Quality of life and socioeconomic and educational status in patients with congenital hypothyroidism.

BACKGROUND: The aim of this study was to investigate the influence of primary congenital hypothyroidism (CH) on quality of life, level of education and socioeconomic status (SES). METHODS: Two independent study cohorts, a national and a regional, were collected from Finnish national registers and patient records. Data on social security benefits, SES, marital status, and education were collected from Statistics Finland. Health-related quality of life (HRQoL) was studied in the regional patient cohort with the standardized 15D and 16D instruments. RESULTS: There were no statistically significant differences in education level, marital status, or SES between CH patients (n = 40) and their matched controls at the age of 25 years. The mean 15D score was both statistically significantly and clinically importantly lower in CH patients (n = 29) than controls (0.904 vs. 0.953, p = 0.008). CH patients reported significantly lower scores across various dimensions of physical and mental HRQoL, including breathing, sleeping, speech, excretion, mental function, distress, and vitality. The mean 16D score was lower in CH patients compared to controls (0.917, vs. 0.947), but without statistical significance. CONCLUSION: SES of CH patients did not differ from matched controls. Thus, most CH patients integrate well into society, but their HRQoL is impaired. IMPACT: Most patients with primary congenital hypothyroidism integrate well into society. In the current study, their socioeconomic and marital status did not differ from matched controls at the age of 25 years. However, health-related quality of life measured using 15D instrument was impaired. Every fourth patient reported that congenital hypothyroidism influenced everyday life.

Association of Long-Term Habitual Dietary Fiber Intake since Infancy with Gut Microbiota Composition in Young Adulthood.

BACKGROUND: Dietary fiber is an important health-promoting component of the diet, which is fermented by the gut microbes that produce metabolites beneficial for the host's health. OBJECTIVES: We studied the associations of habitual long-term fiber intake from infancy with gut microbiota composition in young adulthood by leveraging data from the Special Turku Coronary Risk Factor Intervention Project, an infancy-onset 20-y dietary counseling study. METHODS: Fiber intake was assessed annually using food diaries from infancy ≤ age 20 y. At age 26 y, the first postintervention follow-up study was conducted including food diaries and fecal sample collection (N = 357). Cumulative dietary fiber intake was assessed as the area under the curve for energy-adjusted fiber intake throughout the study (age 0-26 y). Gut microbiota was profiled using 16S ribosomal ribonucleic acid amplicon sequencing. The primary outcomes were 1) α diversity expressed as the observed richness and Shannon index, 2) ß diversity using Bray-Curtis dissimilarity scores, and 3) differential abundance of each microbial taxa with respect to the cumulative energy-adjusted dietary fiber intake. RESULTS: Higher cumulative dietary fiber intake was associated with decreased Shannon index (ß = -0.019 per unit change in cumulative fiber intake, P = 0.008). Overall microbial community composition was related to the amount of fiber consumed (permutational analysis of variation R2 = 0.005, P = 0.024). The only genus that was increased with higher cumulative fiber intake was butyrate-producing Butyrivibrio (log2 fold-change per unit change in cumulative fiber intake 0.40, adjusted P = 0.023), whereas some other known butyrate producers such as Faecalibacterium and Subdoligranulum were decreased with higher cumulative fiber intake. CONCLUSIONS: As early-life nutritional exposures may affect the lifetime microbiota composition and disease risk, this study adds novel information on the associations of long-term dietary fiber intake with the gut microbiota. This trial was registered at clinicaltrials.gov as NCT00223600.

Association of tobacco smoke exposure with metabolic profile from childhood to early adulthood: the Special Turku Coronary Risk Factor Intervention Project.

