Poor Early Growth Research Articles

Malnourished Microbes: Host-Microbiome Interactions in Child Undernutrition.

Childhood undernutrition is a major global health burden that is only partially resolved by nutritional interventions. Both chronic and acute forms of child undernutrition are characterized by derangements in multiple biological systems including metabolism, immunity, and endocrine systems. A growing body of evidence supports a role of the gut microbiome in mediating these pathways influencing early life growth. Observational studies report alterations in the gut microbiome of undernourished children, while preclinical studies suggest that this can trigger intestinal enteropathy, alter host metabolism, and disrupt immune-mediated resistance against enteropathogens, each of which contribute to poor early life growth. Here, we compile evidence from preclinical and clinical studies and describe the emerging pathophysiological pathways by which the early life gut microbiome influences host metabolism, immunity, intestinal function, endocrine regulation, and other pathways contributing to child undernutrition. We discuss emerging microbiome-directed therapies and consider future research directions to identify and target microbiome-sensitive pathways in child undernutrition.

Anthropometry, body composition, early growth and chronic disease risk factors among Zambian adolescents exposed or not to perinatal maternal HIV.

Early life exposures and growth patterns may affect long-term risk of chronic non-communicable diseases (NCD). We followed up in adolescence two Zambian cohorts (n 322) recruited in infancy to investigate how two early exposures - maternal HIV exposure without HIV infection (HEU) and early growth profile - were associated with later anthropometry, body composition, blood lipids, Hb and HbA1c, blood pressure and grip strength. Although in analyses controlled for age and sex, HEU children were thinner, but not shorter, than HIV-unexposed, uninfected (HUU) children, with further control for socio-demographic factors, these differences were not significant. HEU children had higher HDL-cholesterol than HUU children and marginally lower HbA1c but no other biochemical or clinical differences. We identified three early growth profiles - adequate growth, declining and malnourished - which tracked into adolescence when differences in anthropometry and body fat were still seen. In adolescence, the early malnourished group, compared with the adequate group, had lower blood TAG and higher HDL, lower grip strength (difference: -1·87 kg, 95 % CI -3·47, -0·27; P = 0·02) and higher HbA1c (difference: 0·5 %, 95 % CI 0·2, 0·9; P = 0·005). Lower grip strength and higher HbA1c suggest the early malnourished children could be at increased risk of NCD in later life. Including early growth profile in analyses of HIV exposure reduced the associations between HIV and outcomes. The results suggest that perinatal HIV exposure may have no long-term effects unless accompanied by poor early growth. Reducing the risk of young child malnutrition may lessen children's risk of later NCD.

Poor early childhood growth is associated with impaired lung function: Evidence from a Ghanaian pregnancy cohort.

Nearly 40% of African children under 5 are stunted. We leveraged the Ghana randomized air pollution and health study (GRAPHS) cohort to examine whether poorer growth was associated with worse childhood lung function. GRAPHS measured infant weight and length at birth and 3, 6, 9,12 months, and 4 years of age. At age 4 years, n = 567 children performed impulse oscillometry. We employed multivariable linear regression to estimate associations between birth and age 4 yearsanthropometry and lung function. Next, we employed latent class growth analysis (LCGA) to generate growth trajectories through age 4 years. We employed linear regression to examine associations between growth trajectory assignment and lung function. Birth weight and age 4 weight-for-age and height-for-age z-scores were inversely associated with airway resistance (e.g., R5 , or total airway resistance: birth weightβ = -0.90 cmH2O/L/s, 95% confidence interval [CI]: -1.64, -0.16 per 1 kg increase; and R20 , or large airway resistance: age 4 height-for-age β = -0.40 cmH2O/L/s, 95% CI: -0.57, -0.22 per 1 unit z-score increase). Impaired growth trajectories identified through LCGA were associated with higher airway resistance, even after adjusting for age 4 body mass index. For example, children assigned to a persistently stunted trajectory had higher R5 (β = 2.71 cmH2O/L/s, 95% CI: 1.07, 4.34) and R20 (β = 1.43 cmH2O/L/s, 95% CI: 0.51, 2.36) as compared to normal. Children with poorer anthropometrics through to age 4 years had higher airway resistance in early childhood. These findings have implications for lifelong lung health, including pneumonia risk in childhood and reduced maximally attainable lung function in adulthood.

