Alanine aminotransferase cutoffs for the pediatric fatty liver disease: Major impact of the reference population.

OBJECTIVES AND STUDY: The often-recommended alanine aminotransferase (ALT) cutoffs (girls 21 U/l, boys 25 U/l) are based on a NHANES cohort. A novel concept of metabolic dysfunction associated steatotic liver disease (MASLD) emphasizes the role of ALT. We tested the prevalence of increased ALT and MASLD in children with overweight or obesity applying population-based and NHANES-based cut-offs. METHODS: Six- to seventeen-year-old children underwent data collection in a prospective Physical Activity and Nutrition in Children (PANIC) study. ALT 95th percentiles were calculated from 1167 separate measurements considering various confounders. Test cohort comprised 1044 children with overweight/obesity. RESULTS: ALT values increased at puberty onset (p = 0.031) and correlated negatively with age in girls (r = -0.222, p < 0.001). Particularly overall and central obesity increased ALT, whereas underweight or metabolic abnormalities had smaller effect. After applying the tested exclusions, the age-related ALT 95th percentiles were 24-29 U/l for girls and 29-32 U/l for boys. In 6-8-year-old children with overweight/obesity, the prevalence of increased ALT and MASLD were 21.6% and 2.4% with age-specific PANIC cutoffs. In older children, when NHANES-based cutoffs were used, there was a trend for higher prevalence of increased ALT and MASLD in all age groups for both sexes, reaching significance for increased ALT in 12-16-year-old boys (NHANES 63.5%, 95% confidence interval [CI]: 56.4%-70.0% vs. PANIC 47.1%, 95% CI [40.1%-54.2%]) and 9-11-year-old girls (60.0% [49.4%-69.8%] vs. 31.8% [22.8%-42.3%]), respectively. Increased ALT/MASLD were more common in boys than in girls, and in boys these increased with age, whereas in girls these peaked at age 9-12 years. CONCLUSION: A reference population impacts on the prevalence of increased ALT and MASLD. Considering this help optimizing screening while avoiding unnecessary investigations and surveillance. The prospective part of this study is registered in clinicaltrials.gov; identifier NCT01803776.

Maternal weight, smoking, and diabetes provided early predictors of longitudinal body mass index growth patterns in childhood.

AIM: The aim of this study was to identify factors affecting overweight growth development using extended body mass index (BMI) data combined with birth and maternal records from Finnish national registries. METHODS: The longitudinal data consist of growth measurements of 7372 from six birth cohorts in Finland: 1974 (n = 1109), 1981 (n = 983), 1991 (n = 607), 1994-1995 (n = 829), 2001 (n = 821), and 2003-2004 (n = 3023). Anthropometric data were collected from birth to age 15 years from the health records. Pregnancy health data were included for the four most recent birth cohorts (n = 2810). A statistical method called trajectory analysis was used to identify different BMI development trajectories. Factors associated with abnormal growth tracks were analysed using logistic regression models. RESULTS: High pre-pregnancy BMI, gestational diabetes mellitus, maternal smoking, and greater gestational weight gain than the Institute of Medicine (United States) recommendations were associated with the overweight growth track. Two of the trajectories didn't seem to follow the normal growth pattern: overweight growth track appeared to lead to overweight, while low birth BMI track showed accelerating growth after the adiposity rebound point of BMI growth. CONCLUSION: These findings suggest that maternal overweight before pregnancy, excessive gestational weight gain, gestational diabetes mellitus, and smoking could potentially be associated with the risk of obesity in children.

Prevalence and associated factors of metabolic-associated fatty liver disease in overweight Finnish children and adolescents.

