Absence Of Catch-up Growth Research Articles

Risk Factors for Short Stature in Children Born Small for Gestational Age at Full-Term.

ObjectiveThis study aims to identify the risk factors associated with short stature in children born small for gestational age (SGA) at full-term.MethodsThis was a retrospective study. The subjects were full-term SGA infants who were followed up until the age of 2 years. The risk factors for short stature were identified with univariate and multivariate analyses.ResultsOf 456 full-term SGA children enrolled in this study, 28 cases had short stature at 2 years of age. A significant decrease in placental perfusion was found in the short children group with intravoxel incoherent motion (IVIM) technology, which was an advanced bi-exponential diffusion-weighted imaging (DWI) model of magnetic resonance imaging (MRI) (p = 0.012). Compared to non-short children born SGA at full-term, the short children group underwent an incomplete catch-up growth. Mothers who suffered from systemic lupus erythematosus were more likely to have a short child born SGA (p = 0.023). The morbidity of giant placental chorioangioma was higher in the short children group. The pulsatility index (PI), resistivity index (RI), and systolic-diastolic (S/D) ratio of umbilical artery were higher in the short children group than in the non-short control group (p = 0.042, 0.041, and 0.043). Multivariate analysis demonstrated that decrease of perfusion fraction (fp) in IVIM of placental MRI, chromosomal abnormalities, short parental height, and absence of catch-up growth were associated with a higher risk of short stature in children born SGA at full-term.ConclusionRisk factors for short stature in full-term SGA children at 2 years of age included a decrease of perfusion fraction fp in IVIM of placental MRI, chromosomal abnormalities, and short parental height.

Longitudinal study of the newborn small for gestational age. Growth recovery and conditioning factors

Background: small-for-gestational-age (SGA) newborns present a higher morbidity and mortality rate when compared to infants born appropriate for gestational age (AGA), as well as insufficient growth, with height far from their target and in some cases a low final height (< -2 SDs). Objective: the aim of this study was to determine when catch-up growth (CUG) in height occurs in these children, and which factors are associated with lack of CUG. Material and methods: this is a retrospective study of SGAs born between 2011 and 2015 in a secondary hospital. Anthropometric measurements were taken consecutively until CUG was reached, and fetal, placental, parental, newborn, and postnatal variables were studied. Results: a total of 358 SGAs were included from a total of 5,585 live newborns. At 6 and 48 months of life, 93.6 % and 96.4 % of SGAs achieved CUG, respectively. By subgroups, symmetric SGAs performed worse than asymmetric SGAs with CUG in 84 % and 92 % at 6 and 48 months of life, respectively. The same occurred in the subgroup of preterm SGAs with respect to term SGAs, with worse CUGs of 88.2 % and 91.2 % at 6 and 48 months of life, respectively. Prematurity, symmetrical SGA, intrauterine growth retardation (IUGR), preeclampsia, previous child SGA, perinatal morbidity, and comorbidity during follow-up were associated with absence of CUG. Conclusions: the majority of SGAs had CUG in the first months of life. The worst outcomes were for preterm and symmetric SGAs.

Growth hormone treatment for extremely low birthweight children born small for gestational age.

