Infant Plasma Research Articles

Maternal plasma viral load and neutralizing/enhancing antibodies in vertical transmission of HIV: A non-randomized prospective study

BackgroundWe examined the association and interaction between maternal viral load and antibodies in vertical transmission of HIV in a non-randomized prospective study of 43 HIV-1 infected pregnant women who attended the San Juan City Hospital, Puerto Rico, and their 45 newborn infants. The women and infants received antiretroviral therapy.MethodsA nested PCR assay of the HIV-1 envelope V3 region and infant PBMC culture were performed to determine HIV status of the infants. Maternal and infant plasma were tested for HIV neutralization or enhancement in monocyte-derived macrophages.ResultsTwelve (26.7%) infants were positive by the HIV V3 PCR assay and 3 of the 12 were also positive by culture. There was a trend of agreement between high maternal viral load and HIV transmission by multivariate analysis (OR = 2.5, CI = 0.92, p = 0.0681). Both maternal and infant plasma significantly (p = 0.001 for both) reduced HIV replication at 10-1 dilution compared with HIV negative plasma. Infant plasma neutralized HIV (p = 0.001) at 10-2 dilution but maternal plasma lost neutralizing effect at this dilution. At 10-3 dilution both maternal and infant plasma increased virus replication above that obtained with HIV negative plasma but only the increase by maternal plasma was statistically significant (p = 0.005). There were good agreements in enhancing activity in plasma between mother-infant pairs, but there was no significant association between HIV enhancement by maternal plasma and vertical transmission.ConclusionAlthough not statistically significant, the trend of association between maternal viral load and maternal-infant transmission of HIV supports the finding that viral load is a predictor of maternal-infant transmission. Both maternal and infant plasma neutralized HIV at low dilution and enhanced virus replication at high dilution. The antiretroviral treatments that the women received and the small sample size may have contributed to the lack of association between HIV enhancement by maternal plasma and vertical transmission.

Severe Adverse Effects in a Newborn with Two Defective CYP2D6 Alleles After Exposure to Paroxetine During Late Pregnancy

Paroxetine, like other SSRIs, is reported not to increase the number of malformations in infants exposed to these drugs in utero. However, late pregnancy exposure to SSRIs sometimes leads to perinatal complications resembling the symptoms seen in serotonergic overstimulation. We report here a case of third trimester paroxetine exposure with adverse birth outcome in a newborn. The clinical symptoms in the infant included severe tremor and rigidity as well as loose stools during the first 4 days of life. Plasma paroxetine concentrations in infant plasma were quite low after birth, but she was genotyped to be a poor metabolizer of CYP2D6, the enzyme catalyzing the metabolism of paroxetine. In accordance with an earlier report, we suggest that even low plasma concentrations of paroxetine may be related to perinatal complications in infants exposed to paroxetine during late pregnancy and that the poor metabolizer genotype of CYP2D6 may be a risk factor for these complications.

Acute infections and environmental exposure to organochlorines in Inuit infants from Nunavik.

The Inuit population of Nunavik (Canada) is exposed to immunotoxic organochlorines (OCs) mainly through the consumption of fish and marine mammal fat. We investigated the effect of perinatal exposure to polychlorinated biphenyls (PCBs) and dichlorodiphenyldichloroethylene (DDE) on the incidence of acute infections in Inuit infants. We reviewed the medical charts of a cohort of 199 Inuit infants during the first 12 months of life and evaluated the incidence rates of upper and lower respiratory tract infections (URTI and LRTIs, respectively), otitis media, and gastrointestinal (GI) infections. Maternal plasma during delivery and infant plasma at 7 months of age were sampled and assayed for PCBs and DDE. Compared to rates for infants in the first quartile of exposure to PCBs (least exposed), adjusted rate ratios for infants in higher quartiles ranged between 1.09 and 1.32 for URTIs, 0.99 and 1.39 for otitis, 1.52 and 1.89 for GI infections, and 1.16 and 1.68 for LRTIs during the first 6 months of follow-up. For all infections combined, the rate ratios ranged from 1.17 to 1.27. The effect size was similar for DDE exposure but was lower for the full 12-month follow-up. Globally, most rate ratios were > 1.0, but few were statistically significant (p < 0.05). No association was found when postnatal exposure was considered. These results show a possible association between prenatal exposure to OCs and acute infections early in life in this Inuit population.

