Postnatal Growth Failure Research Articles

A rare heterozygous IGFI variant causing postnatal growth failure and offering novel insights into IGF-I physiology

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Growth Velocity of the Preterm Infant Managed with a Standardized Nutritional Protocol in a Tertiary Care Hospital

Prematurity is one of the major causes of neonatal death in developing countries like Bangladesh. Appropriate protocol for nutritional support of the preterm infants is essential to achieve a postnatal growth rate similar to that of a normal fetus. Objective of the study was to assess the effects of the existing nutritional support protocol of Bangabandhu Sheikh Mujib Medical University (BSMMU) in the early postnatal growth velocity of the preterm infants.This quasi-experimental study was conducted in the Department of Neonatology, BSMMU, Bangladesh from January to December 2015. All admitted infants aged <48 hours and born <_32 weeks of gestational age were included in this study. Infants were provided with nutritional support as per the BSMMU feeding guideline. The subsequent growth of the children was followed up routinely to measure the growth velocity. Of the 38 infants of our study, the mean calorie intake was 66.71 Kcal/kg/day. Overall mean growth velocity of weight, length and occipitofrontal circumference (OFC) up to discharge were 8.97 g/kg/day, 0.85 cm/week, and 0.41 cm/week respectively. Very low birth weight (VLBW) infants got significantly more calories compared to low birth weight (LBW) infants (p = 0.009). Mean growth velocity in weight of LBW infants were 8.18 g/kg/day and VLBW were 9.95 g/kg/day (p = 0.233). At birth, only 2.6% of infants had weight <10th centile, but at discharge, it was 52.6%. Early postnatal nutritional supplementation was not adequate, and postnatal growth failure remains very high in the hospital admitted preterm infants. Faridpur Med. Coll. J. 2020;15(2): 79-84

Cumulative impact of multiple evidence based strategies on postnatal growth of extremely-low-birth-weight infants

Postnatal growth failure is common in very preterm infants and is associated with worse neurodevelopmental outcome. To evaluate the cumulative impact of multiple evidence based strategies on the postnatal growth of extremely-low-birth-weight (ELBW) infants. We conducted a prospective observational study. Based on current literature, changes were implemented to provide optimal parenteral and enteral nutrition. Daily intakes of calories, protein, lipids and carbohydrates were calculated. The average growth velocity (GV) was calculated using 2-point exponential model and is reported as grams/kg/day. The length and head circumference gains are reported as centimeters/week. The mean gestational age and birth weight for 38 ELBW survivors were 27.0±2.1 weeks and 752±147g respectively. The GV was 13.2±2.2g/kg/day (range 8.8-17.4) and gains in length and head circumference were 0.88±0.9 (range 0.15-1.42) and 0.71±0.5 (range 0.22-0.96) centimeters/week respectively. Twenty nine (76.3%) infants were small-for-gestational-age (SGA) at discharge and 23 of these (60.5% of all infants) had weight below 3rd percentile. All 11 infants who were SGA at birth were SGA at discharge as well. Of 25 appropriate-for-gestational-age (AGA) infants at birth, 16 (64%) were SGA at discharge. The number of infants with length and head circumference below 10th percentile at birth and discharge were 11 (28.9%) and 29 (76.3%) for length and 20 (52.6%) and 27 (71.1%) for head circumference. Infants with multiple morbidities and more hospital days with no enteral feeds had lower GV. All infants born SGA at birth and majority of ELBW survivors born AGA at birth had weight, length and head circumference below 10th percentile at discharge despite aggressive nutrition supplementation.

