Early Life Growth Research Articles

Early Life Interventions Can Shape Aging.

It is well documented that the environment of the developing fetus, including availability of nutrients and presence of toxins, can have major impact on adult phenotype, age-related traits and risk of chronic disease. There is also accumulating evidence that postnatal environment can impact adult characteristics related to evolutionary fitness, health, and aging. To determine whether early life hormonal interventions can alter trajectory of aging, we have examined the effects of early life growth hormone (GH) replacement therapy in Prop1df (Ames dwarf) mice which are GH deficient and remarkably long lived. Twice-daily GH injections between the ages of two and eight weeks completely normalized (“rescued”) a number of adult metabolic characteristics believed to contribute to extended longevity of these mutants. Importantly, longevity of Ames dwarf mice was reduced by early life GH treatment. This was associated with histone H3 modifications. We conclude that the trajectory of mammalian aging can be modified by early life interventions. Mechanistic links among interventions during postnatal development, adult metabolic characteristics, aging, and longevity, apparently involve epigenetic phenomena.

Skeletal Growth Status in a Physically Abused Child from the Kellis 2 Cemetery, Egypt

ABSTRACT Differences between estimated dental and skeletal ages can provide a gauge of an individual’s growth status, which more broadly reflects an individual’s health status. This case study provides a summary of the skeletal growth status in a dentally aged 2.0–2.5-year-old (Burial 519) victim of chronic physical abuse from the Kellis 2 cemetery (cal AD 100–450), Egypt. Absolute size of postcranial elements in Burial 519 is generally more similar to a dentally aged 1.5–1.9-year-old cohort than to an age-matched cohort. Growth deficits are least in the skull and greatest in the leg supporting previous studies demonstrating that these regions may be less sensitive and more sensitive, respectively, to environmental stressors. Within the postcranial skeleton, growth deficits are least in the clavicle which may have methodological implications for the skeletal ageing of children. This case study provides an opportunity to examine broader biocultural sources of adversity on skeletal growth in early life.

Analysis of Early-Life Growth and Age at Pubertal Onset in US Children

Earlier pubertal onset may be associated with an increased risk of chronic diseases. However, the extent to which growth in the first 5 years of life-an important developmental life stage that lays the foundation for later health outcomes-is associated with pubertal onset remains understudied. To assess whether changes in weight, length or height, and body mass index (BMI, calculated as weight in kilograms divided by height in meters squared) during the first 5 years of life are associated with earlier pubertal onset. This cohort study used data from 36 cohorts participating in the Environmental Influences on Child Health Outcomes program from January 1, 1986, to December 31, 2015. Participant inclusion required at least 1 anthropometric measure in the first 5 years of life and at least 1 measure of pubertal onset. Data were analyzed from January 1 to June 30, 2021. Standardized velocities of weight, length or height, and BMI gain in early infancy (0-0.5 years), late infancy (0.5-2 years), and early childhood (2-5 years). Markers of pubertal onset for boys and girls, including age at peak height velocity (APHV), time to puberty score greater than 1, time to Tanner pubic hair stage greater than 1, and time to menarche. Multivariable regression models were used to estimate mean differences in APHV by growth periods. Of 7495 children included in the study, 3772 (50.3%) were girls, 4505 (60.1%) were White individuals, and 6307 (84.1%) were born during or after the year 2000. Girls had a younger APHV (10.8 vs 12.9 years) than boys. In boys, faster weight gain (per 1-SD increase) in early infancy (β, -0.08 years; 95% CI, -0.10 to -0.06), late infancy (β, -0.10 years; 95% CI, -0.12 to -0.08), and early childhood (β, -0.07 years; 95% CI, -0.08 to -0.05) was associated with younger APHV after adjusting for the child's birth year, race, and Hispanic ethnicity as well as maternal age at delivery; educational level during pregnancy; annual household income during pregnancy; prenatal cigarette smoking; whether the mother was nulliparous; whether the mother had gestational diabetes, hypertension, or preeclampsia; mode of delivery; prepregnancy BMI; gestational weight gain; and gestational age at delivery. Similar associations were observed for length or height and BMI gains during the same age periods. In girls, faster gains (per 1-SD increase) in weight (β, -0.03 years; 95% CI, -0.05 to -0.01) and height (β, -0.02 years; 95% CI, -0.04 to 0.00) in early childhood were associated with younger APHV. Faster BMI gain in late infancy was associated with earlier time to menarche, whereas faster BMI gain in early childhood was associated with earlier time to Tanner pubic hair stage greater than 1. This cohort study found that faster gains in weight, length or height, or BMI in early life were associated with earlier pubertal onset. The results suggest that children who experience faster early growth should be monitored closely for earlier onset of puberty and referred as appropriate for supportive services.