Poly chlorinated biphenyls in colostral milk and visual function at 12 months of life

Environmental contaminants such as persistent organic chlorines and heavy metals, which are supplied to the foetus by transplacental transfer and to breastfed infants by the milk, may impair cognitive functions. Long-chain polyunsaturated fatty acids, which are known to enhance development during foetal life and early infancy, may counteract the toxic effect of environmental contaminants. In this study, we have investigated whether polychlorinated biphenyls (PCBs) impair early development of vision, and whether such impairment can be modulated by essential long-chain polyunsaturated fatty acids. Healthy term infants born in Milan and its surroundings, and who were exclusively breastfed for at least 4 mo, were prospectively examined up to the age of 12 mo. Samples from colostrums, the first 2 d after delivery, and of mature breast-milk after 1 and 3 mo were collected. The samples were analyzed for PCB 105, 118, 138, 153, 156 and 180 and for DDT and DDE. In all infants, the plasma levels of the long-chain polyunsaturated fatty acids (LC-PUFAs), C18:2 n-6, C18:3 n-3, C20:4 n-6, C20:5 n-3 and C22:6 n-3 were analysed within the first three postnatal days. The PCB levels in colostral milk, as well as of LC-PUFAs in plasma, were considered to mirror perinatal supply. Visual function was evaluated by P100 with latency evoked potentials (VEPs) at 12 mo of age. Statistical analysis was based on simple and partial correlation coefficients (p < 0.05). On bivariate analysis, wave latency VEP at 15 min was significantly related to the colostral levels of DDT, DDE and all examined PCBs except PCB 105 (with correlation coefficient r = 0.401 to 0.618), whereas P100 wave latency VEP at 60 min was related to DDT (r = 0.513) and PCB 180 (r = 0.504). Infant plasma levels of C22:6 n-3 were inversely associated with P100 wave latency at 60 min (r = -0.418) and at 1Hz-2J (r = -0.466). After controlling for C22:6 n-3, the partial correlation coefficient of P100 wave latency VEP at 15 min to the colostral level of PCB 180 was 0.403 (p = 0.07). Within the population of this study, a weak relation was found between impaired visual function at 12 mo of age of healthy infants and the levels of PCBs, DDT and DDE in colostral milk. The effect of impairment was no longer evident after controlling for the plasma level of LC-PUFAs as found in the infant a few days after birth.

Pooled analysis of antidepressant levels in lactating mothers, breast milk, and nursing infants.

The available data on antidepressant levels in nursing infants were analyzed in order to calculate average infant drug levels and determine what factors influence plasma drug levels in breast-feeding infants of mothers treated with antidepressants. Electronic searches of MEDLINE, PreMEDLINE, Current Contents, Biological Abstracts, and PsycINFO from 1966 through July 2002 followed by bibliographic searches identified 67 relevant studies (two unpublished). By consensus the authors identified 57 studies of maternal plasma, breast milk, and/or infant plasma antidepressant levels from nursing mother-infant pairs, measured by liquid chromatography. Infants with recent prenatal exposure and symptomatic infants included in case reports were analyzed separately. Infant plasma levels were standardized against the average maternal level for each drug. The average infant-maternal plasma ratio was calculated for each drug, and correlations of infant plasma level to maternal dose, maternal plasma level, and breast milk level were calculated. Nortriptyline, paroxetine, and sertraline usually produce undetectable infant levels. Of drugs currently used, fluoxetine produces the highest proportion (22%) of infant levels that are elevated above 10% of the average maternal level. Based on smaller numbers, the data on citalopram indicate that it produces elevated levels in 17% of infants. The milk-to-plasma ratios for 11 antidepressants had a statistically significant negative association with the percentage of the drug bound to protein. Nortriptyline, paroxetine, and sertraline may be preferred choices in breast-feeding women. Minimizing the maternal dose may be helpful with citalopram. Current data do not support monitoring breast milk levels in individual patients. Future researchers should report maternal, breast milk, and infant antidepressant levels along with other appropriate variables.

