Vitamin K concentrations in the maternal milk of Japanese women

Aim: To determine the concentration of vitamin K including K1 (phylloquinone) and K2 (menaquinone-n; MK-n) in the maternal milk of Japanese women. Methods: We collected human milk samples from more than 4000 mothers living throughout Japan from December 1998 to September 1999, and analysed the contents of vitamin K1 and K2 in 834 of the samples. We defined as group A the 555 samples among them that met the following conditions: breast milk of mothers who were under 40 y old, not in the habit of smoking and/or using vitamin supplements, and whose babies showed no symptoms of atopy and whose birthweights were 2.5 kg or more. Vitamins extracted from the enzymatic hydrolysates of the human milk were purified with a Sep-Pak Plus silica cartridge, and then measured by a method based on high-performance liquid chromatography (HPLC) combined with coulometric reduction and fluorometric detection. Results: The mean concentration of vitamin K (K1 + K2) of mothers of group A and all groups were 0.434 ± 0.293 and 0.517 ± 1.521 μg/100 ml (average ± SD), respectively, and menaquinones containing 4, 6 and 7 isoprenoid residues could be detected in the milk samples. Vitamins K1 and MK-4 were found to be predominant in the milk samples, and the concentration of MK-4 in colostrum was higher than that of MK-4 in mature milk. We also found that the MK-7 concentration in the milk of mothers living in eastern Japan was higher than that of mothers living in western Japan.

Conclusion: The different features of vitamin K1 and MK-7 concentrations in the milk of Japanese women may be due to differences in dietary foods.     

Vitamin K in human milk--still not enough

The breastfed infant has limited sources of vitamin K, as it is transmitted poorly across the placenta and is present in very low concentrations in human milk. The author of this paper reports a concentration of vitamin K in human milk (0.517 ± 1.521 μg/dl) that is about twice the average of earlier reports (0.25 μg/dl). About half of the increased concentration (0.235 ± 0.144 μg/dl) is accounted for by vitamin K ₂ (menaquinone) rather than vitamin K ₁ (phylloquinone); the latter generally thought to be more important in human nutrition. The significance of these findings is discussed.     

Vitamin K status of lactating mothers and their infants

Vitamin K deficiency remains a world-wide problem in the newborn. Vitamin K traverses the placenta from mother to infant very poorly and is present only in very low concentrations in human milk. Thus, it is not surprising that the newborn infant has undetectable vitamin K serum levels with abnormal amounts of the coagulation proteins and undercarboxylated prothrombin. Hemorrhagic disease of the newborn, secondary to vitamin K deficiency, remains largely a disease of breastfed infants. Lactating mothers easily achieve the recommended dietary allowance for vitamin K (1 microg kg(-1) d(-1)) and the breast milk concentration is readily increased by increasing maternal vitamin K intake. Breastfed infants do not receive the recommended vitamin K intake via human milk. To prevent vitamin K deficiency in the newborn, intramuscular or oral vitamin K prophylaxis is necessary.     

Vitamin K prophylaxis and late vitamin K deficiency bleeding in infants: Fifth nationwide survey in Japan

Background: In 1980, the first nationwide survey on late vitamin K deficiency bleeding (VKDB) in infants was conducted in Japan, and it was followed by the second, third and fourth nationwide surveys in 1985, 1988 and 1991, respectively. The fifth nationwide survey was designed to ascertain the epidemiology of late VKDB between January 1999 and December 2004. Patients and methods: Questionnaires were sent to 2161 hospitals in Japan that employed members of the Japan Pediatric Society in March 2005. Responses were received from 1373 hospitals, for a response rate of 63.5%. Results: The total number of reported cases was 71, including 21 idiopathic type and 16 secondary type. The incidence of late VKDB was estimated to be 1.9 cases per 100 000 births (95% confidence interval: 1.2–3.0) during this survey period. In 34 cases, the presence or absence of any underlying disease was not clarified. A total of 67/71 infants were entirely breast‐fed. Intracranial hemorrhaging was observed in 26 (63.4%) out of 41 infants whose bleeding sites were described in the questionnaires. In 63 cases (88.7%) of late VKDB found in the present survey, however, vitamin K had been given at least once either during or after the neonatal period. Conclusions: A reevaluation of the current prophylaxis strategy for late VKDB in infants is necessary.     

