Fat-soluble vitamins in breast-fed preterm and term infants.

OBJECTIVE: To examine the supply and status of fat-soluble vitamins in very low birth weight (VLBW) infants compared to a reference group of normal birth weight (NBW) infants. DESIGN: A longitudinal study of VLBW infants in the early neonatal period. Blood samples were drawn at 1 week of age and at discharge from hospital. Plasma was analyzed for the fat-soluble vitamins: retinol, 25-OH-vitamin D, alpha-tocopherol and phylloquinone (vitamin K(1)) using high-performance liquid chromatography. SUBJECTS: A total of 40 VLBW infants were included in the study. A reference group of 33 NBW infants was randomly selected from one of our previous studies. RESULTS: The VLBW infants received fortified human milk, and daily oral vitamin supplement (Multibionta). In VLBW infants, plasma retinol concentrations decreased and plasma 25-OH-vitamin D increased during the study period. VLBW infants had significantly lower plasma retinol (0.3 vs 0.7 mu M) and higher plasma 25-OH-vitamin D (166 vs 25 nM) at discharge compared to NBW infants. Plasma phylloquinone concentration in VLBW infants was very high (53 ng/ml) at one week of age, especially in the youngest infants (192 ng/ml), but decreased rapidly during the study period resulting in low/normal plasma concentrations (0.9 ng/ml) at discharge. CONCLUSIONS: We observed alterations in plasma concentration of retinol and 25-OH-vitamin D in VLBW infants in the early neonatal period, resulting in marked differences between VLBW at discharge and NBW. Further trials are needed to evaluate whether changes in vitamin supplementation may improve clinical outcome in VLBW infants.

Fatty acid composition in maternal milk and plasma during supplementation with cod liver oil.

OBJECTIVE: We investigated how cod liver oil influences the amount of essential fatty acids in mothers' breast milk. DESIGN AND INTERVENTION: Lactating mothers (n =22) were randomized into four groups 3-8 weeks after parturition. They were supplemented for 14 days with 0, 2.5, 5 and 10 ml cod liver oil (7.7 g eicosapentaenoic acid (EPA, 20:5n-3), 10.2 g docosahexaenoic acid (DHA, 22:6n-3) and 22.9 g n-3 fatty acids in total per 100 ml). RESULTS: In maternal plasma phospholipids there was an increase in the content of EPA and DHA in the group supplemented with 10 ml cod liver oil daily (P < or = 0.05). DHA concentrations in breast milk pre-supplementation ranged from 0.15 to 1.56 wt% and increased in all supplemented groups (P< or =0.05). The concentration of EPA in breast milk increased in the groups supplemented with 5 or 10 ml cod liver oil (P< or =0.05), whereas the concentration of arachidonic acid (AA, 20:4n-6) did not change in any of the supplemented groups. Total intake of DHA adjusted to body mass index (BMI), correlated to DHA concentrations in plasma (r = 0.49, P = 0.02) and breast milk (r = 0.45, P = 0.04). The concentration of tocopherol did not change during the supplementation period, neither in plasma nor in breast milk. CONCLUSION: Dietary intake of DHA is reflected in the concentration of DHA in breast milk, without affecting the concentration of AA or tocopherol.

Addition of both platelets and thrombin in combination accelerates tumor cells to adhere to endothelial cells in vitro.

Platelets and coagulation are involved in the pathogenesis of blood-borne metastases. The aim of this study is to obtain more information about the mechanisms involved in the initial adhesion of tumor cells to endothelial cells. In short term experiments with tumor cells, suspended in the medium of cultured endothelial cells, we tested whether addition of both platelets and thrombin cause more tumor cell adhesion to endothelial cells, than when either platelets or thrombin are acting alone. HeLa cells or HT29 cells, prelabeled with radioactive 51Cr, human platelets, and thrombin were added to human endothelial cell cultures. Following 15 min of shaking at 37 degrees C, the percentage of tumor cell adhesion was calculated. The percentages of adhering tumor cells with the presence of both platelets and thrombin were greatly increased compared to controls. Addition of hirudin 2 min before thrombin lowered the adhesion percentage of tumor cells. Hirudin added immediately before and 2 min after thrombin gave only minor effects. When the endothelium was treated with superoxide dismutase, catalase, and mannitol, the adhesion of tumor cells was lowered with catalase and superoxide dismutase. The cause of tumor cell-endothelial cell interaction is probably complex. Our results show that activated platelets enhance the tumor cell adhesion, and that generation of active oxygen species may be important in the initial phase of the interaction.

Leptin levels in pregnant women and newborn infants: gender differences and reduction during the neonatal period.