A lifecourse approach to the relationship between lung function and cognition function in late life: findings from the Mysore studies of Natal effect on Ageing and Health (MYNAH) in South India

Background: Emerging evidence from high income settings indicates that lung function may be an independent determinant of cognitive abilities in late life. Despite a high burden of chronic lung disorders and neurocognitive disorders, there are limited data exploring the relationship between lung and cognitive function in later life in low- and middle-income (LMIC) settings. Methods: Between 2013 and 2016, 721 men and women from the Mysore Birth Records Cohort in South India, aged 55-80 years, were retraced and underwent standardised assessments for sociodemographic characteristics, cardiometabolic risk factors, lung function, cognitive function and mental health. Approximately 20 years earlier, a subset of them had assessments for cardiometabolic risk factors (n=522) and lung function (n=143). Results: Forced Expiratory Volume at one second (FEV1) and six seconds (FEV6) were higher among men than women. Women had higher immediate and delayed recall scores compared to men. Multivariate models indicated that those with lower FEV1 (lts) and FEV1/FEV6 ratio in late life had lower composite cognitive score (SD, standard deviation), independent of growth and environment in early life and childhood, attained education, socioeconomic position, cardiometabolic disorders in mid-and late life and lifestyle factors (0.29 SD per litre 95% confidence interval [CI] (0.10, 0.50) p=0.006 for FEV1 and 1.32 SD (0.20, 2.50) p=0.02 for FEV1/FEV6 ratio). Lung function in midlife was unrelated to cognitive outcomes in late life. Conclusions: Causality cannot be inferred from cross sectional associations. Therefore, causality is best explored in longitudinal studies with serial, but contemporaneous measurements of both lung and cognitive function. Mechanistic studies that examine the role of shared risk factors like environmental pollutants and biomass exposure on this relationship are urgently required in LMICs.

Effect of Dietary Vitamin D3 and Ultraviolet B Light on Growth Performance, Blood Serum Parameters, Gut Histology, and Welfare Indicators of Broilers

Stressors are commonly encountered by all farmed species, including chickens, but the impact of these stressors on the animal and their productivity can be influenced by the environmental conditions in which they are kept. This study investigated the effects of dietary vitamin D3 (vitD3) and ultraviolet light (UVB) on growth performance, organ weight, serum corticosterone levels (CORT), serum 25-hydroxy vitamin D (25-OH-D3) status, gut histology, and welfare indicators of broiler chickens challenged with social isolation stress. One day (d) old Ross 308 broiler chicks (n = 192) were individually weighed, wing-tagged, and allocated to non-isolated (control) and isolated groups; control birds were never isolated, while isolated birds were subjected to regular sessions of social isolation for about 15-min periods over the course of 3 d a week for 2 weeks starting from d 10 (1.30 h total exposure) with inter treatment interval of 48 h. Birds were treated with either dietary vitD3 at 4,000 IU/kg (HD) or UVB light (UVB). The UVB lamp (24 Watt 12% UVB D3, 55 cm) with wavelength: 280–315 nm, intensity; 28.12 μW/cm2 hung 50 cm above the substrate was used for the broilers in all the treatment groups but were filtered to remove UVB in the HD group. Growth performance measure; body weight gain, feed intake, and feed conversion ratio were estimated at the end of starter (day 10), grower (day 24), and finisher periods (day 38). Broilers were feather and gait scored to measure welfare at 22/35 and 24/37 days of age, respectively. The selected birds were weighed and euthanized to obtain serum to determine 25-OH-D3 and CORT levels, GIT weights, and gut histology. Subjecting the birds to 2-week social isolation (for 15 min, three times per week) increased CORT levels but did not alter GP and 25-OH-D3 levels of broilers. However, UVB-treated broilers demonstrated better welfare, duodenal absorptive capacity, and reduced FCR compared to HD chickens. Results suggest some beneficial effects of UVB lighting on welfare indicators and the potential to support early life growth of commercial broilers reared indoors, which are often challenged with stressors.