Stratifying the Genetic Aetiology in Children Born Small for Gestational Age With Persistent Short Stature (SGA-SS)

Background: Ten percent of children born small for gestational age with a birth weight and/or length of below -2 SD for their gestational age fail to catch-up and remain short during childhood (SGA-SS). The etiology of SGA-SS is heterogeneous: some children have specific phenotypic features that allow targeted genetic testing; in others, elucidating genetic or environmental background is more challenging. Aim: To decipher genetic etiologies among a large single-center cohort of SGA-SS children and to stratify them according to molecular mechanisms leading to pre- and postnatal growth failure. Patients/Methods: In our center 447 children (223 females) fulfilled the criteria of SGA-SS. Of these 182 families agreed to take part and offered the child’s and both parents’ DNA for genetic testing by a panel of 399 growth-related genes, or by Whole Exome Sequencing (WES). The results were processed by a bioinformatic pipeline and detected variants were filtered using variant analysis software. Pathogenic or likely pathogenic variants (according to ACMG standards and guidelines) were confirmed by Sanger sequencing. Results: The genetic etiology was elucidated in 73/182 (40%) children so far. We confirmed (likely) pathogenic gene variants affecting pituitary development and/or the GH-IGF-1 axis in 10/73 (14%) patients (PTCH1, HGMA2 [in two], OTX2, LHX4, GHSR, STAT3, IGFALS, IGF1R [in two]), abnormal components of cartilaginous matrix in 17/73 (23%) (ACAN [in two], FLNB [in three], FBLN5, COL11A1[in four], COL1A2, COL2A1[in five], MATN3), impaired paracrine regulation of chondrocytes in 4/73 (6%) (NPR2 [in three], FGFR3), SHOX gene defects in 12/73 (16%), gene variants affecting other components of intracellular regulation and signaling in 9/73 (12%) (CDC42, KMT2A, KMT2D, NSD1, SRCAP, PRG4, PTPN11, SON, LMNA), Silver-Russell syndrome (11p15 [in seven] or UPD7) in 11/73 (15%), and miscellaneous single-gene or chromosomal conditions (TRPS1, TRHR, RAI1, chromosomal microdeletions and/or translocations) in an additional ten (14%) children. Conclusions: In our study we showed that by using current genetic techniques we were able to elucidate the genetic cause in a significant number of patients born SGA-SS. The genetic etiology spectrum of SGA-SS reflects the complex system of growth regulation, with a significant role of growth plate genes that are causative in 33/73 (45%) cases clarified thus far. Acknowledgements: The study was co-funded by grants AZV NV18-07-00283 and GAUK 408120.

Maternal Uniparental Disomy of Chromosome 20 (UPD(20)mat) as Differential Diagnosis of Silver Russell Syndrome: Identification of Three New Cases.

Silver Russell Syndrome (SRS, MIM #180860) is a rare growth retardation disorder in which clinical diagnosis is based on six features: pre- and postnatal growth failure, relative macrocephaly, prominent forehead, body asymmetry, and feeding difficulties (Netchine–Harbison clinical scoring system (NH-CSS)). The molecular mechanisms consist in (epi)genetic deregulations at multiple loci: the loss of methylation (LOM) at the paternal H19/IGF2:IG-DMR (chr11p15.5) (50%) and the maternal uniparental disomy of chromosome 7 (UPD(7)mat) (10%) are the most frequent causes. Thus far, about 40% of SRS remains undiagnosed, pointing to the need to define the rare mechanisms in such a consistent fraction of unsolved patients. Within a cohort of 176 SRS with an NH-CSS ≥ 3, a molecular diagnosis was disclosed in about 45%. Among the remaining patients, we identified in 3 probands (1.7%) with UPD(20)mat (Mulchandani–Bhoj–Conlin syndrome, OMIM #617352), a molecular mechanism deregulating the GNAS locus and described in 21 cases, characterized by severe feeding difficulties associated with failure to thrive, preterm birth, and intrauterine/postnatal growth retardation. Our patients share prominent forehead, feeding difficulties, postnatal growth delay, and advanced maternal age. Their clinical assessment and molecular diagnostic flowchart contribute to better define the characteristics of this rare imprinting disorder and to rank UPD(20)mat as the fourth most common pathogenic molecular defect causative of SRS.

Recombinant IGF-1 Induces Sex-Specific Changes in Bone Composition and Remodeling in Adult Mice with Pappa2 Deficiency.

