Visual, cognitive, and language assessments at 39 months: A follow-up study of children fed formulas containing long-chain polyunsaturated fatty acids to 1 year of age
Visual, cognitive, and language assessments at 39 months: A follow-up study of children fed formulas containing long-chain polyunsaturated fatty acids to 1 year of age
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DOI：
10.1542/peds.112.3.e177
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发表时间：
2003-09-01
期刊：
影响因子：
8
通讯作者：
Hall, RT
中科院分区：
文献类型：
--
作者：
Auestad, N;Scott, DT;Hall, RT
客观的。二十二碳六烯酸 (DHA) 和花生四烯酸 (ARA) 是母乳中发现的长链多不饱和脂肪酸，最近被添加到婴儿配方奶粉中。它们在婴儿营养中的重要性得到了认可，因为出生后第一年这些脂肪酸在大脑中的快速积累、母乳喂养儿童智力发育增强的报告以及动物模型研究中认识到 DHA 在视觉和神经系统中的生理重要性。这些考虑因素引发了临床试验，以评估补充 DHA 或同时补充 DHA 和 ARA 的婴儿配方奶粉是否会增强视觉和认知发育，或者婴儿配方奶粉中亚油酸和 α-亚麻酸（ARA 和 DHA 的必需脂肪酸前体）的转化是否足以支持充分的视觉和认知发育。在一些研究中，补充 DHA 或同时添加 DHA 和 ARA 的研究报告了在配方奶粉中添加 DHA 或 DHA 和 ARA 的好处，但视觉和认知发育并没有不同。首批试验之一是对喂养补充 DHA 或 DHA 和 ARA 的配方奶粉的足月婴儿进行生长、视力（视觉诱发电位；视力卡程序）、智力和运动发育（贝利婴儿发育量表）和早期语言发育（麦克阿瑟交际发育量表）的评估。 3个配方奶粉组之间或母乳喂养和配方奶喂养婴儿在一岁内的生长、视力、智力和运动发育没有差异。 14 个月大时，喂食含有 DHA 但不含 ARA 的配方奶粉的婴儿的词汇量和理解力得分分别低于喂食未补充对照配方奶粉或母乳喂养的婴儿。本后续研究评估了原始试验儿童在 39 个月大时的智商、接受性和表达性词汇、视觉运动功能和视力。方法。婴儿在出生后 1 周内随机分组，喂养对照配方奶粉 (n = 65)、含有 DHA 的配方奶粉 (n = 65) 或同时含有 ARA 和 DHA 的配方奶粉 (n = 66) 至 1 岁。对照组 (n = 80) 纯母乳喂养至少 3 个月，此后婴儿继续纯母乳喂养或补充婴儿配方奶粉和/或断奶。 39 个月时，进行了智商（斯坦福比奈智商）、接受性词汇（皮博迪图片词汇测试修订版）、表达性词汇（平均话语长度）、视觉运动功能（Beery 视觉运动指数）和视敏度（视力卡程序）的标准测试。还评估了生长、红细胞脂肪酸水平和发病率。结果。使用方差分析或线性回归模型对结果进行分析。智商、接受性和表达性语言以及视觉运动指数的回归模型控制了地点、出生体重、性别、母亲教育程度、母亲年龄和测试时孩子的年龄。视力回归模型仅针对站点进行控制。变量选择模型还确定了不同类别（喂养群体、儿童和家庭人口统计、出生后疾病指标和环境）中 22 个潜在预后变量中的哪一个对智商和表达词汇影响最大。在 197 名 12 个月大的婴儿中，共有 157 名 (80%) 参与了这项后续研究。这些家庭的特征代表了有 5 岁以下儿童的美国家庭，并且随机配方奶粉组之间的人口或家庭特征没有差异。正如预期的那样，配方奶喂养组和母乳喂养组在种族、婚姻状况、父母教育程度和吸烟率方面存在差异。参与研究的人与未参与研究的人在性别、种族、出生孕龄和 39 个月时的出生体重方面没有差异。参与的孩子 12 个月的贝利心理和运动得分以及 14 个月的词汇得分也与未参与的孩子没有差异。 39 个月时，3 个随机配方奶粉组之间或母乳喂养组和配方奶粉组之间的智商、接受性和表达性语言、视觉运动功能和视力没有差异。对照组、ARA + DHA、DHA 和母乳喂养组的调整后平均值如下： IQ 得分，104、101、100、106；皮博迪图片词汇测试，99.2、97.2、95.1、97.4；平均话语长度，3.64、3.75、3.93、4.08；视觉运动指数，2.26、2.24、2.05、2.40；视力（周期/度）分别为30.4、27.9、27.5、28.6。智商与女性性别和母亲教育呈正相关，与兄弟姐妹的数量以及子宫内和/或产后吸烟暴露呈负相关。表达性语言还与母亲教育呈正相关，与每周平均育儿时间和出生后住院时间呈负相关，但仅当母乳喂养组纳入分析时才如此。母亲教育与儿童智商分数之间的关联与之前的报告一致，产前接触香烟烟雾与智商和早期语言发展之间的关联也是如此。大约三分之一的智商差异是由性别、母亲教育程度、兄弟姐妹数量和接触香烟烟雾造成的。各组的生长成绩、红细胞脂肪酸水平和发病率没有差异。结论。我们之前报道过，在 12 个月内喂养未补充配方奶粉或含 DHA 或同时含 DHA 和 ARA 的婴儿或母乳喂养的婴儿在智力和运动发育方面没有表现出差异，但与喂养未补充配方奶粉或母乳喂养的婴儿相比，喂养不含 ARA 的 DHA 的婴儿在 14 个月大时在标准化家长报告工具上的词汇得分较低。当婴儿在 39 个月大时使用适合年龄的接受性和表达性语言测试以及智商、视觉运动功能和视力重新评估时，发现配方奶组之间或配方奶组和母乳喂养组之间没有差异。因此，14 个月的观察可能是补充 DHA（不含 ARA）对早期词汇发展的短暂影响，也可能是偶然发生的。生长成绩没有差异进一步证明 DHA 与或不与 ARA 均可支持足月婴儿的正常生长。总之，在婴儿配方奶粉中添加长链多不饱和脂肪酸时添加 DHA 和 ARA 可支持 39 个月内的视觉和认知发育。
Objective. Docosahexaenoic acid (DHA) and arachidonic acid (ARA) are long-chain polyunsaturated fatty acids found in breast milk and recently added to infant formulas. Their importance in infant nutrition was recognized by the rapid accretion of these fatty acids in the brain during the first postnatal year, reports of enhanced intellectual development in breastfed children, and recognition of the physiologic importance of DHA in visual and neural systems from studies in