膳食不饱和脂肪酸与儿童相关健康问题的人群研究
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摘要
第一部分母乳不同n-6:n-3多不饱和脂肪酸对小儿生长发育的影响
研究目的:
通过调查两类不同膳食脂肪酸模式地区的孕母—小儿配对样本,观察不同n-6:n-3多不饱和脂肪酸(PUFAs)膳食比例对小儿不同阶段肥胖及生长发育的影响,计划得到预期结果:证明孕哺期母亲膳食中PUFAs含量及不同n-6/n-3PUFAs比例可能对乳汁和小儿血浆磷脂脂肪酸浓度、肥胖相关指标、小儿生长发育状况和认知发育的水平具有不同的调节作用。前瞻性地纵向随访必需脂肪酸对儿童健康和发育的影响。拟印证前期动物试验的部分结果。达到通过膳食的管理来阻抑肥胖、糖尿病、过敏和心血管疾病的迅速增加这一预防目的。
研究方法:
前瞻性队列研究是本项目的主要研究方法。
1.研究选取两种不同膳食模式地区:普通中国南方膳食模式(江苏省常州市),及海洋食品消费模式(浙江省温州市),对两地样本医院孕晚期(孕28周以后)孕母的膳食模式取向及膳食状况进行了调查。采用持续7日的前瞻实时膳食调查,根据《2002年中国食物成分数据》计算膳食脂肪酸含量,比较两种膳食模式下,孕母膳食脂肪酸的差异。
2.哺乳期母亲乳汁PUFAs的水平对小儿血中PUFAs、体格生长和发育的影响:于胎儿出生、5天、42天及1岁时采集脐血及婴儿静脉血,并在5天、42天、4月时留取母乳样本,采用高效毛细气相色谱分析技术检测母乳及婴儿血浆磷脂中脂肪酸浓度。
3.小儿生长发育指标包括:体格发育、认知发育和BMI情况。通过随访出生、5天、42天、12及18月小儿的体重、身高、头围;6月、12月时Gesell发育量表认知发育评估结果;及BMI变化来达到目标。
研究结果:
(一)基本资料
常州地区及温州地区孕母年龄、体重、身高、以及胎儿胎龄、出生体重、出生身长、性别比例、产次均无显著性差异(P＞0.05),仅分娩方式以及母亲体重指数(BMI)存在显著差异(p＜0.05)。
(二)不同膳食模式地区孕晚期膳食种类及膳食脂肪酸水平比较
1.膳食种类比较
两地孕晚期孕母摄入各类膳食总量无差异(p＞0.05)。常州地区孕母在乳制品、畜肉类、河鲜类以及油脂类的摄入量上明显高于温州地区(p＜0.05)。在谷类以及海鲜类的摄入量上明显低于温州地区(p＜0.05)。
2.膳食脂肪酸水平比较
常州与温州地区孕母7天膳食脂肪酸摄入总量无统计学差异(p＞0.05)。常州孕母摄入的PUFAs、C16:2、亚油酸(LA)、α-亚麻酸(ALA)高于温州地区(p＜0.05);二十碳五烯酸(EPA)、二十二碳六烯酸(DHA)、C22:3、C22:5低于温州地区(p＜0.05)。花生四烯酸(AA)摄入量无差异(p＞0.05)。
(三)不同膳食模式地区乳汁脂肪酸比较
1、两地5天母初乳脂肪酸组成比较
1)常州地区5天母初乳脂肪酸中PUFAs、n-6PUFAs、n-6/n-3 PUFAs比例以及LA、ALA、AA/DHA、C18:3n6、单不饱和脂肪酸(MUFAs)、饱和脂肪酸(SFA)及不饱和指数(USI)都大于温州地区(p＜0.05);
2)温州地区5天母初乳中的DHA、EPA+DHA、AA、C20:3n6及C24:1n9、C16:1n7和SFA中的C16:0、C18:0、C20:0、C22:0、C24:0都大于常州地区(p＜0.05);EPA、n-3 PUFAs无统计学差异(p＞0.05)。
3)除EPA外,两地其余脂肪酸如PUFAs、LA、ALA、AA和DHA均呈现与膳食脂肪酸一致的趋势。
2、两地42天母成熟乳脂肪酸组成比较
1)常州地区42天母乳脂肪酸中PUFAs、n-6 PUFAs、n-6/n-3PUFAs比例以及LA、AA/DHA都大于温州地区(p＜0.05);DHA、EPA+DHA,AA、EPA都小于温州地区(p＜0.05);
2)SFA;MUFAs;ALA、C18:3n6、C20:2n6、C20:3n6、C20:3n9、USI无统计学差异(p＞0.05)。
3、两地初乳和成熟乳的脂肪酸成分变化
1) 5天到42天,常州地区母乳脂肪酸中n-3PUFAs的百分比值有明显上升(p＜0.05),n-6/n-3PUFAs比例明显下降。PUFAs、AA、n-6 PUFAs以及DHA、EPA、EPA+DHA、LA及ALA均无明显变化(p＞0.05);
2) 5天到42天,温州地区母乳脂肪酸中n-3 PUFAs、DHA、EPA、EPA+DHA、LA、ALA及PUFAs的百分比值有明显上升(p＜0.05),n-6/n-3PUFAs比例及AA明显下降。n-6 PUFAs略有上升,但无统计差异(p＞0.05)
(四)不同膳食模式地区血浆磷脂脂肪酸组成比较
1、两地脐血血浆磷脂脂肪酸组成比较
常州地区(N=123)脐血血浆磷脂脂肪酸中PUFAs及n-6 PUFAs、n-6/n-3 PUFAs比例、LA、ALA、AA、AA/DHA与MUFAs以及USI都大于温州地区(N=30)(p＜0.05);EPA小于温州地区(p＜0.05);两地脐血n-3 PUFAs、DHA、EPA+DHA均无统计学差异(p＞0.05)。
2、两地小儿5天血血浆磷脂脂肪酸组成比较
常州地区(N=122)5天血血浆磷脂脂肪酸中PUFAs及n-6 PUFAs、AA、AA/DHA与USI都大于温州地区(N=36)(p＜0.05);而SFAs及不饱和指数USI均小于温州地区(p＜0.05);
两地n-3 PUFAs、DHA、EPA、EPA+DHA、ALA、LA、n-6/n-3 PUFAs比例及MUFAs均无统计学差异(p＞0.05)。
3、两地小儿42天血血浆磷脂脂肪酸组成比较
常州地区(N=115)42天血血浆磷脂脂肪酸中的PUFAs及n-6 PUFAs、n-6/n-3PUFAs比例、LA、AA、ALA、以及AA/DHA都大于温州地区(N=14)(p＜0.05);而n-3 PUFAs、DHA、EPA+DHA及SFAs、C16:0、C22:0及C24:0小于温州地区(p＜0.05);两地EPA、MUFA及USI未见统计学差异(p＞0.05)。
4、两地小儿脐血、5和42天血脂肪酸水平的时间变化
1)从出生经5天到42天,温州地区小儿血浆磷脂中n-3 PUFAs水平明显上升(5→42天,p＜0.05),n-6 PUFAs水平也逐渐上升(0→5天,p＜0.05),而n-6/n-3 PUFAs比例先杨后抑,至42天时明显下降(p均＜0.05)。
2)从出生经5天到42天,常州地区小儿血浆磷脂中n-3 PUFAs水平稍有下降(p＞0.05),n-6PUFAs水平持续上升(p均＜0.05),而n-6/n-3PUFAs比例上升明显并持续到42天(0→5天,p＜0.05;5→42天,p＞0.05)。
(五)相同时点的乳汁脂肪酸与血浆磷脂脂肪酸相关性
1.常州地区5天母乳ALA、DHA及DHA+EPA与小儿5天血浆磷脂中相应脂肪酸有显著性的正相关(n=45,r=0.36,r=0.39,r=0.39,P＜均0.05)。而5天母乳中LA及AA与小儿5天血相应的脂肪酸未见相关性(P＞0.05)。
2.常州地区42天母乳中LA,ALA,AA,DHA及DHA+EPA与小儿42天血浆磷脂中相应脂肪酸均具有相关性(n=45,r=0.50,r=0.49,r=0.46,r=0.42,r=0.46,P均＜0.01)。
(六)婴儿早期血浆磷脂脂肪酸水平与生长发育
1、4个月内两地婴儿体重差异
两地小儿平均体重在出生、5、42天均无差异(p＞0.05),在4个月时温州小儿平均体重明显低于常州小儿(p=0.01)
2、早期脂肪酸水平与体重的相关性
小儿脐血、5,42天及12月血浆磷脂中的DHA与42天、2,4,6,12及18个月时的体重基本呈负相关趋势,其中脐血DHA与12月体重、42天DHA与6月体重呈显著负相关。
小儿血浆磷脂中不同时点的n-3 PUFAs百分值与42天、2,4,6,12及18个月时的体重基本呈负相关,其中脐血n-3 PUFAs与12月体重、42天n-3 PUFAs与6月体重呈显著负相关。
小儿血n-6/n-3PUFAs比例与42天、2,4,6,12及18个月时的体重基本呈正相关趋势,其中脐血n-6/n-3PUFAs比例与12月龄体重、42天n-6/n-3PUFAs比例与6月龄体重呈显著正相关。
3、早期脂肪酸水平与BMI的相关性
脐血、5及42天血血浆磷脂DHA及n-3 PUFAs与婴儿12月龄BMI Z分值呈负相关,同期n-6/n-3 PUFAs比例则与12月龄BMI呈正相关;脐血、42天血DHA及n-3PUFAs还与小儿18月龄BMI Z分值呈负相关,而n-6/n-3PUFAs比例则与其呈正相关。5天血脂肪酸与18月龄BMI Z分值未见相关性。
(七)两种膳食模式地区小儿认知发育比较
从目前已经随访的两地6月小儿认知发育水平可见,温州组小儿的大动作、语言和社交能区发育商(DQ)明显高于常州组(p均＜0.01);适应性能区两地未见差异。
小结
1.膳食模式不同的两个地区,孕晚期孕母膳食摄入种类及膳食脂肪酸摄入量存在差异,并且这种差异可以影响母乳及小儿血血浆磷脂脂肪酸组成,从而对胎儿及婴幼儿的生长发育产生影响。
2.婴幼儿早期血浆磷脂n-3 PUFAs水平可能对婴幼儿晚期生长具有显著影响:n-3 PUFAs(主要是DHA)水平越高而n-6/n-3PUFAs比例越低,则在婴儿晚期可以得到更为理想的BMI。早期发育(DQ)的差异有待于进一步的验证。
3.可以通过调整膳食结构达到改善膳食脂肪酸组成,进一步影响孕期及哺乳期母亲膳食脂肪酸组成的变化,从而改善乳汁及婴儿血液中脂肪酸组成和n-3/n-6PUFAs浓度比例的格局,影响婴儿生长发育的目的。
第二部分n-3PUFAs对ADHD及智力可疑人群脂代谢影响和功能改善的研究
研究目的:
检验智力发育在临界(智商70—85分)与中上优秀(智商115—130分)、具有或不具有注意缺陷行为的儿童体内PUFAs和n-6PUFAs、n-3PUFAs的水平是否具有差异性;同时对智力发育临界水平和注意缺陷行为患儿进行n-3 PUFAs的人群饮食干预,观察其对血红细胞脂肪酸水平、智力、学校成绩和注意缺陷行为的干预效果。为儿童期必需脂肪酸促进智力发育及注意缺陷行为的干预提供研究依据和干预模式。
研究方法:
选择中等发达地区的乡镇为样本地区,整群抽取样本地区中等水平两所小学的全部研究对象(2～5年级全体学生,1555名)进行智力筛查、注意行为问卷调查、划消试验。筛选出IQ临界和IQ优秀的学生;按照DSMⅣ的诊断标准遴选出符合标准的ADHD学生。检测IQ临界和IQ优秀及ADHD人群血红细胞膜中PUFAs、n-6PUFAs及n-3PUFAs的浓度。比较IQ临界和优秀、具有和不具有注意缺陷行为学生的PUFAs差异。对每位入选小儿进行视力测量。
采用随机、对照和双盲原则,分别将智力临界组和注意缺陷组学生随机分为干预组和对照组,对干预组补充n-3 PUFAs(n-3鸡蛋)和对照组补充普通鸡蛋一个学期(3个月)。观察干预组和对照组学生干预前后以下几个方面指标的变化:血红细胞膜长链多不饱和脂肪酸的代谢变化:PUFAs、n-6PUFAs及n-3PUFAs的变化;智力及注意力功能改善状况:IQ、注意缺陷行为、学校成绩及视力改善状况。
研究结果:
(一)基本资料
整群抽取1555名7—12岁乡镇小学的学生为研究对象,经过家长知情同意。在智力筛查和注意行为问卷后,最后入组的ADHD学生为79名;IQ临界的学生总计48人(男26名),年龄在8～12岁之间;IQ中上优秀学生总计50人(男24名),年龄在7～11岁之间。
(二)智力临界和中上优秀学生血脂肪酸水平差异
智力中上优秀学生血红细胞膜脂肪酸中n-3PUFAs(p=0.003)、EPA(p=0.000)、DHA(p=0.026)、AA(p=0.000)及C22:4(n-6)(p=0.002)明显高于智力临界水平的学生;而n-6/n-3PUFAs比例(p=0.004)、C20:3(n-6)(p=0.002)及LA(p=0.021)则明显低于智力临界水平的学生;在智力临界水平的学生中,血红细胞膜脂肪酸中的饱和脂肪酸C20:0、C24:0、单不饱和脂肪酸C15:1、C18:1、C24:1水平亦相对较高(p均＜0.05)。
(三) n-3 PUFAs饮食干预对智力临界小儿血脂肪酸代谢的影响
IQI临界学生干预后,干预组学生血红细胞膜ALA、DHA、EPA、n-3 PUFAs水平以及C20:2(n6)和部分SFAs及MUFAs较干预前明显提高(p均＜0.05),而n-6/n-3PUFAs比例、C20:3(n6)及n-6PUFAs则显著降低(p均＜0.05)。
而在对照组,干预后除C15:1、C22:0、24:0水平较干预前提高明显(p均＜0.05),C16:0、18:0、16:1、20:1及EPA较干预前显著降低(p均＜0.05),其余脂肪酸尤其是n-3类脂肪酸干预前后未见明显变化(p均＞0.05)。
(四)智力临界学生补充n-3类脂肪酸前后智力、视力水平变化
1、智力变化
智力临界的学生,其IQ成绩在n-3类脂肪酸补充干预后有明显提高(p＜0.01),对照组干预后IQ成绩也见明显增加(p＜0.01)。
2、视力变化
智力临界的学生,其在n-3类脂肪酸补充干预后仅见左眼视力有明显提高(p0.=0.01),右眼及对照组双眼视力干预后未见明显变化。
(五)智力临界学生补充n-3类脂肪酸前后学习成绩差异
在IQ临界的学生中,干预组语文及数学成绩都较干预前有明显提高(p＜0.01),而对照组则未见有明显差异(p＞0.01)。
(六) ADHD和非ADHD脂肪酸水平比较
ADHD儿童血红细胞膜的C15:0、16:0明显高于非ADHD组儿童(p＜0.05);AA、C22:4(n6)、EPA及n-6PUFAs则明显低于非ADHD组儿童(p均＜0.01)。
虽见非ADHD组儿童DHA、n-3PUFAs高于ADHD儿童,但未达统计学差异;ADHD组LA及n-6/n-3PUFAs略低于非ADHD组,也未见显著差异。
(七) ADHD学生补充n-3 PUFAs后小儿血脂肪酸代谢变化
ADHD干预组学生补充富含n-3类脂肪酸的鸡蛋后,其体内的DHA和n-3PUFAs水平较干预前明显提高,而n-6/n-3PUFAs比例则显著降低(p均＜0.05),C20:3(n6)略有上升。
而在ADHD对照组,干预后学生体内的DHA、n-3PUFAs、n-6PUFAs、AA及C22:4(n6)水平较干预前明显提高(p均＜0.05),而n-6/n-3PUFAs比例没有变化(p＞0.05)。
(八) ADHD学生补充n-3 PUFAs前后注意缺陷行为变化
补充富含n-3类脂肪酸前共有注意缺陷行为的学生79人,补充n-3 PUFAs后减少为45人,降低幅度为43%。其中干预组和对照组好转人数无统计学差异(17/24 V.S,18/20,P=0.693)。
(九) ADHD学生补充n-3 PUFAs前后视力变化
n-3类脂肪酸干预后,ADHD学生的左、右眼视力均有明显改善(p均＜0.05),而ADHD对照组干预前后视力未见明显变化(p均＞0.05)。
(十) ADHD学生补充n-3 PUFAs前后学校成绩变化
虽然干预组和对照组的语文和数学成绩在干预后均有不同程度的改善,但未见统计学上的差异。
小结
1.智力临界或智力优秀学生体内的n-3不饱和脂肪酸具有不同组成,人群的DHA和n-3PUFAs、n-6/n-3PUFAs可能与其智力水平具有相关性。补充n-3PUFAs可提高IQ临界学生体内红细胞膜n-3水平、IQ分数及学校成绩。
2.运用流行病学和临床试验的方法,观察及检测到具有和不具有注意缺陷行为的学龄期儿童,其体内的PUFAs及n-3 PUFAs水平具有显著差异。补充n-3PUFAs后ADHD学生的DHA和n-3PUFAs水平较干预前明显提高,而n-6/n-3PUFAs比例则显著降低;注意缺陷行为及视力得到明显改善。
3.本项目可以为探索LCPUFAs优化儿童智力发育及改善注意缺陷效果提供研究依据和干预模式。将儿童营养学研究引入ADHD发病及干预机制的研究领域。潜在应用价值是可以通过膳食的管理来达到改善智力水平和注意缺陷行为及学校成绩,而不单靠药物治疗这一预防目的,具有潜在重大意义。
Part One A study on different n-6:n-3 PUFAs ratio of breast milk for growth and development in infants and children
Objective
●To investigate the influence of two different dietary patterns with maternal fatty acid(FA) intake and different n-6:n-3 PUFAs ratio during pregnancy and lactation on FA composition of breast milk and infants' plasma phospholipids.