Introduction: Data on the prevalence of pediatric fatty liver disease remain limited, partly due to challenges in diagnosis. A novel concept of metabolic-associated fatty liver disease (MAFLD) makes it possible to establish the diagnosis in overweight children with sufficiently elevated alanine aminotransferase (ALT). We investigated the prevalence, risk factors, and metabolic co-morbidities of MAFLD in a large group of overweight children. Methods: Data on 703 patients aged 2-16 years examined due to overweight in different levels of healthcare in 2002-2020 were collected retrospectively from patient records. MAFLD was here defined as ALT >2x reference (>44 U/l in girls and >50 U/l in boys) in overweight children according to recently updated definition. Patients with MAFLD and without it were compared, and subgroup analyses were conducted among boys and girls. Results: Median age was 11.5 years, and 43% were girls. Altogether 11% were overweight, 42% obese and 47% severely obese. Abnormal glucose metabolism was present in 44%, dyslipidemia in 51%, hypertension in 48% and type 2 diabetes (T2D) in 2%. MAFLD prevalence varied between 14-20% in examined years without significant change (p=0.878). The pooled prevalence over the years was 15% (boys 18%, girls 11%; p=0.018), peaking in girls at early puberty and increasing in boys with age and puberty. Associated factors in boys were T2D (OR 7.55, 95% CI 1.23-46.2), postpubertal stage (5.39, 2.26-12.8), increased fasting insulin (3.20, 1.44-7.10), hypertriglyceridemia (2.97, 1.67-5.30), hyperglycemia (2.88, 1.64-5.07), decreased high-density lipoprotein (HDL) cholesterol (2.16, 1.18-3.99), older age (1.28, 1.15-1.42) and higher body-mass-index (1.01, 1.05-1.15), and in girls T2D (18.1, 3.16-103), hypertriglyceridemia (4.28, 1.99-9.21), and decreased HDL (4.06, 1.87-8.79). Conclusion: Prevalence of MAFLD was 15%, with no statistically significant increase in the 2000s. The condition was associated in general with male gender, puberty stage and disturbances in glucose and lipid metabolism, and higher age and BMI in boys.

Association of concomitant autoimmunity with the disease features and long-term treatment and health outcomes in Celiac disease.

Background: Celiac disease (CeD) is often accompanied by other autoimmune diseases (AID). However, the association of co-existing autoimmunity with the presentation and treatment success in CeD is unclear. We investigated these issues with a large and well-defined cohort of Finnish patients. Methods: Adult CeD patients (n = 806) were collected from multiple heath care sites via nationwide recruitment. They were interviewed, underwent measurement of CeD autoantibodies, and filled out questionnaires to ascertain quality of life (PGWB) and gastrointestinal symptoms (GSRS) after a median of 9.7 years on a gluten-free diet. Data were supplemented retrospectively from patient records. The results were compared between CeD patients with and without a coexisting AID. Results: Altogether 185 patients had CeD+AID and 621 had CeD only. At CeD diagnosis, patients with CeD+AID were older (median 42 vs. 36 years, p = 0.010) and had more joint symptoms (9.1 vs. 4.2%, p = 0.011), whereas the groups were comparable in sex, family history of CeD, other presenting symptoms, proportion of screen-detected subjects, and severity of duodenal lesion. During follow-up on gluten-free diet, CeD+AID patients experienced poorer general health (median score 12 vs. 14, p < 0.001) in PGWB, more overall gastrointestinal symptoms (2.1 vs. 1.9, p = 0.001), and constipation (2.0 vs. 1.7, p < 0.001) in GSRS, whereas there was no difference in histological and serological recovery, dietary adherence, use of gluten-free oats, smoking, and presence of regular follow-up. Conclusions: Co-existing AID was not significantly associated with the baseline features or with most long-term outcomes in CeD. However, the increased prevalence of gastrointestinal symptoms and reduced poorer self-perceived health during treatment indicates these patients' need for special support.

Prevalence and evolution of snoring and the associated factors in two-year-old children.

OBJECTIVES: To evaluate the prevalence and persistence of snoring during the first two years of life in two Finnish birth cohorts and to assess the associated factors. STUDY DESIGN: The study population comprised 947 children from the CHILD-SLEEP (CS) and 1393 children from the FinnBrain (FB) birth cohorts. Questionnaires were provided to both parents when the child was 24 months of age. The questionnaire consisted of parts concerning the child's sleep and environmental factors. RESULTS: The combined prevalence of habitual snoring in the two birth cohorts at the age of 24 months was 2.3% (95% CI 1.5-3.1), which is markedly lower than reported previously. Children suffering from recurrent infections (CS odds ratio (OR) 3.9, 95% CI 1.2-12.5) or asthma (FB OR 4.3, 1.4-13.5) snored habitually more often. Both the mother's (CS OR 3.2, 1.2-9.0) and father's (CS OR 3.4, 1.4-8.0) snoring every night added to the risk of the child snoring. In the multivariate models, parental snoring (CS adjusted odds ratio (ORa) 2.8, 1.1-6.8), the mother's lower level of education (CS ORa 2.9, 1.2-7.5, FB ORa 2.1, 1.0-4.5), and the mother's lower monthly income (FB ORa 2.9, 1.3-6.3) associated with the child's habitual snoring. CONCLUSIONS: The prevalence of habitual snoring in two Finnish birth cohorts is lower than reported previously. The independent risk factors for habitual snoring at the age of two years were the parents' snoring and the mother's low income and low education.

