Reference limits for osteocalcin in infancy and early childhood: A longitudinal birth cohort study.

OBJECTIVE: The longitudinal variations in serum levels of the hormone osteocalcin is largely unknown during infancy and early childhood. Our aim was to establish reference limits for total serum osteocalcin during specific time points from birth until 5 years of age and present those in the context of sex, breastfeeding practices and gestational age (GA). DESIGN: Blood samples from 551 Swedish children were analysed at birth, 4, 12, 36 and 60 months of age. Total serum osteocalcin was measured using the IDS-iSYS N-MID Osteocalcin assay technique. Information about the mother, birth, anthropometrics and a food diary were collected. RESULTS: Sex-specific and age-specific reference limits were established for the five time points. The median osteocalcin levels over time were 40.8, 90.0, 67.8, 62.2 and 80.9 µg/L for boys and 38.1, 95.5, 78.3, 73.9 and 92.6 µg/L for girls. Lower GA was associated to higher osteocalcin at birth, and ongoing breastfeeding was associated to higher osteocalcin levels. CONCLUSION: Osteocalcin followed a wavelike pattern with low levels in the umbilical cord and a postnatal peak during the first year which then declined and rose again by the age of five. Knowledge of this wavelike pattern and association to factors as sex, breastfeeding and GA may help clinicians to interpret individual osteocalcin levels and guide in future research.

Prevalence of attention-deficit/hyperactivity disorder and autism in 12-year-old children: A population-based cohort.

AIM: To investigate the prevalence of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) in a population-based birth cohort and correlate the findings with prenatal and perinatal factors. We hypothesized that children born preterm, having experienced preeclampsia or maternal overweight, would have an increased risk of ADHD or ASD. METHOD: A Swedish cohort of 2666 children (1350 males, 1316 females) has been followed from birth with parental and perinatal data. The National Board of Health and Welfare's registries were used to collect data regarding perinatal status and assigned diagnoses at the age of 12 years. RESULTS: The prevalence of ADHD and ASD was 7.6% and 1.1% respectively. Maternal obesity early in pregnancy resulted in a three-fold increased risk of ADHD in the child. Similarly, paternal obesity resulted in a two-fold increased risk. The association was significant also when adjusted for sex, preterm birth, smoking, and lower educational level. The prevalence of ASD was too low for statistically relevant risk factor analyses. INTERPRETATION: Our results corroborate earlier findings regarding prevalence and sex ratio for both ADHD and ASD. Maternal body mass index and preterm birth were correlated with an ADHD diagnosis at the age of 12 years.

Family screening for neurodevelopmental problems and its associations with child cognitive function enable tailored treatment for childhood obesity.

AIM: To identify neurodevelopmental disorders in children with obesity, and investigate associations to cognitive functions as well as parents' self-reported neurodevelopmental problems. METHODS: Eighty children were included at two outpatient obesity clinics in Sweden 2018-2019. Of these, 50 children without previously diagnosed neurodevelopmental disorders were screened, and so were their parents. Children who screened positive for neurodevelopmental problems were referred to a specialised psychiatry unit for further diagnosis. Test results of cognitive functioning were compared with the norm and between study groups by neurodevelopmental diagnoses. RESULTS: Of the screened families, 17/50 children were diagnosed by the psychiatric unit with attention deficit-hyperactivity disorder (ADHD) and 15/82 parents screened positive for neurodevelopmental problems. Having a mother who screened positive for neurodevelopmental problems was associated with child ADHD (p < 0.05). The children's full-scale intelligence quotient (92.86 ± 12.01, p < 0.001) and working memory index (90.62 ± 12.17, p < 0.001) were lower than the norm. Working memory index was lower in children with ADHD compared to without ADHD: 84.76 ± 9.58 versus 94.09 ± 12.29 (p ≤ 0.01). Executive constraints were associated with verbal deviances. CONCLUSION: Increased awareness is needed about the overlap between neurodevelopmental problems and obesity in obesity clinics.

Pre- and peripubertal sex steroids are inversely associated with birth weight in preterm boys.