Assessment of pre- and postnatal exposure to polychlorinated biphenyls: lessons from the Inuit Cohort Study.

Polychlorinated biphenyls (PCBs) are food-chain contaminants that have been shown to induce adverse developmental effects in humans. In the course of an epidemiologic study established to investigate neurodevelopmental deficits induced by environmental PCB exposure in the Inuit population of northern Québec (Nunavik, Canada), we compared three biomarkers of prenatal exposure and models to predict PCB plasma concentration at 6 months postpartum. Concentrations of 14 PCB congeners were measured by high-resolution gas chromatography with electron capture detection in lipids extracted from maternal plasma, cord plasma, breast milk (collected at approximately 1 month postpartum), and 6-month-old infant plasma samples. Similar congener profiles were observed in all biologic samples, and PCB-153, the most abundant and persistent PCB congener, was strongly correlated with other frequently detected PCB congeners in all biologic media. When expressed on a lipid basis, maternal plasma, cord plasma, and milk concentrations of this congener were strongly intercorrelated, indicating that PCB concentration in any of these biologic media is a good indicator of prenatal exposure to PCBs. A multivariate model that included maternal PCB-153 plasma lipid concentration, breast-feeding duration, and the sum of two skin-fold thicknesses (an index of infant body fat mass) explained 72% of PCB-153 plasma concentration variance at 6 months postpartum (p < 0.001). By contrast, based on the product of breast-feeding duration times the concentration of PCBs in plasma lipids, which was used as an index of postnatal PCB exposure in several studies, only 36% of infant plasma concentration was explained.

Adsorption of proteins from infant and adult plasma to biomaterial surfaces.

The hemostatic mechanism of the newborn is immature. In general, the clotting times in screening tests are prolonged, the coagulation factors are low, and the coagulation inhibitors (with the exception of alpha-2-macroglobulin) are low. Recognizing that many of the proteins present in infant plasma are at low levels, it is of interest to determine if, following exposure to artificial surfaces, the profile of adsorbed proteins is different for infant versus adult plasma. The question of whether differences in protein profiles could lead to differences in thromboembolic episodes associated with the use of central venous catheters (or other blood-contacting devices) in infant versus adult subjects also is relevant. To address these issues, the adsorption of proteins from pooled infant plasma and pooled normal adult plasma to three different polymer surfaces (polyvinyl chloride, PVC; polymethyl methacrylate, PMMA; and polyethylene oxide-modified polyurethane, PEO-PU) was studied using SDS-PAGE and immunoblotting techniques. The total amount of protein adsorbed to each surface also was determined. It was found that the PMMA and PVC surfaces adsorbed considerably more protein than the PEO-PU surface. Furthermore, the amount of protein adsorbed to the PMMA and PVC surfaces from infant plasma was significantly less than that adsorbed from adult plasma. No such difference was seen for the protein-repellent PEO-PU surface. The immunoblot responses of proteins bound to the PMMA and PVC surfaces from infant plasma were, in general, weaker than those bound from adult plasma. It is likely that these differences were due to decreased protein levels in infant plasma.

