire Behavior Rating Inventory of Executive Function (BRIEF; Behavioral Regulation Index (BRI) and Metacognition Index (MI)), were co-primary outcomes 6 months post-intervention. Secondary outcomes included neuropsychological tests and a complex naturalistic task (Children's Cooking Task). RESULTS: Seventy-three participants (96%) completed allocated interventions and 71 (93%) attended the 6-month follow-up. The results demonstrated no significant difference in effectiveness for the two interventions on parent-reported EF: For BRIEFBRI, mean (SD) raw score for pGMT was 42.7 (8.8) and 38.3 (9.3) for pBHW. Estimated difference was - 2.3 (95% CI - 5.1 to 0.6). For BRIEFMI, the corresponding results were 80.9 (20.4) for GMT and 75.5 (19.3) for pBHW. Estimated difference was - 1.4 (95% CI -8.5 to 5.8). In performance-based tests, pGMT was associated with improved inhibition and executive attention, while pBHW was associated with fewer errors in the naturalistic task. CONCLUSIONS: In pABI, metacognitive training (pGMT) did not demonstrate additional effectiveness on parent-reported daily life EF at 6-month follow-up, when compared to a psychoeducative control. Both interventions were well-tolerated and demonstrated distinct improvements at different EF assessment levels. To conclude on pGMT efficacy, larger studies are needed, including further investigation of appropriate assessment levels and possible differences in effect related to treatment duration, developmental factors, and injury characteristics. TRIAL REGISTRATION: ClinicalTrials.gov , NCT0321534211, 11 July 2017.

Gestational age and the risk of autism spectrum disorder in Sweden, Finland, and Norway: A cohort study.

INTRODUCTION: The complex etiology of autism spectrum disorder (ASD) is still unresolved. Preterm birth (<37 weeks of gestation) and its complications are the leading cause of death of babies in the world, and those who survive often have long-term health problems. Length of gestation, including preterm birth, has been linked to ASD risk, but robust estimates for the whole range of gestational ages (GAs) are lacking. The primary objective of this study was to provide a detailed and robust description of ASD risk across the entire range of GAs while adjusting for sex and size for GA. METHODS AND FINDINGS: Our study had a multinational cohort design, using population-based data from medical registries in three Nordic countries: Sweden, Finland, and Norway. GA was estimated in whole weeks based on ultrasound. Children were prospectively followed from birth for clinical diagnosis of ASD. Relative risk (RR) of ASD was estimated using log-binomial regression. Analyses were also stratified by sex and by size for GA. The study included 3,526,174 singletons born 1995 to 2015, including 50,816 (1.44%) individuals with ASD. In the whole cohort, 165,845 (4.7%) were born preterm. RR of ASD increased by GA, from 40 to 24 weeks and from 40 to 44 weeks of gestation. The RR of ASD in children born in weeks 22-31, 32-36, and 43-44 compared to weeks 37-42 were estimated at 2.31 (95% confidence interval [CI] 2.15-2.48; 1.67% vs 0.83%; p-value < 0.001), 1.35 (95% CI 1.30-1.40; 1.08% vs 0.83%; p-value < 0.001), and 1.37 (95% CI 1.21-1.54; 1.74% vs 0.83%; p-value < 0.001), respectively. The main limitation of this study is the lack of data on potential causes of pre- or postterm birth. Also, the possibility of residual confounding should be considered. CONCLUSION: In the current study, we observed that the RR of ASD increased weekly as the date of delivery diverged from 40 weeks, both pre- and postterm, independently of sex and size for GA. Given the unknown etiology of ASD and the lifelong consequences of the disorder, identifying groups of increased risk associated with a potentially modifiable risk factor is important.

The Burden of Human Metapneumovirus and Respiratory Syncytial Virus Infections in Hospitalized Norwegian Children.