●To prove the relationship between FA status of breast milk or infants' blood and the infants' growth and development.
Methods
Method design was prospective cohort study.
●Two districts with different dietary patterns were selected for study:one was an inland city with traditional Chinese southern dietary pattern;the other was a coastal city with seafood dietary pattern.A 7-day dietary record was completed by women in their last trimester of pregnancy from these two places respectively.The FA composition in maternal diet was calculated and compared using the 2002 Chinese food composition database.
●Blood of umbilical cord,day 5,day 42 and 1 year of the infants were obtained. Breast milk samples were collected on day 5,day 42 and month 4.The FA composition of blood and breast milk was analyzed by capillary gas-liquid chromatography to explore the effect of maternal dietary intake with fatty acid(FA) on FA composition of blood,growth and development in infants and children.
●Subject anthropometric indices like weight,height,and head circumference were measured at ages 0,5 and 42 days,12,18 and 24 months.Cognitive assessment was completed at 6 months and 1 years of age,using Gesell Developmental Diagnosis.
Results
1.Sociodemographic characteristics of the samples
There were no differ for mean maternal age,weight,height,and gestational age, infant's birth weight,birth length,infant sex,No.of para and obstetrical complications (P＞0.05).However,there was differ for BMI,and delivery manner.between two city (p＜0.05).
2.The compare of two different dietary patterns on maternal dietary intakes and maternal total fatty acids intakes
1) There were no differ of 7 days total dietary intakes of pregnant mothers between the coastal city Wenzhou and the inland city Changzhou.(p＞0.05).The intakes of cereal and sea food were higher in Wenzhou than in Changzhou,while the intakes of milk,red meat,fresh-water food and vegetable oil were lower(p＜0.05).
2) There were no significant differences in maternal 7 days total fatty acids intakes between these two areas(p＞0.05).The intakes of total polyunsaturated fatty acids (PUFAs),C16:2、C18:2(LA)、C18:3(ALA);C13 and C18(SFAs) as well as C14 and C22(MUFAs)of mothers in Wenzhou were significantly lower than that of Changzhou. The intakes of eicosapentaenoic acid(EPA,C20:5),C22:3,C22:5 and docosahexaenoic acid(DHA,C22:6) were higher than in Changzhou.
3.Fatty acid profile of breast colostrums of two cities
1) Fatty acid profile of breast colostrums
The total PUFAs,n-6 and n-3 PUFAs as well LA、ALA、AA/DHA、C18:3n6、MUFA、SFA and USI of breast colostrum in Wenzhou were significantly lower than that of Changzhou(p＜0.05),but DHA、EPA+DHA、AA、C20:3n6、and C16:1n7、C24:1n9 as well C14:0、C16:0、C18:0、C22:0、C24:0 were higher than that of Changzhou(p＜0.05).
There were same trend of PUFAs、LA、ALA、AA and DHA but EPA in breast colostrum with diatery PUFAs.
2) Fatty acid profile of day 42 breast milk
The total PUFAs,n-6 and n-6/n-3PUFAs ratio as well LA、AA/DHA of day 42 breast milk in Wenzhou were significantly lower than that of Changzhou(p＜0.05),but DHA、EPA+DHA、AA、EPA were higher than that of Changzhou(p＜0.05);there were no differ for SFA;MUFA;ALA、C18:3n6、C20:2n6、C20:3n6、C20:3n9 and USI.
3) The changes of PUFAs from breast colostrum to day 42 milk
There was significant increase of n-3PUFAs(p＜0.05),significant decrease of n-6/n-3PUFAs ratio from breast colostrum to day 42 milk in Changzhou and no differ for PUFA、AA、n-6 and DHA、EPA、EPA+DHA、LA、ALA(p＞0.05).
There was significant increase of n-3PUFAs、DHA、EPA、EPA+DHA、LA、ALA and PUFAs,significant decrease of n-6/n-3PUFAs ratio and AA from colostrum to day 42 milk in Whangzhou(p＜0.05) and no differ for n-6(p＞0.05).
4、Fatty acid profile of blood of two cities
1) Fatty acid profile of cord blood
The total PUFAs,LA,AA,n-6 PUFAs,ALA,AA/DHA,n-6/n-3 and USI,MUFA in cord blood phospholipids of Wenzhou(N=30) were significantly lower than in that of Changzhou(N=123),while EPA was higher than that of Changzhou(p＜0.05).There were no differ in n-3 PUFAs,DHA and EPA+DHA of two sites.
2) Fatty acid profile of day 5 blood
The total PUFAs,AA,n-6 PUFAs,AA/DHA,n-6/n-3 and USI in day 5 blood phospholipids of Wenzhou(N=36) were significantly lower than in that of Changzhou (N=122)(p＜0.05),while SFA and USI was higher than that of Changzhou(p＜0.05). There were no differ in n-3 PUFAs,DHA EPA、EPA+DHA、ALA、LA、n-6/n-3 and MUFA of two sites.
3) Fatty acid profile of day 42 blood
The total PUFAs,AA,n-6 PUFAs,AA/DHA,n-6/n-3 and LA,ALA in day 42 blood phospholipids of Wenzhou(N=14)were significantly lower than in that of Changzhou(N=115)(p＜0.05),while n-3 PUFA,DHA,EPA+DHA,SFA and C16:0、 C22:0,C24:0 were higher than that of Changzhou(p＜0.05).There were no differ in EPA、MUFA and USI of two sites.(p＞0.05)
4)The changes of PUFAs composition from cord,day 5 to day 42 blood
There was significant increase of n-3PUFAs(5→42day,p＜0.05),and n-6 (0→5day,p＜0.05).There was significant increase of n-6(day 0→5),and significant decrease(day 5→42) of blood in Whangzhou(p＜0.05).
There was significant increase of n-6PUFAs from cord to day 5 to day42 blood in Changzhou(p＜0.05).There was significant increase of n-6/n-3 from cord to day 5 (p＜0.05).
5.The correlation of PUFAs between breast milk and blood phospholipids
There was positive correlation between breast milk and blood PL at day 5 for ALA、DHA and DHA+EPA in Changzhou(n=45,r=0.36,r=0.39,r=0.39,P＜0.05). There was no correlation between breast milk and blood PL at day 5 for LA and AA in Changzhou(P＞0.05).
There was positive correlation between breast milk and blood PL at day 42 for LA,ALA,AA,DHA and DHA+EPA in Changzhou(n=45,r=0.50,r=0.49,r=0.46, r=0.42,r=0.46,P＜0.01).
6.The effect of fatty acid status of plasma phospholipids during early infancy on growth incomes
1) Average weight at birth,day 5,42 and 4 months
There was no differ of average weight for infants at birth,day5 and day 42 in Changzhou and Wenzhou(p＞0.05).The average weight of infants at 4 months was significant lower in Wenzhou than in Changzhou(p=0.01)
2) The relationships of PUFAs in early life and weight at different intervals
●There was negative correlation trend of infant's blood PL DHA and n-3 PUFAs at cord,day 5,day42 and 12 mons with infant's weight at day 42,2,4,6,12 and 18 mons.There were significant negative correlation between cord DHA、n-3 PUFAs and weight of 12 mons;DHA、n-3 PUFAs at day 42 and weight of 6 mons.(P＜0.05, P＜0.05;P＜0.01,P＜0.01)
●There was positive correlation trend of infant's blood PL n-6/n-3 PUFAs at cord,day 5,day42 and 12 mons with infant's weight at day 42,2,4,6,12 and 18 mons. There were significant positive correlation between cord n-6/n-3 PUFAs and weight of 12 mons;n-6/n-3 PUFAs at day 42 and weight of 6 mons.(P＜0.05,P＜0.01)
3) The relationships of PUFAs in early life and BMI at different intervals
●There were significant negative correlation between DHA,n-3 PUFAs of cord, day5,day42 with BMI of 12 mons,significant positive correlation between n-6/n-3 PUFAs of cord,day5,day42 with BMI of 12 mons.
●There were significant negative correlation between DHA,n-3 PUFAs of cord, day42 with BMI of 18 mons,significant positive correlation between n-6/n-3 PUFAs of cord,day42 with BMI of 18 mons.
7.The effect of fatty acid status of plasma phospholipids during early infancy on infant's DQ
There were significant higher of Gesell DQ for the personal/social,language,and motor in Wenzhou than Changzhou at age 6 months.But no differ for adaptive/cognitive.
Conclusion
1.The significant differences in maternal intakes of FAs depending on their dietary habits and these dietary differences appear to influence the FA composition of breast milk and infant's blood as well the growth and development of infants and children.
2.The n-3 PUFA content in plasma phospholipids during early infancy may have great impact on child physical growth in later infancy.Higher blood DHA content and lower the n-6/n-3 ratio in early infancy may help the infants to achieve optimal body weight later.
3.The adjusts of dietary structure may affect the changes on composition of dietary PUFAs during pregnancy and lactation,and improve FA composition and n-6/n-3 PUFAs ratio of breast milk and infants' plasma phospholipids.To optimize the infant's growth and development.
Part Two A study on effect of dietary supplements with n-3PUFAs in children with ADHD and IQ critical:lipid metabolism influence and the function improvement
Objective
To investigate the difference of PUFAs and n-6:n-3 PUFAs ratio during two groups children at age 7-12 years old:1) IQ 70-85 VS IQ 115-130,2) with ADHD VS not with ADHD.Meanwhile to conduct the dietary supplements with n-3PUFAs in children with ADHD and IQ critical and analyze effects of lipid metabolism influence and the function improvement including red blood corpuscle PUFAs,IQ,behavior of Attention-deficit hyperactivity disorder and scholastic achievement.
Methods
1555 primary school students,aged 7-12 years were recruited using cluster sampling from the mid-level district of Zhejiang province.Intelligence and behaviour were assessed using IQ screen test and scale for ADHD(DSMⅣ).The students of IQ 70-85 and IQ 115-130 as well ADHD were diagnosed,their red blood corpuscle PUFAs and n-6:n-3 PUFAs ratio was analyzed,their vision was tested.
Randomised,double-blind and controlled design was used for intervention study. The students with IQ 70-85 and with ADHD were divided into intervention and control groups respectively.The egg contained n-3 PUFAs was supplemented to intervention group,and the egg no n-3 PUFAs for control group.The effects of red blood corpuscle PUFAs,IQ,behavior of Attention-deficit hyperactivity disorder and scholastic achievement were assessed.
Results
1.Sociodemographic characteristics of the samples
The study population consisted of 1555 primary school students,aged 7-12 years. After the intelligence being test and behavior questionnaire investigated,finally ADHD students were 79;The students of IQ critical were 48 people(male 26),aged 8～12 years old;Students whose IQ on the outstanding were 50 people(male 24),aged 7～11 years.
2.The FA composition of two different IQ groups
Red blood corpuscle AA、C22:4(n-6)、EPA、DHA and n-3PUFAs in students whose IQ on the outstanding were significant higher than that of the students of IQ critical, however,n-6/n-3PUFAs ratio,LA and C20:3(n-6) were lower than that of the students of IQ critical.C20:0、C24:0、C15:1、C18:1、C24:1 were higher in the students of IQ critical than students whose IQ on the outstanding.
3.Effect of dietary supplements with n-3PUFAs in children with IQ critical:lipid metabolism influence
The ALA、EPA、DHA and n-3 PUFAs,C20:2(n-6),partly SFA were significant increased;n-6 PUFAs and n-6/n-3 ratio,C20:3(n-6)、were significant reduced after intervention with n-3 PUFAs supplement on students of IQ critical.
The C15:1、C22:0 were significant increased;C16:0、C18:0、C16:1、C20:1、EPA were significant reduced after intervention with control egg on control students of IQ critical.
4.Effect of dietary supplements with n-3PUFAs in children with IQ critical:IQ and vision improvement
1) IQ and vision improvement:
The IQ score was significant improved after intervention with n-3 PUFAs supplement on students of IQ critical while IQ was also improved after intervention in control group.
2)Vision improvement:
The vision of left eye was significant improved after intervention with n-3 PUFAs supplement on students of IQ critical while the vision of right eye and control group was no improved after intervention.
5.Effect of dietary supplements with n-3PUFAs in children with IQ critical: scholastic achievement improvement
The scholastic achievement was significant improved after intervention with n-3 PUFAs supplement on students of IQ critical while there was no differ in control group.
6.The compare of blood PUFAs composition of ADHD and normal students
C15:0、16:0、20:0 were sig.higher,and AA,C20:3(n-6),EPA,n-6 were significant lower in ADHD students than normal group.No differ for DHA,n-3,LA and n-6/n-3.
7.The effect of dietary supplements with n-3PUFAs in children with ADHD: lipid metabolism influence
The DHA and∑n-3PUFAs were significant elevated after intervention with n-3 PUFAs supplement on students of ADHD while n-6/n-3 ratio was significant decreased. But no differ in control group before and after intervention,especially n-3 PUFAs.
8.The change of attention behavior before and after dietary supplements with n-3PUFAs in children with ADHD
After dietary supplements with n-3PUFAs in children with ADHD,the reduction of ADHD was 45 people,reduced percent was 43%.
9.The change of vision before and after dietary supplements with n-3PUFAs in children with ADHD
After dietary supplements with n-3PUFAs in children with ADHD,the students' lfet and right vision with ADHD was significant improved,but no differ in control group.
10.The change of scholastic achievement before and after dietary supplements with n-3PUFAs in children with ADHD
After dietary supplements with n-3PUFAs in children with ADHD,There were no sig.differ for scholastic achievement in intervention and control groups..
Conclusion
1.The intelligence critical or the intelligence outstanding student had the different composition of n-3 unsaturated fatty acid.There was possible relationship between DHA,n-3PUFAs,the n-6/n-3 unsaturated fatty acid and the intelligence level.To supplemented n-3PUFAs for the IQ critical student may raise their red blood cell n-3 PUFAs level,the IQ score and the scholastic achievement.
2.We used the epidemiology and the clinical trial method to observe and examine the sample,the results shown that the PUFAs and n-3 PUFAs level had remarkable difference of students with and no with ADHD.After supplemented n-3PUFAs,DHA and n-3PUFAs remarkable enhanced,but n-6/n-3 ratio obviously reduced;ADHD behavior and the vision had distinct improvement.
3.This project may offer research evidence and intervention model for optimizing the intelligence development and improving ADHD behavior;to introduce child nutriology research into the ADHD morbidity and the intervention mechanism research area.The potential value is the project result may improve intelligence level,the ADHD behavior and the school achievement through the dietary management,not merely depends on the medicine to treat and prevent ADHD or IQ critical students.