Deficiency of pregnancy-associated plasma protein-A2 (PAPP-A2), an IGF-1 availability regulator, causes postnatal growth failure and dysregulation of bone size and density. The present study aimed to determine the effects of recombinant murine IGF-1 (rmIGF-1) on bone composition and remodeling in constitutive Pappa2 knock-out (ko/ko) mice. To address this challenge, X-ray diffraction (XRD), attenuated total reflection-fourier transform infra-red (ATR-FTIR) spectroscopy and gene expression analysis of members of the IGF-1 system and bone resorption/formation were performed. Pappa2ko/ko mice (both sexes) had reduced body and bone length. Male Pappa2ko/ko mice had specific alterations in bone composition (mineral-to-matrix ratio, carbonate substitution and mineral crystallinity), but not in bone remodeling. In contrast, decreases in collagen maturity and increases in Igfbp3, osteopontin (resorption) and osteocalcin (formation) characterized the bone of Pappa2ko/ko females. A single rmIGF-1 administration (0.3 mg/kg) induced short-term changes in bone composition in Pappa2ko/ko mice (both sexes). rmIGF-1 treatment in Pappa2ko/ko females also increased collagen maturity, and Igfbp3, Igfbp5, Col1a1 and osteopontin expression. In summary, acute IGF-1 treatment modifies bone composition and local IGF-1 response to bone remodeling in mice with Pappa2 deficiency. These effects depend on sex and provide important insights into potential IGF-1 therapy for growth failure and bone loss and repair.

UPD(14)mat and UPD(14)mat in concomitance with mosaic small supernumerary marker chromosome 14 in two new patients with Temple syndrome

Temple syndrome (TS14) can be originated by maternal uniparental disomy (UPD(14)mat), paternal deletion, or epimutation, leading to disturbances in 14q32.2 imprinted region. The most frequent phenotypic manifestations are prenatal and postnatal growth failure, hypotonia, developmental delay, small hands/feet, precocious puberty, and truncal obesity. However, the diagnosis can be challenging due to the clinical overlap with other imprinting disorders such as Silver-Russell or Prader-Willi syndromes. Although rare, TS14 has been also reported in patients with concomitant UPD(14)mat and mosaic trisomy 14. In the present report, the clinical and genetic profiles of two new patients with TS14 are described. SNParray and MS-MLPA, allowed the determination of segmental UPD(14)mat and the hypomethylation of MEG3 gene. Additionally, in one of our patients we also observed by cytogenetics a small supernumerary marker chromosome that led to partial trisomy 14 in mosaic. Only few patients with concomitant UPD(14)mat and mosaic partial trisomy 14 have been reported. Our patients share cardinal TS14 phenotypic features that are associated to the genetic abnormalities detected; however, we also observed some clinical features such as fatty liver disease that had not previously been reported as part of this syndrome. The detailed clinical, cytogenetical and molecular description of these two new patients, contributes to a more accurately delineation of this syndrome.

Predictive ability of postnatal growth failure for adverse feeding-related outcomes in preterm infants: an exploratory study comparing Fenton with INTERGROWTH-21st preterm growth charts

Background Postnatal growth failure (PGF) can impact the short- and long-term health outcomes in preterm infants. However, PGF rates vary according to the way it is defined and the growth chart used to monitor the postnatal growth. Fenton-2013 growth charts which suggest following intrauterine fetal growth compared to INTERGROWTH-21st, one specifically constructed for monitoring preterm extrauterine growth. Objective Exploratory study to determine the PGF definition at first per oral (PO) that is most predictive of adverse oral feeding-related outcomes in preterm infants. Methods Prospectively collected data of preterm infants 24–32 weeks gestation, who were started on cue-based oral feeds at ≤34 weeks gestation were reviewed. Anthropometric data at first PO (weight, length, and head circumference) were compared according to Fenton and INTERGROWTH-21st growth charts. PGF was defined either as <10th percentile, Z-score change (ZSC) of ≥–1.5 from birth, or ZSC of ≥–2.0. Top-quartile (Q4) of feeding-related outcomes (days from first PO to full PO, post-menstrual age at full PO, days from first PO to discharge, and length of hospital stay) was considered as adverse outcome. Results Of the 125 infants included, the median birth gestation and weight were 29.4 weeks and 1235 g, respectively. Incidence of appropriate, small, and large for gestational age was similar at birth by both growth charts. ZSC −1.5 for weight by Fenton was significantly higher at first PO vs. INTERGROWTH-21st (p=.02), while percentile <10th and ZSC −2.0 rates were similar. The PGF definition based on individual anthropometrics at first PO that has the best area under the curve (AUC) for adverse feeding-related outcomes was used to create a combined PGF definition for each growth chart. The AUC for the combined PGF for the Fenton and INTERGROWTH-21st was similar (p>.05) and both have moderate sensitivity and negative predictive value, but have low specificity, positive predictive value, and positive likelihood ratio for adverse feeding-related outcomes. Conclusions The tested definitions of PGF at first PO have only small to moderate predictive ability for adverse feeding-related outcomes in preterm infants.