Abstract 91: Large Vessel Occlusion Stroke Patients With Rapid Early Infarct Progression And Poor Collaterals Are Vulnerable To Blood Pressure Reductions

Introduction: The precise interactions between collateral perfusion, hemodynamics, and infarct growth after large vessel occlusion (LVO) require further definition. This study examined whether patients with poor collateral circulation and rapid early infarct progression are more vulnerable to reductions in blood pressure (BP). Methods: We prospectively enrolled patients with LVO stroke who underwent thrombectomy. Volumes of arterial tissue delay and relative cerebral blood flow (CBF) were estimated with RAPID software; a poor collateral profile was defined by a hypoperfusion intensity ratio >0.4. Early infarct growth rate (EIGR) was defined as ischemic core volume (CBF<30%) divided by the time from symptom onset to imaging. A fast progressor profile was assigned to patients whose EIGR was >10 mL/h. The final infarct growth rate (FIGR) was the quotient of final infarct volume (FIV) and time from symptom onset to reperfusion. BP reduction was measured as the difference between admission mean arterial pressure (MAP) and lowest MAP before reperfusion. Results: Fifty-five patients (mean age 69 + 15, mean NIHSS 13) with successful reperfusion (TICI 2B/3) were included in the analysis. The median MAP reduction was 17 (IQR 9, 32). Poor collateral perfusion and EIGR were independent predictors of FIV after adjusting for age and admission NIHSS (mean FIV 70 vs. 31 mL, p=0.012 and 60 vs. 29 mL, p=0.01, respectively). A significant interaction was found between MAP reduction and both collateral status (p=0.04) and progressor profile (p=0.01). For every 10 mmHg MAP reduction, patients with poor collaterals experienced an average increase in FIGR of 3.6 mL/h (Fig. 1A). Above a critical MAP reduction threshold of 30 mmHg, mean FIV was significantly larger in patients with rapidly progressing infarcts (p<0.01, Fig. 1B). Conclusions: Patients with poor collaterals and rapid early infarct growth are at higher risk of accelerated infarct growth and larger FIV related to BP reductions.

Seed Priming with Potassium Nitrate and Gibberellic Acid Enhances the Performance of Dry Direct Seeded Rice (Oryza sativa L.) in North-Western India

Poor early growth and uneven crop establishment are reported as the major bottlenecks in wide-scale adoption and optimal yield realization of dry direct-seeded rice (DSR). Seed priming can potentially help overcome these problems in DSR. Therefore, laboratory and field studies were conducted at Punjab Agricultural University, Ludhiana, India, during kharif/wet-season 2018 and 2019 to evaluate the effect of different priming techniques on germination, establishment, growth, and grain yield of rice under DSR conditions. The following priming treatments were evaluated: dry non-primed seed (control), hydropriming with distilled water, halopriming with 2.0% potassium nitrate, hormopriming with 50 ppm gibberellic acid (GA3), and osmopriming with polyethylene glycol (PEG)(−0.6 MPa), each with 12 and 24 h priming duration. In 2019, priming treatments were tested under two DSR establishment methods—conventional DSR (sowing in dry soil followed by irrigation) and soil mulch DSR (locally known as vattar DSR) (sowing in moist soil after pre-sowing irrigation), whereas in 2018, priming treatments were evaluated under conventional DSR only. In both years, halopriming and hormopriming resulted in a 7–11% increase in rice yields compared to non-primed dry seed (control). Osmopriming resulted in a 4% yield increase compared to control in 2018 but not in 2019. The higher yields in halopriming and hormopriming were attributed to higher and rapid germination/crop emergence, better root growth, and improvement in yield attributes. Priming effect on crop emergence, growth, and yield did not differ by DSR establishment methods and duration of priming. Conventional DSR and soil mulch DSR did not differ in grain yield, whereas they differed in crop emergence, growth, and yield attributes. These results suggest that halopriming with 2.0% potassium nitrate and hormopriming with 50 ppm GA3 has good potential to improve crop establishment and yield of rice in both conventional and soil mulch DSR systems.

