Nutrition, Other Environmental Influences, and Genetics in the Determination of Human Stature.

Linear growth during three distinct stages of life determines attained stature in adulthood: namely, in utero, early postnatal life, and puberty and the adolescent period. Individual host factors, genetics, and the environment, including nutrition, influence attained human stature. Each period of physical growth has its specific biological and environmental considerations. Recent epidemiologic investigations reveal a strong influence of prenatal factors on linear size at birth that in turn influence the postnatal growth trajectory. Although average population height changes have been documented in high-income regions, stature as a complex human trait is not well understood or easily modified. This review summarizes the biology of linear growth and its major drivers, including nutrition from a life-course perspective, the genetics of programmed growth patterns or height, and gene-environment interactions that determine human stature in toto over the life span. Implications for public health interventions and knowledge gaps are discussed.

Building Block Metal Nanocluster-Based Growth in 1D Direction.

Metal nanoclusters with precisely modulated structures at the nanoscale give us the opportunity to synthesize and investigate 1D nanomaterials at the atomic level. Herein, it realizes selective 1D growth of building block nanocluster "Au13 Cd2 " into three structurally different nanoclusters: "hand-in-hand" (Au13 Cd2 )2 O, "head-to-head" Au25 , and "shoulder-to-shoulder" Au33 . Detailed studies further reveals the growth mechanism and the growth-related tunable properties. This work provides new hints for the predictable structural transformation of nanoclusters and atomically precise construction of 1D nanomaterials.

Iron overload disorders: Growth and gonadal dysfunction in childhood and adolescence.

Hemochromatosis (HC) is characterized by the progressive accumulation of iron in the body, resulting in organ damage. Endocrine complications are particularly common, especially when the condition manifests in childhood or adolescence, when HC can adversely affect linear growth or pubertal development, with significant repercussions on quality of life even into adulthood. Therefore, a timely and accurate diagnosis of these disorders is mandatory, but sometimes complex for hematologists without endocrinological support. This is a narrative review focused on puberty and growth disorders during infancy and adolescence aiming to offer guidance for diagnosis, treatment, and proper follow-up. Additionally, it aims to highlight gaps in the existing literature and emphasizes the importance of collaboration among specialists, which is essential in the era of precision medicine.

The association between atopic dermatitis and linear growth in children- a systematic review.

To evaluate the association between atopic dermatitis (AD) and linear growth in children, and determine factors associated with compromised linear growth in children with AD. A PRISMA-compliant systematic review was conducted. Databases (PubMed, Embase, Scopus and Cochrane) were searched from inception to June 2024 for articles that reported a quantitative relationship between AD and linear growth in children (< 18 years old). Quality of included articles was assessed using the Joanna Briggs Institute Critical Appraisal Tools while quality of evidence in these studies was evaluated using Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria. Fourteen studies (comprising 50,146 patients with AD) were included. Seven studies reported a strong positive or positive association between AD and reduced height standard deviation score (SDS) in children; the others reported no association. Only 3 studies had moderate quality of evidence, all of which reported an association between AD and poorer height SDS; the remaining 11 studies scored low in quality of evidence. Three studies reported the impact of AD on height to be transient. Secondary analysis showed AD severity, earlier AD onset, sleep disruption and, food restriction, to be risk factors for linear growth impairment in patients with AD. Topical steroid use was not associated with shorter stature in patients with AD. Conclusion: Current evidence on the association between childhood AD and poor linear growth is weak and inconsistent. However, patients with more severe AD, earlier disease onset, poorer sleep quality and higher nutritional restrictions appear more susceptible to linear growth impairment. What is known? • There is inconsistent evidence of the association between atopic dermatitis (AD) and linear growth in children in current literature, with some studies suggesting that AD may negatively impact linear height while other studies do not report similar associations. What is new? • There is no strong association between AD in childhood and poorer linear growth. • There may be a transient slowing of linear growth in children with AD, mimicking constitutional growth delay. • Children with severe AD, earlier disease onset, poorer sleep quality and nutritional restrictions may be at risk of more significant linear growth impairment. • Topical steroid use does not appear to contribute to shorter height in children with AD.

Maternal factors promoting normal linear growth of children from impoverished Rwandan households: a cross-sectional study.

