Oral nutritional supplementation with dietary counseling improves linear catch-up growth and health outcomes in children with or at risk of undernutrition: a randomized controlled trial.

Introduction: Childhood undernutrition is associated with increased morbidity, mortality and a high socio-economic burden. Methods: Supporting Pediatric GRowth and Health OUTcomes (SPROUT) is a randomized, controlled trial evaluating the effects of an oral nutritional supplement (ONS) with dietary counseling (DC; n = 164) compared to a DC-only group who continued consuming their habitual milk (n = 166; NCT05239208). Children aged 24-60 months who were at risk or with undernutrition, as defined by weight-for-age [WAZ] < -1 and height-for-age [HAZ] < -1 according to the WHO Growth Standards, and who also met the criterion of weight-for-height [WHZ] < 0, were enrolled in Vietnam. Results: ONS + DC had a larger WAZ increase at day 120 (primary endpoint) vs. DC (least squares mean, LSM (SE): 0.30 (0.02) vs. 0.13 (0.02); p < 0.001), and larger improvements in all weight, BMI and weight-for-height indices at day 30 and 120 (all p < 0.01). Height gain was larger in ONS + DC in all indices, including height-for-age difference [HAD; cm: 0.56 (0.07) vs. 0.10 (0.07); p < 0.001], at day 120. ONS + DC had larger arm muscle but not arm fat indices, higher parent-rated appetite, physical activity and energy levels, longer night sleep, fewer and shorter awakenings, and better sleep quality than DC. Conclusion: Adding ONS to DC, compared to DC-alone, improves growth in weight and height, linear catch-up growth, and health outcomes in children with or at risk of undernutrition.

Role of ghrelin in promoting catch-up growth and maintaining metabolic homeostasis in small-for-gestational-age infants.

Small-for-gestational age (SGA) has been a great concern in the perinatal period as it leads to adverse perinatal outcomes and increased neonatal morbidity and mortality, has an impact on long-term health outcomes, and increases the risk of metabolic disorders, cardiovascular, and endocrine diseases in adulthood. As an endogenous ligand of the growth hormone secretagotor (GHS-R), ghrelin may play an important role in regulating growth and energy metabolic homeostasis from fetal to adult life. We reviewed the role of ghrelin in catch-up growth and energy metabolism of SGA in recent years. In addition to promoting SGA catch-up growth, ghrelin may also participate in SGA energy metabolism and maintain metabolic homeostasis. The causes of small gestational age infants are very complex and may be related to a variety of metabolic pathway disorders. The related signaling pathways regulated by ghrelin may help to identify high-risk groups of SGA metabolic disorders and formulate targeted interventions to prevent the occurrence of adult dwarfism, insulin resistance-related metabolic syndrome and other diseases.

The impact of maternal intrahepatic cholestasis during pregnancy on the growth trajectory of offspring: a population-based nested case‒control cohort study.

BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP) is associated with an increased risk of adverse fetal outcomes, yet its influence on offspring growth remains unclear. Our study dynamically tracks growth rates in children from ICP and healthy mothers and investigates the link between maternal liver function and developmental abnormalities in offspring. METHOD: Our case‒control study involved 97 women with ICP and 152 with uncomplicated pregnancies nested in a cohort of their offspring, including 50 from the ICP group and 87 from the uncomplicated pregnancy group. We collected pediatric growth and development data, with a maximum follow-up duration of 36 months. Stratified analyses of children's height, weight, and head circumference were conducted, and Spearman's rank correlation was applied to examine the relationships between maternal serological markers and pediatric growth metrics. RESULT: Maternal liver and renal functions, along with serum lipid profiles, significantly differed between the ICP and normal groups. In the ICP group, the offspring showed elevated alanine aminotransferase (ALT), direct bilirubin (DBIT), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and apolipoprotein B (APOB) levels. Notably, the length-for-age z score (LAZ), weight-for-age z score (WAZ), and head circumference-for-age z score (HCZ) were lower in ICP offspring compared with those from normal pregnancies within the 1- to 12-month age range (P < 0.05). However, no significant differences in LAZ, weight-for-length z score (WLZ), BMI-for-age z score (BAZ), or HCZ were observed between groups in the 13- to 36-month age range. Maternal maximum lactate dehydrogenase (LDH) and total bile acids (TBA) levels during pregnancy were inversely correlated with LAZ and WAZ in the first year. Furthermore, offspring of mothers with ICP exhibited a greater incidence of stunting (24% vs. 6.9%, P = 0.004) and abnormal HCZ (14% vs. 3.7%, P = 0.034). CONCLUSIONS: Growth disparities in offspring of ICP-affected pregnancies were most significant within the 1- to 12-month age range. During this period, maximum maternal LDH and TBA levels were negatively correlated with LAZ and WAZ values of offspring. The observation of similar growth rates between ICP and control group offspring from 13 to 36 months suggested catch-up growth in the ICP group.

