Project description:A low total nephron number, which is associated with low birth weight (LBW), may indicate increased susceptibility to early-onset renal diseases in children. However, few studies have assessed renal biopsy findings in LBW children. We examined the relationship between LBW and glomerular density (GD) and/or glomerular volume (GV) in renal biopsy samples as a surrogate for total nephron number.Renal biopsy findings of children of LBW were compared with those of age-matched control subjects of normal birth weight (NBW) who were histopathologically diagnosed with FSGS or minimal change nephrotic syndrome (MCNS) from 1995 to 2011. The GD and GV were estimated on the basis of measurements obtained by computerized image analysis.A total of 31 subjects (mean age 11 years; eight with low birth weight-FSGS [LBW-FSGS], 10 with normal birth weight-FSGS [NBW-FSGS], and 13 with normal birth weight-minimal change nephrotic syndrome [NBW-MCNS]) were analyzed. The mean birth weight of each group was 777 g (629-1000), 3110 g (2888-3358), and 3120 g (2748-3398), respectively (median [25th-75th percentile]). Age, body mass index, BP, and degrees of globally sclerotic glomeruli at biopsy were comparable between the groups. The GD was lower (LBW-FSGS, 1.4±0.6/mm2; NBW-FSGS, 3.3±1.2/mm2; and NBW-MCNS, 3.6±1.1/mm2; P<0.05) and the GV was greater (LBW-FSGS, 4.1 [3.1-5.1]×106µm3; NBW-FSGS, 1.6 [1.5-2.1]×106µm3; and NBW-MCNS, 1.3 [1.1-1.8]×106µm3 [median, (25th-75th percentile)]; P<0.05) in patients with LBW-FSGS than in the other patient groups. The GD showed close positive correlations with birth weight (r=0.48) and gestational age (r=0.54), independent of renal function and degree of global glomerular sclerosis.A low GD together with marked glomerular enlargement characterizes renal biopsy samples of children born with a LBW at an early stage of gestation.
Project description:OBJECTIVE: To evaluate the risk of long term behavioural problems and psychiatric disorders associated with being born with low birth weight. DESIGN/STUDY GROUPS: A population based, controlled follow up study at 11 years of age of 130 low birthweight (LBW) children weighing less than 2000 g at birth who were without major handicaps, and a random sample of 131 normal birthweight (NBW) children born at term weighing over 3000 g. MAIN OUTCOME MEASURES: Validated questionnaires addressing behaviour completed by mothers and teachers and child evaluation by child psychiatrist using a semistructured interview. RESULTS: Behavioural problems, as defined by abnormal scores on more than four of 32 measures, were found in 40% of LBW children compared with 7% of NBW children (odds ratio (OR) 8.2, 95% confidence interval (CI) 3 to 25, p = 0001). A psychiatric disorder was diagnosed in 27% of the LBW children compared with 9% of the NBW children (OR 3.1, 95% CI 1.5 to 6.5, p = 0.001). The LBW children were more often inattentive, had social problems, and low self esteem. None of the pre-, neo-, or peri-natal variables in the LBW group were statistically significant predictors of behavioural outcomes or the presence of psychiatric disorders. Behavioural problems and psychiatric disorders were as common in those with birth weight less than 1500 g as those with birth weight 1500-2000 g. CONCLUSION: An increased risk of behavioural problems and psychiatric disorders persists in LBW adolescents.
