Correlation Analysis Of Bile Acid And Insulin-like Growth Factor-1 With Catch-up Growth In Preterm Infants

Part one:Correlation Analysis of Bile Acids and Catch-up Growth in Preterm InfantsBackground and objective:Bile acids,the main component of bile,are produced in the liver by the metabolism of cholesterol.Bile acids not only promote the absorption of nutrients in the intestine and maintain cholesterol homeostasis.It also act as a signaling molecule to regulate lipid,glucose and energy metabolic homeostasis by activating nuclear and cell surface receptors.Preterm infants with immature hepatobiliary system and impaired liver uptake have high bile acids levels in early postnatal period.Especially when combined with infection,fasting and long-term use of intravenous nutrition,the increase of bile acids is more significant.If the metabolism of bile acids is abnormal,the feedback regulation of bile acids synthesis and transport is impaired and the signaling mediated by bile acids are dysregulated,which can also lead to diseases of the hepatobiliary system,lung damage,myocardial damage,necrotizing small intestinal colitis and disorders of glucose metabolism.At present,most of the studies on bile acids in China and abroad focus on neonatal parenteral nutrition-associated cholestasis,neonatal jaundice and other diseases of the hepatobiliary system,while relatively little research has been done on other neonatal diseases.In clinical practice,it has been observed that bile acids levels in preterm infants with good weight gain during hospitalization are lower than those in preterm infants with unsatisfactory weight gain.This article investigates whether elevated bile acids in preterm infants affect physical growth and development in the early postnatal period,to understand the correlation between bile acids and catch-up growth in preterm infants.Providing clinicians with some information from another perspective.If bile acids are abnormally elevated,we can actively control the underlying disease,dynamically monitor bile acid levels,actively treat the symptoms,strengthen nutritional management,pay attention to monitoring growth and developmental indicators,and individualize the management of preterm babies for a more comprehensive and systematic approach to disease management.Methods:A total of 119 preterm infants admitted to the neonatal ward of XXX from December 2019 to February 2022 who were hospitalized for more than 7 days and discharged with complete oral feeding（excluding those with serious diseases affecting feeding and development）were selected.The EUGR group and the no EUGR group were divided according to whether the discharge weight was less than the 10th percentile of the corresponding gestational age.Preterm infants were divided into a normal bile acid group（TBA<10umol/L）,an elevated bile acid group（TBA 10-24.8umol/L）and a hypercholesterolemic group（TBA>24.8umol/L）according to their peak bile acid levels during hospitalization.Bile acid,albumin,prealbumin and creatinine were retrospectively collected from all study subjects at the time of admission and at the time of discharge,and physical developmental indicators of preterm infants were also collected,including time of birth,week of gestation at birth,birth weight,birth length,birth head circumference,birth chest circumference and physical indicators such as corrected gestational age,weight,length,head circumference and chest circumference at discharge.The△Z score of weight was calculated.All data were collated and analysed to investigate whether bile acids affect the physical growth of preterm infants in the early postnatal period and whether there is any correlation between bile acids and catch-up growth.Results:1.There were 119 preterm infants meeting the criteria,including 72（60.5%）male and 47（39.5%）female infants.25 cases（21%）were small for gestational age,86 cases（72.2%）were suitable for gestational age,and 8 cases（0.67%）were larger than gestational age;The gestational weeks of delivery are 30-36⁺⁴weeks;The birth weight is2139±662g（850g to 4350g）,the birth head circumference is 30.6±2.8cm（21.0cm to38.0cm）,the birth length is 43.2±4.0cm（32.0cm to 50.0cm）,and the median hospital stay is 12（7 to 70）days.2.The weight percentile of premature infants in the hyperbolic acidemia group at discharge was significantly lower than that in the normal bile acid group and the elevated bile acid group（H=20.147,P<0.05）.There was no significant difference between the normal bile acid group and the elevated bile acid