Rapid Postnatal Growth Research Articles

Early postnatal moderate catch‑up growth in rats with nutritional intrauterine growth restriction preserves pulmonary vascular and cognitive function in adulthood.

Intrauterine growth restriction (IUGR) with rapid postnatal catch-up growth is strongly associated with pulmonary vascular dysfunction in adulthood, whereas IUGR with delayed growth in early postnatal life results in long-term brain deficits. In the present study, it was hypothesized that IUGR with early moderate catch-up growth may alleviate pulmonary vascular remodeling in adulthood without affecting memory function. An IUGR model was established by restricting maternal nutrition during pregnancy. Different growth patterns were achieved by adjusting the litter size in each group during lactation. Rats meeting the weight requirement at weaning were selected for subsequent studies at three time points (3, 9 and 13 weeks). Cognitive function was evaluated using a Y-maze. Invasive hemodynamic measurements were conducted to measure the mean pulmonary arterial pressure (mPAP). In addition, primary pulmonary artery smooth muscle cells (PASMCs) and pulmonary vascular endothelial cells (PVECs) were cultured to investigate their role in the increase in mPAP following rapid catch-up growth. The results showed that memory function deficits in the rats in the delayed growth group were associated with reduced proliferation of neural stem cells in the subgranular zone of the hippocampus. Furthermore, moderate catch-up growth at the three time points improved memory function while maintaining a normal mPAP. In adult IUGR rats experiencing rapid catch-up growth, although memory function improved, elevated mPAP and medial thickening of pulmonary arterioles were observed. Additionally, PASMCs exhibited excessive proliferation, migration and anti-apoptotic activity in the rapid catch-up group, and PVECs also displayed excessive proliferation. These results suggested that moderate catch-up growth after IUGR is a better strategy for optimal cognition and cardiovascular health in adulthood compared with rapid catch-up growth or delayed growth.

Growth patterns of preterm and small for gestational age children during the first 10 years of life.

Preterm and small for gestational age (SGA) remain significant public health concerns worldwide. Yet limited evidence exists on their growth patterns during childhood from low-or middle-income countries. We investigated the postnatal growth patterns of preterm and SGA compared to term appropriate for gestational age (AGA) children from birth to 10-11y, and examined the impact of birth status on child nutritional status during the school age years. Children born to women who participated in a double-blinded randomized controlled trial of preconception micronutrient supplementation in Vietnam were classified into three groups: preterm AGA (n = 130), full-term SGA (n = 165) and full-term AGA (n = 1,072). Anthropometric data (weight and height) were collected prospectively at birth, 3, 6, 12, 18, 24 months and at 6-7 and 10-11y. We used ANOVA and multiple regression models to examine the differences in growth patterns from birth to 10-11y as well as child undernutrition and overnutrition by birth status. Children who were born preterm exhibited rapid postnatal growth, but still had lower HAZ at 1y and 2y and showed catch up to the AGA group at 6y. Compared to those born AGA, SGA infants had higher risk of thinness (BMIZ < -2) at 2y and 6y (adjusted Odds Ratio, AOR [95% CI] 2.5 [1.0, 6.1] and 2.6 [1.4, 4.6], respectively); this risk reduced at 10-11y (1.6 [0.9, 2.8]). The risk of stunting (HAZ < -2) was also 2.4 [1.5, 3.8] and 2.3 times [1.2, 4.1] higher in SGA than AGA group at ages 2y and 6-7y, respectively, with no differences at 10y. Although preterm children had higher rates of thinness and stunting at 2y compared to AGA children, these differences were not statistically significant. No associations were found between preterm or SGA and overweight /obesity at age 10-11y. Children who were born term-SGA continued to demonstrate deficits in weight and height during childhood whereas those born preterm showed catch-up growth by age 6-7y. Additional efforts to reduce the burden of these conditions are needed, particularly during school-age and early adolescents when children are exposed to challenging environments and have higher demands for nutrition.

Weight Gain from Birth to Adolescence and TyG Index at Age 18 Years: A Cohort Study in Northeast Brazil.