Vitamin D status of mothers and their neonates in Kuwait

BACKGROUND: There has been a resurgence of nutritional rickets in children in many developing countries and some of the developed countries. Children between 6 and 18 months old are commonly affected. In order to find out the association between vitamin D and rickets we studied the vitamin D status of the neonates and their mothers in Kuwait. METHODS: Two hundred and fourteen full-term pregnant mothers and their neonates were selected from two hospitals in Kuwait. All mothers had normal vaginal delivery. On the day of delivery 2.5 mL of maternal blood and 2.5 mL of cord blood samples were withdrawn. Serum 25-hydroxyvitamin D (25OHD) was determined in duplicate by radioimmunoassay using an Incstar kit. Quality control analyses were done using several between and within run experiments. RESULTS: A total of 128 mother-neonate pairs were selected from the Al-Adan hospital and 86 from the Maternity Hospital. The mean age and parity of the mothers were similar in both hospitals. The mean (+/- SD) 25OHD levels of the mothers and the neonates in the Adan hospital were 13.3 (6.5) ng/mL and 8.2 (6.5) ng/mL, respectively. The corresponding values in the Maternity Hospital were 17.6 (12.4) and 8.1 (7.3) ng/mL for the mothers and the neonate, respectively. Serum 25OHD of the mothers and their newborn infants were highly correlated (r = 0.790, P < 0.001). CONCLUSIONS: Results demonstrate that 40% of the mothers and 60% of the neonates are vitamin D deficient on the day of delivery. The vitamin D of the mothers and neonates are highly correlated (r = 0.790, P < 0.001).     

Vitamin K-Dependent Coagulation Parameters During the First Six Days of Life: Incidence of PIVKA II in Newborns

The vitamin K-dependent carboxylation of the prothrombin precursor PIVKA II (protein induced by vitamin K absence analogous to Factor II) is essential for the synthesis of prothrombin. The noncarboxylated precursor is found in peripheral blood in the presence of vitamin K deficiency. In this study prothrombin time, Factor II and Factor VII activity, and PIVKA II were investigated in 57 newborns without vitamin K prophylaxis in order to assess their vitamin K status. Two-dimensional Immunoelectrophoresis demonstrated the presence of PIVKA II in 21% of the newborns, predominantly on the second day. The PIVKA-II positive group showed significantly lower prothrombin times than the PIVKA II-negative group. An oral dose of 3 mg vitamin K (Konakion®) was administered to 35 healthy newborns in a second group with the first feeding. On the second day of life, these infants showed significantly higher vitamin K-dependent laboratory parameters than the group not given vitamin K; only 9% of the treated infants were positive for PIVKA II.     

Iodine status of breastfed infants and their mothers' breast milk iodine concentration

Iodine is an essential nutrient for growth and development during infancy. Data on iodine status of exclusively (EBF) and partially breastfed (PBF) infants as well as breast milk iodine concentration (BMIC) are scarce. We aimed to assess (a) infant iodine nutrition at the age of 5.5 months by measuring urinary iodine concentration (UIC) in EBF (n = 32) and PBF (n = 28) infants and (b) mothers' breast milk iodine concentration (n = 57). Sixty mother–infant pairs from three primary health care centres in Reykjavik and vicinities provided urine and breast milk samples for iodine analysis and information on mothers' habitual diet. The mother–infant pairs were participants of the IceAge2 study, which focuses on factors contributing to infant growth and development, including body composition and breast‐milk energy content. The median (25th–75th percentiles) UIC was 152 (79–239) μg/L, with no significant difference between EBF and PBF infants. The estimated median iodine intake ranged from 52 to 86 μg/day, based on urinary data (assuming an average urine volume of 300–500 ml/day and UIC from the present study). The median (25th–75th percentiles) BMIC was 84 (48–114) μg/L. It is difficult to conclude whether iodine status is adequate in the present study, as no ranges for median UIC reflecting optimal iodine nutrition exist for infants. However, the results add important information to the relatively sparse literature on UIC, BMIC, and iodine intake of breastfed infants.     