Project description:Multiple studies have reported that individuals with low birth weights (LBW, <2500?g) have a lower intelligence quotient (IQ) than those with normal birth weights (NBW, ?2500?g). Based on 57 eligible individual studies including 12,137 participants, we performed a meta-analysis to estimate the association between low birth weight and individuals' IQ scores (IQs). The pooled weight mean difference (WMD) in IQs between NBW and LBW individuals was 10 (95% CI 9.26-11.68). The WMD was stable regardless of age. No publication bias was detected. The mean IQs of the extremely low birth weight (ELBW, <1000?g), very low birth weight (VLBW, 1000-1499?g), moderately low birth weight (MLBW, 1500-2499?g) and NBW individuals were 91, 94, 99 and 104, respectively. Additionally, the WMD in IQs with NBW were 14, 10 and 7 for ELBW, VLBW, and MLBW individuals, respectively. Two studies permitted estimates of the influence of social determinants of health to the discrepancy in IQs, which was 13%. Since IQ is inherited and influenced by environmental factors, parental IQs and other factors contribute to residual confounding of the results. As the conclusion was based on population studies, it may not be applicable to a single individual.
Project description:INTRODUCTION:Low birth weight (LBW, <2500 g) may predict an increased risk of an adverse cardiometabolic profile later in life, but long-term effects in different populations and birth weight strata are still unclear. We explored laboratory markers of cardiometabolic risk in children born with marginally LBW (2000-2500 g). METHODS:This was a prospective longitudinal cohort study including 285 Swedish marginally LBW children and 95 normal birth weight (NBW, 2501-4500 g) controls. At 3.5 and 7 years of age, blood samples for glucose, insulin, homeostatic model assessment for insulin resistance (HOMA-IR), cholesterol, triglycerides, high- and low density lipoprotein (HDL and LDL), apolipoprotein B (ApoB) and apolipoprotein A1 (ApoA1) were assessed and compared between the groups. RESULTS:No significant differences in levels of insulin, HOMA-IR, hs-CRP or blood lipids were observed between marginally LBW and NBW children. At 7 years there was a higher proportion of marginally LBW children with elevated levels of insulin, defined as above the 90th percentile of the control group (21% vs 8.6%, p = 0.038). This association was, however, confounded by maternal ethnicity. In marginally LBW children born small for gestational age (SGA), mean fasting glucose was significantly higher compared to controls (4.7 vs 4.5 mmol/L, p = 0.020). CONCLUSIONS:There were no significant differences in insulin, insulin resistance, hs-CRP or blood lipids between the marginally LBW children and controls. The subgroup of marginally LBW children born SGA may present early signs of glucose imbalance already at school age.
Project description:BACKGROUND:The effectiveness of rotavirus vaccines in low and very low birth weight infants (LBW and VLBW) weighing <2500 and <1500 g at birth, respectively, a high-risk population for severe rotavirus gastroenteritis, has not been well examined. METHODS:We analyzed inpatient commercial claims data for US children <5 years of age from July 2001 to June 2015. Claims for acute gastroenteritis (AGE) and rotavirus-coded hospitalizations and LBW, VLBW and normal birth weight (NBW) infants were identified. Receipt of rotavirus vaccine was defined using Current Procedural Terminology. Rate reductions were calculated using prevaccine (2001-2006) and postvaccine (2007-2015) annual AGE and rotavirus hospitalization rates. RESULTS:As of December 2014, rotavirus vaccine coverage was 87%, 82% and 64%, for NBW, LBW and VLBW infants, respectively. For 2014-2015, among NBW, LBW and VLBW children <5 years of age, AGE hospitalization rate reductions relative to the prevaccine introduction period were 60% [95% confidence interval (CI): 58%-61%], 64% (95% CI: 57%-70%) and 55% (95% CI: 39%-67%), respectively. Rotavirus hospitalization rate reductions were 91% (95% CI: 90%-92%), 98% (95% CI: 93%-100%) and 93% (95% CI: 70%-98%). Rotavirus vaccines resulted in a 62% (95% CI: 51%-71%), 72% (95% CI: 44%-86%) and 71% (95% CI: 7%-91%) reduction in AGE hospitalization rates comparing vaccinated versus unvaccinated NBW, LBW and VLBW children 3-23 months of age, respectively. CONCLUSIONS:Rotavirus vaccines have substantially reduced AGE hospitalizations and are highly effective in LBW and VLBW infants, similar to NBW infants. Efforts to improve vaccination coverage, particularly in LBW and VLBW infants, should continue.
