A modified vitamin regimen for vitamin B2, A, and E administration in very-low-birth-weight infants

INTRODUCTION: Very-low-birth-weight (VLBW; birth weight, <1,500 g) infants receive preterm infant formulas and parenteral multivitamin preparations that provide more riboflavin (vitamin B2) than does human milk and more than that recommended by the American Society of Clinical Nutrition. VLBW infants who are not breast-fed may have plasma riboflavin concentrations up to 50 times higher than those in cord blood. The authors examined a vitamin regimen designed to reduce daily riboflavin intake, with the hypothesis that this new regimen would result in lower plasma riboflavin concentrations while maintaining lipid-soluble vitamin levels. METHODS: Preterm infants with birth weight < or =1,000 g received either standard preterm infant nutrition providing 0.42 to 0.75 mg riboflavin/kg/day (standard group), or a modified regimen providing 0.19 to 0.35 mg/kg/day (modified group). The modified group parenteral vitamin infusion was premixed in Intralipid. Enteral feedings were selected to meet daily riboflavin administration guidelines. Plasma riboflavin, vitamin A, and vitamin E concentrations were measured weekly by high-performance liquid chromatography. Data were analyzed with the independent t test, chi, and analysis of variance. RESULTS: The 36 infants (17 standard group, 19 modified group) had birth weight and gestational age of 779 +/- 29 g and 25.5 +/- 0.3 weeks (mean +/- SEM) with no differences between groups. Modified group infants received 38% less riboflavin (0.281 +/- 0.009 mg/kg/day), 35% more vitamin A (318.3 +/- 11.4 microg/kg/day), and 14% more vitamin E (3.17 +/- 0.14 mg/kg/day) than standard group infants. Plasma riboflavin rose from baseline in both groups but was 37% lower in the modified group during the first postnatal month (133.3 +/- 9.9 ng/mL). Riboflavin intake and plasma riboflavin concentrations were directly correlated. Plasma vitamin A (0.222 +/- 0.022 microg/mL) and vitamin E (22.26 +/- 1.61 /mL) concentrations were greater in the modified group. CONCLUSIONS: The modified vitamin regimen resulted in reduced riboflavin intake and plasma riboflavin concentration, suggesting plasma riboflavin concentration is partially dose dependent during the first postnatal month in VLBW infants. Modified group plasma vitamin A and vitamin E concentrations were greater during the first month, possibly because the vitamins were premixed with parenteral lipid emulsion. Because of the complexity of this protocol, the authors suggest that a parenteral multivitamin product designed for VLBW infants which uses weight-based dosing should be developed.     

Serum vitamin A levels in mothers and their breast-fed term infants with or without supplemental vitamin A

Serum concentrations of vitamin A were measured in term infants (n = 72) and their mothers at delivery and after 20 weeks of breast-feeding (n = 48). During the 20 weeks the infants received either no supplemental vitamin A (but the mothers were given 3,000 IU vitamin A daily) (n = 16) or a daily vitamin A supplementation of 600 (n = 17) or 1,500 IU (n = 15). After 20 weeks of breast-feeding the vitamin A levels in the unsupplemented infants were similar to those at birth. The infants supplemented either with 600 or 1,500 IU had higher vitamin A serum levels than at birth (p less than 0.01), however, there was no difference between the two supplemented groups. During lactation, the serum vitamin A concentrations of the mothers increased significantly in all groups with or without vitamin A supplementation.     

Maternal-neonatal serum vitamin A concentrations

Prevention of neonatal vitamin A deficiency is related to the adequacy of maternal vitamin A stores. In this study we investigated maternal and cord serum vitamin A and retinol-binding protein (RBP) values in an Indian population including, for the first time, clinically vitamin A-deficient mothers. Twenty-eight maternal-neonatal pairs were selected from maternal cohorts of high socioeconomic status without clinical evidence of vitamin A deficiency (group I) and low socioeconomic status with conjunctival xerosis and Bitot's spots (group II). Maternal education, caloric and vitamin A intakes, weight, height, hemoglobin, and birth weight were significantly lower in group II. Serum vitamin A levels were significantly higher in group I mothers and newborns as were RBP levels in group I mothers. However, a significant difference between groups I and II in cord blood RBP was not observed. Upon correlation of maternal vitamin A levels with cord blood vitamin A levels, a logarithmic relationship was revealed, suggesting saturable transplacental transport of vitamin A.     