Vitamin K status of lactating mothers, human milk, and breast-feeding infants

Hemorrhagic disease of the newborn is a disease of breast-feeding newborns. There is little information on longitudinal breast milk concentrations of phylloquinone (vitamin K1) or the effects of maternal phylloquinone supplements on breast milk. In study part 1, 11 lactating mothers, who received 20 mg of phylloquinone orally, had rises in plasma (less than 1 to 64.2 +/- 31.5 ng/mL by 6 hours) and breast milk concentrations (from 1.11 +/- 0.82 to 130 +/- 188 ng/mL by 12 hours). In part 2, 23 lactating mothers and their infants were observed longitudinally along with a formula-fed control group of infants (n = 11). Mean breast milk concentrations of phylloquinone at 1, 6, 12, and 26 weeks were 0.64 +/- 0.43, 0.86 +/- 0.52, 1.14 +/- 0.72, and 0.87 +/- 0.50 ng/mL, respectively, in the infants fed human milk. Maternal phylloquinone intakes (72-hour dietary recalls) exceeded the recommended daily allowance of 1 microgram/kg per day. Infant phylloquinone intakes did not achieve the recommended daily allowance of 1 microgram/kg per day in any infant. Plasma phylloquinone concentrations in the infants fed human milk remained extremely low (mean less than 0.25 ng/mL) throughout the first 6 months of life compared with the formula-fed infants (4.39 to 5.99 ng/mL). In this small sample, no infant demonstrated overt vitamin K deficiency. Despite very low plasma phylloquinone concentrations, vitamin K supplements (other than in the immediate newborn period) cannot be recommended for exclusively breast-fed infants based on these data.     

Vitamin K status in cystic fibrosis

Appearance of PIVKA-II (protein induced by vitamin K absence-II) in serum is a biochemical sign of insufficient vitamin K-dependent carboxylation of prothrombin. Plasma concentrations of PIVKA-II and vitamin K1 were determined in 24 children with cystic fibrosis. Eight were supplemented with vitamin K1. The purpose of the study was to determine the occurrence of vitamin K deficiency in cystic fibrosis and to evaluate the effect of vitamin K supplementation. PIVKA-II was detectable in only one unsupplemented child. In this patient, the concentration of vitamin K1 was below the limit of detection of 60 ng/l. Vitamin K1 levels in the other unsupplemented children were normal (mean 476 ng/l = 1 mmol/l). The supplemented patients showed extremely high levels of vitamin K1 (mean 22445 ng/l = 50 nmol/l). In conclusion, vitamin K deficiency occurs infrequently in cystic fibrosis. Checking the coagulation system is advised, but routine vitamin K supplementation is not recommended. If additional vitamin K is needed, the starting dose should not exceed 1 mg daily.     

早产母乳营养成分的分析

目的 探讨早产儿母亲乳汁营养成分的特点及动态变化。方法 收集2012 年11 月至2014 年1月在北京协和医院产科分娩产妇170 人的母乳339 份,用MIRIS 母乳分析仪检测母乳中宏量营养素及能量,比较各组母乳营养成分的差异。结果 （1）早产母乳中蛋白质含量：初乳> 过渡乳> 成熟乳（2.22±0.49 g/dL vs1.83±0.39 g/dL vs 1.40±0.28 g/dL;PPPPP+1~33+6 周组（2.11±0.25 g/dL）和≥ 34 周组（2.22±0.39 g/dL）比较差异有统计学意义（P+1~33+6 周（51±6 kcal/dL vs 58±8 kcal/dL,P+1~33+6 周组和≥ 34 周组（P+1~33+6 周成熟乳蛋白质显著高于≤ 30 周和≥ 34 周组（P结论 （1）早产初乳、过渡乳和成熟乳营养成分差异显著;（2）早产初乳蛋白质显著高于足月初乳,这种差异未能持续到成熟乳阶段;（3）不同孕周早产产妇母乳营养成分亦存在差异,以适应不同胎龄早产儿的营养需要。     

Use of Serum Iron Status and Hemoglobin A2 Levels for Discrimination Between Iron Deficiency and Thalassemia Minor

The vitamin K-dependent carboxylation of the prothrombin precursor PIVKA II (protein induced by vitamin K absence analogous to Factor II) is essential for the synthesis of prothrombin. The noncarboxylated precursor is found in peripheral blood in the presence of vitamin K deficiency. In this study prothrombin time, Factor II and Factor VII activity, and PIVKA II were investigated in 57 newborns without vitamin K prophylaxis in order to assess their vitamin K status. Two-dimensional Immunoelectrophoresis demonstrated the presence of PIVKA II in 21% of the newborns, predominantly on the second day. The PIVKA-II positive group showed significantly lower prothrombin times than the PIVKA II-negative group. An oral dose of 3 mg vitamin K (Konakion®) was administered to 35 healthy newborns in a second group with the first feeding. On the second day of life, these infants showed significantly higher vitamin K-dependent laboratory parameters than the group not given vitamin K; only 9% of the treated infants were positive for PIVKA II.     

