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BackgroundLow birthweight small-for-gestational-age (SGA-LBW) (birthweight below the 10th percentile for gestational age; SGA-LBW) infants are at an increased risk of poor postnatal growth outcomes. Linear growth trajectories of SGA-LBW infants are less studied in South Asian settings including India.ObjectivesTo describe the linear growth trajectories of the SGA-LBW infants compared with appropriate-for-gestational-age LBW (AGA-LBW) infants during the first 6 months of life. In addition, we estimated catch-up growth (ΔLAZ > 0.67) in SGA-LBW infants and their performance against the WHO linear growth velocity cut-offs. Additionally, we studied factors associated with poor catch-up growth in SGA-LBW infants.MethodsThe data utilized came from an individually randomized controlled trial that included low birthweight (LBW) infants weighing 1,500–2,250 g at birth. A total of 8,360 LBW infants were included. For comparison between SGA-LBW and AGA-LBW infants, we presented unadjusted and adjusted estimates for mean differences (MDs) or risk ratios (RRs) for the outcomes of length, linear growth velocity, length for age z-score (LAZ) score, and stunting. We estimated the proportion of catch-up growth. Generalized linear models of the Poisson family with log links were used to identify factors associated with poor catch-up growth in SGA-LBW infants.ResultsLow birthweight small-for-gestational-age infants had a higher risk of stunting, lower attained length, and a lower LAZ score throughout the first 6 months of life compared with AGA-LBW infants, with differences being maximum at 28 days and minimum at 6 months of age. The linear growth velocity in SGA-LBW infants compared with AGA-LBW infants was significantly lower during the birth–28 day period [MD −0.19, 95% confidence interval (CI): −0.28 to −0.10] and higher during the 3- to 6-month period (MD 0.17, 95% CI: 0.06–0.28). Among the SGA-LBW infants, 55% showed catch-up growth for length at 6 months of age. Lower wealth quintiles, high birth order, home birth, male child, term delivery, non-exclusive breastfeeding, and pneumonia were associated with the higher risk of poor catch-up in linear growth among SGA-LBW infants.ConclusionSmall for gestational age (SGA) status at birth, independent of gestational age, is a determinant of poor postnatal linear growth. Promotion of institutional deliveries, exclusive breastfeeding, and prevention and early treatment of pneumonia may be helpful to improve linear growth in SGA-LBW infants during early infancy.Clinical Trial Registration[https://clinicaltrials.gov/], identifier [NCT02653534].

Catch-up growth (CUG) in childhood is defined as periods of growth acceleration, after the resolution of growth attenuation causes, bringing the children back to their original growth trajectory. Sometimes, however, CUG is incomplete, leading to permanent growth deficit and short stature. The aim of this study was to investigate the mechanisms that limit nutritional-CUG. Specifically, we focused on the crosstalk between leptin, increased by re-feeding, and sex hormones, which increase with age. In vivo studies were performed in young male Sprague Dawley rats fed ad libitum or subjected to 10/36 days of 40% food restriction followed by 90-120 days of re-feeding. In vitro studies were performed on ATDC5 cells. Analyses of mRNA and protein levels were done using qPCR and Western blot, respectively. CUG was complete in body weight and humerus length in animals that were food-restricted for 10 days but not for those food-restricted for 36 days. In vitro studies showed that leptin significantly increased aromatase gene expression and protein level as well as the expression of estrogen and leptin receptors in a dose- and time-dependent manner. The effect of leptin on aromatase was direct and was mediated through the MAPK/Erk, STAT3 and PI3K pathways. The crosstalk between leptin and aromatase in the growth plate suggests that re-feeding during puberty may lead to increased estrogen level and activity, and consequently, irreversible premature epiphyseal growth plate closure. These results may have important implications for the development of novel treatment strategies for short stature in children. [ABSTRACT FROM AUTHOR]