AIMS: To investigate the associations between passive tobacco smoke exposure and daily smoking with a comprehensive metabolic profile, measured repeatedly from childhood to adulthood. METHODS AND RESULTS: Study cohort was derived from the Special Turku Coronary Risk Factor Intervention Project (STRIP). Smoking status was obtained by questionnaire, while serum cotinine concentrations were measured using gas chromatography. Metabolic measures were quantified by nuclear magnetic resonance metabolomics at 9 (n = 539), 11 (n = 536), 13 (n = 525), 15 (n = 488), 17 (n = 455), and 19 (n = 409) years. Association of passive tobacco smoke exposure with metabolic profile compared participants who reported less-than-weekly smoking and had serum cotinine concentration <1 ng/mL (no exposure) with those whose cotinine concentration was ≥10 ng/mL (passive tobacco smoke exposure). Associations of daily smoking with metabolic profile in adolescence were analysed by comparing participants reporting daily smoking with those reporting no tobacco use and having serum cotinine concentrations <1 ng/mL. Passive tobacco smoke exposure was directly associated with the serum ratio of monounsaturated fatty acids to total fatty acids [ß = 0.34 standard deviation (SD), (0.17-0.51), P < 0.0001] and inversely associated with the serum ratios of polyunsaturated fatty acids. Exposure to passive tobacco smoke was directly associated with very-low-density lipoprotein particle size [ß = 0.28 SD, (0.12-0.45), P = 0.001] and inversely associated with HDL particle size {ß = -0.21 SD, [-0.34 to -0.07], P = 0.003}. Daily smokers exhibited a similar metabolic profile to those exposed to passive tobacco smoke. These results persisted after adjusting for body mass index, STRIP study group allocation, dietary target score, pubertal status, and parental socio-economic status. CONCLUSION: Both passive and active tobacco smoke exposures during childhood and adolescence are detrimentally associated with circulating metabolic measures indicative of increased cardio-metabolic risk.

A substantial proportion of children are affected by tobacco smoke exposure worldwide, and early life exposure to passive tobacco smoke may be even more harmful than active smoking in terms of cardiovascular disease risk. Our study suggests the following: Passive tobacco smoke exposure during childhood is associated with metabolic measures indicative of increased cardio-metabolic risk and that the association profile is similar with active daily smoking during adolescence.Reducing both active and passive tobacco smoke exposures during childhood and adolescence could reduce the risk of future cardio-metabolic disease.

Blood Pressure at Different Life Stages Over the Early Life Course and Intima-Media Thickness.

Importance: Although cardiovascular disease (CVD) begins in early life, the extent to which blood pressure (BP) at different life stages contributes to CVD is unclear. Objective: To determine the relative contribution of BP at different life stages across the early-life course from infancy to young adulthood with carotid intima-media thickness (IMT). Design, setting, and participants: The analyses were performed in 2022 using data gathered from July 1989 through January 2018 within the Special Turku Coronary Risk Factor Intervention Project, a randomized, infancy-onset cohort of 534 participants coupled with annual BP (from age 7 months to 20 years), biennial IMT measurements (from ages 13 to 19 years), who were followed up with again at age 26 years. Exposures: BP measured from infancy (aged 7 to 13 months), preschool (2 to 5 years), childhood (6 to 12 years), adolescence (13 to 17 years), and young adulthood (18 to 26 years). Main outcomes and measures: Primary outcomes were carotid IMT measured in young adulthood at age 26 years. Bayesian relevant life-course exposure models assessed the relative contribution of BP at each life stage. Results: Systolic BP at each life stage contributed to the association with young adulthood carotid IMT (infancy: relative weight, 25.3%; 95% credible interval [CrI], 3.6-45.8; preschool childhood: relative weight, 27.0%; 95% CrI, 3.3-57.1; childhood: relative weight, 18.0%; 95% CrI, 0.5-40.0; adolescence: relative weight, 13.5%; 95% CrI, 0.4-37.1; and young adulthood: relative weight, 16.2%; 95% CrI, 1.6-46.1). A 1-SD (at single life-stage) higher systolic BP accumulated across the life course was associated with a higher carotid IMT (0.02 mm; 95% CrI, 0.01-0.03). The findings for carotid IMT were replicated in the Cardiovascular Risk in Young Finns Study that assessed systolic BP from childhood and carotid IMT in adulthood (33 to 45 years). Conclusion and relevance: In this cohort study, a life-course approach indicated that accumulation of risk exposure to BP levels at all life stages contributed to adulthood carotid IMT. Of those, the contribution attributed to each observed life stage was approximately equal. These results support prevention efforts that achieve and maintain normal BP levels across the life course, starting in infancy.