The composition of polyunsaturated fatty acids in erythrocytes of lactating mothers and their infants

Long-chain polyunsaturated fatty acids (LCPUFA) in breastmilk, specifically docosahexaenoic acid (DHA), are important for infant brain development. Accretion of DHA in the infant brain is dependent on DHA-status, intake and metabolism. The aim of this study was to describe changes in maternal and infant erythrocyte (RBC) DHA-status during the first four months of lactation. We examined 17 mothers and their term infants at 1, 2 and 4 months of age. Milk samples and RBC from the mothers and infants were obtained and analysed for fatty acid composition. Comparative analysis of the results showed that the content of DHA in maternal RBC-phosphatidylcholine (PE) decreased over the four month period and this was not accompanied by a decrease in DHA in infant RBC-PE (P = 0.005). The ratio of n-6 PUFA to n-3 PUFA increased over time in maternal RBC-PE, but not in infant RBC-PE (P < 0.001). The level of 22:5n-6 and the ratio of LCPUFA to precursor PUFAs in infant RBC was higher than in maternal RBC phospholipids. (P = and P < 0.001 respectively). We found a decrease in the level of LCPUFA in milk, specifically AA. However, we did not observe a significant decrease in milk DHA, which may have been due to two outliers. These results indicate better DHA-status and a higher n-3/n-6 PUFA in RBC of infants than in mothers. Whether these differences reflect preferential n-3 PUFA transfer via breastmilk or differences in PUFA-metabolism and utilization remains to be shown.     

低体重早产儿维生素K缺乏与脑室出血的关系

目的　研究低体重早产儿维生素K缺乏状况及其与脑室出血的相关性。方法　采用酶联免疫吸附法 (ELISA)检测 5 4例孕周 <34周、体质量 90 4～ 2 15 7g早产儿静脉血凝血酶原前体蛋白 (PIVKA Ⅱ ) ,并于生后3～ 5d行头颅B超检查 ,诊断有无脑室出血。结果　PIVKA Ⅱ阳性 17例 ,低体重早产儿维生素K缺乏发生率为 31.5 % (17/ 5 4 ) ,低体重早产儿脑室出血发生率为 4 8.7% (19/ 39) ,维生素K缺乏并脑室出血 4例 ,其中重度脑室出血 3例。窒息、低出生体重是主要致病因素。结论　低体重早产儿存在维生素K缺乏 ,相当一部分早产儿存在脑室出血 ,维生素K缺乏虽不是脑室出血的主要致病因素 ,但其他致病因素也可能加重脑室出血的严重程度 ,应予重视     

Vitamin K in preterm breastmilk with maternal supplementation

Six healthy lactating mothers who gave birth to preterm infants at a median post conceptional age of 29.5 (range 26-30) weeks were given 2.5 mg phylloquinone (vitamin K1) orally daily for 2 weeks beginning at a median postconceptional age of 31.5 (range 28–32) weeks. Phylloquinone was measured in the breastmilk daily for 14 d. Trough plasma phylloquinone concentrations were also determined on four occasions. Phylloquinone levels in the breastmilk increased from a baseline of 3 ± 2.3ngml^-1 to 22.6 ± 16.3 ng ml^-1 (mean ± SD) after the first dose ( p < 0:05); a gradual increase was noted until phylloquinone levels reached a plateau of 64.2 ± 31.4ng ml^-1 after the sixth daily dose.     

Adiponectin in breast milk: relation to serum adiponectin concentration in lactating mothers and their infants

