Mean Growth Velocity Research Articles

Efficacy of exclusive human milk diet in preterm infants weighing ≤1500 g: a single-center COHORT study

Background: Preterm infants have high nutrition needs for growth and survival as they are at high risk of mortality and morbidity. An exclusive human milk diet (EHMD) that comprises human milk (HM) either expressed breast milk (EBM) or pasteurized donor human milk (PDHM), fortified with a 100% human milk-based fortifier (HMBF) could provide with safe nutritional strategy in preterm infants. Methods: This single-center, prospective cohort study included a cohort of 25 preterm infants ≤34 weeks of gestation weighing ≤1500 g at birth who were fed with EHMD when the feed volume reached 100 ml/kg/day until the infant was fit for discharge. Results: Of the 25 infants enrolled in the study the mean gestational age was 29.6±1.6 weeks and birth weight was 1171±230.7 g. The mean weight gain was 25.5±5.5 g/day and the mean growth velocity was 17.8±3.4 g/kg/day. Feeding intolerance was observed in 4 infants (16%), the average days to reach full feeds was 12.4±4.9 days and there was no necrotizing enterocolitis (NEC) observed. Conclusions: EHMD was well tolerated by the infants with better weight gain. These findings demonstrate that EHMD is a safe and effective nutritional strategy in the management of preterm infants. However, a large RCT (randomized clinical trial) is required to evaluate the efficacy of EHMD.

A Phase3, Open-Label, Single-Arm Trial of the Efficacy and Safety of Triptorelin 6-Month Formulation in Chinese Children with Central Precocious Puberty.

This phase3 study assessed the efficacy, safety, and pharmacokinetics of the 6-month prolonged release (PR) formulation in Chinese children with central precocious puberty (CPP). In this open-label study (NCT05029622), Chinese children (girls < 9years, boys < 10years) received two doses of triptorelin pamoate 22.5mg (day1 and month6). Primary endpoint was the proportion at month6 with luteinizing hormone (LH) suppression (stimulated peak LH ≤ 5IU/L after gonadotropin-releasing hormone stimulation). Secondary endpoints included safety assessments, hormone level changes, and clinical parameters from baseline. Overall, 66 children completed the study (93.9% girls; median age 8.0 [range 5-9] years). At month6, all patients had LH suppression; this was maintained at month12 in 98.5% of patients. Mean basal and peak LH and follicle-stimulating hormone levels were suppressed throughout follow-up. All patients at months3 to 12had sex hormone suppression to prepubertal levels. Stable or reduced breast development was seen for 98.4% and 93.5% of girls at month6 and 12, respectively; all boys had regression or stable genital development until month12. Compared with baseline (9.82cm/year), mean growth velocity was 5.88cm/year at month6 and 5.17cm/year at month12. Mean bone age/chronological age ratio decreased from 1.27 at baseline to 1.23 and 1.21 at month6 and 12, respectively. In girls, 64.5% showed decreased uterine length at month6 and 12 versus baseline, while 75.0% of boys showed stable testicular volume versus baseline. Thirteen patients (19.7%) had 22 drug-related treatment emergent adverse events (TEAEs); no grade ≥ 3 TEAEs were reported. The efficacy and safety profile of triptorelin 6-month PR in Chinese children with CPP was consistent with data previously reported in non-Chinese children with CPP, supporting this as a viable treatment option for Chinese children with CPP. Trial registration:ClinicalTrials.gov identifier, NCT05029622.

The role of early aggressive nutrition on growth of very preterm or very low birth weight infants

Background Very preterm infants (&lt;32 weeks gestational age) are at high risk of poor neurodevelopmental outcomes. Early aggressive parenteral nutrition (protein ³ 2g/kg/day) can reduce the incidence of malnutrition in very preterm infants. At present, Fatmawati General Hospital does not have a standard nutritional protocol for preterm infant. Objective To determine the difference in growth (days to regain birth weight and growth velocity) of very preterm (&lt;32 weeks gestational age) or very low birth weight (VLBW) (&lt;1500g) infants who were born and hospitalized in the Neonatal Unit of Fatmawati General Hospital, Jakarta, before and after applying early aggressive parenteral nutrition using a nutrition protocol from Cipto Mangunkusumo Hospital, Jakarta. Methods A quasi-experimental study was conducted on 23 very preterm or VLBW infants in the Neonatal Unit of Fatmawati General Hospital, from July to November 2019. Control group data were taken from medical records of very preterm or VLBW babies discharged from our unit from January 2018 – to June 2019 and compared to those of the intervention group. Results The intervention group regained their birth weight significantly faster than the control group [mean 7.43 (SD 3.5) vs. 16.73 (SD 5.1) days, respectively; (P=0.00)]. Mean growth velocity was also significantly higher in the intervention group than in the control group [14.6 (SD 6.0) vs. 8.9 (SD 6.9) gram/kg/day, respectively; (P=0.002)]. Conclusion Provision of early aggressive parenteral nutrition reduces the time to regain birth weight and leads to higher growth velocity in very preterm/VLBW infants.