Background: The burden of severe human metapneumovirus (HMPV) respiratory tract infections (RTIs) in European children has not been clarified. We assessed HMPV in Norwegian children and compared hospitalization rates for HMPV and respiratory syncytial virus (RSV). Methods: We prospectively enrolled children (<16 years old) hospitalized with RTI and asymptomatic controls (2006-2015). Nasopharyngeal aspirate samples were analyzed with polymerase chain reaction (PCR) tests for HMPV, RSV, and 17 other pathogens. We genotyped HMPV-positive samples and assessed shedding time in 32 HMPV-infected children. Results: In children with RTI, HMPV was detected in 7.3% (267 of 3650) and RSV in 28.7% (1048 of 3650). Among controls, 2.1% (7 of 339) had low HMPV levels detected by PCR, but all were culture negative. HMPV primarily occurred from January to April and in regular epidemics. At least 2 HMPV subtypes occurred each season. The average annual hospitalization rates in children <5 years old with lower RTI were 1.9/1000 (HMPV) and 10.4/1000 (RSV). Among children with RTI, the median HMPV shedding time by PCR was 13 days (range, 6-28 days), but all were culture negative (noninfectious) after 13 days. Conclusions: HMPV appears in epidemics in Norwegian children, with a hospitalization rate 5 times lower than RSV. Low levels of HMPV are rarely detected in healthy children.

Associations of Maternal Vitamin B12 Concentration in Pregnancy With the Risks of Preterm Birth and Low Birth Weight: A Systematic Review and Meta-Analysis of Individual Participant Data.

Vitamin B12 (hereafter referred to as B12) deficiency in pregnancy is prevalent and has been associated with both lower birth weight (birth weight <2,500 g) and preterm birth (length of gestation <37 weeks). Nevertheless, current evidence is contradictory. We performed a systematic review and a meta-analysis of individual participant data to evaluate the associations of maternal serum or plasma B12 concentrations in pregnancy with offspring birth weight and length of gestation. Twenty-two eligible studies were identified (11,993 observations). Eighteen studies were included in the meta-analysis (11,216 observations). No linear association was observed between maternal B12 levels in pregnancy and birth weight, but B12 deficiency (<148 pmol/L) was associated with a higher risk of low birth weight in newborns (adjusted risk ratio = 1.15, 95% confidence interval (CI): 1.01, 1.31). There was a linear association between maternal levels of B12 and preterm birth (per each 1-standard-deviation increase in B12, adjusted risk ratio = 0.89, 95% CI: 0.82, 0.97). Accordingly, B12 deficiency was associated with a higher risk of preterm birth (adjusted risk ratio = 1.21, 95% CI: 0.99, 1.49). This finding supports the need for randomized controlled trials of vitamin B12 supplementation in pregnancy.

Inotropic Therapy in Newborns, A Population-Based National Registry Study.

OBJECTIVE: To describe the use of inotropic drugs and the characteristics of neonates receiving such treatment in a national cohort of patients admitted to neonatal ICUs in Norway. DESIGN: A national registry study of patients included in the Norwegian Neonatal Network database 2009-2014. Demographic and treatment data, including the use of inotropic drugs (dopamine, dobutamine, epinephrine, norepinephrine, milrinone, and levosimendan) and outcomes, were retrieved and analyzed. SETTING: Neonatal ICUs in Norway. PATIENTS: All patients admitted to Norwegian neonatal ICUs 2009-2014 with a postmenstrual age of less than 310 days at admission, corresponding to a postnatal age of less than 28 days for a child born at term (n = 36 397). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Inotropic drugs were administered to 974 of 361,803 live born infants (0.27%) in the study period, representing 2.7% of the neonatal ICU patient population. The relative proportion of neonatal ICU patients receiving inotropes decreased with increasing gestational age, yet 41% of the patients receiving inotropes were born at term. Of note, 89.8% of treated patients received dopamine. Use of inotropes was particularly prevalent in patients with necrotizing enterocolitis (72.4%) and pulmonary hypertension (42.1%) and in patients with gestational age less than 28 weeks (28.2%). Inotropic treatment initiated in the first week of life (84.2%) was associated with birth asphyxia and pulmonary hypertension, whereas treatment initiated after the first week of life was associated with extremely preterm birth, neonatal surgery, neonatal sepsis, cardiac disease, and necrotizing enterocolitis. CONCLUSIONS: This comprehensive epidemiologic study indicates that less than 0.3% of newborns receive inotropic support in the neonatal period. Dopamine was the most commonly used drug. Relating inotrope use to clinical condition, gestational age, and postnatal age may be useful for clinicians and helpful in delineating relevant patient populations for future clinical trials.

Bronchial reactivity and asthma at school age after early-life metapneumovirus infection.