OBJECTIVE: The relationship between sex hormone concentrations during childhood and birth weight (BW) is poorly understood. We aimed to investigate this relationship and the associations with anthropometric data at 5, 6, 7, 8, and 10 years of age in preterm boys. DESIGN: A prospective longitudinal single-centre study, including 58 boys with a BW of 1325-3320 g and gestational age (GA) of 32 + 2 to 36 + 6 weeks. PATIENTS AND MEASUREMENTS: Data on GA, BW and anthropometric data between 5 and 10 years of age were recorded. Testicular development was assessed at 8 and 10 years of age. Serum concentrations of sex steroids were analysed with gas chromatography-tandem mass spectrometry at 5-10 years and luteinizing hormone (LH) and follicle-stimulating hormone (FSH) with immunoassays at 10 years of age. RESULTS: At 8 years of age, testosterone and estrone correlated negatively with BW, (ρ = -0.35, p = .021) and (ρ = -0.34, p = .024), respectively. At 10 years of age, testosterone, dihydrotestosterone, estrone and estradiol correlated negatively with BW (ρ = -0.39, p = .010), (ρ = -0.38, p = .013), (ρ = -0.44, p = .003) and (ρ = -0.36, p = .019), respectively. Weight gain from birth correlated with testosterone at 5 years (ρ = 0.40, p = .002), 7 years (ρ = 0.30, p = .040), 8 years (ρ = 0.44, p = .003) and 10 years (ρ = 0.40, p = .008) of age. At 10 years of age, testosterone correlated with LH (ρ = 0.42, p = .006) and FSH (ρ = 0.33, p = .033) but not with testicular volume. CONCLUSIONS: Lower BW was associated with increased sex steroid concentrations from 8 years of age, independently of clinical signs of puberty.

Magnetic resonance imaging of the knee for chronological age estimation-a systematic review.

INTRODUCTION: Radiographs of the hand and teeth are frequently used for medical age assessment, as skeletal and dental maturation correlates with chronological age. These methods have been criticized for their lack of precision, and magnetic resonance imaging (MRI) of the knee has been proposed as a more accurate method. The aim of this systematic review is to explore the scientific and statistical evidence for medical age estimation based on skeletal maturation as assessed by MRI of the knee. MATERIALS AND METHODS: A systematic review was conducted that included studies published before April 2021 on living individuals between 8 and 30 years old, with presumptively healthy knees for whom the ossification stages had been evaluated using MRI. The correlation between "mature knee" and chronological age and the risk of misclassifying a child as an adult and vice versa was calculated. RESULTS: We found a considerable heterogeneity in the published studies -in terms of study population, MRI protocols, and grading systems used. There is a wide variation in the correlation between maturation stage and chronological age. CONCLUSION: Data from published literature is deemed too heterogenous to support the use of MRI of the knee for chronological age determination. Further, it is not possible to assess the sensitivity, specificity, negative predictive value, or positive predictive value for the ability of MRI to determine whether a person is over or under 18 years old. KEY POINTS: • There is an insufficient scientific basis for the use of magnetic resonance imaging of the knee in age determination by skeleton. • It is not possible to assess the predictive value of MRI of the knee to determine whether a person is over or under 18 years of age.

Associations between pain, health, and lifestyle factors in 10-year-old boys and girls from a Swedish birth cohort.