Effect of novel human milk oligosaccharides-based human milk fortifier containing lactoferrin, docosahexaenoic acid, and arachidonic acid on the growth of preterm infants with birth weight of 700–1800 g

Background: Premature infants with low birth weight are at risk of growth failure and neurodevelopmental impairment. Human milk oligosaccharides (HMOs) are bioactive components of human milk that may enhance growth and development. The novel HMO-based human milk fortifier (HMoF), which also contains lactoferrin, docosahexaenoic acid (DHA), and arachidonic acid (ARA), can help provide a safer nutritional option for the growth of premature infants. Materials and Methods: We conducted a non-comparative observational study using data from multiple centers that used novel HMO-based HMF (HMoF) in premature infants (n=14) with birth weights of 700–1800 g. The primary outcome of the study was to assess tolerability (in terms of feed tolerance), and secondary outcomes included growth outcomes defined by weight, length, and head circumference during the stay in the NICU and at discharge. Results: A cohort consisting of 14 infants with a mean gestational age of 30.21±2.04 weeks and a birth weight of 1246.36±39.98 g comprised the study. During the study period, incidences of feed interruptions due to feed intolerability were nil, and no infant presented with any signs of adverse effects. The novel HMO-based HMF (HMoF)-fed infant cohort had a mean weight gain of 21.89±5.23 g/day, a mean length gain of 1.01±0.48 cm/week, and mean head circumference gain of 0.89±0.32 cm/week. The mean growth velocity recorded was 16.03±1.73 g/kg/day. Conclusions: Novel HMO-based HMF (HMoF) containing lactoferrin, DHA, and ARA demonstrated acceptable feed tolerance and weight gain without any clinically significant adverse effects. Data indicates that the novel HMoF containing lactoferrin, DHA, and ARA is a safe option for supporting the growth of preterm babies. However, further studies are needed to compare novel HMO-based HMF (HMoF) with standard HMF in a randomized controlled trial.

Efficacy and Safety of Triptorelin 3-Month Formulation in Chinese Children with Central Precocious Puberty: A Phase3, Open-Label, Single-Arm Study.

Triptorelin is available as 1- and 3-month prolonged-release (PR) formulations; at the time of the study, only the former was approved for central precocious puberty (CPP) in China. This study assessed the efficacy and safety of the triptorelin 3-month PR formulation in Chinese children with CPP. In this 12-month, prospective, open-label, multicentre, single-arm study (NCT04736602), Chinese children (mean age [standard deviation (SD)], 7.6 ± 0.8years) with CPP received triptorelin pamoate 15mg on day1 and at months 3, 6 and 9. The primary endpoint was the proportion with luteinizing hormone (LH) suppression (stimulated peak LH ≤ 3IU/L after gonadotropin-releasing hormone [GnRH] stimulation) at month 3. Secondary endpoints included changes from baseline in hormone levels and clinical parameters, as well as safety assessments. Overall, 32 children were enrolled, including three boys. LH suppression to prepubertal levels (≤ 3IU/L) after GnRH stimulation was observed in 100%, 93.5% and 93.5% of participants at months 3, 6 and 12, respectively. Basal and peak LH and follicle-stimulating hormone levels were substantially suppressed at months 3, 6 and 12, and most participants showed sex hormone suppression. At months 6 and 12 respectively 92.9% and 89.3% of girls had stable breast development, and all boys had stable genital development. There was a decrease in mean growth velocity from baseline (8.96cm/year) to months 3, 6 and 12 (8.07, 5.24 and 6.94cm/year, respectively). The mean difference between bone and chronological age decreased from baseline (2.85years) to month 12 (2.39years). In girls, uterine length was stable or reduced at month 12; in boys, testicular volume was reduced. Triptorelin was well tolerated. The triptorelin 3-month PR formulation demonstrated similar efficacy to that previously reported in non-Chinese patients with CPP and had an acceptable safety profile. This supports triptorelin 3-month PR as a viable option for Chinese children with CPP.

