Postnatal Growth Restriction Research Articles

Der Stellenwert von Muttermilch für die gesunde Entwicklung Frühgeborener – aktuelle Übersicht und praktische Aspekte

Over the last decades the immense benefit of human milk on the nutrition of preterm infants has become increasingly evident. Research has confirmed that human milk has significant advantages for the preterm infant in terms of host defense, gastrointestinal development and maturation, neurological development, reduction of necrotizing enterocolitis, retinopathy of prematurity and chronic lung disease as well as mental and physical benefits for the mother. Computing these factors into ahealth-cost-benefit equation, positive economic consequences for anational public health system were demonstrated.Therefore, international feeding guidelines recommend human milk to be the first choice for preterm infants, the primary source being the infant's mother. The first alternative is milk from an established donor milk bank. To meet the unique nutritional demands of preterm infants and to avoid postnatal growth restriction, human milk must be fortified with additional micro- and macronutrients. Concerns about microbial colonization and contamination and hygienic aspects concerning milk handling need to be addressed when feeding human milk to preterm infants.Early initiation and maintenance of lactation is challenging for mothers of preterm infants and their caregivers. Providing lactation support from educated staff, optimal nursing environments, and the positive attitude of an experienced NICU (neonatal intensive care unit) team will contribute to successful lactation and breastfeeding even beyond discharge of the infant.

Dose-response Relationship Between Donor Human Milk, Mother's Own Milk, Preterm Formula, and Neonatal Growth Outcomes.

A dose-response relationship between proportions of donor human milk (DHM) intake and in-neonatal intensive care unit (in-NICU) growth rates, if any, remains poorly defined. Objective was to evaluate interrelationships between percentages of DHM, mother's own milk (MOM), and preterm formula (PF) intake and neonatal growth parameters at 36 weeks postmenstrual age or NICU discharge. Infants eligible for this single-center retrospective study were inborn at ≤32 weeks gestation or ≤1800 g, stayed in the NICU for ≥7 days, and received enteral nutrition consisting of human milk fortified with Enfamil human milk fortifier acidified liquid. Study exposures were defined as 10% increments in the total volumetric proportions of infant diet provided as MOM, DHM, or PF. Outcomes were growth parameters at 36 weeks postmenstrual age or NICU discharge. Multivariable linear regression modeled the adjusted additive effect of infant diet on individual growth parameters. A total of 314 infants records were eligible for analysis. Using MOM as reference, the adjusted mean growth velocity for weight significantly decreased by 0.17 g · kg · day for every 10% increase in DHM intake, but did not vary with PF intake. The adjusted mean change in weight z score significantly decreased with increasing proportion of DHM intake but significantly improved with increasing PF intake. The adjusted mean head circumference velocity was significantly decreased by 0.01 cm/wk for every 10% increase in DHM intake, in reference to MOM, but did not vary with PF intake. Neither proportion of DHM nor PF intake was associated with length velocity. When DHM and MOM are fortified interchangeably, preterm infants receiving incremental amounts of DHM are at increased risk of postnatal growth restriction. The dose-response relationship between DHM, MOM, and PF and long-term growth and neurodevelopmental outcomes warrants further research.

Timing of gestational exposure to Zika virus is associated with postnatal growth restriction in a murine model