研究目的:
通过调查两类不同膳食脂肪酸模式地区的孕母—小儿配对样本,观察不同n-6:n-3多不饱和脂肪酸(PUFAs)膳食比例对小儿不同阶段肥胖及生长发育的影响,计划得到预期结果:证明孕哺期母亲膳食中PUFAs含量及不同n-6/n-3PUFAs比例可能对乳汁和小儿血浆磷脂脂肪酸浓度、肥胖相关指标、小儿生长发育状况和认知发育的水平具有不同的调节作用。前瞻性地纵向随访必需脂肪酸对儿童健康和发育的影响。拟印证前期动物试验的部分结果。达到通过膳食的管理来阻抑肥胖、糖尿病、过敏和心血管疾病的迅速增加这一预防目的。
研究方法:
前瞻性队列研究是本项目的主要研究方法。
1.研究选取两种不同膳食模式地区:普通中国南方膳食模式(江苏省常州市),及海洋食品消费模式(浙江省温州市),对两地样本医院孕晚期(孕28周以后)孕母的膳食模式取向及膳食状况进行了调查。采用持续7日的前瞻实时膳食调查,根据《2002年中国食物成分数据》计算膳食脂肪酸含量,比较两种膳食模式下,孕母膳食脂肪酸的差异。
2.哺乳期母亲乳汁PUFAs的水平对小儿血中PUFAs、体格生长和发育的影响:于胎儿出生、5天、42天及1岁时采集脐血及婴儿静脉血,并在5天、42天、4月时留取母乳样本,采用高效毛细气相色谱分析技术检测母乳及婴儿血浆磷脂中脂肪酸浓度。
3.小儿生长发育指标包括:体格发育、认知发育和BMI情况。通过随访出生、5天、42天、12及18月小儿的体重、身高、头围;6月、12月时Gesell发育量表认知发育评估结果;及BMI变化来达到目标。
研究结果:
(一)基本资料
常州地区及温州地区孕母年龄、体重、身高、以及胎儿胎龄、出生体重、出生身长、性别比例、产次均无显著性差异(P＞0.05),仅分娩方式以及母亲体重指数(BMI)存在显著差异(p＜0.05)。
(二)不同膳食模式地区孕晚期膳食种类及膳食脂肪酸水平比较
1.膳食种类比较
两地孕晚期孕母摄入各类膳食总量无差异(p＞0.05)。常州地区孕母在乳制品、畜肉类、河鲜类以及油脂类的摄入量上明显高于温州地区(p＜0.05)。在谷类以及海鲜类的摄入量上明显低于温州地区(p＜0.05)。
2.膳食脂肪酸水平比较
常州与温州地区孕母7天膳食脂肪酸摄入总量无统计学差异(p＞0.05)。常州孕母摄入的PUFAs、C16:2、亚油酸(LA)、α-亚麻酸(ALA)高于温州地区(p＜0.05);二十碳五烯酸(EPA)、二十二碳六烯酸(DHA)、C22:3、C22:5低于温州地区(p＜0.05)。花生四烯酸(AA)摄入量无差异(p＞0.05)。
(三)不同膳食模式地区乳汁脂肪酸比较
1、两地5天母初乳脂肪酸组成比较
1)常州地区5天母初乳脂肪酸中PUFAs、n-6PUFAs、n-6/n-3 PUFAs比例以及LA、ALA、AA/DHA、C18:3n6、单不饱和脂肪酸(MUFAs)、饱和脂肪酸(SFA)及不饱和指数(USI)都大于温州地区(p＜0.05);
2)温州地区5天母初乳中的DHA、EPA+DHA、AA、C20:3n6及C24:1n9、C16:1n7和SFA中的C16:0、C18:0、C20:0、C22:0、C24:0都大于常州地区(p＜0.05);EPA、n-3 PUFAs无统计学差异(p＞0.05)。
3)除EPA外,两地其余脂肪酸如PUFAs、LA、ALA、AA和DHA均呈现与膳食脂肪酸一致的趋势。
2、两地42天母成熟乳脂肪酸组成比较
1)常州地区42天母乳脂肪酸中PUFAs、n-6 PUFAs、n-6/n-3PUFAs比例以及LA、AA/DHA都大于温州地区(p＜0.05);DHA、EPA+DHA,AA、EPA都小于温州地区(p＜0.05);
2)SFA;MUFAs;ALA、C18:3n6、C20:2n6、C20:3n6、C20:3n9、USI无统计学差异(p＞0.05)。
3、两地初乳和成熟乳的脂肪酸成分变化
1) 5天到42天,常州地区母乳脂肪酸中n-3PUFAs的百分比值有明显上升(p＜0.05),n-6/n-3PUFAs比例明显下降。PUFAs、AA、n-6 PUFAs以及DHA、EPA、EPA+DHA、LA及ALA均无明显变化(p＞0.05);
2) 5天到42天,温州地区母乳脂肪酸中n-3 PUFAs、DHA、EPA、EPA+DHA、LA、ALA及PUFAs的百分比值有明显上升(p＜0.05),n-6/n-3PUFAs比例及AA明显下降。n-6 PUFAs略有上升,但无统计差异(p＞0.05)
(四)不同膳食模式地区血浆磷脂脂肪酸组成比较
1、两地脐血血浆磷脂脂肪酸组成比较
常州地区(N=123)脐血血浆磷脂脂肪酸中PUFAs及n-6 PUFAs、n-6/n-3 PUFAs比例、LA、ALA、AA、AA/DHA与MUFAs以及USI都大于温州地区(N=30)(p＜0.05);EPA小于温州地区(p＜0.05);两地脐血n-3 PUFAs、DHA、EPA+DHA均无统计学差异(p＞0.05)。
2、两地小儿5天血血浆磷脂脂肪酸组成比较
常州地区(N=122)5天血血浆磷脂脂肪酸中PUFAs及n-6 PUFAs、AA、AA/DHA与USI都大于温州地区(N=36)(p＜0.05);而SFAs及不饱和指数USI均小于温州地区(p＜0.05);
两地n-3 PUFAs、DHA、EPA、EPA+DHA、ALA、LA、n-6/n-3 PUFAs比例及MUFAs均无统计学差异(p＞0.05)。
3、两地小儿42天血血浆磷脂脂肪酸组成比较
常州地区(N=115)42天血血浆磷脂脂肪酸中的PUFAs及n-6 PUFAs、n-6/n-3PUFAs比例、LA、AA、ALA、以及AA/DHA都大于温州地区(N=14)(p＜0.05);而n-3 PUFAs、DHA、EPA+DHA及SFAs、C16:0、C22:0及C24:0小于温州地区(p＜0.05);两地EPA、MUFA及USI未见统计学差异(p＞0.05)。
4、两地小儿脐血、5和42天血脂肪酸水平的时间变化
1)从出生经5天到42天,温州地区小儿血浆磷脂中n-3 PUFAs水平明显上升(5→42天,p＜0.05),n-6 PUFAs水平也逐渐上升(0→5天,p＜0.05),而n-6/n-3 PUFAs比例先杨后抑,至42天时明显下降(p均＜0.05)。
2)从出生经5天到42天,常州地区小儿血浆磷脂中n-3 PUFAs水平稍有下降(p＞0.05),n-6PUFAs水平持续上升(p均＜0.05),而n-6/n-3PUFAs比例上升明显并持续到42天(0→5天,p＜0.05;5→42天,p＞0.05)。
(五)相同时点的乳汁脂肪酸与血浆磷脂脂肪酸相关性
1.常州地区5天母乳ALA、DHA及DHA+EPA与小儿5天血浆磷脂中相应脂肪酸有显著性的正相关(n=45,r=0.36,r=0.39,r=0.39,P＜均0.05)。而5天母乳中LA及AA与小儿5天血相应的脂肪酸未见相关性(P＞0.05)。
2.常州地区42天母乳中LA,ALA,AA,DHA及DHA+EPA与小儿42天血浆磷脂中相应脂肪酸均具有相关性(n=45,r=0.50,r=0.49,r=0.46,r=0.42,r=0.46,P均＜0.01)。
(六)婴儿早期血浆磷脂脂肪酸水平与生长发育
1、4个月内两地婴儿体重差异
两地小儿平均体重在出生、5、42天均无差异(p＞0.05),在4个月时温州小儿平均体重明显低于常州小儿(p=0.01)
2、早期脂肪酸水平与体重的相关性
小儿脐血、5,42天及12月血浆磷脂中的DHA与42天、2,4,6,12及18个月时的体重基本呈负相关趋势,其中脐血DHA与12月体重、42天DHA与6月体重呈显著负相关。
小儿血浆磷脂中不同时点的n-3 PUFAs百分值与42天、2,4,6,12及18个月时的体重基本呈负相关,其中脐血n-3 PUFAs与12月体重、42天n-3 PUFAs与6月体重呈显著负相关。
小儿血n-6/n-3PUFAs比例与42天、2,4,6,12及18个月时的体重基本呈正相关趋势,其中脐血n-6/n-3PUFAs比例与12月龄体重、42天n-6/n-3PUFAs比例与6月龄体重呈显著正相关。
3、早期脂肪酸水平与BMI的相关性
脐血、5及42天血血浆磷脂DHA及n-3 PUFAs与婴儿12月龄BMI Z分值呈负相关,同期n-6/n-3 PUFAs比例则与12月龄BMI呈正相关;脐血、42天血DHA及n-3PUFAs还与小儿18月龄BMI Z分值呈负相关,而n-6/n-3PUFAs比例则与其呈正相关。5天血脂肪酸与18月龄BMI Z分值未见相关性。
(七)两种膳食模式地区小儿认知发育比较
从目前已经随访的两地6月小儿认知发育水平可见,温州组小儿的大动作、语言和社交能区发育商(DQ)明显高于常州组(p均＜0.01);适应性能区两地未见差异。
小结
1.膳食模式不同的两个地区,孕晚期孕母膳食摄入种类及膳食脂肪酸摄入量存在差异,并且这种差异可以影响母乳及小儿血血浆磷脂脂肪酸组成,从而对胎儿及婴幼儿的生长发育产生影响。
2.婴幼儿早期血浆磷脂n-3 PUFAs水平可能对婴幼儿晚期生长具有显著影响:n-3 PUFAs(主要是DHA)水平越高而n-6/n-3PUFAs比例越低,则在婴儿晚期可以得到更为理想的BMI。早期发育(DQ)的差异有待于进一步的验证。
3.可以通过调整膳食结构达到改善膳食脂肪酸组成,进一步影响孕期及哺乳期母亲膳食脂肪酸组成的变化,从而改善乳汁及婴儿血液中脂肪酸组成和n-3/n-6PUFAs浓度比例的格局,影响婴儿生长发育的目的。
第二部分n-3PUFAs对ADHD及智力可疑人群脂代谢影响和功能改善的研究
研究目的:
检验智力发育在临界(智商70—85分)与中上优秀(智商115—130分)、具有或不具有注意缺陷行为的儿童体内PUFAs和n-6PUFAs、n-3PUFAs的水平是否具有差异性;同时对智力发育临界水平和注意缺陷行为患儿进行n-3 PUFAs的人群饮食干预,观察其对血红细胞脂肪酸水平、智力、学校成绩和注意缺陷行为的干预效果。为儿童期必需脂肪酸促进智力发育及注意缺陷行为的干预提供研究依据和干预模式。
研究方法:
选择中等发达地区的乡镇为样本地区,整群抽取样本地区中等水平两所小学的全部研究对象(2～5年级全体学生,1555名)进行智力筛查、注意行为问卷调查、划消试验。筛选出IQ临界和IQ优秀的学生;按照DSMⅣ的诊断标准遴选出符合标准的ADHD学生。检测IQ临界和IQ优秀及ADHD人群血红细胞膜中PUFAs、n-6PUFAs及n-3PUFAs的浓度。比较IQ临界和优秀、具有和不具有注意缺陷行为学生的PUFAs差异。对每位入选小儿进行视力测量。
采用随机、对照和双盲原则,分别将智力临界组和注意缺陷组学生随机分为干预组和对照组,对干预组补充n-3 PUFAs(n-3鸡蛋)和对照组补充普通鸡蛋一个学期(3个月)。观察干预组和对照组学生干预前后以下几个方面指标的变化:血红细胞膜长链多不饱和脂肪酸的代谢变化:PUFAs、n-6PUFAs及n-3PUFAs的变化;智力及注意力功能改善状况:IQ、注意缺陷行为、学校成绩及视力改善状况。
研究结果:
(一)基本资料
整群抽取1555名7—12岁乡镇小学的学生为研究对象,经过家长知情同意。在智力筛查和注意行为问卷后,最后入组的ADHD学生为79名;IQ临界的学生总计48人(男26名),年龄在8～12岁之间;IQ中上优秀学生总计50人(男24名),年龄在7～11岁之间。
(二)智力临界和中上优秀学生血脂肪酸水平差异
智力中上优秀学生血红细胞膜脂肪酸中n-3PUFAs(p=0.003)、EPA(p=0.000)、DHA(p=0.026)、AA(p=0.000)及C22:4(n-6)(p=0.002)明显高于智力临界水平的学生;而n-6/n-3PUFAs比例(p=0.004)、C20:3(n-6)(p=0.002)及LA(p=0.021)则明显低于智力临界水平的学生;在智力临界水平的学生中,血红细胞膜脂肪酸中的饱和脂肪酸C20:0、C24:0、单不饱和脂肪酸C15:1、C18:1、C24:1水平亦相对较高(p均＜0.05)。
(三) n-3 PUFAs饮食干预对智力临界小儿血脂肪酸代谢的影响
IQI临界学生干预后,干预组学生血红细胞膜ALA、DHA、EPA、n-3 PUFAs水平以及C20:2(n6)和部分SFAs及MUFAs较干预前明显提高(p均＜0.05),而n-6/n-3PUFAs比例、C20:3(n6)及n-6PUFAs则显著降低(p均＜0.05)。
而在对照组,干预后除C15:1、C22:0、24:0水平较干预前提高明显(p均＜0.05),C16:0、18:0、16:1、20:1及EPA较干预前显著降低(p均＜0.05),其余脂肪酸尤其是n-3类脂肪酸干预前后未见明显变化(p均＞0.05)。
(四)智力临界学生补充n-3类脂肪酸前后智力、视力水平变化
1、智力变化
智力临界的学生,其IQ成绩在n-3类脂肪酸补充干预后有明显提高(p＜0.01),对照组干预后IQ成绩也见明显增加(p＜0.01)。
2、视力变化
智力临界的学生,其在n-3类脂肪酸补充干预后仅见左眼视力有明显提高(p0.=0.01),右眼及对照组双眼视力干预后未见明显变化。
(五)智力临界学生补充n-3类脂肪酸前后学习成绩差异
在IQ临界的学生中,干预组语文及数学成绩都较干预前有明显提高(p＜0.01),而对照组则未见有明显差异(p＞0.01)。
(六) ADHD和非ADHD脂肪酸水平比较
ADHD儿童血红细胞膜的C15:0、16:0明显高于非ADHD组儿童(p＜0.05);AA、C22:4(n6)、EPA及n-6PUFAs则明显低于非ADHD组儿童(p均＜0.01)。
虽见非ADHD组儿童DHA、n-3PUFAs高于ADHD儿童,但未达统计学差异;ADHD组LA及n-6/n-3PUFAs略低于非ADHD组,也未见显著差异。
(七) ADHD学生补充n-3 PUFAs后小儿血脂肪酸代谢变化
ADHD干预组学生补充富含n-3类脂肪酸的鸡蛋后,其体内的DHA和n-3PUFAs水平较干预前明显提高,而n-6/n-3PUFAs比例则显著降低(p均＜0.05),C20:3(n6)略有上升。
而在ADHD对照组,干预后学生体内的DHA、n-3PUFAs、n-6PUFAs、AA及C22:4(n6)水平较干预前明显提高(p均＜0.05),而n-6/n-3PUFAs比例没有变化(p＞0.05)。
(八) ADHD学生补充n-3 PUFAs前后注意缺陷行为变化
补充富含n-3类脂肪酸前共有注意缺陷行为的学生79人,补充n-3 PUFAs后减少为45人,降低幅度为43%。其中干预组和对照组好转人数无统计学差异(17/24 V.S,18/20,P=0.693)。
(九) ADHD学生补充n-3 PUFAs前后视力变化
n-3类脂肪酸干预后,ADHD学生的左、右眼视力均有明显改善(p均＜0.05),而ADHD对照组干预前后视力未见明显变化(p均＞0.05)。
(十) ADHD学生补充n-3 PUFAs前后学校成绩变化
虽然干预组和对照组的语文和数学成绩在干预后均有不同程度的改善,但未见统计学上的差异。
小结
1.智力临界或智力优秀学生体内的n-3不饱和脂肪酸具有不同组成,人群的DHA和n-3PUFAs、n-6/n-3PUFAs可能与其智力水平具有相关性。补充n-3PUFAs可提高IQ临界学生体内红细胞膜n-3水平、IQ分数及学校成绩。
2.运用流行病学和临床试验的方法,观察及检测到具有和不具有注意缺陷行为的学龄期儿童,其体内的PUFAs及n-3 PUFAs水平具有显著差异。补充n-3PUFAs后ADHD学生的DHA和n-3PUFAs水平较干预前明显提高,而n-6/n-3PUFAs比例则显著降低;注意缺陷行为及视力得到明显改善。
3.本项目可以为探索LCPUFAs优化儿童智力发育及改善注意缺陷效果提供研究依据和干预模式。将儿童营养学研究引入ADHD发病及干预机制的研究领域。潜在应用价值是可以通过膳食的管理来达到改善智力水平和注意缺陷行为及学校成绩,而不单靠药物治疗这一预防目的,具有潜在重大意义。
Part One A study on different n-6:n-3 PUFAs ratio of breast milk for growth and development in infants and children
Objective
●To investigate the influence of two different dietary patterns with maternal fatty acid(FA) intake and different n-6:n-3 PUFAs ratio during pregnancy and lactation on FA composition of breast milk and infants' plasma phospholipids.
●To prove the relationship between FA status of breast milk or infants' blood and the infants' growth and development.
Methods
Method design was prospective cohort study.
●Two districts with different dietary patterns were selected for study:one was an inland city with traditional Chinese southern dietary pattern;the other was a coastal city with seafood dietary pattern.A 7-day dietary record was completed by women in their last trimester of pregnancy from these two places respectively.The FA composition in maternal diet was calculated and compared using the 2002 Chinese food composition database.
●Blood of umbilical cord,day 5,day 42 and 1 year of the infants were obtained. Breast milk samples were collected on day 5,day 42 and month 4.The FA composition of blood and breast milk was analyzed by capillary gas-liquid chromatography to explore the effect of maternal dietary intake with fatty acid(FA) on FA composition of blood,growth and development in infants and children.
●Subject anthropometric indices like weight,height,and head circumference were measured at ages 0,5 and 42 days,12,18 and 24 months.Cognitive assessment was completed at 6 months and 1 years of age,using Gesell Developmental Diagnosis.
Results
1.Sociodemographic characteristics of the samples
There were no differ for mean maternal age,weight,height,and gestational age, infant's birth weight,birth length,infant sex,No.of para and obstetrical complications (P＞0.05).However,there was differ for BMI,and delivery manner.between two city (p＜0.05).
2.The compare of two different dietary patterns on maternal dietary intakes and maternal total fatty acids intakes
1) There were no differ of 7 days total dietary intakes of pregnant mothers between the coastal city Wenzhou and the inland city Changzhou.(p＞0.05).The intakes of cereal and sea food were higher in Wenzhou than in Changzhou,while the intakes of milk,red meat,fresh-water food and vegetable oil were lower(p＜0.05).
2) There were no significant differences in maternal 7 days total fatty acids intakes between these two areas(p＞0.05).The intakes of total polyunsaturated fatty acids (PUFAs),C16:2、C18:2(LA)、C18:3(ALA);C13 and C18(SFAs) as well as C14 and C22(MUFAs)of mothers in Wenzhou were significantly lower than that of Changzhou. The intakes of eicosapentaenoic acid(EPA,C20:5),C22:3,C22:5 and docosahexaenoic acid(DHA,C22:6) were higher than in Changzhou.
3.Fatty acid profile of breast colostrums of two cities
1) Fatty acid profile of breast colostrums
The total PUFAs,n-6 and n-3 PUFAs as well LA、ALA、AA/DHA、C18:3n6、MUFA、SFA and USI of breast colostrum in Wenzhou were significantly lower than that of Changzhou(p＜0.05),but DHA、EPA+DHA、AA、C20:3n6、and C16:1n7、C24:1n9 as well C14:0、C16:0、C18:0、C22:0、C24:0 were higher than that of Changzhou(p＜0.05).
There were same trend of PUFAs、LA、ALA、AA and DHA but EPA in breast colostrum with diatery PUFAs.
2) Fatty acid profile of day 42 breast milk
The total PUFAs,n-6 and n-6/n-3PUFAs ratio as well LA、AA/DHA of day 42 breast milk in Wenzhou were significantly lower than that of Changzhou(p＜0.05),but DHA、EPA+DHA、AA、EPA were higher than that of Changzhou(p＜0.05);there were no differ for SFA;MUFA;ALA、C18:3n6、C20:2n6、C20:3n6、C20:3n9 and USI.
3) The changes of PUFAs from breast colostrum to day 42 milk
There was significant increase of n-3PUFAs(p＜0.05),significant decrease of n-6/n-3PUFAs ratio from breast colostrum to day 42 milk in Changzhou and no differ for PUFA、AA、n-6 and DHA、EPA、EPA+DHA、LA、ALA(p＞0.05).
There was significant increase of n-3PUFAs、DHA、EPA、EPA+DHA、LA、ALA and PUFAs,significant decrease of n-6/n-3PUFAs ratio and AA from colostrum to day 42 milk in Whangzhou(p＜0.05) and no differ for n-6(p＞0.05).