BACKGROUND: Pain is common in children and its associations with various biopsychosocial factors is complex. Comprehensive pain assessments could contribute to a better understanding of pediatric pain, but these assessments are scarce in literature. The aim of this study was to examine differences in pain prevalence and pain patterns in 10-year-old boys and girls from a Swedish birth cohort and to study associations between pain, health-related quality of life and various lifestyle factors stratified by sex. METHODS: 866 children (426 boys and 440 girls) and their parents from the "Halland Health and Growth Study" participated in this cross-sectional study. Children were categorized into two pain groups, "infrequent pain" (never-monthly pain) or "frequent pain" (weekly-almost daily pain), based on a pain mannequin. Univariate logistic regression analyses, stratified by sex, were performed to study associations between frequent pain and children's self-reports of disease and disability and health-related quality of life (Kidscreen-27, five domains), and parents' reports of their child's sleep (quality and duration), physical activity time, sedentary time, and participation in organized physical activities. RESULTS: The prevalence of frequent pain was 36.5% with no difference between boys and girls (p = 0.442). Boys with a longstanding disease or disability had higher odds of being in the frequent pain group (OR 2.167, 95% CI 1.168-4.020). Higher scores on health-related quality of life in all five domains for girls, and in two domains for boys, was associated with lower odds of being categorized into the frequent pain group. Frequent pain was associated with poor sleep quality (boys OR 2.533, 95% CI 1.243-5.162; girls OR 2.803, 95% CI 1.276-6.158) and more sedentary time (boys weekends OR 1.131, 95% CI 1.022-1.253; girls weekdays OR 1.137, 95% CI 1.032-1.253), but not with physical activity. CONCLUSIONS: The high prevalence of frequent pain needs to be acknowledged and treated by school health-care services and the healthcare sector in order to prevent pain from influencing health and lifestyle factors negatively in children.

Mini review shows that a testicular volume of 3 mL was the most reliable clinical sign of pubertal onset in males.

AIM: We aimed to evaluate aspects of pubertal development to identify the most reliable clinical sign of pubertal onset in males. METHODS: We performed a mini review of the literature. RESULTS: In 1951 Reynolds and Wines categorised pubic hair growth and genital development in five stages by visual inspection. Today the Tanner scale is used to assess the five stages of pubertal development, The second genital stage, characterised by enlargement of the scrotum defines pubertal onset in males. Testicular volume may be evaluated by using a calliper or by ultrasound scan. The Prader orchidometer, described in 1966, offers a method for evaluating testicular growth by palpation. Pubertal onset is commonly defined as testicular volume >3 or ≥4 mL. The development of sensitive laboratory methods has enabled studies analysing hormonal activity in the hypothalamus-pituitary-gonadal axis. We review the relationships between physical and hormonal signs of puberty. We also discuss the results of studies assessing different aspects of pubertal development with a focus on identifying the most reliable clinical sign of pubertal onset in males. CONCLUSION: A substantial amount of evidence supports testicular volume of 3 mL as the most reliable clinical sign of male pubertal onset.

A prediction model could foresee adequate height response in children eligible for growth hormone treatment.

AIM: Prediction models may be useful in accurately identifying children who will benefit from growth hormone (GH) treatment. We aimed to validate the Gothenburg prediction model for this purpose. METHODS: The study included prepubertal children with GH deficiency who started treatment with GH during 2004-2016 at Queen Silvia Children's Hospital, Gothenburg, based on a first-year growth prediction of ≥0.7 SDS in height according to the Gothenburg prediction model on a GH dose of 33 µg/kg/day. Observed heights retrieved from medical charts were compared with predicted heights. RESULTS: The study included 121 patients (64% boys) with at least one year of data after the start of GH treatment. The median (range) GH dose was 30 (10-43) µg/kg/day for the first year and age at start of treatment was 5.32 (3-11.8) years. The model correctly excluded poor responders resulting in 119/121 (98%) patients having a height gain of at least ≥0.5 SDS in a year. However, the model underestimated relatively low predictions and overestimated relatively high predictions, with a residual standard deviation of 0.31 SDS. CONCLUSION: By using a validated prediction model for GH in a clinical context, unnecessarily treating short children with an expected poor height outcome can be avoided.

Serum osteocalcin levels at 4 months of age were associated with neurodevelopment at 4 years of age in term-born children.