Interrelationship between diarrhea and vitamin A deficiency: is vitamin A deficiency a risk factor for diarrhea?

A cross-sectional study, a follow-up study and an evaluation of impact of community-based distribution of vitamin A capsules (200,000 IU) were conducted in Omdurman (Sudan) between November, 1988, and March, 1989. In the cross-sectional survey 1441 children less than 5 years of age participated, which established the baseline values for plasma retinol-binding protein. During the follow-up period 290 cases of diarrhea occurred. Low concentrations of plasma retinol-binding protein (less than 1.85 mg/dl) proved to be a risk factor for diarrhea, especially in girls. The relative risk increased after the second year of life. Children who received vitamin A supplementation before commencement of the study had a lower incidence of diarrhea. The protective effect of vitamin A supplementation was greater in girls (relative risk, 0.297; 95% confidence interval, 0.240 to 0.368) than in boys (relative risk, 0.404; 95% confidence interval, 0.352 to 0.464).     

维生素A联合其他微量营养素干预对铁代谢稳态的影响

目的 观察维生素A、维生素A+铁和7+1多种微量营养素联合补充对学龄前儿童铁代谢稳态的影响.方法 研究为随机、互相对照、盲法现场干预试验.采用分层与整群抽样相结合的方法从该地区随机选取3所幼儿园全部226名2～7岁学龄前儿童纳入计划干预对象,分别补充100％ RNI的维生素A、维生素A+铁和“7+1”维生素A、铁、维生素B1、核黄素、叶酸、尼克酸、锌和钙.干预前后分别采用氰化高铁法测定全血中血红蛋白含量,反相高效液相色谱法( HPLC)测定血清视黄醇浓度,酶联免疫定量检测法测定血清铁蛋白(serum ferritin,SF),微粒子增强透射免疫法检测可溶性转铁蛋白受体(soluble transferrin receptor,sTfR),并计算sTfR-SF指数(TFR-F指数)及机体总铁含量;同时利用问卷方式调查这些儿童的人口学资料、社会经济状况以及饮食习惯等.结果 完成干预试验儿童共有226名,平均年龄(均数±标准差)为(4.0±0.85)岁.贫血发生率为23.5％,储铁不足发生率为15.0％,维生素A缺乏以及边缘型维生素A缺乏发生率分别是6.3％和25.9％.干预后6个月各组SF水平均较干预前下降(x2=8.3298,x2=16.1471,x=15.1371,P均＜0.01),而维生素A+铁组和“7+1”多种微量营养素组下降最为明显(x2=16.1471,x2=15.1371,P均＜0.05).干预后各组sTfR水平均出现降低(x2=15.1171,x2=5.2617,x2=4.8844,P均＜0.01),尤以维生素A组最明显(x2 =15.1171,P＜0.05);维生素A组TFR-F指数以及机体总铁含量在干预前后无明显变化(t =0.1817,t=1.7736,P均＞0.05),而维生素A+铁组和“7+1”多种微量营养素组的TFR-F指数明显下降、机体总铁含量明显增加(t=5.3561,t=6.5979,t=11.1663,t =8.7306,P均＜0.05).结论 单独维生素A补充对铁动员和铁利用均有明显影响,但对铁在肠道的吸收作用不明显;维生素A联合铁剂或“7+1”多种微量营养素的补充比单独维生素A可更好地改善学前儿童铁缺乏.     