The effectiveness of growth hormone (GH) treatment for height gain in short-stature children born small for gestational age (SGA) with extremely low birthweight (ELBW; birthweight <1,000g) remains largely unknown. In study 1, 35 prepubertal Japanese children born SGA with ELBW were categorized into three groups based on the presence or absence of catch-up growth by age 3 (CU(+) and CU(-), respectively) and GH treatment (GH(+) and GH(-), respectively). Height standard deviation (SD) scores (HT-SDS) in the CU-/GH+ group (n = 19) were compared with those in the age-matched CU+/GH- (n = 9) and CU-/GH- groups (n = 7). In study 2, 66 prepubertal Japanese SGA children treated with GH were divided into three groups by birthweight: <1,000g (n = 19), 1,000-2,000g (n = 20), and >2,000g (n = 27). Changes in HT-SDS during the initial 3years of GH treatment were compared among the three groups. In study 1, the mean HT-SDS in the CU-/GH+ group (-1.15 SD) was similar to that in the CU+/GH- group (-1.39 SD) but higher than that in the CU-/GH- group (-2.24 SD). In study 2, GH achieved a height gain of +1.62 SD in the ELBW group, which was similar to that in the other groups (1,000-2,000g: +1.46 SD, >2,000g: +1.53 SD). Growth hormone treatment in short-stature children born SGA with ELBW increased HT-SDS, which was similar to that in SGA children born with a birthweight ≥1,000g. These results indicate that GH treatment may be an effective approach to promote adequate growth recovery for short-stature children born SGA with ELBW.

Marginally low birthweight increases the risk of underweight and short stature at three and a half years of age.

Little is known about the long-term health of marginally low birthweight (LBW) children. This study characterised growth among infants weighing 2000 g-2500 g and explored the prevalence and predictors of sustained growth restriction. This prospective observational trial followed the weight and height of 281 Swedish marginally LBW children from birth to 3.5 years of age. Children with a standard deviation score (SDS) for body mass index or height below -2 were considered underweight and short, respectively. The mean SDS for weight and height showed a rapid increase before 12-19 weeks of age. The most rapid weight gain was in infants born small for gestational age. However, at 3.5 years of age, 9.5% of the children remained underweight and 6.5% had short stature. Regression models showed that slow weight gain before 19 weeks of age was the strongest predictor for lasting underweight, while slow height gain before 19 weeks of age and male sex were associated with short stature. Marginally LBW infants were more likely to be underweight and have a short stature at 3.5 years of age and the absence of catch-up growth during the first five months after birth identified those at highest risk.

Cdkn1c Boosts the Development of Brown Adipose Tissue in a Murine Model of Silver Russell Syndrome.

The accurate diagnosis and clinical management of the growth restriction disorder Silver Russell Syndrome (SRS) has confounded researchers and clinicians for many years due to the myriad of genetic and epigenetic alterations reported in these patients and the lack of suitable animal models to test the contribution of specific gene alterations. Some genetic alterations suggest a role for increased dosage of the imprinted CYCLIN DEPENDENT KINASE INHIBITOR 1C (CDKN1C) gene, often mutated in IMAGe Syndrome and Beckwith-Wiedemann Syndrome (BWS). Cdkn1c encodes a potent negative regulator of fetal growth that also regulates placental development, consistent with a proposed role for CDKN1C in these complex childhood growth disorders. Here, we report that a mouse modelling the rare microduplications present in some SRS patients exhibited phenotypes including low birth weight with relative head sparing, neonatal hypoglycemia, absence of catch-up growth and significantly reduced adiposity as adults, all defining features of SRS. Further investigation revealed the presence of substantially more brown adipose tissue in very young mice, of both the classical or canonical type exemplified by interscapular-type brown fat depot in mice (iBAT) and a second type of non-classic BAT that develops postnatally within white adipose tissue (WAT), genetically attributable to a double dose of Cdkn1c in vivo and ex-vivo. Conversely, loss-of-function of Cdkn1c resulted in the complete developmental failure of the brown adipocyte lineage with a loss of markers of both brown adipose fate and function. We further show that Cdkn1c is required for post-transcriptional accumulation of the brown fat determinant PR domain containing 16 (PRDM16) and that CDKN1C and PRDM16 co-localise to the nucleus of rare label-retaining cell within iBAT. This study reveals a key requirement for Cdkn1c in the early development of the brown adipose lineages. Importantly, active BAT consumes high amounts of energy to generate body heat, providing a valid explanation for the persistence of thinness in our model and supporting a major role for elevated CDKN1C in SRS.