Developmental models suggest that the phenotypes may arise from an immediate or mediated adaptive metabolic response of the perinatal growth. Evidence on the cumulative effects of growth and factors associated with risk of insulin resistance in adolescents is lacking. To investigate the association between birthweight, weight gain during infancy, childhood and adolescence and the triglyceride-glucose index in adolescents. This is a cohort of 217 children born at term, followed for the first six months, and reassessed at 8 and 18 years of age. The variables of interest were birthweight, postnatal growth defined as rapid postnatal growth when the weight gain from birth to six months of age was greater than 0.67 z-score, and the same criterion was used for high BMI gain from ages 6 months to 8 years, and from 8 to 18 years. Socioeconomic condition, nutritional status, practice of physical exercises and consumption of ultra-processed foods were verified. Multivariate linear regression analysis was used to verify the effect of the variables on the triglyceride-glucose index. Birthweight was not associated with triglyceride-glucose index in adolescence. Rapid postnatal growth during the first 6 months, higher BMI gain from 8 to 18 years and higher waist circumference contributed significantly to explain higher triglyceride-glucose index. Our findings suggest that rapid postnatal growth may be one of the first signs of a higher triglyceride-glucose index in adolescence and that attention should be paid to the greater gain in body mass between childhood and adolescence for the risk of a higher triglyceride-glucose index.

Specific features of endocrine regulation of plastic processes in premature infants and children small for gestational age

Low-birthweight and preterm infants have high risk of obesity and obesity-related diseases in the future. This review article identifies risk factors and endocrine biomarkers with greatest predictive value to the metabolic diseases development. Low concentrations of IGF-1 in low-birthweight children are associated with adipogenesis. Low leptin levels may be considered as a biomarker of catch-up growth. Long term programming effects of in utero exposure to leptin extend beyond infancy into early childhood. Adiponectin levels are positively correlated with obesity in early life, but not at ages older than three years. Rapid postnatal growth rate is associated with metabolic syndrome. Conclusion. Specific features of endocrine regulation of growth and dynamics of plastic processes in premature infants and SGA children are associated with excessive accumulation of adipose tissue, which can function as a mechanism for metabolic programming of distant endocrine and cardiometabolic disorders.

Cardiovascular Risk in Pediatrics: A Dynamic Process during the First 1000 Days of Life.

The early childhood period, encompassing prenatal and early stages, assumes a pivotal role in shaping cardiovascular risk factors. We conducted a narrative review, presenting a non-systematic summation and analysis of the available literature, focusing on cardiovascular risk from prenatal development to the first 1000 days of life. Elements such as maternal health, genetic predisposition, inadequate fetal nutrition, and rapid postnatal growth contribute to this risk. Specifically, maternal obesity and antibiotic use during pregnancy can influence transgenerational risk factors. Conditions at birth, such as fetal growth restriction and low birth weight, set the stage for potential cardiovascular challenges. To consider cardiovascular risk in early childhood as a dynamic process is useful when adopting a personalized prevention for future healthcare and providing recommendations for management throughout their journey from infancy to early adulthood. A comprehensive approach is paramount in addressing early childhood cardiovascular risks. By targeting critical periods and implementing preventive strategies, healthcare professionals and policymakers can pave the way for improved cardiovascular outcomes. Investing in children's health during their early years holds the key to alleviating the burden of cardiovascular diseases for future generations.

Identification of an alternative triglyceride biosynthesis pathway

Triacylglycerols (TAGs) are the main source of stored energy in the body, providing an important substrate pool for mitochondrial beta-oxidation. Imbalances in the amount of TAGs are associated with obesity, cardiac disease and various other pathologies1,2. In humans, TAGs are synthesized from excess, coenzyme A-conjugated fatty acids by diacylglycerol O-acyltransferases (DGAT1 and DGAT2)3. In other organisms, this activity is complemented by additional enzymes4, but whether such alternative pathways exist in humans remains unknown. Here we disrupt the DGAT pathway in haploid human cells and use iterative genetics to reveal an unrelated TAG-synthesizing system composed of a protein we called DIESL (also known as TMEM68, an acyltransferase of previously unknown function) and its regulator TMX1. Mechanistically, TMX1 binds to and controls DIESL at the endoplasmic reticulum, and loss of TMX1 leads to the unconstrained formation of DIESL-dependent lipid droplets. DIESL is an autonomous TAG synthase, and expression of human DIESL in Escherichiacoli endows this organism with the ability to synthesize TAG. Although both DIESL and the DGATs function as diacylglycerol acyltransferases, they contribute to the cellular TAG pool under specific conditions. Functionally, DIESL synthesizes TAG at the expense of membrane phospholipids and maintains mitochondrial function during periods of extracellular lipid starvation. In mice, DIESL deficiency impedes rapid postnatal growth and affects energy homeostasis during changes in nutrient availability. We have therefore identified an alternative TAG biosynthetic pathway driven by DIESL under potent control by TMX1.

