Background: Congenital hypothyroidism (CH) is defined as the lack of thyroid hormones at birth. Mutations in at least 15 different genes have been associated with this disease. While up to 20% of CH cases are hereditary, the majority of cases are sporadic with unknown etiology. Apart from a monogenic pattern of inheritance, multigenic mechanisms have been suggested to play a role in CH. The genetics of CH has not been studied in Finland so far. Therefore, multigenic sequencing of CH candidate genes was performed in a Finnish patient cohort with both familial and sporadic CH.Methods: A targeted next-generation sequencing (NGS) panel, covering all exons of the major CH genes, was applied for 15 patients with sporadic and 11 index cases with familial CH.Results: Among the familial cases, six pathogenic mutations were found in the TPO, PAX8, and TSHR genes. Furthermore, pathogenic NKX2.1 and TG mutations were identified from sporadic cases, together with likely pathogenic variants in the TG, NKX2.5, SLC26A4, and DUOX2 genes. All identified novel pathogenic mutations were confirmed by Sanger-sequencing and characterized in silico and/or in vitro.Conclusion: In summary, the CH panel provides an efficient, cost-effective, and multigenic screening tool for both known and novel CH gene mutations. Hence, it may be a useful method to identify accurately the genetic etiology for dyshormogenic, familial, or syndromic forms of CH.

BackgroundAccording to current evidence, the prevention of obesity should start early in life. Even the prenatal environment may expose a child to unhealthy weight gain; maternal gestational diabetes is known to be among the prenatal risk factors conducive to obesity. Here we report the effects of antenatal dietary and physical activity counselling on pregnancy and infant weight gain outcomes.MethodsThe study was a non-randomised controlled pragmatic trial aiming to prevent childhood obesity, the setting being municipal maternity health care clinics. The participants (n = 185) were mothers at risk of developing gestational diabetes mellitus and their offspring. The children of the intervention group mothers were born between 2009 and 2010, and children of the control group in 2008. The intervention started between 10–17 gestational weeks and consisted of individual counselling on diet and physical activity by a public health nurse, and two group counselling sessions by a dietician and a physiotherapist. The expectant mothers also received a written information leaflet to motivate them to breastfeed their offspring for at least 6 months. We report the proportion of mothers with pathological glucose tolerance at 26–28 weeks’ gestation, the mother’s gestational weight gain (GWG) and newborn anthropometry. Infant weight gain from 0 to 12 months of age was assessed as weight-for-length standard deviation scores (SDS) and mixed effect linear regression models.ResultsIntervention group mothers had fewer pathological oral glucose tolerance test results (14.6% vs. 29.2%; 95% CI 8.9 to 23.0% vs. 20.8 to 39.4%; p-value 0.016) suggesting that the intervention improved gestational glucose tolerance. Mother’s GWG, newborn anthropometry or infant weight gain did not differ significantly between the groups.ConclusionSince the intervention reduced the prevalence of gestational diabetes mellitus, it may have the potential to diminish obesity risk in offspring. However, results from earlier studies suggest that the possible effect on the offspring’s weight gain may manifest only later in childhood.Trial registrationClinical Trials gov: NCT00970710

Rare CNVs contribute possibly pathogenic alleles to a substantial fraction of children with early-onset obesity. The involved genes might provide insights into pathogenic mechanisms and involved cellular pathways. These findings highlight the importance of CNV screening in children with early-onset obesity.

ObjectiveTo investigate the effect of intensified lifestyle counselling targeting infants' mothers on offspring weight development during the first 4 years of life.Design and settingFollow-up of a cluster-randomised controlled trial in primary care child health clinics during 2004–2006 in Finland. Participants received a follow-up survey during 2010 concerning weight and height measurements of their offspring. Number of clusters was six and the response rate to the follow-up 71.9% (N=64/89).ParticipantsThe participants (N=89) were mothers of infants aged 2–10 months.InterventionThe intervention included individual counselling on diet and physical activity when the infant was 2–10 months of age and an option to attend supervised group exercise sessions.Primary and secondary outcome measuresThe authors analysed the secondary outcome of the intervention study: the weight development of the offspring. The primary outcome was the proportion of women returning to their prepregnancy weight by 10 months post partum, reported earlier.ResultsMultilevel mixed effect non-linear regression models included group, age of the child and interaction between group and age of the child. The increase of BMI z-score between 24 and 48 months was slower among the intervention group offspring (−0.034 to −0.002, p=0.028) as compared with control group. Z-scores for weight-for-length/height did not differ between groups when the period 0–48 months was analysed (p=0.23) but for the period of 24–48 months, between-group differences were significant (p=0.012).ConclusionsLifestyle counselling targeting mothers during the child's first year may be effective in slowing offspring weight gain until 4 years of age. However, larger studies are needed to confirm the findings which may have the potential in combatting the obesity epidemic.Trial registration numberCurrent Controlled Trials ISRCTN21512277.

BackgroundFetal conditions are known to be partly responsible for the child’s risk for obesity. Our pilot study aimed to determine the effect of gestational lifestyle counseling on the offspring weight gain until 4 years of age and to estimate power for future studies.Design and methodsFirst-time pregnant mothers participated in a controlled trial conducted in maternity health clinics during 2004 – 2006. The intervention included individual counseling on physical activity and diet, and an option to attend supervised group exercise sessions. The participant mothers (N = 109) received a follow-up questionnaire concerning 13 repeated growth measurements of their offspring. Response rate to the follow-up questionnaire was 66.1% (N = 72/109).ResultsThe increase of BMI z-score between 24–48 months was not significantly slower among the intervention group offspring (95% CI −0.025 to 0.009, p = 0.34) compared to control group. Z-scores for weight-for-length/height did not differ between groups when the period 0–48 months was analyzed (95% CI −0.010 to 0.014, p = 0.75).ConclusionsIn this pilot study gestational lifestyle counseling did not significantly slow the weight gain of the offspring. Gestational intervention studies with at least 300 mothers per group are needed to confirm the possible effect on offspring’s risk for obesity.Trial registrationCurrent Controlled Trials ISRCTN21512277.