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1、孕妇钙营养及钙需要的系列研究孕妇钙营养及钙需要的系列研究 研究背景l孕期钙营养需要的特殊性孕期钙营养需要的特殊性l成熟新生儿体内含钙约成熟新生儿体内含钙约30g，孕末期需储钙约孕末期需储钙约300mg/d；lWHO/FAO制订孕期钙推荐供给量的依据包括制订孕期钙推荐供给量的依据包括 是以非孕妇女为基础加上胎儿发育所需钙量；是以非孕妇女为基础加上胎儿发育所需钙量；考虑钙的吸收率；考虑钙的吸收率；l1988年中国营养学会制订钙年中国营养学会制订钙RDA为为1500mg/d;研究背景l钙的供给现状钙的供给现状l1992年全国营养调查显示，城乡人均钙摄入量年全国营养调查显示，城乡人均钙摄入量为为405
2、.2mg/d，为，为RDA49.2%;l广东城乡居民人均钙摄入量为广东城乡居民人均钙摄入量为387.5mg/d，为，为RDA46.5%;l各地孕妇钙实际摄入量各地孕妇钙实际摄入量398721mg/d，为，为RDA 的的1/31/2。问题的提出l我国孕妇缺钙？l我国孕妇对传统低钙膳食适应？l传统低钙膳食对孕妇、胎儿或新生儿有什么影响？研究的实验设计 一、动物实验一、动物实验l以非孕雌性大鼠为对照；以非孕雌性大鼠为对照；l用含钙用含钙1.0、0.25、0.05三种饲料干预妊三种饲料干预妊娠大鼠至产后，观察不同钙供给时，妊娠大鼠娠大鼠至产后，观察不同钙供给时，妊娠大鼠钙代谢的差异；钙代谢的差异；l钙
3、代谢试验；钙代谢试验；l45Ca小肠吸收试验；小肠吸收试验；研究的实验设计二、人体追踪研究二、人体追踪研究l对象对象 36名孕名孕18周妇女周妇女;l分组分组 I（传统膳食组）传统膳食组）钙摄入钙摄入478.5 139.7 mg/d；II(膳食钙干预组膳食钙干预组)传统膳食传统膳食+45g奶粉，钙摄奶粉，钙摄入入823.9 82.0mg/d；III(膳食加钙剂联合干预组膳食加钙剂联合干预组)传统膳食传统膳食+45g奶奶粉粉+600mg钙，钙摄入量钙，钙摄入量1274.6 147.8 mg/d;研究研究的实验设计二、人体追踪研究二、人体追踪研究内容内容 膳食钙干预，从孕中至产后膳食钙干预，从孕中
4、至产后45天；天；母体：钙代谢试验；母体：钙代谢试验；相关生化指标；相关生化指标；激素水平测定；激素水平测定；产后骨密度；产后骨密度；子代：胎儿发育，新生儿体格；子代：胎儿发育，新生儿体格；一、妊娠机体对低钙供给的代谢改变（一）动物试验 Table 1 Indices of calcium metabolism in pregnant rats（x s）n 1.0%Ca 0.25%Ca 0.05%CaDiet consumption(g/d)30 14.73 1.57 16.28 2.68a 18.65 1.86a bCalcium intake(mg/d)30 147.92 18.33 39
5、.24 6.76a 9.24 0.94a bCa of feces(mg/d)21 115.85 21.79 19.27 6.69a 13.10 1.69a bCa of urine(mg/d)21 0.52 0.06 0.38 0.07a -AA of Ca(%）21 21.49 0.48 49.54 6.14a -Retention of Ca(mg/d)21 31.56 14.70 19.59 7.62a -4.12 1.88Note:a:compared with 1.0%Ca,p 0.05;b:compared with 0.25%Ca,p 0.05;一一、妊娠机体对低钙供给的代谢改
6、变Table 2 Indices of calcium metabolism of rats in 24hoursGroup Diet intake Ca intake AA of Ca Retention of Ca (g)(mg)（%）(mg)No-preg-1.0%Ca 12.09 1.31 121.00 14.85 17.45 7.01 20.59 6.540.25%Ca 13.02 1.21 32.77 3.43 35.40 11.42a 11.39 3.18aPregnancy1.0%Ca 14.73 1.57 147.92 18.33 21.49 0.48 31.56 14.70
7、0.25%Ca 16.28 2.68a 39.24 6.76a 49.54 6.14a b 19.59 7.62a bNote：a:compared with1.0%Ca,p0.01;b:compared with No-pregnancy，p0.01;一一、妊娠机体对低钙供给的代谢改变Table3 45CaCl2 uptake in duodenum,jejunum and ileum in pregnant rats(cpm/mg)1.0%Ca 0.25%Ca 0.05%CaDuodenum 95.92 18.52 136.75 23.93a 169.19 35.41a bJejunum