Vertical transmission of Zika virus leads to infection of neuroprogenitor cells and destruction of brain parenchyma. Recent evidence suggests that the timing of infection as well as host factors may affect vertical transmission. As a result, congenital Zika virus infection may only become clinically apparent in the postnatal period. We sought to develop an outbred mouse model of Zika virus vertical transmission to determine if the timing of gestational Zika virus exposure yields phenotypic differences at birth and through adolescence. We hypothesized that later gestational inoculations would only become apparent in adolescence. To better recapitulate human exposures, timed pregnant Swiss-Webster dams (n= 15) were subcutaneously inoculated with 1× 104 plaque-forming units of first passage contemporary Zika virus HN16 strain or a mock injection on embryonic day 4, 8, or 12 with bioactive antiinterferon alpha receptor antibody administered in days preceding and proceeding inoculation. The antibody was given to prevent the robust type I interferon signaling cascade that make mice inherently resistant to Zika virus infection. At birth and adolescence (6 weeks of age) offspring were assessed for growth, brain weight, and biparietal head diameters, and Zika virus viral levels by reverse transcription-polymerase chain reaction or in situ hybridization. Pups of Zika virus-infected dams infected at embryonic days 4 and 8 but not 12 were growth restricted (P < .003). Brain weights were significantly smaller at birth (P= .01) for embryonic day 8 Zika virus-exposed offspring. At 6 weeks of age, biparietal diameters were smaller for all Zika virus-exposed males and females (P < .05), with embryonic day 8-exposed males smallest by biparietal diameter and growth-restriction measurements (weight >2 SD, P= .0007). All pups and adolescent mice were assessed for Zika virus infection by reverse transcription-polymerase chain reaction. Analysis of all underweight pups reveled 1 to be positive for neuronal Zika virus infection by in situ hybridization, while a second moribund animal was diffusely positive at 8 days of age by Zika virus infectivity throughout the brain, kidneys, and intestine. These findings demonstrate that postnatal effects of infection occurring at single time points continue to be detrimental to offspring in the postnatal period in a subset of littermates and subject to a window of gestational susceptibility coinciding with placentation. This model recapitulates frequently encountered clinical scenarios in nonendemic regions, including the majority of the United States, where travel-related exposure occurs in short and well-defined windows of gestation. Our low rate of infection and relatively rare evidence of congenital Zika syndrome parallels human population-based data.

Early prenatal alcohol exposure alters imprinted gene expression in placenta and embryo in a mouse model.

Prenatal alcohol exposure (PAE) can harm the embryonic development and cause life-long consequences in offspring’s health. To clarify the molecular mechanisms of PAE we have used a mouse model of early alcohol exposure, which is based on maternal ad libitum ingestion of 10% (v/v) ethanol for the first eight days of gestation (GD 0.5–8.5). Owing to the detected postnatal growth-restricted phenotype in the offspring of this mouse model and both prenatal and postnatal growth restriction in alcohol-exposed humans, we focused on imprinted genes Insulin-like growth factor 2 (Igf2), H19, Small Nuclear Ribonucleoprotein Polypeptide N (Snrpn) and Paternally expressed gene 3 (Peg3), which all are known to be involved in embryonic and placental growth and development. We studied the effects of alcohol on DNA methylation level at the Igf2/H19 imprinting control region (ICR), Igf2 differentially methylated region 1, Snrpn ICR and Peg3 ICR in 9.5 embryonic days old (E9.5) embryos and placentas by using MassARRAY EpiTYPER. To determine alcohol-induced alterations globally, we also examined methylation in long interspersed nuclear elements (Line-1) in E9.5 placentas. We did not observe any significant alcohol-induced changes in DNA methylation levels. We explored effects of PAE on gene expression of E9.5 embryos as well as E9.5 and E16.5 placentas by using quantitative PCR. The expression of growth promoter gene Igf2 was decreased in the alcohol-exposed E9.5 and E16.5 placentas. The expression of negative growth controller H19 was significantly increased in the alcohol-exposed E9.5 embryos compared to controls, and conversely, a trend of decreased expression in alcohol-exposed E9.5 and E16.5 placentas were observed. Furthermore, increased Snrpn expression in alcohol-exposed E9.5 embryos was also detected. Our study indicates that albeit no alterations in the DNA methylation levels of studied sequences were detected by EpiTYPER, early PAE can affect the expression of imprinted genes in both developing embryo and placenta.