Lateralization of major white matter tracts during infancy is time-varying and tract-specific.

Lateralization patterns are a major structural feature of brain white matter and have been investigated as a neural architecture that indicates and supports the specialization of cognitive processing and observed behaviors, e.g. language skills. Many neurodevelopmental disorders have been associated with atypical lateralization, reinforcing the need for careful measurement and study of this structural characteristic. Unfortunately, there is little consensus on the direction and magnitude of lateralization in major white matter tracts during the first months and years of life-the period of most rapid postnatal brain growth and cognitive maturation. In addition, no studies have examined white matter lateralization in a longitudinal pediatric sample-preventing confirmation of if and how white matter lateralization changes over time. Using a densely sampled longitudinal data set from neurotypical infants aged 0-6months, we aim to (i) chart trajectories of white matter lateralization in 9 major tracts and (ii) link variable findings from cross-sectional studies of white matter lateralization in early infancy. We show that patterns of lateralization are time-varying and tract-specific and that differences in lateralization results during this period may reflect the dynamic nature of lateralization through development, which can be missed in cross-sectional studies.

Birth weight and hypertension: nature or nurture?

Birth weight and hypertension: nature or nurture?

Update information on type 1 diabetes in children/adolescents and adults.

Update information on type 1 diabetes in children/adolescents and adults.

Catch-Up Growth as a Risk Factor for Rapid Weight Gain, Earlier Menarche and Earlier Pubertal Growth Spurt in Girls Born Small for Gestational Age (SGA)—A Longitudinal Study

Most children born small for gestational age (SGA) have rapid postnatal growth. Despite its positive aspects, catch-up growth may affect the level of adipose tissue in the pre-pubertal and pubertal periods and therefore affect the age of puberty. The aim of this study was to determine the associations between size at birth, catch-up growth in infancy, BMI in peripubertal period, age at menarche, and the parameters of adolescent growth spurt of body height in girls born SGA. For 297 girls (22.6% SGA; 77.4% appropriate for gestational age (AGA)) complete body weight and height measurements and age at menarche were obtained. Adolescent growth spurt parameters were estimated using the JPA2 model (AUXAL SSI 3.1). Calculations were made in the Statistica 13 program using the Kruskal-Wallis and Kaplan-Meier tests. Girls born SGA with catch-up had the highest BMIs at the age of 8 years (H = 94.22, p < 0.001) and at menarche (H = 58.21, p < 0.001), experienced menarche earliest (H = 21.77, p < 0.001), same as the onset (H = 6.54, p = 0.012) and peak height velocity (H = 11.71, p = 0.003) of their adolescent growth spurt compared to SGA girls without catch-up and AGA girls. In SGA girls, catch-up growth has far-reaching consequences such as increased risk of fat accumulation and a rapid transition to puberty.

Fetal exposure to cannabis, neonatal adiposity, and postnatal growth trajectories: The Healthy Start study