animal models. These considerations led to clinical trials to evaluate whether infant formulas that are supplemented with DHA or both DHA and ARA would enhance visual and cognitive development or whether conversion of linoleic acid and alpha-linolenic acid, the essential fatty acid precursors of ARA and DHA, respectively, at the levels found in infant formulas is sufficient to support adequately visual and cognitive development. Visual and cognitive development were not different with supplementation in some studies, whereas other studies reported benefits of adding DHA or both DHA and ARA to formula. One of the first trials with term infants that were fed formula supplemented with DHA or both DHA and ARA evaluated growth, visual acuity ( Visual Evoked Potential; Acuity Card Procedure), mental and motor development (Bayley Scales of Infant Development), and early language development (MacArthur Communicative Developmental Inventories). Growth, visual acuity, and mental and motor development were not different among the 3 formula groups or between the breastfed and formula-fed infants in the first year of life. At 14 months of age, infants who were fed the formula with DHA but no ARA had lower vocabulary production and comprehension scores than infants who were fed the unsupplemented control formula or who were breastfed, respectively. The present follow-up study evaluated IQ, receptive and expressive vocabulary, visual-motor function, and visual acuity of children from the original trial when they reached 39 months of age.Methods. Infants were randomized within 1 week after birth and fed a control formula (n = 65), one containing DHA ( n = 65), or one containing both ARA and DHA ( n = 66) to 1 year of age. A comparison group ( n = 80) was exclusively breastfed for at least 3 months after which the infants continued to be exclusively breastfed or were supplemented with and/or weaned to infant formula. At 39 months, standard tests of IQ ( Stanford Binet IQ), receptive vocabulary (Peabody Picture Vocabulary Test-Revised), expressive vocabulary ( mean length of utterance), visual-motor function ( Beery Visual-Motor Index), and visual acuity ( Acuity Card Procedure) were administered. Growth, red blood cell fatty acid levels, and morbidity also were evaluated.Results. Results were analyzed using analysis of variance or linear regression models. The regression model for IQ, receptive and expressive language, and the visual-motor index controlled for site, birth weight, sex, maternal education, maternal age, and the child's age at testing. The regression model for visual acuity controlled for site only. A variable selection model also identified which of 22 potentially prognostic variables among different categories ( feeding groups, the child and family demographics, indicators of illness since birth, and environment) were most influential for IQ and expressive vocabulary. A total of 157 (80%) of the 197 infants studied at 12 months participated in this follow-up study. Characteristics of the families were representative of US families with children up to 5 years of age, and there were no