Statewide Initiative to Reduce Postnatal Growth Restriction among Infants

To decrease the incidence of postnatal growth restriction, defined as discharge weight <10th percentile for postmenstrual age, among preterm infants cared for in New York State Regional Perinatal Centers. The quality improvement cohort consisted of infants <31 weeks of gestation admitted to a New York State Regional Perinatal Center within 48 hours of birth who survived to hospital discharge. Using quality improvement principles from the Institute for Healthcare Improvement and experience derived from successfully reducing central line-associated blood stream infections statewide, the New York State Perinatal Quality Collaborative sought to improve neonatal growth by adopting better nutritional practices identified through literature review and collaborative learning. New York State Regional Perinatal Center neonatologists were surveyed to characterize practice changes during the project. The primary outcome-the incidence of postnatal growth restriction-was compared across the study period from baseline (2010) to the final (2013) years of the project. Secondary outcomes included differences in z-score between birth and discharge weights and head circumferences. We achieved a 19% reduction, from 32.6% to 26.3%, in postnatal growth restriction before hospital discharge. Reductions in the difference in z-score between birth and discharge weights were significant, and differences in z-score between birth and discharge head circumference approached significance. In survey data, regional perinatal center neonatologists targeted change in initiation of feedings, earlier breast milk fortification, and evaluation of feeding tolerance. Statewide collaborative quality improvement can achieve significant improvement in neonatal growth outcomes that, in other studies, have been associated with improved neurodevelopment in later infancy.

Effect of Eicosapentaenoic Acid and Docosahexaenoic Acid on Myogenesis and Mitochondrial Biosynthesis during Murine Skeletal Muscle Cell Differentiation.

Polyunsaturated fatty acids are important nutrients for human health, especially omega-3 fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which have been found to play positive roles in the prevention of various diseases. However, previous studies have reported that excessive omega-3 fatty acids supplement during pregnancy caused side effects such as slower neural transmission times and postnatal growth restriction. In this study, we investigated the effect of EPA and DHA on mitochondrial function and gene expression in C2C12 myoblasts during skeletal muscle differentiation. C2C12 myoblasts were cultured to confluency and then treated with differentiation medium that contained fatty acids (50-µM EPA and DHA). After 72 h of myogenic differentiation, mRNA was collected, and gene expression was analyzed by real-time PCR. Microscopy was used to examine cell morphology following treatment with fatty acids. The effect of EPA and DHA on cellular oxygen consumption was measured using a Seahorse XF24 Analyzer. Cells treated with fatty acids had fewer myotubes formed (P ≤ 0.05) compared with control cells. The expression of the genes related to myogenesis was significantly lower (P ≤ 0.05) in cells treated with fatty acids, compared with control cells. Genes associated with adipogenesis had higher (P ≤ 0.05) expression after treatment with fatty acids. Also, the mitochondrial biogenesis decreased with lower (P ≤ 0.05) gene expression and lower (P ≤ 0.05) mtDNA/nDNA ratio in cells treated with fatty acids compared with control cells. However, the expression of genes related to peroxisome biosynthesis was higher (P ≤ 0.05) in cells treated with fatty acids. Moreover, fatty-acid treatment reduced (P ≤ 0.05) oxygen consumption rate under oligomycin-inhibited (reflecting proton leak) and uncoupled conditions. Our data imply that fatty acids might reduce myogenesis and increase adipogenesis in myotube formation. Fatty acids may also decrease cell metabolism by reducing mitochondrial biogenesis as well as respiration rate. This study suggests that the maternal overdosage of EPA and DHA may influence fetal muscle development, increase intramuscular adipose tissue deposition in offspring, and have a long-term effect on the development of metabolic diseases such as obesity and diabetes in adult offspring.

The associations between adult body composition and abdominal adiposity outcomes, and relative weight gain and linear growth from birth to age 22 in the Birth to Twenty Plus cohort, South Africa.

BackgroundThe growing prevalence of overweight and obesity in low- or middle-income countries precipitates the need to examine early life predictors of adiposity.ObjectivesTo examine growth trajectories from birth, and associations with adult body composition in the Birth to Twenty Plus Cohort, Soweto, South Africa.MethodsComplete data at year 22 was available for 1088 participants (536 males and 537 females). Conditional weight and height indices were generated indicative of relative rate of growth between years 0–2, 2–5, 5–8, 8–18, and 18–22. Whole body composition was measured at year 22 (range 21–25 years) using dual energy x-ray absorptiometry (DXA). Total fat free soft tissue mass (FFSTM), fat mass, and abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were recorded.ResultsBirth weight was positively associated with FFSTM and fat mass at year 22 (β = 0.11, p<0.01 and β = 0.10, p<0.01 respectively). Relative weight gain from birth to year 22 was positively associated with FFSTM, fat mass, VAT, and SAT at year 22. Relative linear growth from birth to year 22 was positively associated with FFSTM at year 22. Relative linear growth from birth to year 2 was positively associated with VAT at year 22. Being born small for gestational age and being stunted at age 2 years were inversely associated with FFSTM at year 22.ConclusionsThe importance of optimal birth weight and growth tempos during early life for later life body composition, and the detrimental effects of pre- and postnatal growth restriction are clear; yet contemporary weight-gain most strongly predicted adult body composition. Thus interventions should target body composition trajectories during childhood and prevent excessive weight gain in early adulthood.