AIM: The hormone osteocalcin influenced neurodevelopment and cognition in mice models; this human study explored potential associations between total serum levels in human infants and neurodevelopment at 4 years of age. METHODS: The data were based on two Swedish birth cohorts from 2008 to 2009. We followed 158 healthy full-term vaginal births (51% girls) by measuring serum osteocalcin in cord blood and at 4, 12 and 36 months. The values were compared with neurodevelopment tests at 4 years of age. RESULTS: There was an association between osteocalcin at 4 months and later full-scale intelligence quotient (IQ; r2 0.031, p < 0.05). Children with osteocalcin levels in the highest quartile scored 5.6 (95% confidence interval [1.3, 9.9]) points higher than those in the lowest quartile, with mean scores of 118.8 ± 8.8 and 113.2 ± 9.2 (p < 0.05). They also scored higher on gross motor skills (p < 0.05) and showed greater ability during the drawing trail test (p < 0.005). Cord levels of osteocalcin were negatively associated with processing speed and fine motor development at 4 years, but levels at 12 and 36 months were not associated with later neurodevelopment. CONCLUSION: Osteocalcin levels in infancy appeared to be associated with later IQ and motor development, but more research is needed.

Gene expression signatures predict response to therapy with growth hormone.

Recombinant human growth hormone (r-hGH) is used as a therapeutic agent for disorders of growth including growth hormone deficiency (GHD) and Turner syndrome (TS). Treatment is costly and current methods to model response are inexact. GHD (n = 71) and TS patients (n = 43) were recruited to study response to r-hGH over 5 years. Analysis was performed using 1219 genetic markers and baseline (pre-treatment) blood transcriptome. Random forest was used to determine predictive value of transcriptomic data associated with growth response. No genetic marker passed the stringency criteria for prediction. However, we identified an identical set of genes in both GHD and TS whose expression could be used to classify therapeutic response to r-hGH with a high accuracy (AUC > 0.9). Combining transcriptomic markers with clinical phenotype was shown to significantly reduce predictive error. This work could be translated into a single genomic test linked to a prediction algorithm to improve clinical management. Trial registration numbers: NCT00256126 and NCT00699855.

Half of the children with overweight or obesity and attention-deficit/hyperactivity disorder reach normal weight with stimulants.

AIM: Treatment of childhood obesity is often insufficient and may be aggravated by high co-occurrence of attention-deficit/hyperactivity disorder (ADHD). We aimed to investigate whether children with overweight or obesity normalised in weight when receiving stimulant treatment for ADHD. METHODS: Growth data of 118 children were obtained from medical records at outpatient paediatric and children's psychiatric services in the Gothenburg area, Sweden. The children were diagnosed with ADHD and were between 6 and 17 years at the start of stimulant treatment. The pre-treatment data act as an internal control where every child is their own control. RESULTS: At the start of treatment, 74 children had normal weight and 44 had either overweight or obesity. During the year with stimulants, the mean (SD) body mass index (BMI) in standard deviation score (SDS) decreased significantly: -0.72 (0.66) compared with 0.17 (0.43) during the year before treatment (p < 0.01). After one year with treatment, 43% of those with overweight or obesity had reached normal weight. CONCLUSIONS: Stimulant treatment for ADHD yields significant weight loss. In children with overweight or obesity and ADHD, this is an important finding showing additional benefit in terms of weight management.

Adrenal androgen trajectories are established during childhood in preterm boys.

AIM: We investigated longitudinal adrenal androgen concentrations and any relationship between gestational age, birth size, anthropometric parameters and adrenal androgen concentrations during childhood in boys born moderate to late preterm. METHODS: This longitudinal, prospective study included 58 boys born at 32+0 to 36+6 weeks of gestation. Dehydroepiandrosterone sulphate and androstenedione were analysed by liquid chromatography-tandem mass spectrometry, and anthropometric data were recorded from 5 to 10 years of age. RESULTS: Dehydroepiandrosterone sulphate concentrations correlated with weight standard deviations scores (SDS) from 7 to 10 years of age and waist-to-height ratios at seven and 10 years of age. Androstenedione correlated with weight SDS from 7 to 10 years of age and waist-to-height ratios at 10 years of age. Longitudinal analysis showed a relationship between weight SDS and waist-to-height SDS and dehydroepiandrosterone sulphate (p < 0.001 and p < 0.001, respectively) and androstenedione (p = 0.002 and p = 0.003, respectively), independently of age. CONCLUSION: The trajectories of anthropometric parameters and adrenal androgen secretion were consistent from 5 to 10 years of age in this cohort. The body composition reflected by current weight and the waist-to-height ratio, rather than gestational age and birth size, was associated with adrenal androgen secretion.

