Extrauterine Growth Restriction Research Articles

Metabolomic profiling of human feces and plasma from extrauterine growth restriction infants.

Extrauterine growth restriction (EUGR) affects a substantial proportion of preterm infants and may influence both short-term complications and long-term sequelae. While many preterm infants with EUGR are secondary to small for gestational age (SGA) or very low birth weight (VLBW), a subset of EUGR infants do not exhibit these conditions. The purpose of this study is to investigate the metabolic profiles and biomarkers of EUGR infants in the absence of SGA and VLBW. A total of 100 feces (n = 50) and plasma samples (n = 50) were collected from participants categorized as either EUGR (EUGR group) or non-EUGR (NonEUGR group) in the absence of SGA and VLBW. Metabolites were characterized via UPLC-MS/MS using the Discovery HD4® platform. Data normalization, partial least squares discriminant analysis (PLSDA), and KEGG enrichment analysis of metabolite profiles were performed using the MetaboAnalyst 6.0. The clinical characteristics of preterm infants differed significantly between the EUGR and NonEUGR groups at discharge, including length of stay, weight Z-score, weight, height Z-score, height, head circumference, and fat-free mass. The PLSDA model exhibited clustering within groups and separation between groups. A total of 58 and 71 differential metabolites were identified in feces and plasma samples, respectively. They were involved in pathways such as caffeine, galactose, glutathione, cysteine, and methionine metabolisms. In the feces sample, 1-palmitoyl-galactosylglycerol exhibited a significant negative correlation with the growth characteristics of preterm infants, while 1-palmitoyl-2-palmitoleoyl-GPC displayed the opposite pattern. In plasma samples, androsterone glucuronide displayed a significant positive correlation with the growth characteristics of preterm infants, whereas 2-methoxyhydroquinone sulfate generated an opposite pattern. Moreover, 2-oleoylglycerol and sphinganine-1-phosphate exhibited the highest area under the curve in feces and plasma samples, respectively, according to diagnostic ROC curves. Preterm infants with EUGR, in the absence of SGA and VLBW, exhibit specific clinical characteristics and metabolomic profiles. Sphinganine-1-phosphate and 2-oleoylglycerol may hold promise as diagnostic markers for EUGR in the absence of SGA and VLBW. The objective of this study is to identify the differential metabolites in preterm infants with extrauterine growth restriction (EUGR) in the absence of small for gestational age (SGA) or very low birth weight (VLBW). Preterm infants with EUGR without SGA and VLBW exhibit specific clinical characteristics and metabolomic profiles. Sphinganine-1-phosphate and 2-oleoylglycerol emerged as potential diagnostic biomarkers for EUGR. This study enhances our understanding of the metabolomic profile in preterm infants with EUGR without SGA or VLBW. Our findings will offer valuable evidence for improving nutritional management and shedding light on the associated pathophysiological mechanisms of EUGR.

Prevalence and factors associated with extrauterine growth restriction in premature infants

Background Extrauterine growth restriction (EUGR) is common in preterm infants and has been shown to affect their neurodevelopment. Significant variability exists in the criteria used to define EUGR and a standard definition has not yet been established. Several factors associated with EUGR have been identified, yet EUGR remains a problem in preterm infants. There is still much to be explored regarding risk factors associated with EUGR. Objective To determine the prevalence and factors associated with EUGR in preterm infants. Methods This cross-sectional study included randomly selected premature infants (<37 weeks gestational age) who were admitted to levels II and III Neonatal Ward at Prof. Dr. I.G.N.G. Ngoerah Hospital from May 2022 to August 2023. Results Of 185 subjects, the prevalence of EUGR in preterm infants was 47% and there were significant associations between EUGR and birth weight <1500 g (PR 8.814; 95%CI: 3.943 to 19.7; P=0.000), small for gestational age/SGA (PR 28.95; 95%CI: 3.79 to 220.1; P=0.000), neonatal sepsis (PR 4.29; 95%CI: 2.21 to 8.31; P=0.000), hyaline membrane disease/HMD (PR 2.12; 95%CI: 1.16 to 3.88; P=0.021), use of respiratory support (PR 2.57; 95%CI: 1.35 to 4.92; P=0.005), initiation of enteral nutrition at >48 hours (PR 2.23; 95%CI: 1.21 to 4.09; P=0.014) and length of stay/LOS >14 days (PR 8.11; 95%CI: 4.13 to 15.9; P=0.000). Multivariate analysis revealed birth weight <1500 g (aPR 5.14; 95%CI: 1.55 to 17.06; P=0.007), SGA (aPR 24.26; 95%CI: 2.64 to 222.6; P=0.005), presence of sepsis (aPR 2.35; 95%CI: 1.00 to 5.5; P=0.049), and length of hospital stay >14 days (aPR 4.93; 95%CI: 2.15 to 11.31; P=0.000) maintained positive significant associations with EUGR. Conclusion The prevalence of EUGR in preterm infants is 47%. Birth weight <1500 g, small for gestational age, sepsis, and length of stay >14 days are associated with EUGR in preterm infants.