The Influence of Dietary Counseling Over 20 Years on Tracking of Non-High-Density Lipoprotein Cholesterol from Infancy to Young Adulthood.

This 26-year study found that non-high-density lipoprotein cholesterol (non-HDL-C) levels tracked from infancy to young adulthood suggesting early-life non-HDL-C could predict future levels. However, infancy-onset dietary counseling reduced the odds of maintaining at-risk non-HDL-C, highlighting the potential importance of early interventions in preventing cardiovascular risk associated with high pediatric non-HDL-C.

Metformin Versus Insulin for Gestational Diabetes: Cognitive and Neuropsychological Profiles of Children Aged 9 years.

OBJECTIVE: We compared cognitive profile and neuropsychological performance in 9-year-old offspring of mothers who were treated with metformin or insulin for gestational diabetes mellitus (GDM). METHODS: A total of 172 children whose mothers were randomly assigned to receive either metformin or insulin for GDM were studied at the age of 9 years. Of these children, 127 were from Turku, Finland (63 metformin and 64 insulin), and 45 from Oulu, Finland (19 metformin and 26 insulin). Clinical and demographic background characteristics were obtained at enrolment, birth, and 9-year follow-up. Cognitive profiles were examined at age 9 years with the Wechsler Intelligence Scale for Children. Neuropsychological functions were examined with 2 subtests of the Developmental Neuropsychological Assessment test battery assessing comprehension of instructions and narrative memory, Trail Making Test assessing attention and with Behavioral Rating Inventory of Executive Functioning, including parent-rated and teacher-rated evaluations. Academic functioning was studied with reading fluency subtest of the Screening test for reading, writing, and calculus for first to sixth grades and information about educational support received at school reported by parents. RESULTS: The cognitive profiles, including indexes of verbal comprehension, perceptual reasoning, working memory, and processing speed, did not differ significantly between metformin-treated and insulin-treated groups. Significant differences were not found between the treatment groups in assessed neuropsychological functions, reading fluency, or received level of support at school. CONCLUSION: Cognitive and neuropsychological outcomes were similar in 9-year-old children whose mothers had either metformin or insulin treatment of GDM.

Weekday and weekend physical activity patterns and their correlates among young adults.

BACKGROUND: Accelerometers enable assessment of within and between day variation in physical activity. The main aim was to examine weekday and weekend physical activity patterns among young adults. Additionally, correlates of the physical activity patterns were examined. METHODS: Overall 325 adults (mean age 26.0 years, standard deviation 0.03) from the Special Turku Coronary Risk Factor Intervention Project used a wrist-worn ActiGraph accelerometer continuously for 1 week. Physical activity patterns over weekdays and weekends were identified by using the group-based trajectory modeling. Adolescent leisure time physical activity (LTPA) and sociodemographic characteristics (sex, marital and family status, education, work status, occupation, and health consciousness) were examined as possible correlates of physical activity patterns using multinomial regression analysis. RESULTS: Five patterns were identified: consistently low activity (45%), active on weekday evenings and weekends (32%), consistently moderate activity (11%), active on weekdays (7%), and consistently high activity (5%). Low adolescent LTPA was associated with consistently low activity pattern in young adulthood. Women were more likely than men to belong in the more physically active groups (all other groups except active on weekdays, odds ratios between 2.26 and 6.17). Those in the active on weekdays group had lower education, were more often in the working life and in manual occupations than those in the consistently low activity group. CONCLUSIONS: Marked heterogeneity in physical activity patterns across the week was observed among young adults. Especially history of physical activity, sex, education, work status, and occupation were associated with different physical activity patterns.

Plasma calprotectin is extremely high in patients with lysinuric protein intolerance.