Puerarin Affects 1HMR Spectroscopy Quantified Hepatic Fat Signal Fraction in Intrauterine Growth Restricted Rats.

OBJECTIVE: This study aimed to investigate the impact of puerarin early intervention on growth parameters and Hepatic Fat Signal Fraction (HFF) quantification in Intrauterine Growth Restricted(IUGR)rats through Proton Magnetic resonance spectroscopy (1H-MRS). METHODS: Pregnant rats were divided into three groups: control, IUGR with puerarin treatment, and IUGR without treatment. The treatment and nontreatment groups were received a low-protein diet during pregnancy, while the control group received a normal diet. After birth, pups in the treatment group received a unilateral intraperitoneal injection of 50 mg/kg/d puerarin. Male rats were evaluated at 3,8 and 12 weeks, including measurements of weight, body length and waist circumference and body mass index (BMI). Conventional magnetic resonance imaging and 1HMRS were conducted using a 3.0 T whole-body MR scanner. RESULTS: Newborn pups in the treatment and non-treatment groups showed significantly lower body weight, BMI, and body length at 3 weeks compared to the control group. However, there were no significant differences in HFF and waist circumference between the three groups at 3 weeks. At 8 and 12 weeks post-delivery, significant differences in body weight, BMI, waist circumference were observed in newborn pups of IUGR non-treatment rats compared to the control group. In contrast, there were no significant differences in body weight, BMI, waist circumference between the treatment group and the control group at 8 and 12 weeks. Moreover, the treatment group exhibited notably higher HFF compared to the control group at both time points. At 12 weeks post-birth, a significant difference in HFF was observed between the IUGR non-treatment and treatment groups, although no significant difference was found at 8 weeks. CONCLUSION: Early intervention with puerarin following birth has a significant impact on liver fat content and may potentially reduce adult obesity among IUGR rats.

Behavior and circadian glucocorticoids in prepubertal monozygotic twins with birthweight differences: A prospective longitudinal cohort study on twin-to-twin transfusion syndrome patients.

