A role for subchondral bone changes in the process of osteoarthritis; a micro-CT study of two canine models

BACKGROUND: This study evaluates changes in peri-articular bone in two canine models for osteoarthritis: the groove model and the anterior cruciate ligament transection (ACLT) model. METHODS: Evaluation was performed at 10 and 20 weeks post-surgery and in addition a 3-weeks time point was studied for the groove model. Cartilage was analysed, and architecture of the subchondral plate and trabecular bone of epiphyses was quantified using micro-CT. RESULTS: At 10 and 20 weeks cartilage histology and biochemistry demonstrated characteristic features of osteoarthritis in both models (very mild changes at 3 weeks). The groove model presented osteophytes only at 20 weeks, whereas the ACLT model showed osteophytes already at 10 weeks. Trabecular bone changes in the groove model were small and not consistent. This contrasts the ACLT model in which bone volume fraction was clearly reduced at 10 and 20 weeks (15-20%). However, changes in metaphyseal bone indicate unloading in the ACLT model, not in the groove model. For both models the subchondral plate thickness was strongly reduced (25-40%) and plate porosity was strongly increased (25-85%) at all time points studied. CONCLUSION: These findings show differential regulation of subchondral trabecular bone in the groove and ACLT model, with mild changes in the groove model and more severe changes in the ACLT model. In the ACLT model, part of these changes may be explained by unloading of the treated leg. In contrast, subchondral plate thinning and increased porosity were very consistent in both models, independent of loading conditions, indicating that this thinning is an early response in the osteoarthritis process

IGF-I, Growth, and Body Composition in Preterm Infants up to Term Equivalent Age

Context: There are concerns that a higher fat mass in the early life of preterm infants is associated with adverse cardiometabolic outcomes in young adulthood. Objective: To investigate the role of IGF-I and growth in determining body composition of preterm infants at term equivalent age. Methods: An observational study was conducted from August 2015 to August 2018. From birth to term equivalent age, IGF-I levels were measured bi-weekly and growth was assessed weekly. At term equivalent age, body composition was assessed through air displacement plethysmography; 65 infants with a gestational age of 24 to 32 weeks were assessed at term equivalent age, of whom 58 completed body composition measurement. The main outcome measures were fat (free) mass (g) and fat (free) mass percentage at term equivalent age. Results: In the first month of life, each 0.1 nmol/L per week increase in IGF-I was associated with a 465 g (SE 125 g) increase in fat free mass. A greater increase in weight SDS in the first month of life was associated with a higher fat free mass percentage (B 200.9; 95% CI, 12.1-389.6). A higher head circumference SDS was associated with more fat free mass (r = 0.46; 95% CI, 0.21-0.65). However, a greater increase in weight SDS up to term equivalent age was associated with a lower fat free mass percentage (B -55.7, SE 9.4). Conclusion: These findings suggest that impaired growth in the first month of life is associated with a less favorable body composition at term equivalent age

Follow-up of a randomized trial on postdischarge nutrition in preterm-born children at age 8 y

Background: Early nutritional interventions may modulate health risks in preterm-born infants. Previously, we showed that pretermborn infants fed an isocaloric protein- and mineral-enriched postdischarge formula (PDF) from term age to 6-mo corrected age (CA) gained more lean mass than did those fed term formula (TF). Longterm follow-up of randomized nutritional trials is important to test the hypothesis that short-term positive effects on health are sustainable. Objective: The aim of this follow-up study was to compare body size, body composition, and metabolic health at age 8 y in pretermborn children who were randomly assigned to receive either PDF or TF from term age until 6-mo CA. Design: A total of 79 of 152 children (52%) from the original randomized controlled trial were enrolled for follow-up at age 8 y. Weight, height, and head circumference were measured by using standard methods. Body composition, including fat mass, lean mass, bone mineral content, and bone mineral density, was determined by dual-energy X-ray absorptiometry. Blood pressure was measured in the supine position by using an automatic device. Metabolic variables, including glucose, insulin, insulin-like growth factor I, triglycerides, cholesterol, cortisol, and leptin, were measured after an overnight fast. Nutritional habits at age 8 y were assessed by using a 3-d nutritional diary. Results: At age 8 y, no differences were found in body size, body composition, bone variables, and metabolic health variables when comparing children fed PDF with those fed TF. Adjustment for known and possible confounders did not change these results. Conclusions: In this follow-up study in preterm-born children, we showed that the favorable effects of PDF at 6-mo CA either were not maintained or could not be confirmed because of attrition at the age of 8 y. We suggest that future research should focus on nutritional interventions in the pre- and postdischarge period as a continuum rather than as separate entities