group（P>0.05）.3.The group with EUGR accounted for 31%（37/119）and the group without EUGR accounted for 68.9%（82/119）;There were statistically significant differences in Ln bile acid（t=5.110,P<0.05）and Ln creatinine（t=1.247,P<0.05）between the EUGR group and the non-EUGR group;There was no significant difference between the two groups in albumin（t=-0.831,P>0.05）and prealbumin（t=-0.801,P>0.05）.4.There was a negative correlation between bile acids and the△Z score of weight in preterm infants（r_s=-0.358,p<0.05）.Conclusion:Abnormal increase of bile acid may affect the physical growth of premature infants in the early postnatal period,and has a negative correlation with catch-up growth.Part Two:Correlation of Insulin-like Growth Factor-1 with Catch-up Growth in Preterm InfantsBackground and objective:Catch-up growth is defined as accelerated growth in normal preterm infants after growth fails to reach the growth reference value for a period of time.Most preterm infants have catch-up growth after birth.However,factors such as postnatal malnutrition or diseases can affect the early postnatal growth of premature infants,leading to increased risk of growth retardation,infectious diseases and death.In recent years,it has been shown that insulin-like growth factor 1（IGF-1）,a major growth regulator,has a role in fetal and neonatal growth and is strongly associated with catch-up growth.In this study,we investigated the correlation between IGF-1 and early postnatal catch-up growth of preterm infants and the correlation between bile acids and IGF-1 by analyzing biochemical metabolic indicators and physical developmental indicators in preterm infants.Methods: A total of 32 preterm infants admitted to the neonatal ward of XXX from March 2022 to February 2023,who were hospitalized for more than 7 days and discharged from the hospital with complete oral feeding,were selected for the study（preterm infants with serious diseases affecting feeding and development were excluded）.The time of birth,week of gestation,birth weight,birth length,birth head circumference,and physical indicators such as corrected gestational age,weight,length,and head circumference at discharge were collected,and the results of IGF-1,IGFBP-3,albumin,prealbumin,creatinine,HDL,LDL,total cholesterol,and triglycerides were also recorded.The△Z score of weight and Kaup index（KI）were calculated.All data were compiled and analyzed to elaborate the change pattern of IGF-1 in preterm infants and to explore the relationship between biochemical metabolic indexes and physical growth indexes in preterm infants and the correlation between IGF-1 and catch-up growth in early postnatal period.Results: 1.A total of 32 cases of preterm infants meeting the criteria were included in this study,including 17 males（53.1%）and 15 females（46.8%）;3 cases（9.3%）were small for gestational age,28 cases（87.5%）were appropriate for gestational age and 1 case（3.1%）was lager for gestational age;gestational age ranged from 30 to 35+6 weeks,birth weight was 1940.47 g（850 g to 4010 g）,birth head circumference 29.88 cm（21 cm to 49 cm）,birth length 41.35 cm（33 cm to 49 cm）,median hospital stay 25.5（7 to 65）days.2.IGF-1 and IGFBP-3 were significantly different in preterm infants at different gestational weeks,and the smaller the gestational week,the lower the IGF-1 and IGFBP-3,and the differences were statistically different（F= 5.5 and 3.66,p < 0.05）.3.KI index and the△Z score of weight score were positively correlated with IGF-1（rs = 0.67,0.517,p < 0.05）,head circumference was positively correlated with prealbumin（r = 0.303,p < 0.05）,and chest circumference was positively correlated with albumin,prealbumin,and Ln creatinine（r =0.275,0.317,0.433,p < 0.05）4.There was a negative correlation between IGF-1 and bile acids in preterm infants（rs =-0.422,p < 0.05）.Conclusion: 1.There were differences between IGF-1 and IGFBP-3 in preterm infants at different gestational weeks,and positive correlation between IGF-1 and KI index and the△Z score of weight,suggesting a positive correlation between IGF-1 and catch-up growth in preterm infants.2.Some of the biochemical metabolic indicators of prematurity such as albumin,pre-albumin and creatinine correlate to varying degrees with physical indicators such as head circumference and chest circumference,and also predict growth and development in preterm infants..3.There was a negative correlation between IGF-1 and bile acids in preterm infants.It is speculated that IGF-1 in premature infants may be affected by bile acid.