Type 1 tyrosinemia in Finland: a nationwide study.

BACKGROUND: Introduction of nitisinone and newborn screening (NBS) have transformed the treatment of type 1 tyrosinemia, but the effects of these changes on the long-term outcomes remain obscure. Also, the predictors for later complications, the significance of drug levels and the normalization of laboratory and imaging findings are poorly known. We investigated these issues in a nationwide study. RESULTS: Type 1 tyrosinemia was diagnosed in 22 children in 1978-2019 in Finland. Incidence was 1/90,102, with a significant enrichment in South Ostrobothnia (1/9990). Median age at diagnosis was 5 (range 0.5-36) months, 55% were girls and 13 had homozygotic Trp262X mutation. Four patients were detected through screening and 18 clinically, their main findings being liver failure (50% vs. 100%, respectively, p = 0.026), ascites (0% vs. 53%, p = 0.104), renal tubulopathy (0% vs. 65%, p = 0.035), rickets (25% vs. 65%, p = 0.272), growth failure (0% vs. 66%, p = 0.029), thrombocytopenia (25% vs. 88%, p = 0.028) and anaemia (0% vs. 47%, p = 0.131). One patient was treated with diet, seven with transplantation and 14 with nitisinone. Three late-diagnosed (6-33 months) nitisinone treated patients needed transplantation later. Kidney dysfunction (86% vs. 7%, p = 0.001), hypertension (57% vs. 7%, p = 0.025) and osteopenia/osteoporosis (71% vs. 14%, p = 0.017) were more frequent in transplanted than nitisinone-treated patients. Blood/serum alpha-fetoprotein decreased rapidly on nitisinone in all but one patient, who later developed intrahepatic hepatocellular carcinoma. Liver values normalized in 31 months and other laboratory values except thrombocytopenia within 18 months. Imaging findings normalized in 3-56 months excluding five patients with liver or splenic abnormalities. Low mean nitisinone concentration was associated with higher risk of severe complications (r = 0.758, p = 0.003) despite undetectable urine succinylacetone. CONCLUSIONS: Prognosis of type 1 tyrosinemia has improved in the era of nitisinone, and NBS seems to provide further benefits. Nevertheless, the long-term risk for complications remains, particularly in the case of late diagnosis and/or insufficient nitisinone levels.

Parental reports showed that snoring in infants at three and eight months associated with snoring parents and smoking mothers.

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.

Dysbiosis in Snoring Children: An Interlink to Comorbidities?

BACKGROUND AND OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Change in prevalence of overweight and obesity in Finnish children - comparison between 1974 and 2001.

OBJECTIVE: To analyse the possible changes in the prevalence of overweight and obesity comparing birth cohorts from four different decades in Finland. DESIGN: A retrospective longitudinal growth study. METHODS: The subjects representing five birth cohorts: 1974 (n = 1109), 1981 (n = 987), 1991 (n = 586), 1995 (n = 856) and 2001 (n = 766) in the city of Tampere and three rural municipalities in Finland. Data included five consecutive height and weight measurements from 2 to 15 years of age. Normal weight, overweight and obesity at the time points were classified by body mass index (BMI, kg/m(2) ) according to international age- and gender-specific BMI cut-off points. The chi-square test was used to analyse the differences in the between birth cohorts. RESULTS: The combined prevalence of overweight and obesity decreased significantly in 2-year-old boys (p = 0.009) and girls (p = 0.002) from 1974 to 2001. Insignificant fluctuation was seen in 5- and 7-year-old children. Both the prevalence of obesity and the combined prevalence of overweight and obesity showed a significant increase in 12- (p = 0.031 and p < 0.001) and 15-year-old boys (p < 0.001 in both) from the 1970s to 2000s. In girls, the prevalence of obesity as well as the combined prevalence of overweight and obesity increased significantly in the age group of 12 years (p = 0.023), but not in that of 15 years. CONCLUSIONS: During the last three decades, overweight and obesity have become clearly more prevalent in Finnish young adolescents. This trend has been more obvious in boys than in girls. At the same time, 2-year-old children have shown an opposite trend.