Reference curves of birth weight, length, and head circumference for gestational ages in Yogyakarta, Indonesia

Background: The birth weight reference curve to estimate the newborns at risk in need of assessment and monitoring has been established. The previous reference curves from Indonesia, approximately 8 years ago, were based on the data collected from teaching hospitals only with limited gestational ages. The aims of the study were to update the reference curves for birth weight, supine length and head circumference for Indonesia, and to compare birth weight curves of boys and girls, first child and later children, and the ones in the previous studies. Methods: Data were extracted from the Maternal-Perinatal database between 1998-2007. Only live singletons with recorded gestational ages of 26 to 42 weeks and the exact time of admission to the neonatal facilities delivered or referred within 24 h of age to Sardjito Hospital, five district hospitals and five health centers in Yogyakarta Special Territory were included. Newborns with severely ill conditions, congenital anomaly and chromosomal abnormality were excluded. Smoothening of the curves was accomplished using a third-order polynomial equation. Results: Our study included 54,599 singleton live births. Growth curves were constructed for boys (53.3%) and girls (46.7%) for birth weight, supine length, and head circumference. At term, mean birth weight for each gestational age of boys was significantly higher than that of girls. While mean birth weight for each gestational age of first-born-children, on the other hand was significantly lower than that of later-born-children. The mean birth weight was lower than that of Lubchenco's study. Compared with the previous Indonesian study by Alisyahbana, no differences were observed for the aterm infants, but lower mean birth weight was observed in preterm infants. Conclusions: Updated neonatal reference curves for birth weight, supine length and head circumference are important to classify high risk newborns in specific area and to identify newborns requiring attention

Sensory modulation in preterm children: Theoretical perspective and systematic review

Background Neurodevelopmental sequelae in preterm born children are generally considered to result from cerebral white matter damage and noxious effects of environmental factors in the neonatal intensive care unit (NICU). Cerebral white matter damage is associated with sensory processing problems in terms of registration, integration and modulation. However, research into sensory processing problems and, in particular, sensory modulation problems, is scarce in preterm children. Aim This review aims to integrate available evidence on sensory modulation problems in preterm infants and children ( <37 weeks of gestation) and their association with neurocognitive and behavioral problems. Method Relevant studies were extracted from PubMed, EMBASE.com and PsycINFO following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Selection criteria included assessment of sensory modulation in preterm born children ( <37 weeks of gestation) or with prematurity as a risk factor. Results Eighteen studies were included. Results of this review support the presence of sensory modulation problems in preterm children. Although prematurity may distort various aspects of sensory modulation, the nature and severity of sensory modulation problems differ widely between studies. Conclusions Sensory modulation problems may play a key role in understanding neurocognitive and behavioral sequelae in preterm children. Some support is found for a dose-response relationship between both white matter brain injury and length of NICU stay and sensory modulation problem

Sensory processing difficulties in school-age children born very preterm: An exploratory study

Background Very preterm birth has a detrimental impact on the developing brain, including widespread white matter brain abnormalities that threaten efficient sensory processing. Yet, sensory processing difficulties in very preterm children are scarcely studied, especially at school age. Aims To investigate somatosensory registration, multisensory integration and sensory modulation. Participants 57 very preterm school-age children (mean age = 9.2 years) were compared to 56 gender and age matched full-term children. Methods Group differences on somatosensory registration tasks (Registration of Light Touch, Sensory Discrimination of Touch, Position Sense, Graphestesia), a computerized multisensory integration task, and the parent-reported Sensory Profile were investigated using t-tests and Mann-Whitney U tests. Results In comparison to full-term children, very preterm children are less accurate on somatosensory registration tasks, including Registration of Light Touch (d = 0.34), Position Sense (d = 0.31) and Graphestesia (d = 0.42) and show more sensory modulation difficulties (d = 0.41), including both behavioral hyporesponsivity (d = 0.52) and hyperresponsivity (d = 0.56) to sensory stimuli. Tactile discrimination and multisensory integration efficiency were not affected in very preterm children. Aspects of sensory processing were only modestly related. Conclusion Very preterm children show sensory processing difficulties regarding somatosensory registration and sensory modulation, and preserved multisensory (audio-visual) integration. Follow-up care for very preterm children should involve screening of sensory processing difficulties at least up to school age