Construction and validation of a risk prediction model for extrauterine growth restriction in preterm infants born at gestational age less than 34 weeks.

This study aimed to develop and validate a model for predicting extrauterine growth restriction (EUGR) in preterm infants born ≤34 weeks gestation. Preterm infants from Guangxi Maternal and Child Health Hospital (2019-2021) were randomly divided into training (80%) and testing (20%) sets. Collinear clinical variables were excluded using Pearson correlation coefficients. Predictive factors were identified using Lasso regression. Random forest (RF), support vector machine (SVM), and logistic regression (LR) models were then built and evaluated using the confusion matrix, area under the curve (AUC), and the F1 score. Additionally, calibration curves and decision curve analysis (DCA) were plotted to assess the performance and practical utility of the models. The study included 387 infants, with no significant baseline differences between training (n = 310) and testing (n = 77) sets. LR identified gestational age, birth weight, premature rupture of membranes, patent ductus arteriosus, cholestasis, and neonatal sepsis as key EUGR predictors. The RF model (19 variables) demonstrated an accuracy of greater than 90% during training, and superior AUC (0.62), F1 score (0.80), and accuracy (0.72) in testing compared to other models. Gestational age, birth weight, premature rupture of membranes, patent ductus arteriosus, cholestasis, and neonatal sepsis are significant EUGR predictors in preterm infants ≤34 weeks. The model shows promise for early EUGR prediction in clinical practice, potentially enhancing screening efficiency and accuracy, thus saving medical resources.

PSII-18 Prematurity alters nutrient signaling and protein synthesis in skeletal muscle of neonatal piglets

Abstract Extrauterine growth restriction is common in infants born preterm, and negatively affects lean mass accretion and health. Prematurity has been shown to inhibit the feeding-induced stimulation of protein synthesis in skeletal muscle. We hypothesized that nutrient signaling, activation of the mechanistic target of rapamycin complex 1 (mTORC1), and protein synthesis in the muscle are limited in preterm infants which negatively impacts muscle growth. The objective of this study was to examine how prematurity influences the mechanisms involved in insulin- and amino acid-induced signaling and protein synthesis in skeletal muscle of piglets delivered either 9 d preterm (104 d, n = 25) or at term (112 d, n = 26) by cesarean section. After resuscitation, they were surgically implanted with jugular vein and carotid artery catheters and placed in individual incubators. They were randomly allotted to one of three treatments within each preterm and term birth groups: euaminoacidemic-euglycemic (FAST), hyperinsulinemic-euaminoacidemic-euglycemic (INS), or euinsulinemic-hyperaminoacidemic-euglycemic (AA) clamps on 4 d after birth. After the clamp procedure, the piglets were euthanized to collect longissimus dorsi muscle for estimating in vivo fractional protein synthesis rates and the abundance and activation of components related to insulin and amino acid signaling. Data were analyzed using the MIXED procedure of SAS. The leucine sensor, Sestrin1 bound to GATOR2 (P < 0.05) was reduced in response to AA whereas the abundance of the mTOR-RagA and mTOR-RagC complexes increased (P < 0.05). The phosphorylation of Akt was increased (P < 0.05) in response to INS and the phosphorylation of mTORC1 and protein synthesis increased (P < 0.05) in response to both AA and INS. Prematurity did not affect the protein abundances of the AA transporters for glutamine (SLC38A2), leucine (SLC7A5), and arginine (SLC38A9). However, prematurity reduced (P < 0.05) the abundances of the leucine sensors SAR1B, the Sestrin1-GATOR complex, the AA sensor, RAB1A, and the threonine sensor, TARS2 (P < 0.05). The abundances of the glutamine sensor, ARF1, the arginine sensor, CASTOR, and the methionine-SAMTOR GATOR complex were similar. Prematurity reduced (P < 0.05) the abundance of the mTOR-RagA and mTOR-RagC complexes, the phosphorylation of mTORC1 and muscle protein synthesis (P < 0.05). In conclusion, prematurity negatively affects protein synthesis in skeletal muscle of neonatal preterm piglets by blunting anabolic pathways responsible for nutrient-sensing and mTORC1 activation. The reduced anabolic response likely contributes to reduced lean growth and extrauterine growth restriction following preterm birth.