Dissociable effects of dietary sodium in early life upon somatic growth, fluid homeostasis, and spatial memory in mice of both sexes.

Postnatal growth failure is a common morbidity for preterm infants and is associated with adverse neurodevelopmental outcomes. Although sodium (Na) deficiency early in life impairs somatic growth, its impact on neurocognitive functions has not been extensively studied. We hypothesized that Na deficiency during early life is sufficient to cause growth failure and program neurobehavioral impairments in later life. C57BL/6J mice were placed on low- (0.4), normal- (1.5), or high- (3 g/kg) Na chow at weaning (PD22) and continued on the diet for 3 wk (to PD40). Body composition and fluid distribution were determined serially by time-domain NMR and bioimpedance spectroscopy, and anxiety, learning, and memory were assessed using the elevated plus maze and Morris water maze paradigms in later adulthood (PD63-PD69). During the diet intervention, body mass gains were suppressed in the low- compared with normal- and high-Na groups despite similar caloric uptake rates across groups. Fat mass was reduced in males but not in females fed low-Na diet. Fat-free mass and hydration were significantly reduced in both males and females fed the low-Na diet, although rapidly corrected after return to normal diet. Measures of anxiety-like behavior and learning in adulthood were not affected by diet in either sex, yet memory performance was modified by a complex interaction between sex and early life Na intake. These data support the concepts that Na deficiency impairs growth and that the amount of Na intake which supports optimal somatic growth during early life may be insufficient to fully support neurocognitive development.

Neonatal Total Parenteral Nutrition: Clinical Implications From Recent NICE Guidelines

Postnatal growth failure and its impact on the long term outcomes in preterm neonates is a long-standing problem. Optimal and aggressive nutrition strategies are required to ameliorate these concerns. Total parenteral nutrition (TPN) is widely practiced in management of preterm neonates. Recently published National Institute for Health and Care Excellence (NICE) guidelines provide recommendations for best practices for parenteral nutrition in neonates. However, healthcare associated sepsis, expertise as well as infrastructure of TPN, monitoring facilities and cost remain major constraints for widespread use of TPN in resource limited settings. Current update is aimed to summarize NICE and European society for Clinical Nutrition and Metabolism (ESPEN) guidelines to inform best practice for TPN for neonatologists in India.

Poor postnatal weight growth is a late finding after sepsis in very preterm infants

ObjectiveTo characterise the association between sepsis and postnatal weight growth when accounting for the degree of growth restriction present at birth.DesignRetrospective matched cohort study using data from the Postnatal Growth...

Genome-wide methylation analysis in Silver\u2013Russell syndrome, Temple syndrome, and Prader\u2013Willi syndrome