Serum vitamin A in premature and term neonates

Serum vitamin A was determined in premature and term neonates by a specific spectrofluorometric method. Premature neonates (N = 42; gestational age = 32 +/- 0.4 weeks) had a serum vitamin A level (14.9 +/- 0.98 microgram/dl) significantly lower (P less than 0.001) than that of term neonates (N = 51; 22.4 +/- 0.99 microgram/dl). The vitamin A mean serum values of infants of 36 weeks' gestational age were not statistically different from those of the term neonates. Linear regression analysis for serum vitamin A values vs gestational age showed no significant correlation. A linear correlation (P less than 0.05), however, was found between serum vitamin A and serum protein protein concentrations, perhaps indicative of a lower concentration of retinol-binding protein. Since vitamin A is involved in the promotion of mucous-secreting cells, the premature neonate may be at greater risk than the term infant for diseases involving the mucosal epithelium, including necrotizing enterocolitis.     

Teratogenic interaction of hyperthermia and vitamin A.

Exposure of pregnant hamsters to 60--75 min of hyperthermia on the 8th day of gestation causes malformations in some of the fetuses recovered near term. The feeding of large doses of vitamin A to pregnant hamsters on the 8th day of gestation causes many of the same types of malformations. When pregnant hamsters are treated with the minimal teratogenic hyperthermic stress plus the minimal teratogenic dose of vitamin A there is a clear augmentation of the teratogenic effect on the embryo. The implication that maternal hyperthermia may be an important synergistic factor for a variety of potentially teratogenic influences during pregnancy is discussed.     

Risk of vitamin A toxicity from candy-like chewable vitamin supplements for children

Numerous vitamin supplements are available over-the-counter to the general public. Some such supplements are available as candy-like chewable preparations to encourage consumption by children. We report 3 cases of overdose of such preparations. Each patient had taken an estimated 200,000 to 300,000 IU of vitamin A. Their circulating vitamin A (retinol and retinyl palmitate) concentrations were monitored over a 6-month period. There were no clinical or biochemical complications noted. However, there were marked increases in both retinol and retinyl palmitate concentrations above age-related reference ranges. In particular, it took 1 to 3 weeks for the serum retinol concentrations to peak and many months for them to normalize. Parents should be warned about the dangers of excessive vitamin consumption. Clinicians should be aware of the late peak in serum retinol concentrations, which may lead to late complications of vitamin A overdose.     

1型糖尿病患儿血清维生素A特点及与辅助性T淋巴细胞因子水平的关联分析

目的探讨1型糖尿病(T1DM)患儿体内维生素A的代谢情况及维生素A对T1DM患儿辅助性T淋巴细胞(Th)1/Th2平衡的影响。方法选取32例T1DM患儿,并以28例健康儿童为对照组,微量荧光法检测血清维生素A水平,化学发光法、激光散射比浊法分别测定血清C-肽、糖化血红蛋白(HbA1C);在无菌条件下获取T1DM患儿以及对照儿童外周血单个核细胞(PBMC),T1DM患儿的PBMC分为维生素A干预组及未干预组2份,均体外培养48h,酶联免疫吸附(ELISA)法检测培养上清液中干扰素-γ(IFN-γ)、白介素-4(IL-4)水平变化。结果 T1DM患儿的血清维生素A水平、血清C-肽均明显低于对照组,HbA1C明显高于对照组,差异有统计学意义(P<0.01);T1DM患儿血清维生素A水平与空腹血清C-肽水平呈正相关(r=0.356,P<0.05),与HbA1C呈负相关(r=–0.394,P<0.05)。体外培养,T1DM患儿的PBMC产生IFN-γ水平高于对照组,IFN-γ/IL-4比值明显高于对照组,差异均有统计学意义(P均<0.01);T1DM患儿的PBMC经维生素A干预,产生IFN-γ水平明显低于未干预组(P<0.01),IFN-γ/IL-4比值也明显低于未干预组(P<0.01)。结论维生素A干预可能改善T1DM患儿的Th1/Th2失衡状态。