Change in the prevalence of extra-uterine growth restriction in very low birthweight infants, following the introduction of a written nutrition protocol, in a tertiary neonatal unit

Background: Advances in neonatal medicine, resulting in improved survival, have brought the concept of extra-uterine growth restriction (EUGR), defined as postnatal growth failure secondary to protein and energy deficits, to the forefront as an important cause of morbidity, particularly in very low birthweight (VLBW) neonates. Objectives: This study’s main objective was to determine the prevalence of EUGR in Steve Biko Academic Hospital in VLBW infants. Methods: This was a pre- (epoch 1) and post- (epoch 2) intervention study. The intervention was the introduction of a written nutritional protocol in the neonatal unit in mid-November 2017. Three definitions were used to identify EUGR, namely: (1) discharge weight < 10th percentile, (2) a change by −1.28 z-score in weight at discharge, and (3) the discharge weight percentile below the nadir percentile. Results: The prevalence of EUGR in epoch 1 was 85.7%, 63.5%, and 88.0% using the above definitions, respectively. The prevalence of EUGR in epoch 2 was 73.9%, 65.8%, and 89.4% using the above definitions, respectively. EUGR using the three definitions combined was present in 95.2% and 92.8% of infants in epochs 1 and 2, respectively. None of the differences in EUGR prevalence between the two epochs were significant. Conclusion: The prevalence of EUGR was not significantly different between the two epochs, although it had been proposed that the introduction of a written nutritional protocol would have decreased the prevalence of EUGR in epoch 2. One of the reasons proposed for this finding was poor adherence to the nutritional protocol during epoch 2.

Effect of Gender on Metabolic and Neurodevelopmental Parameters of Postnatally Growth-Restricted Rats Undergoing Catch-Up Growth.

To determine the long-term effects of early postnatal malnutrition and various degrees of catch-up growth on metabolic (serum glucose, leptin, triacylglycerides) and neurodevelopmental parameters (learning and memory) among male and female rodent models, mimicking human preterm infants. Randomized controlled trial. Place and Duration of the Study: CMH Multan Insitute of Medical Sciences, from September 2021 to December 2021. This study included 142 neonatal Wister rats, stratified into subgroups to mimic the human preterm infant model of postnatal malnutrition and catch-up growth. Metabolic consequences were assessed via serum analysis of glucose, leptin, and triacylglycerides. The neurocognitive comparison was made among subgroups via a passive avoidance test. Gender-specific comparison of all quantitative parameters was made among subgroups. Malnourished rats with accelerated catch-up growth achieved similar weight gain as normally fed rats when provided with adlibitum feeding in both males (p = 0.92) and females (p >0.99). Rats undergoing accelerated catch-up growth exhibited higher fasting serum glucose levels compared to those undergoing no, or normal catch-up growth (p <0.001). Malnourished female rats undergoing accelerated (p = 0.007), or no catchup growth (p = 0.004) exhibited significant deficits in learning and memory as compared to normally fed rats. Female malnourished rats with normal catchup growth exhibited no neurocognitive deficit as compared to normally fed rats (p = 0.08). Accelerated catch-up growth effectively addresses somatic growth disparities, while normal catch-up growth offers more favourable metabolic and neurodevelopmental outcomes. Particularly, female malnourished rats exhibited poor neurodevelopment in response to both accelerated and no catch-up growth. Gender-specific variations in neurodevelopment underscore the need for personalised care approaches for preterm nutritional care. Growth retardation, Leptin, Extrauterine growth restriction, Malnutrition, Neurodevelopment.

Impact of the Choice of Diagnostic Criteria and Growth Reference on the Prevalence of Extrauterine Growth Restriction in Extremely-Low-Birthweight Infants.