BackgroundImprinting disorders (IDs) show overlapping phenotypes, particularly in Silver–Russell syndrome (SRS), Temple syndrome (TS14), and Prader–Willi syndrome (PWS). These three IDs include fetal and postnatal growth failure, feeding difficulty, and muscular hypotonia as major clinical features. However, the mechanism that causes overlapping phenotypes has not been clarified. To investigate the presence or absence of methylation signatures associated with overlapping phenotypes, we performed genome-wide methylation analysis (GWMA).ResultsGWMA was carried out on 36 patients with three IDs (SRS [n = 16], TS14 [n = 7], PWS [n = 13]) and 11 child controls using HumanMethylation450 BeadChip including 475,000 CpG sites across the human genome. To reveal an aberrantly methylated region shared by SRS, TS14, and PWS groups, we compared genome-wide methylation data of the three groups with those of control subjects. All the identified regions were known as SRS-, TS14-, and PWS-related imprinting-associated differentially methylated regions (iDMRs), and there was no hypermethylated or hypomethylated region shared by different ID groups. To examine the methylation pattern shared by SRS, TS14, and PWS groups, we performed clustering analysis based on GWMA data. The result focusing on 620 probes at the 62 known iDMRs (except for SRS-, TS14-, and PWS-related iDMRs) classified patients into two categories: (1) category A, grossly normal methylation patterns mainly consisting of SRS group patients; and (2) category B, broad and mild hypermethylation patterns mainly consisting of TS14 and PWS group patients. However, we found no obvious relationship between these methylation patterns and phenotypes of patients.ConclusionsGWMA in three IDs found no methylation signatures shared by SRS, TS14, and PWS groups. Although clustering analysis showed similar mild hypermethylation patterns in TS14 and PWS groups, further study is needed to clarify the effect of methylation patterns on the overlapping phenotypes.

Prenatal intrauterine growth restriction and risk of retinopathy of prematurity

Low birthweight and decreased postnatal weight gain are known predictors of worse retinopathy of prematurity (ROP) but the role of prenatal growth patterns in ROP remains inconclusive. To distinguish small for gestational age (SGA) from intrauterine growth restriction (IUGR) as independent predictors of ROP, we performed a retrospective cohort study of patients who received ROP screening examinations at a level IV neonatal intensive care unit over a 7-year period. Data on IUGR and SGA status, worst stage of and need for treatment for ROP, and postnatal growth was obtained. 343 infants were included for analysis (mean gestational age = 28.6 weeks and birth weight = 1138.2 g). IUGR infants were more likely to have a worse stage of ROP and treatment-requiring ROP (both p < 0.0001) compared to non-IUGR infants. IUGR infants were more likely to be older at worst stage of ROP (p < 0.0001) and to develop postnatal growth failure (p = 0.01) than non-IUGR infants. Independent of postnatal growth failure status, IUGR infants had a 4–5 × increased risk of needing ROP treatment (p < 0.001) compared to non-IUGR infants. SGA versus appropriate for gestational age infants did not demonstrate differences in retinopathy outcomes, age at worst ROP stage, or postnatal growth failure. These findings emphasize the importance of prenatal growth on ROP development.

Genetic causes of growth hormone insensitivity beyond GHR.

Growth hormone insensitivity (GHI) syndrome, first described in 1966, is classically associated with monogenic defects in the GH receptor (GHR) gene which result in severe post-natal growth failure as consequences of insulin-like growth factor I (IGF-I) deficiency. Over the years, recognition of other monogenic defects downstream of GHR has greatly expanded understanding of primary causes of GHI and growth retardation, with either IGF-I deficiency or IGF-I insensitivity as clinical outcomes. Mutations in IGF1 and signaling component STAT5B disrupt IGF-I production, while defects in IGFALS and PAPPA2, disrupt transport and release of circulating IGF-I, respectively, affecting bioavailability of the growth-promoting IGF-I. Defects in IGF1R, cognate cell-surface receptor for IGF-I, disrupt not only IGF-I actions, but actions of the related IGF-II peptides. The importance of IGF-II for normal developmental growth is emphasized with recent identification of defects in the maternally imprinted IGF2 gene. Current application of next-generation genomic sequencing has expedited the pace of identifying new molecular defects in known genes or in new genes, thereby expanding the spectrum of GH and IGF insensitivity. This review discusses insights gained and future directions from patient-based molecular and functional studies.

Postnatal growth of preterm infants 24 to 26 weeks of gestation and cognitive outcomes at 2 years of age.