Early Metabolic Defects in Dexamethasone-Exposed and Undernourished Intrauterine Growth Restricted Rats

Poor fetal growth, also known as intrauterine growth restriction (IUGR), is a worldwide health concern. IUGR is commonly associated with both an increased risk in perinatal mortality and a higher prevalence of developing chronic metabolic diseases later in life. Obesity, type 2 diabetes or metabolic syndrome could result from noxious “metabolic programming.” In order to better understand early alterations involved in metabolic programming, we modeled IUGR rat pups through either prenatal exposure to synthetic glucocorticoid (dams infused with dexamethasone 100 µg/kg/day, DEX) or prenatal undernutrition (dams feeding restricted to 30% of ad libitum intake, UN). Physiological (glucose and insulin tolerance), morphometric (automated tissue image analysis) and transcriptomic (quantitative PCR) approaches were combined during early life of these IUGR pups with a special focus on their endocrine pancreas and adipose tissue development. In the absence of catch-up growth before weaning, DEX and UN IUGR pups both presented basal hyperglycaemia, decreased glucose tolerance, and pancreatic islet atrophy. Other early metabolic defects were model-specific: DEX pups presented decreased insulin sensitivity whereas UN pups exhibited lowered glucose-induced insulin secretion and more marked alterations in gene expression of pancreatic islet and adipose tissue development regulators. In conclusion, these results show that before any catch-up growth, IUGR rats present early physiologic, morphologic and transcriptomic defects, which can be considered as initial mechanistic basis of metabolic programming.

Are compensatory growth and catch-up growth two sides of the same coin?

Compensatory growth refers to an animal’s ability to grow extremely rapidly after it has experienced a period of reduced growth. It is also widely held that the growth trajectories of animals showing compensatory growth converge towards those followed by conspecifics that have experienced favorable growth conditions throughout their lives. In other words, it is often assumed that animals undergoing compensatory growth also show some recovery, and thereby exhibit catch-up growth. This belief has resulted in the terms compensatory growth, recovery growth, and catch-up growth being used as synonyms, and has also created some problems with regard to data analysis and interpretation. Following a discussion of methods of analysis and their limitations, a series of growth simulations is presented to illustrate why the terms should not be used as synonyms. The simulations, based upon the assumption that compensatory growth results in a restoration of body composition (using condition index as a surrogate), show that compensatory growth is not always accompanied by a convergence of growth trajectories. Compensatory growth can occur in the absence of catch-up growth, and the simultaneous observation of compensatory growth and a recovery of body mass is a special combination of events. Further, it is possible for growth trajectories to converge even when animals that have experienced a period of reduced growth do not display compensatory growth. Definitions are proposed that distinguish between the terms compensatory growth, recovery growth, and catch-up growth, and guidelines are given relating to the analysis of the results of fish compensatory growth studies.

Growth Rate of Lung Function in Healthy Preterm Infants

It remains unclear whether premature birth, in the absence of neonatal respiratory disease, results in abnormal growth and development of the lung. We previously reported that a group of healthy infants born at 32-34 weeks' gestation and without respiratory complications had decreased forced expiratory flows and normal forced vital capacities at 2 months of age. Our current study evaluated whether these healthy infants born prematurely exhibited improvement or "catch-up" in their lung function during the second year of life. Longitudinal measurements of forced expiratory flows by the raised volume rapid thoracic compression technique were obtained in the first and the second years of life for infants born prematurely at 32.7 (range, 30-34) weeks' gestation (n = 26) and infants born at full term (n = 24). Healthy infants born prematurely demonstrate decreased forced expiratory flows and normal forced vital capacities in the first and second years of life. In addition, the increases in lung function with growth were similar to full-term infants. Persistently reduced flows in the presence of normal forced vital capacity and the absence of catch-up growth in airway function suggest that premature birth is associated with altered lung development.