4、Fatty acid profile of blood of two cities
1) Fatty acid profile of cord blood
The total PUFAs,LA,AA,n-6 PUFAs,ALA,AA/DHA,n-6/n-3 and USI,MUFA in cord blood phospholipids of Wenzhou(N=30) were significantly lower than in that of Changzhou(N=123),while EPA was higher than that of Changzhou(p＜0.05).There were no differ in n-3 PUFAs,DHA and EPA+DHA of two sites.
2) Fatty acid profile of day 5 blood
The total PUFAs,AA,n-6 PUFAs,AA/DHA,n-6/n-3 and USI in day 5 blood phospholipids of Wenzhou(N=36) were significantly lower than in that of Changzhou (N=122)(p＜0.05),while SFA and USI was higher than that of Changzhou(p＜0.05). There were no differ in n-3 PUFAs,DHA EPA、EPA+DHA、ALA、LA、n-6/n-3 and MUFA of two sites.
3) Fatty acid profile of day 42 blood
The total PUFAs,AA,n-6 PUFAs,AA/DHA,n-6/n-3 and LA,ALA in day 42 blood phospholipids of Wenzhou(N=14)were significantly lower than in that of Changzhou(N=115)(p＜0.05),while n-3 PUFA,DHA,EPA+DHA,SFA and C16:0、 C22:0,C24:0 were higher than that of Changzhou(p＜0.05).There were no differ in EPA、MUFA and USI of two sites.(p＞0.05)
4)The changes of PUFAs composition from cord,day 5 to day 42 blood
There was significant increase of n-3PUFAs(5→42day,p＜0.05),and n-6 (0→5day,p＜0.05).There was significant increase of n-6(day 0→5),and significant decrease(day 5→42) of blood in Whangzhou(p＜0.05).
There was significant increase of n-6PUFAs from cord to day 5 to day42 blood in Changzhou(p＜0.05).There was significant increase of n-6/n-3 from cord to day 5 (p＜0.05).
5.The correlation of PUFAs between breast milk and blood phospholipids
There was positive correlation between breast milk and blood PL at day 5 for ALA、DHA and DHA+EPA in Changzhou(n=45,r=0.36,r=0.39,r=0.39,P＜0.05). There was no correlation between breast milk and blood PL at day 5 for LA and AA in Changzhou(P＞0.05).
There was positive correlation between breast milk and blood PL at day 42 for LA,ALA,AA,DHA and DHA+EPA in Changzhou(n=45,r=0.50,r=0.49,r=0.46, r=0.42,r=0.46,P＜0.01).
6.The effect of fatty acid status of plasma phospholipids during early infancy on growth incomes
1) Average weight at birth,day 5,42 and 4 months
There was no differ of average weight for infants at birth,day5 and day 42 in Changzhou and Wenzhou(p＞0.05).The average weight of infants at 4 months was significant lower in Wenzhou than in Changzhou(p=0.01)
2) The relationships of PUFAs in early life and weight at different intervals
●There was negative correlation trend of infant's blood PL DHA and n-3 PUFAs at cord,day 5,day42 and 12 mons with infant's weight at day 42,2,4,6,12 and 18 mons.There were significant negative correlation between cord DHA、n-3 PUFAs and weight of 12 mons;DHA、n-3 PUFAs at day 42 and weight of 6 mons.(P＜0.05, P＜0.05;P＜0.01,P＜0.01)
●There was positive correlation trend of infant's blood PL n-6/n-3 PUFAs at cord,day 5,day42 and 12 mons with infant's weight at day 42,2,4,6,12 and 18 mons. There were significant positive correlation between cord n-6/n-3 PUFAs and weight of 12 mons;n-6/n-3 PUFAs at day 42 and weight of 6 mons.(P＜0.05,P＜0.01)
3) The relationships of PUFAs in early life and BMI at different intervals
●There were significant negative correlation between DHA,n-3 PUFAs of cord, day5,day42 with BMI of 12 mons,significant positive correlation between n-6/n-3 PUFAs of cord,day5,day42 with BMI of 12 mons.
●There were significant negative correlation between DHA,n-3 PUFAs of cord, day42 with BMI of 18 mons,significant positive correlation between n-6/n-3 PUFAs of cord,day42 with BMI of 18 mons.
7.The effect of fatty acid status of plasma phospholipids during early infancy on infant's DQ
There were significant higher of Gesell DQ for the personal/social,language,and motor in Wenzhou than Changzhou at age 6 months.But no differ for adaptive/cognitive.
Conclusion
1.The significant differences in maternal intakes of FAs depending on their dietary habits and these dietary differences appear to influence the FA composition of breast milk and infant's blood as well the growth and development of infants and children.
2.The n-3 PUFA content in plasma phospholipids during early infancy may have great impact on child physical growth in later infancy.Higher blood DHA content and lower the n-6/n-3 ratio in early infancy may help the infants to achieve optimal body weight later.
3.The adjusts of dietary structure may affect the changes on composition of dietary PUFAs during pregnancy and lactation,and improve FA composition and n-6/n-3 PUFAs ratio of breast milk and infants' plasma phospholipids.To optimize the infant's growth and development.
Part Two A study on effect of dietary supplements with n-3PUFAs in children with ADHD and IQ critical:lipid metabolism influence and the function improvement
Objective
To investigate the difference of PUFAs and n-6:n-3 PUFAs ratio during two groups children at age 7-12 years old:1) IQ 70-85 VS IQ 115-130,2) with ADHD VS not with ADHD.Meanwhile to conduct the dietary supplements with n-3PUFAs in children with ADHD and IQ critical and analyze effects of lipid metabolism influence and the function improvement including red blood corpuscle PUFAs,IQ,behavior of Attention-deficit hyperactivity disorder and scholastic achievement.
Methods
1555 primary school students,aged 7-12 years were recruited using cluster sampling from the mid-level district of Zhejiang province.Intelligence and behaviour were assessed using IQ screen test and scale for ADHD(DSMⅣ).The students of IQ 70-85 and IQ 115-130 as well ADHD were diagnosed,their red blood corpuscle PUFAs and n-6:n-3 PUFAs ratio was analyzed,their vision was tested.
Randomised,double-blind and controlled design was used for intervention study. The students with IQ 70-85 and with ADHD were divided into intervention and control groups respectively.The egg contained n-3 PUFAs was supplemented to intervention group,and the egg no n-3 PUFAs for control group.The effects of red blood corpuscle PUFAs,IQ,behavior of Attention-deficit hyperactivity disorder and scholastic achievement were assessed.
Results
1.Sociodemographic characteristics of the samples
The study population consisted of 1555 primary school students,aged 7-12 years. After the intelligence being test and behavior questionnaire investigated,finally ADHD students were 79;The students of IQ critical were 48 people(male 26),aged 8～12 years old;Students whose IQ on the outstanding were 50 people(male 24),aged 7～11 years.
2.The FA composition of two different IQ groups
Red blood corpuscle AA、C22:4(n-6)、EPA、DHA and n-3PUFAs in students whose IQ on the outstanding were significant higher than that of the students of IQ critical, however,n-6/n-3PUFAs ratio,LA and C20:3(n-6) were lower than that of the students of IQ critical.C20:0、C24:0、C15:1、C18:1、C24:1 were higher in the students of IQ critical than students whose IQ on the outstanding.
3.Effect of dietary supplements with n-3PUFAs in children with IQ critical:lipid metabolism influence
The ALA、EPA、DHA and n-3 PUFAs,C20:2(n-6),partly SFA were significant increased;n-6 PUFAs and n-6/n-3 ratio,C20:3(n-6)、were significant reduced after intervention with n-3 PUFAs supplement on students of IQ critical.
The C15:1、C22:0 were significant increased;C16:0、C18:0、C16:1、C20:1、EPA were significant reduced after intervention with control egg on control students of IQ critical.
4.Effect of dietary supplements with n-3PUFAs in children with IQ critical:IQ and vision improvement
1) IQ and vision improvement:
The IQ score was significant improved after intervention with n-3 PUFAs supplement on students of IQ critical while IQ was also improved after intervention in control group.
2)Vision improvement:
The vision of left eye was significant improved after intervention with n-3 PUFAs supplement on students of IQ critical while the vision of right eye and control group was no improved after intervention.
5.Effect of dietary supplements with n-3PUFAs in children with IQ critical: scholastic achievement improvement
The scholastic achievement was significant improved after intervention with n-3 PUFAs supplement on students of IQ critical while there was no differ in control group.
6.The compare of blood PUFAs composition of ADHD and normal students
C15:0、16:0、20:0 were sig.higher,and AA,C20:3(n-6),EPA,n-6 were significant lower in ADHD students than normal group.No differ for DHA,n-3,LA and n-6/n-3.
7.The effect of dietary supplements with n-3PUFAs in children with ADHD: lipid metabolism influence
The DHA and∑n-3PUFAs were significant elevated after intervention with n-3 PUFAs supplement on students of ADHD while n-6/n-3 ratio was significant decreased. But no differ in control group before and after intervention,especially n-3 PUFAs.
8.The change of attention behavior before and after dietary supplements with n-3PUFAs in children with ADHD
After dietary supplements with n-3PUFAs in children with ADHD,the reduction of ADHD was 45 people,reduced percent was 43%.
9.The change of vision before and after dietary supplements with n-3PUFAs in children with ADHD
After dietary supplements with n-3PUFAs in children with ADHD,the students' lfet and right vision with ADHD was significant improved,but no differ in control group.
10.The change of scholastic achievement before and after dietary supplements with n-3PUFAs in children with ADHD
After dietary supplements with n-3PUFAs in children with ADHD,There were no sig.differ for scholastic achievement in intervention and control groups..
Conclusion
1.The intelligence critical or the intelligence outstanding student had the different composition of n-3 unsaturated fatty acid.There was possible relationship between DHA,n-3PUFAs,the n-6/n-3 unsaturated fatty acid and the intelligence level.To supplemented n-3PUFAs for the IQ critical student may raise their red blood cell n-3 PUFAs level,the IQ score and the scholastic achievement.
2.We used the epidemiology and the clinical trial method to observe and examine the sample,the results shown that the PUFAs and n-3 PUFAs level had remarkable difference of students with and no with ADHD.After supplemented n-3PUFAs,DHA and n-3PUFAs remarkable enhanced,but n-6/n-3 ratio obviously reduced;ADHD behavior and the vision had distinct improvement.
3.This project may offer research evidence and intervention model for optimizing the intelligence development and improving ADHD behavior;to introduce child nutriology research into the ADHD morbidity and the intervention mechanism research area.The potential value is the project result may improve intelligence level,the ADHD behavior and the school achievement through the dietary management,not merely depends on the medicine to treat and prevent ADHD or IQ critical students.
引文
1 全国营养学会第九次学术会议,2002年中国居民营养与健康状况调查专题报告,2004.10.10-14,北京
2 Godfrey KM and Barker DJ.Fetal nutrition and adult disease.Am J Clin Nutr 2000,71;5 Suppl:1344S-52S.
3 Singhal A,Cole TJ,and Lucas A.Early nutrition in preterm infants and later blood pressure:two cohorts after randomised trials.Lancet 2001,357:413-9.
4 Koletzko B,Sauerwald T,et al.Breast feeding and obesity:cross sectional study.BMJ 1999,319:147-50.
5 Nancy Auestad,David T.S,Jeri S.J,et al.Visual,Cognitive,and Language Assessments at 39Months:A Follow-up Study of Children Fed Formulas Containing Long-Chain Polyunsaturated Fatty Acids to 1 Year of Age.PEDIATRICS Vol.112 No.3 September 2003,pp.e177-e183
6 Eileen E Birch,Yolanda S Castaneda,Dianna H Wheaton,David G Birch,Ricardo D Uauy and Dennis R Hoffman.Visual maturation of term infants fed long-chain polyunsaturated fatty acid-supplemented or control formula for 12 too.American Journal of Clinical Nutrition,Vol.81,No.4,871-879,April 2005
7 Clarke SD.Polyunsaturated fatty acid regulation of gene transcription:a mechanism to improve energy balance and insulin resistance Br J Nutr 2000;83(Suppl 1):S59-66.
8 Maloney CA,Gosby AK,Phuyal JL,Denyer GS,Bryson JM,Caterson ID.Site-specific changes in the expression of fat-partitioning genes in weanling rats exposed toa low-protein diet in utero.Obes Res 2003;11:461-8.
9 Rocquelin G,Tapsoba S,Dop MC,Mbemba F,Traissae P,Martin-Prevel Y.Lipid content and essential fatty acid(EFA) composition of mature Congolese breast milk are influenced by mothers' nutritional status:impact on infants' EFA supply.Eur J Clin Nutr.1998Mar;52(3):164-71.
10 Xiang M,Harbige LS,Zetterstrom R.Long-chain polyunsaturated fatty acids in Chinese and Swedish mothers:diet,breast milk and infant growth.Acta Paediatr.2005 Nov;94(11):1543-9
11 Neuringer M.Infant vision and retinal function in studies of dietary long-chain polyunsaturated fatty acids:methods,results,and implications.Am J Clin Nutr 2000,71;1 Suppl:256S-67S.
12 Lefkowitz W,Lim SY,Lin YH and Salem N,JR.Where Does the Developing Brain Obtain Its Docosahexaenoic Aci d? Relative Contributions of Dietary α-Linolenic Acid,Docosahexaenoic Acid,and Body Stores in the Developing Rat Pediatric Research 2005:57:157-165.
13 Korotkova M,Telemo E,Yamashiro Y,Hanson LA,Strandvik B.The ratio of n-6 to n-3 fatty acids in maternal diet influences the induction of neonatal immunological tolerance to ovalbumin.Clin Exp Immunol.2004 Aug;137(2):237-44.
14 Amusquivar E,Ruperez FJ,Barbas C,et al.Low arachidonic acid rather than alpha-tocopherol is responsible for the delayed postnatal development in offspring of rats fed fish oil instead of olive oil during pregnancy and lactation.J Nutr 2000,130:2855-65.
15 Uauy R,Mena P,and Rojas C.Essential fatty acids in early life:structural and functional role.Proc Nutr Soc 2000,59:3-15.
16 Simopoulos AP,Evolutionary aspects of diet,the omega-6/omega-3 ratio and genetic variation:nutritional implications for chronic diseases.Biomedicine & Pharmacotherapy 2006,60:502-507
17 Sanders TA.Polyunsaturated fatty acids in the food chain in Europe.Am J Clin Nutr 2000,71;1Suppl:176S-8S.
18 Fidler N and Koletzko B.The fatty acid composition of human colostrum.Eur J Nutr 2000,39:31-7.
19 Dariush M;Alberto A;Frank B;Meir J;Walter CW;David SS;Eric BR.Interplay Between Different Polyunsaturated Fatty Acids and Risk of Coronary Heart Disease in Men.Circulation.2005;111:157-164.
20 Baylin A Kabagambe EK,Ascherio A,Spiegelman D,Campos H.Adipose tissue α-linolenic acid and nonfatal acute myocardial infarction in Costa Rica.Circulation.2003;107:1586-1591.
21 Kris-Etherton PM,Taylor DS,Yu-Poth S,Huth P,Moriarty K,Fishell V,Hargrove RL,Zhao G,Etherton TD.Polyunsaturated PUFAs in the food chain in the United States.Am J Clin Nutr.2000;71:179S-188S.
22 de Lorgeril,M.,Salen,P.(2000).Modified Cretan Mediterranean diet in the prevention of coronary heart disease and cancer.In:Simopoulos,A.P.,Visioli,F.,eds.Mediterranean Diets.Vol.87.World Rev.Nutr.Diet,1-23.
23 Das UN.Beneficial effect(s) of n-3 fatty acids in cardiovascular diseases:but,why and how?Prostaglandins Leukot Essent Fatty Acids 2000,63:351-62.
24 Dewailly EE,Blanchet C,Gingras S,et al.Relations between n-3 fatty acid status and cardiovascular disease risk factors among Quebecers.Am J Clin Nutr 2001,74:603-11.
25 Weisinger HS,Armitage JA,Sinclair AJ,et al.Perinatal omega-3 fatty acid deficiency affects blood pressure later in life.Nat Med 2001,7:258-9.
26 Korotkova M.,Holmang A.,Latsson B-M.,Gabrielsson B.,Hanson L.A.,Strandvik B.Perinatal essential fatty acids affect weight blood pressure and serum insulin levels in adult rats.Pediatric Res[J],2003.53(6)supp15:p.17A-17A.
27 Bouwstra H,Dijck-Brouwer DA,Wildeman JA,Tjoonk HM,van der Heide JC,Boersma ER,Muskiet FA,Hadders-Algra M.Long-chain polyunsaturated fatty acids have a positive effect on the quality of general movements of healthy term infants.Am J Clin Nutr.2003:78(2):313-8.
28 Auestad N,Scott DT,Janowsky JS,et al.Visual,cognitive,and language assessments at 39months:a follow-up study of children fed formulas containing long-chain polyunsaturated fatty acids to 1 year of age.Pediatrics.2003 Sep;112(3 Pt 1):e177-83
29 Singh,R.B.,Dubnov,G.,Niaz,M.,et al.Effect of an Indo-Mediterranean diet on progression of coronary artery disease in high-risk patients(Indo-Mediterranean Diet Heart Study):a randomized single-blind trial.2002:Lancet 360:1455-1461
30 周婷婷,张婷艳,strandvik B,王琴,留佩宁,Zenerstr(o|¨)m R,彭咏梅,孕期不同膳食模式对膳食脂肪酸含量及母初乳脂肪酸组成的影响,中国儿童保健杂志,2008,16(2):160-165
31 B anerjee T D, M iddleton F, Faraone S V. Environmental risk factors for attention deficit hyperactivity disorder. Acta Paediatr, 2007;96 (9): 1269-1274
32 Brown RT, Freeman WS, Perrin JM, et al. Prevalence and assessment of attention2 deficit /hyperactivity disorder in primary care settings. Pediatrics, 2004; 114 (2): 511-512
33 Marianna Mazza, Massimiliano Pomponi, Luigi Janiri. Omega-3 fatty acids and antioxidants in neurological and psychiatric diseases: An overview. Progress in Neuro-Psychopharmacology & Biological Psychiatry 2007;31: 12-26
34 A.J. Richardson, P. Montgomery, The Oxford-Durham study: a randomised, controlled trial of dietary supplementation with fatty acids in children with developmental coordination disorder. Pediatrics 2005; 115:1360-1366.
