【作者】 徐亚萍；

【导师】 俞惠民；

【作者基本信息】 浙江大学 ， 儿科学、新生儿专业， 2001， 硕士

【摘要】 体内99％的钙存在于骨骼中，血循环中钙含量不到体内总量的1％。胎儿期约80％的钙、磷蓄积出现在孕25周到足月，在此期间，体内钙以2.3～2.98mmol/kg.d的速率增加，峰蓄积率出现在孕36～38周。早产儿体内骨矿物质储备较少，生长速率较快，容易发生骨质疏松。影响早产儿骨矿化的因素除了胎龄、出生体重、肝肾功能及母亲因素外，食物中钙磷及维生素D的供给量尤为重要。根据以往钙平衡试验，早产儿每天钙推荐量，肠道内营养者为3.0～5.6mmol/kg，静脉内营养者为1.5～2.2mmol/kg；磷推荐量，肠道内营养者为1.9～4.5mmol/kg，静脉内营养者为1.5～2.2mmol/kg，肠道对母乳及早产儿奶方喂养的钙吸收率为35～75％。 衡量小儿骨代谢状况的传统方法为血钙、磷浓度测定及X线长骨摄片。近几年，国外用骨蛋白与骨胶原形成与分解的生化标志物研究新生儿及婴幼儿的骨代谢变化，如骨形成标志物血骨碱性磷酸酶（Bone alkaline phosphatase，BALP）、血骨钙素（Osteocalcin，OC），骨吸收标志物血Ⅰ型胶原羧基端肽（Carboxyterminaltelopeptide type I collangen，ICTP）、尿吡啶啉、脱氧吡啶啉等，而国内对早产儿这方面的研究甚少。本研究以血钙、磷、碱性磷酸酶（Alkaline phosphatase，AKP）、骨钙素、Ⅰ型胶原羧基端肽及尿钙、尿磷为观察指标，研究早产儿骨转化生化标志物的动态变化及补钙对其影响，并与足月儿对照，旨在探讨早产儿骨转化特点及早期补钙是否增加早产儿骨形成，减少骨吸收，以及补钙对血钙、血磷、尿钙、尿磷的影IJ④，为早产儿生后合理补充矿物质提供科学依据。 对象与方法： 研究对象： 2000年 1月～2000年7月在本院新生儿科住院的病人，共62例。其中 40例早产儿（胎龄＜35周），按入院先后随机分补钙组：20例，男12例，女8例，胎龄34．15士0、87周，出生体重2085．50士296，64克，出生24小时起给10％葡萄糖酸钙4ml／kgd （即元素钙 lmmol／kg．d），24小时均匀静脉补给共 10无，同时静脉注射维生素 K； （Zing／d）3天；对照组：20例，男门例，女9例，胎龄34＊ 士1刀7周，出生体重 2099．50士355．03克，常规补足液体量及维生素 KI （21g／d 3大。22例足月儿：男12例，女10例，胎龄39．95士l．00周，出生体重3320．45士305．36克。早产儿给予雀巢早产儿奶方，足月儿给予多美滋婴）［奶方。 方法： 所有新生儿分别于出生 24小时与 11日龄，早晨 6～8时，抽取不抗凝静脉血。采用美国 BECKMAN公司 Cx duta全自动生化分析仪测血钙（偶氮肿 Ill法）、磷（紫外分光光度法）、镁（Calmagite染料比色法）、碱性磷酸酶（速率法，AMP缓冲液）。采用酶联免疫吸附法测血骨钙素（试剂从美国Inc．公司进口）。用放射免疫法测血1型胶原梭基端肽（试剂盒从芬兰Orion公司进口）。 甲·产儿组于出生第门天，留24小时尿，用美国BECKMAN公司CX dLItl全自动生化分析仪测 24小时尿钙（偶氮叩I＊法）、尿磷（紫外分光光度法）。尿肌配（碱性苫味酸法）。 补钙组于出生12天检测尿常规及双肾B超。 统计学处理： 2 所有数据采川SPSS刀统计软件进行分析。多个样本间比较采用方差分析。正态分布且方差齐者，用 LSD（Least－significant dfference）法进行两两比较，不同日龄各数值采用配对 t检验，非正态分布资料采用非参数检验（M。fin、WhitflCy U Test）o 结 果 出生时，血钙、磷及钙磷乘积各组无显著差别，血．AKP、ICTP早产儿（214．35士67．06 IU，62．88士4．07 Ug／I）显著高于足月儿（147．86士44．87 IU，57．36士6．34 Llg／I）p＜0．01］，与胎龄及出生体重呈负相关（相关系数分别为－O．52＊尸＜0刀IZ刀石14，p＜0．of），而血 OC早产）匕（648．77士238．89 nmol／l）显著低于足月）L（851．68士238．69flflol／l）b＜0刀1］，与胎龄及出生体重呈正相关（相关系数分别为 0．359，尸＜0．05；0．376，p＜0刀 1）。 出生 11日龄，早产）恤 OC水平（947．25士335．47 nmol／l）显著升高，达足月）L水平（941．65士297．28 nmol／l），而血AKP及uTP早产）L（206．53土53．9 IU，65．44士6二4＜g／！）始终高于足月儿（165．18士43．抢IU，57．10士3．陀＜g／叭p＜0刀5，尸功刀1］。 补钙后，早产儿 OC及 ICTP （84．59士267．24 nmol／l，65．94士5．96 ＂g／1）与对照组 （947·25士 335．47 nmol／l；65．44 t 6．24 ＂g／l）无显著差异 e0．05］，AKP补钙组 （246．00士66。64lU）显著高于对照组（206．53士53．gIU）b＜0、051，血．钙、尿钙升高， 血磷、尿磷降低，尿钙补钙组（0．179士0．156mm。l／kg）显著高于对照组（0刀65士 0．33mmol／kg）［t＝3．18，P＜更多还原