BACKGROUND: Linear growth faltering remains a pervasive public health concern that affects many children worldwide. This study aimed to investigate possible maternal factors promoting normal linear growth among children aged 6-23 months of age from impoverished Rwandan households. METHODS: We used a three-stage cluster sampling procedure. The study population consisted of children aged six to 23 months and their mothers who lived in the study districts. A structured questionnaire helped to collect data from 807 selected mother-child dyads. The primary outcome variable was height-for-age Z scores. The main predictors were maternal income-generating activity, maternal education, maternal depression, household decision making, number of ANC visits, use of family planning method, types of family planning, and mode of delivery. We used univariate analysis to establish median, frequencies, and percentages. Furthermore, we used the Kruskal-Wallis, Mann-Whitney U, and Spearman rank correlation tests for bivariate analysis. We included in the final model of robust linear regression for multivariate analysis the potential confounding variables identified as significantly associated with the outcome (child age, participation in works for both parents, good handwashing practice, owning a vegetable garden, and the total number of livestock) along with maternal factors. RESULTS: Maternal factors that promoted normal linear growth of children were the presence of maternal income generation activity (ß= 0.640 [0.0269 1.253], p value = 0.041), the participation of the mother in the decision-making process of the household (ß=0.147 [0.080 0.214], p-value < 0.001), and the higher frequency of consultations with ANC (ß=0.189 [0.025 0.354], p-value = 0.024). Additionally, a combination of household decision-making with the number of ANC visits predicted an increase in the linear growth of the child (ß=0.032 [0.019 0.045], p-value < 0.001). CONCLUSION: Maternal factors such as maternal income-generating activity, maternal participation in household decision making, and increased number of ANC visits were found to promote normal child linear growth. These results contribute valuable information to the formulation of interventions and policies to improve child nutrition and growth in the community studied.

Early childhood height is a determinant of young adult stature in rural Nepal.

BACKGROUND: Does preschool height predict adult stature in undernourished settings? The extent to which preschool length or height forecasts young adult stature is unclear in chronically undernourished populations. METHODS: In 2006-8, we assessed height in a cohort of 2074 young adults, aged 16-23 years, in rural Nepal who, as preschoolers (≤ 4 year), were measured at baseline and again 16 months later during a vitamin A supplementation trial in 1989-91. We assessed by linear regression the ability of preschool length (L, measured < 24 mo) or height (Ht, 24-59 mo), at each year of age to predict 16-23 year old height, adjusted for month of young adult age, interval duration (in months), caste, preschool weight-for-height z-score and, in young women, time since menarche, marriage status and pregnancy history. RESULTS: Young women were a mean of 0.81, 1.11, 0.82, 0.24, 0.44 cm taller (all p < 0.01) and young men, 0.84, 1.18, 0.74, 0.64 and 0.48 cm taller (all p < 0.001) per cm of attained L/Ht at each successive preschool year of age and, overall, were 2.04 and 2.40 cm taller for each unit increase in preschool L/Ht z-score (L/HAZ) (both p < 0.001). Coefficients were generally larger for 16-month follow-up measurements. The percent of young adult height attained by children with normal L/HAZ (>-1) increased from 38-40% mid-infancy to ∼ 69-74% by 6 years of age. By 3-6 years of age heights of stunted children (L/HAZ<-2) were consistently ∼ 4-7% lower in their young adult height versus normal statured children. There was no effect of preschool vitamin A receipt. CONCLUSIONS: Shorter young children become shorter adults but predictive effects can vary by sex, age assessed, and may be influenced by year or season of measurement.

Impact of indoor Air Pollution on the Linear growth of children in Jimma, Ethiopia.