IL-6 Predicts Poor Early Post-Natal Growth in Very Low-Birth-Weight Infants in a Low-Middle Income Setting.

Extra-uterine growth restriction (EUGR) is common in preterms and may be associated with elevated pro-inflammatory cytokines. Describe postnatal growth in a cohort of very low-birth-weight (VLBW) infants and determine the association of interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF-α) in umbilical cord blood with growth at 40 weeks and 12 months postmenstrual age (PMA). Single-centre, prospective cohort study conducted from 1 June 2017 to 31 January 2019 with follow-up to 31 March 2020. Infants <1500 g at birth were enrolled, cord blood collected for IL-6 and TNF-α assays and postnatal care, including anthropometry, provided to 12 months PMA. Informed consent and ethics approval were obtained. In total, 279 patients were enrolled; 84 (30.1%) died before 12 months and 91 (32.6%) lost to follow-up. Anthropometry was available for 151 infants at 40 weeks and 105 at 12 months. Z-Scores at 40 weeks for males and females combined were -2.5, -2.1 and -1.2 for weight, length and head circumference. EUGR occurred in 103/113 (91.2%), 98/107 (91.6%) and 70/109 (64.2%) participants for weight, length and head circumference. Elevated IL-6 was associated with restricted weight (56.0 vs. 14.5 pg/ml, p = 0.02) and length (60.4 vs. 7.3 pg/ml, p = 0.01) at 40 weeks. There was no difference in IL-6 at 12 months and no difference in TNF-α at 40 weeks or 12 months. The study reports significant EUGR. Elevated IL-6 was associated with growth restriction at 40 weeks but not 12 months PMA.

Soil biota from newly established orchards are more beneficial to early growth of cherry trees than biota from older orchards

Growth of young fruit trees replanted into old orchard soil is often poor relative to growth in soil that has not previously been planted with fruit trees. There is evidence that a consortium of deleterious soil biota, commonly referred to as the replant disease complex, are responsible for this poor early growth. We used a bioassay, comparing cherry plant growth in sterilized and non-sterilized subsamples of soil, to assess the net effect of soil biota from 18 orchards in the Okanagan Valley of British Columbia, Canada with differing histories of fruit tree production (previously cropped ‘old’ orchards, and not previously cropped ‘young’ orchards). Generally, shoot height increment was larger in non-sterile soil from young orchards than from old orchards (two-factor ANOVA; P < .001). When soil from young orchards was sterilized plant weight was lower, compared to the non-sterilized counterpart (two-factor ANOVA; P = .006). Pratylenchus populations in root tissue were greater in plants grown in old orchard soils than in young orchard soils (one-factor ANOVA; P < .001). Multiple regression analyses showed that FDA hydrolysis, an indicator of microbial activity, was the only variable that significantly predicted plant growth response to sterilization for the variables shoot height increment (R2 = 0.6; P = .001) and plant weight (R2 = 0.5; P = .002). Overall, results from this study suggest that management practices that stimulate microbial activity will benefit growth of cherry trees in previously cropped ‘old’ orchards, and not previously cropped ‘young’ orchards.

Poor Early Growth and Age-Associated Disease.

The prevalence of age-associated disease is increasing at a striking rate globally and there is evidence to suggest that the ageing process may actually begin before birth. It has been well-established that the status of both the maternal and early postnatal environments into which an individual is exposed can have huge implications for the risk of developing age-associated disease, including cardiovascular disease (CVD), type-2 diabetes (T2D) and obesity in later life. Therefore, the dissection of underlying molecular mechanisms to explain this phenomenon, known as 'developmental programming' is a highly investigated area of research. This book chapter will examine the epidemiological evidence and the animal models of suboptimal maternal and early postnatal environments and will discuss the progress being made in the development of safe and effective intervention strategies which ultimately could target those 'programmed' individuals who are known to be at-risk of age-associated disease.

