Background: Very preterm infants often receive donor milk from mothers who deliver at term, but its composition differs from that of their own mother

Gender-specific differences in hypothalamus–pituitary–adrenal (HPA) axis activity have been postulated to emerge during puberty. We conducted a systematic review and meta-analysis to test the hypothesis that gender-specific differences in HPA axis activity are already present in childhood. From inception to January 2016, PubMed and EMBASE.com were searched for studies that assessed non-stimulated cortisol in serum or saliva or cortisol in 24-h urine in healthy males and females aged ≤18 years. Studies that conform with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement were reported. Standardized mean differences (95% CIs) were calculated and analyzed using fixed-effect meta-analysis stratified for age: <8 years (prepubertal) and 8–18 years (peri-/postpubertal). For comparison, we ran the same analyses using random-effects models. Two independent assessors selected 413 out of 6158 records (7%) for full-text screening, of which 79 articles were included. Of these, 58 (with data on 16,551 subjects) were included in the meta-analysis. Gender differences in cortisol metabolism differed per age group. Boys aged <8 years had 0.18 (0.06; 0.30) nmol/L higher serum and 0.21 (0.05; 0.37) nmol/L higher salivary cortisol levels, while between 8 and 18 years, boys had 0.34 (0.28; 0.40) nmol/L lower serum and 0.42 (0.38; 0.47) nmol/L lower salivary cortisol levels. In 24-h urine, cortisol was consistently higher in boys, being 0.34 (0.05; 0.64) and 0.32 (0.17; 0.47) μg/24 h higher in the <8- and 8–18-year groups, respectively. However, gender-differences in serum cortisol <8 years and between 8 and 18 years were absent when using random-effects models. Gender differences in cortisol metabolism are already present in childhood, with higher salivary cortisol in boys aged <8 years compared to girls. This pattern was reversed after the age of 8 years. In contrast, the gender-specific difference in cortisol production as assessed through 24-h urine did not change with age. Although differences were small, and analyses of gender differences in serum cortisol were inconclusive, they might contribute to gender-specific origins of health and disease.

Summary: Recent studies report negative mental health effects of the COVID‐19 related lockdown measures in general paediatric cohorts. Since obesity is a risk factor for COVID‐19 in adults, children (including adolescents) with obesity might perceive themselves to be vulnerable. Using a combined quantitative and qualitative approach, we explored COVID‐19 related anxiety in paediatric patients with severe obesity in the Netherlands using semi‐structured telephone interviews and the Paediatric Quality of Life Inventory (PedsQL) questionnaire, which had also been completed by the study population at baseline in the year prior to the COVID‐19 outbreak. In total, 75 families participated in the semi‐structured telephone interviews during the lockdown, April 2020. Characteristics of included patients were: median age 10.5 years (interquartile range = 7.6‐15.2); 52% female; mean BMI standard deviation score 3.8 (SD = 1.0). COVID‐19 related anxiety was reported for 24/75 (32%) children. The mean decrease in PedsQL score between baseline visit and COVID‐19 outbreak did not differ between children for whom anxiety was reported vs those for whom it was not (mean change −10.3 ± 36.5 vs −3.3 ± 24.4, P = .54). Self‐imposed strict quarantine measures were taken by 19/75 (25%) families. During follow‐up, several families reported that the previous contact alleviated their anxiety. In conclusion, healthcare professionals should address possible COVID‐19 related anxiety in children with severe obesity. Addressing COVID‐19 related anxiety could mitigate its potential negative effects.

Summary: Increasing evidence points to a relation between increased glucocorticoid (GC) exposure and weight gain. In support, long‐term cortisol measurements using hair analysis revealed that many individuals with obesity appear to have cortisol values in the high physiological range. The mechanisms behind this relationship need to be determined in order to develop targeted therapy to reach sustainable weight loss in these subgroups.The effect of GCs is not only determined by the plasma concentration of GCs but also by individual differences in GC sensitivity and the target tissue, which can be analyzed by functional GC assays. GC sensitivity is influenced by multiple genetic and acquired (e.g., disease‐related) factors, including intracellular GC availability, hormone binding affinity, and expression levels of the GC receptors and their isoforms, as well as factors involved in the modulation of gene transcription. Interindividual differences in GC sensitivity also play a role in the response to exogenous GCs, with respect to both therapeutic and adverse effects.Accordingly, in this review, we summarize current knowledge on mechanisms that influence GC sensitivity and their relationships with obesity and discuss personalized treatment options targeting the GC receptor.