BACKGROUND: Stunting in children is the term for reduced linear growth and development, which is frequently brought on by a persistently inadequate diet, recurrent infections and chronic diseases or poor health conditions. Apart from the classic covariates of stunting, which include diet and illness, the relative contribution of household air pollution to chronic nutrition conditions is least studied. Hence, this study is conducted to investigate the impact of household air pollution on the linear growth of under-five children in Jimma town, Ethiopia. METHODS: A prospective cohort study was employed to collect data from 280 under-five children who lived in households using solid fuel (exposed group, n = 140) and clean fuel (unexposed group, n = 140). Height-for-age Z scores were compared in both groups over a 12-month follow-up period. The difference in differences estimators were used for comparison of changes in the height-for-age Z scores from baseline to end line in exposed and non-exposed groups. The independent effect of the use of solid fuels on height-for-age Z scores was analyzed through a multivariable linear regression model. Statistical Significances were declared at P < 0.05 and 95% CI level. RESULTS: In an unadjusted model (Model 1), compared with the clean fuel type, the mean difference in the height-for-age Z score of children in households using solid fuel was lower by 0.54 (-0.54, 95% CI -0.97, -0.12, P = 0.011). The beta coefficient remained negative after adjusting for age and sex (Model 2 -0.543, 95% CI -1.373, -0.563) and sociodemographic variables (Model 3: -0.543, 95% CI -1.362, -0.575). In the final model (Model 4), which adjusted for wealth quantile, dietary practice, water, sanitation and hygiene status and household food insecurity access scale, the beta coefficient held the same and significant (beta: -0.543, 95% CI -1.357, -0.579, P < 0.001). Higher HAZ scores were observed among female child (ß: = 0.48, 95%CI: 0.28, 0.69), Child with father attended higher education (ß: = 0.304 95%CI: 0.304, 95% CI 0.19, 0.41) as compared to male gender and those who did not attend a formal education, respectively. In contrast, child living in households with poor hygiene practices had lower HAZ score (ß: -0.226, 95% CI: -0.449, -0.003), P < 0.001. CONCLUSIONS: Exposure to indoor air pollution was inversely related to linear growth. Furthermore, sex, educational status and hygiene were found relevant predictors of linear growth. In such a setting, there is a need to step up efforts to design and implement public education campaigns regarding the health risks associated with exposure to household air pollution. Promoting improvements to kitchen ventilation and the use of improved cooking stoves, which will help to mitigate the detrimental effects of indoor air pollution on child growth impairment and its long-term effects.

Anthropometric and sociodemographic variables, but not preconception or prenatal maternal nutrition supplementation, predict neurodevelopment in offspring of the 'Women First' trial.

Multiple factors influence infant and child neurodevelopment in low resource settings. In offspring of participants in the preconception maternal nutrition trial, Women First (WF), we examined the impact of providing a preconception (Arm 1) or prenatal (Arm 2) nutrient supplement (compared to controls, Arm 3) on neurodevelopmental outcomes at 24 months; predictors of neurodevelopment scores; and associations of infant anthropometrics with neurodevelopmental scores. Follow-up visits for anthropometry were conducted at 6-, 12-, 18- and 24-month of age. At 24-months, in a randomized subset, the Bayley Scales of Infant Development, 3rd edition (BSID-III), including cognitive, motor and social-emotional subscales, and the Family Care Indicators (FCI) questionnaire, assessing family and home environment, were completed. Multiple covariates (intervention arm, site, maternal sociodemographic characteristics, FCI subscales, birthweight and 6-24 months' change in anthropometry z-scores, (e.g., ΔLAZ6-2 4) were evaluated by linear regression to predict BSID-III outcomes and to assess associations of anthropometric changes with BSID-III scores. The analysis consisted of 1386 infants (n = 441, 486, 459 for Arms 1, 2 and 3, respectively). None of the domain-specific BSID-III subscale scores differed by maternal intervention arm. Four covariates significantly predicted (p ≤ 0.01) all 3 BSID-III subscales: secondary maternal education, ΔLAZ6 - 24, birthweight >2500 g, and FCI play materials. Linear growth was associated with all domains of neurodevelopment. The results underscore the multi-dimensional aspects of child development represented by the nurturing care framework, including prenatal maternal nutrition, post-natal growth, maternal education for responsive caregiving and opportunities for early learning.

Perspective: Connecting the dots between domestic livestock ownership and child linear growth in low- and middle-income countries.