Poor early growth and high salt intake in Indian infants

The influence of feeding patterns on the growth of infants and how salt is included in the diet are unknown in the area of West Bengal, India. A cross-sectional study was carried on 517 infants (median age 6.5 months). Negative Z-scores were observed for all anthropometric parameters. About 72.7% of infants aged 0–6 months received exclusive breastfeeding. In the 6–12-month-old group (n = 235), 91.5% had salt added to foods. In a regression model adjusted for age, a low salt diet resulted a significant factor in increasing weight-for-length and BMI for age z-scores, with increments equal to 0.637 SD (p = 0.037) and 0.650 SD (p = 0.036), respectively.In West Bengal infants showing poor growth, breastfeeding was associated with better anthropometric indexes, but early in life salt is added to their diet. Early life low weight coupled with high salt intake may be a risk factor for arterial hypertension in Indian children.

Organically acceptable practices to improve replant success of temperate tree-fruit crops

For most temperate perennial fruit crops, replanting into soil that was used previously to grow the same or a related crop species usually results in poor early growth, preventing new plantings from reaching potential levels of productivity and economic returns to growers. Increases in population densities of root pathogens along with deleterious changes in soil quality under the preceding crops are largely responsible for these replant disease complexes. Driven by the rise in organic fruit production and new restrictions on fumigants and fumigation practices in the conventional sector, considerable research has been aimed, over the past two decades, to the development of non-chemical and organically-acceptable means of managing replant disease complexes. As apple is the most widely grown temperate perennial fruit crop, the majority of this research has been directed at the apple replant disease complex. This review summarizes knowledge of the causes of replant disease complexes of temperate orchard crops, and recent applied research on organically-acceptable practices to reduce the impacts of these disease complexes. Brassica seed meal amendments and composts show considerable promise as pre-plant soil amendments to improve replanted tree establishment. Composts have the added benefit of contributing to improvements in overall soil health that may enhance productivity in the long-term. Additional research to understand better the mechanisms by which compost amendments enhance replanted tree establishment would lead to improvements in the effectiveness and reliability of their utilization to alleviate replant disease.

Nitrogen management to optimise canola production in Australia

The expansion of canola production in Australia coincided with an increase in cropping intensity and a reduction in pastures and tillage. These changes mean that nitrogen (N) is often recognised as the most limiting nutrient in canola production, and is the largest single input cost for many growers. Canola responds to added N by producing larger plants that results in a longer leaf area duration, building a larger photosynthetic canopy for seed filling. Although the crop can compensate for poor early growth, a larger canopy is able to compete more effectively against weeds and helps reserve water for crop transpiration rather than soil evaporation. Nitrogen uptake is most rapid during stem elongation, and the N acquired can be remobilised to developing pods and then to seeds. Unlike wheat, N uptake can continue until drought or high temperatures prevent further assimilate supply to the reproductive apex. Data from Australian experiments that measured N uptake over the whole growth period showed that each tonne of seed required ~80 kg N to be taken up, and this forms the basis of a budgeting approach for determining N supply. Typically, added N reduces seed oil concentration at a rate of between –0.03 and –0.13%/kg N. Despite this decline due to added N, oil yield usually increases and the overall value of the crop also increases. Nitrogen has little impact on oil quality or seed glucosinate concentration. The efficiency and effectiveness of N management depends first on selecting a rate appropriate to the water-limited yield potential. Most growers estimate the N rate required using an N budget based on supplying 80 kg N/t less indigenous N supply. The budgeted N can be split over two, three or even more applications with little loss in agronomic efficiency. Splitting application enables growers to make decisions about N when there is more certainty about seasonal conditions. Urea is the most common N source used, and unless there are particular loss processes that are likely to occur, it is cheap and effective. Suggested areas for future N research on canola are to develop tools that can assess in-crop N status, an evaluation of late season N product rate and timing particularly on seed oil concentration, N management for grazed canola, and the development of guidelines to identify, and then address, particular N loss pathways using enhanced efficiency fertilisers.