Rapid Growth in Malnutrition Children Associated with Higher Systolic Blood Pressure in Adolescent

BACKGROUND: Several studies found that children experiencing rapid growth earlier in life might increase the risk of chronic disease. Cardiovascular disease and hypertension are common risk factors and have been the leading cause of death worldwide. However, studies investigating the effects of rapid growth in early life on blood pressure later in life are limited. AIM: This study aimed to analyze the association between rapid growth after the first 1000 days of life and blood pressure at 17−19 years old. METHODS: We analyzed 17-year follow-up cohort using secondary data from the Indonesian Family Life Survey from the second (1997), third (2000), and fifth wave (2014). The survey was conducted in 13 provinces in Indonesia. No more than 672 children under 2 years old were included in the study. Rapid growth was defined as an alteration in length or height-per-age and weight-per-age z-score, based on WHO Child Growth Standard, on 1997 and 2000 time frame which was greater than 0.67, experienced by children with malnutrition (low birth weight, stunted, underweight, and wasting). Blood pressure was measured three times by an oscillometric method in 2014. In addition, we used a one-way ANOVA (analysis of variance) test to assess the association of rapid growth on systolic blood pressure. RESULTS: Malnutrition children at 0-2-year-old that grow rapidly in length or height, had higher systolic blood pressure than normal children (p = 0.029). In contrast, there was no difference observed in systolic blood pressure in children with malnutrition and children who did not experience rapid growth in weight. CONCLUSIONS: Children who had a history of malnutrition earlier in life (0−23 months) and had rapid growth in length or height after the first 1000 days of life had higher systolic blood pressure than normal children and children with malnutrition who did not grow rapidly.

A live yeast supplementation to gestating ewes improves bioactive molecule composition in colostrum with no impact on its bacterial composition and beneficially affects immune status of the offspring.

Colostrum quality is of paramount importance in the management of optimal ruminant growth and infectious disease prevention in early life. Live yeast supplementation effect during the last month of gestation was evaluated on ewes' colostrum composition. Two groups of ewes (n = 14) carrying twin lambs were constituted and twins were separated into groups (mothered or artificially fed) 12 h after birth. Nutrient, oligosaccharides (OS), IgG and lactoferrin concentrations were measured over 72 h after lambing, and bacterial community was described in colostrum collected at parturition (T0). Immune passive transfer was evaluated through IgG measurement in lamb serum. In both groups, colostral nutrient, OS concentrations and IgG concentrations in colostrum and lamb serum decreased over time (P < 0⋅01), except for lactose, which slightly increased (P < 0⋅001), and lactoferrin, which remained stable. Bacterial population was stable over time with high relative abundances of Aerococcaceae, Corynebacteriaceae, Moraxellaceae and Staphylococcaceae in T0 colostrum. No effect of supplementation was observed in nutrient and lactoferrin concentrations. In supplemented ewes, the level of colostral IgG was higher at T0 and a higher level of serum IgG was observed in lambs born from supplemented mothers and artificially fed, while no effect of supplementation was observed in the mothered lamb groups. Using a metabolomic approach, we showed that supplementation affected OS composition with significantly higher levels of colostral Neu-5Gc compounds up to 5 h after birth. No effect of supplementation was observed on bacterial composition. Our data suggest that live yeast supplementation offsets the negative impact of early separation and incomplete colostrum feeding in neonate lambs.