High prevalence of neurodevelopmental problems in adolescents eligible for bariatric surgery for severe obesity.

AIM: To assess the prevalence of neurodevelopmental problems in adolescents with severe obesity and their associations with binge eating and depression. METHODS: Data were collected at inclusion in a randomised study of bariatric surgery in 48 adolescents (73% girls; mean age 15.7 ± 1.0 years; mean body mass index 42.6 ± 5.2 kg/m2 ). Parents completed questionnaires assessing their adolescents' symptoms of attention-deficit/hyperactivity disorder and autism spectrum disorder and reported earlier diagnoses. Patients answered self-report questionnaires on binge eating and depressive symptoms. RESULTS: The parents of 26/48 adolescents (54%) reported scores above cut-off for symptoms of the targeted disorders in their adolescents, but only 15% reported a diagnosis, 32% of adolescents reported binge eating, and 20% reported symptoms of clinical depression. No significant associations were found between neurodevelopmental problems and binge eating or depressive symptoms. Only a third of the adolescents reported no problems in either area. CONCLUSION: Two thirds of adolescents seeking surgical weight loss presented with substantial mental health problems (reported by themselves or their parents). This illustrates the importance of a multi-professional approach and the need to screen for and treat mental health disorders in adolescents with obesity.

An eHealth Framework for Managing Pediatric Growth Disorders and Growth Hormone Therapy.

BACKGROUND: The use of technology to support health and health care has grown rapidly in the last decade across all ages and medical specialties. Newly developed eHealth tools are being implemented in long-term management of growth failure in children, a low prevalence pediatric endocrine disorder. OBJECTIVE: Our objective was to create a framework that can guide future implementation and research on the use of eHealth tools to support patients with growth disorders who require growth hormone therapy. METHODS: A total of 12 pediatric endocrinologists with experience in eHealth, from a wide geographical distribution, participated in a series of online discussions. We summarized the discussions of 3 workshops, conducted during 2020, on the use of eHealth in the management of growth disorders, which were structured to provide insights on existing challenges, opportunities, and solutions for the implementation of eHealth tools across the patient journey, from referral to the end of pediatric therapy. RESULTS: A total of 815 responses were collected from 2 questionnaire-based activities covering referral and diagnosis of growth disorders, and subsequent growth hormone therapy stages of the patient pathway, relating to physicians, nurses, and patients, parents, or caregivers. We mapped the feedback from those discussions into a framework that we developed as a guide to integration of eHealth tools across the patient journey. Responses focused on improved clinical management, such as growth monitoring and automation of referral for early detection of growth disorders, which could trigger rapid evaluation and diagnosis. Patient support included the use of eHealth for enhanced patient and caregiver communication, better access to educational opportunities, and enhanced medical and psychological support during growth hormone therapy management. Given the potential availability of patient data from connected devices, artificial intelligence can be used to predict adherence and personalize patient support. Providing evidence to demonstrate the value and utility of eHealth tools will ensure that these tools are widely accepted, trusted, and used in clinical practice, but implementation issues (eg, adaptation to specific clinical settings) must be addressed. CONCLUSIONS: The use of eHealth in growth hormone therapy has major potential to improve the management of growth disorders along the patient journey. Combining objective clinical information and patient adherence data is vital in supporting decision-making and the development of new eHealth tools. Involvement of clinicians and patients in the process of integrating such technologies into clinical practice is essential for implementation and developing evidence that eHealth tools can provide value across the patient pathway.

Depression, anxiety, and suicidal ideation in young adults 5 years after undergoing bariatric surgery as adolescents.