Aims: The aims of the study were to determine human breast milk adiponectin concentration and to investigate its relationship with serum adiponectin concentration in lactating mothers and their infants and also to evaluate the relationship between serum adiponectin concentration and anthropometric parameters in nurses and infants. Methods: We enrolled 60 healthy term breastfed (BF) infants and their lactating mothers. Adiponectin was determined by radioimmunoassay test in serum and by enzyme‐linked immunosorbent assay test in human milk (HM). Infants’ and mothers’ anthropometric parameters were measured. Results: Median (25‰, 75‰) adiponectin concentration in HM was 9.99 (3.59, 20.52) ng/mL. Serum adiponectin concentration in infants was 60.49 (45.76, 74.24) μg/mL and in lactating mothers 21.14 (12.61, 29.66) μg/mL. Adiponectin concentration in HM correlated positively with adiponectin in mothers’ serum; r = 0.60 (p < 0.001) and in infants’ serum r = 0.37 (p = 0.015). Adiponectin in HM correlated negatively with infants’ age r = ?0.3 (p = 0.04). Infants’ serum adiponectin correlated negatively with their weight r = ?0.35 (p = 0.005), length r = ?0.35 (p = 0.006) and age r = ?0.46 (p < 0.001) and mothers’ serum adiponectin with their weight r = ?0.37 (p = 0.02) and body mass index r = ?0.45 (p = 0.004). Conclusions: The observed correlations between adiponectin in mothers, HM and BF infants may be suggestive for a metabolic link between nurses and infants through milk.     

足月儿母乳淀粉酶活性动态变化

为了解我国足月儿母乳淀粉酶活性的动态变化规律,测定40例足月顺产儿乳母不同泌乳期及一次喂奶时前、中、后段乳及母血中淀粉酶的活性。结果显示初乳中淀粉酶活性为(9772.37±1.70)IU/L;随着泌乳期的延长,淀粉酶活性逐渐下降;一次喂奶前、中、后段乳中淀粉酶的活性差异无显著性意义;母乳淀粉酶98％为唾液型淀粉酶;母乳中淀粉酶活性高于母血100倍;产妇年龄与母乳淀粉酶活性无显著性相关。提示母乳中含有丰富的淀粉酶,对母乳喂养儿的淀粉消化和潜在的抗感染作用具有积极意义,应向广大群众大力提倡母乳喂养。     

婴儿维生素K缺乏出血症临床研究

目的：探讨维生素K缺乏在新生及婴幼儿出血中的作用。方法：选择出生－6个月婴儿临床出血病例，维生素K治疗前后检测血酶原时间、部分凝血活酶时间及凝血酶原前体蛋白（PIVKA－Ⅱ）进行判断。结果：婴儿维生素K缺乏出血症88例，其中早发型16例占18．2％，典型型10例占11．4％，迟发型62例占70．4％，颅内出血占63．6％，胃肠道出血占22．7％，皮肤出血占20．5％，病列率12．5％。结论：维生素K缺乏出血症目前仍是我国婴儿发病和死亡的重要原因，严重危害婴儿生命健康，应积极有效地开展防治工作。     

Vitamin K to Neonates: Peroral versus Intramuscular Administration

ABSTRACT. In a randomized study of 300 infants, the effect of 1 mg of peroral vitamin K given at birth was compared to the same dose given as an intramuscular injection. The combined activity of coagulation factor II + VII + X taken after 48 and before 72 hours after delivery served as the primary endpoint. Prothrombin (antigen) and PIVKA II (acarboxyprothrombin) were also measured. All infants were observed for events of bleeding until discharge from the hospital, normally on the fifth day. No significant differences between the groups in any of the biochemical markers were observed. The 95% confidence limits of the differences were very narrow for all factors. No cases of bleeding were observed. We conclude that administration of 1 mg peroral vitamin K is as efficient as intramuscular administration of the same dose in the prevention of classical hemorrhagic disease of the newborn.     

Vitamin K prophylaxis and vitamin K deficiency bleeding (VKDB) in early infancy

The efficacy of vitamin K prophylaxis (1 mg im or sc, or 1-2 mg orally both given as a single dose at birth) in the prevention of vitamin K deficiency bleeding in early infancy was estimated in Germany during a 15-month period between 1988 and 1989. Cases were identified by a survey of all paediatric hospitals and population denominators by a survey of all obstetric hospitals. Response rates were 85% and 68%, respectively. Thirteen cases of vitamin K deficiency bleeding in early infancy with confirmed prophylactic states were confirmed, seven of whom had intracranial haemorrhage. The estimated efficacy of single parenteral administration of vitamin K versus no prophylaxis was 96.7% (95% confidence interval: 74-99.6%) and for single oral administration versus no prophylaxis 80.4% (9.1-95.6%). Single parenteral vitamin K prophylaxis gave substantial protection against vitamin K deficiency bleeding in early infancy. Single oral prophylaxis appeared to be less effective, although the difference was not significant, as indicated by the wide overlap of the respective 95% confidence intervals.