Objective: Cannabis use during pregnancy is associated with lower birth weight and may influence postnatal growth. We estimated associations of fetal exposure to cannabis with neonatal adiposity and body mass index (BMI) z-score trajectories through age 3 years, as well as effect modification by breastfeeding. Methods: We leveraged a subsample of 130 mother-child pairs from a Colorado-based cohort. Twelve cannabinoids/metabolites (including delta 9-tetrahydrocannabinol [THC] and cannabidiol [CBD]) were measured in maternal urine collected at ~27 weeks gestation. Fetal exposure to cannabis was dichotomized as exposed (any cannabinoid&amp;#x2265;limit of quantification) and not exposed (cannabinoids&amp;#x3c;limit of quantification). Generalized linear models estimated the associations between fetal exposure to cannabis with birth weight and neonatal adiposity (measured by air displacement plethysmography). A mixed-effects model estimated the association between fetal cannabis exposure and BMI z-score trajectories. Interaction by breastfeeding duration was assessed by including a product term (with fetal exposure to cannabis) in a mixed-effects model. Results: Fetal exposure to cannabis was associated with lower birth weight (-206g; 95% CI: -393, -18; p=0.03) and neonatal adiposity (-2.0%; 95% CI: -3.7, -0.02; p=0.03) followed by rapid postnatal growth through 3 years (0.37 increase in BMI z-score per square root year; 95% CI: 0.01, 0.60; p=0.02). Breastfeeding modified this association (p for interaction&amp;#x3c;0.01). Among cannabis-exposed offspring who were not breastfed, BMI z-scores were 0.42 lower at 6 months (95% CI: -1.15, 0.31) but 0.54 higher at 36 months (95% CI: -0.36, 1.44). Conversely, BMI z-scores were no different by fetal cannabis exposure among offspring who were breastfed for ~5 months. Conclusions: Our data suggests that fetal exposure to cannabis alters fetal and postnatal growth, and that breastfeeding may stabilize over-compensatory growth among cannabis-exposed offspring. Although the impact of lactational exposure to cannabis requires further investigation, it remains important to caution against cannabis use during pregnancy and lactation.

Cord blood metabolites and rapid postnatal growth as multiple mediators in the prenatal propensity to childhood overweight

BackgroundThe mechanisms underlying childhood overweight and obesity are poorly known. Here, we investigated the direct and indirect effects of different prenatal exposures on offspring rapid postnatal growth and overweight in childhood, mediated through cord blood metabolites. Additionally, rapid postnatal growth was considered a potential mediator on childhood overweight, alone and sequentially to each metabolite.MethodsWithin four European birth-cohorts (N = 375 mother-child dyads), information on seven prenatal exposures (maternal education, pre-pregnancy BMI, weight gain and tobacco smoke during pregnancy, age at delivery, parity, and child gestational age), selected as obesogenic according to a-priori knowledge, was collected. Cord blood levels of 31 metabolites, associated with rapid postnatal growth and/or childhood overweight in a previous study, were measured via liquid-chromatography-quadrupole-time-of-flight-mass-spectrometry. Rapid growth at 12 months and childhood overweight (including obesity) between four and eight years were defined with reference to WHO growth charts. Single mediation analysis was performed using the imputation approach and multiple mediation analysis using the extended-imputation approach.ResultsSingle mediation suggested that the effect of maternal education, pregnancy weight gain, parity, and gestational age on rapid postnatal growth but not on childhood overweight was partly mediated by seven metabolites, including cholestenone, decenoylcarnitine(C10:1), phosphatidylcholine(C34:3), progesterone and three unidentified metabolites; and the effect of gestational age on childhood overweight was mainly mediated by rapid postnatal growth. Multiple mediation suggested that the effect of gestational age on childhood overweight was mainly mediated by rapid postnatal growth and that the mediating role of the metabolites was marginal.ConclusionOur findings provide evidence of the involvement of in utero metabolism in the propensity to rapid postnatal growth and of rapid postnatal growth in the propensity to childhood overweight. We did not find evidence supporting a mediating role of the studied metabolites alone between the studied prenatal exposures and the propensity to childhood overweight.

Evaluating the efficacy of different treatment modalities in cases of infantile hemangioma