BACKGROUND/OBJECTIVE: Low birthweight may have adverse sequelae in later life. Therefore, we analyzed behavioral difficulties and salivary glucocorticoid profiles in monozygotic twins with intra-twin birthweight differences due to twin-to-twin transfusion syndrome (TTTS). METHODS: 46 monozygotic TTTS twin pairs with birthweight differences of <1SDS (concordant; n=29) and ≥1SDS (discordant; n=17) were recruited at a mean age of 6.9 years for a prospective longitudinal cohort study. For glucocorticoid analysis, saliva samples were collected (at 7 h, 13 h, 18 h and 21 h) and analyzed with liquid chromatography-tandem mass spectrometry. Parents completed the Strengths and Difficulties Questionnaire. RESULTS: From the parents' perspective, the formerly smaller twins had statistically higher scores regarding hyperactivity (mean 4.63 vs 3.48, p=0.003) and emotional problems (mean 2.67 vs 2.02, p=0.042). Less catch-up growth (Δintra-twin height SDS 4 years of age - Δintra-twin birth length SDS) of the smaller twins was associated with higher scores for hyperactivity (Adj. R²=0.261, p<0.001, ß=-1.88, F(1.44)=16.86, n=46, f²=0.35), while smaller birthweight (Adj. R²=0.135, p=0.007, ß=-0,87, F(1.44)=8.03, n=46, f²=0.16) and birth length (Adj. R²=0.085, p=0.028, ß=-0,78, F(1.44)=5.19, n=46, f²=0.09) were associated with higher scores for peer problems. Greater Δintra-twin for cortisol (7 h: rho=0.337, p=0.029; cumulative: rho=0.458; p=0.024) and cortisone (7 h: rho=0.329, p=0.029; 13 h: rho=0.436, p=0.005) correlated with a greater Δintra-twin for conduct problems. In the discordant group, circa 1 SDS in head circumference persisted from birth (mean SDS: smaller twin -1.18, larger twin -0.08, p<0.001) to present (mean SDS: smaller twin -1.16, larger twin -0.14, p<0.001). CONCLUSION: Higher cortisol and cortisone concentrations in smaller twins were associated with higher scores for conduct problems. Lower birthweight and absent catch-up growth affected the parents' perspective on the smaller twins' behavior. They saw those children as more hyperactive, with more peer problems and emotional problems. Thus, it seems important to introduce regular check-ups where behavioral difficulties can be assessed, and assistance and advice can be given to the families. Due to the persisting smaller head circumference in the smaller discordant twins, this should be measured regularly.

Inadequate linear catch-up growth in children born small for gestational age: Influencing factors and underlying mechanisms.

A minority of children born small for gestational age (SGA) may experience catch-up growth failure and remain short in adulthood. However, the underlying causes and mechanisms of this phenomenon are not yet fully comprehended. We reviewed the present state of research concerning the growth hormone-insulin-like growth factor axis and growth plate in SGA children who fail to achieve catch-up growth. Additionally, we explored the factors influencing catch-up growth in SGA children and potential molecular mechanisms involved. Furthermore, we considered the potential benefits of supplementary nutrition, specific dietary patterns, probiotics and drug therapy in facilitating catch-up growth.

Prospective cohort study on facial profile changes in infants with Robin sequence and healthy controls.

BACKGROUND: Various conservative and surgical approaches exist to treat Robin sequence (RS), but their effects on facial profile and mandibular catch-up growth are unclear. A functional treatment concept, used in our centre for 25 years, includes an individualized palatal plate with a velo-pharyngeal extension and intensive feeding training. METHODS: We performed a prospective study to objectively describe facial profiles in infants with RS treated with the above concept. Infants with isolated RS were admitted to our tertiary perinatal and national referral centre for craniofacial malformations between May 2018 and Nov 2019. Infants with RS received 3D-photographs during clinically indicated visits. Healthy controls were recruited from Dec 2018 to Sep 2019 and received 3D-photographs every 3 months. The digitally measured jaw index (JI), defined as alveolar overjet (O) x maxillary arch (U)/mandibular arch (L), and the soft tissue reference points A'-point, Nasion', B'-point angle (ANB'), describing the relative position of maxilla to mandible, were evaluated. Linear mixed models were used to examine time trajectories in JI and ANB'. RESULTS: A total of 207 3D images, obtained in 19 infants with RS and 32 controls, were analysed. JI and ANB' decreased over time in both groups [for JI - 0.18 (95% CI - 0.25 to - 0.10); for ANB': - 0.40° per month [(95% CI - 0.48 to - 0.32)]] but remained lower in controls [for JI - 2.5 (95% CI - 3.2 to - 1.8); for ANB'-1.7° (95% CI - 2.4 to - 1.0)]. Also, the ANB' model showed a significant effect of the interaction term diagnosis x age. CONCLUSIONS: Based on longitudinal 3D images, we describe changes in objective parameters of facial profile in infants with and without RS during the first year of life. Our findings indicate catch-up growth in infants treated for RS. Video Abstract.