Background: The association between early-life lower respiratory tract infection (LRTI) and asthma is well established. Knowledge about bronchial hyperresponsiveness (BHR) and asthma after metapneumovirus (MPV) LRTI is scarce. The aim of this study was to assess BHR and current asthma in school-aged children after hospital admission for early-life LRTI with MPV, and to compare with more well-known viruses, rhinovirus (RV) and respiratory syncytial virus (RSV), and with controls. Methods: A cohort consisting of children admitted for LRTI and controls was followed-up at school age with a clinical research assessment and lung function tests, including a methacholine provocation test. Current asthma was defined based on objective variable airway obstruction and clinical symptoms. BHR and asthma were compared according to viral groups. Results: 135 children (median age 9.3 years) were included (16 MPV, 34 RV, 51 RSV, 13 mixed infections and 21 controls). Compared with controls there was increased BHR after MPV and RV LRTI (provocative dose causing a 20% fall in forced expiratory volume in 1 s and dose-response slope; p<0.05). Using Kaplan-Meier statistics, BHR was increased for MPV compared with both controls and RSV (p=0.02 and p=0.01). The proportion of children with current asthma at follow-up was higher in the LRTI children compared with the controls (46% versus 24%; p=0.06). Among children who had undergone MPV and RV infection, 50% fulfilled the asthma criteria compared with 43% in the RSV group (p=0.37). Conclusion: We found increased BHR and a high prevalence of asthma in school-aged children after early-life MPV infection, and findings were similar to RV, and less to RSV, compared with controls.

Association between parental psychiatric disorders and risk of offspring autism spectrum disorder: a Swedish and Finnish population-based cohort study.

Background: Roughly more than one in six adults worldwide suffer from psychiatric conditions. Sporadic studies have associated parental psychiatric disorders with autism spectrum disorder in offspring. Comprehensively examining the association between parental psychiatric disorders and offspring autism spectrum disorder is needed to guide health policies, and to inform etiologic studies. Methods: We included all children born in Sweden and Finland 1997-2016. Diagnoses were clinically ascertained from National Registers through 2017. We calculated adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for autism spectrum disorder in offspring of fathers and mothers with psychiatric disorders, in both parents jointly and across co-occurring conditions. Findings: Among 2,505,842 children, 33,612 were diagnosed with autism spectrum disorder, of which 20% had a parent with psychiatric disorders. The risk of autism spectrum disorder was increased across all psychiatric disorders in fathers (Sweden: aHR = 2.02, 95% CI = 1.92-2.12; Finland: aHR = 1.63, 95% CI = 1.50-1.77), mothers (Sweden: aHR = 2.34, 95% CI = 2.24-2.43; Finland aHR = 2.12, 95% CI = 1.92-2.28), or both parents (Sweden: aHR = 3.76, 95% CI = 3.48-4.07; Finland aHR = 3.61, 95% CI = 3.20-4.07), compared to neither parents. Co-occurrence of parental psychiatric disorders further increased risk (e.g., Sweden: for one, two or ≥three different diagnostic categories compared to no diagnosis, in fathers aHR = 1.81, 2.07, 2.52; in mothers aHR = 2.05, 2.63, 3.57). Interpretation: Psychiatric disorders in both parents conveyed the highest risk of offspring autism spectrum disorder, followed by mothers and then fathers. The risk increased with number of co-occurring disorders. All parental psychiatric disorders were associated with increased the risk of autism spectrum disorder. To reliably assess the risk of autism spectrum disorder in children, a comprehensive history incorporating the full range of parental psychiatric disorders is needed beyond solely focusing on familial autism spectrum disorder. Funding: Swedish-Research-Council-2021-0214.

Maternal infection in pregnancy and risk of asthma in offspring.

This study estimates the effect of maternal infections during pregnancy on childhood asthma. One-thousand four-hundred and twenty-eight pregnant women were prospectively followed using structured interviews and chart review until their child's 6th year of life. Infections were identified from outpatient and hospital visits. Childhood asthma was defined as physician diagnosis with symptoms at age six. Adjusted odds ratios were calculated from multivariable logistic regression models. Six-hundred and thirty-five women experienced an infection during pregnancy. Among antepartum infections, maternal urinary tract infections were significantly associated with childhood asthma (aOR 1.60, 95 % CI 1.12-2.29). Chorioamnionitis and maternal group beta streptococcus colonization were not significantly associated with an increased risk in childhood asthma. This study found an increased risk of asthma in children of women diagnosed with urinary tract infections during pregnancy, while other maternal infections did not increase the risk.