Child stunting due to linear growth faltering remains a pervasive issue in low- and middle-income countries. Two schools of thought have existed pertaining to the role of domestic livestock ownership (DLO) in child linear growth. On one hand, it is argued that DLO leads to greater income and financial security, resulting in better child-raising conditions, including greater animal-source food (ASF) consumption, having protective effects towards child stunting. On the other hand, researchers argue that DLO contributes to faecal contamination and transmission of zoonotic enteric infections from animals to children, thus having destructive effects on child growth. Reviews of this association have revealed ambiguous findings. In this perspective, we argue that measuring the association between exposures to domesticated animals and child stunting is difficult and the ambiguous associations revealed are a result of confounding and differences in the management of DLO. We also argue that the increasingly prominent area of research of environmental enteric dysfunction, a sub-clinical condition of the small intestine thought to be due to frequent faecal pathogen exposure and associated with stunting, will be a useful tool to measure the potential destructive effects of DLO on child growth. We present our argument and identify challenges and considerations and directions for future research.

Growth in Infancy and Childhood and Age at Menarche in Five Low- or Middle-Income Countries: Consortium of Health Orientated Research in Transitional Societies (COHORTS).

BACKGROUND: Earlier age at menarche is associated with behavioral and noncommunicable disease risks. The influence of birth weight (BW) (intrauterine) and postnatal growth on age at menarche is not well studied in low- and middle-income countries (LMICs). OBJECTIVE: Therefore, we investigated these associations in 5 LMIC birth cohorts. METHODS: We analyzed data from Brazil, Guatemala, India, the Philippines, and South Africa (n = 3983). We derived stunting (< -2 SD scores) at 24 mo using the WHO child growth standards. We generated interaction terms with categorized BW and conditional weight (lighter < 0 or heavier ≥ 0), and height (shorter < 0 or taller ≥ 0) z-scores. We categorized early-, modal-, and late-onset menarche and used multilevel ordinal regression. We used multilevel linear regression on continuous age at menarche. RESULTS: Mean age at menarche was 12.8 y (95% CI: 12.7 12.9). BW was not associated with age at menarche. Conditional height at 24 mo and mid-childhood (OR: 1.35; 95% CI: 1.27, 1.44 and 1.32; 1.25, 1.41, respectively) and conditional weight at 24 mo and mid-childhood (OR: 1.15; 1.08, 1.22 and 1.18; 1.11, 1.25, respectively) were associated with increased likelihood of early-onset menarche. Being heavier at birth and taller at 24 mo was associated with a 4-mo (95% CI: 0.8, 7.6) earlier age at menarche than being lighter at birth and shorter at 24 mo. Being heavier at birth but lighter in mid-childhood was associated with a 3-mo (95% CI: 0.8, 4.8) later age at menarche than being lighter at birth and mid-childhood. Age at menarche was 7 mo later in stunted than nonstunted girls. CONCLUSION: Age at menarche is inversely related to relative weight gain but also to rapid linear growth among those born shorter but remained stunted, and those born taller and grew excessively. These findings do not deter the global health goal to reduce growth faltering but emphasize the potential adverse effects of an obesogenic environment on adolescent development.

Associations between maternal and infant selenium status and child growth in a birth cohort from Dhaka, Bangladesh.

Deficiency of essential trace element, Se, has been implicated in adverse birth outcomes and in child linear growth because of its important role in redox biology and associated antioxidant effects. We used data from a randomised controlled trial conducted among a cohort of pregnant and lactating women in Dhaka, Bangladesh to examine associations between Se biomarkers in whole blood (WBSe), serum and selenoprotein P (SEPP1) in maternal delivery and venous cord (VC) blood. Associations between Se biomarkers, birth weight and infant growth outcomes (age-adjusted length, weight, head circumference and weight-for-length z-scores) at birth, 1 and 2 years of age were examined using regression analyses. WB and serum Se were negatively associated with birth weight (adjusted ß, 95 % CI, WBSe delivery: −26·6 (­44·3, −8·9); WBSe VC: −19·6 (­33·0, −6·1)); however, delivery SEPP1 levels (adjusted ß: −37·5 (­73·0, −2·0)) and VC blood (adjusted ß: 82·3 (30·0, 134·7)) showed inconsistent and opposite associations with birth weight. Positive associations for SEPP1 VC suggest preferential transfer from mother to fetus. We found small associations between infant growth and WBSe VC (length-for-age z-score ß, 95 % CI, at birth: −0·05 (­0·1, −0·01)); 12 months (ß: −0·05 (­0·08, −0·007)). Weight-for-age z-score also showed weak negative associations with delivery WBSe (at birth: −0·07 (­0·1, −0·02); 12 -months: −0·05 (­0·1, −0·005)) and in WBSe VC (at birth: −0·05 (­0·08, −0·02); 12 months: −0·05 (­0·09, −0·004)). Given the fine balance between essential nutritional and toxic properties of Se, it is possible that WB and serum Se may negatively impact growth outcomes, both in utero and postpartum.