Cellular Energy Sensor Sirt1 Augments Mapk Signaling to Promote Hypoxia/Reoxygenation-Induced Catch-up Growth in Zebrafish Embryo.

Animal growth is blunted in adverse environments where catabolic metabolism dominates; however, when the adversity disappears, stunted animals rapidly catch up to age-equivalent body size. This phenomenon is called catch-up growth, which we observe in various animals. Since growth retardation and catch-up growth are sequential processes, catabolism or stress response molecules may remain active, especially immediately after growth resumes. Sirtuins (Sirt1-7) deacetylate target proteins in a nicotinamide adenine dinucleotide-dependent manner, and these enzymes govern diverse alleys of cellular functions. Here, we investigated the roles of Sirt1 and its close paralog Sirt2 in the hypoxia/reoxygenation-induced catch-up growth model using zebrafish embryos. Temporal blockade of Sirt1/2 significantly reduced the growth rate of the embryos in reoxygenation, but it was not evident in constant normoxia. Subsequent gene knockdown and chemical inhibition experiments demonstrated that Sirt1, but not Sirt2, was required for the catchup growth. Inhibition of Sirt1 significantly reduced the activity of mitogen-activated kinase (Mapk) of embryos in the reoxygenation condition. In addition, co-inhibition of Sirt1- and Igf-signaling did not further reduce the body growth or Mapk activation compared to those of the Igf-signaling-alone-inhibited embryos. Furthermore, in the reoxygenation condition, Sirt1- or Igf-signaling inhibition similarly blunted Mapk activity, especially in anterior tissues and trunk muscle, where the sirt1 expression was evident in the catching-up embryos. These results suggest that the catch-up growth requires Sirt1 action to activate the somatotropic Mapk pathway, likely by modifying the Igf-signaling.

Early developmental carry-over effects on exploratory behaviour and DNA methylation in wild great tits (Parus major).

Adverse, postnatal conditions experienced during development are known to induce lingering effects on morphology, behaviour, reproduction and survival. Despite the importance of early developmental stress for shaping the adult phenotype, it is largely unknown which molecular mechanisms allow for the induction and maintenance of such phenotypic effects once the early environmental conditions are released. Here we aimed to investigate whether lasting early developmental phenotypic changes are associated with post-developmental DNA methylation changes. We used a cross-foster and brood size experiment in great tit (Parus major) nestlings, which induced post-fledging effects on biometric measures and exploratory behaviour, a validated personality trait. We investigated whether these post-fledging effects are associated with DNA methylation levels of CpG sites in erythrocyte DNA. Individuals raised in enlarged broods caught up on their developmental delay after reaching independence and became more explorative as days since fledging passed, while the exploratory scores of individuals that were raised in reduced broods remained stable. Although we previously found that brood enlargement hardly affected the pre-fledging methylation levels, we found 420 CpG sites that were differentially methylated between fledged individuals that were raised in small versus large sized broods. A considerable number of the affected CpG sites were located in or near genes involved in metabolism, growth, behaviour and cognition. Since the biological functions of these genes line up with the observed post-fledging phenotypic effects of brood size, our results suggest that DNA methylation provides organisms the opportunity to modulate their condition once the environmental conditions allow it. In conclusion, this study shows that nutritional stress imposed by enlarged brood size during early development associates with variation in DNA methylation later in life. We propose that treatment-associated DNA methylation differences may arise in relation to pre- or post-fledging phenotypic changes, rather than that they are directly induced by the environment during early development.

Early postnatal moderate catch­up 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.

Association between maternal blood or cord blood metal concentrations and catch-up growth in children born small for gestational age: an analysis by the Japan environment and children's study.