【Abstract】 Ninety-nine percent of total calcium in body is stored in bone, calcium content in circulation is less than 1%. Approximate 80% of calcium and phosphorus are accumulated in the fetus from 25 weeks of gestation to term. During this period, the estimated daily calcium accretion is 2.3 to 2.98 mmol/kg.d. The peak accretion rate occurs between 36 to 38 weeks of gestation. Osteopenia is a common problem in preterm infant due to less the intrauterine accumulation of bone minerals and more rapidly growth.The mean intake of calcium, phosphorus, vitamine D are the main factors of impacting bone mineralization in preterm infants, besides gestational age, birth weight, liver and kidney function, maternal factors. According to calcium balance test in the past, daily calcium intake recommended was 3.0 to 5.6 mmol/kg.d in the preterm infants of enteral nutrient, 1.5 to 2.2 mmol/kg.d in the preterm infants of parenteral nutrient; daily phosphorus intake recommended was 1.95to 4.5 mmol/kg.d in the preterm infants of enteral nutrient; 1.5 to 2.2 mmol/kg.d in the preterm infants of parenteral nutrient. The intestinal absorption rate of calcium in the preterm infant with both breast and preterm formula feeding were 35~75%.The tradational assessments of bone metabolism in children were the measurements of serum calcium and phosphorus, radiographic studies of the skeleton. Recently, biochemical markers of bone formation and bone resorption have been used to determine the dynamic changes of bone metabolism in neonates, infants and early children. Markers of bone formation generally include serum osteocalcin (OC), total and bone-specific alkaline phosphatase (ALP, BALP). Markers of bone resorption generally include serum carboxy-terminal telopeptide type I collangen (ICTP), urine pyridinoline and deoxypyridinoline. We study serum calcium, phosphorus, ALP, OC, ICTP and urine calcium, phosphorus in preterm infants before and after parenteral calcium supply, to explore the features of preterm infants bone turnover, and to test the hypothesis that early parenteral calcium supply can increase bone formation and decrease bone resorption in preterm infants, and to determine the effect of early parenteral calcium supply on calcium and phosphorus level in serum and urine.Materials and methodsSixty-two newborn infants were recruited from the department of neonatology, Children Hospital, Zhejiang University School of Medicine from January though July 2000. Forty preterm infants were divided into parental calcium supply group and control group at random according to admission time. The parental calcium supply group consisted of 20 preterm infants (12 males, 8 females), with gestational age of 34.15?.87 weeks, birth weight of 2085.50?96.64 gram. Intravenous administration of 10% calcium gluconate6(4ml/kg.d, equal to calcium lmmol/kg.d) was given from postnatal 24 hour to 11th day. The control group consisted of 20 preterm infants (11 males, 9 females), with gestational age of 34.10?1.0 weeks, birth weight of 2099.50?55.03 gram. Except for the different parental calcium contents, the formula (Nestle, preterm infant formula) and vitamine K1 (2mg/d from birth to third day) were equivalent in both groups. Twenty-two term infants (12 males, 10 females), with gestational age of 39.95?.00 weeks, birth weight of 3320.45 ?305.36 gram, were recruited as compared with preterm infants. The formula was Dumex infant formula.The blood samples in all neonates were drawn by vein puncture at 6~8 Am at 24 hour and 12th day. Serum concentration of total calcium (arsenazo III method), phosphorus (ultraviolet spectrometry), magnesium (calmagite chromometry) and vitality of ALP (velocity method) were measured by automatic biochemical analyzer techniques (Cx duta, BACKMAN corporation, USA). Serum concentration of OC was assayed by ELISA (Diagnostic Systems Laboratories, Inc. USA). Serum concentration of ICTP was assayed by radioimmunoassay (Orion Corporation, Finland). At 11th day, the u更多还原