Despite Catch-Up, Prolonged Growth Has Detrimental Fitness Consequences in a Long-Lived Vertebrate

Individuals experiencing poor growth early in life may later make up their size deficit. Compensatory growth or growth prolongation may lead to such catch-up, involving different life-history trade-offs under natural conditions. Frequent recaptures and detailed monitoring of animals surviving to asymptotic size are required to compare growth tactics and their fitness consequences. No study to date has obtained such detailed information for wild animals. We used repeated mass measurements (mean 11.6/animal) spanning the lifetime of 104 bighorn ewes (Ovis canadensis) to quantify growth tactics and identify the determinants and life-history costs of these tactics. Growth prolongation, not compensatory growth, led to partial catch-up: mass difference at age 7 was reduced to 4%, for two groups that differed by nearly 20% as yearlings. Ewes that had been light as yearlings prolonged their growth regardless of density or age of primiparity. Growth prolongation did not affect fecundity or longevity. Ewes that experienced poor early growth prolonged growth at the expense of reproductive fitness, weaning a smaller proportion of their lambs. By tracking multiyear growth patterns and comparing events at different life-history stages, we quantified a trade-off between growth and reproduction that would be overlooked if only the adult phenotype was considered. Compensatory growth in long-lived animals appears unlikely when early growth restrictions are mostly density dependent.

Effect of gender on long‐term effects of catch‐up growth in neonatal rats

Poor early growth in preterm infants leads to impaired neurodevelopment but may reduce the risk of metabolic syndrome. Although elevated leptin levels in young animals may increase the risk of later leptin resistance, hepatic steatosis and metabolic syndrome, it is required for normal neurocognitive development. We therefore examined the effect of differences in early growth rates on serum leptin, triglycerides (TG) and cognition. Newborn rat pups were randomized into normal (N, n=10) or reduced growth (R, n=16) litters. On d11, R pups were re‐randomized into litters creating catch‐up (R‐6, n=6), normal (R‐10, n=10) or reduced growth (R‐16, n=10). Serum leptin, serum TG and hepatic TG were measured at d 10, 22, and 60; cognition in a T‐maze on d35. Leptin was higher in N pups than R on d10 (p&lt;0.0001), and N animals scored highest on the T‐maze. In females, leptin on d22 and T‐maze score were significantly lower in the R‐16 group than other R groups. On d10, serum TG was significantly higher in N than R pups (p=0.001). In females, hepatic TG was significantly greater in R‐6 and N animals than in R‐10 or R‐16. We conclude that early growth restriction leads to lower serum leptin, serum TG, and impaired long‐term cognitive development. Subsequent catch‐up growth improves cognition, but worsens hepatic steatosis, in female rats. This model may contribute to our understanding of poor developmental outcomes in preterm infants.Grant Funding Source: UC Davis Department of Pediatrics

Maternal Mental Health and Its Association with Infant Growth at 6 Months in Ethnic Groups: Results from the Born-in-Bradford Birth Cohort Study

ObjectiveTo identify factors associated with infant growth up to 6 months, with a particular focus on maternal distress, and to explore the effect of ethnicity on any relation between maternal distress and infant growth.MethodsCohort study recruiting White and Pakistani women in the United Kingdom (UK). Infant growth was measured at birth and 6 months. Standard assessment of mental health (GHQ-28) was undertaken in pregnancy (26–28 weeks gestation) and 6 months postpartum. Modelling included social deprivation, ethnicity, and other known influences on infant growth such as maternal smoking and alcohol consumption.ResultsMaternal distress improved markedly from pregnancy to 6 months postpartum. At both times Pakistani women had more somatic and depression symptoms than White women. Depression in pregnancy (GHQ subscale D) was associated with lower infant growth at 6 months. Self-reported social dysfunction in pregnancy (GHQ subscale C) was associated with lower gestational age.. Pakistani women reported higher GHQ scores during pregnancy associated with smaller infants at birth. They lived in areas of higher social deprivation, reported less alcohol consumption and smoking postnatally, all independent influences on growth at 6 months.ConclusionsMaternal mental health in pregnancy is an independent influence on infant growth up to 6 months and is associated with ethnicity which was itself associated with deprivation in our sample. There is a complex relationship between symptoms of maternal distress, ethnicity, deprivation, health behaviours, and early infant growth. Measures should include both emotional and somatic symptoms and interventions to reduce risks of poor early growth need to include psychological and social components.