Variable diagnostic criteria and growth charts have been used for extrauterine growth restriction (EUGR). The objective was to assess the prevalence and concordance of EUGR in extremely-low-birthweight (ELBW) infants with the most frequent diagnostic criteria and growth charts. An observational, retrospective and multicenter study was conducted from 2011 to 2020 including ELBW infants from the Spanish SEN1500 Network. EUGR prevalence was calculated at discharge using different definitions: cross-sectional (anthropometry less than the 10th centile), longitudinal (decrease of more than 1 SD from birth to discharge), "true" cross-sectional and "true" longitudinal (using the criteria previously described, excluding infants small for gestational age at birth). Concordance among Fenton, Olsen and INTERGROWTH-21st was assessed with Fleiss' Kappa coefficient. The prevalence of EUGR was variable with the different definitions and growth references studied in the 7914 ELBW infants included. Overall, it was higher with Fenton for all the EUGR criteria studied by weight and length. The agreement among growth charts was substantial (κ > 0.6) for all the definitions except for longitudinal EUGR by weight (moderate, κ = 0.578). The prevalence of EUGR was variable in our cohort with the different diagnostic criteria and growth charts. The agreement among charts was good for all the definitions of EUGR except longitudinal EUGR by weight.

Extrauterine growth restriction in very-low-birthweight infants: prevalence and concordance according to Fenton, Olsen, and INTERGROWTH-21st growth charts in a multicenter Spanish cohort

Multiple criteria and growth references have been proposed for extrauterine growth restriction (EUGR). We hypothesized that these may impact the diagnosis of EUGR. The objective was to evaluate the prevalence of EUGR with its different definitions and the concordance according to Fenton, Olsen, and INTERGROWTH-21st in very-low-birthweight (VLBW) infants. This is an observational, retrospective, and multicenter study including VLBW infants from the Spanish SEN1500 Network from 2011 to 2020. Patients with major congenital anomalies, embryopathies, and gestational age less than 24 weeks were excluded. EUGR prevalence was calculated at discharge with cross-sectional, longitudinal, “true” cross-sectional, and “true” longitudinal definitions. Concordance was assessed with Fleiss’ kappa coefficient. 23582 VLBW infants from 77 NICUs were included. In total, 50.4% were men with a median of gestational age of 29 (4) weeks. The prevalence of EUGR (cross-sectional, longitudinal, and “true”) was variable for weight, length, and head circumference. Overall, the prevalence was higher with Fenton and lower with Olsen (cross-sectional and “true” cross-sectional) and INTERGROWTH-21st (longitudinal and “true” longitudinal). Agreement among the charts by weight was good only for cross-sectional EUGR and moderate for longitudinal, “true” cross-sectional, and “true” longitudinal. Concordance was good or very good for EUGR by length and head circumference.Conclusions: The prevalence of EUGR with the most commonly used definitions was variable in the cohort. Agreement among growth charts was moderate for all the definitions of EUGR by weight except cross-sectional and good or very good for length and head circumference. The choice of reference chart can impact the establishment of the diagnosis of EUGR.What is known:• EUGR has been defined in the literature and daily practice considering weight, length and head circumference with multiple criteria (cross-sectional, longitudinal, and “true” definition)• Different growth charts have been used for EUGR diagnosisWhat is new:• Prevalence of EUGR is variable depending on the definition and growth chart used in our cohort of VLBW infants• For the most frequently EUGR criteria used, traditionally considering weight, concordance among Fenton, Olsen and INTERGROWTH-21st growth charts is only moderate for all the definitions of EUGR by weight except cross-sectional definition. Concordance among the charts is good or very good for the different criteria of EUGR by head circumference and length

Intergrowth 21 Versus Fenton 2013 Growth Charts: Congruence in Assessing the Birth Size and the Proportion of Extra-uterine Growth Restriction in Preterm Babies