35 N. Sinn, J. Bryan, Effect of supplementation with polyunsaturated fatty acids and micronutrients on ADHD-related problems with attention and behavior, J. Dev. Behav. Pediatr. 2007; 28: 82-91.
36 Joshi K, Lad S, Kale M, et al. Supplementation with flax oil and vitamin C improves the outcome of attention deficit hyperactivity disorder (ADHD). Prostaglandins Leukotri Essen Fatty Acids, 2006;74:17-21
37 Stevens L, Zhang W, Peck L, et al. EFA supplementation in children with inattention, hyperactivity and other disruptive behaviors. Lipids 2003; 38:1007-1021
38 James C. DeMar, Jr., Kiazong Ma, Jane M. Bell, Miki Igarashi, Deanna Greenstein, and Stanley I. Rapoport. One generation of n-3 polyunsaturated fatty acid deprivation increases depression and aggression test scores in rats. Lipid Res., Jan 2006; 47:172-180
39 Maes M, Smith RS (1998), Fatty acids, cytokines and major depression. Biol Psychiatry 43(5):313-314.Smith RS (1991), The macrophage theory of depression. (Erratum appears in Med Hypotheses 36[2]:178.) Med Hypotheses 35(4):298-306.
40 Stoll AL, Sachs GS, Cohen BM et al. (1996), Choline in the treatment of rapid-cycling bipolar disorder: clinical and neurochemical findings in lithium-treated patients. Biol Psychiatry 40(5):382-388.
41 Haag M. Essential fatty acids and the brain. Can J Psychiatry. 2003 ;48:195-203
42 Richardson AJ, Ross MA. Fatty acid metabolism in neurodevelopmentaldisorder: a new perspective on associations between attention-deficit/hyperactivity disorder, dyslexia, dyspraxia and the autistic spectnm.Prostaglandins Leukot Essent Fatty Acids. 2000;63:1-9
43 Voigt RG,Llorente AM Jensen CL ,etal. A randomized .double blind ,placebo2controlled trial of docosahexaenoic acid supplementation in children with attention2deficit/ hyperactivity disorder [J]. J Pediatr 2001; 139 (2): 189-196
44 Natan Gadoth. On fish oil and omega-3 supplementation in children: The role of such supplementation on attention and cognitive dysfunction. Brain & Development 2008;30:309-312
45 A. Eilander, D.C. Hundscheid, S.J. Osendarp, C. Transler, P.L. Zock, Effects of n-3 long chain polyunsaturated fatty acid supplementationon visual and cognitive development throughout childhood: A review of human studies. Prostaglandins, Leukotrienes and Essential Fatty Acids 2007; 76:189-203
46 ALEXANDRA J. RICHARDSON, Omega-3 fatty acids in ADHD and related neurodevelopmental disorders. International Review of Psychiatry, 2006;18(2): 155-172.
47 Busch B. Polyunsaturated fatty acid supplementation for ADHD? Fishy, fascinating, and far from clear. Polyunsaturated Fatty Acid Supplementation for ADHD Symptoms: Response to Commentary J Dev Behav Pediatr 2007; 28 (2):139-144
48 MICHELE GERMANO, DOMENICO MELELEO, GIGLIOLA MONTORFANO. Plasma, red blood cells phospholipids and clinical evaluation after long chain omega-3 supplementation in 49 children with attention deficit hyperactivity disorder (ADHD). Nutritional Neuroscience 2007; 10(1/2): 1-9c
50 Korotkova M, Gabrielsson B, Strandvik B, et al. Leptin levels in rat offspring are modified by the ratio of linoleic to alpha-linolenic acid in the maternal diet[J]. J Lipid Res. 2002;43(10):1743-9.
51 Uauy R, Hoffman DR, Peirano P, et al. Essential fatty acids in visual and brain development[J]. Lipids.2001;36(9):885-95.
52 Dutta-Roy AK. Transport mechanisms for long-chain polyunsaturated fatty acids in the human placenta[J]. Am J Clin Nutr. 2000;71(Suppl):315S-22S
53 Salem NJ, Wegher B, Mena P, et al. Arachidonic and docosahexaenoic acids are biosynthesized from their 18-carbon precursors in human infants[J]. Proc Natl Acad Sci USA. 1996;93(1):49-54.
54 artner LM, Morton J, Lawrence RA, et al. Breastfeeding and the use of human milk. Pediatrics. Feb2005;115(2):496-506.
55 Pickering LK, Morrow AL, Ruiz-Palacios GM, Schanler RJ (eds). Protecting Infants through human milk: Advancing the Scientific Evidence. Kluwer/Plenum Publishers. 2004.
56 Hamosh M: Bioactive factors in human milk. Pediatr Clin North Am 48(1): 69-86,2001.
57 Morrow AL, Ruiz-Palacios GM, Altaye M, et al. Human milk oligosaccharides are associated with protection against diarrhea in breastfed infants. J Pediatr 2004; 145:297-303.
58 Newburg DS, Ruiz-Palacios GM, Morrow AL. Human milk oligosaccharides protect against enteric pathogens. Annu Rev Nutr 2005; 25:37-58.
59 Innis SM: Polyunsaturated fatty acids in human milk: an essential role in infant development. Adv Exp Med Biol 554: 27-43, 2004
60 YM Peng, TY Zhang, Q Wang, R Zetterstrom, B Strandvik. Fatty acid composition in breast milk and serum phospholipids of healthy term Chinese infants during first 6 weeks of life. Acta Paediatrica 2007; 96. pp1640-1645
61 Chen ZY, Kwan KY, Tong KK, et al. Breast milk fatty acid composition: a comparative study between Hong Kong and Chongqing Chinese[J]. Lipids, 1997,32: (10): 1061-1067.
62 Michihiro Sugano, Fumiko Hiranara. Polyunsattmated fatty acids in the food chain in Japan. Am J CAin Nutr, 2000, 71 (supple) :189-196.
63 De Vriese SR, Dhont M, Christophe AB. FA composition of cholesteryl esters and phospholipids in maternal plasma during pregnancy and at delivery and in cord plasma at birth[J]. Lipids. 2003 ;38(1):1-7.
64 Dutta-Roy AK.Transport mechanisms for long-chain polyunsaturated fatty acids in the human placenta[J].Am J ClinNutr.2000;71(Suppl):315S-22S.
65 Amusquivar E,Herrera E.Influence of changes in dietary fatty acids during pregnancy on placental and fetal fatty acid profile in the rat[J].Biol Neonate.2003;83(2):136-45.
66 De Vriese SR,Matthys C,De Henauw S,et al.Maternal and umbilical fatty acid status in relation to maternal diet[J].Prostaglandins Leukot Essent Fatty Acids.2002;67(6):389-96.
67 Salem NJ,Wegher B,Mena P,et al.Arachidonic and docosahexaenoic acids are biosynthesized from their 18-carbon precursors in human infants[J].Proc Natl Acad Sci U S A.1996;93(1):49-54.
68 Kurlak LO,Stephenson TJ.Plausible explanations for effects of long chain polyunsaturated fatty acids(LCPUFA) on neonates[J].Arch Dis Child Fetal Neonatal Ed.1999;80(2):F148-54.
69 Lucas A,Fewtrell MS,and Cole TJ.Fetal origins of adult disease-the hypothesis revisited.BMJ 1999,319:245-9.
70 Godfrey KM and Barker DJ.Fetal nutrition and adult disease.Am J Clin Nutr 2000,71;5 Suppl:1344S-52S.
71 Lucas A.Programming by early nutrition:an experimental approach.J Nutr 1998,128;2 Suppl:401S-406S
72 Aalinkeel R,Srinivasan M,Song F,Patel MS.Programming into adulthood of islet adaptations induced by early nutritional intervention in the rat.Am J Physiol Endocrinol Metab 2001;281:E640-8.
73 ESPGAN Committee on Nutrition.Comment on the content and composition of lipids in infant formulas.Acta Paediatr Scand 1991;80:887-96.
74 Crawford MA.Fatty-acid ratios in free-living and domestic animals.Lancet 1968;1:1329-33.
75 Uauy R,Mena P,and Rojas C.Essential fatty acids in early life:structural and functional role.Proc Nutr Soc 2000,59:3-15.
76 Neuringer M.Infant vision and retinal function in studies of dietary long-chain polyunsaturated fatty acids:methods,results,and implications.Am J Clin Nutr 2000,71;1 Suppl:256S-67S.
77 Leaf A,Albert CM,Josephson M,Steinhaus D,Kluger J,Kang JX,Cox B,Zhang H,Schoenfeld D.Prevention of fatal arrhythmias in high-risk subjects by fish oil n-3 fatty acid intake.Circulation.2005 Nov 1;112(18):2762-8.
78 Kratz M,yon Eckardstein A,Fobker M,Buyken A,Posny N,Schulte H,Assmann G,Wahrburg U.The impact of dietary fat composition on serum leptin concentrations in healthy nonobese men and women.J Clin Endocrinol Metab[J],2002.87(11):p.5008-14
79 Perez-Matute P,Marti A,Martinez JA,Moreno-Aliaga MJ.Effects of araehidonic acid on leptin secretion and expression in primary cultured rat adipocytes.J Physiol Biochem[J],2003.59(3):p.201-8.
80.van Niel MH,Beynen AC.The intake of polyunsaturated fatty acids by cats is reflected in their adipose tissue.Vet Q[J],1997.19(4):p.150-3
81 王琴,周婷婷,张婷艳,Strandvik B,Zetterstr(o|¨)m R,彭咏梅,婴儿早期血浆磷脂脂肪酸 水平对体质指数的影响,复旦学报(医学版),2008Nov,35(6)824-828
82 Gartner LM,Morton J,Lawrence RA,et al.Breastfeeding and the use of human milk.Pediatrics.Feb 2005;115(2):496-506
83 Pickering LK,Morrow AL,Ruiz-Palacios GM,Schanler RJ(eds).Protecting Infants through human milk:Advancing the Scientific Evidence.Kluwer/Plenum Publishers.2004.
84 Hamosh M:Bioactive factors in human milk.Pediatr Clin North Am 48(1):69-86,2001.
85.Paul J Sorgi,Edward M Hallowell,Heather L Hutchins et al.Effects of an open-label pilot study with high-dose EPA/DHA concentrates on plasma phospholipids and behavior in children with attention deficit hyperactivity disorder.Nutrition Journal 2007;Jul 13:6-16
86 Uauy RD,Mena P,Hoffman DR.Essential fatty acid metabolism and requirements for LBW infants.Acta Pediatr 1994;405(Suppl):78-85.
87 Whalley LJ,Fox HC,Wahle KW,Starr JM,Deary IJ.Cognitive aging,childhood intelligence,and the use of food supplements:possible involvement of n-3 fatty acids.Am J Clin Nutr.2004Dec;80(6):1650-7.
88 Bakker EC,Hornstra G,Blanco CE,et al.Relationship between long-chain polyunsaturated fatty acids at birth and motor function at 7 years of age[J].Eur J Clin Nutr.2007 Dec 19;[Epub ahead of print]
89 Birch EE,Castaneda YS,Wheaton DH,et al.Visual maturation of term infants fed long-chain polyunsaturated fatty acid-supplemented or control formula for 12 mo[J].Am J Clin Nutr.2005;81(4):871-9.
90 Kang JX,Wang J,Wu L,Kang ZB.Transgenic mice:fat-1 mice convert n-6 to n-3 fatty acids.Nature.2004 Feb 5;427(6974):504.
91 Food and Agriculture Organization(FAO).Fats and Oils in Human Nutrition.Report of a Joint Expert Consultation.Food and Nutrition Paper No.57.Rome:FAO,1994.
92 Fleith M,Clandinin MT.Dietary PUFA for preterm and term infants:review of clinical studies[J].Crit Rev Food Sci Nutr.2005;45(3):205-29..
93 Hoffman DR,Birch EE,Castenade YS,et al:Visual function in breast-fed term infants weaned to formula with or without long-chain polyunsaturates at 4 to 6 months:A randomized clinical trial[J].J Pediatr 2003;142:669-677.
94 Auestad N,Scott DT,Janowsky JS,et al.Visual,cognitive and language assessments at 39months:a follow-up study of children fed formulas containing long-chain polyunsaturated fatty acids to 1 year of age[J].Pediatrics 2003;112:e177-183.
95 Auestad N,Halter R,Hall RT,et al.Growth and development in term infants fed long-chain polyunsaturated fatty acids:a double-masked,randomized,parallel,prospective,multivariate study[J].Pediatrics 2001;108:372-81.
96 Bouwstra H,Dijck-Brouwer DAJ,Boehm G,et al:Long-chain polyunsaturated fatty acids and neurological developmental outcome at 18 months in healthy term infants[J].Acta Paediatr 2005;94:26-32.
97 Dunstan JA,Simmer K,Dixon G,et al.Cognitive assessment of children at age 2(1/2) years after maternal fish oil supplementation in pregnancy:a randomised controlled trial[J].Arch Dis Child Fetal Neonatal Ed.2008;93(1):F45-50.
98 Judge MP,Harel O,Lammi-Keefe CJ.Maternal consumption of a docosahexaenoic acid-containing functional food during pregnancy:benefit for infant performance on problem-solving but not on recognition memory tasks at age 9 mo[J].Am J Clin Nutr.2007;85(6):1572-7.
99 SanGiovanni JP,Parra-Cabrera S,Colditz GA,et al.Meta-analysis of dietary essential fatty acids and long-chain polyunsaturated fatty acids as they relate to visual resolution acuity in healthy preterm infants[J].Pediatrics.2000;105(6):1292-8.
100 Fleith M,Clandinin MT.Dietary PUFA for preterm and term infants:review of clinical studies[J].Crit Rev Food Sci Nutr.2005;45(3):205-29
101 Caryl J.Antalisa,Laura J.Stevensa,Mary Campbell et al.Omega-3 fatty acid status in attention-deficit/hyperactivity disorder Prostaglandins,Leukotrienes and Essential Fatty Acids,2006;75:299-308.
102 魏宏伟,徐通.注意缺陷多动障碍与多不饱和脂肪酸关联性研究进展.中国儿童保健杂志2004;12(3):244-246
103 A.Assisi,R.Banzi,C.Buoinocore,et al.,Fish oil and mental health:the role of n-3 long-chain polyunsaturated fatty acids in cognitive development and neurological disorders,Int.Clin.Psychopharmacol.2006;21:319-336
104 G.Young,J.Conquer,Omega-3 fatty acids and neuropsychiatric disorders,Reprod.Nutr.Dev.2005;45:1-28
105 J-R.Chen,S.-F.Hsu,C.-D.Hsu,L.-H.Hwang,Y.Suh-Ching,Dietary patterns and blood fatty.acid composition in children with attention-deficit hyperactivity disorder in Taiwan,J.Nutr.Biochem.2004;15:467-472
106 Richardson AJ,Puri BK.A randomized double-blind,placebocontrolled study of the effects of supplementation with highly unsaturated fatty acids on ADHD-related symptoms in children with specific learning difficulties.Prog Neuropsychopharmacol Biol Psychiatry.2002;26:233-239
107 Stevens L,Zhang W,Peck L,et al.EFA supplementation in children with inattention,hyperactivity,and other disruptive behaviours.Lipids.2003;38:1007-1021
108 Moriguchi T,Greiner RS,Salem N Jr.Behavioral deficits associated with dietary induction of decreased brain docosahexaenoic acid concentration,J Neurochem.2000;75:2563-2573
109 Hellgren L,Gillberg C,Gillberg IC,Enerskog I.Children with deficits in attention,motor control and perception(DAMP) almost grown up:general health at 16 years.Dev Med Child Neurol.1993;35:881-892
110 Matin MC,Sanjurjo A,Rodrigo MA,de Alaniz MJ.Long-chain polyunsaturated fatty acids in breast milk in La Plata,Argentina:relationship with maternal nutritional status[J].Prostaglandins Leukot Essent Fatty Acids.2005;73(5):355-60.
111 Boris J,Jensen B,Salvig JD,et al.A randomized controlled trial of the effect of fish oil supplementation in late pregnancy and early lactation on the n-3 fatty acid content in human breast milk[J].Lipids,2004,39(12):1191-1196
112 Carlson SE.Long-chain polyunsaturated fatty acids and development of human infants.Acta Paediatr 1999,suppl 88:72-7
113 Christian A.Drevon,Ingrid B.Helland,Lars Smith,etc.Effect of Supplementing Pregnant and Lactating Mothers With n-3 Very-Long-Chain Fatty Acids on Children's IQ and Body Mass Index at 7 Years of Age Pediatrics 2008;122;e472-e479
114 Helland IB,Smith L,Saarem K,Saugstad OD,Drevon CA.Maternal supplementation with very-long-chain n-3 fatty acids during pregnancy and lactation augments children's IQ at 4 years of age.Pediatrics.2003;111(1).
115 Helland IB,Saugstad OD,Smith L,et al.Similar effects on infants of n-3 and n-6 fatty acids supplementation to pregnant and lactating women.Pediatrics.2001;108(5).Available at:www.pediatrics.org/cgi/content/full/108/5/e82
116 魏梅,姚国英,张晶,马士薇,上海市2005年0～6岁儿童体格发育研究,《中国儿童保健杂志》2007年 第15卷 第04期
1.Lucas A,Fewtrell MS,and Cole TJ.Fetal origins of adult disease-the hypothesis revisited.BMJ 1999,319:245-9.
2.Godfrey KM and Barker DJ.Fetal nutrition and adult disease.Am J Ciin Nutr 2000,71;5 Suppl:1344S-52S.
3.Lucas A.Programming by early nutrition:an experimental approach.J Nutr 1998,128;2 Suppl:401S-406S.
4.Aalinkeel R,Srinivasan M,Song F,Patel MS.Programming into adulthood of islet adaptations induced by early nutritional intervention in the rat.Am J Physiol Endocrinol Metab 2001;281:E640-8.
