Postnatal Growth Failure Research Articles

Early postnatal growth failure in infants

BackgroundPostnatal growth failure (PGF), a multifactorial condition is common in preterm infants and infants born weighing <1500 g and is associated with impaired neurodevelopmental and growth outcomes. In low-resource settings, like Uganda, parenteral nutrition and breastmilk fortifier are often unavailable, and preterm infants rely solely on their mother’s expressed breastmilk, which can be inadequate. This retrospective cohort study, conducted in a level II neonatal unit in eastern Uganda, aimed to evaluate the incidence of and risk factors for postnatal growth failure among infants <1500 g.MethodsThe study included infants with birthweight <1500 g, admitted within 24 h of birth, and who spent 7 or more days in the neonatal unit. Major congenital malformations or a diagnosis of hypoxic ischemic encephalopathy were exclusion criteria. PGF was defined as a decrease in weight Z score between birth and discharge of more than − 1.28. Data on feeding, anthropometry, co-morbidities, and clinical measures were extracted from medical records. Statistical analyses were performed using Stata 17.0 with crude and adjusted relative risks (RR) were reported.ResultsOne hundred and four infants were recruited, including 47 (45.2%) male and 57 (54.8%) female, with a mean birth weight of 1182 g (SD 18 g, 95% CI: 1140, 1210). Almost half were small for gestational age, most were singletons (66.3%), and most were born by spontaneous vaginal delivery (82.7%). PGF was observed at discharge in 75.9% (N = 79). Clinical risk factors for PGF included: small for gestational age (cRR 1.25, 95% CI: 1.01, 1.53), respiratory distress syndrome (aRR 1.30 95% CI: 1.01, 1.67), duration of bubble continuous positive airway pressure use (aRR 1.35, 95% CI: 1.10, 1.66), sepsis requiring second line (aRR 1.58, 95% CI: 1.22, 2.04) and third line treatment (aRR 1.46, 95% CI: 1.20, 1.77), prolonged time to achieve full feeds (aRR 1.30, 95% CI: 1.01, 1.66) and prolonged hospitalisation (aRR 1.85, 95% CI: 1.31, 2.61).ConclusionPGF was common among infants <1500 g in this hospitalised cohort who were primarily fed on their mother’s own milk. Urgent action is needed to enhance postnatal growth in this vulnerable patient group. Future research should focus on exploring multidisciplinary interventions that can improve growth outcomes in this population and understanding the long-term implications and need for care for these infants.

Distinguishing genetic alterations versus (epi)mutations in Silver-Russell syndrome and focus on the IGF1R gene.

Silver-Russell Syndrome (SRS) is a growth retardation disorder characterized by pre- and post-natal growth failure, relative macrocephaly at birth, prominent forehead, body asymmetry, and feeding difficulties. The main molecular mechanisms are imprinting alterations at multiple loci, though a small number of pathogenic variants have been reported in the SRS genes IGF2-PLAG1-HMGA2 and CDKN1C. However, around 40% of clinically suspected SRS cases do not achieve a molecular diagnosis, highlighting the necessity to uncover the underlying mechanism in unsolved cases. evaluate the frequency of genetic variants in undiagnosed SRS patients (NH-CSS≥4), and investigate whether (epi)genetic patients may be distinguished from genetic patients. 132 clinically SRS patients without (epi)genetic deregulations were investigated by Whole Exome (n=15) and Targeted (n=117) Sequencing. Clinical data from our cohort and from an extensive revision of literature were compared. pathogenic variants were identified in 9.1% of this cohort: 3% in IGF2, PLAG1, and HMGA2 genes, while 3% in the IGF1R gene, associated with IGF-1 resistance (IGF1RES), an SRS differential diagnosis. Overall, IGF2-PLAG1-HMGA2 and IGF1R account for 3.6% of SRS with NH-CSS score ≥ 4. A clinical cross-comparison of (epi)genetic versus genetic SRS underlined (epi)genotype-phenotype correlation, highlighted the prevalence of body asymmetry and relative macrocephaly in mosaic (epi)genetic SRS and recurrence of genetic familial cases. Furthermore, overlapping features were evidenced in (epi)genetic SRS and IGF1RES patients. Our study explores the frequency of genetic SRS, underscores body asymmetry as distinctive phenotype in (epi)genetic SRS and suggests IGF1R sequencing in SRS diagnostic flow-chart.