X-linked Cornelia de Lange Syndrome - Remembering a dysmorphology case in Neonatology

Cornelia de Lange Syndrome is a rare disease characterized by prenatal and postnatal growth restriction, mild to severe intellectual disability, characteristic facial dysmorphisms, and other anomalies. The diagnosis is based on clinical criteria or on detection of a pathological variant in one of the five disease causing genes - NIPBL, RAD21, SMC3, HDAC8 or SMC1A. The prognosis may depend on the precocity of malformations’ treatment, early institution of therapies and careful follow-up of possible complications. We present a case of Cornelia de Lange Syndrome whose clinical diagnosis was made during perinatal period due to a suspicious prenatal history followed by characteristic dysmorphisms and anomalies. The molecular confirmation was only possible after two years, revealing a pathogenic variant in SMC1A gene, located at X chromosome, which occurred as de novo event. The clinical suspicion during perinatal period made it possible to start an earlier multidisciplinary follow-up and to offer a better management for the child and a proper genetic counseling for the parents.

Association Between the 7-Day Moving Average for Nutrition and Growth in Very Low Birth Weight Infants.

Very low birth weight (VLBW) infants remain at risk for postnatal growth restriction. Clinicians may have difficulty identifying growth patterns resulting from nutrition interventions, impeding prompt management changes intended to increase growth velocity. This study aimed to quantify the association between growth and nutrition intake through 7-day moving averages (SDMAs). The first 6 weeks of daily nutrition intake and growth measurements were collected from VLBW infants admitted to a level 4 neonatal intensive care unit (2011-2014). The association between SDMA for energy and macronutrients and subsequent 7-day growth velocities for weight, length, and head circumference were determined using mixed effects linear regression. Analyses were adjusted for fluid intake, infant characteristics, and comorbid conditions. Detailed enteral and parenteral caloric provisions were ascertained for 115 infants (n = 4643 patient-days). Each 10-kcal/kg/d increase over 7 days was independently associated with increased weight (1.7 g/kg/d), length (0.4 mm/wk), and head circumference (0.9 mm/wk; P < .001, for weight and head circumference; P = .041 for length). Each 1 g/kg/d macronutrient increase was also associated with increased weight (protein, P = .027; fat and carbohydrates, P < .001), increased length (fat, P = .032), and increased head circumference (fat and carbohydrates, P < .001). The SDMA identifies clinically meaningful associations among total energy, macronutrient dosing, and growth in VLBW infants. Whether SDMA is a clinically useful tool for providing clinicians with prompt feedback to improve growth warrants further attention.

Postnatal growth at hospital discharge in extremely premature newborns in Spain

Postnatal growth restriction is considered a universal problem in extremely premature infants (EPI), and causes great concern due to the possible relationship between nutrition, sub-optimal postnatal growth, and neurodevelopment delay. To describe the weight gain in EPI and to determine the changes in the length and head circumference (HC) at hospital discharge in survivors. The study included 4,520 Caucasian EPI from single pregnancies and without severe malformations, born in the centres participating in the Spanish SEN1500 network (2002-2011). The weight was recorded at birth, 28 days, 36 weeks post-menstrual age (PMA), and at discharge. The length and HC were measured at birth and at discharge. The rate of weight gain (exponential method) was 8.0g/kg/d (birth - 28 days); 14.3g/kg/d (28 days - 36 weeks); and 11.7g/kg/d (36 weeks - discharge). At discharge, postnatal growth restriction was greater for length (z-score between -1.78 and -2.42, depending on GA), followed by weight (-1.67 to -1.79), and HC (-0.69 to -0.81). Weight gain in the first weeks after birth is slow in EPI, and they exhibit an almost universal postnatal growth restriction that involves mainly length and weight. In addition to weight, a close control of longitudinal growth and HC are essential for nutritional assessment and detection of patients at risk for poor growth and neurodevelopment after hospital discharge.