OBJECTIVE: Leptin is a highly hydrophilic protein that circulates in plasma as a 16-kDa protein. It is produced in adipose tissue and also recently described to be synthesized by placental tissue. Plasma concentration of leptin is positively correlated to body fat mass, and administration of recombinant leptin to mice indicates that leptin participates in the regulation of food intake and energy expenditure. Leptin may have a role during initiation of human pubertal development. Gender differences have been reported among adults as well as among children, even after correction for body fat content. Little is known about variation in leptin levels during pregnancy or the level or function of leptin in the growing fetus and infants. The aim of the present study was to examine plasma concentration of leptin in pregnant women and their newborn infants during the first 3 months of life, and to relate plasma leptin concentration to body weight and gender during this period. MATERIALS AND METHODS: Among 609 women recruited to study the effect of very long-chain n-3 fatty acids during pregnancy, 180 women were selected to study leptin as well. The women were all healthy and nulli- or primiparas, and 16% were smokers. The study was randomized and double-blinded, and the participants received either 10 mL of cod liver oil (Peter Moller, avd.av Orkla ASA, Oslo, Norway) daily or the same amount of corn oil. Blood samples were taken from the mothers during pregnancy in weeks 18 and 35, and from the umbilical cord and from 4- and 14-week-old infants. The mothers' body mass index (BMI) at 18 and 35 weeks of pregnancy was calculated by using body weight recorded within 1 week or, if this was missing, by using means from weights at the closest time points before and after the sampling. The infants were weighed and measured at local health care centers. Plasma leptin concentration was measured by radio immunoassay (Linco Research, St Charles, MO) using recombinant 125I-leptin as tracer. RESULTS: We found no differences between the group receiving cod liver oil and the group receiving corn oil in any of the measured variables; thus, the groups are treated statistically as one. Leptin concentration in maternal plasma increased during pregnancy from 15.5 +/- 9.0 microg/L (n = 175) in week 18 to 17.7 +/- 10.7 microg/L (n = 166) in week 35. Mothers, pregnant with female fetuses (n = 77), had a significant increase in plasma leptin concentration, from 15.5 +/- 8.8 microg/L (n = 83) at 18 weeks to 18.5 +/- 10.9 microg/L (n = 80) at 35 weeks of pregnancy, whereas in mothers pregnant with male fetuses, the increase was insignificant (15.4 +/- 9.3 microg/L (n = 92) to 17.0 +/- 10.5 microg/L (n = 86). BMI increased during the same time period, from 24.2 +/- 3.3 kg/m to 27.8 +/- 3.8 kg/m (n = 174). There was a significant correlation between BMI and plasma leptin concentration at 18 weeks (r = 0.54, n = 169) and at 35 weeks (r = 0.45, n = 160), but we found no change in the relative leptin concentration (plasma leptin concentration/BMI) from week 18 to week 35. We found no significant difference between smokers and nonsmokers in plasma leptin concentration, neither at 18 nor 35 weeks of pregnancy. Gender differences in plasma leptin concentration was present already at birth in umbilical cord plasma (10.8 +/- 9.2 microg/L for girls [n = 65] vs 7.6 +/- 6.6 microg/L for boys [n = 74]). We also observed gender differences in plasma leptin concentration at 4 weeks (3.9 +/- 1.8 microg/L, n = 68 vs 3.2 +/- 1.8 microg/L, n = 71) and 14 weeks of age (4.9 +/- 2.1 microg/L, n = 61 vs 4.1 +/- 3.1 microg/L, n = 73). Plasma leptin levels at 4 and 14 weeks were lower than the level in umbilical cord plasma (n = 101). An increase in plasma leptin concentration was observed from 4 to 14 weeks of age, both for girls (n = 48) and for boys (n = 60). Leptin concentration in umbilical cord plasma correlated with birth weight (r = 0.44, n = 139), and there was significant corre

Smoking related to plasma leptin concentration in pregnant women and their newborn infants.