Background: Hair glucocorticoids (GCs) offer a retrospective view on chronic GC exposure. We assessed whether maternal pre- and postnatal stress was associated with neonatal and maternal hair GCs postpartum (pp). Methods: On the first day pp 172 mother-infant pairs donated hair, of whom 67 had consulted a centre of expertise for psychiatric disorders during pregnancy. Maternal stress was scored on the Hospital Anxiety and Depression Scale during the first/second (n = 46), third trimester (n = 57), and pp (n = 172). Hair cortisol and cortisone levels were determined by liquid chromatography-tandem mass spectrometry, and associations with maternal hospital anxiety subscale (HAS) and hospital depression subscale (HDS) scores, and antidepressant use were analyzed with linear regression. Results: Neonatal hair GCs were negatively associated with elevated HAS-scores during the first/second trimester, log 10 (β [95% CI]) cortisol –0.19 (–0.39 to 0.02) p = 0.07, cortisone –0.10 (–0.25 to 0.05) p = 0.17; third trimester, cortisol –0.17 (–0.33 to 0.00) p = 0.05, cortisone –0.17 (–0.28 to –0.05) p = 0.01; and pp, cortisol –0.14 (–0.25 to –0.02) p = 0.02, cortisone –0.07 (–0.16 to 0.02) p = 0.10. A similar pattern was observed for elevated HDS-scores. Maternal hair GCs were positively associated with elevated HAS-scores pp (cortisol 0.17 [0.01 to 0.32] p = 0.04, cortisone 0.18 [0.06 to 0.31] p = 0.01), but not prenatally or with elevated HDS-scores. Antidepressant use was associated with elevated maternal hair GCs (p ≤ 0.05), but not with neonatal hair GCs. Conclusion: Exposure to excessive pre- and perinatal maternal stress was associated with a decrease in neonatal hair GCs, while elevated stress-scores around birth were associated with increased maternal hair GCs and elevated stress-scores earlier in gestation were not associated with maternal hair GCs pp. Further studies are needed to test associations with infant neurodevelopment.

Summary: Background: Long‐term glucocorticoids (HairGC) measured in scalp hair have been associated with body mass index (BMI), waist circumference (WC), and waist‐hip‐ratio (WHR) in several cross‐sectional studies. We aimed to investigate the magnitude, strength, and clinical relevance of these relations across all ages.Methods: We performed a systematic review and meta‐analysis (PROSPERO registration CRD42020205187) searching for articles relating HairGC to measures of obesity. Main outcomes were bivariate correlation coefficients and unadjusted simple linear regression coefficients relating hair cortisol (HairF) and hair cortisone (HairE) to BMI, WC, and WHR.Results: We includedk = 146 cohorts (n = 34,342 individuals). HairGC were positively related to all anthropometric measurements. The strongest correlation and largest effect size were seen for HairE‐WC: pooled correlation 0.18 (95%CI 0.11–0.24;k = 7;n = 3,158;I² = 45.7%) and pooled regression coefficient 11.0 cm increase in WC per point increase in 10‐log‐transformed HairE (pg/mg) on liquid‐chromatography‐(tandem) mass spectrometry (LC–MS) (95%CI 10.1–11.9 cm;k = 6;n = 3,102). Pooled correlation for HairF‐BMI was 0.10 (95%CI 0.08–0.13;k = 122;n = 26,527;I² = 51.2%) and pooled regression coefficient 0.049 kg/m²per point increase in 10‐log‐transformed HairF (pg/mg) on LC–MS (95%CI 0.045–0.054 kg/m²;k = 26;n = 11,635).Discussion: There is a consistent positive association between HairGC and BMI, WC, and WHR, most prominently and clinically relevant for HairE‐WC. These findings overall suggest an altered setpoint of the hypothalamic–pituitary–adrenal axis with increasing central adiposity.