Effect of protein-energy malnutrition in early life on the dimensions and bone quality of the adult rat mandible

Morphological and biomechanical features of the mandible are negatively affected by protein-energy malnutrition, whose effects are apparently dependent on the time of life of application. The aim here was to investigate, in neonatal rats nursed by dams put on a protein-free diet to depress milk production and thus create a state of protein-energy malnutrition in the offspring, subsequent growth and long-term effects by analyzing mandibular dimensions and bone quality in adulthood. Pregnant Wistar rats were fed a 20% protein diet (control) or a protein-free diet (malnourished) to obtain normal or subnormal milk production, respectively. After weaning, the offspring (males) were fed a 20% protein diet for 70 days. The dimensions of their excised mandibles were measured directly between anatomical points; the geometry and material quality of mandibular bone were assessed by peripheral quantitative computed tomography. Pups suckling from malnourished dams weighed 49.4% of those suckling from control dams at weaning; the actual difference between control and malnourished pups was 25.1 g, which persisted until day 91 of age, indicating the absence of catch-up growth. As with body size, the mandibular base length, height and area (an index of mandibular size) were significantly smaller in malnourished than control rats at the end of the study. The mandibular cortical area, volumetric cortical bone mineral content and volumetric cortical bone mineral density assessed by peripheral quantitative computed tomography were similar in both groups of rats at the end of the observation period, but there was a significant reduction in the cortical axial moment of inertia in malnourished rats at this time of postnatal life. These findings suggest that catch-up growth was incomplete in rats malnourished during the suckling period and that the adaptation of mandibular bone architecture to body growth was apparently insufficient to attain normal values, thus not allowing complete compensation in mechanical competence at the end of the study because of an inadequate spatial distribution of resistive material through its cross-section rather than qualitative or quantitative impairment of cortical bone.

Intellectual and psychological performance in males born small for gestational age with and without catch-up growth.

Infants born small for gestational age (SGA) have an increased risk of neurologic and intellectual dysfunction. Most of these infants catch up in growth and attain normal height, although some do not. Whether catch-up growth influences intellectual function is not known. To analyze whether intellectual and psychological performance of males in early adulthood are associated with body size at birth or by catch-up growth in height among boys, a population-based cohort was studied. This cohort included all male singletons born without congenital malformations in Sweden from 1973 to 1978 and alive at 18 y (n = 276,033). Information from the Swedish Birth Register was individually linked to the Swedish Conscript Register. Of 254,426 conscripted males, information on intellectual and psychological performance was available for 97% and 91%, respectively. Low birth weight, short birth length, small head circumference at birth, and preterm birth increased the risk of subnormal intellectual and psychological performance. Among SGA-born males, the most important predictor was the absence of catch-up growth. Being born SGA is associated with increased risk of subnormal intellectual and psychological performance. The data strongly support the view that, for males born SGA, it is an advantage to have catch-up growth in length.

Growth hormone during catch-up growth and failure of catch-up growth in rats.

Male Long-Evans rats were fasted or given cortisone injections beginning at 37 days of age in order to produce growth retardation. They were then allowed to recover for periods of up to 28 days. GH concentration was measured in trunk blood plasma of rats decapitated after minimal stress. During the recovery period there was a significant increase in plasma GH in both experimental groups. Organ weight/body weight ratios for liver and heart, protein/tissue, DNA/tissue, and DNA/protein ratios of liver, heart, and skeletal muscle were found to remain normal or to return to normal values during the recovery periods in both experimental groups. DNA content was reduced in both liver and heart at 14 days. At later recovery periods no significant differences from controls were observed. The findings indicate that increased GH release is common to the growth recovery period after both fasting or cortisone treatment. GH concentration in plasma does not correlate with presence or absence of catch-up growth. The organ weight/body weight ratios correlate with previous findings showing prompt return to normal proportions of body weight to tail length in both the cortisone and fast models irrespective of presence or absence of catch-up growth. The results indicate that failure of catch-up growth after cortisone treatment is not the result of decreased pituitary GH secretion. It is probable that multiple factors working in concert are responsible for recovery after transient growth retardation.