The Contribution of Viruses and Bacteria to Childhood Community-acquired Pneumonia: 11-Year Observational Study From Norway.

BACKGROUND: Viruses are associated with pediatric community-acquired pneumonia (CAP) but are also common in the upper airways of healthy children. We have determined the contribution of respiratory viruses and bacteria by comparing children with CAP and hospital controls. METHODS: Children less than 16 years old with radiologically confirmed CAP (n = 715) were enrolled over an 11-year period. Children admitted for elective surgery during the same period served as controls (n = 673). Nasopharyngeal aspirates were tested for 20 respiratory pathogens by semiquantitative polymerase chain reaction tests and cultivated for bacteria and viruses. We used logistic regression to calculate adjusted odds ratios [aOR; 95% confidence intervals (CIs)], and estimated population-attributable fractions (95% CI). RESULTS: At least 1 virus was detected in 85% of cases and 76% of controls, and greater than or equal to 1 bacterium was detected in 70% of cases and controls. The presence of respiratory syncytial virus (RSV) (aOR, 16.6; 95% CI: 9.81-28.2), human metapneumovirus (HMPV) (13.0; 6.17-27.5) and Mycoplasma pneumoniae (27.7; 8.37-91.6) were most strongly associated with CAP. For RSV and HMPV, there were significant trends between lower cycle-threshold values indicating higher viral genomic loads, and higher aORs for CAP. The population-attributable fraction estimates of RSV, HMPV, human parainfluenza virus, influenza virus and M. pneumoniae were 33.3% (32.2-34.5), 11.2% (10.5-11.9), 3.7% (1.0-6.3), 2.3% (1.0-3.6) and 4.2% (4.1-4.4), respectively. CONCLUSIONS: RSV, HMPV and M. pneumoniae were most strongly related to pediatric CAP and accounted for half of all cases. There were positive trends between increasing viral genomic loads of RSV and HMPV, and higher odds for CAP.

Preterm birth and the risk of multimorbidity in adolescence: a multiregister-based cohort study.

BACKGROUND: Multimorbidity affects people of all ages, but the risk factors of multimorbidity in adolescence are unclear. The aim of this study was to examine preterm birth (<37 weeks) as a shared risk factor for multiple health outcomes and the role of gestational age (degree of prematurity) in the development of increasingly complex multimorbidity (two, three, or four health outcomes) in adolescence (age 10-18 years). METHODS: We used population-wide data from Finland (1 187 610 adolescents born 1987-2006) and Norway (555 431 adolescents born 1998-2007). Gestational age at birth was ascertained from medical birth registers and categorised as 23-27 weeks (extremely preterm), 28-31 weeks (very preterm), 32-33 weeks (moderately preterm), 34-36 weeks (late preterm), 37-38 weeks (early term), 39-41 weeks (term, reference category) and 42-44 weeks (post-term). Children who died or emigrated before their 10th birthday, and those with missing or implausible data on gestational age, birthweight, or covariates, were excluded. Health outcomes at age 10-18 years were ascertained from specialised health care and mortality registers. We calculated hazard ratios (HRs) and population attributable fractions (PAFs) with 95% CIs for multiple health outcomes during adolescence. FINDINGS: Individuals were followed up from age 10 to 18 years (mean follow-up: 6 years, SD: 3 years). Preterm birth was associated with increased risks of 20 hospital-treated malignant, cardiovascular, endocrinological, neuropsychiatric, respiratory, genitourinary, and congenital health outcomes, after correcting for multiple testing and ignoring small effects (HR <1·2). Confounder-adjusted HRs comparing preterm with term-born adolescents were 2·29 (95% CI 2·19-2·39) for two health outcomes (PAF 9·0%; 8·3-9·6), and 4·22 (3·66-4·87) for four health outcomes (PAF 22·7%; 19·4-25·8) in the Finnish data. Results in the Norwegian data showed a similar pattern. We observed a consistent dose-response relationship between an earlier gestational age and elevated risks of increasingly complex multimorbidity in both datasets. INTERPRETATION: Preterm birth is associated with increased risks of diverse multimorbidity patterns at age 10-18 years. Adolescents with a preterm-born background could benefit from diagnostic vigilance directed at multimorbidity and a multidisciplinary approach to health care. FUNDING: European Union Horizon 2020, Academy of Finland, Foundation for Pediatric Research, Sigrid Jusélius Foundation, Signe and Ane Gyllenberg Foundation.