Early human milk feeding: Relationship to intestinal barrier maturation and postnatal growth.

Early exposure to mother's own milk (MOM) promotes intestinal barrier maturation in preterm infants. We hypothesized (1) donor human milk (DHM) supplementation reduces intestinal permeability (IP) similar to exclusive MOM and (2) early HM exposure and low IP at 7-10 days postnatal age (PNA) are associated with improved growth outcomes. IP was measured by the standard sugar absorption test (SAT) in infants <33 weeks gestation between 7-10 days PNA. Nutritional and anthropometric data were recorded. Postnatal growth failure (PNGF) was defined as a decrease in weight z-score >1 from birth to discharge to home. Of 158 preterm infants, the mean (SD) gestational age was 29.9(2.3) weeks and birthweight 1388(424) g. Diet prior to SAT was exclusive MOM [N = 55(35%)], DHM ± MOM [N = 52(33%)], or preterm formula±MOM [N = 51(32%)]. The mean Lactulose(La)/Rhamnose(Rh) ratio was lower in the exclusive MOM [0.06(0.07)] and DBM ± MOM [0.05(0.07)] groups compared to the preterm formula±MOM group [0.11(0.11)], p < 0.01). Cumulative intake >150 ml/kg MOM ± DHM, but not preterm formula within 7-10 days PNA was associated with early intestinal barrier maturation. Low IP was not associated with lower risk of PNGF at discharge. Low IP is associated with cumulative intake of MOM alone or supplemented with DHM > 150 ml/kg within 7-10 days PNA. Clinicaltrials.gov NCT01756040 ; web link to study on registry: https://clinicaltrials.gov/study/NCT01756040 . Key message Early intestinal barrier maturation is associated with cumulative intake of exclusive MOM alone or supplemented with DHM > 150 ml/kg within 7-10 days after birth, but is not associated with lower risk of PNGF at time of discharge. What it adds to existing literature? This observational study is the first study to demonstrate that supplemental DHM promotes intestinal barrier maturation similar to MOM alone. What is the impact? The findings underscore the importance of early introduction of human milk feeds as MOM or MOM supplemented with DHM in sufficient volume to promote early intestinal barrier maturation.

QSOX2 Deficiency-induced short stature, gastrointestinal dysmotility and immune dysfunction.

Postnatal growth failure is often attributed to dysregulated somatotropin action, however marked genetic and phenotypic heterogeneity exist. We report five patients from three families who present with short stature, immune dysfunction, atopic eczema and gastrointestinal pathology associated with recessive variants in QSOX2. QSOX2 encodes a nuclear membrane protein linked to disulphide isomerase and oxidoreductase activity. Loss of QSOX2 disrupts Growth hormone-mediated STAT5B nuclear translocation despite enhanced Growth hormone-induced STAT5B phosphorylation. Moreover, patient-derived dermal fibroblasts demonstrate Growth hormone-induced mitochondriopathy and reduced mitochondrial membrane potential. Located at the nuclear membrane, QSOX2 acts as a gatekeeper for regulating stabilisation and import of phosphorylated-STAT5B. Altogether, QSOX2 deficiency modulates human growth by impairing Growth hormone-STAT5B downstream activities and mitochondrial dynamics, which contribute to multi-system dysfunction. Furthermore, our work suggests that therapeutic recombinant insulin-like growth factor-1 may circumvent the Growth hormone-STAT5B dysregulation induced by pathological QSOX2 variants and potentially alleviate organ specific disease.

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.

Determining Deviation of the Growth Pattern of Preterm Infants and Its Causes According to the Fenton Growth Chart: A Longitudinal Follow-up Study