The effect of sex on retinopathy of prematurity severity among premature mixed-sex multiple gestation infants

This retrospective study of 68 premature infants examined whether there was a difference between male and female mixed-sex multiple gestation infants with regard to stage of retinopathy of prematurity (ROP) developed or need for ROP treatment. We found that among mixed-sex twin infants there was no statistically significant difference between sexes in most severe ROP stage developed or need for ROP treatment, but males were treated at an earlier postmenstrual age (PMA) than females, despite females having a lower mean birthweight and slower mean growth velocity compared to males.

Second-trimester growth velocities in twin and singleton pregnancies.

Previous small studies used individualized growth assessment (IGA) to characterize prenatal growth velocities of singletons and twins. We aimed to compare second-trimester growth velocities of individual anatomical parameters between monochorionic diamniotic (MCDA) twins, dichorionic diamniotic (DCDA) twins and singleton fetuses in a larger study. This was a study of a novel cohort of 222 MCDA twins and previously published cohorts of 40 DCDA twins and 118 singletons with serial ultrasound data. Fetal biometric measurements of biparietal diameter, head circumference, abdominal circumference and femur diaphysis length from prenatal ultrasound examinations were used to calculate second-trimester growth velocities using direct calculation or linear regression analysis. Linear fit was assessed based on the coefficient of determination (R2 ). Mean growth velocities and variances were compared among the three groups. The majority of cases underwent three second-trimester ultrasound examinations with fetal biometry available. All fetuses had linear growth, with R2 > 99% for all parameters. Only 1-2% of all MCDA and DCDA anatomical parameters had abnormal growth velocity scores outside the 95% reference range for singletons. There were no significant differences in mean growth velocity for any parameter between MCDA twins and singletons. Femur diaphysis length growth velocity was significantly lower in DCDA twins than in both MCDA twins and singletons. There were no other significant differences among the groups. Expanding on prior work using IGA, we found that second-trimester growth velocity of the four major anatomical parameters overall was similar between twins and singletons and between MCDA and DCDA twins, supporting the use of singleton-derived growth standards for IGA in twins. Twin growth potential appears to be similar to that of singletons in the second trimester, suggesting that subsequent growth divergence may be due to third-trimester physiological or pathological changes in twin pregnancies. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

ODP397 Small-volume, Subcutaneous, 6-month Leuprolide Acetate Effectively Reduces Growth Velocity to Prepubertal Levels in Children with Central Precocious Puberty

Abstract Introduction Clinical signs of puberty, growth rate, rate of bone maturation, luteinizing hormone concentrations and estimates of change in predicted adult height are the common variables for assessing efficacy of central precocious puberty (CPP) therapies. (1, 2) All clinical and laboratory parameters are essential when interpreting treatment response. (3) Preservation of adult height potential is an important goal of CPP treatment and accelerated growth velocity can contribute to reduced adult height. (4) We present secondary analyses of growth velocity data from the pivotal trial of the first small-volume, long-acting, subcutaneously administered GnRH agonist for central precocious puberty (CPP), approved in 2020. (5) Methods: 62 children (60 girls, 2 boys) with treatment-naïve CPP received 2 doses of 45 mg subcutaneous leuprolide acetate at 24-week intervals. We measured standing height with a calibrated stadiometer at Baseline and Weeks 4, 12, 20, 24, 36, 44, and 48. Growth velocity (cm/year) was calculated as a change in height (cm) between visits/((number of weeks between visits)/52). Results Mean growth velocity decreased throughout treatment from 10.4 cm/year for the time period from screening to baseline to 6. 0 cm/year for Week 34 to 48. The proportion of children who achieved growth velocity 4-6 cm/year increased 2.5-fold from baseline (10%) to Week 48 (25%). Conclusions Subcutaneous leuprolide acetate effectively decreased growth velocity to prepubertal rates in children with CPP. Mean growth velocity from Week 24 to 48 was similar to what is seen in children of the same age without CPP (5.8-6.1 cm/year, depending on sex and race). (6) These data indicate that subcutaneous leuprolide acetate may increase adult height and improve the likelihood of achieving genetic target height range. References Cited 1. Klein KO, et al. Phase 3 trial of a small-volume subcutaneous 6-month duration leuprolide acetate treatment for central precocious puberty. JCEM. 2020. 2. Lee HS, et al. Increased final adult height by gonadotropin-releasing hormone agonist in girls with idiopathic central precocious puberty. PLoS One. 2018. 3. Klein KO, Lee PA. Gonadotropin-releasing hormone (GnRHa) therapy for central precocious puberty (CPP): Review of nuances in assessment of height, hormonal suppression, psychosocial issues, and weight gain, with patient examples. PER. 4. Chen M, Eugster EA. Central Precocious Puberty: Update on Diagnosis and Treatment. Paediatr Drugs. 2015. 5. FENSOLVI® (leuprolide acetate) for injectable suspension, for subcutaneous use [prescribing information]. 2020. 6. Kelly A, et al. Age-based reference ranges for annual height velocity in US children. JCEM. 2014. Presentation: No date and time listed