Cognitive rehabilitation in paediatric acquired brain injury-A 2-year follow-up of a randomised controlled trial.

Background: Goal management training (GMT), a metacognitive rehabilitation method that has been demonstrated to improve executive function (EF) in adults with acquired brain injury (ABI), could potentially be effective for children in the chronic phase of ABI. In a previously published randomised controlled trial (RCT), the efficacy of a paediatric adaptation of GMT (pGMT) compared to a psychoeducative control intervention (paediatric Brain Health Workshop, pBHW) was investigated. Comparable improvements in EF in both groups were found at 6-month follow-up. However, a specific effect of pGMT could not be conclusively proven. The present study reports 2-year follow-up data (T4; T1: baseline, T2: post-intervention, T3: 6-month follow-up, and T4: 2-year follow-up) from this original RCT. Methods: A total of 38 children and adolescents and also their parents completed questionnaires tapping into daily life EF. Explorative analyses were conducted comparing the 2-year follow-up data (T4) with the baseline (T1) and 6-month follow-up data (T3) for T4-participants in the two intervention groups (pGMT; n = 21, pBHW; n = 17), and we also assessed T4-participants vs. non-responders (n = 38) in the RCT. Primary outcome measures were the Behavioural Regulation Index (BRI) and the Metacognition Index (MI) derived from the Behaviour Rating Inventory of Executive Function (BRIEF) parent report. Results: No difference between intervention groups was found (BRI, F = 2.25, p = 0.143, MI, F = 1.6, p = 0.213), and no time*group interaction (BRI, F = 0.07, p = 0.976, MI, F = 0.137, p = 0.937) could be seen at the 2-year follow-up. Nevertheless, both pGMT and the pBHW groups improved daily EF as measured by parental reports over time from the baseline to T4 (p = 0.034). T4 participants and non-responders shared similar baseline characteristics. Conclusion: Our results extend the findings from the 6-month follow-up previously published. Both pGMT and pBHW groups sustained their improvements in daily life EFs from the baseline, but additional effectiveness of pGMT relative to pBHW was not found.

The Burden of Human Bocavirus 1 in Hospitalized Children With Respiratory Tract Infections.

BACKGROUND: Human bocavirus 1 (HBoV1) is frequently codetected with other viruses, and detected in asymptomatic children. Thus, the burden of HBoV1 respiratory tract infections (RTI) has been unknown. Using HBoV1-mRNA to indicate true HBoV1 RTI, we assessed the burden of HBoV1 in hospitalized children and the impact of viral codetections, compared with respiratory syncytial virus (RSV). METHODS: Over 11 years, we enrolled 4879 children <16 years old admitted with RTI. Nasopharyngeal aspirates were analyzed with polymerase chain reaction for HBoV1-DNA, HBoV1-mRNA, and 19 other pathogens. RESULTS: HBoV1-mRNA was detected in 2.7% (130/4850) samples, modestly peaking in autumn and winter. Forty-three percent with HBoV1 mRNA were 12-17 months old, and only 5% were <6 months old. A total of 73.8% had viral codetections. It was more likely to detect HBoV1-mRNA if HBoV1-DNA was detected alone (odds ratio [OR]: 3.9, 95% confidence interval [CI]: 1.7-8.9) or with 1 viral codetection (OR: 1.9, 95% CI: 1.1-3.3), compared to ≥2 codetections. Codetection of severe viruses like RSV had lower odds for HBoV1-mRNA (OR: 0.34, 95% CI: 0.19-0.61). The yearly lower RTI hospitalization rate per 1000 children <5 years was 0.7 for HBoV1-mRNA and 8.7 for RSV. CONCLUSIONS: True HBoV1 RTI is most likely when HBoV1-DNA is detected alone, or with 1 codetected virus. Hospitalization due to HBoV1 LRTI is 10-12 times less common than RSV.

Intelligence and executive function are associated with age at insult, time post-insult, and disability following chronic pediatric acquired brain injury.