Background: Birth weight is a crucial indicator of infant health. In Iran, child growth monitoring for children under six years old is integrated into the healthcare system. However, existing growth charts have limitations in accurately representing preterm infants. Objectives: This study was conducted to determine the frequency of postnatal growth retardation and its causes in preterm infants from hospitalization to six months after birth. Methods: After informing parents, we recruited 255 preterm singleton infants born at the Afzalipour Medical Education and Health Center in Kerman, Iran, over one year. The Fenton growth chart was used to compare the anthropometric characteristics of the infants at birth, and at ages 7, 14, and 28 days, and then monthly up to 6 months. A special questionnaire also recorded the type of feeding, length of hospital stay, use of mechanical ventilation and oxygen, duration of total parenteral nutrition (TPN), and associated causes and complications. Results: The mean Z-score weights at birth, discharge, one month, three months, and six months were -0.34, -1.19, -0.85, -0.94, and -1.79, respectively. The mean Z-score heights at birth, discharge, one month, three months, and six months were 0.74, 0.20, -0.07, -0.79, and -2.5, respectively. Additionally, the mean Z-scores for head circumference at birth, discharge, one month, and three months were 0.41, -0.19, -0.53, and -1.17, respectively. Deviation from the Fenton preterm growth chart was detected in 109 infants (42.7%) at the time of discharge, 79 infants (31%) at one month, 82 infants (32.2%) at three months, and 134 infants (52.5%) at six months of age. Conclusions: The weight at discharge and the length of NPO [due to surgical problems, feeding intolerance, necrotizing enterocolitis (NEC), etc.] were significantly inversely related. Preterm infants grow more slowly in hospitals, so their longitudinal growth data should be interpreted carefully. The incidence of postnatal growth failure can be reduced by improving NICU quality, optimizing nutrition, and increasing enteral feeding rates.

IGF1 Haploinsufficiency: Phenotype and Response to Growth Hormone Treatment in 9 Patients.

The clinical features of bi-allelic IGF1 defects are well established, i.e., severe growth failure and microcephaly, delayed psychomotor development, and sensorineural deafness. However, information on clinical and endocrine consequences of heterozygous IGF1 variants and treatment options is scarce. We aimed at extending the knowledge base of the clinical presentation and growth response to recombinant human growth hormone (rhGH) of patients carrying such variants. Retrospective case series of patients with pathogenic heterozygous IGF1 variants. Nine patients from six families were included, harbouring five whole or partial gene deletions and one frameshift variant resulting in a premature stop codon (three de novo, one unknown inheritance). In the other two families, variants segregated with short stature. Mean (SD) birth length was -1.9 (1.3) SDS (n = 7), height -3.8 (0.6) SDS, head circumference -2.5 (0.6) SDS, serum IGF-I -1.9 (0.7) SDS, serum IGFBP-3 1.1 (0.4) SDS (n = 7), and GH peak range 5-31 μg/L (n = 4). Five patients showed feeding problems in infancy. Average height increased after 1 and 2 years of rhGH treatment by 0.8 SDS (range 0.3-1.3 SDS) and 1.3 SDS (range 0.5-2.0 SDS), respectively. Adult height in 2 patients was -2.8 and -1.3 SDS, which was, respectively, 1.3 and 2.9 SDS taller than predicted before start of treatment. Haploinsufficiency of IGF1 causes a variable phenotype of prenatal and postnatal growth failure, microcephaly, feeding difficulties, low/low-normal serum IGF-I values in contrast to serum IGFBP-3 in the upper-normal range. Treatment with rhGH increased growth in the first 2 years of treatment, and in 2 patients adult height after treatment was higher than predicted at treatment initiation.

Pathogenic sequence variant and microdeletion affecting HMGA2 in Silver–Russell syndrome: case reports and literature review

Silver–Russell syndrome (SRS) is a representative imprinting disorder characterized by pre- and postnatal growth failure. We encountered two Japanese SRS cases with a de novo pathogenic frameshift variant of HMGA2 (NM_003483.6:c.138_141delinsCT, p.(Lys46Asnfs*16)) and a de novo ~ 3.4 Mb microdeletion at 12q14.2–q15 involving HMGA2, respectively. Furthermore, we compared clinical features in previously reported patients with various genetic conditions leading to compromised IGF2 expression, i.e., HMGA2 aberrations, PLAG1 aberrations, IGF2 aberrations, and H19/IGF2:IG-DMR epimutations (hypomethylations). The results provide further support for HMGA2 being involved in the development of SRS and imply some characteristic features in patients with HMGA2 aberrations.

