Extrauterine Growth Restriction Research Articles

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 > 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.

Gut microbial network signatures of early colonizers in preterm neonates with extrauterine growth restriction

BackgroundExtrauterine growth restriction (EUGR) represents a prevalent condition observed in preterm neonates, which poses potential adverse implications for both neonatal development and long-term health outcomes. The manifestation of EUGR has been intricately associated with perturbations in microbial and metabolic profiles. This study aimed to investigate the characteristics of the gut microbial network in early colonizers among preterm neonates with EUGR.MethodsTwenty-nine preterm infants participated in this study, comprising 14 subjects in the EUGR group and 15 in the normal growth (AGA) group. Meconium (D1) and fecal samples were collected at postnatal day 28 (D28) and 1 month after discharge (M1). Subsequently, total bacterial DNA was extracted and sequenced using the Illumina MiSeq system, targeting the V3-V4 hyper-variable regions of the 16S rRNA gene.ResultsThe outcomes of principal coordinates analysis (PCoA) and examination of the microbial network structure revealed distinctive developmental trajectories in the gut microbiome during the initial three months of life among preterm neonates with and without EUGR. Significant differences in microbial community were observed at the D1 (P = 0.039) and M1 phases (P = 0.036) between the EUGR and AGA groups, while a comparable microbial community was noted at the D28 phase (P = 0.414). Moreover, relative to the AGA group, the EUGR group exhibited significantly lower relative abundances of bacteria associated with secretion of short-chain fatty acids, including Lactobacillus (P = 0.041) and Parabacteroides (P = 0.033) at the D1 phase, Bifidobacterium at the D28 phase, and genera Dysgonomonas (P = 0.042), Dialister (P = 0.02), Dorea (P = 0.042), and Fusobacterium (P = 0.017) at the M1 phase.ConclusionOverall, the present findings offer crucial important insights into the distinctive gut microbial signatures exhibited by earlier colonizers in preterm neonates with EUGR. Further mechanistic studies are needed to establish whether these differences are the cause or a consequence of EUGR.

Early postnatal nutrition and renal consequences in preterm infants.

Perinatal nutritional factors may lead to decreased nephron endowment, decreased kidney function, and long-term development of chronic kidney disease and non-communicable diseases. At the same time, optimal postnatal nutrition and catch-up growth are associated with better neurodevelopmental outcomes in preterm infants. Therefore, nutritional management of preterm infants is a major challenge for neonatologists. In this context, the Section of Nutrition, Gastroenterology and Metabolism reviewed the current knowledge on nutritional issues related to kidney function. This narrative review discusses the clinical impact of early postnatal nutrition on long-term kidney function. In preterm infants, data are largely lacking to determine the extent to which early nutrition contributes to nephrogenesis and nephron endowment. However, some nutritional principles may help clinicians better protect the developing kidney in preterm infants. IMPACT: Clinical data show that preterm infants are an emerging population at high risk for chronic kidney disease. Both undernutrition and overnutrition can alter long-term kidney function. In preterm infants, data are largely lacking to determine the extent to which early postnatal nutrition contributes to nephrogenesis, nephron endowment and increased risk for chronic kidney disease. Some nutritional principles may help clinicians better protect the developing kidney in preterm infants: avoiding extrauterine growth restriction; providing adequate protein and caloric intakes; limiting exposure to high and prolonged hyperglycaemia; avoiding micronutrient deficiencies and maintaining acid-base and electrolyte balance.

Extrauterine Growth Restriction and Catch-up Growth Following NICU Discharge: A Tale of two Standards

Aim: Extrauterine growth restriction (EUGR) is common in premature infants, but the progression after neonatal intensive care unit (NICU) discharge is not well described. We aimed to assess EUGR after NICU discharge and to identify factors associated with catch-up growth (CUG) and neurodevelopmental outcomes at 2 years of age. Methods: Growth parameters at birth, 36 weeks postmenstrual age (PMA), and two neurodevelopmental follow-up visits for preterm graduates of our NICU were reviewed. EUGR was assessed using Fenton and Intergrowth-21 standards. Factors associated with outpatient growth and neurodevelopmental outcomes at 2 years of age were evaluated using logistic and linear regression. Results: 369 infants born at 24–32 weeks gestation comprised the cohort. EUGR prevalence was 14.9% for Intergrowth-21 versus 56.4% for Fenton ( p &lt; .001). Although there was a significant decrease in weight z-score from birth to 36 weeks PMA, weight z-scores returned to their birth weight values at the second clinic visit (86 weeks PMA). Infants who received formula as opposed to human milk (HM) showed faster CUG. Higher scores in the Bayley-III scale at 2 years of age were associated with HM feeding. Discussion/Conclusion: Fewer infants were identified as EUGR when Intergrowth-21 versus Fenton growth standards were used, which categorizes infants with adverse clinical courses and poorer neurodevelopmental outcomes more distinctly. While growth failure during the birth hospitalization is common in preterm infants, outpatient CUG was demonstrated, with return to birth weight z-score. Our findings suggest that HM feeding may have a positive impact on cognitive, language, and motor developmental outcomes for preterm infants despite less rapid CUG.