BACKGROUND: Catch-up growth issues among children born small for gestational age (SGA) present a substantial public health challenge. Prenatal exposure to heavy metals can cause adverse effects on birth weight. However, comprehensive studies on the accurate assessment of individual blood concentrations of heavy metals and their effect on the failure to achieve catch-up growth remain unavailable. This study aimed to evaluate the effects of uterine exposure to toxic metals cadmium, lead, and mercury and essential trace metals manganese and selenium at low concentrations on the postnatal growth of children born SGA. METHODS: Data on newborn birth size and other factors were obtained from the medical record transcripts and self-administered questionnaires of participants in the Japan Environment and Children's Study. The blood concentrations of lead, cadmium, mercury, selenium, and manganese in pregnant women in their second or third trimester were determined by inductively coupled plasma mass spectrometry. These heavy metal concentrations were also assessed in pregnant women's cord blood. Furthermore, the relationship between each heavy metal and height measure/catch-up growth in SGA children aged 4 years was analyzed using linear and logistic regression methods. These models were adjusted for confounders. RESULTS: We studied 4683 mother-child pairings from 103,060 pregnancies included in the Japan Environment and Children's Study. Of these, 278 pairs were also analyzed using cord blood. At 3 and 4 years old, 10.7% and 9.0% of children who were born below the 10th percentile of body weight had height standard deviation scores (SDSs) below 2, respectively. Cord blood cadmium concentrations were associated with the inability to catch up in growth by 3 or 4 years old and the height SDS at 3 years old. In maternal blood, only manganese was positively associated with the height SDS of SGA children aged 2 years; however, it was not significantly associated with catch-up growth in these children. CONCLUSION: Cadmium exposure is associated with failed catch-up development in SGA children. These new findings could help identify children highly at risk of failing to catch up in growth, and could motivate the elimination of heavy metal (especially cadmium) pollution to improve SGA children's growth.

Bolus Feeding Via Gastric Versus Oral Routes in Very Preterm Neonates.

BACKGROUND: We intend to investigate the association of bolus orogastric tube (BOG) and nipple bottle (N) feedings with postnatal growth in very premature neonates (VPN: gestational age between 28 and 33 weeks). MATERIAL AND METHODS: The days of life (DOL) to achieve full combined oral and gastric enteral nutrition (FEN) and attain body weight (BW) of 2200 g (Wt22) and the length of hospitalization (LOH) were retrospectively associated with clinical and BOG and N feeding-related variables via multivariate regression analyses. Correlations were performed to ascertain the strength of associations. RESULTS: In a cohort of 127 VPN, FEN demonstrated negative associations with gestational age (GA) and LOH and Wt22 with birth weight (BW). FEN showed positive associations with nil by mouth and intravenous fluid-nutrition days and with DOL to start and achieve full nipple feeding. LOH was associated with days on antibiotics and DOL to start and achieve full nipple feeding. Wt22 was associated with DOL to achieve full nipple feeding. The start day of BOG feeding had no independent associations and weak, highly significant positive correlations with Wt22, LOH, and FEN. CONCLUSION: Bolus orogastric tube feeding has no independent implications for postnatal growth, duration of hospitalization, or chronological age to attain full enteral nutrition in VPN unless combined with nipple feeding to provide enteral nutrition. Oral bottle feeding accelerates postnatal catch-up growth and full enteral nutrition acquisition while reducing hospitalization duration. Initiating nipple feeding at 32 weeks of postmenstrual age may be safe in stable VPN. Antibiotic therapy increases hospitalization duration.

Hokkaido birth cohort study in Japan on the growth trajectory of children born with low birth weight until 7 years of age.