Background:Weight z scores at 36 weeks of postmenstrual age (PMA) define postnatal growth failure (PGF) and malnutrition. This study aimed to determine weight z scores at 36 weeks PMA that are associated with adverse cognitive outcomes at 2 years of age.Methods:In this retrospective cohort study, 350 infants 24 to 26 weeks of gestation born between 2006 and 2014 and followed at 2 years were included. Weight z scores at birth and at 36 weeks PMA were calculated using the INTERGROWTH-21st growth curves. The primary outcome was cognitive delay at 2 years of age (Bayley-III cognitive score < 85).Results:Neither the traditional definition of PGF (z score below −1.3) nor the recently proposed definition of malnutrition (z score decline of 1.2 or greater) was associated with cognitive delay. Both a weight z score below −1.0 at 36 weeks PMA (RR: 1.65; 95% CI: 1.10 - 2.49; p <0.05) and a decline below −1.0 in weight z score from birth to 36 weeks PMA (RR: 1.40; 95% CI: 1.00 – 1.94; p <0.05) were associated with a higher risk of cognitive delay.Conclusion:With optimal cutoffs, INTERGROWTH-21st weight z scores can predict the risk of cognitive delay.

The Wiedemann-Rautenstrauch or Neonatal Progeroid Syndrome: Report of a Patient with Gingival Hyperplasia and Severe Anterior Open Bite

Introduction: The Wiedemann-Rautenstrauch syndrome (WRS) is a rare progeroid syndrome with an autosomal recessive pattern of inheritance. The main clinical features include severe intrauterine and postnatal growth failure, distinctive facial appearance, hydrocephaly, prominent scalp veins, absence of subcutaneous fat, sparse hair of the scalp, eyebrows, and eyelashes, generalized lipoatrophy, psychomotor delay, progressive neurological deterioration, and short life expectancy. Natal teeth and micrognathia are reported as the oral manifestations of this syndrome. Case Presentation: Here is the report of a 6.5-year-old female patient with clinical signs of WRS referred to the Department of Periodontology of Shiraz School of Dentistry with the chief complaint of toothache and gingival hyperplasia. Carious teeth were extracted, and excess gingival tissue was removed through a surgical procedure under general anesthesia. The patient was the first case with a concomitant severe anterior open bite. Conclusions: Therapies for WRS are symptomatic, requiring the coordinated efforts of a team of specialists. Dentists and oral surgeons can be recruited by pediatricians and family physicians to improve the quality of life of such patients.

Elevated blood pressure in high-fat diet-exposed low birthweight rat offspring is most likely caused by elevated glucocorticoid levelsdue to abnormal pituitary negative feedback.

Being delivered as a low birthweight (LBW) infant is a risk factor for elevated blood pressure and future problems with cardiovascular and cerebellar diseases. Although premature babies are reported to have low numbers of nephrons, some unclear questions remain about the mechanisms underlying elevated blood pressure in full-term LBW infants. We previously reported that glucocorticoids increased miR-449a expression, and increased miR-449a expression suppressed Crhr1 expression and caused negative glucocorticoid feedback. Therefore, we conducted this study to clarify the involvement of pituitary miR-449a in the increase in blood pressure caused by higher glucocorticoids in LBW rats. We generated a fetal low-carbohydrate and calorie-restricted model rat (60% of standard chow), and some individuals showed postnatal growth failure caused by growth hormone receptor expression. Using this model, we examined how a high-fat diet (lard-based 45kcal% fat)-induced mismatch between prenatal and postnatal environments could elevate blood pressure after growth. Although LBW rats fed standard chow had slightly higher blood pressure than control rats, their blood pressure was significantly higher than controls when exposed to a high-fat diet. Observation of glomeruli subjected to periodic acid methenamine silver (PAM) staining showed no difference in number or size. Aortic and cardiac angiotensin II receptor expression was altered with compensatory responses. Blood aldosterone levels were not different between control and LBW rats, but blood corticosterone levels were significantly higher in the latter with high-fat diet exposure. Administration of metyrapone, a steroid synthesis inhibitor, reduced blood pressure to levels comparable to controls. We showed that high-fat diet exposure causes impairment of the pituitary glucocorticoid negative feedback via miR-449a. These results clarify that LBW rats have increased blood pressure due to high glucocorticoid levels when they are exposed to a high-fat diet. These findings suggest a new therapeutic target for hypertension of LBW individuals.