Early Extra-Uterine Growth Restriction in Very-Low-Birth-Weight Neonates with Normal or Mildly Abnormal Brain MRI: Effects on a 2-3-Year Neurodevelopmental Outcome.

Extra-uterine growth restriction (EUGR) is a common complication and a known risk factor for impaired development in very-low-birth-weight (VLBW) neonates. We report a population of 288 patients with no or with low-grade MRI lesions scanned at a term equivalent age (TEA) born between 2012 and 2018. Griffiths Mental Development Scale II (GMDS II) at 2 and 3 years, preterm complications and weight growth were retrospectively analyzed. EUGR was defined for weight z-score ˂ 10 percentile at TEA, 6 and 12 months of correct age or as z-score decreased by 1-point standard deviation (SDS) from birth to TEA and from TEA to 6 months. Multivariate analysis showed that a higher weight z-score at 6 months is protective for the global developmental quotient (DQ) at 2 years (OR 0.74; CI 95% 0.59-0.93; p = 0.01). EUGR at 6 months was associated with worse locomotor, personal/social, language and performance DQ at 2 years and worse language and practical reasoning DQ at 3 years. In conclusion, a worse weight z-score at 6 months of age seems to be an independent risk factor for significantly reduced GMDS in many areas. These results suggest that we should invest more into post-discharge nutrition, optimizing family nutritional education.

Association of Neonatal Antibiotic Exposure with Long-Term Growth Trajectory Faltering in Preterm-Birth Children

Plain Language SummaryPreterm infants often receive a variety of antibiotic exposure duration during admission. This study was to evaluate whether neonatal antibiotic exposure is associated with longitudinal growth problems in preterm-birth children. This study followed a cohort of 328 very preterm infants born <32 weeks of gestation, who were discharged from a tertiary hospital without documented neonatal bacterial infection from 2004 to 2016 and received longitudinal follow-up for growth outcomes at their corrected age (CA) 6, 12, 24, and 60 months. We collected perinatal demographics, neonatal morbidities, extrauterine growth restriction, and antibiotic exposure duration by term equivalent age, to associate with trajectories in z-scores of bodyweight (zBW), body height (zBH), and body mass index (zBMI) from CA 6–60 months. We found antibiotic exposure duration was negatively associated with zBW and zBH at CA 6, 12, and 60 months, and zBMI at CA 60 months. After adjustments, antibiotic exposure duration was associated with decreased growth velocity in zBW and zBH from CA 6–60 months. Children with longer antibiotic exposure >15 days had significantly lower zBW, zBH, and zBMI at CA 6, 12, 24, and 60 months compared with children with antibiotic exposure ≤15 days (all p < 0.01), suggesting that longer antibiotic exposure duration was associated with inferior weight and height gains. This study concludes that long-term growth increments may negatively associate with neonatal antibiotic exposure duration in children born very premature, implicating that antibiotic stewardship and growth follow-up for preterm neonates are thus warranted.

Music therapy and weight gain in preterm infants: Secondary analysis of the randomized controlled LongSTEP trial.

This study assessed the association between MT and weight gain among preterm infants hospitalized in Neonatal Intensive Care Units. Data collected during the international, randomized, Longitudinal Study of Music Therapy's Effectiveness for Premature Infants and their Caregivers (LongSTEP) study were compared between the MT group and the standard care (SC) group. Weights were recorded at birth, enrollment, and discharge. Weight percentiles, Z-scores, weight gain velocity, and extrauterine growth restriction (EUGR) were calculated. Among 201 preterm infants included, no significant differences in weight parameters (weight, weight percentiles, weight Z-scores; all p ≥ 0.23) were found between the MT group (n = 104) and the SC (n = 97) group at birth, enrollment, or discharge. No statistical differences in EUGR represented by change in Z-scores from birth to discharge were recorded between MT and SC (0.8 vs. 0.7). Among perinatal parameters, younger gestational age (p = 0.005) and male sex (p = 0.012) were associated with increased risk of EUGR at discharge. Antenatal steroid treatment, systemic infection, bronchopulmonary dysplasia, neurological morbidities, retinopathy of prematurity, necrotizing enterocolitis, parental factors (amount of skin-to-skin care, bonding, anxiety, and depression questionnaire scores), and type of enteral nutritiondid not significantly influence weight gain parameters (all p > 0.05). In the LongSTEP study, MT for preterm infants and families was not associated with better weight parameters compared to the SC group. The degree of prematurity remains the main risk factor for unfavorable weight parameters.