Lysinuric protein intolerance (LPI) is a rare autosomal recessive disorder affecting the transport of cationic amino acids. Elevated plasma zinc concentrations have been described in patients with LPI. Calprotectin is a calcium- and zinc-binding protein, produced by polymorphonuclear leukocytes and monocytes. Both zinc and calprotectin have an important role in immune system. In this study, we describe plasma zinc and plasma calprotectin concentrations in Finnish LPI patients. Plasma calprotectin concentration was measured from 10 LPI patients using an enzyme-linked immunosorbent assay (ELISA) and it was remarkably high in all LPI patients (median: 622 338 µg/L) compared to that in healthy controls (608 µg/L). Plasma zinc concentration was measured by photometry and it was normal or only mildly elevated (median: 14.9 µmol/L). All the patients had decreased glomerular infiltration rate (median: 50 mL/min/1.73 m2). In conclusion, we observed extremely high plasma calprotectin concentration in patients with LPI. Mechanism of this phenomenon is unknown.

Prediction of pre-diabetes and type 2 diabetes nine years postpartum using serum metabolome in pregnant women with gestational diabetes requiring pharmacological treatment.

AIMS: We examined the association between serum metabolome in women with pharmacologically treated gestational diabetes (GDM) and measures of glucose metabolism 9 years postpartum. METHODS: Serum targeted metabolome, adiponectin, inflammatory markers, and insulin-like growth factor-binding protein-1 phosphoisoforms were analyzed at the time of diagnosing GDM. Glucose metabolism and insulin resistance were assessed at 9 years postpartum. Data from 119 subjects were available for analyses. Associations between baseline measures and future measures of glycemia were examined with univariate regressions and multivariate prediction models. This is a secondary analysis of a previous prospective trial (NCT02417090). RESULTS: Baseline serum markers were most strongly related to measures of insulin resistance at 9-years follow-up. In multivariate analyses combination of IDL cholesterol, early gestational weight gain and in oral glucose tolerance test fasting and 2-h glucose predicted development of disorders of glucose metabolism (pre-diabetes and/or type 2 diabetes) better than clinical predictors alone (ROC-AUC 0.75 vs. 0.65, p = 0.020). CONCLUSIONS: Serum metabolome in pregnancy in women with GDM is related to future glucose metabolism and insulin resistance. Compared to clinical variables alone metabolome might result in better prediction of future disorders of glucose metabolism and could facilitate personalized risk stratification for postpartum interventions and follow-up.

Metformin versus insulin for gestational diabetes: Adiposity variables and adipocytokines in offspring at age of 9 years.

AIMS: To compare body composition, visceral adiposity, adipocytokines, and low-grade inflammation markers in prepubertal offspring of mothers who were treated with metformin or insulin for gestational diabetes mellitus (GDM). METHODS: 172 offspring of 311 mothers randomized to receive metformin (n = 82) or insulin (n = 90) for GDMwere studied at 9 years of age (follow-up rate 55%). Measurements included anthropometrics, adipocytokines, markers of the low-grade inflammation, abdominal magnetic resonance imaging (MRI), magnetic liver spectrometry (MRS), and whole body dual-energy X-ray absorptiometry (DXA). RESULTS: Serum markers of low-grade inflammation, visceral adipose tissue volume, total fat percentage, and liver fat percentage were similar between the study groups. Serum adiponectin concentration was higher in children in the metformin group compared to insulin group (median 10.37 vs 9.50 µg/ml, p = 0.016). This difference between groups was observed in boys only (median 12.13 vs 7.50 µg/ml, p < 0.001). Leptin/adiponectin-ratio was lower in boys in the metformin group than in the insulin group (median 0.30 vs 0.75; p = 0.016). CONCLUSIONS: Maternal metformin treatment for GDM had no effects on adiposity, body composition, liver fat, or inflammation markers in prepubertal offspring compared to maternal insulin treatment but was associated with higher adiponectin concentration and lower leptin/adiponectin-ratio in boys.

Tracking of Cardiorespiratory Fitness and Physical Activity from Youth to Young Adulthood: Findings from the Prospective Special Turku Coronary Risk Factor Intervention Project (STRIP).