Background: Insulin resistance has been implicated in the pathogenesis of children born small for gestational age (SGA) with catch-up growth (CUG). Adipose tissue macrophages (ATMs) regulate insulin resistance by secreting exosomes containing microRNA (miRNA) cargo; however, their pathogenic roles and molecular mechanism are not fully understood. This study aimed to investigate the role of miR-210-5p in rats born SGA with CUG and insulin resistance., Methods: The dietary needs of pregnant rats were restricted to ensure the birth of SGA rats. Transmission electron microscopy (TEM) and Western blot analysis were used to identify the exosomes from ATMs of CUG-SGA and adequate-for-gestational-age (AGA) rats. PKH-67 staining was performed to confirm the uptake of exosomes. miR-210-5p expression was measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Glucose uptake and output were detected with glucose uptake and output assays, respectively. Insulin resistance was detected with glucose and insulin tolerance tests in viv o. The interaction between miR-210-5p and SID1 transmembrane family member 2 (SIDT2) was validated with dual-luciferase reporter assay., Results: miR-210-5p was observed to be highly expressed in the exosomes derived from the ATMs of CUG-SGA rats. ATM-derived exosomes can serve as vehicles to deliver miR-210-5p into adipocytes, myocytes, and hepatocytes, where it can enhance cellular insulin resistance. SIDT2 was identified as a direct target gene of miR-210-5p. The miR-210-5p-induced insulin resistance was reversed by the restored SIDT2 expression. However, overexpression of SIDT2 abolished the inhibitory effect of CUG-SGA-ATM-exosomal miR-210-5p on insulin sensitivity in vivo ., Conclusions: ATM-derived exosomal miR-210-5p promoted insulin resistance in CUG-SGA rats by targeting SIDT2 , which may act as a new potential therapeutic target for children born SGA with CUG., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tp.amegroups.com/article/view/10.21037/tp-23-142/coif). The authors have no conflicts of interest to declare., (2023 Translational Pediatrics. All rights reserved.)

Background: Low birthweight small-for-gestational-age (SGA-LBW) (birthweight below the 10th percentile for gestational age; SGA-LBW) infants are at an increased risk of poor postnatal growth outcomes. Linear growth trajectories of SGA-LBW infants are less studied in South Asian settings including India., Objectives: To describe the linear growth trajectories of the SGA-LBW infants compared with appropriate-for-gestational-age LBW (AGA-LBW) infants during the first 6 months of life. In addition, we estimated catch-up growth (ΔLAZ > 0.67) in SGA-LBW infants and their performance against the WHO linear growth velocity cut-offs. Additionally, we studied factors associated with poor catch-up growth in SGA-LBW infants., Methods: The data utilized came from an individually randomized controlled trial that included low birthweight (LBW) infants weighing 1,500-2,250 g at birth. A total of 8,360 LBW infants were included. For comparison between SGA-LBW and AGA-LBW infants, we presented unadjusted and adjusted estimates for mean differences (MDs) or risk ratios ( RR s) for the outcomes of length, linear growth velocity, length for age z -score (LAZ) score, and stunting. We estimated the proportion of catch-up growth. Generalized linear models of the Poisson family with log links were used to identify factors associated with poor catch-up growth in SGA-LBW infants., Results: Low birthweight small-for-gestational-age infants had a higher risk of stunting, lower attained length, and a lower LAZ score throughout the first 6 months of life compared with AGA-LBW infants, with differences being maximum at 28 days and minimum at 6 months of age. The linear growth velocity in SGA-LBW infants compared with AGA-LBW infants was significantly lower during the birth-28 day period [MD -0.19, 95% confidence interval ( CI ): -0.28 to -0.10] and higher during the 3- to 6-month period (MD 0.17, 95% CI : 0.06-0.28). Among the SGA-LBW infants, 55% showed catch-up growth for length at 6 months of age. Lower wealth quintiles, high birth order, home birth, male child, term delivery, non-exclusive breastfeeding, and pneumonia were associated with the higher risk of poor catch-up in linear growth among SGA-LBW infants., Conclusion: Small for gestational age (SGA) status at birth, independent of gestational age, is a determinant of poor postnatal linear growth. Promotion of institutional deliveries, exclusive breastfeeding, and prevention and early treatment of pneumonia may be helpful to improve linear growth in SGA-LBW infants during early infancy., Clinical Trial Registration: [https://clinicaltrials.gov/], identifier [NCT02653534]., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sinha, Choudhary, Nitika, Kumar, Mazumder, Taneja and Bhandari.)