Cerebral Arterial Growth in Childhood

BackgroundImproved understanding of cerebral arterial growth in children may lead to advances in the diagnosis and treatment of pediatric cerebrovascular disease. We correlated cross-sectional diameters of major cerebral arterial structures with age, sex, head circumference, weight, and height in children without cerebrovascular disease. MethodsChildren with normal brain magnetic resonance imaging (MRI) were retrospectively identified and stratified into 23 age cohorts from birth to age 18 years. Absence of vascular disease was verified by medical record review. Demographic and biometric data were obtained from medical records. Intracranial arterial diameter (IAD) was measured on T2-weighted fast spin echo brain MRI of vertebral, basilar, internal carotid artery, and circle of Willis arterial segments. ResultsA total of 307 subjects are included in the analysis, including 5833 vessel segments (mean age 8.4 years, 53% female). Indications for imaging were headache (73%), seizure (26%) and concussion (1%). IAD rapidly increased during the first year of life (mean growth velocity 0.064 to 0.213 mm/month) and then plateaued or slightly decreased between age one and 18 years (mean growth velocity −0.002 to 0.003 mm/month). Multivariable analysis shows strongest correlation with head circumference as a predictor of IAD. Weaker correlations are associated with weight and age. Height and sex are not well correlated with IAD. ConclusionsIntracranial arteries grow rapidly during the first year of life and then sharply plateau or slightly decrease in luminal diameter between infancy and early adulthood. IAD is more closely correlated with head circumference than age.

LGG-40. Growth hormone replacement in children on therapy with Vemurafenib for Low Grade Glioma

BRAF inhibitors (iBRAF) are a therapeutical option for pediatric Low-Grade-Gliomas (pLGG), but their chronic use may be needed to prevent tumor regrowth. Growth hormone (GH) replacement in children with GH deficiency (GHD) and on oncological treatment is under debate. We report on our experience of recombinant human GH (rhGH) replacement in two children (1 Female, 1 Male) which started Vemurafenib therapy, at 5 (F) and 9,25 (M) years of age, for recurrent/progressive chiasmatic-hypothalamic pLGG, with partial response (RANO criteria) and subsequent stable disease. A diagnosis of GHD was established at 9,2 (F) and 11,2 (M) years of age (GH peaks to stimulation tests <3mcg/L), 4,2 (F) and 1,9 (M) years after Vemurafenib start. Both patients were treated with GnRH analogues for precocious puberty. rhGH dose was titrated to 0.020 mg/kg/day during follow-up based on IGF-1 levels < +2 SDS. Height remained stable in both (F: -3,4SDS; M: 0SDS), with a mean growth velocity after 2 years around 6 cm/yr. BMI increased in the F (1,59 to 1,78 SDS) and decreased in the M (2,66 to 2,56 SDS); Dual-X-ray absorbiometry confirmed high fat mass at T0 (F:54,6%; M:48%) and at T24 (F:49,2%; M:48,1%). Lipid profile improved in both patients (F: Triglycerides 175 to 152 mg/dl, LDL 195 to 155 mg/dl; M: Triglycerides 138 to 118 mg/dl, LDL 147 to 147 mg/dl, at T0 and T24, respectively), while baseline blood glucose increased (F: 83 to 96 mg/dl; M 82 to 91 mg/dl). Residual tumor was stable in both patients. CONCLUSIONS: In 2 GHD patients due to pLGG and treated with Vemurafenib, two-years of low-dose rhGH showed beneficial effects on height stabilization and on lipid profile, and a different impact on body composition parameters; rhGH was safe and not associated with residual tumor growth.