5. Singhal A, Cole TJ, and Lucas A. Early nutrition in preterm infants and later blood pressure: two cohorts after randomised trials. Lancet 2001,357:413-9.
6. Wilson AC, Forsyth JS, Greene SA, et al. Relation of infant diet to childhood health: seven year follow up of cohort of children in Dundee infant feeding study. BMJ 1998,316:21-5.
7. Pettitt DJ, Forman MR, Hanson RL, et al. Breastfeeding and incidence of non-insulin-dependent diabetes mellitus in Pima Indians. Lancet 1997,350:166-8.
8. von Kries R, Koletzko B, Sauerwald T, et al. Breast feeding and obesity: cross sectional study. BMJ 1999, 319:147-50.
9. Stubbs CD, Smith AD. The modification of mammalian membrane polyunsaturated fatty acid composistion in relation to membrane fluidity and function. Biochim Biophys Acta 1984; 779: 89-137.
10. Strandvik B. Perinatal development of liver enzymes. In: Perinatal Nutrition. (Ed. B.S. Lindblad.) Academic Press, New York: 143-150,1988
11. Clarke SD. Polyunsaturated fatty acid regulation of gene transcription: a mechanism to improve energy balance and insulin resistance Br J Nutr 2000; 83 (Suppl 1): S59-66.
12. Maloney CA, Gosby AK, Phuyal JL, Denyer GS, Bryson JM, Caterson ID. Site-specific changes in the expression of fat-partitioning genes in weanling rats exposed toa low-protein diet in utero. Obes Res 2003; 11:461-8.
13. Carlson SE. Long-chain polyunsaturated fatty acids and development of human infants. Acta Paediatr 1999, suppl 88: 72-7.
14. A. J. Hulbert, N. Turner, L. H. Storlien, Dietary fats and membrane function: implications for metabolism and disease, Biol. Rev. (2005), 80, pp. 155-169
15. Simopoulos AP. Essential fatty acids in health and chronic disease. Am J Clin Nutr 1999, 70; 3 Suppl: 560S-569S.
16. Uauy R, Mena P, and Valenzuela A. Essential fatty acids as determinants of lipid requirements in infants, children and adults. Eur J Clin Nutr 1999,53 Suppl 1: S66-77.
17. Sanders TA. Polyunsaturated fatty acids in the food chain in Europe. Am J Clin Nutr 2000, 71; 1 Suppl: 176S-8S.
18. Chen ZY, Kwan KY, Tong KK, Ratnayake WMN, Li HQ, Leung SSF. Breast milk fatty acid composition: a comparative study between HongKong and Chongqing Chinese. Lipids 1997; 32:1061-7.
19. Fidler N and Koletzko B. The fatty acid composition of human colostrum. Eur J Nutr 2000, 39: 31-7.
20. ESPGAN Committee on Nutrition. Comment on the content and composition of lipids in infant formulas. Acta Paediatr Scand 1991;80: 887-96.
21. Crawford MA. Fatty-acid ratios in free-living and domestic animals. Lancet 1968;1: 1329-33.
22. Uauy R, Mena P, and Rojas C. Essential fatty acids in early life: structural and functional role. Proc Nutr Soc 2000,59: 3-15.
23. Neuringer M. Infant vision and retinal function in studies of dietary long-chain polyunsaturated fatty acids: methods, results, and implications. Am J Clin Nutr 2000, 71; 1 Suppl: 256S-67S.
24. Dvorak B and Stepankova R. Effects of dietary essential fatty acid deficiency on the development of the rat thymus and immune system. Prostaglandins Leukot Essent Fatty Acids 1992,46:183-90.
25. Carlson SE, Werkman SH, Peeples JM, et al. Arachidonic acid status correlates with first year growth in preterm infants. Proc Natl Acad Sci USA 1993,90:1073-7.
26. Amusquivar E, Ruperez FJ, Barbas C, et al. Low arachidonic acid rather than alpha-tocopherol is responsible for the delayed postnatal development in offspring of rats fed fish oil instead of olive oil during pregnancy and lactation. J Nutr 2000,130: 2855-65.
27. DeFronzo RA. Insulin resistance: a multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidaemia and atherosclerosis. Neth J Med 1997,50:191-7.
28. Storlien LH, James DE, Burleigh KM, et al. Fat feeding causes widespread in vivo insulin resistance, decreased energy expenditure, and obesity in rats. Am J Physiol 1986,251: E576-83.
29. Storlien LH, Jenkins AB, Chisholm DJ, et al. Influence of dietary fat composition on development of insulin resistance in rats. Relationship to muscle triglyceride and omega-3 fatty acids in muscle phospholipid. Diabetes 1991,40: 280-9.
30. Storlien LH, Kraegen EW, Chisholm DJ, et al. Fish oil prevents insulin resistance induced by high-fat feeding in rats. Science 1987,237:885-8.
31. Das UN. Beneficial effect(s) of n-3 fatty acids in cardiovascular diseases: but, why and how? Prostaglandins Leukot Essent Fatty Acids 2000, 63: 351-62.
32. Dewailly EE, Blanchet C, Gingras S, et al. Relations between n-3 fatty acid status and cardiovascular disease risk factors among Quebecers. Am J Clin Nutr 2001,74:603-11.
33. Innis SM and Kuhnlein HV. Long-chain n-3 fatty acids in breast milk of Inuit women consuming traditional foods. Early Hum Dev 1988,18:185-9.
34. Weisinger HS, Armitage JA, Sinclair AJ, et al. Perinatal omega-3 fatty acid deficiency affects blood pressure later in life. Nat Med 2001, 7: 258-9.
35. Baur LA, O'Connor J, Pan DA, Kriketos AD, Storlien LH. The fatty acid composition of skeletal muscle membrane phospholipid: its relationship with the type of feeding and plasma glucose levels in young children. Metabolism 1998,47:106-1235.
36. Persson PG, Ahlbom A, Hellers G. Crohn's disease and ulcerative colitis. A review of dietary studies with emphasis on methodologic aspects. Scand J Gastroenterol 1987:22:385-9.
37. Shoda R, Matsueda K, Yamato S, Umeda N. Epidemiologic analysis of Crohn disease in Japan: increased dietary intake of n-6 polyunsaturated fatty acids and animal protein relates to the increased incidence of Crohn disease in Japan. Am J Clin Nutr 1996;63:741-5.
38. Korotkova M, Strandvik B.: Essential fatty acid deficiency affects the fatty acid composition of the rat small intestinal and colonic mucosa differently. Biochim Biophys Acta 2000,1487 :319-25.
39. Branski D, Hurvitz H, Halevi A, Klar A, Navon P, Weidenfeld J. Eicosanoids content in small intestinal mucosa of children with celiac disease. J Pediatr Gastroenterol Nutr 1992; 14:173-6.
40. Carty E, De Brabander M, Feakins RM, Rampton DS. Mesaurement of in vivo rectal mucosal cytokine and eicosanoid production in ulcerative colitis using filter paper. Gut 2000; 46:487-92.
41. Thomson ABR, Keelan M, Garg ML, Clandinin MT. Influence of dietary fat composition on intestinal absorption in the rat. Lipids 1989; 24:494-501.
42. Campos FG, Waitzberg DL, Habr-Gama A, Logullo AF, Noronha IL, Jancar S, Torrinhas RS, Fiirst P. Impact of parenteral n-3 fatty acids on experimental acute colitis. Br J Nutr 2002; 87:suppl 1: S83-8.
43. Korotkova M.,Holmang A.,Latsson B-M.,Gabrielsson B.,Hanson L.A.,Strandvik B.Perinatal essential fatty acids affect weight blood pressure and serum insulin levels in adult rats. Pediatric Res[J],2003.53(6)suppl 5:p.17A-17A
44. Korotkova M, Ohlsson C, Gabrielsson B, Hanson LA, Strandvik B. Perinatal essential fatty acid deficiency influences body weight and bone parameters in adult male rats.Biochim Biophys Acta. 2005 Jan 5;1686 3:248-54
45. Korotkova M, Ohlsson C, Hanson LA, Strandvik B. Dietary n-6:n-3 fatty acid ratio in the perinatal period affects bone parameters in adult female rats. Br J Nutr. 2004 Oct;92(4):643-8
46. Korotkova M, Telemo E, Yamashiro Y, Hanson LA, Strandvik B. The ratio of n-6 to n-3 fatty acids in maternal diet influences the induction of neonatal immunological tolerance to ovalbumin.Clin Exp Immunol. 2004 Aug;137(2):237-44.
[1]B anerjee T D,M iddleton F,Faraone S V.Environmental risk factors for attention deficit hyperactivity disorder.Acta Paediatr,2007;96(9):1269-1274
[2]Brown RT,Freeman WS,Perrin JM,et al.Prevalence and assessment of attention2 deficit /hyperactivity disorder in primary care settings.Pediatrics,2004;114(2):511-512
[3]Marianna Mazza,Massimiliano Pomponi,Luigi Janiri.Omega-3 fatty acids and antioxidants in neurological and psychiatric diseases:An overview.Progress in Neuro-Psychopharmaeology &Biological Psychiatry 2007;31:12-26
[4]Caryl J.Antalisa,Laura J.Stevensa,Mary Campbell et al.Omega-3 fatty acid status in attention-deficit/hyperactivity disorder Prostaglandins,Leukotrienes and Essential Fatty Acids,2006;75:299-308
[5】魏宏伟,徐通.注意缺陷多动障碍与多不饱和脂肪酸关联性研究进展.中国儿童保健杂志2004;12(3):244-246
[6]A.Assisi,R.Banzi,C.Buoinocore,et al.,Fish oil and mental health:the role of n-3 long-chain polyunsaturated fatty acids in cognitive development and neurological disorders,Int.Clin.Psychopharmacol.2006;21:319-336
[7]G.Young,J.Conquer,Omega-3 fatty acids and neuropsychiatric disorders,Reprod.Nutr.Dev.2005;45:1-28
[8]J.-R.Chen,S.-F.Hsu,C.-D.Hsu,L.-H.Hwang,Y.Suh-Ching,Dietary patterns and blood fatty acid composition in children with attention-deficit hyperactivity disorder in Taiwan,J.Nutr.Biochem.2004;15:467-472
[9]Schohraya Spahis a,b,Michel Vanasse a,c,Stacey A.Be'langer,et al.Lipid profile,fatty acid composition and pro-and anti-oxidantstatus in pediatric patients with attention-deficit/hyperactivity disorder,Prostaglandins,Leukotdenes and Essential Fatty Acids 2008;79:47-53
[10].N.Sinn,Physical fatty acid deficiency signs in children with ADHD symptoms.Prostaglandins,Leukotrienes and Essential Fatty Acids,2007;77:109-115
[11]J.M.Osendarp,K.I.Baghurst,J.Bryan,et al.Effect of a twelve month micronutrient intervention on learning and memory in well-nourished and marginally nourished school-aged children:two parallel randomized,placebo-controlled studies in Australia and Indonesia,Am.J.Clin.Nutr.(in press).
[12]Yehuda S.Omega-6/Omega-3 ratio and brain related functions.World Rev Neur Diet,2003;92:37-56
[13]A.J.Richardson,P.Montgomery,The Oxford-Durham study:a randomised,controlled trial of dietary supplementation with fatty acids in children with developmental coordination disorder.Pediatrics 2005;115:1360-1366.
[14]N.Sinn,J.Bryan,Effect of supplementation with polyunsaturated fatty acids and micronutrients on ADHD-related problems with attention and behavior,J.Dev.Behav.Pediatr.2007;28:82-91.
[15]Joshi K,Lad S,Kale M,et al.Supplementation with flax oil and vitamin C improves the outcome of attention deficit hyperactivity disorder(ADHD).Prostagland Leukotri Essen Fatty Acids,2006;74:17-21
[16]Stevens L,Zhang W,Peck L,et al.EFA supplementation in children with inattention,hyperactivity and other disruptive behaviors.Lipids 2003;38:1007-1021
[17].Paul J Sorgi,Edward M Hallowell,Heather L Hutchins et al.Effects of an open-label pilot study with high-dose EPA/DHA concentrates on plasma phospholipids and behavior in children with attention deficit hyperactivity disorder.Nutrition Journal 2007;Jul 13:6-16
[18】 张丽,刘先洋,岳虹霓.注意缺陷多动障碍与长链多不饱和脂肪酸相关性探讨【J】.现代中西医结合杂志.2008;(15):2310-2311
[19】.雷晓梅,杨玉凤.注意缺陷多动障碍与多不饱和脂肪酸及神经生化因素关系的研究进展预防医学论坛.2007;13(3):241-243
[20].Voigt RG,Llorente AM,Jensen CL,etal.A randomized,double blind,placebo2controlled trial of docosahexaenoic acid supplementation in children with attention2deficit/hyperactivity disorder [J].J Pediatr 2001;139(2):189-196
[21].LUKE T.CURTIS M.D.,C.I.H.M.S.,and KALPANA PATEL,M.D..Nutritional and Environmental Approaches to Preventing and Treating Autism and Attention Deficit Hyperactivity Disorder(ADHD).THE JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE 2008;14(1):79-85
[22].A.Eilander,D.C.Hundscheid,S.J.Osendarp,C.Transler,P.L.Zock,Effects of n-3 long chain polyunsaturated fatty acid supplementationon visual and cognitive development throughout childhood:A review of human studies.Prostaglandins,Leukotrienes and Essential Fatty Acids 2007;76:189-203
[23].ALEXANDRA J.RICHARDSON,Omega-3 fatty acids in ADHD and related neurodevelopmental disorders.International Review of Psychiatry,2006;18(2):155-172
[24]Natan Gadoth.On fish oil and omega-3 supplementation in children:The role of such supplementation on attention and cognitive dysfunction.Brain & Development 2008;30:309-312
[25].Busch B.Polyunsaturated fatty acid supplementation for ADHD? Fishy,fascinating,and far from clear.Polyunsaturated Fatty Acid Supplementation for ADHD Symptoms:Response to Commentary J Dev Behav Pediatr 2007;28(2):139-144
[26]Natalie Sinn PhD,BPsych(Hons).Polyunsaturated Fatty Acid Supplementation for ADHD Symptoms:Response to Commentary.Journal of Developmental & Behavioral Pediatrics 2007;28(3):262-263
[27].MICHELE GERMANO,DOMENICO MELELEO,GIGLIOLA MONTORFANO.Plasma,red blood cells phospholipids and clinical evaluation after long chain omega-3 supplementation in children with attention deficit hyperactivity disorder(ADHD).Nutritional Neuroscience 2007;10(1/2):1-9
2 Godfrey KM and Barker DJ.Fetal nutrition and adult disease.Am J Clin Nutr 2000,71;5 Suppl:1344S-52S.
3 Singhal A,Cole TJ,and Lucas A.Early nutrition in preterm infants and later blood pressure:two cohorts after randomised trials.Lancet 2001,357:413-9.
4 Koletzko B,Sauerwald T,et al.Breast feeding and obesity:cross sectional study.BMJ 1999,319:147-50.
5 Nancy Auestad,David T.S,Jeri S.J,et al.Visual,Cognitive,and Language Assessments at 39Months:A Follow-up Study of Children Fed Formulas Containing Long-Chain Polyunsaturated Fatty Acids to 1 Year of Age.PEDIATRICS Vol.112 No.3 September 2003,pp.e177-e183
6 Eileen E Birch,Yolanda S Castaneda,Dianna H Wheaton,David G Birch,Ricardo D Uauy and Dennis R Hoffman.Visual maturation of term infants fed long-chain polyunsaturated fatty acid-supplemented or control formula for 12 too.American Journal of Clinical Nutrition,Vol.81,No.4,871-879,April 2005
7 Clarke SD.Polyunsaturated fatty acid regulation of gene transcription:a mechanism to improve energy balance and insulin resistance Br J Nutr 2000;83(Suppl 1):S59-66.
8 Maloney CA,Gosby AK,Phuyal JL,Denyer GS,Bryson JM,Caterson ID.Site-specific changes in the expression of fat-partitioning genes in weanling rats exposed toa low-protein diet in utero.Obes Res 2003;11:461-8.
9 Rocquelin G,Tapsoba S,Dop MC,Mbemba F,Traissae P,Martin-Prevel Y.Lipid content and essential fatty acid(EFA) composition of mature Congolese breast milk are influenced by mothers' nutritional status:impact on infants' EFA supply.Eur J Clin Nutr.1998Mar;52(3):164-71.
10 Xiang M,Harbige LS,Zetterstrom R.Long-chain polyunsaturated fatty acids in Chinese and Swedish mothers:diet,breast milk and infant growth.Acta Paediatr.2005 Nov;94(11):1543-9
11 Neuringer M.Infant vision and retinal function in studies of dietary long-chain polyunsaturated fatty acids:methods,results,and implications.Am J Clin Nutr 2000,71;1 Suppl:256S-67S.
12 Lefkowitz W,Lim SY,Lin YH and Salem N,JR.Where Does the Developing Brain Obtain Its Docosahexaenoic Aci d? Relative Contributions of Dietary α-Linolenic Acid,Docosahexaenoic Acid,and Body Stores in the Developing Rat Pediatric Research 2005:57:157-165.
13 Korotkova M,Telemo E,Yamashiro Y,Hanson LA,Strandvik B.The ratio of n-6 to n-3 fatty acids in maternal diet influences the induction of neonatal immunological tolerance to ovalbumin.Clin Exp Immunol.2004 Aug;137(2):237-44.
14 Amusquivar E,Ruperez FJ,Barbas C,et al.Low arachidonic acid rather than alpha-tocopherol is responsible for the delayed postnatal development in offspring of rats fed fish oil instead of olive oil during pregnancy and lactation.J Nutr 2000,130:2855-65.
15 Uauy R,Mena P,and Rojas C.Essential fatty acids in early life:structural and functional role.Proc Nutr Soc 2000,59:3-15.
16 Simopoulos AP,Evolutionary aspects of diet,the omega-6/omega-3 ratio and genetic variation:nutritional implications for chronic diseases.Biomedicine & Pharmacotherapy 2006,60:502-507
17 Sanders TA.Polyunsaturated fatty acids in the food chain in Europe.Am J Clin Nutr 2000,71;1Suppl:176S-8S.
18 Fidler N and Koletzko B.The fatty acid composition of human colostrum.Eur J Nutr 2000,39:31-7.
19 Dariush M;Alberto A;Frank B;Meir J;Walter CW;David SS;Eric BR.Interplay Between Different Polyunsaturated Fatty Acids and Risk of Coronary Heart Disease in Men.Circulation.2005;111:157-164.