Postnatal growth at hospital discharge in extremely premature newborns in Spain

Abstract Introduction Postnatal growth restriction is considered a universal problem in extremely premature infants (EPI), and causes great concern due to the possible relationship between nutrition, sub-optimal postnatal growth, and neurodevelopment delay. Objectives To describe the weight gain in EPI and to determine the changes in the length and head circumference (HC) at hospital discharge in survivors. Patients and methods The study included 4520 Caucasian EPI from single pregnancies and without severe malformations, born in the centres participating in the Spanish SEN1500 network (2002–2011). The weight was recorded at birth, 28 days, 36 weeks post-menstrual age (PMA), and at discharge. The length and HC were measured at birth and at discharge. Results The rate of weight gain (exponential method) was 8.0 g/kg/day (birth to 28 days); 14.3 g/kg/day (28 days to 36 weeks); and 11.7 g/kg/day (36 weeks to discharge). At discharge, postnatal growth restriction was greater for length (z-score between −1.78 and −2.42, depending on GA), followed by weight (−1.67 to −1.79), and HC (−0.69 to −0.81). Conclusions Weight gain in the first weeks after birth is slow in EPI, and they exhibit an almost universal postnatal growth restriction that involves mainly length and weight. In addition to weight, a close control of longitudinal growth and HC are essential for nutritional assessment and detection of patients at risk for poor growth and neurodevelopment after hospital discharge.

Mosaic UPD(7q)mat in a patient with silver Russell syndrome

BackgroundSilver-Russell syndrome (SRS) is one of the imprinting disorders characterized by prenatal and postnatal growth restriction, relative macrocephaly, body asymmetry and characteristic facial features. ~ 10% of SRS cases are known to be associated with maternal uniparental disomy of chromosome 7 (UPD(7)mat). Mosaic maternal segmental UPD of 7q (UPD(7q)mat) is very rare, had only been described in one case before.Case presentationWe reported a second case of mosaic segmental UPD involving 7q. The patient presented with dysmorphic features including thin and short stature, triangular face, moderate protruding forehead, relative macrocephaly, fifth toe clinodactyly and irregular teeth, meeting the clinical diagnosed criteria of SRS. This case indicated that ~ 80% of mosaic UPD(7q)mat lead to the manifestation of main phenotypes of Silver-Russell syndrome.ConclusionsOur case support the notion that there are genes control postnatal growth on long arm of chromosome 7 and indicate that ~ 80% of UPD(7q)mat mosaicism level was contributed to the SRS phenotype.

An essential role for IGF2 in cartilage development and glucose metabolism during postnatal long bone growth.

Postnatal bone growth involves a dramatic increase in length and girth. Intriguingly, this period of growth is independent of growth hormone and the underlying mechanism is poorly understood. Recently, an IGF2 mutation was identified in humans with early postnatal growth restriction. Here, we show that IGF2 is essential for longitudinal and appositional murine postnatal bone development, which involves proper timing of chondrocyte maturation and perichondrial cell differentiation and survival. Importantly, the Igf2 null mouse model does not represent a simple delay of growth but instead uncoordinated growth plate development. Furthermore, biochemical and two-photon imaging analyses identified elevated and imbalanced glucose metabolism in the Igf2 null mouse. Attenuation of glycolysis rescued the mutant phenotype of premature cartilage maturation, thereby indicating that IGF2 controls bone growth by regulating glucose metabolism in chondrocytes. This work links glucose metabolism with cartilage development and provides insight into the fundamental understanding of human growth abnormalities.