Infant plasma trans , n−6, and n−3 fatty acids and conjugated linoleic acids are related to maternal plasma fatty acids, length of gestation, and birth weight and length

Arachidonic acid (AA) and docosahexaenoic acid (DHA) are important for growth and neural development. trans Fatty acids (TFAs) may inhibit desaturation of linoleic acid (LA) and alpha-linolenic acid (ALA) to AA and DHA, respectively. Conjugated linoleic acids (CLAs) also alter lipid metabolism and body fat. We determined the associations of birth outcome with maternal and infant plasma concentrations of TFAs, CLAs, AA, and DHA. In healthy women, we sampled maternal blood at 35 wk gestation (n = 58) and umbilical cord blood at birth (n = 70). Mean (+/- SEM) TFA concentrations (% by wt) in infant plasma were as follows: triacylglycerol, 2.83 +/- 0.19 (range: 0.63-12.79); phospholipid, 0.67 +/- 0.03 (0.11-1.33); and cholesteryl ester, 2.04 +/- 0.01 (0.86-4.24). LA, AA, DHA, TFA, and CLA concentrations in infant phospholipids correlated with the same fatty acid in maternal plasma phospholipids (n = 44; P < 0.05). Infant plasma cholesteryl ester and triacylglycerol TFAs and cholesteryl ester CLAs (r = -0.33, -0.42, and -0.49, respectively) were significantly inversely related to length of gestation. Triacylglycerol and cholesteryl ester AA were positively related to length of gestation (r = 0.41 and 0.37, respectively) and birth weight (r = 0.27 and 0.23, respectively). Inverse correlations occurred between infant plasma TFA and DHA concentrations in triacylglycerols (r = -0.33) and between TFA and AA concentrations in cholesteryl esters (r = -0.23). The results suggest possible important effects of TFAs and of AA on fetal growth and length of gestation.

Are breast-fed infants vitamin K deficient?

Hemorrhagic disease of the newborn is a disease of breast-fed infants. We have followed 119 exclusively breast-fed infants for up to 6 months of age, who received 1 mg of vitamin K, intramuscularly at birth. As vitamin K is undetectable in cord blood, the only other source in breast-fed infants is human milk. We found persistently low vitamin K1 plasma concentrations in these infants by 4 weeks, and vitamin K concentrations at 2, 4, 6, 8, 12, and 26 weeks averaged 1.18+/-0.99, 0.50+/-0.70, 0.16 +/-0.07, 0.20+/-0.20, 0.25+/-0.34, and 0.24+/-0.23 ng/mL, respectively (lower limit of adult normal = 0.5ng/mL). Vitamin K, in breast milk at 2, 6, 12, and 26 weeks was also very low, averaging 1.17+/-0.70, 0.95+/-0.50, 1.15+/-0.62, and 0.87+/-0.50 mg/mL, respectively. This may be secondary to low maternal vitamin K1 intakes or inability of vitamin K1 to penetrate human milk. We had previously reported a relatively high mean vitamin K intake of 316+/-548 microg in 20 lactating women during the first 6 months of lactation (mean of 60, 3-day dietary recalls) which greatly exceeded the recommended daily allowance of 1 microg/kg/day. The vitamin K content of foods was recently revised downward utilizing newer analytical methods (Booth et al. 1995). Recalculating maternal vitamin K intakes in this original cohort resulted in a dramatic decrease in intake to 74+/-57 microg/day, an amount closely approximating 1 microg/kg/day. We have completed 69 new dietary recalls in 23 lactating women and, combining these data with the previous study, determined a maternal vitamin K1 mean intake of 65+/-48 microg/day (0.8-1.3 microg/kg/day). Other than plasma vitamin K1 concentrations, PIVKA (undercarboxylated prothrombin produced in the absence of vitamin K) is a marker of vitamin K deficiency. We measured PIVKA in 156 cord bloods of full-term infants. Seventy-five (48%) had a significantly elevated PIVKA (> or =0.1 absorption units per milliliter). Seventy-seven of these infants who were exclusively breast-fed subsequently had no detectable PIVKA at 4 weeks, but by 8 weeks, 3 were again positive for PIVKA (prothrombin times were normal). Breast-fed infants may benefit from increased maternal vitamin K intakes (>1 microg/kg/day) during pregnancy and lactation. A supplement of 5 mg of vitamin K to lactating mothers will increase the concentration in human milk to 80.0+/-37.7 ng/mL and significantly increase infant plasma vitamin K (Greer et al. 1997).