ObjectiveThis study aimed to evaluate different treatment modalities of infantile hemangiomas with their benefits and side effects within 3 months of treatment.BackgroundThe most common vascular tumors in infants are infantile hemangiomas, usually present as a premonitory mark with rapid postnatal growth, followed by slow involution. For those requiring systemic medications, early treatment is critical.Patients and methodsA randomized-controlled trial was conducted on 120 patients with hemangioma distributed into four treatment groups. The first group was treated by placebo, the second group was treated by topical timolol only, the third group was treated by topical timolol + oral propranolol and the fourth group was treated by topical timolo + intralesional steroid.ResultsSignificant response was found in 90.9% of the patients in the topical timolol + oral propranolol group, 78.1% of the patients in the topical timolol-only group and 72.7% of the patients in the topical timolol + intralesional steroid group. In terms of the side effects, the topical timolol + intralesional steroid had the most side effects (54.5%), followed by the topical timolol + propranolol group (45.5%) and the topical timolol-only group (18.8%). There was a statistically significant difference in lesion size, the visual analog scale, side effects, and response.ConclusionThe combination of topical timolol with oral propranolol is a very rapid, effective, simple, and safe treatment for compound hemangiomas, achieving more remarkable clinical results and fewer side effects than other methods of treatment. Therefore, we can use this combination as the first line of treatment.

Developmental Diversity and Unique Sensitivity to Injury of Lung Endothelial Subtypes During a Period of Rapid Postnatal Growth

Developmental Diversity and Unique Sensitivity to Injury of Lung Endothelial Subtypes During a Period of Rapid Postnatal Growth

Childhood obesity and adverse cardiometabolic risk in large for gestational age infants and potential early preventive strategies: a narrative review.

Accumulating evidence indicates that obesity and cardiometabolic risks become established early in life due to developmental programming and infants born as large for gestational age (LGA) are particularly at risk. This review summarizes the recent literature connecting LGA infants and early childhood obesity and cardiometabolic risk and explores potential preventive interventions in early infancy. With the rising obesity rates in women of childbearing age, the LGA birth rate is about 10%. Recent literature continues to support the higher rates of obesity in LGA infants. However, there is a knowledge gap for their lifetime risk for adverse cardiometabolic outcomes. Potential factors that may modify the risk in early infancy include catch-down early postnatal growth, reduction in body fat growth trajectory, longer breastfeeding duration, and presence of a healthy gut microbiome. The early postnatal period may be a critical window of opportunity for active interventions to mitigate or prevent obesity and potential adverse metabolic consequences in later life. A variety of promising candidate biomarkers for the early identification of metabolic alterations in LGA infants is also discussed. IMPACT: LGA infants are the greatest risk category for future obesity, especially if they experience rapid postnatal growth during infancy. Potential risk modifying secondary prevention strategies in early infancy in LGA infants include catch-down early postnatal growth, reduction in body fat growth trajectory, longer breastfeeding duration, and presence of a healthy gut microbiome. LGA infants may be potential low-hanging fruit targets for early preventive interventions in the fight against childhood obesity.

Building better brains with iron

Iron is a critical nutrient for brain development. Extremely low birth weight infants are at high risk because they are deprived of iron transfer late in pregnancy. The Committee on Nutrition of the American Academy of Pediatrics recommends an iron intake of at least 2 mg/kg/day for all preterm infants through 12 months of age. Iron deficiency in that population is exacerbated by rapid postnatal growth and blood loss through phlebotomies. These deficits may be counterbalanced by red cell transfusions; however, there are concerns about iron overload in infants transfused multiple times and receiving an enteral supplementation.

Mapping the Evidence on Human Milk Fortification and Cardiovascular Risk Factors and Outcomes among Low Birth Weight Infants: A Scoping Review

Introduction: Preterm and low birth weight infants receiving a diet of human milk require fortification with protein, carbohydrates, vitamins, and minerals due to missed growth and nutrient accretion that would otherwise occur in utero. Although rapid catch-up growth improves anthropometric and neurodevelopmental indices, research has suggested that accelerated postnatal growth may be associated with poor long-term cardiometabolic outcomes. Methods: We conducted a scoping review to map the evidence on human milk fortification and cardiometabolic risk factors and outcomes among low birth weight infants. We searched Ovid Medline, Ovid Embase, CINAHL, and Web of Science from inception to June 2021 and examined grey literature for relevant referenced articles. Studies were included if they were a primary study focused on fortified human milk and cardiometabolic risk factors or outcomes among low birth weight infants. A modified version of the Cochrane Collaboration Randomized Controlled Trial data collection form guided data collection. We conducted a narrative synthesis of the results structured around the Population, Concept, Context framework. Results: We included 19 articles (14 randomized controlled trials, three quasi-randomized trials and two cohort studies) on cardiometabolic risk factors among 1,955 low birth weight infants who received fortified human milk. None of the included studies addressed long-term cardiometabolic outcomes. Body weight was the most examined risk factor in all included studies, with 13 studies observing benefit from human milk fortification. Two studies linked rapid growth with cardiometabolic risk factors. Discussion: The focus across the 19 included studies was the anthropometric advantages of fortified HM among LBW infants. A meta-analysis was not performed for this review, but if completed may yield a different inference. Conclusion: Limited evidence is available regarding the long-term cardiometabolic outcomes among low birth weight infants who received fortified human milk. Existing literature is focused on the short-term anthropometric benefits of fortification post-hospital discharge. Yet, some reports have linked rapid early postnatal growth with the development of cardiometabolic risk factors later in life. Future studies should explore the long-term cardiometabolic outcomes among low birth weight infants with the goal of optimizing anthropometric and brain growth while minimizing long-term cardiometabolic risk.