20 Baylin A Kabagambe EK,Ascherio A,Spiegelman D,Campos H.Adipose tissue α-linolenic acid and nonfatal acute myocardial infarction in Costa Rica.Circulation.2003;107:1586-1591.
21 Kris-Etherton PM,Taylor DS,Yu-Poth S,Huth P,Moriarty K,Fishell V,Hargrove RL,Zhao G,Etherton TD.Polyunsaturated PUFAs in the food chain in the United States.Am J Clin Nutr.2000;71:179S-188S.
22 de Lorgeril,M.,Salen,P.(2000).Modified Cretan Mediterranean diet in the prevention of coronary heart disease and cancer.In:Simopoulos,A.P.,Visioli,F.,eds.Mediterranean Diets.Vol.87.World Rev.Nutr.Diet,1-23.
23 Das UN.Beneficial effect(s) of n-3 fatty acids in cardiovascular diseases:but,why and how?Prostaglandins Leukot Essent Fatty Acids 2000,63:351-62.
24 Dewailly EE,Blanchet C,Gingras S,et al.Relations between n-3 fatty acid status and cardiovascular disease risk factors among Quebecers.Am J Clin Nutr 2001,74:603-11.
25 Weisinger HS,Armitage JA,Sinclair AJ,et al.Perinatal omega-3 fatty acid deficiency affects blood pressure later in life.Nat Med 2001,7:258-9.
26 Korotkova M.,Holmang A.,Latsson B-M.,Gabrielsson B.,Hanson L.A.,Strandvik B.Perinatal essential fatty acids affect weight blood pressure and serum insulin levels in adult rats.Pediatric Res[J],2003.53(6)supp15:p.17A-17A.
27 Bouwstra H,Dijck-Brouwer DA,Wildeman JA,Tjoonk HM,van der Heide JC,Boersma ER,Muskiet FA,Hadders-Algra M.Long-chain polyunsaturated fatty acids have a positive effect on the quality of general movements of healthy term infants.Am J Clin Nutr.2003:78(2):313-8.
28 Auestad N,Scott DT,Janowsky JS,et al.Visual,cognitive,and language assessments at 39months:a follow-up study of children fed formulas containing long-chain polyunsaturated fatty acids to 1 year of age.Pediatrics.2003 Sep;112(3 Pt 1):e177-83
29 Singh,R.B.,Dubnov,G.,Niaz,M.,et al.Effect of an Indo-Mediterranean diet on progression of coronary artery disease in high-risk patients(Indo-Mediterranean Diet Heart Study):a randomized single-blind trial.2002:Lancet 360:1455-1461
30 周婷婷,张婷艳,strandvik B,王琴,留佩宁,Zenerstr(o|¨)m R,彭咏梅,孕期不同膳食模式对膳食脂肪酸含量及母初乳脂肪酸组成的影响,中国儿童保健杂志,2008,16(2):160-165
31 B anerjee T D, M iddleton F, Faraone S V. Environmental risk factors for attention deficit hyperactivity disorder. Acta Paediatr, 2007;96 (9): 1269-1274
32 Brown RT, Freeman WS, Perrin JM, et al. Prevalence and assessment of attention2 deficit /hyperactivity disorder in primary care settings. Pediatrics, 2004; 114 (2): 511-512
33 Marianna Mazza, Massimiliano Pomponi, Luigi Janiri. Omega-3 fatty acids and antioxidants in neurological and psychiatric diseases: An overview. Progress in Neuro-Psychopharmacology & Biological Psychiatry 2007;31: 12-26
34 A.J. Richardson, P. Montgomery, The Oxford-Durham study: a randomised, controlled trial of dietary supplementation with fatty acids in children with developmental coordination disorder. Pediatrics 2005; 115:1360-1366.
35 N. Sinn, J. Bryan, Effect of supplementation with polyunsaturated fatty acids and micronutrients on ADHD-related problems with attention and behavior, J. Dev. Behav. Pediatr. 2007; 28: 82-91.
36 Joshi K, Lad S, Kale M, et al. Supplementation with flax oil and vitamin C improves the outcome of attention deficit hyperactivity disorder (ADHD). Prostaglandins Leukotri Essen Fatty Acids, 2006;74:17-21
37 Stevens L, Zhang W, Peck L, et al. EFA supplementation in children with inattention, hyperactivity and other disruptive behaviors. Lipids 2003; 38:1007-1021
38 James C. DeMar, Jr., Kiazong Ma, Jane M. Bell, Miki Igarashi, Deanna Greenstein, and Stanley I. Rapoport. One generation of n-3 polyunsaturated fatty acid deprivation increases depression and aggression test scores in rats. Lipid Res., Jan 2006; 47:172-180
39 Maes M, Smith RS (1998), Fatty acids, cytokines and major depression. Biol Psychiatry 43(5):313-314.Smith RS (1991), The macrophage theory of depression. (Erratum appears in Med Hypotheses 36[2]:178.) Med Hypotheses 35(4):298-306.
40 Stoll AL, Sachs GS, Cohen BM et al. (1996), Choline in the treatment of rapid-cycling bipolar disorder: clinical and neurochemical findings in lithium-treated patients. Biol Psychiatry 40(5):382-388.
41 Haag M. Essential fatty acids and the brain. Can J Psychiatry. 2003 ;48:195-203
42 Richardson AJ, Ross MA. Fatty acid metabolism in neurodevelopmentaldisorder: a new perspective on associations between attention-deficit/hyperactivity disorder, dyslexia, dyspraxia and the autistic spectnm.Prostaglandins Leukot Essent Fatty Acids. 2000;63:1-9
43 Voigt RG,Llorente AM Jensen CL ,etal. A randomized .double blind ,placebo2controlled trial of docosahexaenoic acid supplementation in children with attention2deficit/ hyperactivity disorder [J]. J Pediatr 2001; 139 (2): 189-196
44 Natan Gadoth. On fish oil and omega-3 supplementation in children: The role of such supplementation on attention and cognitive dysfunction. Brain & Development 2008;30:309-312
45 A. Eilander, D.C. Hundscheid, S.J. Osendarp, C. Transler, P.L. Zock, Effects of n-3 long chain polyunsaturated fatty acid supplementationon visual and cognitive development throughout childhood: A review of human studies. Prostaglandins, Leukotrienes and Essential Fatty Acids 2007; 76:189-203
46 ALEXANDRA J. RICHARDSON, Omega-3 fatty acids in ADHD and related neurodevelopmental disorders. International Review of Psychiatry, 2006;18(2): 155-172.
47 Busch B. Polyunsaturated fatty acid supplementation for ADHD? Fishy, fascinating, and far from clear. Polyunsaturated Fatty Acid Supplementation for ADHD Symptoms: Response to Commentary J Dev Behav Pediatr 2007; 28 (2):139-144
48 MICHELE GERMANO, DOMENICO MELELEO, GIGLIOLA MONTORFANO. Plasma, red blood cells phospholipids and clinical evaluation after long chain omega-3 supplementation in 49 children with attention deficit hyperactivity disorder (ADHD). Nutritional Neuroscience 2007; 10(1/2): 1-9c
50 Korotkova M, Gabrielsson B, Strandvik B, et al. Leptin levels in rat offspring are modified by the ratio of linoleic to alpha-linolenic acid in the maternal diet[J]. J Lipid Res. 2002;43(10):1743-9.
51 Uauy R, Hoffman DR, Peirano P, et al. Essential fatty acids in visual and brain development[J]. Lipids.2001;36(9):885-95.
52 Dutta-Roy AK. Transport mechanisms for long-chain polyunsaturated fatty acids in the human placenta[J]. Am J Clin Nutr. 2000;71(Suppl):315S-22S
53 Salem NJ, Wegher B, Mena P, et al. Arachidonic and docosahexaenoic acids are biosynthesized from their 18-carbon precursors in human infants[J]. Proc Natl Acad Sci USA. 1996;93(1):49-54.
54 artner LM, Morton J, Lawrence RA, et al. Breastfeeding and the use of human milk. Pediatrics. Feb2005;115(2):496-506.
55 Pickering LK, Morrow AL, Ruiz-Palacios GM, Schanler RJ (eds). Protecting Infants through human milk: Advancing the Scientific Evidence. Kluwer/Plenum Publishers. 2004.
56 Hamosh M: Bioactive factors in human milk. Pediatr Clin North Am 48(1): 69-86,2001.
57 Morrow AL, Ruiz-Palacios GM, Altaye M, et al. Human milk oligosaccharides are associated with protection against diarrhea in breastfed infants. J Pediatr 2004; 145:297-303.
58 Newburg DS, Ruiz-Palacios GM, Morrow AL. Human milk oligosaccharides protect against enteric pathogens. Annu Rev Nutr 2005; 25:37-58.
59 Innis SM: Polyunsaturated fatty acids in human milk: an essential role in infant development. Adv Exp Med Biol 554: 27-43, 2004
60 YM Peng, TY Zhang, Q Wang, R Zetterstrom, B Strandvik. Fatty acid composition in breast milk and serum phospholipids of healthy term Chinese infants during first 6 weeks of life. Acta Paediatrica 2007; 96. pp1640-1645
61 Chen ZY, Kwan KY, Tong KK, et al. Breast milk fatty acid composition: a comparative study between Hong Kong and Chongqing Chinese[J]. Lipids, 1997,32: (10): 1061-1067.
62 Michihiro Sugano, Fumiko Hiranara. Polyunsattmated fatty acids in the food chain in Japan. Am J CAin Nutr, 2000, 71 (supple) :189-196.
63 De Vriese SR, Dhont M, Christophe AB. FA composition of cholesteryl esters and phospholipids in maternal plasma during pregnancy and at delivery and in cord plasma at birth[J]. Lipids. 2003 ;38(1):1-7.
64 Dutta-Roy AK.Transport mechanisms for long-chain polyunsaturated fatty acids in the human placenta[J].Am J ClinNutr.2000;71(Suppl):315S-22S.
65 Amusquivar E,Herrera E.Influence of changes in dietary fatty acids during pregnancy on placental and fetal fatty acid profile in the rat[J].Biol Neonate.2003;83(2):136-45.
66 De Vriese SR,Matthys C,De Henauw S,et al.Maternal and umbilical fatty acid status in relation to maternal diet[J].Prostaglandins Leukot Essent Fatty Acids.2002;67(6):389-96.
67 Salem NJ,Wegher B,Mena P,et al.Arachidonic and docosahexaenoic acids are biosynthesized from their 18-carbon precursors in human infants[J].Proc Natl Acad Sci U S A.1996;93(1):49-54.
68 Kurlak LO,Stephenson TJ.Plausible explanations for effects of long chain polyunsaturated fatty acids(LCPUFA) on neonates[J].Arch Dis Child Fetal Neonatal Ed.1999;80(2):F148-54.
69 Lucas A,Fewtrell MS,and Cole TJ.Fetal origins of adult disease-the hypothesis revisited.BMJ 1999,319:245-9.
70 Godfrey KM and Barker DJ.Fetal nutrition and adult disease.Am J Clin Nutr 2000,71;5 Suppl:1344S-52S.
71 Lucas A.Programming by early nutrition:an experimental approach.J Nutr 1998,128;2 Suppl:401S-406S
72 Aalinkeel R,Srinivasan M,Song F,Patel MS.Programming into adulthood of islet adaptations induced by early nutritional intervention in the rat.Am J Physiol Endocrinol Metab 2001;281:E640-8.
73 ESPGAN Committee on Nutrition.Comment on the content and composition of lipids in infant formulas.Acta Paediatr Scand 1991;80:887-96.
74 Crawford MA.Fatty-acid ratios in free-living and domestic animals.Lancet 1968;1:1329-33.
75 Uauy R,Mena P,and Rojas C.Essential fatty acids in early life:structural and functional role.Proc Nutr Soc 2000,59:3-15.
76 Neuringer M.Infant vision and retinal function in studies of dietary long-chain polyunsaturated fatty acids:methods,results,and implications.Am J Clin Nutr 2000,71;1 Suppl:256S-67S.
77 Leaf A,Albert CM,Josephson M,Steinhaus D,Kluger J,Kang JX,Cox B,Zhang H,Schoenfeld D.Prevention of fatal arrhythmias in high-risk subjects by fish oil n-3 fatty acid intake.Circulation.2005 Nov 1;112(18):2762-8.
78 Kratz M,yon Eckardstein A,Fobker M,Buyken A,Posny N,Schulte H,Assmann G,Wahrburg U.The impact of dietary fat composition on serum leptin concentrations in healthy nonobese men and women.J Clin Endocrinol Metab[J],2002.87(11):p.5008-14
79 Perez-Matute P,Marti A,Martinez JA,Moreno-Aliaga MJ.Effects of araehidonic acid on leptin secretion and expression in primary cultured rat adipocytes.J Physiol Biochem[J],2003.59(3):p.201-8.
80.van Niel MH,Beynen AC.The intake of polyunsaturated fatty acids by cats is reflected in their adipose tissue.Vet Q[J],1997.19(4):p.150-3
81 王琴,周婷婷,张婷艳,Strandvik B,Zetterstr(o|¨)m R,彭咏梅,婴儿早期血浆磷脂脂肪酸 水平对体质指数的影响,复旦学报(医学版),2008Nov,35(6)824-828
82 Gartner LM,Morton J,Lawrence RA,et al.Breastfeeding and the use of human milk.Pediatrics.Feb 2005;115(2):496-506
83 Pickering LK,Morrow AL,Ruiz-Palacios GM,Schanler RJ(eds).Protecting Infants through human milk:Advancing the Scientific Evidence.Kluwer/Plenum Publishers.2004.
84 Hamosh M:Bioactive factors in human milk.Pediatr Clin North Am 48(1):69-86,2001.
85.Paul J Sorgi,Edward M Hallowell,Heather L Hutchins et al.Effects of an open-label pilot study with high-dose EPA/DHA concentrates on plasma phospholipids and behavior in children with attention deficit hyperactivity disorder.Nutrition Journal 2007;Jul 13:6-16
86 Uauy RD,Mena P,Hoffman DR.Essential fatty acid metabolism and requirements for LBW infants.Acta Pediatr 1994;405(Suppl):78-85.
87 Whalley LJ,Fox HC,Wahle KW,Starr JM,Deary IJ.Cognitive aging,childhood intelligence,and the use of food supplements:possible involvement of n-3 fatty acids.Am J Clin Nutr.2004Dec;80(6):1650-7.
88 Bakker EC,Hornstra G,Blanco CE,et al.Relationship between long-chain polyunsaturated fatty acids at birth and motor function at 7 years of age[J].Eur J Clin Nutr.2007 Dec 19;[Epub ahead of print]
89 Birch EE,Castaneda YS,Wheaton DH,et al.Visual maturation of term infants fed long-chain polyunsaturated fatty acid-supplemented or control formula for 12 mo[J].Am J Clin Nutr.2005;81(4):871-9.
90 Kang JX,Wang J,Wu L,Kang ZB.Transgenic mice:fat-1 mice convert n-6 to n-3 fatty acids.Nature.2004 Feb 5;427(6974):504.
91 Food and Agriculture Organization(FAO).Fats and Oils in Human Nutrition.Report of a Joint Expert Consultation.Food and Nutrition Paper No.57.Rome:FAO,1994.
92 Fleith M,Clandinin MT.Dietary PUFA for preterm and term infants:review of clinical studies[J].Crit Rev Food Sci Nutr.2005;45(3):205-29..
93 Hoffman DR,Birch EE,Castenade YS,et al:Visual function in breast-fed term infants weaned to formula with or without long-chain polyunsaturates at 4 to 6 months:A randomized clinical trial[J].J Pediatr 2003;142:669-677.
94 Auestad N,Scott DT,Janowsky JS,et al.Visual,cognitive and language assessments at 39months:a follow-up study of children fed formulas containing long-chain polyunsaturated fatty acids to 1 year of age[J].Pediatrics 2003;112:e177-183.
95 Auestad N,Halter R,Hall RT,et al.Growth and development in term infants fed long-chain polyunsaturated fatty acids:a double-masked,randomized,parallel,prospective,multivariate study[J].Pediatrics 2001;108:372-81.
96 Bouwstra H,Dijck-Brouwer DAJ,Boehm G,et al:Long-chain polyunsaturated fatty acids and neurological developmental outcome at 18 months in healthy term infants[J].Acta Paediatr 2005;94:26-32.
97 Dunstan JA,Simmer K,Dixon G,et al.Cognitive assessment of children at age 2(1/2) years after maternal fish oil supplementation in pregnancy:a randomised controlled trial[J].Arch Dis Child Fetal Neonatal Ed.2008;93(1):F45-50.
98 Judge MP,Harel O,Lammi-Keefe CJ.Maternal consumption of a docosahexaenoic acid-containing functional food during pregnancy:benefit for infant performance on problem-solving but not on recognition memory tasks at age 9 mo[J].Am J Clin Nutr.2007;85(6):1572-7.
99 SanGiovanni JP,Parra-Cabrera S,Colditz GA,et al.Meta-analysis of dietary essential fatty acids and long-chain polyunsaturated fatty acids as they relate to visual resolution acuity in healthy preterm infants[J].Pediatrics.2000;105(6):1292-8.
100 Fleith M,Clandinin MT.Dietary PUFA for preterm and term infants:review of clinical studies[J].Crit Rev Food Sci Nutr.2005;45(3):205-29
101 Caryl J.Antalisa,Laura J.Stevensa,Mary Campbell et al.Omega-3 fatty acid status in attention-deficit/hyperactivity disorder Prostaglandins,Leukotrienes and Essential Fatty Acids,2006;75:299-308.