Outcome-based comparative analysis of five fetal growth velocity models to define slow growth.

OBJECTIVE: Fetal growth surveillance includes assessment of size as well as rate of growth, and various definitions for slow growth have been adopted into clinical use. The aim of this study was to evaluate the effectiveness of different models to identify stillbirth risk, in addition to risk represented by the fetus being small-for-gestational age (SGA). METHODS: This was a retrospective analysis of a routinely collected and anonymized dataset of pregnancies that had two or more third-trimester ultrasound measurements of estimated fetal weight (EFW). SGA was defined as EFW < 10th customized centile, and slow growth was defined according to five published models in clinical use: (1) a fixed velocity limit of 20 g per day (FVL20 ); (2) a fixed > 50 centile drop, regardless of scan-measurement interval (FCD50 ); (3) a fixed > 30 centile drop, regardless of scan interval (FCD30 ); (4) growth trajectory slower than the third customized growth-centile limit (GCL3 ); and (5) EFW at second scan below the projected optimal weight range (POWR), based on partial receiver-operating-characteristics-curve-derived  cut-offs specific to the scan interval. RESULTS: The study cohort consisted of 164 718 pregnancies with 480 592 third-trimester ultrasound scans (mean ± SD, 2.9 ± 0.9). The last two scans in each pregnancy were performed at an average gestational age of 33 + 5 and 37 + 1 weeks. At the last scan, 12 858 (7.8%) EFWs were SGA, and of these, 9359 were also SGA at birth (positive predictive value, 72.8%). The rate at which slow growth was defined varied considerably (FVL20 , 12.7%; FCD50 , 0.7%; FCD30 , 4.6%; GCL3 , 19.8%; POWR, 10.1%), and there was varying overlap between cases identified as having slow growth and those identified as SGA at the last scan. Only the POWR method identified additional non-SGA pregnancies with slow growth (11 237/16 671 (67.4%)) that had significant stillbirth risk (relative risk, 1.58 (95% CI, 1.04-2.39)). These non-SGA cases resulting in stillbirth had a median EFW centile of 52.6 at the last scan and a median weight centile of 27.3 at birth. Subgroup analysis identified methodological problems with the fixed-velocity model because it assumes linear growth throughout gestation, and with the centile-based methods because the non-parametric distribution of centiles at the extremes does not reflect actual difference in weight gain. CONCLUSION: Comparative analysis of five clinically used methods to define slow fetal growth has shown that only the measurement-interval-specific POWR model can identify non-SGA fetuses with slow growth that are at increased risk of stillbirth. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Early corticosteroid withdrawal is associated with improved adult height in pediatric kidney transplant recipients.

BACKGROUND: Catch-up growth after pediatric kidney transplantation (kTx) is usually insufficient to reach normal adult height. We aimed to analyze the effect of pre-transplant recombinant human growth hormone (rhGH) and corticosteroid withdrawal on linear growth in the first year after kidney transplantation and identify factors associated with final height (FH). METHODS: Patients who underwent kTx between 1996 and 2018 at below 18 years old in five Belgian and Dutch centers were included. We analyzed the differences between height Z-scores at kTx and 1 year post-transplant (Δ height Z-score) in children with and without corticosteroids at 1 year (CS + /CS -) and with and without rhGH treatment before kTx (rhGH + /rhGH -). Univariable and multivariable linear regression analysis was applied to identify factors associated with height Z-score at 1 year post-kTx, Δ height Z-score, and FH Z-score. RESULTS: A total of 177 patients were included, with median age 9.3 years at kTx. Median height Z-scores pre-kTx and 1 year later in the CS - /rhGH - , CS + /rhGH - , CS - /rhGH + , and CS + /rhGH + groups were - 1.42/ - 0.80, - 0.90/ - 0.62, - 1.35/ - 1.20, and - 1.30/ - 1.60 (p = 0.001). CS use 1 year post-kTx was the only factor associated with Δ height (p = 0.003) on multivariable analysis. CS use at 1 year was the only variable associated with FH (p = 0.014) in children with pre-transplant height Z-score below - 1 (n = 52). CONCLUSIONS: Increase in height Z-score in the first year post-kTx was highest in the CS - /rhGH - group and lowest in the CS + /rhGH + group. The use of corticosteroids at 1 year post-kTx is associated with catch-up growth and in children with pre-transplant height Z-score below - 1 also with final height. A higher resolution version of the Graphical abstract is available as Supplementary information.