UNLABELLED: Leptin, a hormone produced in adipose tissue and placenta, is potentially important in relation to energy metabolism and growth. We investigated the effect of cigarette smoking on maternal plasma leptin concentration during pregnancy, and on plasma leptin concentration and weight among infants up to 13 wk of age. Plasma leptin concentration was measured in women in week 18 (n = 203) and week 35 (n = 164) of pregnancy, while cotinine (nicotine metabolite) was measured in plasma sampled from mothers in week 35 of pregnancy (n = 159). Leptin concentration was also measured in plasma from the umbilical cord (n = 133) and from 4-wk-old (n = 129) and 13-wk-old (n = 130) infants. There was no difference in plasma leptin concentration between smoking and non-smoking mothers at 18 wk and at 35 wk of pregnancy. Plasma cotinine concentration was higher in smoking than in non-smoking mothers, and a negative correlation between plasma cotinine and leptin concentrations was found. The leptin concentrations in umbilical cord plasma were similar, although the birthweights of newborns from smoking mothers were significantly lower than those from non-smoking mothers. The plasma leptin concentrations were similar between the two groups also at 4 wk of age. At 13 wk of age, infants of smoking mothers had significantly higher plasma leptin concentrations than infants of non-smoking mothers. CONCLUSION: Our results indicate that a lower birthweight of neonates among smoking mothers is not due to altered plasma leptin concentration.

Similar effects on infants of n-3 and n-6 fatty acids supplementation to pregnant and lactating women.

OBJECTIVE: There have been indications that high intake of n-3 long-chain polyunsaturated fatty acids (PUFAs) during pregnancy may increase birth weight and gestational length. In addition, n-3 long-chain PUFAs may be important for the neurobiological development of the infants. High levels of docosahexaenoic acid (DHA, 22:6 n-3) are found in the gray matter of the cerebral cortex and in the retina, and it seems as if the availability of long-chain PUFAs may be limiting cerebral development. The fetus and the newborn are dependent on a high supply from their mothers, either via the placenta or via breast milk. We supplemented pregnant and lactating women with n-3 or n-6 long-chain PUFAs to evaluate the effect on birth weight, gestational length, and infant development. DESIGN: We performed a double-blind, randomized study recruiting 590 pregnant, healthy, nulli- or primiparous women (19-35 years old) in weeks 17 to 19 of pregnancy. The women were provided 10 mL of either cod liver oil or corn oil daily until 3 months after delivery. MAIN OUTCOME MEASURES: Primary outcomes were gestational length and birth weight. Electroencephalography (EEG) was done on the second day of life and at 3 months of age. Novelty preference (Fagan test) was used as an indicator of cognitive function at 6 and 9 months of age. The fatty acid pattern in umbilical plasma phospholipids and in breast milk was measured, and dietary assessments were performed, both on the mothers during pregnancy and on the infants at 3 months of age. The growth of the infants was followed up to 1 year of age. RESULTS: Three hundred forty-one mothers took part in the study until delivery. There were no significant differences in maternal body mass index before pregnancy and at birth, or parity between the 2 groups. Smoking habits and parental education were also similar in the 2 groups. The mean age of the mothers receiving cod liver oil was, by chance, 1 year higher than the age of the mothers receiving corn oil (28.6 [3.4] vs 27.6 [3.2] years). The maternal dietary intake in the 2 groups receiving cod liver oil or corn oil was similar, except for the supplementation. There were no differences in gestational length or birth weight between the cod liver oil group and the corn oil group (279.6 [9.2] vs 279.2 [9.3] days; 3609 [493] vs 3618 [527] g, respectively). Birth length, head circumference, and placental weight were also similar in the 2 groups. The concentrations of the n-3 fatty acids eicosapentaenoic acid (20:5 n-3), docosapentaenoic acid (22:5 n-3), and DHA in umbilical plasma phospholipids were higher in the cod liver oil group compared with the corn oil group (10.8 [7.6] vs 2.5 [1.8] microg/mL, 5.0 [2.6] vs 2.9 [1.3] microg/mL, 55.8 [20.6] vs 45.3 [12.8] microg/mL, respectively). Neonates with high concentration of DHA in umbilical plasma phospholipids (upper quartile) had longer gestational length than neonates with low concentration (lower quartile; 282.5 [8.5] vs 275.4 [9.3] days). No differences in EEG scores or Fagan scores were found, but neonates with mature EEG (N = 70) had a higher concentration of DHA in umbilical plasma phospholipids than neonates with immature EEG (N = 51) on the second day of life. Dietary information from 251 infants at 3 months of age was collected and 85% of these infants were exclusively breastfed, in addition to 12% who were partly breastfed. The breast milk of mothers supplemented with cod liver oil contained more n-3 long-chain PUFAs and less n-6 long-chain PUFAs than breast milk of mothers supplemented with corn oil. There were no significant differences in infant growth during the first year of life between the 2 groups. CONCLUSIONS: This study shows neither harmful nor beneficial effects of maternal supplementation of long-chain n-3 PUFAs regarding pregnancy outcome, cognitive development, or growth, as compared with supplementation with n-6 fatty acids. However, it confirms that DHA concentration may be related to gestational length and cerebral maturation of the newborn.