8、88.43 18.32 124.87 29.70a 155.24 10.19a bIleum 92.75 27.56 111.12 28.25 152.54 34.65ab Note:n=10;a:compared with 1.0%Ca,p 0.05;b:compared with 0.25%Ca,p 0.05;Fig.1 45CaCl2 uptake in duodenum,jejunum and ileum in pregnant rats Note:n=10;a:compared with 1.0%Ca,p 0.05;b:compared with 0.25%Ca,p 0.05.a a
9、abaabab一一、妊娠机体对低钙供给的代谢改变l妊娠、三种钙水平对妊娠、三种钙水平对肠道肠道45Ca摄取力摄取力 23析因分析析因分析l钙钙在在十十二二指指肠肠摄摄取取力力增增高高是是妊妊娠娠和和低低钙钙供供给给共共同同作用的结果；作用的结果；l空肠和回肠摄取力增高主要是低钙供给的结果；空肠和回肠摄取力增高主要是低钙供给的结果；l妊妊娠娠和和低低钙钙的的共共同同作作用用增增加加了了钙钙在在肠肠道道的的吸吸收收，包括肠道上段的主动吸收和下段的被动扩散；包括肠道上段的主动吸收和下段的被动扩散；l低钙供给时主要增加肠道下段的被动扩散。低钙供给时主要增加肠道下段的被动扩散。一一、妊娠机体对低钙供给的
10、代谢改变(二二)人体研究人体研究Table 4 Calcium metabolism of the 3rd trimestrial pregnant women Group 1(12)Group II(12)Group III(11)Intake of Ca(mg/d)565 129 909 71 1371 25 Ca of feces(mg/d)146 67 307 32 651 93 Ca of urine(mg/d)148 63 284 40 324 84Ca of retention(mg/d)271 74 318 68 396 39 AA of Ca(%)74.68 6.3 66.0
11、3 4.3 52.5 7.0Note:compared with Group 1,p 0.05,p 0.01;compared with Group II,p 0.05,p 0.01;in().n;Fig.2 Calcium metabolism of the 3rd trimestrial pregnant womenNote:compared with Group 1,p 0.05,p 0.01;compared with Group II,p 0.05,p 0.01.Fig.3 Calcium absorption of the 3rd trimestrial pregnant wome
12、nNote:compared with Group 1,p 0.05,p 0.01.一一、妊娠机体对低钙供给的代谢改变l小结小结1.低钙供给时低钙供给时,孕及非孕大鼠饲料消耗增加，钙排出减少孕及非孕大鼠饲料消耗增加，钙排出减少,肠道钙吸收率显著增加，这种改变孕鼠较非孕鼠更明显肠道钙吸收率显著增加，这种改变孕鼠较非孕鼠更明显;2.2.妊娠状态、低钙供给，通过增加摄食量、调节肠道和肾妊娠状态、低钙供给，通过增加摄食量、调节肠道和肾脏的功能，使机体在有限的钙供给时储留更多的钙脏的功能，使机体在有限的钙供给时储留更多的钙;3.3.妊娠和低钙共同作用使钙在十二指肠摄取力增高妊娠和低钙共同作用使钙在十二指
13、肠摄取力增高,低钙供低钙供给主要使空肠和回肠摄取力增高给主要使空肠和回肠摄取力增高;4.4.妊娠和低钙的共同作用增加了钙在肠道上段的主动吸收，妊娠和低钙的共同作用增加了钙在肠道上段的主动吸收，低钙供给时主要增加肠道下段的被动扩散。低钙供给时主要增加肠道下段的被动扩散。二、孕期低钙摄入对骨健康的影响(一一)动物实验动物实验 Table 5 Contents of ash and calcium in femur of the pregnant rats 1.0%Ca 0.25%Ca 0.05%CaWeight of femur(g)0.44 0.04 0.40 0.06 0.38 0.04Con
14、tents of ash(mg)0.26 0.02 0.24 0.04 0.22 0.02Contents of Ca(mg)96.43 7.5 75.18 2.2 66.84 50.5 lNote:compared with 1.0%,p 0.05;compared with 0.25%,p 0.05;二、孕期低钙摄入对骨健康的影响(一一)动物实验动物实验Table 6 Contents of ash and calcium in femur(xs)No-pregnancy pregnancy Group 1.0%Ca(7)*0.25%Ca(7)1.0%Ca(7)0.25%(7)Weight