Using data from the Special Turku Coronary Risk Factor Intervention Project, cardiorespiratory fitness (rank-order correlation coefficient = 0.60-0.62) tracked stronger than physical activity (rank-order correlation coefficient = 0.27-0.38) between youth (age = 17 years) and young adulthood (age = 26 years). Cardiorespiratory fitness could help identify individuals at risk of maintaining poor fitness levels or developing adverse health in adulthood.

Comorbidity in Congenital Hypothyroidism-A Nationwide, Population-based Cohort Study.

CONTEXT: Patients with congenital hypothyroidism (CH) are affected more often than the general population by other chronic diseases and neurological difficulties. OBJECTIVE: The aim of this nationwide population-based register study was to investigate the incidence of congenital malformations, comorbidities, and the use of prescribed drugs in patients with primary CH. METHODS: The study cohort and matched controls were identified from national population-based registers in Finland. All diagnoses from birth until the end of 2018 were collected from the Care Register, and subject-specific prescription drug purchases were identified from The Prescription Register from birth until the end of 2017. RESULTS: Diagnoses of neonatal and chronic diseases were collected for 438 full-term patients and 835 controls (median follow-up time 11.6 years; range, 0-23 years). Newborns with CH were more often found to have neonatal jaundice (11.2% and 2.0%; P < .001), hypoglycemia (8.9% and 2.8%; P < .001), metabolic acidemia (3.2% and 1.1%; P = .007), and respiratory distress (3.9% and 1.3%; P < .003) as compared to their matched controls.Congenital malformations were diagnosed in 66 of 438 (15.1%) CH patients and in 62 of 835 (7.4%) controls (P < .001). The most commonly affected extrathyroidal systems were the circulatory and musculoskeletal systems. The cumulative incidence of hearing loss and specific developmental disorders was higher among CH patients than controls. The use of antidepressant and antipsychotic drugs was similar in CH patients and their controls. CONCLUSION: CH patients have more neonatal morbidity and congenital malformations than their matched controls. The cumulative incidence of neurological disorders is higher in CH patients. However, our results do not support the existence of severe psychiatric comorbidity.

Associations of breastfeeding duration with serum lipid values from infancy until age 20 years - the STRIP study.

BACKGROUND AND AIMS: The effect of breastfeeding duration on childhood lipid levels has remained controversial. In this study, we aimed to establish the long-term associations of breastfeeding duration with future levels of total cholesterol, high-density lipoprotein (HDL) cholesterol, non-HDL cholesterol and low-density lipoprotein cholesterol. In addition, we report lipid levels at the age of seven months depending on the child receiving any breastmilk. METHODS: The sample comprised 999 children participating in the prospective Special Turku Coronary Risk Factor Intervention Project (STRIP). Serum lipid profile was studied at the ages of seven months and 13 months, and annually thereafter until the age of 20 years. Duration of breastfeeding was inquired, and infants were divided into those who received or did not receive any breast milk at the age of seven months (n=533 and n=466, respectively). In addition, breastfeeding duration groups (any breastfeeding for 0-4 months, 4-6 months, 6-9 months, and >9 months) were formed. RESULTS: At the age of seven months infants who at that time received breast milk had higher serum HDL cholesterol (0.95±0.21mmol/l vs. 0.90±0.19 mmol/l; p=0.0018), non-HDL cholesterol (3.38±0.78 mmol/l vs. 3.01±0.67 mmol/l; p<0.001) and total cholesterol levels (4.33±0.80 mmol/l vs. 3.91±0.69 mmol/l; p<0.001) than their peers who did not receive breast milk. From two to 20 years of age serum lipid levels showed no consistent differences between the breastfeeding duration groups. CONCLUSIONS: Our long-term data showed that duration of breastfeeding has no consistent associations with serum lipid concentrations in healthy individuals aged two to 20 years. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov, unique identifier NCT00223600.

What is the role of puberty in the development of islet autoimmunity and progression to type 1 diabetes?