Using linear and natural cubic splines, SITAR, and latent trajectory models to characterise nonlinear longitudinal growth trajectories in cohort studies

BackgroundLongitudinal data analysis can improve our understanding of the influences on health trajectories across the life-course. There are a variety of statistical models which can be used, and their fitting and interpretation can be complex, particularly where there is a nonlinear trajectory. Our aim was to provide an accessible guide along with applied examples to using four sophisticated modelling procedures for describing nonlinear growth trajectories.MethodsThis expository paper provides an illustrative guide to summarising nonlinear growth trajectories for repeatedly measured continuous outcomes using (i) linear spline and (ii) natural cubic spline linear mixed-effects (LME) models, (iii) Super Imposition by Translation and Rotation (SITAR) nonlinear mixed effects models, and (iv) latent trajectory models. The underlying model for each approach, their similarities and differences, and their advantages and disadvantages are described. Their application and correct interpretation of their results is illustrated by analysing repeated bone mass measures to characterise bone growth patterns and their sex differences in three cohort studies from the UK, USA, and Canada comprising 8500 individuals and 37,000 measurements from ages 5–40 years. Recommendations for choosing a modelling approach are provided along with a discussion and signposting on further modelling extensions for analysing trajectory exposures and outcomes, and multiple cohorts.ResultsLinear and natural cubic spline LME models and SITAR provided similar summary of the mean bone growth trajectory and growth velocity, and the sex differences in growth patterns. Growth velocity (in grams/year) peaked during adolescence, and peaked earlier in females than males e.g., mean age at peak bone mineral content accrual from multicohort SITAR models was 12.2 years in females and 13.9 years in males. Latent trajectory models (with trajectory shapes estimated using a natural cubic spline) identified up to four subgroups of individuals with distinct trajectories throughout adolescence.ConclusionsLME models with linear and natural cubic splines, SITAR, and latent trajectory models are useful for describing nonlinear growth trajectories, and these methods can be adapted for other complex traits. Choice of method depends on the research aims, complexity of the trajectory, and available data. Scripts and synthetic datasets are provided for readers to replicate trajectory modelling and visualisation using the R statistical computing software.

Phase 3 trial of a small-volume subcutaneous 6-month duration leuprolide acetate treatment for central precocious puberty

CONTEXT Gonadotropin-releasing hormone agonists (GnRHas) are standard of care for central precocious puberty (CPP). A 6-month subcutaneous injection has recently been approved by the Food and Drug Administration. OBJECTIVE Determine efficacy, pharmacokinetics, and safety of 6-month 45-mg subcutaneous leuprolide acetate for CPP. DESIGN Phase 3 multicenter, open-label, single-arm study. SETTING 25 sites in 6 countries. SUBJECTS 64 GnRHa-naive children with CPP (age: 7.5 ± 0.1 years) received study drug: 59 completed the study. INTERVENTION(S) 2 doses of 45-mg subcutaneous leuprolide acetate (0.375 mL) at 0 and 24 weeks; children were followed for 48 weeks. MAIN OUTCOME MEASURE(S) Percentage of children with serum luteinizing hormone (LH) <4 IU/L 30 minutes following GnRHa stimulation at week 24. RESULTS 54/62 (87%) children achieved poststimulation LH <4 IU/L at week 24; 49/56 (88%) girls and 1/2 boys maintained peak LH <4 IU/L at week 48. Mean growth velocity decreased from 8.9 cm/year at week 4 to 6.0 cm/year at week 48. Mean bone age was advanced 3.0 years beyond chronological age at screening and 2.7 years at week 48. Breast pubertal stage regressed or was stable in 97% of girls and external genitalia development regressed in both boys. Adverse events were mild and did not cause treatment discontinuation. CONCLUSIONS A small volume of 45-mg subcutaneous leuprolide acetate administered at a 6-month interval effectively suppressed pubertal hormones and stopped or caused regression of pubertal progression. This long-acting GnRHa preparation of leuprolide acetate is a new, effective, and well-tolerated therapy for children with CPP.

Growth Velocity of the Preterm Infant Managed with a Standardized Nutritional Protocol in a Tertiary Care Hospital