Comparative effectiveness of explainable machine learning approaches for extrauterine growth restriction classification in preterm infants using longitudinal data

IntroductionPreterm birth is a leading cause of infant mortality and morbidity. Despite the improvement in the overall mortality in premature infants, the intact survival of these infants remains a significant challenge. Screening the physical growth of infants is fundamental to potentially reducing the escalation of this disorder. Recently, machine learning models have been used to predict the growth restrictions of infants; however, they frequently rely on conventional risk factors and cross-sectional data and do not leverage the longitudinal database associated with medical data from laboratory tests.MethodsThis study aimed to present an automated interpretable ML-based approach for the prediction and classification of short-term growth outcomes in preterm infants. We prepared four datasets based on weight and length including weight baseline, length baseline, weight follow-up, and length follow-up. The CHA Bundang Medical Center Neonatal Intensive Care Unit dataset was classified using two well-known supervised machine learning algorithms, namely support vector machine (SVM) and logistic regression (LR). A five-fold cross-validation, and several performance measures, including accuracy, precision, recall and F1-score were used to compare classifier performances. We further illustrated the models’ trustworthiness using calibration and cumulative curves. The visualized global interpretations using Shapley additive explanation (SHAP) is provided for analyzing variables’ contribution to final prediction.ResultsBased on the experimental results with area under the curve, the discrimination ability of the SVM algorithm was found to better than that of the LR model on three of the four datasets with 81%, 76% and 72% in weight follow-up, length baseline and length follow-up dataset respectively. The LR classifier achieved a better ROC score only on the weight baseline dataset with 83%. The global interpretability results revealed that pregnancy-induced hypertension, gestational age, twin birth, birth weight, antenatal corticosteroid use, premature rupture of membranes, sex, and birth length were consistently ranked as important variables in both the baseline and follow-up datasets.DiscussionThe application of machine learning models to the early detection and automated classification of short-term growth outcomes in preterm infants achieved high accuracy and may provide an efficient framework for clinical decision systems enabling more effective monitoring and facilitating timely intervention.

Comparison of Intergrowth-21st and Fenton growth standards to evaluate and predict the postnatal growth in eastern Chinese preterm infants

ObjectivesThe aim of this article was to compare the differences between Intergrowth-21st (IG-21) and Fenton growth standards in the classification of intrauterine and extrauterine growth restriction (EUGR) in eastern Chinese preterm infants, and detect which one can better relate to neonatal diseases and predict the physical growth outcomes at 3–5 years old.MethodsPremature infants admitted to a tertiary pediatric hospital in Shanghai, China, from 2016 to 2018 were enrolled. Prenatal information, neonatal diseases during hospitalization, and anthropometric data (weight, height, and head circumference) at birth and at discharge were collected and analyzed. Physical growth outcomes (short stature, thinness, and overweight) were examined by telephone investigations in 2021 at age 3–5 years.ResultsThe medium gestational age and birth weight of the included 1,065 preterm newborns were 33.6 weeks and 1,900 g, respectively. The IG-21 curves diagnosed more newborns with small for gestational age (SGA) (19% vs. 14.7%) and fewer newborns with longitudinal EUGR on height (25.5% vs. 27.9%) and head circumference (17.9% vs. 24.7%) compared to Fenton curves. Concordances between Fenton and IG-21 standards were substantial or almost perfect in the classification of SGA and longitudinal EUGR, but minor in cross-sectional EUGR. EUGR identified by Fenton curves was better related to neonatal diseases than IG-21 curves. There were no statistical significances in the prediction of short stature, thinness, and overweight at 3–5 years old between the two charts.ConclusionsIG-21 growth standards are not superior to Fenton in assessing preterm growth and development in the eastern Chinese population.