Project description:Subjects born with low birth weight (LBW) display a more energy-conserving response to fasting compared with normal birth weight (NBW) subjects. However, the molecular mechanisms explaining these metabolic differences remain unknown. Environmental influences may dynamically affect epigenetic marks, also in postnatal life. Here, we aimed to study the effects of short-term fasting on leptin (LEP) and adiponectin (ADIPOQ) DNA methylation and gene expression in subcutaneous adipose tissue (SAT) from subjects with LBW and NBW.Twenty-one young LBW men and 18 matched NBW controls were studied during 36 h fasting. Eight subjects from each group completed a control study (overnight fast). We analyzed SAT LEP and ADIPOQ methylation (Epityper MassARRAY), gene expression (q-PCR), and adipokine plasma levels.After overnight fast (control study), LEP and ADIPOQ DNA methylation levels were higher in LBW compared to those in NBW subjects (p???0.03) and increased with 36 h fasting in NBW subjects only (p???0.06). Both LEP and ADIPOQ methylation levels were positively associated with total body fat percentage (p???0.05). Plasma leptin levels were higher in LBW versus NBW subjects after overnight fasting (p?=?0.04) and decreased more than threefold in both groups after 36 h fasting (p???0.0001).This is the first study to demonstrate that fasting induces changes in DNA methylation. This was shown in LEP and ADIPOQ promoters in SAT among NBW but not LBW subjects. The altered epigenetic flexibility in LBW subjects might contribute to their differential response to fasting, adipokine levels, and increased risk of metabolic disease.
Project description:The aim of this study was to determine how maternal undernutrition during pregnancy and offspring birth-weight can affect the postnatal development of offspring under farm conditions, which may lead to consequences in its meat and carcass quality. The current study involved a total of 80 litters from Iberian sows fed a diet fulfilling daily requirements (n?=?47; control) or providing 70% daily requirements (n?=?33; underfed) from d 38 to d 90 of gestation when fetal tissue development begins. After birth, piglets born live were classified as low birth-weight (LBW; <?1 kg) and normal birth-weight (NBW; ?1 kg). During the growing phase, 240 control and 230 underfed pigs (50% males and females) distributed by BW category and sex were studied until the slaughter.At birth and weaning, there were significant differences in all morphological measures and weight between NBW and LBW piglets as expected (P?<?0.0005), but few effects of the gestational feed restriction. During the growing phase, NBW pigs continued with higher weight than LBW pigs on all the days of evaluation (P?<?0.05), even though control-LBW-females and LBW-males showed a catch-up growth. However, underfed pigs showed slower growth and higher feed conversion ratio than control pigs (P?<?0.0001) at 215 days old. Moreover, the average daily weight gain (ADWG) for the overall period was greater for NBW, male and control pigs than for their LBW, female and underfed pigs (P?<?0.0001, P<?0.0005 and P<?0.05, respectively) and NBW pigs were slaughtered at a younger age than LBW pigs (P?<?0.0001). After slaughtering, control pigs also had higher carcass yield and backfat depth than underfed pigs (P?<?0.0005) and the maternal nutritional effect caused main changes in the polar lipid fraction of liver and loin. The fatty acid composition of loin in control pigs had higher C18:1n-9 and n-3 FA concentrations, as well as lower ?n-6/?n-3 ratio, than in underfed pigs (P?<?0.005).In brief, results showed that the effects of maternal nutritional restriction appeared and increased with offspring age, causing worse developmental patterns for underfed pigs than for control pigs.