Introgression from farmed escapees affects the full life cycle of wild Atlantic salmon.

After a half a century of salmon farming, we have yet to understand how the influx of genes from farmed escapees affects the full life history of Atlantic salmon (Salmo salar L.) in the wild. Using scale samples of over 6900 wild adult salmon from 105 rivers, we document that increased farmed genetic ancestry is associated with increased growth throughout life and a younger age at both seaward migration and sexual maturity. There was large among-population variation in the effects of introgression. Most saliently, the increased growth at sea following introgression declined with the population’s average growth potential. Variation at two major-effect loci associated with age at maturity was little affected by farmed genetic ancestry and could not explain the observed phenotypic effects of introgression. Our study provides knowledge crucial for predicting the ecological and evolutionary consequences of increased aquaculture production worldwide.

DNA methylation mediates the association between breastfeeding and early-life growth trajectories

BackgroundThe role of breastfeeding in modulating epigenetic factors has been suggested as a possible mechanism conferring its benefits on child development but it lacks evidence. Using extensive DNA methylation data from the ALSPAC child cohort, we characterized the genome-wide landscape of DNA methylation variations associated with the duration of exclusive breastfeeding and assessed whether these variations mediate the association between exclusive breastfeeding and BMI over different epochs of child growth.ResultsExclusive breastfeeding elicits more substantial DNA methylation variations during infancy than at other periods of child growth. At the genome-wide level, 13 CpG sites in girls (miR-21, SNAPC3, ATP6V0A1, DHX15/PPARGC1A, LINC00398/ALOX5AP, FAM238C, NATP/NAT2, CUX1, TRAPPC9, OSBPL1A, ZNF185, FAM84A, PDPK1) and 2 CpG sites in boys (IL16 and NREP), mediate the association between exclusive breastfeeding and longitudinal BMI. We found enrichment of CpG sites located within miRNAs and key pathways (AMPK signaling pathway, insulin signaling pathway, endocytosis). Overall DNA methylation variation corresponding to 3 to 5 months of exclusive breastfeeding was associated with slower BMI growth the first 6 years of life compared to no breastfeeding and in a dose–response manner with exclusive breastfeeding duration.ConclusionsOur study confirmed the early postnatal period as a critical developmental period associated with substantial DNA methylation variations, which in turn could mitigate the development of overweight and obesity from infancy to early childhood. Since an accelerated growth during these developmental periods has been linked to the development of sustained obesity later in life, exclusive breastfeeding could have a major role in preventing the risks of overweight/obesity and children and adults through DNA methylation mechanisms occurring early in life.

Sex Reversal and Performance in Fitness-Related Traits During Early Life in Agile Frogs

Sex reversal is a mismatch between genetic sex (sex chromosomes) and phenotypic sex (reproductive organs and secondary sexual traits). It can be induced in various ectothermic vertebrates by environmental perturbations, such as extreme temperatures or chemical pollution, experienced during embryonic or larval development. Theoretical studies and recent empirical evidence suggest that sex reversal may be widespread in nature and may impact individual fitness and population dynamics. So far, however, little is known about the performance of sex-reversed individuals in fitness-related traits compared to conspecifics whose phenotypic sex is concordant with their genetic sex. Using a novel molecular marker set for diagnosing genetic sex in agile frogs (Rana dalmatina), we investigated fitness-related traits in larvae and juveniles that underwent spontaneous female-to-male sex reversal in the laboratory. We found only a few differences in early life growth, development, and larval behavior between sex-reversed and sex-concordant individuals, and altogether these differences did not clearly support either higher or lower fitness prospects for sex-reversed individuals. Putting these results together with earlier findings suggesting that sex reversal triggered by heat stress may be associated with low fitness in agile frogs, we propose the hypothesis that the fitness consequences of sex reversal may depend on its etiology.

