Statistical models for pediatric endocrinology

Background: Modelling references for biomarkers as reference curves enables calculation of patient z-scores that are adjusted for both gender and covariance with age during childhood.Aim: To establish biomarker reference curves using the ‘LMS’ method previously employed for conventional growth charts.Design, Setting and Participants: Cross-sectional study of healthy Norwegian girls (n=647) and boys (n=465) in ages 6 to 16 years were recruited in the Bergen Growth Study (2016). Blood samples were analyzed using state-of-the-art instruments.Results: Reference curves for several biomarkers were established in the ‘LMS’ framework and provided here for clinical implementation. Conclusion: The ‘LMS’ reference framework is already used to create conventional growth charts and may also be applied in clinical biochemistry.

The chemostratigraphy and environmental significance of the Marlstone and Junction Bed (Beacon Limestone, Toarcian, Lower Jurassic, Dorset, UK)

Two fallen blocks of the Marlstone and stratigraphically overlying Junction Bed sampled on the beach below Doghouse Cliff in Dorset, UK (Wessex Basin) have been examined for carbon and oxygen isotopes of bulk carbonate as well as for strontium, carbon and oxygen isotopes and Mg:Ca ratios in the contained belemnites. The sequence, which contains most of the Toarcian zones and subzones within a metre or less of grey to yellow to pink, red and brown fossil-rich nodular limestone, is extremely condensed and lithologically similar to pelagic red limestones of the Tethyan Jurassic that are locally mineralized with Fe-Mn oxyhydroxides (e.g., Rosso Ammonitico). Strontium-isotope ratios of the contained belemnites are compatible with existing reference curves and both blocks show a rise to more radiogenic values post-dating the Pliensbachian–Toarcian boundary. The high degree of correlation between the relatively negative carbon and oxygen isotopes of the bulk carbonate is compatible with significant diagenetic overprint, and contrasts with higher carbon-isotope values in coeval condensed coccolith-rich limestones elsewhere. Evidence for the characteristic signature of the Toarcian Oceanic Anoxic Event, as represented by organic-rich sediment, is absent, possibly owing to a stratigraphic gap. Both blocks exhibit abrupt carbon-isotope shifts to lower values, one of which could represent the limbs of an incompletely recorded negative excursion associated with the Toarcian Oceanic Anoxic Event. That the Toarcian Oceanic Anoxic Event was also a significant hyperthermal is illustrated in both blocks by a drop in oxygen-isotope values and rise in Mg:Ca ratios of belemnites close to the base of the Junction Bed in the lowest part of the serpentinum zone.

Reference Curves of Selected Circumferential Parameters for Czech Children Aged 6 to 11 Years

(1) Background/objective: the globally discussed current issue is the increasing body weight of the population. This trend is observed in all age categories. Pediatricians and anthropologists use BMI percentile curves to determine the optimal body weight of children, based on which the child is categorized in the category of underweight, normal weight, overweight, or obese. Medical or anthropological examinations also use some methods to determine the amount of body fat. In addition to evaluating amounts of body fat, it is important to assess its distribution. The distribution of fat in the body, especially in terms of disproportionate distribution, is a risk factor for health complications, especially in terms of metabolic and health risk. Part of monitoring children’s growth is also measuring and evaluating circumferential parameters, such as abdominal circumference, gluteal circumference, and waist circumference. This study aimed to define age- and gender-specific reference curves for waist circumference (WC), abdominal circumference (AbC), and gluteal circumference (GC) in Czech children. (2) Methods: data on children’s circumferential parameters were collected via anthropometric measurements. The research sample consisted of 2093 children aged 6–11 years (boys, n = 1008; girls, n = 1085). Only children with parental informed consent were included. The statistical analysis was performed separately by age and gender using SPSS v. 22. Anthropometric data were summarized by mean and standard deviation. The percentile curves of WC, AbC, and GC were calculated (P3, P10, P25, P50, P75, P90, P97) in R 3.4.2 software (R Foundation for Statistical Computing, Vienna, Austria) using the gamlss package. (3) Results and conclusions: the study developed age- and gender-specific percentile curves of WC, AbC, and GC for Czech children aged 6–11 years. All parameters increased with age in both boys and girls. Generally, the boys had higher WC and AbC than did girls, but girls had higher GC than did boys. Female and male median WC percentiles (M) increased from the age of 6. Both girls’ and boys’ median percentiles showed a continuous increase. We found similar trends in the median GC and AbC percentile curves. All percentile curves showed similar trends in both sexes, but the 90th and 97th WC percentiles in boys were exceptions: from the age of 10, they exceeded the values of girls, reaching their peak at the age of 11 followed by a decrease in the case of the 97th percentile and a plateau in the case of the 90th percentile. This study serves as a reference to enrich the methods of evaluation of somatic and medical status in Czech children. Up–to–date percentile curves would be a practical addition to the BMI percentiles for the screening and evaluation of overweight and obese conditions and the related risks of abdominal obesity in the pediatric population.