Project description:The low birth weight (LBW) individual had greater risk of developing metabolic dysfunction in adulthood. The aim of this study was to test whether the LBW individual is more prone to glucose intolerance on a high nutrient dense (HND) diet, and to investigate the associated hypothalamic gene expressions using pigs as model. The intake of digestible energy intake, if calculated on a body weight basis, was greater in LBW pigs than that of normal birth weight (NBW) pigs. The LBW pigs fed the HND diet had greater digestible energy intake than those fed the NND diet at adulthood, which did not occur for NBW pigs. Notably, up-regulated hypothalamic toll-like receptor 4, interleukin 6 and phospho-NF?B p65 expressions, and the altered expressions of hypothalamic leptin receptor, suppressor of cytokine signaling 3, agouti-related protein and proopiomelanocortin predicted the overconsumption of energy intake and development of glucose intolerance in LBW pigs fed the HND diet. Collectively, pigs born with LBW had a distinct hypothalamic leptin signaling to a high nutrient dense diet, which contributed to greater energy intake and glucose intolerance.
Project description:BACKGROUND:Uric acid has been identified as an important factor in the development of hypertension. If low birth weight (LBW) combined with catch-up growth (CUG) is associated with continuously elevated serum uric acid levels (SUA) level trajectories, LBW children who experience CUG may have an increased risk of hypertension later in life. Therefore, this cohort study analyzed longitudinal trends in SUA levels and changes in blood pressure in relation to pre- and postnatal growth over an extended follow-up period. METHODS:This prospective cohort study of 364 children from the Ewha Birth and Growth Cohort assessed the effects of pre- and postnatal growth status on SUA at 3, 5, and 7?years of age using a linear mixed model and the change in blood pressure over the 7-year follow-up period using a generalized linear model (analysis of covariance). CUG was defined as a change in weight (between birth and age 3) with a z-score?>?0.67 for LBW subjects. The multivariate model considered sex, gestational age, and uric acid, height, and weight at 3?years of age. RESULTS:Children with LBW and CUG had higher SUA for the first 7?years of life compared to the normal birth weight group. This trend was particularly evident when comparing LBW children at term to children with normal birth weight. Within the group with LBW at term, children with greater CUG had higher SUA than children with normal birth weight, and this difference increased with age. Changes in the systolic blood pressure between 3 and 7?years of age were higher by 7.9?mmHg in children who experienced LBW and CUG compared with those who had a normal birth weight after adjusting for sex, gestational age, and height, weight, and uric acid at 3?years of age (p-value?=?0.08). CONCLUSIONS:The uric acid levels and changes in systolic blood pressure were consistently higher among LBW children who experienced CUG compared with NBW children for the first 7?years of life. LBW children who experienced greater weight gain from birth to age 3 had even higher uric acid levels compared with NBW children.
Project description:Recent evidence suggests that adverse prenatal development alters physiological response to physical activity, but longitudinal epidemiologic evidence is scant. This study tested the hypothesis that lower physical activity during adolescence and young adulthood is more strongly associated with later cardiovascular disease (CVD) risk and diabetes or prediabetes (DM/PDM) in women and men who were born with high or low birth weight (HBW, LBW), compared to normal birth weight (NBW). We analyzed data from the National Longitudinal Study of Adolescent to Adult Health, a cohort study of US adolescents followed into adulthood (1994-2009). Using sex-stratified multivariable regression, 30-year CVD risk score (calculated using objective measures; n=12,775) and prevalent DM/PDM (n=15,138) at 24-32years of age were each modeled as a function of birth weight category, self-reported moderate-to-vigorous physical activity frequency in adolescence (MVPA1) and young adulthood (MVPA3), and MVPA-birth weight interactions. Greater MVPA1 was associated with lower 30-year CVD risk score and DM/PDM risk in HBW women but not NBW or LBW women. Associations between MVPA1 and 30-year CVD risk or DM/PDM were not modified by HBW in men; or by LBW in women or men. Additionally, birth weight did not modify estimated effects of MVPA3. Findings suggest that frequent MVPA in adolescence may be a particularly important cardiometabolic risk reduction strategy in girls born HBW; however, we found no evidence that birth weight and MVPA interact in cardiometabolic disease risk in men, for MVPA in adulthood, or for LBW.