Stunting and its associated factors in children aged 6–59 months in Ilubabor zone, Southwest Ethiopia

PurposeStunting, which refers to low height-for-age, is one of the most important public health problems in Ethiopia, and it more accurately reflects nutritional deficiencies and illness that occur during the most critical periods for growth and development in early life. Given this, this paper aims at determining the magnitude and factors associated with stunting among 6–59 month old children in Ilubabor Zone, Southwest Ethiopia.Design/methodology/approachThis paper opted for a descriptive study using an interviewer-administered questionnaire and anthropometric measurements of 617 children aged 6–59 months. A systematic random sampling technique was used to select the study participants. Data was analyzed using Statistical Package for Social Sciences (SPSS) version 25 and World Health Organization (WHO) Anthro software. Multivariate logistic regression analysis was used to identify independent predictors of stunting.FindingsAbout 33.7% of children aged 6–59 months included in this study were stunted. The proportion of moderate and severe stunting among the stunted children was 26.4% and 7.3%, respectively. Large family size (AOR = 4.0; 95% confidence interval [CI]: 2.5, 6.4), low dietary diversity score (AOR = 7.8; 95% CI: 4.6, 13.0) and household food insecurity (AOR = 16.4; 95% CI: 10.0, 26.7) were independent predictors of stunting.Research limitations/implicationsReporting and recall bias related to food groups consumed over the past seven days and seasonal variation may affect the findings related to factors associated with stunting.Practical implicationsGlobally, it is estimated that nearly 165 million children under the age of five are stunted. Outcomes associated with stunting include increased risk of mortality, increased disease risk, developmental delays, diminished ability to learn and lower school achievement and reduced lifelong productivity. So, determining the level of stunting in a particular community is important to design strategies for curbing the contributing factors.Originality/valueThis study’s community-based design yields a representative sample of study subjects in the Hurumu district, which is valuable for intervention methods and actions. Standardized tools that are validated for use by the World Health Organization are used. Besides, anthropometric data were analyzed using the updated WHO Anthro software.

Late-Gestation in utero Heat Stress Limits Dairy Heifer Early-Life Growth and Organ Development

Dairy calves exposed to late-gestation heat stress weigh less, have impaired immunity, produce less milk across multiple lactations, and have reduced productive life. However, less is known about the relationship between in utero heat stress and organ morphology and development. Herein, we characterized the consequences of late-gestation in utero heat stress on body and organ growth trajectories during early-life development. Holstein heifers were either in utero heat-stressed (IU-HT, n = 36, dams exposed to THI &amp;gt; 68) or cooled (IU-CL, n = 37, dams exposed to THI &amp;gt; 68 with access to active cooling) during late gestation (54 ± 5 d prepartum). All heifers were reared identically from birth to weaning. Upon birth, calves were weighed and fed 3.78 L of colostrum followed by 0.87 kg DM/d milk replacer (MR) over two feedings and ad libitum starter concentrate daily. Weaning began at 49 d and ended at 56 d of age. Feed intake was recorded daily, and body weight (BW) and other growth measures were recorded at 0, 28, 56, and 63 d. Blood was collected at d 1 then weekly. Subsets of heifers were selected for euthanasia at birth and 7 d after complete weaning (n = 8 per group each) to harvest and weigh major organs. Reduced BW and stature measures persisted in IU-HT heifers from 0 to 63 d of age with a 7% lower average daily gain and reduced starter consumption relative to IU-CL heifers. IU-HT heifers had lower hematocrit percentages and reduced apparent efficiency of absorption of IgG relative to IU-CL heifers. Additionally, IU-HT heifers had reduced gross thymus, spleen, thyroid gland, and heart weight at birth and larger adrenal glands and kidneys but smaller ovaries relative to BW at 63 d. The mammary gland of IU-HT heifers was smaller relative to IU-CL heifers at birth and 63 d adjusted for BW, suggesting mechanisms leading to impaired milk yield in mature IU-HT cows are initiated early in development. In summary, in utero heat stress reduces whole-body size and limits development of key organs with potential repercussions on dairy calf metabolic adaptation, immune function, and future productivity.