15、 of femur(g)0.450.02 0.420.02 0.440.04 0.400.06Contents of ash(mg)0.260.01 0.260.01 0.260.02 0.240.04Contents of Ca(mg)95.882.5 8.247.3 96.437.4 75.182.2 lNote:compared with 1.0%Ca,p 0.05;compared with No-preg,p 0.01;in()*：n;二、孕期低钙摄入对骨健康的影响(一一)动物实验动物实验1.1.相关分析相关分析 骨钙量与大鼠钙摄入量骨钙量与大鼠钙摄入量、机体钙贮留量均显著正机体钙贮
16、留量均显著正相关相关（r=0.7527r=0.7527和和0.7021,0.7021,p0.001p0.001）;钙存留量与钙存留量与钙摄入量显著正相关（钙摄入量显著正相关（r=0.7519r=0.7519，p0.01p0.01）。）。2.2.股骨病理改变股骨病理改变 当钙水平为当钙水平为0.25%0.25%时，可维持机体的正钙平衡，时，可维持机体的正钙平衡，但出现明显的股骨钙动员的病理学体征。但出现明显的股骨钙动员的病理学体征。0.05%0.05%钙组，形态学上骨动员体征更为明显。钙组，形态学上骨动员体征更为明显。二、孕期低钙摄入对骨健康的影响（二）人体研究 Table 7 Lumber b
17、one mineral density in different groups(g/cm2)Position Group 1(12)Group II(12)Group III(11)Right spinea 0.8940.054 0.9550.054 1.0540.043 Lateral middle spinea 0.6090.059 0.6680.046 0.7490.043Lateral spinea 0.6400.039 0.6850.030 0.7580.033Note:a,Average of L2L4;in()n;,compared with group 1,p0.05,p 0.
18、01;b:compared with group II p0.05,p 0.01;Right spine Lateral middle spine Lateral spine Fig.4 Lumber bone mineral density in different groups Note:,compared with group 1,p0.05,p 0.01;b:compared with group II p0.05,p 0.01.二、孕期低钙摄入对骨健康的影响（二）人体研究Table 8 BMD percentage of non-pregnancy of the same agePo
19、sition Group 1(12)Group II(12)Group III(11)Right spinea 86.675.41 92.585.48 102.454.37Lateral spinea 82.835.02 88.583.94 97.734.29Average 85.146.61 90.746.53 100.445.19lNote:a,Average of L2L4;in()n;,compared with group 1,p0.01;:compared with group II,p 0.01;Right spine Lateral spine Average Fig.5 BM
20、D percentage of non-pregnancy of the same age Note:,compared with group 1,p0.01;:compared with group II,p 0.01.二、孕期低钙摄入对骨健康的影响l（二）人体研究 Table3 Weight and length of the newbornGroup n length(cm)weight(g)score of the riskI 12 51.3 3.5 3437 293 82.5 3.4II 12 53.3 2.7 3584 365 86.7 4.4III 11 53.8 2.4 343
21、1 287 87.3 3.4Note:Compared with group I,p0.01;二、孕期低钙摄入对骨健康的影响l小结小结1.1.传统膳食传统膳食(低钙摄入低钙摄入)，不影响胎儿及新生儿体格，不影响胎儿及新生儿体格发育发育;2.2.低钙供给时，尽管母体钙代谢有一系列适应性低钙供给时，尽管母体钙代谢有一系列适应性改变，但钙存留量降低，股骨钙含量也减少改变，但钙存留量降低，股骨钙含量也减少;3.3.传统膳食传统膳食(低钙摄入低钙摄入),),腰椎各部位骨密度显著低腰椎各部位骨密度显著低于膳食钙干预组及膳食加钙剂联合干预组于膳食钙干预组及膳食加钙剂联合干预组;4.4.传统膳食传统膳食(低钙