In many populations, the peak period of incidence of type 1 diabetes (T1D) has been observed to be around 10-14 years of age, coinciding with puberty, but direct evidence of the role of puberty in the development of T1D is limited. We therefore aimed to investigate whether puberty and the timing of its onset are associated with the development of islet autoimmunity (IA) and subsequent progression to T1D. A Finnish population-based cohort of children with HLA-DQB1-conferred susceptibility to T1D was followed from 7 years of age until 15 years of age or until a diagnosis of T1D (n = 6920). T1D-associated autoantibodies and growth were measured at 3- to 12-month intervals, and pubertal onset timing was assessed based on growth. The analyses used a three-state survival model. IA was defined as being either positive for islet cell antibodies plus at least one biochemical autoantibody (ICA + 1) or as being repeatedly positive for at least one biochemical autoantibody (BC1). Depending on the IA definition, either 303 (4.4%, ICA + 1) or 435 (6.3%, BC1) children tested positive for IA by the age of 7 years, and 211 (3.2%, ICA + 1)) or 198 (5.3%, BC1) developed IA during follow-up. A total of 172 (2.5%) individuals developed T1D during follow-up, of whom 169 were positive for IA prior to the clinical diagnosis. Puberty was associated with an increase in the risk of progression to T1D, but only from ICA + 1-defined IA (hazard ratio 1.57; 95% confidence interval 1.14, 2.16), and the timing of pubertal onset did not affect the association. No association between puberty and the risk of IA was detected. In conclusion, puberty may affect the risk of progression but is not a risk factor for IA.

Gut microbiota composition and function in pregnancy as determinants of prediabetes at two-year postpartum.

AIMS: Deep metagenomics offers an advanced tool for examining the relationship between gut microbiota composition and function and the onset of disease; in this case, does the composition and function of gut microbiota during pregnancy differ in women who develop prediabetes and those who do not at two-year postpartum, and whether the gut microbiota composition associates with glycemic traits. METHODS: In total, 439 women were recruited in early pregnancy. Gut microbiota was assessed by metagenomics analysis in early (13.9 ± 2.0 gestational weeks) and late pregnancy (35.1 ± 1.0 gestational weeks). Prediabetes was determined using American Diabetes Association criteria as fasting plasma glucose 5.6-6.9 mmol/l analyzed by an enzymatic hexokinase method. Of the women, 39 (22.1%) developed prediabetes by two-year postpartum. RESULTS: The relative abundances of Escherichia unclassified (FDR < 0.05), Clostridiales bacterium 1_7_ 47FAA (FDR < 0.25) and Parabacteroides (FDR < 0.25) were higher, and those of Ruminococcaceae bacterium D16 (FDR < 0.25), Anaerotruncus unclassified (FDR < 0.25) and Ruminococcaceae noname (FDR < 0.25) were lower in early pregnancy in those women who later developed prediabetes. In late pregnancy, Porphyromonas was higher and Ruminococcus sp 5_1_39BFAA was lower in prediabetes (FDR < 0.25). Furthermore, fasting glucose concentrations associated inversely with Anaerotruncus unclassified in early pregnancy and directly with Ruminococcus sp 5_1_39BFAA in late pregnancy (FDR < 0.25). α-Diversity or ß-diversity did not differ significantly between the groups. Predictions of community function during pregnancy were not associated with prediabetes. CONCLUSIONS: Our study shows that some bacterial species during pregnancy contributed to the onset of prediabetes within two-year postpartum. These were attributable primarily to a lower abundance of short-chain fatty acids-producing bacteria.

Aberrations in the early pregnancy serum metabolic profile in women with prediabetes at two years postpartum.

