GH, IGF-I, and growth

Recent studies have confirmed the importance of the growth hormone (GH)-insulin-like growth factor-I (IGF-I) axis as the major determinant of whole body growth in animals and humans and have highlighted the significance of IGF-I to human growth. Pharmacological studies in rodents and therapeutic studies in humans demonstrate that recombinant human (rh)IGF-I can induce a significant statural growth response. Mouse gene knockout studies have shown that IGF-I, rather than GH, is the major hormone controlling whole body growth. The relative importance of endocrine versus local IGF-I remains unresolved. In children who are GH- and IGF-I-deficient, treatment with GH stimulates a robust growth response. In children who are IGF-I-deficient but GH-sufficient, rhIGF-I might also be a useful treatment. Furthermore, pharmacological and genetic studies in animals show effects requiring the combined presence of GH and IGF-I, suggesting that rhGH and rhIGF-I together might be the optimal treatment for some children with short stature.     

Bone metabolism and circulating IGF-I and IGFBPs in dexamethasone-treated preterm infants

AIM: To characterize the ontogeny of circulating IGF-I, the IGF binding proteins (IGFBPs) and biochemical markers of bone turnover in dexamethasone (DEX)-treated preterm infants with chronic lung disease. METHODS: Plasma and urine samples from 17 infants were obtained prior to DEX, after 9-12 days of DEX and 10 days after the completion of DEX to assess plasma IGF-I, IGFBPs, osteocalcin and urinary N-telopeptide. Nutrient intakes and growth were monitored from birth until term corrected age at which time body composition was evaluated by dual energy X-ray absorptiometry. RESULTS: Although nutrient intakes did not differ during or after DEX, weight gain (115 vs. 174 g/week) and length gain (0.7 vs. 1.0 cm/week) were higher after DEX treatment. Plasma IGF-I, IGFBP-3 and osteocalcin increased over time. N-telopeptide was the only biochemical parameter which appeared to be suppressed during DEX (1342 nM bone collagen equivalents/mM creatinine vs. 2486 (pre-DEX) and 2292 (post-DEX)). At term corrected age, bone mineral content was lower in dexamethasone-treated infants compared to preterm and term reference infants. CONCLUSION: Changes in circulating IGFBP-2 and IGFBP-3 paralleled the changes reported in non-steroid-treated infants; however, it remains uncertain whether the natural rise in IGF-I was suppressed by DEX treatment. Assessment of these circulating components provided limited insight into the mechanisms by which DEX alters growth and bone turnover.     

早产儿视网膜病的高危因素分析

为了研究早产儿视网膜病（ＲＯＰ）的发病率、高危因素及预后，对１４９例极低出生体重儿与ＲＯＰ的关系进行了回顾性分析。结果：ＲＯＰ５９例（４０％）；其中ＲＯＰ１期３２例（５４％），ＲＯＰ２期１６例（２７％），ＲＯＰ３期１１例（１９％）。所有ＲＯＰ３期患儿均患有散光或散光＋近视。通过对用氧时间，出生体重等２０种高危因素与ＲＯＰ严重程度的综合分析，发现长期使用氧气和出生低体重是造成ＲＯＰ的重要原因。建议缺乏用氧指征的早产儿切勿用氧。     

早产儿视网膜病病因及发病因素的研究进展

早产儿视网膜病(retinopathy of prematurity,ROP),原称晶体后纤维增生症,1942年首先由Terry报道,1984年正式定名为早产儿视网膜病。该病是一种增殖性视网膜病变,其特征为视网膜缺血、新生血管形成,可造成视网膜变性、脱离、并发白内障、继发青光眼、斜视、弱视,严重者可致盲。目前ROP已成为世界范围内儿童致盲的重要原因,约占儿童致盲原因的6%~18%[1]。早产低体重是ROP的根本原因,但该病的发病机制目前尚无定论,可能与新生儿期的一些高危因素如吸氧、酸中毒、贫血、感染等有关。现将ROP的病因及发病因素作一综述。一、早产低出生体重…     

Early postnatal growth in preterm infants

Changes in weight of 50 preterm infants (gestational age 32.7 +/- 0.3 weeks, birthweight 1772 +/- 49 g) were studied during the period of the 0-4 postnatal weeks. Intrauterine weight gain of fetuses with equivalent gestational age, weight percentile position and sex was calculated and used as a control. Study infants achieved significantly less weight by age of 4 weeks (116.2 +/- 1.2%) than it could have been expected theoretically (144.7 +/- 1.0%). Growth performance did not correlate significantly with calorie intake, but was closely related with gestational age.     