BACKGROUND: Low birth weight (LBW) is a significant global health concern with potential health risks and developmental implications for infants. Catch-up growth, an accelerated growth following an inhibition period, may partially compensate for growth deficits in LBW children. AIMS: This study investigated the prevalence of LBW and catch-up growth in height, weight, and body mass index (BMI) among LBW children in Japan, identified factors associated with LBW, and explored the potential for catch-up growth at different ages up to seven years. STUDY DESIGN AND SUBJECTS: The Hokkaido birth cohort study included 20,926 pregnant Japanese women recruited during their first trimester from 37 hospitals and clinics. Follow-up assessments were conducted in children up to seven years of age, tracking LBW children's growth and development using the Maternal and Child Health Handbook, and providing valuable insights into catch-up growth patterns. OUTCOME MEASURES: LBW was defined as a neonatal birth weight of <2500 g. The primary outcomes were catch-up growth in height, weight, and BMI at different ages. Z-scores were calculated to assess growth parameters with catch-up growth, defined as a change in z-score (> 0.67) between two time points. RESULTS AND CONCLUSIONS: A LBW was prevalent in 7.6 % of the cohort, which was lower than that reported in other Japanese studies. Among LBW children, 19.3 % achieved catch-up growth in height by age seven, and 10.6 % in weight. Catch-up growth in LBW children could partially offset these deficits. Further research will help understand the long-term outcomes and inform interventions for healthy development.

Catch-up growth and overweight adults in the offspring of young gecko mothers resembling low birth weight infants.

Endothermic and ectothermic amniotes differ in the timing of reproductive onset, with reptiles initiating reproduction before reaching final body size. Long-term consequences of maternal effect for early reptile offspring are poorly explored. We conducted growth experiments to compare the growth of offspring produced by young and older females of gecko Paroedura picta. Young, not fully grown females lay smaller eggs leading to production of smaller offspring. These offspring undergo accelerated growth and ultimately reach a comparable sex-specific final body length as do offspring of older females. Final body length is thus canalized with respect to the maternal effect on egg size. Notably, the offspring of young mothers have a tendency towards larger body mass. Ontogeny of the offspring of young females shares similarities with that of mammalian offspring with low birth weight or early malnutrition, exhibiting catch-up growth and a predisposition to obesity. We highlight the important consequences of early reproduction for offspring in animals that initiate reproduction prior to reaching final body size. Both life-history models and conservation practices should take into account that female lizards might produce the most fit offspring only between reaching their final body length and the onset of reproductive senescence.

[Longitudinal study on catch-up growth in preterm infants with small for gestational age at corrected ages 0-24 months]. / æ—©äº§å°äºŽèƒŽé¾„å„¿æ ¡æ­£0~24æœˆé¾„è¿½èµ¶ç”Ÿé•¿çš„çºµå‘ç ”ç©¶.

OBJECTIVES: To understand the growth and development status and differences between small for gestational age (SGA) and appropriate for gestational age (AGA) preterm infants during corrected ages 0-24 months, and to provide a basis for early health interventions for preterm infants. METHODS: A retrospective study was conducted, selecting 824 preterm infants who received regular health care at the Guangzhou Women and Children's Medical Center from July 2019 to July 2022, including 144 SGA and 680 AGA infants. The growth data of SGA and AGA groups at birth and corrected ages 0-24 months were analyzed and compared. RESULTS: The SGA group had significantly lower weight and length than the AGA group at corrected ages 0-18 months (P<0.05), while there were no significant differences between the two groups at corrected age 24 months (P>0.05). At corrected age 24 months, 85% (34/40) of SGA and 79% (74/94) of AGA preterm infants achieved catch-up growth. Stratified analysis by gestational age showed that there were significant differences in weight and length at corrected ages 0-9 months between the SGA subgroup with gestational age <34 weeks and the AGA subgroups with gestational age <34 weeks and 34 weeks (P<0.05). In addition, the weight and length of the SGA subgroup with gestational age 34 weeks showed significant differences compared to the AGA subgroups with gestational age <34 weeks and 34 weeks at corrected ages 0-18 months and corrected ages 0-12 months, respectively (P<0.05). Catch-up growth for SGA infants with gestational age <34 weeks and 34 weeks mainly occurred at corrected ages 0-12 months and corrected ages 0-18 months, respectively. CONCLUSIONS: SGA infants exhibit delayed early-life physical growth compared to AGA infants, but can achieve a higher proportion of catch-up growth by corrected age 24 months than AGA infants. Catch-up growth can be achieved earlier in SGA infants with a gestational age of <34 weeks compared to those with 34 weeks.