Background: Pediatric acquired brain injury (pABI) profoundly affects cognitive functions, encompassing IQ and executive functions (EFs). Particularly, young age at insult may lead to persistent and debilitating deficits, affecting daily-life functioning negatively. This study delves into the intricate interplay of age at insult, time post-insult, and their associations with IQ and EFs during chronic (>1 year) pABI. Additionally, we investigate cognitive performance across different levels of global function, recognizing the multifaceted nature of developmental factors influencing outcomes. Methods: Drawing upon insult data and baseline information analyzing secondary outcomes from a multicenter RCT, including comprehensive medical and neuropsychological assessments of participants aged 10 to 17 years with pABI and parent-reported executive dysfunctions. The study examined associations between age at insult (early, EI; ≤7y vs. late, LI; > 7y) and time post-insult with IQ and EFs (updating, shifting, inhibition, and executive attention). Additionally, utilizing the Pediatric Glasgow Outcome Scale-Extended, we explored cognitive performance across levels of global functioning. Results: Seventy-six participants, median 8 years at insult and 5 years post-insult, predominantly exhibiting moderate disability (n = 38), were included. Notably, participants with LI demonstrated superior IQ, executive attention, and shifting compared to EI, [adjusted mean differences with 95% Confidence Intervals (CIs); 7.9 (1.4, 14.4), 2.48 (0.71, 4.24) and 1.73 (0.03, 3.43), respectively]. Conversely, extended post-insult duration was associated with diminished performances, evident in mean differences with 95% CIs for IQ, updating, shifting, and executive attention compared to 1-2 years post-insult [-11.1 (-20.4, -1.7), -8.4 (-16.7, -0.1), -2.6 (-4.4, -0.7), -2.9 (-4.5, -1.2), -3.8 (-6.4, -1.3), -2.6 (-5.0, -0.3), and -3.2 (-5.7, -0.8)]. Global function exhibited a robust relationship with IQ and EFs. Conclusion: Early insults and prolonged post-insult durations impose lasting tribulations in chronic pABI. While confirmation through larger studies is needed, these findings carry clinical implications, underscoring the importance of vigilance regarding early insults. Moreover, they dispel the notion that children fully recover from pABI; instead, they advocate equitable rehabilitation offerings for pABI, tailored to address cognitive functions, recognizing their pivotal role in achieving independence and participation in society. Incorporating disability screening in long-term follow-up assessments may prove beneficial.

Gestational age at birth and hospitalisations for infections among individuals aged 0-50 years in Norway: a longitudinal, register-based, cohort study.

Background: Preterm birth is associated with increased risk of childhood infections. Whether this risk persists into adulthood is unknown and limited information is available on risk patterns across the full range of gestational ages. Methods: In this longitudinal, register-based, cohort study, we linked individual-level data on all individuals born in Norway (January 01, 1967-December 31, 2016) to nationwide hospital data (January 01, 2008-December 31, 2017). Gestational age was categorised as 23-27, 28-31, 32-33, 34-36, 37-38, 39-41, and 42-44 completed weeks. The analyses were stratified by age at follow-up: 0-11 months and 1-5, 6-14, 15-29, and 30-50 years. The primary outcome was hospitalisation due to any infectious disease, with major infectious disease groups as secondary outcomes. Adjusted hospitalisation rate ratios (RRs) for any infection and infectious disease groups were estimated using negative binomial regression. Models were adjusted for year of birth, maternal age at birth, parity, and sex, and included an offset parameter adjusted for person-time at risk. Findings: Among 2,695,830 individuals with 313,940 hospitalisations for infections, we found a pattern of higher hospitalisation risk in lower gestational age groups, which was the strongest in childhood but still evident in adulthood. Comparing those born very preterm (28-31) and late preterm (34-36) to full-term (39-41 weeks), RRs (95% confidence interval) for hospitalisation for any infectious disease at ages 1-5 were 3.3 (3.0-3.7) and 1.7 (1.6-1.8), respectively. At 30-50 years, the corresponding estimates were 1.4 (1.2-1.7) and 1.2 (1.1-1.3). The patterns were similar for the infectious disease groups, including bacterial and viral infections, respiratory tract infections (RTIs), and infections not attributable to RTIs. Interpretation: Increasing risk of hospitalisations for infections in lower gestational age groups was most prominent in children but still evident in adolescents and adults. Possible mechanisms and groups that could benefit from vaccinations and other prevention strategies should be investigated. Funding: St. Olav's University Hospital and Norwegian University of Science and Technology, Norwegian Research Council, Liaison Committee for education, research and innovation in Central Norway, European Commission, Academy of Finland, Sigrid Jusélius Foundation, Foundation for Pediatric Research, and Signe and Ane Gyllenberg Foundation.