Maternal and neonatal outcomes of twin pregnancies complicated by gestational diabetes mellitus

IntroductionGestational diabetes mellitus (GDM) is associated with a higher risk of adverse maternal outcomes, but its effects on maternal and perinatal outcomes of twin pregnancies remain conflicting.MethodsThis retrospective cohort study included all primipara who delivered twin pregnancies at a single tertiary perinatal center between January 1, 2016 and December 31, 2022. Excluded were those who had a single pregnancy, twin pregnancies with pre-existing diabetes, missing information on GDM screening, a delivery before gestational 28 weeks, complications related to monochorionic placentation, multifetal reduction, fetal anomalies, and monochorionic monoamniotic twins. Maternal outcomes included preterm birth, pre-eclampsia, hypothyroidism, preterm premature rupture of membranes (PROM), placental abruption, severe postpartum hemorrhage, and oligohydramnios. Neonatal outcomes included small-for-gestational-age (SGA), large-for-gestational-age (LGA), birthweight, Apgar score, neonatal intensive care unit (NICU) admission, extrauterine growth restriction (EUGR), and neonatal hypoglycemia.ResultsA total of 3269 twins were delivered, with 897 women (27.4%) diagnosed with GDM during pregnancies; moreover, 72 (8.0%) of these women received insulin treatment. The GDM group showed a significantly higher maternal age at delivery (≥35 years), as well as incidences of overweight and obesity. These factors also elevated the odds of insulin treatment in GDM women with twin pregnancies (OR = 1.881, 95% CI = 1.073–3.295, P = 0.027; OR = 2.450, 95% CI = 1.422–4.223, P < 0.001; OR = 4.056, 95% CI = 1.728–9.522, P < 0.001, respectively). Chronic hypertension prior to pregnancy was identified as a risk factor for GDM during twin pregnancies (OR = 1.896, 95% CI = 1.290–2.785, P < 0.001), although it did not increase the proportion of women requiring insulin treatment (P = 0.808). Aside from a higher incidence of preterm birth before 37 weeks in insulin-treated GDM twins (OR = 2.096, 95% CI = 1.017–4.321, P = 0.045), there were no significant difference in other maternal outcomes (preterm birth before 34 weeks, pre-eclampsia, hypothyroidism, PROM, placental abruption, placenta previa, severe postpartum hemorrhage, and oligohydramnios) between the GDM group and non-GDM group, and between insulin-treated GDM and non-insulin-treated GDM. The rate of newborns with birthweight <1500 g was significantly lower among twins born to GDM women, but the prevalence of EUGR was notably higher. Additionally, the risk of EUGR was elevated in insulin-treated GDM twins (OR = 3.170, 95% CI = 1.639,6.131, P < 0.001). No significant differences were observed between the GDM group and non-GDM group, or between insulin-treated GDM and non-insulin-treated GDM group in terms of mean birthweight, newborn sex ratio, and incidences of other adverse neonatal outcomes, including gestational age at delivery, LGA, birth weight <2500 g, and 1-min and 5-min Apgar scores.ConclusionMaternal age ≥35 years, overweight or obesity, and chronic hypertension are significant risk factors for GDM during twin pregnancies. Women with GDM during twin pregnancies may achieve similar outcomes compared to those without GDM. However, the women with GDM during twin pregnancies receiving insulin therapy may have a higher risk of preterm birth and EUGR.

Extrauterine Growth Restriction: Need for an Accurate Definition.

Neonates show considerable variation in growth that can be recognized through serial measurements of basic variables such as weight, length, and head circumference. If possible, measurement of subcutaneous and total body fat mass can also be useful. These biometric measurements at birth may be influenced by demographics, maternal and paternal anthropometrics, maternal metabolism, preconceptional nutritional status, and placental health. Subsequent growth may depend on optimal feeding, total caloric intake, total metabolic activity, genetic makeup, postnatal morbidities, medications, and environmental conditions. For premature infants, these factors become even more important; poor in utero growth can be an important reason for spontaneous or induced preterm delivery. Later, many infants who have had intrauterine growth restriction (IUGR) and are born small for gestational age (SGA) continue to show suboptimal growth below the 10th percentile, a condition that has been defined as extrauterine growth restriction (EUGR) or postnatal growth restriction (PNGR). More importantly, a subset of these growth-restricted infants may also be at high risk of abnormal neurodevelopmental outcomes. There is a need for well-defined criteria to recognize EUGR/PNGR, so that correctional steps can be instituted in a timely fashion.