Relationship of Glucagon-like Peptide 1 and Peptide YY with Catch-up Growth in Children Born Small for Gestational Age

Objective: Children born small for gestational age (SGA) are at a greater risk of developing insulin resistance, type 2 diabetes, and cardiovascular disease in adulthood. Gastrointestinal peptides, some secreted by intestinal L cells, regulate glucose and lipid metabolism and act on the hypothalamus to regulate energy homeostasis. The aim of this study was to explore whether gastrointestinal peptides are involved in metabolic disorders in SGA, which remains unclear. Methods: The secretion of glucagon-like peptide 1 (GLP-1) and peptide YY (PYY) were investigated in prepubertal children born SGA, the differences between catch-up growth and persistent short stature were compared, and correlation with glucose and lipid metabolism was analyzed. GLP-1, PYY, insulin-like growth factor 1, glucose, insulin, and lipid concentrations were analyzed in prepubertal children aged 4-10 years, stratified into three groups: short-SGA (SGA-s), catch-up growth SGA, and normal growth appropriate for gestational age (AGA). Results: Fasting GLP-1 and PYY concentrations were significantly lower in the SGA group than in the AGA group (p<0.05), and the GLP-1 level in infants born SGA with catch-up growth was lower than that in the SGA-s group (p<0.05). In the SGA population, GLP-1 showed a weak negative correlation with catch-up growth (r=-0.326) and positive correlation with fasting insulin (r=0.331). Conclusion: Lower GLP-1 concentrations may be associated with abnormal glucose metabolism in prepubertal children born SGA with catch-up growth. This is indirect evidence that impaired intestinal L cell function may be involved in the development of metabolic complications in SGA children.

Circulating exosomes decrease in size and increase in number between birth and age 7: relations to fetal growth and liver fat.

Purpose: Exosomes play a key role in cell-to-cell communication by transferring their cargo to target tissues. Little is known on the course of exosome size and number in infants and children. Methods: Longitudinally, we assessed the size and number of circulating exosomes at birth and at ages 2 and 7 yr in 75 infants/children born appropriate-for-gestational-age (AGA; n=40) or small-for-gestational-age (SGA; n=35 with spontaneous catch-up), and related those results to concomitantly assessed measures of endocrine-metabolic health (HOMA-IR; IGF-1), body composition (by DXA at ages 0 and 2) and abdominal fat partitioning (subcutaneous, visceral and hepatic fat by MRI at age 7). Results: Circulating exosomes of AGAs decreased in size (on average by 4.2%) and increased in number (on average by 77%) between birth and age 7. Circulating exosomes of SGAs (as compared to those of AGAs) had a larger size at birth [146.8 vs 137.8 nm, respectively; p=0.02], and were in lower number at ages 2 [4.3x1011 vs 5.6x1011 particles/mL, respectively; p=0.01] and 7 [6.3x1011 vs 6.8x1011 particles/mL, respectively; p=0.006]. Longitudinal changes were thus more pronounced in SGAs for exosome size, and in AGAs for exosome number. At age 7, exosome size associated (P<0.0001) to liver fat in the whole study population. Conclusion: Early-life changes in circulating exosomes include a minor decrease in size and a major increase in number, and these changes may be influenced by fetal growth. Exosome size may become one of the first circulating markers of liver fat in childhood.

Evaluation of Clinical Characteristics and Growth Hormone Response in a Rare Skeletal Dysplasia: Pycnodysostosis.