Prematurity is one of the major causes of neonatal death in developing countries like Bangladesh. Appropriate protocol for nutritional support of the preterm infants is essential to achieve a postnatal growth rate similar to that of a normal fetus. Objective of the study was to assess the effects of the existing nutritional support protocol of Bangabandhu Sheikh Mujib Medical University (BSMMU) in the early postnatal growth velocity of the preterm infants.This quasi-experimental study was conducted in the Department of Neonatology, BSMMU, Bangladesh from January to December 2015. All admitted infants aged &lt;48 hours and born &lt;_32 weeks of gestational age were included in this study. Infants were provided with nutritional support as per the BSMMU feeding guideline. The subsequent growth of the children was followed up routinely to measure the growth velocity. Of the 38 infants of our study, the mean calorie intake was 66.71 Kcal/kg/day. Overall mean growth velocity of weight, length and occipitofrontal circumference (OFC) up to discharge were 8.97 g/kg/day, 0.85 cm/week, and 0.41 cm/week respectively. Very low birth weight (VLBW) infants got significantly more calories compared to low birth weight (LBW) infants (p = 0.009). Mean growth velocity in weight of LBW infants were 8.18 g/kg/day and VLBW were 9.95 g/kg/day (p = 0.233). At birth, only 2.6% of infants had weight &lt;10th centile, but at discharge, it was 52.6%. Early postnatal nutritional supplementation was not adequate, and postnatal growth failure remains very high in the hospital admitted preterm infants. Faridpur Med. Coll. J. 2020;15(2): 79-84

Bimodal Dynamics in Short-Term Growth Among Peruvian Infants at Risk of Growth-Faltering

ObjectivesOver the short term, infants may grow in a ‘bimodal’ manner, with interspersed periods of greater and lesser growth. Our aim was to describe the modality of high-resolution growth dynamics of infants who experienced cumulative growth faltering in the first year of life. MethodsThrice-weekly measurements of length were recorded for n = 58 children enrolled from birth to one year in the Peru cohort of the Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development’ (MAL-ED) study. Finite mixture models were fitted to the length velocity data to test for evidence of multiphasic patterns. We then tested whether evidence of a multiphasic pattern remained after applying a smoothing algorithm to account for measurement error. Data was smoothed using kernel regression with a monotonic constraint. Finite mixture models were fitted to unsmoothed and smoothed data to examine whether growth patterns varied by age and sex. We also fitted stratified models to compare short-term growth patterns between infants who maintained a consistent length-for-age Z-score (LAZ) from 2–12 months of age, versus those whose LAZ decreased by at least 0.25 over the same period. ResultsUnsmoothed data were best described by a biphasic finite mixture model. The growth of children less than 3 months old was described by a mixture of two normal distributions with both means significantly greater than zero (0.110 cm/day, 95%CI: 0.105, 0.114 and 0.291 cm/day, 95%CI: 0.235, 0.347). By 6 months, this transitioned to a pattern of two normal distributions, one with a mean near zero (0.019, 95% CI: 0.0178, 0.020), and one with a mean of 0.102 cm/day (95% CI: 0.098, 0.0107). Children who lost 0.25 or more in LAZ from 2 to 12 months had a similar mean growth velocity in both the ‘low’ and ‘high’ growth phase but spent smore time in the former phase (54.9% of days versus 39.2% of days) than children who either maintained or gained LAZ over the same age. ConclusionsConsistent with other reports, we find that infant growth appears to follow bimodal dynamics characterized by intervals of greater velocities as well as periods of much lower growth. Funding SourcesThis work was supported by the National Institutes of Health and the BMGF.

Efficacy of Growth Hormone Treatment in Children With Chronic Kidney Disease: Tunisian Experience

To study the effect of using recombinant human growth hormone (rhGH) in growth retarded children with chronic kidney disease (CKD). This was a non-randomized controlled study over 2 years including children in CKD stages 4-5 suffering from growth retardation. Children were divided into rhGH-treated or non-rhGH treated groups. A total of 70 children (35 in each group) were enrolled. While the mean (SD) height of 35 children with CKD had increased from 109.5 (26) cm to 116 (26) cm (mean growth velocity 6.5 cm/year; P=0.09) prior to rhGH therapy, the same was found to increase from 116 (26) cm at the start of therapy to 125 (25) cm after one year of therapy (P=0.02). Therapy with rhGH was helpful in catch-up growth in Tunisian children with CKD.

P182125 YEARS OF GROWTH HORMONE TREATMENT IN CHILDREN WITH CHRONIC KIDNEY DISEASE IN POLAND - RESULTS OF NATIONAL MULTICENTER STUDY