Protein Carbonyls and Lipid Peroxidation Products as Oxidation Markers in Preterm Infant Plasma: Associations with Chronic Lung Disease and Retinopathy and Effects of Selenium Supplementation

The purpose of this study was to determine whether protein carbonyls and the lipid peroxidation product malondialdehyde (MDA) are elevated in plasma from very low birth weight (<1500 g) infants, whether they are affected by selenium supplementation, and whether they are associated with poor respiratory outcome or retinopathy. The study group comprised 173 infants enrolled in a randomized controlled trial of selenium supplementation. Plasma samples, collected before randomization, at 7 and 28 d after birth, and at 36 wk postmenstrual age, were analyzed for protein carbonyls and total MDA. Respiratory outcome was assessed as oxygen requirement at 28 d of age or 36 wk postmenstrual age and as number of days on oxygen. Protein carbonyl concentrations in very low birth weight infants were significantly higher than for adults but lower than for cord blood from term infants. Median values decreased significantly by 28 d, and there was no relationship with birth weight. MDA concentrations in very low birth weight infants overlapped the ranges for healthy adults and cord blood from term infants. They correlated positively with birth weight at 28 d but not at other times. Supplementation almost doubled plasma selenium concentrations, but carbonyls and MDA did not differ between the supplemented and unsupplemented groups. There were no significant differences in oxidant marker levels in infants who did or did not develop chronic lung disease or retinopathy. Protein carbonyls and MDA measurements in plasma do not show evidence of systemic oxidative stress in <1500-g infants and are not affected by selenium supplementation. Oxidative injury at sites such as the lung may be important in prematurity, but markers from such sites must be measured to relate to outcome and antioxidant supplementation.

Antidepressants and breast-feeding: a review of the literature.

For every antidepressant so far investigated in the breast milk of mothers prescribed these medications, findings indicate that some amount of drug will be excreted into the breast milk. Nursing infants will be exposed to some, usually a very low, amount of drug and drug metabolites. Levels of drug exposure to infants for the many antidepressants available are examined, discussing milk to plasma drug concentration ratios and the infant dose as a percentage of the maternal dose. Drug concentrations in infant plasma and adverse effects of drug exposures to infants are reviewed. Factors influencing the decision on whether to breast or bottle feed an infant nursed by a mother taking antidepressants are discussed, concluding that the decision needs to be made on an individual basis. The lactating mother, in consultation with her doctor, should be in a position to make an informed decision on whether or not to breast feed. Under certain circumstances the decision to bottle feed may be wise, but more commonly the advantages of breast-feeding will outweigh the very low risk of an adverse event from drug exposure to the infant.

Rearing Experiences and Stress‐Induced Plasma Cortisol as Early Risk Factors for Excessive Alcohol Consumption in Nonhuman Primates

The purpose of this study was to assess the impact of early rearing and stress-induced rise of plasma cortisol collected during infancy as a biological predictors of adult alcohol consumption in nonhuman primates. Ninety-seven female and male rhesus macaques (Macaca mulatta) were investigated. They were reared for their first 6 months of life either without mothers or other adults but with constant access to same-aged peers (peer-reared), or as controls with their mothers (mother-reared). When subjects reached 6 months of age, they underwent a series of four sequential weeks of 4-day social separations. Blood was drawn 1 and 2 hr after initiation of the 4-day separation periods, and the plasma was assayed for plasma cortisol concentrations. When the subjects were young adults (approximately 50 months of age), they were tested for voluntary intake of alcohol for 1 hr per day, 4 days a week, during a period of 5 to 7 weeks under normal living conditions. The social separation challenge increased infant plasma cortisol concentrations, with peer-reared subjects exhibiting higher stress-induced cortisol concentrations than mother-reared animals. Subjects that responded to the social separation challenge with high cortisol levels consumed significantly more alcohol per kilogram of body weight as adults than subjects with a low cortisol response to the separation challenge, regardless of rearing condition. In addition, male and peer-reared subjects consumed significantly more alcohol than female and mother-reared subjects, respectively. These findings suggest that early rearing experiences, such as adult absence, and high plasma cortisol concentrations early in life after a social separation stressor, are useful psychobiological predictors of future high alcohol consumption among nonhuman primates.