39 Early Higher Parenteral Lipid Intake Decreases Extra-Uterine Growth Restriction in Very Low Birth weight Infants: A Randomized Controlled Trial

Abstract Background Approximately 43-65% of very low birth weight (VLBW) infants develop extra-uterine growth restriction (EUGR). EUGR is associated with a significant increase in the risk of neurodevelopmental impairment. Inadequate early postnatal nutrition results in excessive weight loss that cannot be explained by the physiologic contraction of body water alone. EUGR and postnatal growth failure are usually associated with negative early energy and nitrogen balance in the first week of life. Growth trajectories after initial weight loss have similar slopes regardless of gestational age, which indicates that the early excessive weight loss is a lead cause for EUGR. Objectives To study whether an early and higher parenteral lipid intake in the first week after birth would decrease the percentage of weight loss and subsequently the incidence of EUGR. Design/Methods This was a randomized, open-label, control trial of appropriate-for-gestational age VLBW infants admitted to our level III NICU. Lipid intake in the control group started at 0.5-1 g/kg/day and was increased daily by 0.5-1 g/kg/day until 3 g/kg/day was reached. The intervention group was started on 2 g/kg/day then increased to 3 g/kg/day the following day. Triglyceride levels were measured the day after the start and after each increase in lipid intake. Results Among the 176 infants assessed for eligibility, eighty-three were included in the trial. There were no significant differences between the control and the intervention group in mean gestational age (27.3 ± 2.4 vs. 27.1 ± 2.3 weeks respectively) or birth weight (1011 ± 250 vs. 1019 ± 271 g respectively). Infants in the intervention group were started on lipid earlier (13.8±7.8 vs. 17.5±7.8 h; p=0.03) and had higher cumulative lipid intake in the first 7 days of age (13.5±4.2 vs. 10.9±3.5 g/kg; p=0.004) that led to a protein to energy ratio; closer to the recommended values. Total fluid intake was similar between the two groups. Infants in the intervention group had a lower percentage of weight loss (10.4±3.6 vs. 12.7±4.6; p=0.02). The mean triglyceride level was higher in the intervention group (1.91± 0.79 vs. 1.49±0.54 mmol/L; p= 0.01), however, hypertriglyceridemia was similar between the two groups at 2 and 3 g/kg/day of lipid intake. Enteral energy and protein intake calculated weekly between the time of parenteral nutrition discontinuation and 36 weeks corrected gestational age (CGA) were similar between the 2 groups. EUGR at 36 weeks CGA was significantly lower in the intervention group (38.6% vs. 67.6%; p=0.01). Conclusion In VLBW infants, the provision of an early and higher dose of parenteral lipid in the first week of life results in less weight loss and lower incidence of EUGR.

SP3 Evaluating the impact of concentrated standardised parenteral nutrition on growth of preterm infants