Permanent Beds vs. Conventional Tillage in Irrigated Arid Central Asia

Limited or no tillage with residue retention on the soil surface has had mixed success in irrigated agricultural systems. The effects of tillage and crop residue management on soil properties and crop yields were studied on a silt loam soil using a rotation of winter wheat (Triticum aestivum L.) and maize (Zea mays L.) for 2 yr, followed by cotton (Gossypium hirsutum L.) for 2 yr. Permanent beds (PB) with limited reshaping and conventional tillage (CT) were compared, each with both 25% residue retention on a mass basis (R25) and 100% residue retention (R100). There was greater soil compaction and consolidation in the 0.2‐ to 0.3‐m depth with the PB system regardless of residue retention practice. Compared with the CT system and the PB+R25 treatment combination, the PB+R100 treatment combination increased the amount of water‐stable macroaggregates, however only in the fourth year. The soil organic C in the 0‐ to 0.4‐m depth increased at 0.70 Mg ha−1 yr−1 in PB+R100 vs. 0.48 Mg ha−1 yr−1 in CT+R100. Poor early plant growth and reduced plant population in PB caused decreased water use efficiency (WUE) and irrigation water use efficiency (IWUE) of maize and cotton grown consecutively in 2006 and 2007. Generally, R100 improved IWUE and WUE, except for cotton in 2007. For PB+R100, cotton seed‐lint IWUE in 2008 increased to 0.59 kg m−3 from 0.41 earlier. Smaller maize and cotton plant populations and cooler soil temperatures at cotton emergence in PB+R100 decreased crop productivity during the first 3 yr.

Evaluation of cold stress of young industrial chicory (Cichorium intybus L.) plants by chlorophyll a fluorescence imaging. I. Light induction curve

Industrial chicory, Cichorium intybus L., is cultivated for the production of inulin. Most varieties of industrial chicory exhibit rather poor early growth, which limits further yield improvements in their European cultivation area. The poor early growth could be due to suboptimum adaptation of the gene pool to growth at low temperatures, sometimes in combination with high light intensities, which is typical of early-spring mornings. We have used chlorophyll (Chl) a fluorescence to evaluate the response of young plants of the cultivar 'Hera' to low temperatures and high light intensities. Plants were grown at three temperatures: 16°C (reference), 8°C (intermediate), and 4°C (cold stress). Light-response measurements were carried out at different light intensities in combination with different measurement temperatures. Parameters that quantify the photosystem II (PSII) operating efficiency (including PSII maximum efficiency and PSII efficiency factor) and nonphotochemical quenching (NPQ) are important to evaluate the stress in terms of severity, the photosynthetics processes affected, and acclimation to lower growth temperatures. The results clearly demonstrate that in young industrial chicory plants the photosynthetic system adapts to lower growth temperatures. However, to fully understand the plant response to the stresses studied and to evaluate the long-term effect of the stress applied on the growth dynamics, the subsequent dark relaxation dynamics should also be investigated.

Poor early growth and excessive adult calorie intake independently and additively affect mitogenic signaling and increase mammary tumor susceptibility.