Toddlers get slimmer while adolescents get fatter--BMI distribution in five birth cohorts from four decades in Finland.

AIM: To investigate the trends in the size of Finnish children in five birth cohorts from four decades. METHODS: This is a retrospective longitudinal growth pattern study on children representing five birth cohorts: 1974, 1981, 1991, 1995 and 2001 from the city of Tampere and three rural municipalities. Growth data were collected from birth to 15 years of age, except in birth cohorts 1995 and 2001 until 12 and 5 years. Body mass index (BMI, kg/m²) was calculated. Pearson's chi-square test was used in analysis. RESULTS: The 50th percentile of BMI at birth varied between the 1970's and 2000's (boys: p<0.001, girls: p=0.02), with increase seen in girls. The 50th BMI percentile remained unchanged in 6-month-aged boys, whereas in girls, it varied inconsistent (p=0.04). At 1 and 2 years of age, the 15th, 50th, 85th and 95th BMI percentiles decreased (p=0.26 to <0.001). The 50th BMI percentile remained fairly constant at 5 and 7 years of age. In 12- and 15-year-old boys, the 50th, 85th and 95th percentiles of BMI showed a marked increase (p=0.01 to <0.001). In 12-year-old girls, only the 85th BMI percentile increased (p=0.03). CONCLUSIONS: During the last three decades, Finnish toddlers have become markedly slimmer. Concurrently, an opposite change has taken place in adolescent boys.

Parents underestimate their child`s overweight.

AIM: The aim of this study was to evaluate parents' ability to perceive the weight status of their children. METHODS: This cross-sectional study was performed on 5 (n = 310) and 11-year-old (n = 296) children. The height, weight and waist circumference were measured. Body mass index (BMI, kg/m²) was calculated. The International Obesity Task Force criteria and the British cut-off points were used to classify BMI and waist circumference. Parents filled out a questionnaire concerning their perception of the weight class of their child. The parents and the 11-year-old children estimated their own weight class. For analysis, the measured and perceived weight classes were divided into two categories; normal weight (including underweight) and overweight or obese. To measure the agreement cross-tabulation with Cohen's Kappa was used. Explanatory variables associated with misclassification of overweight children as normal weight were examined by logistic regression modelling. RESULTS: The prevalence of overweight (including obese) was 17.4% and 21.6% in 5- and 11-year-old children in this study. Only a few parents misclassified their normal weight children as overweight. By contrast, a majority of parents to the 5-year-old children and about half of the parents to the 11-year-old children misclassified them as normal weight. Using waist circumference for body size classification did not improve parents' performance. Mothers performed best when estimating own weight class. CONCLUSION: A majority of parents fail to recognize overweight or obesity in their 5- and 11-year-old children. The underestimation of overweight may impair the motivation of the parents to adopt weight control.

Prevalence of overweight and obesity in 5- and 12-year-old Finnish children in 1986 and 2006.

OBJECTIVE: To investigate the prevalence and the trends of overweight and obesity in Finnish 5- and 12-year-old children in 1986 and 2006. DESIGN: Retrospective cross-sectional study. SUBJECTS AND METHODS: Anthropometric data were collected retrospectively from health examinations in Tampere and in three rural municipalities. The size of the 5- and 12-year-old cohorts were 2108 in 1986 and 4013 in 2006, respectively. The body mass index (BMI) was calculated. Overweight and obesity was estimated using the International Obesity Task Force cutoff values (ISO BMI). RESULTS: The prevalence of overweight (ISO BMI >25) and obesity (ISO BMI >30) in 5-year-old boys in 2006 was 9.8% and 2.5% and in girls 17.7% and 4.3%, [corrected] respectively. At the age of 12 years, the corresponding figures in boys were 23.6% and 4.7% and in girls 19.1% and 3.2%. Between 1986 and 2006, the prevalence of overweight in 12-year-old children had increased 1.8 fold in boys (p < 0.001) and 1.5 fold in girls (p = 0.008). Overweight was significantly more common in rural than in urban areas. CONCLUSION: During the last 20 years the prevalence of overweight has markedly increased in 12-year-old Finnish children, but remained nearly unchanged in 5-year-old children.