Background and AimConcentrated standardised parenteral nutrition (CSPN) may reduce the delay in commencing parenteral nutrition (PN) in preterm infants compared with conventional individualised PN. Optimisation of early nutrition, with emphasis on earlier commencement of PN to include amino acids and addition of lipids within 24 hours of birth, ameliorates early postnatal growth failure.1 2 Cumulative nutritional deficit often seen in significantly preterm infants may lead to poor neurodevelopmental outcome.3 4 CSPN was introduced in our neonatal unit in December 2017 with the objective of improving early nutrition. The aim of this service evaluation was to assess the suitability of CSPN and its impact on the growth of preterm infants in our tertiary level neonatal unit.MethodsIn December 2017, the neonatal PN provided was switched from individualised PN to CSPN based on a modified ‘SCAMP’ regimen. Retrospective and prospective growth parameter data was collected for infants receiving PN within 24 hours of birth born between September to November 2017 (individualised PN arm) and from September to November 2018 (CSPN arm). Infants were excluded if they died or transferred out of the local neonatal service before day 28 of life, or died before transitioning from PN to full enteral feeds. Weight and head circumference at birth, 28 days old and 36 weeks corrected gestation/discharge were converted to z scores using the LMS method. The Mann-Whitney test was used to compare continuous data. Annual PN expenditure, and wastage of ordered PN, before and after the switch to CSPN, was calculated using the pharmacy stock management system, pharmacist and finance records.Results20 infants (mean gestational age 28 weeks) and 21 infants (mean gestational age 29.6 weeks) were included in the CSPN and individualised PN groups respectively. There were no differences in demographic data of each group. CSPN was commenced earlier (median 8 hours old (n=20)) than individualised PN (median 25 hours old (n=19)), (U=42, p&lt;0.0001). There was no statistical difference in the change in weight z score from birth at 28 days old (median -0.47 (n=20) CSPN vs -0.66 (n=19) individualised PN, U=178.5, p=0.75) and at 36 weeks corrected gestation/discharge (median -0.72 (n=20) CSPN vs -0.86 (n=21) individualised PN, U=106, p=0.7). There was insufficient data collected to analyse effect on head circumference. Replacing individualised PN with CSPN resulted in a 37% reduction in procurement costs, despite an increase in the wastage of ordered PN from 7.2% to 8.5%.ConclusionA PN strategy using concentrated standardised PN can be implemented successfully in a tertiary neonatal unit setting in the United Kingdom and allows earlier commencement of PN. Use of CSPN appeared to have no adverse effect on weight gain, although small sample size may account for the lack of statistical significance in improvement of weight z score seen. Improved rates of head circumference documentation for our patients are required. Introducing CSPN resulted in a considerable reduction in procurement costs, and identifying strategies to minimise wastage of CSPN bags would further improve cost-effectiveness.ReferencesMorgan C, McGowan P, Herwitker S, et al. Postnatal head growth in preterm infants: a randomised controlled parenteral nutrition study. Pediatrics 2014;133:e120–8.Moyses HE, Johnson MJ, Leaf AA, et al. Early parenteral nutrition and growth outcomes in preterm infants: a systematic review and meta-analysis. Am J Clin Nutr 2013;97:816–26.Ehrenkranz RA, Dusick AM, Vohr BR, et al. Growth in the neonatal intensive care unit influences neurodevelopmental and growth outcomes of extremely low birth weight infants. Pediatrics 2006;117:1253–61.Dusick AM, Poindexter BB, Ehrenkranz RA, et al. Growth failure in the preterm infant: can we catch up?Semin Perinatol 2003;27:302–10.

Effect of Parenteral Nutrition-Associated Factors on the Growth of Premature Infants

Objective: To investigate the factors that affect the growth of preterm infants who receive parenteral nutrition (PN).Methods: A retrospective cohort study was performed in Uttaradit hospital, Thailand, using data collected between January 2012 and July 2016. The main outcome measure was postnatal growth failure (PGF), comprising weight gain rate at 36 weeks, weight at 36 weeks, time to regain birth weight and growth failure at 36 weeks.Results: Eighty preterm infants were included in this study, with a mean gestational age of 32 weeks and birth weight of 1468 grams. Multiple regression analysis indicated that the time to achieve full enteral feeding (r = 0.33, 95% CI[0.01,0.48]) was associated with the weight gain rate at 36 weeks of corrected age, birth weight (r = -0.53, 95% CI[-445.04, -216.70]) was associated with weight at 36 weeks of corrected age, the initial timing of PN (r = -0.24, 95% CI[-4.10, -0.40]), average amount of protein in PN (r = 0.39, 95% CI[0.55, 3.43]) and the initial amount of protein in PN (r = -0.46, 95% CI[-3.19, -1.00]) were associated with the time to regain birth weight, and a birth weight classified as small for gestational age (SGA, OR = 15.90, 95% CI[1.54,164.14]) was significantly associated with growth failure at 36 weeks of corrected age.Conclusions: The results of this study indicate that both nutrition and non-nutrition factors affect PGF in preterm infants who receive PN.