Acceleration of skeletal maturation in Central Europe over the last two decades: insights from two cohorts of healthy children.

BACKGROUND: Deviations between the determination of bone age (BA) according to Greulich and Pyle (G&P) and chronological age (CA) are common in Caucasians. Assessing these discrepancies in a population over time requires analysis of large samples and low intra-observer variability in BA estimation, both can be achieved with artificial intelligence-based software. The latest software-based reference curve contrasting the BA determined by G&P to the CA of Central European children dates back over two decades. OBJECTIVE: To examine whether the reference curve from a historical cohort from the Netherlands (Rotterdam cohort) between BA determined by G&P and CA still applies to a current Central European cohort and derive a current reference curve. MATERIALS AND METHODS: This retrospective single-center study included 1,653 children and adolescents (aged 3-17 years) who had received a radiograph of the hand following trauma. The G&P BA estimated using artificial intelligence-based software was contrasted with the CA, and the deviations were compared with the Rotterdam cohort. RESULTS: Among the participants, the mean absolute error between BA and CA was 0.92 years for girls and 0.97 years for boys. For the ages of 8 years (boys) and 11 years (girls) and upward, the mean deviation was significantly greater in the current cohort than in the Rotterdam cohort. The reference curves of both cohorts also differed significantly from each other (P < 0.001 for both boys and girls). CONCLUSION: The BA of the current Central European population and that of the curve from the Rotterdam cohort from over two decades ago differ. Whether this effect can be attributed to accelerated bone maturation needs further evaluation.

Reference growth curves to identify weight status (underweight, overweight or obesity) in children and adolescents: systematic review.

The identification of somatic growth, through reference curves, can be used to create strategies and public policies to reduce public health problems such as malnutrition and obesity and to identify underweight, overweight and obesity. The purpose of this systematic review was to identify studies providing reference growth curves for weight status in children and adolescents. A systematic search was conducted in eight databases and in gray literature (Google scholar). To assess the risk of bias/methodological quality of studies, the National Institutes of Health (NIH) Quality Assessment Tool for Observational Cohort and Cross-sectional Studies (NHLBI) was used. Overall, 86 studies that met the inclusion criteria were included. Through the values   of reference growth curves for the identification of underweight, overweight and obesity, it was possible to verify that there is great variability among percentiles for the identification of underweight, overweight and obesity. The most prevalent percentiles for underweight were P3 and P5; for overweight, the most prevalent was P85 and the most prevalent percentiles for obesity were P95 and P97. The most prevalent anthropometric indicators were Body Mass Index (BMI), Waist Circumference (WC), Body Mass (BM) for age and height for age. Conclusion: Such data can demonstrate that the optimal growth must be reached, through the standard growth curves, but that the reference curves demonstrate a cut of the population growth, raising possible variables that can influence the optimal growth, such as an increase in the practice of physical activities and an awareness of proper nutrition.

Comparison of growth curves in very low birth weight preterm infants after hospital discharge.

Monitoring preterm infants' growth is essential to ensure the best prognosis for their growth and development. We aimed to compare growth curves in very low birth weight preterm infants after hospital discharge. In this retrospective longitudinal study, 178 preterm infants' growth was assessed by z-scores for weight for age and length to age and compared between Fenton and Kim and Intergrowth-21st charts from hospital discharge until 50 weeks postnatal, and between Intergrowth-21st and WHO charts, 50 and 64 weeks postnatal. The Kappa test was used to evaluate the agreement of the number of cases classified above or below the -2 Z-score concerning weight-for-age and length-for-age indicators to each proposed curve. Our results found that the agreement between Fenton and Kim and Intergrowth-21st curves was almost perfect for most of the weeks investigated, except 35-38 (k = 0.79) and 47-50 (k = 0.61) weeks postnatal. When evaluating the agreement between WHO and Intergrowth-21st, it was substantial for most of the weeks investigated, except for 55-58 and 69-64 weeks postnatal, in which the agreement was almost perfect (k = 0.84; k = 0.81, respectively). Furthermore, we observed that Fenton and Kim curve identified 8.4% and WHO, 5.8% more cases of preterm infants below -2 z than Intergrowth-21st.Conclusion: Although the agreement of the curves was substantial to almost perfect, the Fenton and Kim and WHO curve seem to identify more cases of preterm infants compared to the Intergrowth-21st, a finding that deserves more in-depth investigation in clinical practice. What is Known: • The adequate interpretation of postnatal growth depends on the standard growth chart. • Studies comparing the classification of anthropometric indicators of preterm infants between growth curves consider only the period from birth to hospital discharge. What is New: • This is the first study that compares the classification of weight-for-age and length-for-age indicators of VLBW preterm infants between Intergrowth-21st and Fenton and Kim curves until 64 weeks postnatal. • Substantial to almost perfect agreement of length-for-age indicator was found between the two growth curves of preterm infants during outpatient follow-up.