Longitudinal Association of Maternal Pre-Pregnancy BMI and Third-Trimester Glycemia with Early Life Growth of Offspring: A Prospective Study among GDM-Negative Pregnant Women.

Intrauterine modifiable maternal metabolic factors are essential to the early growth of offspring. The study sought to evaluate the associations of pre-pregnancy BMI and third-trimester fasting plasma glucose (FPG) with offspring growth outcomes within 24 months among GDM-negative pregnant women. Four hundred eighty-three mother –offspring dyads were included from the Shanghai Maternal-Child Pairs Cohort. The pregnant women were categorized into four mutually exclusive groups according to pre-pregnancy BMI as normal or overweight/obesity and third-trimester FPG as controlled or not controlled. Offspring growth in early life was indicated by the BAZ (BMI Z-score), catch-up growth, and overweight/obesity. Among those with controlled third-trimester FPG, pre-pregnancy overweight/obesity significantly increased offspring birth weight, BAZ, and risks of overweight/obesity (RR 1.83, 95% CI 1.23 to 2.73) within 24 months. Those who had uncontrolled third-trimester FPG had a reduced risk of offspring overweight/obesity within 24 months by 47%. The combination of pre-pregnancy overweight/obesity and maternal uncontrolled third-trimester FPG increased 5.24-fold risk of offspring catch-up growth within 24 months (p < 0.05). Maternal pre-pregnancy overweight/obesity and uncontrolled third-trimester glycemia among GDM-negative women both have adverse effects on offspring growth within 24 months. With the combination of increasing pre-pregnancy BMI and maternal third-trimester FPG, the possibility of offspring catch-up growth increases.

53: Distinct early life growth trajectories in CF are associated with lung function at 6 years

53: Distinct early life growth trajectories in CF are associated with lung function at 6 years

Myxozoan parasites vary in river herring according to life history stage and habitat.

Anadromous river herring have declined in many parts of their range, leading to fisheries management efforts to help repopulate this species by improving connectivity of rivers and restoring populations by fish transfers. With data lacking on parasites in these species, this study sought to better understand myxozoans across various life stages and habitats in river herring populations in New Jersey, USA. We compared fish from riverine habitats during early-life growth and adults returning to spawn, marine-phase fish, and landlocked Alewife populations. Three myxozoan species were identified in young-of-the-year (YOY) anadromous river herring, including Kudoa clupeidae in the skeletal musculature, Myxobolus mauriensis in the rib cartilage, and an uncharacterized coelozoic myxozoan within the lumen of mesonephric tubules. In YOY river herring, Blueback Herring were 2 times more likely to be infected by K. clupeidae than Alewife (p = 0.019) and in the Maurice River, fish were 4 times more likely to be infected with M. mauriensis than fish from Great Egg Harbor River (p = 0.000) and 11 times more likely than the Delaware River (p = 0.001). Spawning adult river herring were infected with a previously undescribed myxozoan parasite infecting the kidney. Sequencing the 18S rDNA indicated this species is closely related to Ortholinea species. Myxobolus mauriensis and the Ortholinea-like species were absent from marine-phase river herring indicating that infections were linked to river environments occurring during early-life growth and spawning, respectively. No myxozoans were present in landlocked Alewife, showing that similar infections occurring in rivers were absent in lake environments in the region.

The Species-Level Composition of the Fecal Bifidobacterium and Lactobacillus Genera in Indonesian Children Differs from That of Their Mothers.