Evaluating preschool linear growth velocities: an interim reference illustrated in Nepal.

OBJECTIVE: An annualised linear growth velocity (LGV) reference can identify groups of children at risk of growing poorly. As a single velocity reference for all preschool ages does not exist, we present an interim tool, derived from published, normative growth studies, for detecting growth faltering, illustrating its use in Nepali preschoolers. DESIGN: The WHO Child Growth Velocity Standard was adapted to derive 12-month increments and conjoined to the Tanner-Whitehouse Height Velocity Reference data yielding contiguous preschool linear growth annualised velocities. Linear restricted cubic spline regressions were fit to generate sex-specific median and standard normal deviate velocities for ages 0 through 59 months. LGV Z-scores (LGVZ) were constructed, and growth faltering was defined as LGVZ < ­2. SETTING: Use of the reference was illustrated with data from Nepal's Tarai region. PARTICIPANTS: Children contributing the existing growth references and a cohort of 4276 Nepali children assessed from 2013 to 2016. RESULTS: Fitted, smoothed LGV reference curves displayed monotonically decreasing 12-month LGV, exemplified by male/female annual medians of 26·4/25·3, 12·1/12·7, 9·1/9·4, 7·7/7·8 and 7/7 cm/years, starting at 0, 12, 24, 36 and 48 months, respectively. Applying the referent, 31·1 %, 28·6 % and 29·3 % of Nepali children <6, 6­11 and 12­23 months of age, and ∼6 % of children 24­59 months, exhibited growth faltering. Under 24 months, faltering velocities were more prevalent in girls (34·4 %) than boys (25·3 %) (P < 0·05) but comparable (∼6 %) in older preschoolers. CONCLUSIONS: A LGV reference, concatenated from extant data, can identify preschool groups at-risk of growth faltering. Application and limitations are discussed.

Trends and long-term variation explaining nutritional determinants of child linear growth: analysis of Bangladesh Demographic and Health Surveys 1996-2018.

OBJECTIVE: To examine the height-for-age z-score (HAZ) of 0-35 months' children along with stunting prevalence to identify trends, changes and available nutrition-sensitive and specific determinants that could help explain the long-term variation in child linear growth using successive Bangladesh Demographic and Health Surveys (BDHS) data from 1996 to 2018. DESIGN: The BDHS pooled data are used for determining the key outcome variables HAZ, stunting and severe stunting. Trends, kernel-weighted local polynomial smoothing illustrations, pooled multivariable linear probability model (LPM), ordinary least squares method (OLS) and regression decomposition were used. PARTICIPANTS: Mothers having 0-35 months' children, the most critical age range for growth faltering. RESULTS: The mean HAZ increased by 0·91(±1·53) with 0·041 annual average change, while the percentages of stunting (-26·63 ± 0·54) and severe stunting (-21·12 ± 0·48) showed a reduction with 1·21 and 0·96 average annual changes, respectively. The average HAZ improvement (0·42 ± 1·56) in urban areas was less than the rural areas (1·16 ± 1·44). Similar patterns followed for stunting and severe stunting. The prenatal doctor visits (3064·65 %), birth in a medical facility (1054·32 %), breastfeeding initiation (153·18 %) and asset index (144·73 %) demonstrated a huge change. The findings of OLS, LPM and regression decomposition identified asset index, birth order, paternal and maternal education, bottle-fed, prenatal doctor visit, birth in a medical facility, vaccination, maternal BMI and ever-breastfed as influencing factors to predict the long-term changes of stunting and severe stunting. CONCLUSION: The nutrition-sensitive and specific factors identified through regression decomposition describing long-term variation in child linear growth should be focused further to attain the sustainable development goals.

