Placental Apoptosis in Small for Gestational Age Babies: A Comparison between Swedish and Pakistani Populations

Background: Foeto-placental growth is regulated by a complex balance of growth promoting and growth inhibiting factors and hormones, namely the insulin-like growth factors (IGF) and the intracellular caspase proteins. Changes in the IGF-axis appear to affect this balance, with deficiencies possibly triggering apoptosis.Aim: To ascertain levels of apoptosis in the placenta of infants born small for gestational age (SGA) and appropriate for gestational age (AGA), comparing samples from two population groups, Pakistani and Swedish, in an attempt to better understand the mechanism behind foetal-placental growth restriction.Methods: Placental samples were taken immediately following delivery in both Karachi and Stockholm. In total 36 samples were included for further analysis (Pakistani: SGA n = 12, AGA n = 12; Swedish: SGA n = 7, AGA n = 5). Protein extraction was conducted for cell-death ELISA, and the remaining tissue samples were then paraffin embedded for further immunohistochemical and immunoflourescent analysis, looking at the apoptotic proteins, p53, caspase 8, and caspase 3. Furthermore, we compared maternal and newborn anthropometry between populations.Results: A higher apoptotic index, for caspase 8 and caspase 3, was seen in the Pakistani samples, as compared to the Swedish samples (p<0.01). TUNEL assays showed higher levels of apoptosis in the Pakistani population as compared to the Swedish population (p<0.01). Cell death ELISA analysis showed greater apoptotic activity in placenta from the Pakistani population as compared to the Swedish groups (p<0.05) as well as increased apoptotic activity in the SGA groups as compared to the AGA groups within each population (ELISA, p<0.05). No differences were seen in p53 levels as assessed by immunohistochemistry. Pakistani mothers were, on average, shorter than their Swedish counterparts (p<0.01).Conclusion: Increased apoptotic activity in placenta of the Pakistani population, as compared to their Swedish counterparts, may be associated with decreased foetal-placental growth seen in this population, particularly in babies born SGA. These findings, along with previously published results of the IGF-axis, and birth weight outcomes, suggests that lower IGF levels may be involved in the extracellular triggering of apoptosis, through caspase 8. This may further suggest a possible mechanism of foetal-placental growth restriction

Growth reference charts for children with hypochondroplasia

Hypochondroplasia (HCH) is a rare skeletal dysplasia causing mild short stature. There is a paucity of growth reference charts for this population. Anthropometric data were collected to generate height, weight, and head circumference (HC) growth reference charts for children with a diagnosis of HCH. Mixed longitudinal anthropometric data and genetic analysis results were collected from 14 European specialized skeletal dysplasia centers. Growth charts were generated using Generalized Additive Models for Location, Scale, and Shape. Measurements for height (983), weight (896), and HC (389) were collected from 188 (79 female) children with a diagnosis of HCH aged 0-18 years. Of the 84 children who underwent genetic testing, a pathogenic variant in FGFR3 was identified in 92% (77). The data were used to generate growth references for height, weight, and HC, plotted as charts with seven centiles from 2nd to 98th, for ages 0-4 and 0-16 years. HCH-specific growth charts are important in the clinical care of these children. They help to identify if other comorbidities are present that affect growth and development and serve as an important benchmark for any prospective interventional research studies and trials

Maternal nutrition during mid-pregnancy and children’s body composition at seven years of age in the SELMA study

Optimal nutrition during pregnancy is vital for both maternal and child health. Our objective was to explore if prenatal diet is associated with children’s height and body fat. Nutrient intake was assessed through a food-frequency questionnaire from 808 pregnant women and summarized to a nutrition index, "My Nutrition Index"(MNI). The association with children’s height and body fat (bioimpedance) was assessed with linear regression models. Secondary analysis was performed with BMI, trunk fat and skinfolds. Overall, higher MNI score was associated with greater height (β=0.47; (95% CI: 0.00, 0.94), among both sexes. Among boys, higher MNI was associated with 0.15 higher BMI z-scores, 0.12 body fat z-scores, 0.11 trunk fat z-scores, and larger triceps, and triceps + subscapular skinfolds (β=0.05 and β=0.06; on the log2 scale) (p-value<0.05). Among girls, the opposite associations were found with 0.12 lower trunk fat z-scores, and smaller subscapular and suprailiac skinfolds (β= -0.07 and β= -0.10; on the log2 scale) (p-value<0.05). For skinfold measures this would represent a ±1.0 millimeters difference. Unexpectedly, a prenatal diet in line with recommended nutrient intake was associated with higher measures of body fat for boys and opposite to girls at a pre-pubertal stage of development.