Investigation of extrauterine growth restriction in very preterm infants in Chinese neonatal intensive care units

Objective: To comprehensively assess the current status of extrauterine growth restriction (EUGR) in very preterm infants (VPI) and its associated factors in Chinese neonatal intensive care units (NICU). Methods: In this cohort study, 6 179 preterm infants born at <32 weeks' gestation were included, who were admitted to 57 hospitals in the China Neonatal Network in 2019 and hospitalized for ≥7 days. EUGR was evaluated by a cross-sectional definition (weight at discharge<10th percentile for postmenstrual age), a longitudinal definition (decline in weight Z score>1 from birth to discharge), and weight growth velocity. The comparison between infants with and without EUGR was conducted by t-test, Mann-Whitney U test or χ2 test as appropriate. Multivariable Logistic regression models were used to evaluate associations between EUGR with different definitions and maternal and neonatal factors, clinical practices, and neonatal morbidities. Results: A total of 6 179 VPI were enrolled in the study, with a gestational age of (29.8±1.5) weeks and birth weight of (1 365±304) g; 56.2% (3 474) of them were male. Among them, 48.4% (2 992 VPI) were cross-sectional EUGR and 74.9% (4 628 VPI) were longitudinal EUGR. Z score of weight was (0.13±0.78) at birth and decrease to (-1.35±0.99) at discharge. The weight growth velocity was 10.13 (8.42, 11.66) g/(kg·d). Multivariate Logistic regression analysis showed that among the influential factors that could be intervened after birth, late attainment of full enteral feeds (ORadjust=1.01, 95%CI 1.01-1.02, P<0.001; ORadjust=1.01, 95%CI 1.01-1.02, P<0.001), necrotizing enterocolitis≥Ⅱstage (ORadjust=2.64, 95%CI 1.60-4.35, P<0.001; ORadjust=1.62, 95%CI 1.10-2.40, P<0.001) and patent ductus arteriosus (ORadjust=1.94, 95%CI 1.50-2.51, P<0.001; ORadjust=1.63, 95%CI 1.29-2.06, P<0.001) were all associated with increased risks of both cross-sectional and longitudinal EUGR. In addition, late initiation of enteral feeds (ORadjust=1.06, 95%CI 1.02-1.09, P=0.020) and respiratory distress syndrome (ORadjust=1.45, 95%CI 1.24-1.69, P<0.001) were all associated with cross-sectional EUGR. Breast milk feeding (ORadjust=1.33, 95%CI 1.05-1.68, P<0.001) was associated with a higher risk of longitudinal EUGR. Conclusions: The incidence of EUGR in VPI in China is high. Some modifiable risk factors provide priorities to improve postnatal growth for VPI. Nutritional management of VPI and the efforts to decrease the incidence of complications are still the focus of clinical management in China.

Real-world evidence regarding the growth of very premature infants with small for gestational age after birth: a multicenter survey in China

BackgroundTo analyze the real-world growth pattern of very premature infants (VPI) with small for gestational age (SGA) after birth by using the ΔZ value of weight at discharge.MethodsThe clinical data were collected from 28 hospitals in China from September 2019 to December 2020. They were divided into the EUGR(Extrauterine Growth Restriction) and the non-EUGR group according to the criterion of ΔZ value of weight at discharge < –1.28.ResultsThis study included 133 eligible VPI with SGA. Following the criterion of ΔZ value, the incidence of EUGR was 36.84% (49/133). The birth weight, the 5-min Apgar score, and the proportion of male infants in the EUGR group were lower (P < 0.05). The average invasive ventilation time, cumulative duration of the administration of antibiotics, blood transfusion time, blood transfusion ratio, and total days of hospitalization were significantly higher in the EUGR group (P < 0.05). In the EUGR group, several factors exhibited higher values (P < 0.05), including the initiation of enteral feeding, the volume of milk supplemented with human milk fortifier (HMF), the duration to achieve complete fortification, the cumulative duration of fasting, the duration to achieve full enteral feeding, the length of parenteral nutrition (PN), the number of days required to attain the desired total calorie intake and oral calorie intake, as well as the age at which birth weight was regained. The average weight growth velocity (GV) was significantly lower in the EUGR group (P < 0.001). The incidences of patent ductus arteriosus with hemodynamic changes (hsPDA), neonatal necrotizing enterocolitis (NEC) stage≥ 2, late-onset sepsis (LOS), and feeding intolerance (FI) in the EUGR group were higher (P < 0.05). Multivariate logistic regression analysis showed that birth weight, male, and GV were the protective factors, while a long time to achieve full-dose fortification, slow recovery of birth weight, and NEC stage ≥2 were the independent risk factors.ConclusionSGA in VPI can reflect the occurrence of EUGR more accurately by using the ΔZ value of weight at discharge. Enhancing enteral nutrition support, achieving prompt and complete fortification of breast milk, promoting greater GV, reducing the duration of birth weight recovery, and minimizing the risk of NEC can contribute to a decreased occurrence of EUGR.Trial registrationCHICTR, ChiCTR1900023418. Registered 26/05/2019, http://www.chictr.org.cn.