PURPOSE: Metabolic and bariatric surgery (MBS) is increasingly used in adolescents. The aim was to explore symptoms of depression and anxiety in young adults over 5 years' follow-up after undergoing MBS. METHODS: Beck Depression Inventory-2 and the Beck Anxiety Inventory were used to assess symptoms of depression and anxiety in 62 patients 1, 2, and 5 years after having Roux-en-Y gastric bypass at 13-18 years of age. Mental health, eating-related problems, and weight outcomes were tested for association with suicidal ideation at the 5-year follow-up. RESULTS: At the 5-year follow-up, the mean score for depression was 11.4 (± 12.4), indicating minimal symptoms of depression. The mean score for anxiety was 12.82 (± 11.50), indicating mild anxiety symptoms. Still, several participants reported moderate or severe symptoms of depression (26%) and anxiety (32%). Women reported more symptoms than men (P = 0.03 and 0.04). No significant changes were found in self-reported symptoms of depression and anxiety between the 1-year and the 5-year follow-up (P = 0.367 and 0.934). Suicidal ideation was reported by 16% at the 5-year follow-up. Participants reporting suicidal ideation had lost significantly less excess weight than participants without suicidal ideation (P = 0.009). CONCLUSION: Five years after adolescent MBS, a substantial minority still struggles with mental health issues, and women are more burdened than men. Our results indicate an association between less optimal weight loss and suicidal ideation 5 years after MBS. The findings emphasize the importance of offering long-term follow-up and mental health treatment several years after MBS. LEVEL OF EVIDENCE: Level III, cohort study. CLINICAL TRIAL REGISTRATION: The study is registered with ClinicalTrials.gov (NCT00289705). First posted February 10, 2006.

Determination of estrone sulfate, testosterone, androstenedione, DHEAS, cortisol, cortisone, and 17α-hydroxyprogesterone by LC-MS/MS in children and adolescents.

Quantitation of endogenous steroids and their precursors is essential for diagnosis of a wide range of endocrine disorders. Usually, these analyses have been carried out using immunoassays. However, immunoassays often overestimate concentrations due to assay interference by other endogenous steroids, especially for low concentrations. Mass spectrometry based methods offer superior specificity, accuracy, and sensitivity. We therefore present a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method with automated sample preparation for determination of 17α-hydroxyprogesterone (17OHP), cortisol, cortisone, dehydroepiandrosterone sulfate (DHEAS), androstenedione (A4), testosterone (T), and estrone sulfate (E1S). Samples were prepared using protein precipitation and 96-well filter plates, fully automated in a pipetting robot and analyzed by LC-MS/MS. Serum samples from 187 healthy children and adolescents aged 5-18 years were used to study hormone changes in relation to sex and pubertal stage. Lower limit of quantification for 17OHP was 0.7 nmol/L, for cortisol 11 nmol/L, for cortisone 2 nmol/L, for DHEAS 0.1 µmol/L, and for A4, T, and E1S, 0.2 nmol/L. This study showed a general increase in 17OHP, DHEAS, A4, T and E1S in both genders during puberty. In boys, A4 and T increased significantly throughout pubertal development. Girls had significantly higher A4 and E1S concentrations, while boys had higher T concentrations. No sex- or puberty-specific differences were seen in cortisol or cortisone concentrations. To the best of our knowledge, this is the first presentation of changes in serum E1S concentrations during pubertal development in healthy children.

Nutrition- and feeding practice-related risk factors for rapid weight gain during the first year of life: a population-based birth cohort study.

BACKGROUND: Rapid weight gain (RWG) during infancy increases the risk of excess weight later in life. Nutrition- and feeding practices associated with RWG need to be further examined. The present study aimed to examine nutrition- and feeding practice-related risk factors for RWG during the first year of life. METHODS: A population-based longitudinal birth cohort study of 1780 infants, classified as having RWG or non-RWG during 0-3-4, 0-6 and 6-12 months. RWG was defined as a change > 0.67 in weight standard deviation scores. Associations between nutrition- and feeding practice-related factors and RWG were examined with logistic regression models. RESULTS: Of the participating infants, 47% had RWG during 0-3-4 months, 46% during 0-6 months and 8% during 6-12 months. In the fully adjusted models, bottle-feeding at birth and at 3-4 months and nighttime meals containing formula milk were positively associated with RWG during 0-3-4 months (p < 0.05 for all). Breastfeeding at 3-4 months and nighttime meals containing breast milk were negatively associated with RWG during this period (p < 0.001). Bottle-feeding at birth, 3-4 and 6 months and nighttime meals containing formula milk at 3-4 months were positively associated with RWG during 0-6 months (p < 0.01 for all). Breastfeeding at 3-4 and 6 months was negatively associated with RWG (p < 0.01). During 6-12 months, only bottle-feeding at 3-4 months was positively associated with RWG (p < 0.05). CONCLUSIONS: RWG was more common during the first 6 months of life and bottle-feeding and formula milk given at night were risk factors for RWG during this period.