Background: Intergrowth-21st and Fenton 2013 growth charts are used for postnatal growth monitoring in preterms. There is no international consensus on which graph to refer to and why. This study is a local validation, of which graph would be plausible for the Indian population to detect small-for-gestational-age (SGA) and extra-uterine growth restriction (EUGR) babies, abetting in the settlement of this ambiguity. Objectives: The primary objective was to compare the Intergrowth-21st with Fenton 2013 growth charts for birth size classification and to detect the proportion of EUGR in preterms. The secondary objective was to assess the proportion of comorbidities in SGA babies by both these graphs. Methods: The design of the study was a prospective comparative observational study. All preterm newborns (24–&lt;37 weeks of gestation) admitted to the neonatal intensive care unit of Noble Hospital and Research Center, Maharashtra, were the participants. Weight, length, and head circumference were plotted on Intergrowth 21 and Fenton growth charts at birth and at 4 weeks of age or at 36 weeks of postmenstrual age whichever is later. Corresponding Z-scores and percentiles were calculated electronically from their respective online software. Outcome: the reliability of Intergrowth-21st when compared to Fenton 2013 growth charts in assessing the birth size was better, and detection of the proportion of EUGR in preterm babies was better with Fenton charts. Results: A total of 429 preterm babies with a mean gestational age of 33.3 ± 2.4 weeks were included in the study. Fenton (67.1%) overestimated the proportion of EUGR when compared to Intergrowth-21st (18.6%) which was statistically significant (P &lt; 0.001). On the contrary, although the proportion of SGA babies detected was higher with Intergrowth-21st (29.8%) when compared to Fenton (19.6%), there was moderate-to-high statistically significant agreement observed between the two growth charts in detecting SGA babies (Kappa = 0.716, P &lt; 0.001). The proportion of comorbidities did not vary significantly among the SGA babies between the growth charts (P &gt; 0.05). Conclusion: Fenton overestimates EUGR when compared to Intergrowth-21st, whereas both the growth charts are equally good in identifying SGA babies with no differences in the comorbidities detected. Intergrowth-21st standards look more pertinent for growth monitoring in the current study setting for Indian preterm babies.

Implementation of a Standardized Feeding Protocol in a Level III Neonatal Intensive Care Unit

Introduction: The nutritional management of preterm infants in the Neonatal Intensive Care Unit (NICU) can be challenging and can often lead to extrauterine growth restriction (EUGR). A new feeding protocol was recently established and implemented at Ascension St. John’s NICU. Objectives: 1.) To determine the association of a standardized feeding protocol in the NICU and feeding intolerance, as well as growth outcomes and the number of days on parenteral nutrition; and 2.) To determine the association of a standardized feeding protocol and the development of necrotizing enterocolitis and central line associated infections. Methods: This study was a historical cohort study done by retrospective chart review. The pre-feeding protocol period included infants &lt;32 weeks gestation and &lt;1500g who were in the NICU between 1/1/2018 to 12/31/2020. The post-feeding protocol period was from 1/1/2021 to 11/15/2023. Data were recorded on demographics; and measurements at birth, 34 weeks postmenstrual age, and at discharge. Nutritional milestones and clinical outcomes were collected. Statistical analysis was done using Student’s t-test, the chi-squared test, the Mann-Whitney U test and repeated measures analysis of variance. Results: A total of 243 infants were included: 158 pre-implementation and 85 post-implementation of protocol. The mean gestational age was 27.7 ± 2.3 weeks, 61.7% of infants were black and 53.5% were female; there were no significant differences by time period. Results show no statistically significant difference in growth outcomes, days when infants received nothing by mouth; necrotizing enterocolitis, or sepsis. There was a delay in fortification and reaching full feeds, longer parental nutrition and central line days, and higher number of central line associated infections in the post-implementation period. Rates of intraventricular hemorrhage, retinopathy of prematurity and pulmonary outcomes were improving. Conclusions: The data suggest that implementation of a standardized feeding protocol can improve short term morbidities in high-risk neonates. Future studies are needed to optimize feeding protocols with the goal of improving growth, nutrition, and neurodevelopmental outcomes of this high-risk population.

Reducing extrauterine growth restriction in very preterm neonates: A before-after intervention study.

Focus on preterm nutrition strategies is imperative. Extrauterine growth restriction (EUGR) is a clinically relevant, but seemingly elusive consequence, often used to benchmark and compare outcomes. This before-after observational study was designed to study the effect of a multipronged updated "nutrition care bundle" in very preterm infants on rate of EUGR compared with a cohort from a previous period. Eligible participants were neonates born at <32 weeks' gestation who completed care in the unit; a retrospective group from a previous period and a prospective cohort after implementation of the bundle were included. The bundle constituted of three key areas: (1) aggressive parenteral nutrition with high-dose amino acids and lipids from day 1, (2) "rapid-escalation" enteral feed regimens including earlier introduction of human milk fortifier (at 40-ml/kg/day feeds), and (3) colostrum mouth paint and structured oromotor stimulation to promote oral feeding. EUGR was defined as a z score difference of >-1 in weight for postmenstrual age (PMA) at discharge and at birth. Data of 116 infants were retrieved for the retrospective group; 103 infants were included in the prospective group. EUGR was reduced from 71% to 58% (P = 0.039) after implementation of the bundle. Infants in the prospective group achieved full oral feeds at earlier PMA (P < 0.001) and were discharged at earlier PMA (P = 0.002). The proportion of neonates with EUGR was reduced significantly after implementation of the revised nutrition care bundle. Achievement of full oral feeds and discharge readiness were earlier in the prospective group.