Post term dietary-induced changes in DHA and AA status relate to gains in weight, length, and head circumference in preterm infants

Preterms need supplementation with docosahexaenoic (DHA) and arachidonic (AA) acids to prevent steep postnatal declines. Associations between growth and erythrocyte (RBC) DHA and AA were studied in 139 preterms (51% male, gestational age 30.3 +/- 1.5 weeks, birth weight 1341 +/- 288 g) fed human milk with breast milk fortifier or preterm formula until term, followed by postdischarge formula (PDF: n=52, 0.4% DHA, 0.4% AA), term formula (TF; n=41, 0.2% DHA, 0.2% AA), or human milk (HM; n=46). At six months, PDF resulted in higher RBC-DHA than TF and HM, while RBC-AA was higher than TF, but similar to HM. There were no between-group differences in growth between term and six months. RHC-DHA related positively with gain in weight and length and negatively with gain in head circumference. RBC-AA related positively with gain in head circumference and negatively with gain in weight and length. In conclusion, PDF with higher DHA and AA than TF may promote postnatal growth of preterms. (C) 2011 Elsevier Ltd. All rights reserved

Improving long-term health outcomes of preterm infants: how to implement the findings of nutritional intervention studies into daily clinical practice

Preterm-born children are at risk for later neurodevelopmental problems and cardiometabolic diseases; early-life growth restriction and suboptimal neonatal nutrition have been recognized as risk factors. Prevention of these long-term sequelae has been the focus of intervention studies. High supplies of protein and energy during the first weeks of life (i.e., energy > 100 kcal kg−1 day−1 and a protein-to-energy ratio > 3 g/100 kcal) were found to improve both early growth and later neurodevelopmental outcome. Discontinuation of this high-energy diet is advised beyond 32–34 weeks postconceptional age to prevent excess fat mass and possible later cardiometabolic diseases. After discharge, nutrition with a higher protein-to-energy ratio (i.e., > 2.5–3.0 g/100 kcal) may improve growth and body composition in the short term. Conclusion: Preterm infants in their first weeks of life require a high-protein high-energy diet, starting shortly after birth. Subsequent adjustments in nutritional composition, aimed at achieving optimal body composition and minimizing the long-term cardiometabolic risks without jeopardizing the developing brain, should be guided by the growth pattern. The long-term impact of this strategy needs to be studied.What is Known:• Preterm infants are at risk for nutritional deficiencies and extrauterine growth restriction.• Extrauterine growth restriction and suboptimal nutrition are risk factors for neurodevelopmental problems and cardiometabolic disease in later life.What is New:• Postnatally, a shorter duration of high-energy nutrition may prevent excess fat mass accretion and its associated cardiometabolic risks and an early switch to a protein-enriched diet should be considered from 32-34 weeks postconceptional age.• In case of formula feeding, re-evaluate the need for the continuation of a protein-enriched diet, based on the infant’s growth pattern

Salt sensitivity of blood pressure at age 8 years in children born preterm

Preterm birth and low birth weight have been associated with an increased risk of hypertension; postnatal growth and dietary salt intake may contribute to these associations. In adults, the change of blood pressure (BP) in response to modifications in salt intake, i.e., salt sensitivity of BP, has been independently associated with cardiovascular disease. Little is known about salt sensitivity in children. We hypothesize that it may partly explain the association between preterm birth and higher BP in later life. We assessed salt sensitivity of BP at age 8 years in 63 preterm-born children, and explored its association with postnatal growth, sodium intake, and body composition from infancy onwards. BP was measured at baseline and after a 7-day high-salt diet. The difference in mean arterial pressure (MAP) was calculated; salt sensitivity was defined as an increase in MAP of ≥5%. Ten children (16%) showed salt sensitivity of BP, which was associated with neonatal growth restriction as well as with lower fat mass and BMI from infancy onwards. At age 8 years, children classified as salt sensitive had a lower weight-for-age SD-score (-1.5 ± 1.3 vs. -0.6 ± 1.1) and BMI (13.8 ± 1.7 vs. 15.5 ± 1.8 kg/m2) compared to their salt resistant counterparts. Sodium intake was not associated with (salt sensitivity of) BP. Salt sensitivity of BP was demonstrated in preterm-born children at age 8 years and may contribute to the development of cardiovascular disease at later age. Long-term follow-up studies are necessary to assess reproducibility of our findings and to explore clustering with other cardiovascular risk factors