The Impact of Estimated Energy and Protein Balances on Extrauterine Growth in Preterm Infants.

Nutritional support of preterm infants remains a field of debate in the literature and clinical practice varies significantly. Adequate nutrition should promote growth and aim for optimal later neurodevelopment. However, it is often impaired by prematurity-associated morbidity and the physiologic immaturity of preterm infants. This study assessed the impact of energy and macronutrient provision on growth velocity and outcome and explored differences attributed to the heterogeneity of the preterm population. We retrospectively collected clinical and nutritional data from neonates hospitalized in two separate Neonatal Intensive Care Units (NICUs). Estimated energy and protein balance were calculated based on the ESPGHAN guidelines and their association with the growth outcome was explored. Growth assessment was based on somatometry Delta (Δ) z-scores at discharge. In total, 174 neonates were included in the study. By day 14, most preterm infants were exclusively enterally fed, whereas there were infants in the <28 and 28-31+6 subgroups fed exclusively parenterally. Energy balance was positive for all gestational age (GA) subgroups except for those born <28 weeks. Protein balance was consistently positive for extremely premature but negative for late preterms. Cumulative substrates provisions were strong predictors of a positive energy or protein balance in the <34 weeks GA preterms on days 14 (ROC analyses, p < 0.001) and 7 (p < 0.05). A higher GA (p = 0.013) and enteral nutrition (p = 0.005) were additional predictors of a positive energy balance. All GA subgroups had a negative Δ z-score of weight at discharge. In the <34 GA subcohorts, a positive protein balance on day 14 (p = 0.009) and a short time to regain birth weight (exp(B) 3.1 (p = 0.004)) were independently associated with a positive Δ z-score of weight at discharge. Early achievement of a positive energy and protein balance, based on the ESPGHAN guidelines, is crucial to ensure optimal postnatal growth and prevent extrauterine growth restriction, a relatively common occurrence in preterm infants.

The incidence of and risk factors for hyperglycemia and hypoglycemia in preterm infants receiving early-aggressive parenteral nutrition

IntroductionOptimizing nutritional support helps prevent extra uterine growth restriction and adverse long-term outcomes in preterm infants. ObjectivesThis study aimed to analyze the incidence of and risk factors for hyperglycemia and hypoglycemia in preterm infants receiving early-aggressive parenteral nutrition (PN). MethodsThis prospective observational study included preterm infants receiving PN at the Neonatal Intensive Care Unit of Dr. Soetomo General Hospital between April 2018 and May 2019. Potential risk factors analyzed included asphyxia, sepsis, respiratory distress syndrome, multiple congenital anomalies, mortality, necrotizing enterocolitis, retinopathy of prematurity, the postoperative period, inotropic administration, glucose infusion rate (GIR) > 10–12 mg/kg/min, GIR 4–<5.5 mg/kg/min, and increase in GIR <1 mg/kg/min. ResultsOf the 105 preterm infants included, hyperglycemia and hypoglycemia were found in 14 (13.3%) and 26 (24.8%) infants, respectively, with most incidents occurring in the first week (hyperglycemia: 85.7%; hypoglycemia: 88.5%). Sepsis was an independent risk factor for hyperglycemia (odds ratio [OR]: 8.743, 95% confidence interval [CI]: 2.392–31.959; P = 0.001). Hypoglycemia independent risk factors included the postoperative period (OR: 4.425, 95% CI: 1.218–16.073; P = 0.024) and use of GIR 4–<5.5 mg/kg/min (OR: 2.950, 95% CI: 1.035–8.405; P = 0.043). ConclusionHyperglycemia and hypoglycemia can occur in preterm infants receiving early-aggressive PN; most cases occur within the first week of life. Hypoglycemia correlated with low glucose intake, and hyperglycemia correlated with sepsis. Monitoring blood glucose levels in preterm infants receiving PN, especially in the first weeks of life, may decrease morbidity associated with hyperglycemia or hypoglycemia.