Mortality and extrauterine growth restriction of necrotizing enterocolitis in very preterm infants with heart disease: a multi-center cohort study.

Congenital heart disease (CHD) and patent ductus arteriosus (PDA) are risk factors of necrotizing enterocolitis (NEC) in infants. However, it is unclear whether the prognosis of NEC is different between very preterm infants (VPIs) with and without heart diseases. This was an observational cohort study that enrolled VPIs (born between 24+0 and 31+6weeks) admitted to 79 tertiary neonatal intensive care units (NICU) in the Chinese Neonatal Network (CHNN) between 2019 and 2021. The exposure was CHD or isolated PDA, and VPIs with NEC were divided into three groups: complicated with CHD, with isolated PDA, and without heart diseases. The primary outcomes were NEC-related adverse outcomes (death or extrauterine growth restriction (EUGR)). Logistic regression models were used to adjust potential confounders and calculate the odds ratios (ORs) and 95% confidential intervals (CIs) for each outcome. A total of 1335 VPIs with NEC were enrolled in this study, including 65 VPIs with CHD and 406 VPIs with isolated PDA. The VPIs with heart diseases had smaller gestational ages and lower body weights at birth, more antenatal steroids use, and requiring inotrope prior to the onset of NEC. While suffering from NEC, there was no significant increased risks in NEC-related death in VPIs with either CHD (adjusted OR [aOR]: 1.10; 95% CI: 0.41-2.50) or isolated PDA (aOR: 1.25; 95% CI 0.82-1.87), and increased risks in EUGR were identified in either survival VPIs with CHD (aOR: 2.35; 95% CI: 1.31-4.20) or isolated PDA (aOR: 1.53; 95% CI: 1.16-2.01) in survivors. The composite outcome (death or EUGR) was also more often observed in VPIs with either CHD (aOR: 2.07; 95% confidence interval [CI]: 1.20-3.60) or isolated PDA (aOR: 1.51; 95% CI: 1.17-1.94) than that without heart diseases. VPIs with either CHD or isolated PDA were associated with significantly prolonged duration of fasting, extended time to achieve full enteral feeding, and longer ventilation duration and hospitalization duration. Similar characteristics were also seen in VPIs with isolated PDA, with the exception that VPIs with CHD are more likely to undergo surgical intervention and maintain a prolonged fast after NEC. Conclusion: In VPIs with NEC, CHD and isolated PDA are associated with an increased risk in worse outcomes. We recommend that VPIs with cardiac NEC be managed with aggressive treatment and nutrition strategies to prevent EUGR. What is Known: • CHD and PDA are risk factors for NEC in infants, which can lead to adverse outcomes such as death and EUGR. • NEC in infants with heart disease differs clinically from that in infants without heart disease and should be recognized as a separate disease process. What is New: • CHD and isolated PDA are associated with increased risks of EUGR in VPIs with NEC. • Risk factors associated with VPIs with cardiac NEC suggested these patients should be managed with aggressive treatment and nutrition strategies to adverse outcomes.

Association of different doses of antenatal corticosteroids exposure with early major outcomes and early weight loss percentage in extremely preterm infants or extremely low birthweight infants: a multicentre cohort study

ObjectivesTo determine the dose-dependent associations between antenatal corticosteroids (ANS) exposure and the rates of major morbidities, and the early weight loss percentage (EWLP) in hospital among extremely preterm infants (EPI)...

Risk Factors Contributing to Extrauterine Growth Restriction in Very Low Birth Weight Infants

Purpose: Despite advances in neonatal care, extrauterine growth restriction (EUGR) remains common in preterm infants. This retrospective single-center study aimed to determine the incidence and risk factors of EUGR in very low birth weight (VLBW) infants.Methods: Data were collected concerning VLBW infants with gestational age (GA) &lt;32 weeks between 2011 and 2020. EUGR was defined as a decline in weight z-score &gt;1.2 from birth to discharge, using Fenton growth charts.Results: Among 331 eligible preterm infants, the prevalence of EUGR at discharge was 71.6%. Infants with EUGR had lower GA and birth weight than those without EUGR. They also underwent prolonged durations of parenteral nutrition, invasive ventilation, and hospitalization. Neonatal morbidities, such as bronchopulmonary dysplasia, patent ductus arteriosus, necrotizing enterocolitis, gastrointestinal surgery, sepsis, and parenteral nutrition-associated cholestasis were more prevalent in the EUGR group. Multivariate analysis identified lower GA and longer time to reach full enteral feeding as independent risk factors, whereas maternal use of antenatal steroids and history of gestational diabetes mellitus were independent protective factors for EUGR.Conclusion: As VLBW infants are at a high risk of EUGR, continuous attention and efforts to achieve early full enteral nutrition are required to decrease the incidence of EUGR.