Reference ranges for ultrasound measurements of fetal kidneys in a cohort of low-risk pregnant women.

PURPOSE: Alterations in renal dimensions may be an early manifestation of deviation from normality, with possible repercussions beyond intrauterine life. The objective of this study was to establish reference curves for fetal kidney dimensions and volume from 14 to 40 weeks of gestation. METHODS: This is a prospective longitudinal study of 115 Brazilian participants in the "WHO multicentre study for the development of growth standards from fetal life to childhood: the fetal component". Pregnant women with clinical and sociodemographic characteristics allowing the full potential fetal growth were followed up from the first trimester until delivery. These women underwent serial sonographic evaluation of fetal kidneys. The longitudinal, anteroposterior and transverse diameters of both fetal kidneys were measured, in addition to calculation of kidney volume. By quantile regression analysis, reference curves of renal measurements related to gestational age were built. RESULTS: Standard normal sonographic values of renal biometry were defined during pregnancy. Reference values for the 10th, 50th and 90th centiles of different fetal kidney measurements (longitudinal, anteroposterior, transverse and volume) from the 14th to the 40th week of gestation were fitted. CONCLUSION: The reference curves presented should be of the utmost importance for screening and diagnosis of alterations in renal development during the intrauterine period.

Relationship between childhood obesity cut-offs and metabolic and vascular comorbidities: comparative analysis of three growth standards.

BACKGROUND: To compare the association between metabolic and vascular comorbidities and the body mass (BMI)-for-age cut-off criteria from three growth standards [Centers for Disease Control and Prevention (CDC), 2000; World Health Organization (WHO), 2007; Spanish Reference Criteria (Carrascosa Lezcano et al., 2008)] that are used to define being overweight and obese in childhood. METHODS: A prospective study was conducted in 137 children (aged 8-16 years). Based on BMI-for-age Z-scores according to WHO cut-offs, 59 participants were obese, 35 were overweight and 43 were normal-weight. All participating children were subsequently reclassified applying the CDC and Spanish Reference Criteria. Blood pressure (BP), biochemical variables and vascular parameters (stiffness and intima-media thickness) were analysed. RESULTS: According to WHO and CDC references, 48% and 43% of the children, respectively, were categorised as obese, whereas 16% were considered as obese using the Spanish Reference Criteria. Applying WHO criteria, obese children showed significantly higher levels of insulin, homeostasis model assessment index and most vascular parameters, as well as lower high-density lipoprotein (HDL)-cholesterol than overweight children. Moreover, overweight children showed higher BP, insulin and uric acid, and lower HDL-cholesterol than normal weight children. The CDC criteria yielded similar results, although with fewer differences between obese and overweight children. Applying Spanish criteria, the differences between obese and overweight children disappeared. CONCLUSIONS: WHO and CDC BMI-for-age references and cut-offs are useful for defining obesity and being overweight in children because they clearly identify metabolic and vascular comorbidities. The Spanish Reference Criteria underdiagnose obesity because overweight children show comorbidities typical of the obese.

Growth analysis among adolescents with moderate-to-severe atopic dermatitis receiving upadacitinib in combination with topical corticosteroids in Japan: A case study series from a phase 3, randomized, controlled trial (Rising Up).

Background: Treatment options for adolescents with moderate-to-severe atopic dermatitis (AD) are limited. Oral corticosteroid therapies are used to treat children and adolescents with moderate-to-severe AD; however, long-term use is not recommended because of potential growth impairment. Upadacitinib, an oral Janus kinase inhibitor, is approved to treat moderate-to-severe AD in the United States, Japan, and Europe. To investigate potential effects of upadacitinib on growth, we analyzed height and height velocity in 6 adolescent patients in the phase 3 Rising Up study who were in the decline phase of pubertal growth at the time of study entry. Methods: The randomized, double-blind, Rising Up (NCT03661138) study compared upadacitinib plus topical corticosteroids (TCS) to placebo plus TCS in adolescents and adults with moderate-to-severe AD in Japan. Eligible adolescents (aged 12-17 years) were randomized 1:1:1 to receive once-daily upadacitinib 15 mg, upadacitinib 30 mg, or placebo in combination with TCS for 16 weeks. After 16 weeks, patients randomized to receive placebo were rerandomized 1:1 to receive upadacitinib 15 mg or upadacitinib 30 mg. Historical height measurements were obtained when available. Individual growth and growth velocity curves were compared with standard curves for Japanese youths. This non-prespecified analysis used 52-week data. Results: Of the 29 adolescents enrolled, 6 were in the decline phase of pubertal growth at enrollment. Growth curves and growth velocity curves for these 6 patients remained within the normal range for Japanese adolescents throughout the study. Biomarkers of bone metabolism generally remained stable over the course of the study. No musculoskeletal adverse events were reported. Conclusions: No cases suggested that upadacitinib negatively affected adolescent growth. Ongoing studies will continue to assess height and adverse effects related to bone growth to further inform on this patient group. Trial registration: ClinicalTrials.gov Identifier NCT03661138.