Dynamic Changes in Serum IGF-I and Growth During Infancy: Associations to Body Fat, Target Height, and PAPPA2 Genotype

Context IGF-I is important for postnatal growth and may be of diagnostic value in infants suspected of pituitary disease; however, little is known about the impact of IGF-I and its determinants on infant growth. Importantly, detailed reference ranges for IGF-I and IGF binding protein-3 (IGFBP-3) concentrations during infancy are lacking. Objective To evaluate the rapid changes in weight and length as well as their determinants in healthy infants, and to establish age- and sex-specific reference curves for IGF-I and IGFBP-3 in children aged 0 to 1 years. Design Prospective longitudinal study. Setting Cohort study. Participants A total of 233 healthy children (114 girls) with repeated blood samples during the first year of life. Main Outcome Measure(s) Serum concentrations of IGF-I and IGFBP-3, length velocity, weight velocity, and PAPPA2 (rs1325598) genotype. Results Individual trajectories of length and weight velocities were sex specific. We provide detailed reference curves based on longitudinal data for IGF-I and IGFBP-3 during infancy. In both girls and boys, IGF-I decreased during infancy, whereas IGFBP-3 remained stable. IGF-I and IGFBP-3, but not PAPPA2 genotype, were positively associated with weight gain, but not with longitudinal growth. When stratified by sex, the association between weight gain and IGF-I only remained significant in girls. Conclusions Interestingly, we found a significant association between IGF-I and infant weight gain in girls, but not with longitudinal growth in the first year of life. Our findings highlight the role of IGF-I as an important anabolic hormone that is not limited to linear growth.

Prevalence, Patterns, and Determinants of Malaria and Malnutrition in Douala, Cameroon: A Cross-Sectional Community-Based Study

Background. Malaria and malnutrition are major public health problems in developing countries. This studywas mainly focused on the prevalence, patterns, and predictors of these conditions and their associations. Methods. A cross-sectional community study was conducted from February to March 2018 among 281 participants living in two districts in Douala. A questionnaire was used to collect sociodemographic information and parasitological and anthropometric data of participants. Nutritional status was determined using age, weight, and height. Body mass index for age (BMIAZ), height-for-age (HAZ), weight-for-age (WAZ), and weight-for-height (WHZ) Z scores were computed based on the World Health Organization growth reference curves. Malaria infection was diagnosed using light-emitting diode fluorescence microscopy. Results. The overall prevalence of malaria was 18.9%, mostly asymptomatic cases. Malaria infection was associated with study site ( p = 0.04 ), age ( p = 0.01 ), WAZ ( p = 0.0049 ), HAZ ( p = 0.03 ), and BMI ( p = 0.02 ). The overall prevalence of malnutrition was 43.1%, and stunting was the main form of malnutrition recorded in children under five years of age (23.6%). The risk of being stunted in this group was about quintupled in malaria-infected participants ( ARR = 4.70 ; p = 0.02 ). In those aged 5-19 years, the prevalence of underweight was significantly higher in malaria-positive individuals as compared to their negative counterparts ( p = 0.02 ). The overall prevalence of malaria and malnutrition cooccurrence was 8.5% and varied with age ( p < 0.0001 ) and study site ( p = 0.04 ). Conclusion and Recommendation. Malaria was associated with malnutrition among the study participants. Early detection and treatment of these ailments would reduce morbidity and mortality.

Sex- and age-specific reference intervals for diagnostic ratios reflecting relative activity of steroidogenic enzymes and pathways in adults

Objective Diagnostic ratios calculated from urinary steroid hormone metabolites are used as a measure for the relative activity of steroidogenic enzymes or pathways in the clinical investigation of steroid metabolism disorders. However, population-based sex- and age-specific reference intervals and day-night differences in adults are lacking. Methods Sixty-five diagnostic ratios were calculated from steroid metabolites measured by GC-MS in day- and night-time and in 24-hour urine from 1128 adults recruited within the Swiss Kidney Project on Genes in Hypertension (SKIPOGH), a population-based, multicenter cohort study. Differences related to sex, age and day- and night-time were evaluated and reference curves in function of age and sex were modelled by multivariable linear mixed regression for diagnostic ratios and were compared to values from the literature. Results Most ratios had sex- and age-specific relationships. For each ratio, percentiles were plotted in function of age and sex in order to create reference curves and sex- and age-specific reference intervals derived from 2.5th and 97.5th percentiles were obtained. Most ratios reflected a higher enzyme activity during the day compared to the night. Conclusions Sex- and age-specific references for 24 hours, day and night urine steroid metabolite ratios may help distinguishing between health and disease when investigating human disorders affecting steroid synthesis and metabolism. The day-night differences observed for most of the diagnostic ratios suggest a circadian rhythm for enzymes involved in human steroid hormones metabolism.