The infant gut microbiota plays a critical role in early life growth and derives mainly from maternal gut and breast milk. This study aimed to analyze the differences in the gut microbiota, namely Bifidobacterium and Lactobacillus communities at species level among breast milk as well as maternal and infant feces at different time points after delivery. Fifty-one mother–infant pairs from Indonesia were recruited, and the breast milk and maternal and infant feces were collected and analyzed by high throughput sequencing (16S rRNA, Bifidobacterium groEL and Lactobacillus groEL genes). PCoA results showed bacterial composition was different among breast milk and maternal and infant feces within the first two years. The abundance of Bifidobacterium and Bacteroides were significantly higher in infant feces compared to their maternal feces from birth to two years of age, and maternal breast milk within six months after birth (p < 0.05), whereas the abundance of Blautia, Prevotella, and Faecalibacterium was higher in maternal feces compared to that in breast milk within six months and infant feces within one year after birth, respectively (p < 0.05). The relative abundances of Bacteroides and Lactobacillus was higher and lower in infant feces compared to that in maternal feces only between one and two years of age, respectively (p < 0.05). For Bifidobacterium community at species level, B. adolescentis, B. ruminantium, B. longum subsp. infantis, B. bifidum, and B. pseudolongum were identified in all samples. However, the profile of Bifidobacterium was different between maternal and infant feces at different ages. The relative abundances of B. adolescentis and B. ruminantium were higher in maternal feces compared to those in infant feces from birth to one year of age (p < 0.05), while the relative abundances of B. longum subsp. infantis and B. bifidum were higher in infant feces compared to those in maternal feces beyond three months, and the relative abundance of B. pseudolongum was only higher in infant feces between three and six months (p < 0.05). For Lactobacillus community, L. paragasseri showed higher relative abundance in infant feces when the infant was younger than one year of age (p < 0.05). This study showed bacterial composition at the genus level and Bifidobacterium and Lactobacillus communities at the species level were stage specific in maternal breast milk as well as and maternal and infant feces.

Effects of early energy intake on neonatal cerebral growth of preterm newborn: an observational study

Current guidelines for preterm newborns recommend high energy nutrition soon after birth in order to limit growth retardation. However, long-term effects of this nutritional approach are still debated, and it has been demonstrated that cerebral growth depends on protein intake in early life. A negative impact of early high energy intake by parenteral nutrition (PN) has been reported for patients in critically ill conditions, observed in intensive care unit. We aimed at evaluating the impact of energy intake on cerebral growth in preterm neonates early in life. We included preterm newborns with gestational age < 32 weeks or birth weight (BW) < 1500 g. Measurement of cerebral structures was performed by cranial Ultrasonography (cUS) between 3 and 7 days of life (DOL, T0) and at 28 DOL (T1). We evaluated the relation between energy intake and cerebral growth in the first 28 DOL. We observed in 109 preterm newborns a significant (p < 0.05) negative correlation between energy intake received by PN and right caudate head growth (r = − 0.243*) and a positive correlation between total energy intake and transverse cerebellum diameter (r = 0.254*). Multivariate analysis showed that energy intake administered by enteral nutrition (EN), independently increased growth of left caudate head (β = 0.227*) and height cerebellar vermis (β = 0.415*), while PN independently affected growth of both right and left caudate head (β = − 0.164* and β = − 0.228*, respectively) and cerebellum transverse diameter (β = − 0.849*). The route of energy administration may exert different effects on cerebral growth in early life. High energy intake administered through EN seems to be positively correlated to cerebral growth; conversely, PN energy intake results in a poorer cerebral growth evaluated with cUS.

Epigenetic clocks in the pediatric population: when and why they tick?