Systematic review suggests a relationship between moderate to late preterm birth and early childhood caries.

AIM: The aim was to examine the association between moderate to late preterm birth and the prevalence of early childhood caries. METHODS: We searched the PubMed, Scopus, Cochrane Trials Register databases up to February 28, 2020. Two independent reviewers screened the papers for relevance, extracted data and assessed the risk of bias. A random-effects meta-analysis was performed to pool the prevalence of early childhood caries by gestational age. RESULTS: The authors identified 14 studies covering 210,691 children. They were published from 2007-2020 and included birth cohorts, cross-sectional, register-based and case-control studies. We assessed eight of them as having low or moderate risk of bias. The median caries prevalence was 48.8% among children born moderate to late preterm compared to 20.5% for those born full term. The pooled overall odds ratio was 1.48 (95% confidence interval 1.16-1.89; P < .001). The certainty of this finding was low due to heterogeneity and inconsistencies across the studies. CONCLUSION: This systematic review and meta-analysis displayed a significantly higher prevalence of early childhood caries in children born moderate to late preterm compared to full term children. The finding suggests that the gestational age should be collected as a risk factor in the paediatric dental records.

A prospective study of perinatal and metabolic risk factors for early childhood caries.

AIM: To study the relationship between early childhood caries and perinatal and metabolic risk factors in a cohort of preschool children. METHODS: The study population consisted of 208 children followed from birth to 6.5 years. We extracted the perinatal factors from medical records and questionnaires and assessed the occurrence of caries at the age of 5 years. Indicators of the metabolic syndrome (waist circumference, blood pressure, fasting insulin, glucose and dyslipidaemia) were recorded at 6.5 years of age. RESULTS: Infants born moderately to late preterm and infants born small for gestational age were more likely to have early childhood caries at 5 years of age (relative risk 4.2 and 2.3, respectively; P < .05). The presence of metabolic risk factors according to the IDEFICS monitoring levels did not differ between children with or without caries but a statistically significant correlation was found between the fasting glucose values and the number of decayed or filled teeth (r = 0.18; P < .05). CONCLUSION: Being born preterm or small for gestational age increased the risk of early childhood caries. Preschool children with caries had higher fasting glucose levels but no other signs of the metabolic syndrome.

Pre- and postnatal growth failure with microcephaly due to two novel heterozygous IGF1R mutations and response to growth hormone treatment.

AIM: To explore the phenotype and response to growth hormone in patients with heterozygous mutations in the insulin-like growth factor I receptor gene (IGF1R). METHODS: Children with short stature, microcephaly, born SGA combined with biochemical sign of IGF-I insensitivity were analysed for IGF1R mutations or deletions using Sanger sequencing and Multiple ligation-dependent probe amplification analysis. RESULTS: In two families, a novel heterozygous non-synonymous missense IGF1R variant was identified. In family 1, c.3364G > T, p.(Gly1122Cys) was found in the proband and co-segregated perfectly with the phenotype in three generations. In family 2, a de novo variant c.3530G > A, p.(Arg1177His) was detected. Both variants were rare, not present in the GnomAD database. Three individuals carrying IGF1R mutations have received rhGH treatment. The average gain in height SDS during treatment was 0.42 (range: 0.26-0.60) and 0.64 (range: 0.32-0.86) after 1 and 2 years of treatment, respectively. CONCLUSION: Our study presents two heterozygous IGF1R mutations causing pre- and postnatal growth failure and microcephaly and also indicates that individuals with heterozygous IGF1R mutations can respond to rhGH treatment. The findings highlight that sequencing of the IGF1R should be considered in children with microcephaly and short stature due to pre- and postnatal growth failure.