Maturational Changes in Mouse Cutaneous Touch and Piezo2-Mediated Mechanotransduction

The age of studied animals has a profound impact on experimental outcomes in animal-based research. In mice, age influences molecular, morphological, physiological, and behavioral parameters, particularly during rapid postnatal growth and maturation until adulthood (at 12weeks of age). Despite this knowledge, most biomedical studies use a wide-spanning age range from 4 to 12weeks, raising concerns about reproducibility and potential masking of relevant age differences. Here, using mouse behavior and electrophysiology in cultured dorsal root ganglia (DRG), we reveal a decline in behavioral cutaneous touch sensitivity and Piezo2-mediated mechanotransduction invitro during mouse maturation but not thereafter. In addition, we identify distinct transcript changes in individual Piezo2-expressing mechanosensitive DRG neurons by combining electrophysiology with single-cell RNA sequencing (patch-seq). Taken together, our study emphasizes the need for accurate age matching and uncovers hitherto unknown maturational plasticity in cutaneous touch at the level of behavior, mechanotransduction, and transcripts.

Individual Variation of Human Cortical Structure Is Established in the First Year of Life

BackgroundIndividual differences in cortical gray matter (GM) structure are associated with cognitive function and psychiatric disorders with developmental origins. Identifying when individual differences in cortical structure are established in childhood is critical for understanding the timing of abnormal cortical development associated with neuropsychiatric disorders. MethodsWe studied the development of cortical GM and white matter volume, cortical thickness, and surface area using structural magnetic resonance imaging in two unique cohorts of singleton (121 male and 131 female) and twin (99 male and 83 female) children imaged longitudinally from birth to 6 years. ResultsCortical GM volume increases rapidly in the first year of life, with more gradual growth thereafter. Between ages 1 and 6 years, total surface area expands 29%, while average cortical thickness decreases about 3.5%. In both cohorts, a large portion of individual variation in cortical GM volume (81%–87%) and total surface area (73%–83%) at age 6 years is present by age 1 year. Regional heterogeneity of cortical thickness observed at age 6 is largely in place at age 1. ConclusionsThese findings indicate that individual differences in cortical GM structure are largely established by the end of the first year of life, following a period of rapid postnatal GM growth. This suggests that alterations in GM structure associated with psychiatric disorders with developmental origins may largely arise in the first year of life and that interventions to normalize or mitigate abnormal GM development may need to be targeted to very early childhood.

Long-Term Metabolic Consequences of Intrauterine Growth Restriction

To summarize recent findings on the associations of intrauterine growth restriction (IUGR) and long-term metabolic consequences such as obesity, type 2 diabetes (T2D), and cardiovascular diseases and the underlying mechanisms. Recent evidence suggests that metabolic diseases such as obesity, T2D, hypertension, and coronary artery disease are related to developmental programming in fetal period and early childhood. Rapid postnatal catch-up growth is also an important factor that contributes to the development of these long-term metabolic complications. The underlying mechanisms include oxidative stress, changes in hormonal milieu, vascular endothelial dysfunction, epigenetic regulation, and the potential alteration of microbiome. Fetal and early life environment is an important determinant of long-term cardiometabolic risks. Children with IUGR need close follow-up for early detection of these complications.