Metabolic and Low-Grade Inflammation Risk in Young Adults with a History of Extrauterine Growth Restriction.

Children with a history of extrauterine growth restriction (EUGR), later at prepubertal age, exhibit an increased metabolic risk including risen insulin resistance and low-grade inflammation. However, the progression of such metabolic changes after puberty and the lasting health implications have not yet been investigated. The objective of this study was to ascertain whether young adults with a history of EUGR faced increased vulnerability to metabolic disorders. A study was conducted comparing a group of adults with a history of EUGR with a healthy reference group. A total of 110 young adults (36 from the EUGR group and 74 from the control group) were included. Anthropometric variables, blood pressure (BP), general biochemical parameters, plasma inflammatory biomarkers, and adipokines were assessed. Compared to the reference group, the EUGR group had a shorter height and body weight with higher lean mass and waist circumference, as well as a greater percentage of individuals with high BP. In addition, EUGR patients had higher values of insulin, HOMA-IR, nerve growth factor, and leptin, and lower levels of adiponectin and resistin. The present study suggests that young adults with a history of EUGR present increased metabolic risk factors therefore, clinical follow-up should be considered.

Testing the reported long-term advantages of protein-fortified human milk in very low birth weight neonates

Preterm infants are at-risk for extrauterine growth restriction and downward percentile-crossing between birth and discharge. Increased energy and protein intake through fortification of human milk during the first weeks of life has been associated with improved short-term growth and better developmental outcomes. The aim of this study was to evaluate whether these benefits persist up to children school age. The study was designed as an observational study. During hospitalization, 22 very low birth weight preterm infants were fed with increasing protein fortification of human milk (protein supplemented group, PSG). As a control group (CG), 11 preterm infants were fed with standard nutrition regimen. At children school age (9–11 years), we assessed anthropometric data (weight, height, BMI), global health (renal function), and specific psychological outcomes (Child Behavior Checklist 6–18). A global homogeneity between CG and PSG groups emerged: we found no significant differences in weight, height, and BMI, nor in internalizing symptom outcomes (all ps &amp;gt; 0.05). However, mothers reported significantly higher externalizing symptoms for the PSG infants compared to CG infants. Therefore, neonatal enteral protein supplementation in very low birth weight preterm infants leads to no positive nor adverse consequences in long-term assessment, suggesting that benefits are restricted to the neonatal term and first years of age.

Postnatal Growth Assessment and Prediction of Neurodevelopment and Long-Term Growth in Very Low Birth Weight Infants: A Nationwide Cohort Study in Korea.

Background/Objectives: Extrauterine growth restriction (EUGR) is associated with high mortality and an increased incidence of poor neurodevelopmental outcomes in preterm infants. In this study, we aimed to compare the Intergrowth-21ST (IG-21ST) and Fenton charts in predicting long-term neurodevelopmental and anthropometric outcomes of very low birth weight (VLBW) infants. Methods: Data were collected from 2649 VLBW infants registered in the Korean Neonatal Network born between 240/7 and 316/7 weeks of gestational age from January 2013 to December 2017. Follow-up assessments were conducted at 18-24 months of age, corrected for prematurity. Multiple logistic regression analysis was performed to evaluate the association between EUGR and long-term outcomes. Results: Among the 2649 VLBW infants, 60.0% (1606/2649) and 36.9% (977/2649) were diagnosed as having EUGR defined by the Fenton chart (EUGRF) and by the IG-21ST chart (EUGRIG), respectively. The EUGRIG group exhibited a higher proportion of infants with cerebral palsy, neurodevelopmental impairment (NDI), and growth failure. In multiple logistic regression analysis, adjusted for risk factors for long-term outcome, the EUGRIG group showed higher risk of cerebral palsy (adjusted odds ratio [aOR], 1.66; 95% confidence interval [CI], 1.04-2.65), NDI (aOR, 2.09; 95% CI, 1.71-2.55), and growth failure (aOR, 1.57; 95% CI, 1.16-2.13). Infants with EUGRF tended to develop NDI (aOR, 1.29; 95%CI, 1.03-1.63) and experience growth failure (aOR, 2.44; 95% CI, 1.77-3.40). Conclusions: The IG-21ST chart demonstrated a more effective prediction of long-term neurodevelopmental outcomes, whereas the Fenton chart may be more suitable for predicting growth failure at 18-24 months.