Reference Intervals for Non-Fasting CVD Lipids and Inflammation Markers in Pregnant Indigenous Australian Women.

Indigenous Australians experience high rates of cardiovascular disease (CVD). The origins of CVD may commence during pregnancy, yet few serum reference values for CVD biomarkers exist specific to the pregnancy period. The Gomeroi gaaynggal research project is a program that undertakes research and provides some health services to pregnant Indigenous women. Three hundred and ninety-nine non-fasting samples provided by the study participants (206 pregnancies and 175 women) have been used to construct reference intervals for CVD biomarkers during this critical time. A pragmatic design was used, in that women were not excluded for the presence of chronic or acute health states. Percentile bands for non-linear relationships were constructed according to the methods of Wright and Royston (2008), using the xriml package in StataIC 13.1. Serum cholesterol, triglycerides, cystatin-C and alkaline phosphatase increased as gestational age progressed, with little change seen in high-sensitivity C-Reactive Protein and γ glutamyl transferase. Values provided in the reference intervals are consistent with findings from other research projects. These reference intervals will form a basis with which future CVD biomarkers for pregnant Indigenous Australian women can be compared.

Birth weight for gestational age: a reference study in a tertiary referral hospital in the middle region of Turkey.

BACKGROUND: The purpose of this study was to establish a fetal birth weight curve for gestational age for patients who presented to our tertiary referral hospital. The curve can be used for epidemiological analysis and also to develop Turkey's first national nomogram. METHODS: A total of 68,255 live singleton pregnancies delivered during the study period in a tertiary referral hospital were initially reviewed in this study. The data were carefully collected from hospital records and patients' files. Gestational age (weeks) was assessed by either ultrasound examination or according to the patient's last menstrual period, or both. Sex-specific reference tables for fetal birth weight by gestational age were created, and statistical analyses were carried out for descriptive variables using SPSS 15.0 for Windows. RESULTS: Most newborns weighed between 3000 g and 4000 g. The percentile fetal birth weight curves for gestational age showed that fetal birth weight increased with the increase in gestational age. Typically, male infants were noted to have higher birth weights than female infants. When our results were compared with those of previous studies, it was demonstrated that values for the 10(th) percentile were higher in our study, whereas values for the 90(th) percentile were similar to those of previous studies. CONCLUSION: To the best of our knowledge, this is the first study evaluating the correlation between gestational age and fetal birth weight with such a large sample size in Turkey. Therefore, the results of this reference study can be helpful in defining normal and abnormal fetal growth in Turkish newborns.

Standardized percentile curves of body mass index of northeast Iranian children aged 25 to 60 months.

OBJECTIVE: Growth charts are widely used to assess children's growth status and can provide a trajectory of growth during early important months of life. Racial differences necessitate using local growth charts. This study aimed to provide standardized growth curves of body mass index (BMI) for children living in northeast Iran. METHODS: A total of 23730 apparently healthy boys and girls aged 25 to 60 months recruited for 20 days from those attending community clinics for routine health checks. Anthropometric measurements were done by trained health staff using WHO methodology. The LMSP method with maximum penalized likelihood, the Generalized Additive Models, the Box-Cox power exponential distribution distribution, Akaike Information Criteria and Generalized Akaike Criteria with penalty equal to 3 [GAIC(3)], and Worm plot and Q-tests as goodness of fit tests were used to construct the centile reference charts. FINDINGS: The BMI centile curves for boys and girls aged 25 to 60 months were drawn utilizing a population of children living in northeast Iran. CONCLUSION: The results of the current study demonstrate the possibility of preparation of local growth charts and their importance in evaluating children's growth. Also their differences, relative to those prepared by global references, reflect the necessity of preparing local charts in future studies using longitudinal data.