Abstract Background and Aims Growth retardation is one of considerable problems in children with chronic kidney disease (CKD) with a great impact on life activity and quality of life. Recombinant human growth hormone (rhGH) treatment has been used for more than 30 years to improve growth velocity and final growth in children with CKD. In Poland rhGH therapy in children with CKD is available since 1994. The aim of the study was to assess growth velocity in all children with CKD treated with rhGH in Poland since 1994. Method We retrospectively analyzed 321 polish children with CKD (mean age: 10.2±7.60, 210 ♂ (65%) qualified to the rhGH therapy between 1994 and 2019. Among 321 children, 180 (56.1%) were on conservative treatment (CT), 118 (36.7%) on chronic dialysis (RRT) and 23 (7.2%) after kidney transplantation (KTx). In 240 (75%) patients who were treated continuously for at least 12 months we have evaluated: growth velocity and mean annual values of selected biochemical parameters. Results Mean height SDS at the beginning of the treatment was -2.73±1.04 SD, among children on CT -2.22±1.20, on RRT -2.9±1.11, after KTx -3.07±1.30. Mean time of rhGH treatment was 23±10.7 months. During one-year rhGH treatment mean growth velocity in 240 children was: 8.5 ± 2.7 cm (ΔSDS 0.78±1.02) and mean height SDS increased significantly (-2,73±1.04 vs. -1.92±1.11, p&amp;lt;0.0001). Children on CT did not differ significantly in age vs. children on RRT (10.66±3.40 vs. 10.26±3.61 years, p =0.972), and growth velocity was slower in RRT group expressed in cm (7.52±2.59 vs. 9.2±2.30, p&amp;lt;0.0001) and in ΔSDS (0.4±0.83 vs. 0.72±1.15, p=0.045). Growth velocity (ΔSDS) correlated negatively with age of rhGH initiation in children on CT (r=-0.40, p=0.008) and on RRT (r=-0.28, p=0.03). We found no significant relation between growth velocity and sex, cause of CKD, hemoglobin, total protein, albumin, urea, creatinine, calcium, phosphorus, Ca x P, PTH and alkaline phosphatase. Conclusion 1. Growth hormone treatment is highly effective in children with CKD especially those who are treated consevatively. 2. Early initiation of rhGH therapy is the crucial factor determining response to the treatment in children with CKD.

Template-directed growth of copolymers.

The theory of multistate template-directed reversible copolymerization is developed by extending the method based on iterated function systems to matrices, taking into account the possibility of multiple activation states instead of a single one for the growth process. In this extended theory, the mean growth velocity is obtained with an iterated matrix function system and the probabilities of copolymer sequences are given by matrix products defined along the template. The theory allows us to understand the effects of template heterogeneity, which include a fractal distribution of local growth velocities far enough from equilibrium, and a regime of sublinear growth in time close to equilibrium.

Testosterone versus hCG in Hypogonadotropic Hypogonadism - Comparing Clinical Effects and Evaluating Current Practice.

Background. Gonadotropin therapy is not typically used for pubertal induction in hypogonadotropic hypogonadism (HH), however, represents a promising alternative to testosterone. It can potentially lead to the maintenance of future fertility in addition to testicular growth. We compared the pubertal effects of human chorionic gonadotropin (hCG) versus testosterone in adolescent males with HH. We evaluated the current practice, among pediatric endocrinologists, to identify barriers against gonadotropin use. Methods. In this retrospective review, we compared the effect of testosterone versus hCG therapy on mean testicular volume (MTV), penile length, growth velocity, and testosterone levels. We surveyed pediatric endocrinologists at our center, using RedCap. Results. Outcomes were assessed in 52 male patients with HH (hCG, n = 4; T, n = 48) after a mean treatment duration of 13.4 (testosterone) and 13.8 months (hCG; P = .79). Final MTV was higher with hCG (8.25 mL) than testosterone (3.4 mL; P < .001). The groups did not differ in penile length, growth velocity, or testosterone levels. Survey results showed that more than half the providers were aware of the benefits of gonadotropins, however, 91% were uncomfortable prescribing hCG. Commonly reported barriers to prescribing hCG were lack of experience (62%) and insurance coverage concerns (52%). Conclusions. Larger testicular volume predicts faster induction of spermatogenesis. Since hCG promoted better testicular growth, compared to testosterone, it may potentially improve future fertility outcomes in HH patients. Our results identify an opportunity to improve current practice among pediatric endocrinologists worldwide and reduce barriers to prescribing gonadotropins in the adolescent population.

Percutaneous Endoscopic Gastrostomy After Cardiothoracic Surgery in Children Less Than 2 Months Old: An Assessment of Long-Term Malnutrition Status and Gastrostomy Outcomes.