Introduction Pycnodysostosis is a rare osteosclerotic skeletal dysplasia; its clinical features include short stature, characteristic facial features, increased bone fragility, and acro-osteolysis of the distal phalanx. Lack of clear guidelines for treatment and follow-up in rare diseases such as pycnodysostosis with growth hormone (GH) deficiency poses a difficulty for the clinician. This study aims to identify clinical, radiological, and endocrine findings of patients with pycnodysostosis focusing on the first year of recombinant human growth hormone (rhGH) treatment response. The eminence of this study is that it presents clinical experience with rhGH, providing an approach for future similar cases. Methods Three girls and two boys from three different families diagnosed with pycnodysostosis via clinical, radiological, and genetic evaluation followed up in the pediatric endocrinology clinic between 2022 and 2023 were enrolled in this study. Clinical findings, anthropometric measurements (weight, height, body mass index [BMI]), and laboratory, radiological, and genetic examinations were evaluated retrospectively. Participants were evaluated for GH deficiency using L-DOPA and clonidine tests if growth rate was below -2 standard deviation score (SDS) for gender and age after one-year follow-up. Results Complaints on admission were short stature (80%) and recurrent bone fractures (20%). Characteristic facial features and brachydactyly were seen in all the patients. Median height SDS on admission was -3.0 (range: -1.9 to -3.8). Median height SDS on last clinic visit was -3.2 (range: -1.7 to -4.2) at a median age of 8 years (range: 3.5-14 years). BMI was normal in four patients, while one was overweight. Bone mineral densitometry z-score was high, and two patients had bone fractures following minor trauma, while one had recurrent fractures. Two siblings (first and second cases) and the third case were diagnosed with GH deficiency, and anterior pituitary hormones were normal otherwise. One had partial empty sella in hypophyseal magnetic resonance imaging. rhGH (33 mcg/kg/day, subcutaneously) was started. Growth rate of the first, second, and third cases increased from 3.3, 3.1, 3.9 to 5, 4.3, 7.2 cm/year, respectively. Prior to rhGH, two had adenoid hypertrophy which was stable following rhGH. Growth rate follow-up of the fourth case continues, while the fifth case, the only participant who has reached adult height, has normal height according to age and gender normative. Conclusion Although rare, pycnodysostosis should not be overlooked in a patient with characteristic facial features, disproportionate short stature, and recurrent fractures. GH deficiency should be evaluated early if growth rate is declining. rhGH may restore growth rate and the possibility of catch-up in growth in patients with pycnodysostosis and GH deficiency. Hence, after first year of rhGH, growth rate of patients with pycnodysostosis is lower when compared to other etiologies of GH deficiency.

A retrospective study on the physical growth of twins in the first year after birth.

Objectives: This study analyzed the physical growth of small for gestational age (SGA) and appropriate for gestational age (AGA) twins up to one year after birth. Methods: Weight, length, and head circumference data of 0-1 year-old twins were collected from the Child Health Care System from 2010 to 2019. Physical data were presented as Z-scores. Five parameters - growth level of weight, body length, head circumference, growth velocity, and body proportion (weight for length) were compared in twins. Results: A total of 3,909 cases were collected (22.61% SGA, 77.39% AGA). 1. In both groups, WAZ (Weight for age z-score), HCZ (Head circumference for age z-score), and LAZ (Length for age z-score) increased more rapidly in the first 6 months. By one year of age, WAZ, HCZ, and LAZ had reached the normal range, but none had reached the average level of normal singleton children. 2. The mean values of WAZ, HCZ, and LAZ in the AGA group were between -1 and 0, and between -2 and - 1 in the SGA group, in the first year after birth. The SGA group lagged significantly behind the AGA group. The LAZ score of SGA and AGA was lower than the WAZ and HCZ scores. 3. The proportion of preterm AGA was the largest in twins, and the growth rate of preterm AGA was the fastest. Preterm twins had greater growth potential than term twins. However, the growth level of preterm SGA was always low. 4. The WFLZ (Weight for length z-score) in each group was approximately close to 0. The WFLZ of SGA was smaller than that of AGA twins at most time points. After 4 months of age, the WFLZ of twins had a downward trend. The WFLZ of preterm SGA approached -1 at approximately 1 year old. Conclusion: The physical growth of SGA and AGA in twins in the first year can reach the normal range but cannot reach the average level of normal singleton children. More attention should be paid to SGA in twins, especially preterm SGA. We should give proper nutritional guidance after 4 months of age to ensure the appropriate body proportion (weight for length) of SGA in twins. Clinical trial registration: www.chictr.org.cn, CTR2000034761.