INTRODUCTION: Aberrations in circulating metabolites have been associated with diabetes and cardiovascular risk. OBJECTIVES: To investigate if early and late pregnancy serum metabolomic profiles differ in women who develop prediabetes by two years postpartum compared to those who remain normoglycemic. METHODS: An NMR metabolomics platform was used to measure 228 serum metabolite variables from women with pre-pregnancy overweight in early and late pregnancy. Co-abundant groups of metabolites were compared between the women who were (n = 40) or were not (n = 138) prediabetic at two years postpartum. Random Forests classifiers, based on the metabolic profiles, were used to predict the prediabetes status, and correlations of the metabolites to glycemic traits (fasting glucose and insulin, HOMA2-IR and HbA1c) and hsCRP at postpartum were evaluated. RESULTS: Women with prediabetes had higher concentrations of small HDL particles, total lipids in small HDL, phospholipids in small HDL and free cholesterol in small HDL in early pregnancy (p = 0.029; adj with pre-pregnancy BMI p = 0.094). The small HDL related metabolites also correlated positively with markers of insulin resistance at postpartum. Similar associations were not detected for metabolites in late pregnancy. A Random Forests classifier based on serum metabolites and clinical variables in early pregnancy displayed an acceptable predictive power for the prediabetes status at postpartum (AUROC 0.668). CONCLUSION: Elevated serum concentrations of small HDL particles in early pregnancy associate with prediabetes and insulin resistance at two years postpartum. The serum metabolic profile during pregnancy might be used to identify women at increased risk for type 2 diabetes.

Fish Oil And/Or Probiotics Intervention in Overweight/Obese Pregnant Women and Overweight Risk in 24-Month-Old Children.

OBJECTIVES: To evaluate whether a fish oil and/or probiotics intervention in pregnant women with overweight or obesity would influence the tendency of their 24-month-old children to become overweight and alter their body fat percentage. METHODS: Women (n = 439) were double-blindly randomized into 4 intervention groups: fish oil+placebo, probiotics+placebo, probiotics+fish oil, and placebo+placebo (fish oil: 1.9 g docosahexaenoic acid and 0.22 g eicosapentaenoic acid, probiotics: Lacticaseibacillus rhamnosus HN001 and Bifidobacterium animalis ssp. lactis 420, 1010 colony-forming units each). The intervention lasted from early pregnancy until 6 months postpartum. Children's (n = 330) growth data (height, weight, head circumference), a secondary outcome of the trial, were evaluated at birth, 3, 6, 12, and 24 months of age and compared to Finnish growth charts. Body fat percentage was measured with air displacement plethysmography (24 months). Logistic regression and general linear models were used to analyze the data. RESULTS: Probiotics+placebo [weight-for-height% adj. Odds ratio (OR) = 0.36, 95% confidence interval (CI) = 0.14-0.95] and probiotics+fish oil [weight-for-age standard deviation score (SD-score) adj. OR = 0.22, 95% CI = 0.07-0.71] associated with lower overweight odds in 24-month-old children compared to placebo+placebo. Results remained essentially the same, when probiotics' main effect (combined probiotics+placebo and probiotics+fish oil) was estimated; that is, lower overweight odds (weight-for-height% adj. OR = 0.48, 95% CI = 0.25-0.95 and weight-for-age SD-score adj. OR = 0.42, 95% CI = 0.20-0.88) compared to non-probiotics. No fish oil main effect (combined fish oil+placebo and probiotics+fish oil) was seen. The intervention did not influence body fat percentage. CONCLUSIONS: The administration of probiotics solely and in combination with fish oil during pregnancy to women with overweight or obesity lowered the overweight odds of their 24-month-old children.

Association of physical activity with metabolic profile from adolescence to adulthood.

OBJECTIVE: Physical activity benefits cardiometabolic health, but little is known about its detailed links with serum lipoproteins, amino acids, and glucose metabolism at young age. We therefore studied the association of physical activity with a comprehensive metabolic profile measured repeatedly in adolescence. METHODS: The cohort is derived from the longitudinal Special Turku Coronary Risk Factor Intervention Project. At ages 13, 15, 17, and 19 years, data on physical activity were collected by a questionnaire, and circulating metabolic measures were quantified by nuclear magnetic resonance metabolomics from repeatedly assessed serum samples (age 13: n = 503, 15: n = 472, 17: n = 466, and 19: n = 361). RESULTS: Leisure-time physical activity (LTPA;MET h/wk) was directly associated with concentrations of polyunsaturated fatty acids, and inversely with the ratio of monounsaturated fatty acids to total fatty acids (-0.006SD; [-0.008, -0.003]; p < 0.0001). LTPA was inversely associated with very-low-density lipoprotein (VLDL) particle concentration (-0.003SD; [-0.005, -0.001]; p = 0.002) and VLDL particle size (-0.005SD; [-0.007, -0.003]; p < 0.0001). LTPA showed direct association with the particle concentration and size of high-density lipoprotein (HDL), and HDL cholesterol concentration (0.004SD; [0.002, 0.006]; p < 0.0001). Inverse associations of LTPA with triglyceride and total lipid concentrations in large to small sized VLDL subclasses were found. Weaker associations were seen for other metabolic measures including inverse associations with concentrations of lactate, isoleucine, glycoprotein acetylation, and a direct association with creatinine concentration. The results remained after adjusting for body mass index and proportions of energy intakes from macronutrients. CONCLUSIONS: Physical activity during adolescence is beneficially associated with the metabolic profile including novel markers. The results support recommendations on physical activity during adolescence to promote health and possibly reduce future disease risks.