Micronutrients supplementation and the outcome in preterm neonates in a tertiary health centre

Approximately 15 mil[1]lion babies are born preterm each year.1 Preterm infants commonly experience postnatal growth failure due to insufficient intake of micro[1]nutrients. We aim to determine the outcome of preterm neonates that received micronutrients. Methods: The study subjects com[1]prised of 210 preterm neonates admitted to (SCBU) of Federal Medical Centre, Brinin kebbi, Kebbi State from 1st June 2020 to 30st May, 2022. The subjects were randomized into two groups; 100 preterm neonates (Study group) received micronutrients (Reload; Reload Brands, LLC, Salt Lake City, Utah, USA) while, 110 preterm neonates (Control group) did not receive micronutrients. Biodata and other important information were obtained. All the babies (210) received the usual treatment protocol of preterm admitted to our SCBU. Ethical ap[1]proval was obtained from the Research and Ethics Committee. Results: Birth weights of the 210 neonates ranged from 800grams to the highest 2500grams with mean CC –BY 4.0 birth weight of 1.54kg ±0.95. Av[1]erage daily weight gains in 71% of the study subjects ranged from 25grams to a maximum of 29 grams per day while, in the non- micronutrients group, 54% had daily weight gain range of 10- 14grams per day (p = 0.001). Twelve (12%) of the Micronutrient group (MG) and 30% 0f the Non-Micronutrient group (NMG) had need for blood transfusion respectively (p = 0.002). The average ho sp ital stay wa s 22.95±9.68; hospital stay for the MG was 8 to 21 days while that of the NMG was 22 to 42 days (p = 0.001). C o n c l u s i o n s : M i c r o n u t r i - ents intake were in consistent with optimal weight gain, shorter hospital stay and lower need for blood transfusion in preterm newborns. Recommendations: We recommend early commencement of mi c r o n u t r i e n t s u p p leme n t (Reloads) in preterm babies.

Postnatal growth failure of very low-birth-weight infants in Southwest Iran: A descriptive analytical study.

Preterm infants are more prone to poor growth and neurodevelopment. The first few weeks of life play an important role in the growth and neurodevelopment of very-low-birth-weight (VLBW) infants. The Vermont Oxford Network, evaluating the postnatal growth of preterm newborns, considers growth failure as body weight <10th percentile for postmenstrual age. This study aims to assess the frequency of postnatal growth failure in VLBW infants in Southwest Iran. This descriptive analytical study was performed on VLBW infants in the neonatal intensive care unit (NICU) of Imam Khomeini Hospital (Ahvaz, Iran) from September 2019 to August 2020. Growth failure was confirmed when a newborn's weight at discharge was smaller than the 10th percentile corrected age (≤-1.28 Z-score), based on the Fenton growth chart as a standard. This study was performed on 353 infants. Intrauterine growth retardation was detected in 29% of female and 10.6% of male newborns, who were born at a gestational age of 32 and 31 weeks or higher respectively. Upon hospital discharge, postnatal growth failure was detected in all newborn girls, except for those born at 32 weeks of gestation, and all newborn boys, except for those born at a gestational age of 33-34 weeks. Postnatal growth retardation in VLBW infants born in our NICU was much higher than that of other centers. Overcrowding, short length of hospitalization, low nurse-to-patient ratio, and untrained nurses were among the reasons for poor postnatal growth in our center.

Tmem263 deletion disrupts the GH/IGF-1 axis and causes dwarfism and impairs skeletal acquisition

Genome-wide association studies (GWAS) have identified a large number of candidate genes believed to affect longitudinal bone growth and bone mass. One of these candidate genes, TMEM263, encodes a poorly characterized plasma membrane protein. Single nucleotide polymorphisms in TMEM263 are associated with bone mineral density in humans and mutations are associated with dwarfism in chicken and severe skeletal dysplasia in at least one human fetus. Whether this genotype-phenotype relationship is causal, however, remains unclear. Here, we determine whether and how TMEM263 is required for postnatal growth. Deletion of the Tmem263 gene in mice causes severe postnatal growth failure, proportional dwarfism, and impaired skeletal acquisition. Mice lacking Tmem263 show no differences in body weight within the first 2 weeks of postnatal life. However, by P21 there is a dramatic growth deficit due to a disrupted growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis, which is critical for longitudinal bone growth. Tmem263-null mice have low circulating IGF-1 levels and pronounced reductions in bone mass and growth plate length. The low serum IGF-1 in Tmem263-null mice is associated with reduced hepatic GH receptor (GHR) expression and GH-induced JAK2/STAT5 signaling. A deficit in GH signaling dramatically alters GH-regulated genes and feminizes the liver transcriptome of Tmem263-null male mice, with their expression profile resembling wild-type female, hypophysectomized male, and Stat5b-null male mice. Collectively, our data validates the causal role for Tmem263 in regulating postnatal growth and raises the possibility that rare mutations or variants of TMEM263 may potentially cause GH insensitivity and impair linear growth.