differences in the demographic or family characteristics among the randomized formula groups. As expected, the formula and breastfed groups differed in ethnicity, marital status, parental education, and the prevalence of smoking. Sex, ethnicity, gestational age at birth, and birth weight for those who participated at 39 months did not differ from those who did not. The 12-month Bayley mental and motor scores and 14-month vocabulary scores of the children who participated also were not different from those who did not. At 39 months, IQ, receptive and expressive language, visual-motor function, and visual acuity were not different among the 3 randomized formula groups or between the breastfed and formula groups. The adjusted means for the control, ARA + DHA, DHA, and breastfed groups were as follows: IQ scores, 104, 101, 100, 106; Peabody Picture Vocabulary Test, 99.2, 97.2, 95.1, 97.4; mean length of utterance, 3.64, 3.75, 3.93, 4.08; the visual-motor index, 2.26, 2.24, 2.05, 2.40; and visual acuity (cycles/degree), 30.4, 27.9, 27.5, 28.6, respectively. IQ was positively associated with female sex and maternal education and negatively associated with the number of siblings and exposure to cigarette smoking in utero and/or postnatally. Expressive language also was positively associated with maternal education and negatively associated with the average hours in child care per week and hospitalizations since birth but only when the breastfed group was included in the analysis. The associations between maternal education and child IQ scores are consistent with previous reports as are the associations between prenatal exposure to cigarette smoke and IQ and early language development. Approximately one third of the variance for IQ was explained by sex, maternal education, the number of siblings, and exposure to cigarette smoke. Growth achievement, red blood cell fatty acid levels, and morbidity did not differ among groups.Conclusions. We reported previously that infants who were fed an unsupplemented formula or one with DHA or with both DHA and ARA through 12 months or were breastfed showed no differences in mental and motor development, but those who were fed DHA without ARA had lower vocabulary scores on a standardized, parent-report instrument at 14 months of age when compared with infants who were fed the unsupplemented formula or who were breastfed. When the infants were reassessed at 39 months using age-appropriate tests of receptive and expressive language as well as IQ, visual-motor function and visual acuity, no differences among the formula groups or between the formula and breastfed groups were found. The 14-month observation thus may have been a transient effect of DHA ( without ARA) supplementation on early vocabulary development or may have occurred by chance. The absence of differences in growth achievement adds to the evidence that DHA with or without ARA supports normal growth in full-term infants. In conclusion, adding both DHA and ARA when supplementing infant formulas with long-chain polyunsaturated fatty acids supports visual and cognitive development through 39 months.