Recent research efforts have provided compelling evidence of genome-wide DNA methylation alterations in pediatrics. It is currently well established that epigenetic clocks, composed of DNA methylation sites, can estimate the gestational and chronological age of cells and tissues from different ages. Also, extensive research is aimed at their correlation with early life exposure and pediatric diseases. This review aimed to systematically summarize the epigenetic clocks in the pediatric population. Publications were collected from PubMed and Web of Science databases up to Apr 2021. Epigenetic clocks, DNA methylation clocks, epigenetic age acceleration or deceleration, pediatric and the pediatric population were used as search criteria. Here, we first review the currently applicative pediatric epigenetic clocks. We then highlight the interpretation for epigenetic age deviations in the pediatric population and their association with external factors, developmental trajectories, and pediatric diseases. Considering the remaining unknown of pediatric clocks, research strategies into them are also discussed. In all, pediatric epigenetic clocks may act as potent tools to understand development, growth and diseases in early life.

Early-Life Exposure to Per- and Poly-Fluorinated Alkyl Substances and Growth, Adiposity, and Puberty in Children: A Systematic Review.

Per- or polyfluoroalkyl substances (PFAS), a family of synthetic polyfluorinated compounds, are widely used in consumer products. Ubiquitous exposures to PFAS, in consideration of their persistence, bioaccumulation potential, and toxicities have led to concerns regarding possible harmful effects during critical periods of development in early-life and long-term consequences on health. The potential effects of PFAS depend on various factors including the type of PFAS and the timing and level of exposure. We performed a systematic review of the epidemiologic literature to assess the effects of early-life PFAS exposure on prenatal and postnatal growth, adiposity, and puberty in children and adolescents. For birth size, most studies indicated that prenatal PFAS exposure, in particular long-chain PFAS, may impair fetal growth, albeit some reports of null associations with maternal PFAS. For growth within 2 years of age, prenatal PFAS exposure showed no associations with height and either null or negative associations with weight. However, postnatal PFAS exposures were inversely related to height and weight at 2 years in a cross-sectional study. For postnatal adiposity, prenatal PFAS may mostly have negative associations with body mass index in the first 2 years of life, but positive relationships with adiposity in childhood and adolescence, although some studies showed null associations. For puberty, the evidence for associations between early-life PFAS exposure and pubertal development or sex hormone levels were limited and inconclusive. From experimental studies, plausible mechanisms through which PFAS may affect early-life growth and puberty include PFAS-induced activation of peroxisome proliferator-activated receptor, alterations of thyroid or steroid hormone synthesis and metabolism, and their weak estrogenic or anti-androgenic properties. Although the published literature suggests possible effects of PFAS exposures on early-life growth, adiposity, and puberty, current human evidence is limited in establishing PFAS-induced effects on early-life physical development. Further investigation is warranted to clarify PFAS-induced effects on growth and physical development in consideration of the critical time-window of exposure, concomitant exposure to chemical mixtures including various PFAS types, and possible non-monotonic dose-response relationship for growth and adiposity trajectories.

Physical Growth of Patients with Hereditary Tyrosinaemia Type I: A Single-Centre Retrospective Study.

In a retrospective review, we aimed to assess long-term growth in 17 patients (n = 11 males) with hereditary tyrosinaemia type I (HTI). Median age at assessment was 15.6 years (5.7–26.6 years) and median age at diagnosis was 1 month (range: 0–16 months), with 35% (n = 6/17) symptomatic on presentation. From the age of 8 years, there was a noticeable change in median height, weight, and body-mass-index [BMI]-z-scores. Median height-for-age z-scores were consistently ≤ −1 (IQR −1.6, −0.5) during the first 8 years of life but increased with age. Weight-for-age z-scores ranged between −1 to 0 (IQR −1.2, 0.1) in the first 8 years; then increased to > 0.5 (IQR −0.3, 1.3) by age 16 years, and BMI-for-age z-scores ranged from 0 to 1 (IQR −0.7, 1.3) up to 8 years, and >1 (IQR −0.2, 1.9) until 16 years. The percentage of overweight and obesity was lowest in children aged < 5 years, and consistently > 40% in patients aged between 7 to 16 years. The prescribed total protein intake was associated with improved height growth (p < 0.01). Impaired growth in early life improved with age achieving normal population standards. Further studies are needed to investigate factors that influence growth outcome in HTI patients.