Gait in children with achondroplasia – a cross-sectional study on joint kinematics and kinetics

Background: Children with achondroplasia have extreme short stature due to short limbs, as well as several other clinical features that may affect their gait. The purpose of this cross-sectional study was to provide a detailed description of gait in children with achondroplasia compared to age-matched controls. Methods: Between the years 2007 and 2010, 16 children with achondroplasia [mean age 9.6 years (range 5–16; six female)] with no previous history of orthopaedic lower limb surgery and 19 age-matched controls conducted three-dimensional (3D) gait analysis at one occasion. The gait analysis rendered pelvis and lower limb joint kinematics and kinetics, and time and distance data. Descriptive statistics, independent samples t-tests, and Fisher’s exact test were used to describe the cohort including gait data and participant characteristics. Results: Children with achondroplasia had kinematic gait pattern deviations in all three planes, especially in the sagittal plane, when compared to the control group. Peak anterior pelvic tilt and peak ankle dorsiflexion were found to be increased. Increased knee flexion was noted at initial contact and again at terminal stance. During stance, children with achondroplasia had a higher peak hip abduction angle and a higher peak knee varus angle in the frontal plane. In the sagittal plane, kinetic gait pattern deviations were found at the hip, knee, and ankle, consistent with a flexion pattern. Compared to the control group, children with achondroplasia walked with reduced walking speed and step length, and increased cadence. There was no difference in walking speed when leg length was taken into account. Normalised step length and normalised cadence, on the other hand, were found to be increased in children with achondroplasia. Conclusions: The observed gait characteristics in children with achondroplasia are related to anatomical attributes and strategies to increase step length, and hence walking speed

Colombian reference growth curves for height, weight, body mass index and head circumference

Aim Published Growth studies from Latin America are limited to growth references from Argentina and Venezuela. The aim of this study was to construct reference growth curves for height, weight, body mass index (BMI ) and head circumference of Colombian children in a format that is useful for following the growth of the individual child and as a tool for public health. Methods Prospective measurements from 27 209 Colombian children from middle and upper socio‐economic level families were processed using the generalised additive models for location, scale and shape (GAMLSS ). Results Descriptive statistics for length and height, weight, BMI and head circumference for age are given as raw and smoothed values. Final height was 172.3 cm for boys and 159.4 cm for girls. Weight at 18 years of age was 64.0 kg for boys and 54 kg for girls. Growth curves are presented in a ± 3 SD format using logarithmic axes. Conclusion The constructed reference growth curves are a start for following secular trends in Colombia and are also in the presented layout an optimal clinical tool for health care

Dose-Dependent Effect of Growth Hormone on Final Height in Children with Short Stature without Growth Hormone deficiency.

Context: Effect of GH therapy in short non GH deficient children, especially idiopathic short stature (ISS) has not been clearly established owing to lack of controlled trials until final height (FH). Objective: To investigate the effect of two GH doses compared with untreated controls on growth to FH in short children mainly with ISS. Design and Setting: A randomized, controlled, long-term multicenter trial in Sweden. Intervention: Two doses of GH (Genotropin): 33 or 67 microg/kg/d plus untreated controls. Subjects: 177 subjects with short stature were enrolled. Of these, 151 were included in the Intent to Treat (AllITT) Population and 108 in the Per Protocol (AllPP) Population. Analysis of ISS subjects included 126 children in the ITT (ISSITT) Population and 68 subjects in the PP (ISSPP) Population. Main Outcome Measures: FH SDS, difference in SDS to midparenteral height (diff MPHSDS), and gain in HeightSDS. Results: After 5.9+/-1.1 yr on GH therapy, the FHSDS in the AllPP Population treated with GH vs. controls was -1.5+/-0.81 (33 microg/kg/d: -1.7+/-0.70, 67 microg/kg/d: -1.4+/-0.86; P<0.032), vs. -2.4+/-0.85 (P<0.001), the diff MPHSDS -0.2+/-1.0 vs. -1.0+/-0.74 (P<0.001), and the gain in HeightSDS 1.3+/-0.78 vs. 0.2+/-0.69 (P<0.001). GH therapy was safe and had no impact on time to onset of puberty. A dose-response relationship identified after 1 yr remained to FH for all growth outcome variables in all four populations. Conclusion: GH treatment significantly increased FH in ISS children in a dose-dependent manner, with a mean gain of 1.3 SDS (8 cm), and a broad range of response from no gain to 3 SDS compared to a mean gain of 0.2 SDS in the untreated controls

Prevalence of coeliac disease in Turner syndrome

This study was undertaken to investigate the prevalence of coeliac disease in children and adolescents with Turner syndrome. Eighty-seven children and adolescents with Turner syndrome were screened for IgA- antiendomysium antibodies (EMA) and IgA-antigliadin antibodies (AGA), 5% (4/87) being found to be EMA-positive, and 15% (13/87) to have AGA levels above normal. Of the 10 patients who were either AGA- or EMA-positive and further investigated with intestinal biopsy, four manifested villous atrophy (i.e. all three of the EMA-positive patients, but only one of the seven AGA- positive patients). The results suggest EMA-positivity to be a good immunological marker for use in screening for coeliac disease, and such screening to be justified in patients with Turner syndrome

Gene expression signatures predict response to therapy with growth hormone.

From PubMed via Jisc Publications RouterHistory: received 2020-05-10, revised 2021-03-17, accepted 2021-04-23Publication status: aheadofprintRecombinant 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