Genetic disruption of the oncogenic HMGA2\u2013PLAG1\u2013IGF2 pathway causes fetal growth restriction

PurposeFetal growth is a complex process involving maternal, placental and fetal factors. The etiology of fetal growth retardation remains unknown in many cases. The aim of this study is to identify novel human mutations and genes related to Silver–Russell syndrome (SRS), a syndromic form of fetal growth retardation, usually caused by epigenetic downregulation of the potent fetal growth factor IGF2.MethodsWhole-exome sequencing was carried out on members of an SRS familial case. The candidate gene from the familial case and two other genes were screened by targeted high-throughput sequencing in a large cohort of suspected SRS patients. Functional experiments were then used to link these genes into a regulatory pathway.ResultsWe report the first mutations of the PLAG1 gene in humans, as well as new mutations in HMGA2 and IGF2 in six sporadic and/or familial cases of SRS. We demonstrate that HMGA2 regulates IGF2 expression through PLAG1 and in a PLAG1-independent manner.ConclusionGenetic defects of the HMGA2–PLAG1–IGF2 pathway can lead to fetal and postnatal growth restriction, highlighting the role of this oncogenic pathway in the fine regulation of physiological fetal/postnatal growth. This work defines new genetic causes of SRS, important for genetic counseling.

Imaging in cutis laxa syndrome caused by a dominant negative ALDH18A1 mutation, with hypotheses for intracranial vascular tortuosity andwide perivascular spaces.

The autosomal dominant progeroid form of cutis laxa is a recently identified multiple congenital anomaly disorder characterized by thin, wrinkled skin, a progeroid appearance, intra-uterine growth retardation, postnatal growth restriction, psychomotor developmental delay, microcephaly, cataract, hypotonia and contractures. De novo heterozygous mutations in ALDH18A1 have been described in this condition. We present neuroimaging abnormalities in three patients. One patient had intracranial arterial and venous tortuosity, widened ventricular and extra-axial cerebrospinal fluid (CSF) spaces, wide perivascular spaces and increased T2 signal intensity in the cerebral white matter over time. The second patient had vascular tortuosity. The third patient had prominent ventricular and extra-axial cerebrospinal fluid (CSF) spaces on CT. We propose an embryological mechanism for the development of intracranial vascular tortuosity and discuss the anatomical basis of wide perivascular spaces in relation to this syndrome. Although we do not know the clinical implications of these cerebral vascular anomalies, we suggest inclusion of neuroimaging in the baseline evaluation of these patients.

Genome-wide analysis of differential DNA methylation in Silver-Russell syndrome.

Silver-Russell Syndrome (SRS) is clinically heterogeneous disorder characterized by low birth weight, postnatal growth restriction, and variable dysmorphic features. Current evidence strongly implicates imprinted genes as an important etiology of SRS. Although almost half of the patients showed DNA hypomethylation at the H19/IGF2 imprinted domain, and approximately 7%-10% of SRS patients have maternal uniparental disomy of chromosome 7 (UPD (7) mat); the rest of the SRS patients shows unknown etiology. In this study, we investigate whether there are further DNA methylation defects in SRS patients. We measured DNA methylation in seven SRS patients and five controls at more than 485,000 CpG sites using DNA methylation microarrays. We analyzed methylation changes genome-wide and identified the differentially methylated regions (DMRs) using bisulfite sequencing and digital PCR. Our analysis identifies epimutations at the previously characterized domains of H19/IGF2, providing proof of principle that our methodology can detect the changes in DNA methylation at imprinted loci. In addition, our results showed a novel SRS associated imprinted gene OSBPL5 located on chromosome 11p14 with the probe cg25963939, which is hypomethylated in 4/7 patients (P=0.023, β=-0.243). We also report DMRs in other genes including TGFβ3, HSF1, GAP43, NOTCH4 and MYH14. These DMRs were found to be associated with SRS using GO pathway analysis. In this study, we identified the probe cg25963939, located at the 5'UTR of imprinted gene OSBPL5, as a novel DMR that is associated with SRS. This finding provides new insights into the mechanism of SRS etiology and aid the further stratification of SRS patients by molecular phenotypes.

Neonatal high protein intake enhances neonatal growth without significant adverse renal effects in spontaneous IUGR piglets.