22、摄入低钙摄入),),腰椎各部位骨密度下降至腰椎各部位骨密度下降至同龄非孕妇女同龄非孕妇女85.14%;85.14%;膳食加钙剂联合干预膳食加钙剂联合干预(钙钙摄入摄入1274.61274.6 147.8 147.8 mg/d)mg/d)可维持骨密度至同龄非可维持骨密度至同龄非孕妇女同等水平孕妇女同等水平;三、孕期钙代谢调节的相关因素三、孕期钙代谢调节的相关因素(一一)骨钙素骨钙素Table9 Serum BGP contents in the pregnancy phases(xs,g/L)Group 1(12)Group II(12)Group III(11)Middle pregnancy
23、 3.360.53 3.550.46 3.440.57Later pregnancy 3.920.52 4.760.87 4.741.46 After parturition 4.740.61 6.360.93 a 6.201.01 alNote:in()n;,compared with Middle pregnancy,p0.01;:compared with Later pregnancy,p0.05;Middle pregnancy Later pregnancy After parturition Fig.6 Serum BGP contents in the pregnancy ph
24、ases(xs,g/L)Note:,compared with Middle pregnancy,p0.01;:compared with Later pregnancy,p0.05.a a 三、孕期钙代谢调节的相关因素三、孕期钙代谢调节的相关因素二、雌激素二、雌激素Table 10 Serum estradiol contents in the pregnancy phases(xs,pg/ml)Group 1(12)Group II(12)Group III(11)Middle pregnancy 730.9267.2 720.1279.1 742.1665.9Later pregnanc
25、y 1731.5490.5 1502.6458.6 998.7226.2baAfter parturition 426.2296.3 166.7179.4 a 91.625.2 ANote:in()n;compared with Middle pregnancy,p0.01;compared with Later pregnancy,p0.01;compared with group1,a p 0.05,A p0.01;compared with group II,b p0.01;Middle pregnancy Later pregnancy After parturition Fig.7
26、Serum estradiol contents in the pregnancy phases(xs,pg/ml)Note:compared with Middle pregnancy,p0.01;compared with Later pregnancy,p0.01;compared with group1,a p 0.05,A p0.01;compared with group II,b p0.01.baba a A三、孕期钙代谢调节的相关因素三、孕期钙代谢调节的相关因素l相关分析1.1.骨钙素与钙摄入量显著正相关骨钙素与钙摄入量显著正相关（r=0.53,p0.001);r=0.53,p
27、0.001);2.2.骨钙素与多部位骨密度正相关骨钙素与多部位骨密度正相关（r=0.55,p0.01r=0.55,p0.01）;3.3.雌激素与钙摄入量显著负相关雌激素与钙摄入量显著负相关（r=-0.59,p0.01r=-0.59,p0.01）;4.4.钙表观吸收率与雌激素显著正相关钙表观吸收率与雌激素显著正相关（r=0.52,r=0.52,p0.05p0.05）5.5.雌激素水平与侧位、侧位中心骨密度显著负相雌激素水平与侧位、侧位中心骨密度显著负相关关(r r分别为分别为-0.60-0.60，-0.70,-0.70,p0.01p0.01）;三、孕期钙代谢调节的相关因素三、孕期钙代谢调节的相关
28、因素l小结小结1.孕末期充足钙供给，雌激素分泌相对减少，骨钙孕末期充足钙供给，雌激素分泌相对减少，骨钙素分泌增加素分泌增加,腰椎骨密度增加腰椎骨密度增加;2.2.孕末期低钙供给，虽雌激素分泌增加，钙的吸收孕末期低钙供给，虽雌激素分泌增加，钙的吸收增加，但骨钙素分泌下降，腰椎骨钙密度下降增加，但骨钙素分泌下降，腰椎骨钙密度下降;3.3.与孕末期相比，产后期各组雌激素水平显著下降，与孕末期相比，产后期各组雌激素水平显著下降，骨钙素水平显著升高骨钙素水平显著升高,雌激素水平下降、骨钙素雌激素水平下降、骨钙素水平升高与钙摄入量密切相关水平升高与钙摄入量密切相关,推测产后母体骨推测产后母体骨质的恢复依赖充足钙供给质的恢复依赖充足钙供给;