Predictors of stunting among children aged 6-59 months, Zimbabwe.

OBJECTIVE: Stunted children have an increased risk of diminished cognitive development, diabetes, degenerative and CVD later in life. Numerous modifiable factors decrease the risk of stunting in children. This study aimed to assess the role of the individual, household and social factors on stunting in Zimbabwean children. DESIGN: A 1:2 unmatched case-control study. SETTING: This study was conducted in two predominantly rural provinces (one with the highest national prevalence of stunting and one with the lowest prevalence) in Zimbabwe. PARTICIPANTS: Data were obtained from the caregivers of 150 children aged between 6 and 59 months with stunting and from the caregivers of 300 children without stunting. RESULTS: Multiple (39) correlates of stunting were identified. Child's age, birth length, birth weight, and weight-for-age outcome (child-related factors), caregiver's age, maternal HIV status, occupation, and education (parental factors), breast-feeding status, number of meals, and dietary quality (dietary factors), child's appetite, diarrhoeal and worm infection (childhood illnesses), income status, access to safe water, access to a toilet, health clubs and maternal support in infant feeding (household, socio-cultural factors) were all found to be significant predictors of childhood stunting. CONCLUSION: Nearly all aspects under review from the individual-, household- to social-level factors were significantly associated with childhood stunting. These findings add to the growing body of evidence supporting the WHO stunting framework and strengthen the need to focus interventions on a multi-sectoral approach to effectively address stunting in high prevalence countries.

Current and future perspectives on clinical management of classic 21-hydroxylase deficiency.

Optimizing the glucocorticoid dosage has been a major concern in classic 21OHD (21-hydroxylase deficiency) treatment, as it is essential to adjust it meticulously to the needs of the individual patient. Insufficient glucocorticoid treatment will cause adrenal insufficiency, including life-threatening adrenal crisis, while excess of androgen could cause precocious pubertal growth in children, virilization in female patients, and infertility in male and female adult patients. Meanwhile, overtreatment with glucocorticoids causes iatrogenic Cushing's syndrome which could result in growth impairment, obesity, osteoporosis, and hypertension. The dilemma of 21OHD treatment is that glucocorticoid supplementation therapy at physiological dosage does not sufficiently suppress ACTH, consequently leading to adrenal androgen excess. Accordingly, the window for the appropriate glucocorticoid treatment would have to be substantially narrower than that of other types of adrenal insufficiency without androgen excess, such as adrenal hypoplasia. For the appropriate management of classic 21OHD, the physician has to be well versed in the physiology of the adrenal cortex, growth, and reproductive function. Comprehensive understanding of patients' requirements according to their life stage and sex is essential. Furthermore, female patients with 46,XX need to be cared for as differences in sex development (DSD) with careful psychological management. In this review, we aimed to comprehensively summarize the current status of classic 21OHD treatment, including the initial treatment during the neonatal period, management of adrenal insufficiency, maintenance therapy of each life stage, and the importance of clinical management as DSD for 46,XX female patients. The recently developed agents, Chronocort, and Crinecerfont, are also discussed.

Minimizing error in estimates of the effect of interventions by accounting for baseline measurements: A simulation study analyzing effects on child growth.