Tmem263 deletion disrupts the GH/IGF-1 axis and causes dwarfism and impairs skeletal acquisition.

Genome-wide association studies (GWAS) have identified a large number of candidate genes believed to affect longitudinal bone growth and bone mass. One of these candidate genes, TMEM263, encodes a poorly characterized plasma membrane protein. Single nucleotide polymorphisms in TMEM263 are associated with bone mineral density in humans and mutations are associated with dwarfism in chicken and severe skeletal dysplasia in at least one human fetus. Whether this genotype-phenotype relationship is causal, however, remains unclear. Here, we determine whether and how TMEM263 is required for postnatal growth. Deletion of the Tmem263 gene in mice causes severe postnatal growth failure, proportional dwarfism, and impaired skeletal acquisition. Mice lacking Tmem263 show no differences in body weight within the first 2 weeks of postnatal life. However, by P21 there is a dramatic growth deficit due to a disrupted growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis, which is critical for longitudinal bone growth. Tmem263-null mice have low circulating IGF-1 levels and pronounced reductions in bone mass and growth plate length. The low serum IGF-1 in Tmem263-null mice is associated with reduced hepatic GH receptor (GHR) expression and GH-induced JAK2/STAT5 signaling. A deficit in GH signaling dramatically alters GH-regulated genes and feminizes the liver transcriptome of Tmem263-null male mice, with their expression profile resembling wild-type female, hypophysectomized male, and Stat5b-null male mice. Collectively, our data validates the causal role for Tmem263 in regulating postnatal growth and raises the possibility that rare mutations or variants of TMEM263 may potentially cause GH insensitivity and impair linear growth.

An exploratory study of clinical factors associated with IGF-1 and IGFBP-3 in preterm infants.

Despite advances in parenteral nutrition, postnatal growth failure in very low birthweight (VLBW) preterm infants is common and associated with chronic health problems. Insulin-like growth factor 1 (IGF-1) is positively associated with improved infant growth, but factors which promote IGF-1 levels in this population have not been clearly identified. The objective of this study was to explore early factors that influence IGF-1 in VLBW preterm infants. VLBW infants were enrolled into a prospective, randomized controlled nutrition trial (N = 87). Outcome measures included IGF-1 and IGFBP-3 levels measured at 35 weeks PMA. Linear regression analyses tested the relationships between candidate clinical predictors and levels of IGF-1 and IGFBP-3. Higher protein intake, longer duration of parenteral nutrition, and lower IGFBP-3 levels at 1 week of life were associated with lower IGF-1 levels at 35 weeks PMA. Neither early markers of insulin resistance nor degree of illness were associated with IGF-1 levels at 35 weeks PMA. Optimization of early nutrient intake, and attention to route of delivery, may have a lasting influence on IGF-1/IGFBP-3, and in turn, long-term health outcomes. In very low birthweight preterm infants, early protein intake, duration of parenteral nutrition, and insulin-like growth factor binding protein 3 (IGFBP-3) levels at 1 week of life are positively associated with insulin-like growth factor 1 (IGF-1) levels at 35 weeks postmenstrual age. Data from this study highlight the influence of early nutrition on components of the endocrine axis in preterm infants. Strategies aimed at early initiation of enteral nutrition, as well as optimizing composition of parenteral nutrition, may bolster hormones involved in promoting preterm infant growth.

Quantitative DNA Methylation Analysis and Epigenotype-Phenotype Correlations in Taiwanese Patients with Silver-Russell Syndrome.