We previously showed that offspring of rat dams receiving a protein-restricted (low protein) diet throughout pregnancy and lactation develop mammary tumors more quickly. Rapid post-weaning mammary growth and mammary tissue overexpression of insulin receptor, insulin-like growth factor-1 receptor (IGF-1R), estrogen receptor isoform alpha and v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 (ERBB2), correlated with this risk. The objectives of this study were therefore (i) to identify underlying mechanisms of increased risk through candidate and global approaches; (ii) to determine if excessive calorie intake further increased risk and if so, (iii) to identify the molecular mechanisms mediating this. We provide evidence for transcriptional upregulation of IGF-1R by Sp1 in LP mammary tissue (P < 0.01). Cell cycle control and DNA damage repair gene cyclin-dependent kinase inhibitor 1A (CDKN1A) (p21waf1) was also upregulated (P < 0.05) as was transcription factor nuclear factor of kappa light polypeptide gene enhancer in B-cell (P < 0.05) and adhesion gene CDH1 (P < 0.05). Invasion and metastasis markers matrix metalloproteinase 9 and serpin peptidase inhibitor, clade E, member 1 (SERPIN1) were upregulated (both P < 0.05), whereas metastasis suppressor gene NME1 was downregulated (P < 0.01). Feeding a highly palatable diet (HPD) to increase calorie intake from puberty, additively and independently increased early mammary tumor risk, which correlated with increased serum insulin and triglyceride concentrations (P < 0.05). PTEN gene expression was reduced both by early protein restriction (P < 0.05) and HPD (P < 0.01), which may induce Akt in cell survival pathways. Progesterone receptor and ERBB2 (both P < 0.05) expression increased as an effect of an interaction between maternal diet and adult nutrition, with subsequent downstream activation of the mitogen-activated protein kinase pathway. We conclude that poor early growth and excessive calorie intake exert independent and additive effects on mitogenic growth factor signaling to influence mammary tumor susceptibility.

Maternal Diet, Behaviour and Offspring Skeletal Health

Osteoporotic fracture has a major impact upon health, both in terms of acute and long term disability and economic cost. Peak bone mass, achieved in early adulthood, is a major determinant of osteoporosis risk in later life. Poor early growth predicts reduced bone mass, and so risk of fracture in later life. Maternal lifestyle, body build and 25(OH) vitamin D status predict offspring bone mass. Recent work has suggested epigenetic mechanisms as key to these observations. This review will explore the role of the early environment in determining later osteoporotic fracture risk.

Mechanisms Linking Suboptimal Early Nutrition and Increased Risk of Type 2 Diabetes and Obesity1–3

Epidemiological studies have revealed a relationship between poor early growth and development of type 2 diabetes and other features of metabolic syndrome. The mechanistic basis of this relationship is not known. However, compelling evidence suggests that early environmental factors, including nutrition, play an important role. Studies of individuals in utero during a period of famine showed a direct relationship between maternal nutrition and glucose tolerance. Further evidence has come from studies of monozygotic twins who were discordant for type 2 diabetes. Nutrition during the early postnatal period has also been shown to have long-term consequences on metabolic health. Excess nutrition and accelerated growth during the neonatal period has been suggested to be particularly detrimental. Animal models, including maternal protein restriction, have been developed to elucidate mechanisms linking the early environment and future disease susceptibility. Maternal protein restriction in rats leads to a low birth weight and development of type 2 diabetes in the offspring. This is associated with β cell dysfunction and insulin resistance. The latter is associated with changes in expression of key components of the insulin-signaling cascade in muscle and adipocytes similar to that observed in tissue from young men with a low birth weight. These differences occur prior to development of disease and thus may represent molecular markers of early growth restriction and disease risk. The fundamental mechanisms by which these programmed changes occur remain to be fully defined but are thought to involve epigenetic mechanisms.

Birth Weight Deviation and Early Postnatal Growth Are Related to Optic Nerve Morphology at School Age in Children Born Preterm

The aim of this study was to evaluate the influence of early and later postnatal growth variables on optic disc morphology in children (n = 53) born at gestational age <32 wk. On fundus photographs taken at a median age of 5.4 y, the optic discs were evaluated using digital image analysis and compared with those of a control group (n = 203). The results were analyzed in relation to gestational age, birth weight (BW) SD score (SDS), IGF-1 weight at postmenstrual age 32 wk (SDS), and weight, length, and head circumference (SDS) at follow-up. The preterm children's optic disc and neuronal rim areas were smaller than in the control group. Low BW (SDS) and weight at wk 32 (SDS) were associated with larger area of the optic cup and reduced neuronal rim area. Preterm children with known brain lesions (n = 6) had significantly larger cups than preterm children without known brain lesions. The association found between both low BW and poor early growth and later reduced neuronal tissue of the optic nerve indicate that early weight gain is important for neural development in preterm children.