In humans, early high protein (HP) intake has been recommended to prevent postnatal growth restriction and complications of intrauterine growth restriction (IUGR). However, the impact of such a strategy on the kidneys remains unknown, while significant renal hypertrophy, proteinuria, and glomerular sclerosis have been demonstrated in few experimental studies. The objective of this study was to evaluate the effects of a neonatal HP formula on renal structure in IUGR piglets. Spontaneous IUGR piglets were randomly allocated to normal protein (NP, n = 10) formula or to HP formula (+50% protein content, n = 10) up to day 28 after birth. Body weight, body composition, renal functions, and structure were assessed at the end of the neonatal period. While birth weights were similar, 28‐day‐old HP piglets were 18% heavier than NP piglets (P < 0.01). Carcass protein content was 22% higher in HP than in NP offspring (P < 0.01). Despite a HP intake, kidney weight and glomerular fibrosis were unaltered in HP piglets. Only a 20% increase in glomerular volume was noted in HP piglets (P < 0.05) and restricted to the inner cortical area nephrons (P = 0.03). Plasma urea/creatinine ratio and proteinuria were unchanged in HP piglets. In conclusion, neonatal HP feeding in IUGR piglets significantly enhanced neonatal growth and tissue protein deposition but mildly affected glomerular volume. It can be speculated that a sustained tissue protein anabolism in response to HP intake have limited single nephron glomerular hyperfiltration.

Protective effect of maternal uteroplacental insufficiency on oxygen-induced retinopathy in offspring: removing bias of premature birth

To address the hypothesis that maternal uteroplacental insufficiency (UPI) increases severity of retinopathy of prematurity, we developed a composite rat model of UPI and oxygen-fluctuations and removed premature birth as a confounding factor. Timed-pregnant Sprague-Dawley dams underwent bilateral uterine artery ligation or anesthesia (control) at e19.5. Full-term pups developed in room air (RA) or an oxygen-induced retinopathy (OIR) model. Isolectin-stained retinal flat-mounts were analyzed for percent of areas of avascular/total retina (AVA) and of intravitreal neovascular/total retina (IVNV). Pup weights and serum and mRNA of liver and kidney VEGF, IGF-1, and erythropoietin (EPO) were determined. Multivariable mixed effects linear regressions and Pearson correlations were performed using STATA14. Postnatal growth restriction occurred in pups in UPI/RA, but not in UPI/OIR. Weight gain was similar between UPI/OIR and control/OIR pups. AVA was reduced and a trend toward reduced IVNV was seen in UPI/OIR compared to control/OIR. No difference in birth weights of UPI/OIR vs. control/OIR pups occurred. Serum and renal IGF-1 and EPO were significantly increased in UPI/OIR compared to control/OIR pups. In the absence of prematurity, UPI increased angiogenic factors in association with reduced OIR severity, suggesting that ischemia from UPI could yield protective angiogenic effects by offspring.

Metabolic perturbations of postnatal growth restriction and hyperoxia-induced pulmonary hypertension in a bronchopulmonary dysplasia model

Introduction Neonatal pulmonary hypertension (PH) is a common manifestation of bronchopulmonary dysplasia (BPD) and contributes to increased morbidity and mortality of preterm birth. Postnatal growth restriction (PNGR) and hyperoxia are independent contributors to PH development, as indicated by our previous work in a rat model of BPD.

IGF-I and relation to growth in infancy and early childhood in very-low-birth-weight infants and term born infants.

BackgroundIn very-low-birth-weight infants IGF-I plays an important role in postnatal growth restriction and is probably also involved in growth restriction in childhood. We compared IGF-I and its relation to growth in early childhood in very-low-birth-weight infants and term appropriate for gestational age born infants.MethodsWe included 41 very-low-birth-weight and 64 term infants. Anthropometry was performed at all visits to the outpatient clinic. IGF-I and insulin were measured in blood samples taken at 6 months and 2 years corrected age (very-low-birth-weight children) and at 3 months, 1 and 2 years (term children).ResultsOver the first 2 years of life growth parameters are lower in very-low-birth-weight children compared to term children, but the difference in length decreases significantly. During the first 2 years of life IGF-I is higher in very-low-birth-weight children compared to term children. In both groups there is a significant relationship between IGF-I and (change in) length and weight over the first 2 years of life and between insulin and change in total body fat.ConclusionsConsidering the relation of IGF-I to growth and the decrease in difference in length, higher IGF-I levels in very-low-birth-weight infants in early childhood probably have an important role in catch-up growth in length.