Background: Silver-Russell syndrome (SRS; OMIM #180860) is a clinically and genetically heterogeneous imprinting disorder characterized by prenatal and postnatal growth failure. The aim of this study was to identify the epigenotype-phenotype correlations in these patients using quantitative DNA methylation analysis. Methods: One hundred and eighty-three subjects clinically suspected of having SRS were referred for diagnostic testing by the methylation profiling of H19-associated imprinting center (IC) 1 and imprinted PEG1/MEST regions using methylation-specific high-resolution melting analysis and methylation quantification with the MassARRAY assay. Correlations between quantitative DNA methylation status and clinical manifestations of the subjects according to the Netchine-Harbison (N-H) clinical scoring system for SRS were analyzed. Results: Among the 183 subjects, 90 had a clinical diagnosis of SRS [N-H score ≥ 4 (maximum = 6)] and 93 had an SRS score < 4. Molecular lesions were detected in 41% (37/90) of the subjects with a clinical diagnosis of SRS, compared with 3% (3/93) of those with an N-H score < 4. The IC1 methylation level was negatively correlated with the N-H score. The molecular diagnosis rate was positively correlated with the N-H score. Thirty-one subjects had IC1 hypomethylation (IC1 methylation level <35% by the MassARRAY assay), seven had maternal uniparental disomy 7, and two had pathogenic copy number variants. Among the 90 subjects with an N-H score ≥ 4, the IC1 methylation level was significantly different between those with or without some clinical SRS features, including birth length ≤ 10th centile, relative macrocephaly at birth, normal cognitive development, body asymmetry, clinodactyly of the fifth finger, and genital abnormalities. Conclusions: This study confirmed the suitability of the N-H clinical scoring system as clinical diagnostic criteria for SRS. Quantitative DNA methylation analysis using the MassARRAY assay can improve the detection of epigenotype-phenotype correlations, further promoting better genetic counseling and multidisciplinary management for these patients.

From Insight to Eyesight: Unveiling the Secrets of the Insulin-Like Growth Factor Axis in Retinal Health.

Insulin-like growth factor-1 (IGF-1) plays a diverse role in the retina, exerting its effects in both normal and diseased conditions. Deficiency of IGF-1 in humans leads to issues such as microcephaly, mental retardation, deafness, and postnatal growth failure. IGF-1 is produced in the retinal pigment epithelium (RPE) and activates the IGF-1 receptor (IGF-1R) in photoreceptor cells. When IGF-1R is absent in rod cells, it results in the degeneration of photoreceptors, emphasizing the neuroprotective function of IGF signaling in these cells. Contrastingly, in neovascular age-related macular degeneration (AMD), there is an overexpression of both IGF-1 and IGF-1R in RPE. The mechanisms behind this altered regulation of IGF-1 in diseased states are currently unknown. This comprehensive review provides recent insights into the role of IGF-1 in the health and disease of the retina, raising several unanswered questions that still need further investigation.

Prediction of Postnatal Growth Failure in Very Low Birth Weight Infants Using a Machine Learning Model.

Accurate prediction of postnatal growth failure (PGF) can be beneficial for early intervention and prevention. We aimed to develop a machine learning model to predict PGF at discharge among very low birth weight (VLBW) infants using extreme gradient boosting. A total of 729 VLBW infants, born between 2013 and 2017 in four hospitals, were included. PGF was defined as a decrease in z-score between birth and discharge that was greater than 1.28. Feature selection and addition were performed to improve the accuracy of prediction at four different time points, including 0, 7, 14, and 28 days after birth. A total of 12 features with high contribution at all time points by feature importance were decided upon, and good performance was shown as an area under the receiver operating characteristic curve (AUROC) of 0.78 at 7 days. After adding weight change to the 12 features-which included sex, gestational age, birth weight, small for gestational age, maternal hypertension, respiratory distress syndrome, duration of invasive ventilation, duration of non-invasive ventilation, patent ductus arteriosus, sepsis, use of parenteral nutrition, and reach at full enteral nutrition-the AUROC at 7 days after birth was shown as 0.84. Our prediction model for PGF performed well at early detection. Its potential clinical application as a supplemental tool could be helpful for reducing PGF and improving child health.

Early-life sodium deprivation programs long-term changes in ingestive behaviors and energy expenditure in C57BL/6J mice.