Treatment of Congenital Hypothyroidism: Impact of Secular Changes in Levothyroxine Initial Dose on Early Growth.

INTRODUCTION: Newborn screening of congenital hypothyroidism (CH) has enabled early treatment with levothyroxine (LT4), ensuring normal growth and development. The initial LT4 dose recommendation has increased over decades. We evaluated whether the increased LT4 dosing influenced thyroid-stimulating hormone (TSH) and thyroxine (fT4) concentrations, growth, or treatment-related symptoms. METHODS: LT4 doses, TSH, fT4, anthropometrics, and treatment-related symptoms until age 2 years were evaluated in 172 Finnish CH patients born between 1980 and 2018. The patients were grouped according to birth decade: 1980s (n = 19, mean LT4 starting dose 6.8 µg/kg/day), 1990s (n = 50, 7.4 µg/kg/day), 2000s (n = 59, 9.7 µg/kg/day), and 2010s (n = 44, 10.8 µg/kg/day). RESULTS: TSH concentrations were higher during the first 2 years of life in children born in the 1980s compared to children born later. TSH concentrations were often subnormal in children receiving higher LT4 doses (children born in the 2000s and 2010s). However, symptoms of overtreatment were uncommon. Linear or head growth showed no differences between the groups during the first 2 years of life. Although growth was within the normal spectrum, children in all groups were shorter than their target length at 2 years and their weight-for-length was above the mean through the first 2 years of life. DISCUSSION: Current treatment practice with higher LT4 dose normalizes TSH rapidly without significant increase in side effects. However, irrespective of initial LT4 dose, children were shorter than expected at 2 years of age. Effects of different initial LT4 dose on cognitive development urges further investigation.

Incidence of primary congenital hypothyroidism over 24 years in Finland.

BACKGROUND: A rise in the incidence of congenital hypothyroidism (CH) has been reported worldwide. This nationwide study aimed to describe the secular trends and current incidence of CH in Finland. METHODS: Two independent study cohorts, a national and a regional, were collected from national registers and patient records. The national cohort represents all CH cases born in Finland between 1994 and 2017. Birth data, results of the screening test, and the incidence of CH were reviewed. RESULTS: Between 1994 and 2017, 1,400,028 children were born in Finland. Of these children, 503 were diagnosed with primary CH (incidence 1:2783). Male-to-female sex ratio was 1:2.0. The nationwide incidence was 33 cases per 100,000 live births between 1994 and 1999, 38 cases per 100,000 live births between 2000 and 2005, 40 cases per 100,000 live births between 2006 and 2011, and 33 cases per 100,000 live births between 2012 and 2017. In the regional cohort (n = 139), the incidence of transient CH was 3.6%. The incidence of mild, moderate, and severe CH remained constant. CONCLUSIONS: In Finland, the incidence of CH has not changed during the 24-year study period. IMPACT: As opposed to recent reports worldwide, the incidence of congenital hypothyroidism has not changed between 1994 and 2017 in Finland. The proportions of mild, moderate, and severe congenital hypothyroidism did not change significantly over the study period. Lowering the TSH cut-off limit or increasing immigration did not affect the incidence rate of primary congenital hypothyroidism in Finland.