Influence of morbidity, early nutritional intake, and total energy: protein ratio on longitudinal extrauterine growth restriction of very preterm newborns at term-equivalent age: an observational study.

To evaluate the influence of early nutritional intake on the growth pattern of very preterm infants. This was an observational study including 109 newborns (< 32weeks gestational age). Perinatal morbidities, nutritional therapy (first four weeks of life), and weight, length, and head circumference (HC) growth at term-equivalent age were evaluated. Growth restriction was defined as a difference > 1.2 SD between the birth and term age measurements. Growth restriction at term-equivalent age: 52.3% (weight), 42.9% (length), and 22% (HC). Morbidities were positively correlated with nutrition therapy and negatively correlated with the total energy provision: protein ratio. The duration of parenteral nutrition, the time to reach full enteral feedings, and the total energy provision: protein ratio were significantly correlated. Nutrient intake influenced weight, length, and HC growth, and cumulative energy deficit was significantly associated with HC growth restriction. Conclusion: Perinatal morbidities interfere with nutritional therapy and early nutrient intake, leading to insufficient energy and energy provision: protein ratio for growth. What is Known: • The intake of macronutrients early in life, mainly protein, is important for the optimal growth of pretem infants. • The severity of morbidities and low gestational ages impact the nutritional management of preterm infants. What is New: • The number of morbidities, reflecting the severity of the neonatal clinical course, had a detrimental effect on the nutritional therapy and nutrients intake. • The inadequate energy provision per gram of protein ratio was significantly associated with growth restriction in all growth measures at the second week of life, persisting for head circumference up to the fourth week, highlighting the importance of its measurement, as it could be a precocious sign of development risk.

Multidisciplinary evidence-based tools for improving consistency of care and neonatal nutrition.

Extrauterine growth restriction from inadequate nutrition remains a significant morbidity in very low birth weight infants. Participants in the California Perinatal Quality Care Collaborative Quality Improvement Collaborative, Grow, Babies, Grow! developed or refined tools to improve nutrition and reduce practice variation. Five Neonatal Intensive Care Units describe the development and implementation of nutrition tools. Tools include Parenteral Nutrition Guidelines, Automated Feeding Protocol, electronic medical record Order Set, Nutrition Time-Out Rounding Tool, and a Discharge Nutrition Recommendations. 15 of 22 participant sites completed a survey regarding tool value and implementation. Reduced growth failure at discharge was observed in four of five NICUs, 11-32% improvement. Tools assisted with earlier TPN initiation (8 h) and reaching full feeds (2-5 days). TPN support decreased by 5 days. 80% of survey respondents rated the tools as valuable. Evidence and consensus-based nutrition tools help promote standardization, leading to improved and sustainable outcomes.

Variability in Definitions and Criteria of Extrauterine Growth Restriction and Its Association with Neurodevelopmental Outcomes in Preterm Infants: A Narrative Review.

Extrauterine growth restriction (EUGR) has been used in the literature and clinical practice to describe inadequate growth in preterm infants. Significant variability is seen in the criteria for EUGR, with no standard definition reached to date. Moreover, no consensus on the optimal timing for assessment or the ideal growth monitoring tool has been achieved, and an ongoing debate persists on the appropriate terminology to express poor postnatal growth. To ensure an adequate understanding of growth and early intervention in preterm infants at higher risk, it is critical to relate the diagnostic criteria of EUGR to the ability to predict adverse outcomes, such as neurodevelopmental outcomes. This narrative review was conducted to present evidence that evaluates neurodevelopmental outcomes in preterm infants with EUGR, comparing separately the different definitions of this concept by weight (cross-sectional, longitudinal and "true" EUGR). In this article, we highlight the challenges of comparing various published studies on the subject, even when subclassifying by the definition of EUGR, due to the significant variability on the criteria used for each definition and for the evaluation of neurodevelopmental outcomes in different papers. This heterogeneity compromises the obtention of a single firm conclusion on the relation between different definitions of EUGR and adverse neurodevelopmental outcomes.