Infants with critical congenital heart disease undergoing cardiothoracic surgery commonly experience chronic malnutrition and growth failure. We sought to determine whether placement of a percutaneous endoscopic gastrostomy was associated with reduced moderate-severe malnutrition status and to describe percutaneous endoscopic gastrostomy-related clinical and safety outcomes in this population. Single-center, retrospective cohort study. Two hundred fifty-nine-bed, tertiary care, pediatric referral center. Children with congenital heart disease less than 2 months old undergoing cardiothoracic surgery from 2007 to 2013 with and without percutaneous endoscopic gastrostomy. None. Primary outcomes were weight for age z scores during hospitalization, at 6 months, and 1 year after cardiothoracic surgery. Secondary outcomes were frequency of percutaneous endoscopic gastrostomy revision, percutaneous endoscopic gastrostomy complications, and mortality. Statistical analyses included Wilcoxon rank-sum, Fisher exact, and Student t tests. Two hundred twenty-two subjects met study criteria, and 77 (35%) had percutaneous endoscopic gastrostomy placed at a mean of 45 ± 31 days after cardiothoracic surgery. No differences were noted for demographics, comorbidities, and weight for age z score at birth and at the time of cardiothoracic surgery. The percutaneous endoscopic gastrostomy cohort had greater Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery risk category (4 [4-5] vs 4 [2-4]) and length of stay (71 d [49-101 d] vs 26 d [15-42 d]). Mean weight for age z score at the time of percutaneous endoscopic gastrostomy was -2.8 ± 1.3. Frequency of moderate-severe malnutrition (weight for age z score, ≤ -2) was greater in children with percutaneous endoscopic gastrostomy at discharge (78% vs 48%), 6 months (61% vs 16%), and 1 year (41% vs 2%). Index mortality was lower in children with percutaneous endoscopic gastrostomy at 30 days (8% vs 0%) and hospital discharge (19% vs 4%). However, no mortality differences were observed after discharge. Growth velocity after percutaneous endoscopic gastrostomy was greater (44 ± 19 vs 10 ± 9 g/d). Children tolerated percutaneous endoscopic gastrostomy without hemodynamic compromise, minor percutaneous endoscopic gastrostomy complications, and anticipated percutaneous endoscopic gastrostomy revisions. Children without mortality had percutaneous endoscopic gastrostomy removal at a median duration of 253 days (133-545 d). Children with univentricular physiology had improved in-hospital mean growth velocity (6.3 vs 24.4 g/d; p < 0.01) and reduced 1-year rate moderate-severe malnutrition (66.7% vs 36.9%; p < 0.01) after percutaneous endoscopic gastrostomy placement. Percutaneous endoscopic gastrostomy placement was well tolerated and associated with improved postoperative growth velocity in children with critical congenital heart disease undergoing cardiothoracic surgery less than 2 months old. These findings were also noted in our subanalysis of children with univentricular physiology. Persistent rates of moderate-severe malnutrition were noted at 1-year follow-up. Although potential index mortality benefit was observed, definitive data are still needed.

Nutritional therapies in the neonatal intensive care unit and post-natal growth outcomes of preterm very low birthweight Asian infants.

A collaborative study was conducted between two Southeast Asian university hospitals to compare the nutritional intervention and growth outcomes and evaluate the extent of post-natal growth faltering (PNGF) among very low birthweight (VLBW) infants. Data of all infants admitted during the 2011-2012 period to the two hospitals at Singapore (SG) and Malaysia (MY) were pooled and analysed. Of the 236 infants, SG infants received lower total protein and energy intake than MY infants (2.69 vs. 3.54 g/kg/day and 92.4 vs. 128.9 kcal/kg/day respectively; P < 0.001) in enteral feeds, with Singaporean infants predominantly fed fortified breast milk than Malaysian infants (45/48 vs. 10/41; P < 0.01). The mean weight z-score from birth to 36 weeks corrected age was significantly different (SG,-2.2 (0.9) vs. MY, -1.4 (0.7); P = 0.001). More SG than MY extremely low birthweight (ELBW) infants had severe PNGF >-2 SDS (55 vs. 16%; P = 0.001). The greater use of a diuretic in SG to treat haemodynamically significant patent ductus arteriosus (hsPDA) may have contributed to the higher PNGF rate. Mean growth velocity of at least 15 g/kg/day was attained by VLBW infants only from Day 14 and by ELBW infants only from Day 28 post-natally. Overall, severe PNGF rates (z-score change >-2 SDS at 36 weeks' corrected age) were 28.8 and 36.5% for VLBW and ELBW infants, respectively. Being very preterm, ELBW with hsPDA and receiving insufficient protein and energy were risk factors for severe PNGF. Increasing protein and energy content, augmenting fortification of breast milk and concentrating feed volumes, especially if there is an hsPDA, may curb severe PNGF among these infants.