102 魏宏伟,徐通.注意缺陷多动障碍与多不饱和脂肪酸关联性研究进展.中国儿童保健杂志2004;12(3):244-246
103 A.Assisi,R.Banzi,C.Buoinocore,et al.,Fish oil and mental health:the role of n-3 long-chain polyunsaturated fatty acids in cognitive development and neurological disorders,Int.Clin.Psychopharmacol.2006;21:319-336
104 G.Young,J.Conquer,Omega-3 fatty acids and neuropsychiatric disorders,Reprod.Nutr.Dev.2005;45:1-28
105 J-R.Chen,S.-F.Hsu,C.-D.Hsu,L.-H.Hwang,Y.Suh-Ching,Dietary patterns and blood fatty.acid composition in children with attention-deficit hyperactivity disorder in Taiwan,J.Nutr.Biochem.2004;15:467-472
106 Richardson AJ,Puri BK.A randomized double-blind,placebocontrolled study of the effects of supplementation with highly unsaturated fatty acids on ADHD-related symptoms in children with specific learning difficulties.Prog Neuropsychopharmacol Biol Psychiatry.2002;26:233-239
107 Stevens L,Zhang W,Peck L,et al.EFA supplementation in children with inattention,hyperactivity,and other disruptive behaviours.Lipids.2003;38:1007-1021
108 Moriguchi T,Greiner RS,Salem N Jr.Behavioral deficits associated with dietary induction of decreased brain docosahexaenoic acid concentration,J Neurochem.2000;75:2563-2573
109 Hellgren L,Gillberg C,Gillberg IC,Enerskog I.Children with deficits in attention,motor control and perception(DAMP) almost grown up:general health at 16 years.Dev Med Child Neurol.1993;35:881-892
110 Matin MC,Sanjurjo A,Rodrigo MA,de Alaniz MJ.Long-chain polyunsaturated fatty acids in breast milk in La Plata,Argentina:relationship with maternal nutritional status[J].Prostaglandins Leukot Essent Fatty Acids.2005;73(5):355-60.
111 Boris J,Jensen B,Salvig JD,et al.A randomized controlled trial of the effect of fish oil supplementation in late pregnancy and early lactation on the n-3 fatty acid content in human breast milk[J].Lipids,2004,39(12):1191-1196
112 Carlson SE.Long-chain polyunsaturated fatty acids and development of human infants.Acta Paediatr 1999,suppl 88:72-7
113 Christian A.Drevon,Ingrid B.Helland,Lars Smith,etc.Effect of Supplementing Pregnant and Lactating Mothers With n-3 Very-Long-Chain Fatty Acids on Children's IQ and Body Mass Index at 7 Years of Age Pediatrics 2008;122;e472-e479
114 Helland IB,Smith L,Saarem K,Saugstad OD,Drevon CA.Maternal supplementation with very-long-chain n-3 fatty acids during pregnancy and lactation augments children's IQ at 4 years of age.Pediatrics.2003;111(1).
115 Helland IB,Saugstad OD,Smith L,et al.Similar effects on infants of n-3 and n-6 fatty acids supplementation to pregnant and lactating women.Pediatrics.2001;108(5).Available at:www.pediatrics.org/cgi/content/full/108/5/e82
116 魏梅,姚国英,张晶,马士薇,上海市2005年0～6岁儿童体格发育研究,《中国儿童保健杂志》2007年 第15卷 第04期
1.Lucas A,Fewtrell MS,and Cole TJ.Fetal origins of adult disease-the hypothesis revisited.BMJ 1999,319:245-9.
2.Godfrey KM and Barker DJ.Fetal nutrition and adult disease.Am J Ciin Nutr 2000,71;5 Suppl:1344S-52S.
3.Lucas A.Programming by early nutrition:an experimental approach.J Nutr 1998,128;2 Suppl:401S-406S.
4.Aalinkeel R,Srinivasan M,Song F,Patel MS.Programming into adulthood of islet adaptations induced by early nutritional intervention in the rat.Am J Physiol Endocrinol Metab 2001;281:E640-8.
5. Singhal A, Cole TJ, and Lucas A. Early nutrition in preterm infants and later blood pressure: two cohorts after randomised trials. Lancet 2001,357:413-9.
6. Wilson AC, Forsyth JS, Greene SA, et al. Relation of infant diet to childhood health: seven year follow up of cohort of children in Dundee infant feeding study. BMJ 1998,316:21-5.
7. Pettitt DJ, Forman MR, Hanson RL, et al. Breastfeeding and incidence of non-insulin-dependent diabetes mellitus in Pima Indians. Lancet 1997,350:166-8.
8. von Kries R, Koletzko B, Sauerwald T, et al. Breast feeding and obesity: cross sectional study. BMJ 1999, 319:147-50.
9. Stubbs CD, Smith AD. The modification of mammalian membrane polyunsaturated fatty acid composistion in relation to membrane fluidity and function. Biochim Biophys Acta 1984; 779: 89-137.
10. Strandvik B. Perinatal development of liver enzymes. In: Perinatal Nutrition. (Ed. B.S. Lindblad.) Academic Press, New York: 143-150,1988
11. Clarke SD. Polyunsaturated fatty acid regulation of gene transcription: a mechanism to improve energy balance and insulin resistance Br J Nutr 2000; 83 (Suppl 1): S59-66.
12. Maloney CA, Gosby AK, Phuyal JL, Denyer GS, Bryson JM, Caterson ID. Site-specific changes in the expression of fat-partitioning genes in weanling rats exposed toa low-protein diet in utero. Obes Res 2003; 11:461-8.
13. Carlson SE. Long-chain polyunsaturated fatty acids and development of human infants. Acta Paediatr 1999, suppl 88: 72-7.
14. A. J. Hulbert, N. Turner, L. H. Storlien, Dietary fats and membrane function: implications for metabolism and disease, Biol. Rev. (2005), 80, pp. 155-169
15. Simopoulos AP. Essential fatty acids in health and chronic disease. Am J Clin Nutr 1999, 70; 3 Suppl: 560S-569S.
16. Uauy R, Mena P, and Valenzuela A. Essential fatty acids as determinants of lipid requirements in infants, children and adults. Eur J Clin Nutr 1999,53 Suppl 1: S66-77.
17. Sanders TA. Polyunsaturated fatty acids in the food chain in Europe. Am J Clin Nutr 2000, 71; 1 Suppl: 176S-8S.
18. Chen ZY, Kwan KY, Tong KK, Ratnayake WMN, Li HQ, Leung SSF. Breast milk fatty acid composition: a comparative study between HongKong and Chongqing Chinese. Lipids 1997; 32:1061-7.
19. Fidler N and Koletzko B. The fatty acid composition of human colostrum. Eur J Nutr 2000, 39: 31-7.
20. ESPGAN Committee on Nutrition. Comment on the content and composition of lipids in infant formulas. Acta Paediatr Scand 1991;80: 887-96.
21. Crawford MA. Fatty-acid ratios in free-living and domestic animals. Lancet 1968;1: 1329-33.
22. Uauy R, Mena P, and Rojas C. Essential fatty acids in early life: structural and functional role. Proc Nutr Soc 2000,59: 3-15.
23. Neuringer M. Infant vision and retinal function in studies of dietary long-chain polyunsaturated fatty acids: methods, results, and implications. Am J Clin Nutr 2000, 71; 1 Suppl: 256S-67S.
24. Dvorak B and Stepankova R. Effects of dietary essential fatty acid deficiency on the development of the rat thymus and immune system. Prostaglandins Leukot Essent Fatty Acids 1992,46:183-90.
25. Carlson SE, Werkman SH, Peeples JM, et al. Arachidonic acid status correlates with first year growth in preterm infants. Proc Natl Acad Sci USA 1993,90:1073-7.
26. Amusquivar E, Ruperez FJ, Barbas C, et al. Low arachidonic acid rather than alpha-tocopherol is responsible for the delayed postnatal development in offspring of rats fed fish oil instead of olive oil during pregnancy and lactation. J Nutr 2000,130: 2855-65.
27. DeFronzo RA. Insulin resistance: a multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidaemia and atherosclerosis. Neth J Med 1997,50:191-7.
28. Storlien LH, James DE, Burleigh KM, et al. Fat feeding causes widespread in vivo insulin resistance, decreased energy expenditure, and obesity in rats. Am J Physiol 1986,251: E576-83.
29. Storlien LH, Jenkins AB, Chisholm DJ, et al. Influence of dietary fat composition on development of insulin resistance in rats. Relationship to muscle triglyceride and omega-3 fatty acids in muscle phospholipid. Diabetes 1991,40: 280-9.
30. Storlien LH, Kraegen EW, Chisholm DJ, et al. Fish oil prevents insulin resistance induced by high-fat feeding in rats. Science 1987,237:885-8.
31. Das UN. Beneficial effect(s) of n-3 fatty acids in cardiovascular diseases: but, why and how? Prostaglandins Leukot Essent Fatty Acids 2000, 63: 351-62.
32. Dewailly EE, Blanchet C, Gingras S, et al. Relations between n-3 fatty acid status and cardiovascular disease risk factors among Quebecers. Am J Clin Nutr 2001,74:603-11.
33. Innis SM and Kuhnlein HV. Long-chain n-3 fatty acids in breast milk of Inuit women consuming traditional foods. Early Hum Dev 1988,18:185-9.
34. Weisinger HS, Armitage JA, Sinclair AJ, et al. Perinatal omega-3 fatty acid deficiency affects blood pressure later in life. Nat Med 2001, 7: 258-9.
35. Baur LA, O'Connor J, Pan DA, Kriketos AD, Storlien LH. The fatty acid composition of skeletal muscle membrane phospholipid: its relationship with the type of feeding and plasma glucose levels in young children. Metabolism 1998,47:106-1235.
36. Persson PG, Ahlbom A, Hellers G. Crohn's disease and ulcerative colitis. A review of dietary studies with emphasis on methodologic aspects. Scand J Gastroenterol 1987:22:385-9.
37. Shoda R, Matsueda K, Yamato S, Umeda N. Epidemiologic analysis of Crohn disease in Japan: increased dietary intake of n-6 polyunsaturated fatty acids and animal protein relates to the increased incidence of Crohn disease in Japan. Am J Clin Nutr 1996;63:741-5.
38. Korotkova M, Strandvik B.: Essential fatty acid deficiency affects the fatty acid composition of the rat small intestinal and colonic mucosa differently. Biochim Biophys Acta 2000,1487 :319-25.
39. Branski D, Hurvitz H, Halevi A, Klar A, Navon P, Weidenfeld J. Eicosanoids content in small intestinal mucosa of children with celiac disease. J Pediatr Gastroenterol Nutr 1992; 14:173-6.
40. Carty E, De Brabander M, Feakins RM, Rampton DS. Mesaurement of in vivo rectal mucosal cytokine and eicosanoid production in ulcerative colitis using filter paper. Gut 2000; 46:487-92.
41. Thomson ABR, Keelan M, Garg ML, Clandinin MT. Influence of dietary fat composition on intestinal absorption in the rat. Lipids 1989; 24:494-501.
42. Campos FG, Waitzberg DL, Habr-Gama A, Logullo AF, Noronha IL, Jancar S, Torrinhas RS, Fiirst P. Impact of parenteral n-3 fatty acids on experimental acute colitis. Br J Nutr 2002; 87:suppl 1: S83-8.
43. Korotkova M.,Holmang A.,Latsson B-M.,Gabrielsson B.,Hanson L.A.,Strandvik B.Perinatal essential fatty acids affect weight blood pressure and serum insulin levels in adult rats. Pediatric Res[J],2003.53(6)suppl 5:p.17A-17A
44. Korotkova M, Ohlsson C, Gabrielsson B, Hanson LA, Strandvik B. Perinatal essential fatty acid deficiency influences body weight and bone parameters in adult male rats.Biochim Biophys Acta. 2005 Jan 5;1686 3:248-54
45. Korotkova M, Ohlsson C, Hanson LA, Strandvik B. Dietary n-6:n-3 fatty acid ratio in the perinatal period affects bone parameters in adult female rats. Br J Nutr. 2004 Oct;92(4):643-8
46. Korotkova M, Telemo E, Yamashiro Y, Hanson LA, Strandvik B. The ratio of n-6 to n-3 fatty acids in maternal diet influences the induction of neonatal immunological tolerance to ovalbumin.Clin Exp Immunol. 2004 Aug;137(2):237-44.
[1]B anerjee T D,M iddleton F,Faraone S V.Environmental risk factors for attention deficit hyperactivity disorder.Acta Paediatr,2007;96(9):1269-1274
[2]Brown RT,Freeman WS,Perrin JM,et al.Prevalence and assessment of attention2 deficit /hyperactivity disorder in primary care settings.Pediatrics,2004;114(2):511-512
[3]Marianna Mazza,Massimiliano Pomponi,Luigi Janiri.Omega-3 fatty acids and antioxidants in neurological and psychiatric diseases:An overview.Progress in Neuro-Psychopharmaeology &Biological Psychiatry 2007;31:12-26
[4]Caryl J.Antalisa,Laura J.Stevensa,Mary Campbell et al.Omega-3 fatty acid status in attention-deficit/hyperactivity disorder Prostaglandins,Leukotrienes and Essential Fatty Acids,2006;75:299-308
[5】魏宏伟,徐通.注意缺陷多动障碍与多不饱和脂肪酸关联性研究进展.中国儿童保健杂志2004;12(3):244-246
[6]A.Assisi,R.Banzi,C.Buoinocore,et al.,Fish oil and mental health:the role of n-3 long-chain polyunsaturated fatty acids in cognitive development and neurological disorders,Int.Clin.Psychopharmacol.2006;21:319-336
[7]G.Young,J.Conquer,Omega-3 fatty acids and neuropsychiatric disorders,Reprod.Nutr.Dev.2005;45:1-28
[8]J.-R.Chen,S.-F.Hsu,C.-D.Hsu,L.-H.Hwang,Y.Suh-Ching,Dietary patterns and blood fatty acid composition in children with attention-deficit hyperactivity disorder in Taiwan,J.Nutr.Biochem.2004;15:467-472
[9]Schohraya Spahis a,b,Michel Vanasse a,c,Stacey A.Be'langer,et al.Lipid profile,fatty acid composition and pro-and anti-oxidantstatus in pediatric patients with attention-deficit/hyperactivity disorder,Prostaglandins,Leukotdenes and Essential Fatty Acids 2008;79:47-53
[10].N.Sinn,Physical fatty acid deficiency signs in children with ADHD symptoms.Prostaglandins,Leukotrienes and Essential Fatty Acids,2007;77:109-115
[11]J.M.Osendarp,K.I.Baghurst,J.Bryan,et al.Effect of a twelve month micronutrient intervention on learning and memory in well-nourished and marginally nourished school-aged children:two parallel randomized,placebo-controlled studies in Australia and Indonesia,Am.J.Clin.Nutr.(in press).
[12]Yehuda S.Omega-6/Omega-3 ratio and brain related functions.World Rev Neur Diet,2003;92:37-56
[13]A.J.Richardson,P.Montgomery,The Oxford-Durham study:a randomised,controlled trial of dietary supplementation with fatty acids in children with developmental coordination disorder.Pediatrics 2005;115:1360-1366.
[14]N.Sinn,J.Bryan,Effect of supplementation with polyunsaturated fatty acids and micronutrients on ADHD-related problems with attention and behavior,J.Dev.Behav.Pediatr.2007;28:82-91.
[15]Joshi K,Lad S,Kale M,et al.Supplementation with flax oil and vitamin C improves the outcome of attention deficit hyperactivity disorder(ADHD).Prostagland Leukotri Essen Fatty Acids,2006;74:17-21
[16]Stevens L,Zhang W,Peck L,et al.EFA supplementation in children with inattention,hyperactivity and other disruptive behaviors.Lipids 2003;38:1007-1021
[17].Paul J Sorgi,Edward M Hallowell,Heather L Hutchins et al.Effects of an open-label pilot study with high-dose EPA/DHA concentrates on plasma phospholipids and behavior in children with attention deficit hyperactivity disorder.Nutrition Journal 2007;Jul 13:6-16
[18】 张丽,刘先洋,岳虹霓.注意缺陷多动障碍与长链多不饱和脂肪酸相关性探讨【J】.现代中西医结合杂志.2008;(15):2310-2311
[19】.雷晓梅,杨玉凤.注意缺陷多动障碍与多不饱和脂肪酸及神经生化因素关系的研究进展预防医学论坛.2007;13(3):241-243
[20].Voigt RG,Llorente AM,Jensen CL,etal.A randomized,double blind,placebo2controlled trial of docosahexaenoic acid supplementation in children with attention2deficit/hyperactivity disorder [J].J Pediatr 2001;139(2):189-196
[21].LUKE T.CURTIS M.D.,C.I.H.M.S.,and KALPANA PATEL,M.D..Nutritional and Environmental Approaches to Preventing and Treating Autism and Attention Deficit Hyperactivity Disorder(ADHD).THE JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE 2008;14(1):79-85
[22].A.Eilander,D.C.Hundscheid,S.J.Osendarp,C.Transler,P.L.Zock,Effects of n-3 long chain polyunsaturated fatty acid supplementationon visual and cognitive development throughout childhood:A review of human studies.Prostaglandins,Leukotrienes and Essential Fatty Acids 2007;76:189-203
[23].ALEXANDRA J.RICHARDSON,Omega-3 fatty acids in ADHD and related neurodevelopmental disorders.International Review of Psychiatry,2006;18(2):155-172
[24]Natan Gadoth.On fish oil and omega-3 supplementation in children:The role of such supplementation on attention and cognitive dysfunction.Brain & Development 2008;30:309-312
[25].Busch B.Polyunsaturated fatty acid supplementation for ADHD? Fishy,fascinating,and far from clear.Polyunsaturated Fatty Acid Supplementation for ADHD Symptoms:Response to Commentary J Dev Behav Pediatr 2007;28(2):139-144
[26]Natalie Sinn PhD,BPsych(Hons).Polyunsaturated Fatty Acid Supplementation for ADHD Symptoms:Response to Commentary.Journal of Developmental & Behavioral Pediatrics 2007;28(3):262-263
[27].MICHELE GERMANO,DOMENICO MELELEO,GIGLIOLA MONTORFANO.Plasma,red blood cells phospholipids and clinical evaluation after long chain omega-3 supplementation in children with attention deficit hyperactivity disorder(ADHD).Nutritional Neuroscience 2007;10(1/2):1-9