Postnatal growth failure remains a significant problem for infants born prematurely, despite aggressive efforts to improve perinatal nutrition. Though often dysregulated in early life when children are born preterm, sodium (Na) homeostasis is vital to achieve optimal growth. We hypothesize that insufficient Na supply in this critical period contributes to growth restriction and programmed risks for cardiometabolic disease in later adulthood. Thus, we sought to ascertain the effects of prolonged versus early-life Na depletion on weight gain, body composition, food and water intake behaviors, and energy expenditure in C57BL/6J mice. In one study, mice were provided a low (0.04%)- or normal/high (0.30%)-Na diet between 3 and 18 wk of age. Na-restricted mice demonstrated delayed growth and elevated basal metabolic rate. In a second study, mice were provided 0.04% or 0.30% Na diet between 3 and 6 wk of age and then returned to standard (0.15%)-Na diet through the end of the study. Na-restricted mice exhibited growth delays that quickly caught up on return to standard diet. Between 6 and 18 wk of age, previously restricted mice exhibited sustained, programmed changes in feeding behaviors, reductions in total food intake, and increases in water intake and aerobic energy expenditure while maintaining normal body composition. Although having no effect in control mice, administration of the ganglionic blocker hexamethonium abolished the programmed increase in basal metabolic rate in previously restricted mice. Together these data indicate that early-life Na restriction can cause programmed changes in ingestive behaviors, autonomic function, and energy expenditure that persist well into adulthood.

Exploring the Genetic Causes for Postnatal Growth Failure in Children Born Non-Small for Gestational Age.

The most common causes of short stature (SS) in children are familial short stature (FSS) and idiopathic short stature (ISS). Recently, growth plate dysfunction has been recognized as the genetic cause of FSS or ISS. The aim of this study was to investigate monogenic growth failure in patients with ISS and FSS. Targeted exome sequencing was performed in patients categorized as ISS or FSS and the subsequent response to growth hormone (GH) therapy was analyzed. We found 17 genetic causes involving 12 genes (NPR2, IHH, BBS1, COL1A1, COL2A1, TRPS1, MASP1, SPRED1, PTPTN11, ADNP, NADSYN1, and CERT1) and 2 copy number variants. A genetic cause was found in 45.5% and 35.7% of patients with FSS and ISS, respectively. The genetic yield in patients with syndromic and non-syndromic SS was 90% and 23.1%, respectively. In the 11 genetically confirmed patients, a gain in height from -2.6 to -1.3 standard deviations after 2 years of GH treatment was found. The overall diagnostic yield in this study was 41.7%. We identified several genetic causes involving paracrine signaling, the extracellular matrix, and basic intracellular processes. Identification of the causative gene may provide prognostic evidence for the use of GH therapy in non-SGA children.

Higher versus lower sodium intake for preterm infants.

Higher versus lower sodium intake for preterm infants.

Longitudinal growth of children born with gastroschisis or omphalocele

Normal childhood growth is an indicator of good health, but data addressing the growth of children born with abdominal wall defects (AWDs) are limited. The detailed growth phenotypes of children born with gastroschisis or omphalocele are described and compared to peers without AWDs from birth to adolescence. Data from 183 gastroschisis and 144 omphalocele patients born between 1993 and 2017 were gathered from Finnish nationwide registers and electronic health records. Weight (n = 3033), length/height (n = 2034), weight-for-length (0–24 months, n = 909), and body mass index measures (2–15 years, n = 423) were converted into sex- and age-specific Z-scores. Linear mixed models were used for comparisons. Intrauterine growth failure was common in infants with gastroschisis. Birth weight Z-scores in girls and boys were − 1.2 (0.2) and − 1.3 (0.2) and length Z-scores − 0.7 (0.2) and − 1.0 (0.2), respectively (p < 0.001 for all comparisons to infants without AWDs). During early infancy, growth failure increased in infants with gastroschisis, and thereafter, catch-up growth was prominent and faster in girls than in boys. Gastroschisis children gained weight and reached their peers’ weights permanently at 5 to 10 years. By 15 years or older, 30% of gastroschisis patients were overweight. Infants with omphalocele were born with a normal birth size but grew shorter and weighing less than the reference population until the teen-age years.Conclusion: Children with gastroschisis and omphalocele have distinct growth patterns from fetal life onwards. These growth trajectories may also provide some opportunities to modulate adult health.What is Known:• Intrauterine and postnatal growth failure can be seen frequently in gastroschisis and they often show significant catch-up growth later in infancy. It is assumed that part of the children with gastroschisis will become overweight during later childhood.What is New: • The longitudinal growth of girls and boys with gastroschisis or omphalocele is described separately until the teenage years. The risk of gaining excessive weight in puberty was confirmed in girls with gastroschisis.