Effect of dexamethasone treatment on serum GH,IGF-I,and the binding proteins IGFBP-1 and -3 in ventilated very preterm infants

Very preterm infants developing bronchopulmonary dysplasia frequently show a compromised growth in the neonatal period especially when steroids are given to facilitate weaning from the ventilator. The aim of this study was to evaluate the short-term effect of dexamethasone (DEXA) on the GH-IGF axis in ventilated very preterm infants developing bronchopulmonary dysplasia. We studied 10 very preterm artificially ventilated infants with bronchopulmonary dysplasia [median (range) gestational age 27.5 wk (25.9-32.0 wk), median (range) birth weight 970 g (610-2150 g)] immediately before and 2 d after the start of DEXA treatment. On both days of study, serum GH profiles were obtained, and serum IGF-I and IGF binding protein (IGFBP) -1 and -3 levels were measured. The ventilation score and the nutritional intake were calculated. Before the start of DEXA treatment, the median serum mean GH level was 12.0 microg/L (6-28.4 microg/L), whereas 2 d after the start of DEXA treatment the median serum mean GH level declined significantly to a value of 4.4 microg/L (1.7-11.9 microg/L). During DEXA treatment, mean, baseline, and maximal GH levels (Pulsar analysis) were significantly lower compared with pretreatment levels (p < 0.01, p < 0.01, and p < 0.05, respectively). Serum IGF-I and IGFBP-3 levels did not decline during DEXA. Serum IGFBP-1 levels were significantly lower compared with pretreatment levels (p < 0.01). Serum GH levels during DEXA treatment were correlated with neither the time interval between the administration of DEXA and the second GH profile nor the cumulative DEXA dose administered. Ventilation score and nutritional intake did not significantly correlate with serum GH, IGF-I, or IGFBP-1 or -3 levels, either before or after the start of DEXA. Two days of DEXA treatment in very preterm ventilated infants has a suppressive effect on serum GH levels, without an acute decline in serum IGF-I levels. A concomitant decrease in serum IGFBP-1 levels was found.     

Nutrition and early growth of preterm infants

Recent studies have renewed the controversy over what should constitute the best milk for preterm infants. While pooled human breast milk continues to be widely recommended it seems for reasons poorly understood not to allow adequate early post-natal growth. In view of possible programming of later growth and neuropsychological development by early nutritional experiences there is a need to further research the question of what should consitute optimum nutrition for preterm infants. We suggest that modifying or finding natural modifications in human milk rather than further altering cow's milk might provide some of the answers. Particular attention also needs to be given to long-term neurological, anthropometric and psychological assessment to relate functional outcome to early nutritional experiences.     

Usefulness of growth hormone (GH) stimulation tests and IGF-I concentration measurement in GH deficiency diagnosis

The diagnosis of growth hormone (GH) deficiency (GHD) is still problematic for the clinician. There is no gold standard for estimating GH secretion. The aim of this study was to compare the diagnostic usefulness of spontaneous GH secretion test, pharmacological tests with insulin, clonidine, L-dopa, and glucagon, and IGF-I measurement in GHD. We studied 180 prepubertal, short children. Predictive values were calculated for different GH cutoff levels for each diagnostic test. ROC curves were used to estimate the diagnostic usefulness of the tests. The results show that sleep is the strongest stimulatory agent for GH secretion. The estimation of GH secretion after onset of sleep can be used as a screening test in GHD diagnosis. The insulin test has the highest discrimination. A combination of insulin test with another provocative test allows high discrimination and accuracy for standard cut-off GH level. Measurement of IGF-I is characterized by low predictive values. IGF-I level below the mean according to age indicates high probability of GHD. Auxological parameters should be the most important factor in diagnosing GHD.     