Interventions to reduce childhood stunting burden require clinical trials with a primary outcome of linear growth. When growth is measured longitudinally, there are several options for including baseline measurements in the analysis. This study compares the performance of several methods. Randomized controlled trials evaluating a hypothetical intervention to improve length-for-age z-score (LAZ) from birth through 24 months of age were simulated. The intervention effect was evaluated using linear regression and five methods for handling baseline measurements: comparing final measurements only (FINAL), comparing final measurement adjusted for baseline (ADJUST), comparing the change in the measurement over time (DELTA), adjusting for baseline when comparing the changes over time (DELTA+ADJUST) and adjusting for baseline in two-step residuals approach (RESIDUALS). We calculated bias, precision and power of each method for scenarios with and without a baseline imbalance in LAZ. Using a 0.15 effect size at 18 months, FINAL and DELTA required 1200 and 1500 enroled participants, respectively, to reach 80% power, whereas ADJUST, DELTA+ADJUST and RESIDUALS only required 900 participants. The adjusted models also produced unbiased estimates when there was a baseline imbalance, whereas the FINAL and DELTA methods produced biased estimates, as large as 0.07 lower and higher, respectively, than the true effect. Adjusted methods required smaller sample size and produced more precise results than both DELTA and FINAL methods in all test scenarios. If randomization fails, and there is an imbalance in LAZ at baseline, DELTA and FINAL methods can produce biased estimates, but adjusted models remain unbiased. These results warn against using the FINAL or DELTA methods.

Short stature and language development in the United Kingdom: a longitudinal analysis of children from the Millennium Cohort Study.

BACKGROUND: In low- and middle-income countries, poverty and impaired growth prevent children from meeting their cognitive developmental potential. There are few studies investigating these relationships in high-income settings. METHODS: Participants were 12,536 children born between 2000 and 2002 in the UK and participating in the Millennium Cohort Study (MCS). Short stature was defined as having a height-for-age 2 or more standard deviations below the median (≤ - 2 SDS) at age 3 years. Standardized British Abilities Scales II (BAS II) language measures, used to assess language development at ages 3, 5, 7 and 11 years, were the main outcome assessed. RESULTS: Children with short stature at age 3 years (4.1%) had language development scores that were consistently lower from ages 3 to 11 years (- 0.26 standard deviations (SD) (95% CI - 0.37, - 0.15)). This effect was attenuated but remained significant after adjustment for covariates. Trajectory analysis produced four distinct patterns of language development scores (low-declining, low-improving, average and high). Multinomial logistic regression models showed that children with short stature had a higher risk of being in the low-declining group, relative to the average group (relative risk ratio (RRR) = 2.11 (95% CI 1.51, 2.95)). They were also less likely to be in the high-scoring group (RRR = 0.65 (0.52, 0.82)). Children with short stature at age 3 years who had 'caught up' by age 5 years (height-for-age ≥ 2 SDS) did not have significantly different scores from children with persistent short stature, but had a higher probability of being in the high-performing group than children without catch-up growth (RRR = 1.84 (1.11, 3.07)). CONCLUSIONS: Short stature at age 3 years was associated with lower language development scores at ages 3 to 11 years in UK children. These associations remained significant after adjustment for socioeconomic, child and parental factors.

Linear Growth Spurts are Preceded by Higher Weight Gain Velocity and Followed by Weight Slowdowns Among Rural Children in Burkina Faso: A Longitudinal Study.

BACKGROUND: The temporal relationship between length (linear) and weight (ponderal) growth in early life is important to support optimal nutrition program design. Studies based on measures of attained size have established that wasting often precedes stunting, but such studies do not capture responsiveness of growth to previous compared with current conditions. As a result, the temporality of linear and ponderal growth relationships remain unclear. OBJECTIVES: We used growth velocity indicators to assess the temporal bidirectional relationships between linear and ponderal growth in children. METHODS: Using monthly anthropometric measurements from 5039 Burkinabè children enrolled at 6 months of age and followed until 28 months from August 2014 to December 2016, we employed multilevel mixed-effects models to investigate concurrent and lagged associations between linear and ponderal growth velocity, controlling for time trends, seasonality, and morbidity. RESULTS: Faster ponderal growth is associated with faster concurrent and subsequent linear growth (0.21-0.72 increase in length velocity z-score per unit increase in weight velocity z-score), while faster linear growth is associated with slower future weight gain (0.009-0.02 decrease in weight velocity z-score per unit increase in length velocity z-score), especially among children 9-14 months. Ponderal growth slows around the same time as peaks in morbidity, followed roughly a month later by slower linear growth. CONCLUSIONS: Use of velocity measures to assess temporal dependencies between linear and ponderal growth demonstrate that the same growth-limiting conditions likely affect both length and weight velocity, that slow ponderal growth likely limits subsequent linear growth, and that linear growth spurts may not be accompanied by sufficient increases in dietary intake to avoid slowdowns in weight gain.