早产儿宫外生长迟缓

随着新生儿重症监护病房(NICU)的建立以及呼吸支持、营养支持技术的快速发展,早产儿成活率逐年上升.但由于宫内营养储备不足、生后早期生活能力差且多有营养热卡供给不足、加之各种并发症的影响,而导致其生长发育进一步落后.许多患儿在出院时存在累积营养不足及随之而来的生长迟缓,即宫外生长迟缓(EUGR),这已经成为早产儿研究领域的一个新热点.大量研究证实,EUGR患儿在婴幼儿期体重和头围增长较差,这种生长迟缓与后期语言困难、认知能力较差密切相关.因此,了解与EUGR发生的相关因素,探讨如何避免EUGR,早期积极的应用肠外营养(PN)与胃肠道营养(EN),对于减少EUGR的发生、促进早产儿正常生长发育、提高其生存质量具有重要的临床意义.     

Inflammatory and growth mediators in growing preterm infants

Little is understood about the optimal balance between IGF-I and antagonistic inflammatory mediators, such as IL-6, in growing preterm infants. Using a prospective cohort study, we investigated the relationship between postnatal growth of preterm infants and key growth and inflammatory mediators. We studied 51 stable, growing preterm infants (mean gestational age: 27.8 +/- 0.4 weeks, mean birth weight: 1,032.8 +/- 50.6 g). IL-6 and IL-1ra (reflecting stress/ inflammation) and IGF-I and GHBP (reflecting anabolic activity and GH sensitivity) were measured at enrollment and discharge using ELISA. During the observation period (mean 6.1 +/- 0.34 weeks) there was a significant increase in weight (1,396 +/- 81 g, p < 0.0001). IGF-I increased from 46.6 +/- 4.1 to 88.7 +/- 5.2 ng/ml (p < 0.001). In contrast, IL-6 decreased from 9.5 +/- 1.0 to 2.3 +/- 0.34 pg/ml (p <0.001) and IL-1ra from 6,042 +/- 362 to 4,851 +/- 365 ng/ml (p = 0.007). GHBP increased from 65.8 +/- 6.7 to 82.5 +/- 7.9 ng/ml (p = 0.003). IL-6 was inversely correlated with IGF-I (p < 0.001). In addition, a multiple regression model showed IGF-I levels correlated positively and IL-6 levels inversely with various parameters of growth. Growth in preterm infants is characterized by increases in IGF-I and GHBP with simultaneous decreases in IL-6 and IL-1ra. Efforts to optimally balance inflammatory and growth mediators may benefit somatic growth in infants very early in life.     

早产儿校正18~24月龄体格生长和神经发育水平研究

目的 应用动脉自旋标记（arterial spin labeling,ASL）成像技术测量的脑血流值（cerebral blood flow,CBF）评价支气管肺发育不良（bronchopulmonary dysplasia,BPD）早产儿局部大脑皮质血流灌注量。 方法 采用前瞻性研究方法,选择2021年8月—2022年6月在郑州大学第三附属医院产科出生并转入新生儿科的胎龄<32周、出生体重<1 500 g,于纠正胎龄35~40周完成头颅磁共振成像及ASL检查的90例早产儿为研究对象,根据是否诊断为BPD分为BPD组（n=45）和非BPD组（n=45）,比较两组早产儿ASL相同感兴趣区（额叶、颞叶、顶叶、枕叶、丘脑和基底神经节）CBF值的差异。 结果 与非BPD组早产儿相比,BPD组早产儿1 min Apgar评分更低,辅助通气时间更长,胎儿窘迫发生率更高,差异均有统计学意义（P<0.05）。应用多元线性回归分析控制头颅磁共振成像检查时纠正胎龄、日龄等混杂因素后,与非BPD组相比,BPD组左右两侧额叶、颞叶、顶叶、枕叶、基底神经节、丘脑的CBF值仍较高（P<0.05）。 结论 BPD可使早产儿大脑皮质血流灌注量增高,可能与前期缺氧、较长时间辅助通气有关。