Clinical use of antenatal corticosteroids: benefits and risks.

After completing this article, readers should be able to: 1. Describe the rationale for the use of antenatal corticosteroids for human fetal maturation. 2. Delineate recommendations of the 1994 National Institutes of Health Consensus Conference on Antenatal Corticosteroids. 3. Review areas of controversy in the clinical use of antenatal corticosteroids. 4. Describe the potential risks of multiple courses of antenatal corticosteroids. 5. Delineate current recommendations for clinical use of antenatal corticosteroids to promote fetal maturation. Glucocorticoid administration initially was appreciated as a method for accelerating development of the intestine more than 40 years ago. Since that time, developmental effects of these agents have been defined in at least 16 tissues of mammals. More than 30 years ago, while studying the mechanism of initiation of labor in sheep, Liggins made the observation that infusion of corticosteroids into fetal lambs was associated with improved survival and decreased lung disease in animals delivered preterm. Subsequently, numerous studies in cell culture, animal models, and human fetal tissue have delineated the multiple effects of glucocorticoids on the developing lung. These include increases in both the total tissue and alveolar surfactant pools; a decrease in vascular permeability, with less protein leak into the alveolar spaces; enhanced clearance of lung water; maturation of parenchymal structure; increase in lung compliance and maximal lung volume; enhanced response to surfactant treatment; and improvement in respiratory function, outcome, and survival. (See accompanying article on scientific rationale for use of antenatal glucocorticoids.) In 1972, the first randomized clinical trial of administration of antenatal corticosteroids (ANCS) in humans demonstrated decreased mortality and a decreased incidence of respiratory distress syndrome (RDS) in preterm infants born at less than 34 weeks’ gestation, who were treated with betamethasone for at least 24 hours before delivery. Over the ensuing 20 years, multiple clinical investigations continued to document the effectiveness of ANCS on …

Analysis of riboflavin and riboflavin cofactor levels in plasma by high-performance liquid chromatography

We describe an assay which determines simultaneously riboflavin (RF), flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) in plasma, using galactoflavin (GF) as an internal standard. The flavins were extracted on a C 18 Sep-Pack cartridge after protein precipitation with 10% trichloroacetic acid, and were analyzed on a C 18 RP-HPLC with 85% phosphate–magnesium acetate buffer (pH 3.4) and 15% acetonitrile. FAD, FMN, GF and RF extraction recoveries were 101.0±5.6, 97.0±6.5, 97.0±2.0 and 95.0±4.1%, and reproducibilities were 5.9, 6.8, 2.1 and 4.3%, respectively. FAD, FMN and RF values in infant and adolescent plasma were in the range 53.5–108.2, 9.0–25.1 and 12.7–53.4 n M, and 36.5–157.20, 7.1–24.6 and 8.2–57.8 n M, respectively. Using GF as an internal standard improved the quantification of these B2 vitamers.

Breast milk leptin concentrations in initial and terminal milk samples: relationships to maternal and infant plasma leptin concentrations, adiposity, serum glucose, insulin, lipid and lipoprotein levels.

Leptin has recently been shown to be present in human milk and is produced by mammary epithelial cells. We studied leptin concentrations in human milk and its relationships with maternal and infant plasma leptin concentrations, adiposity, serum glucose, insulin, lipid and lipoprotein levels. We also compared the initial and terminal milk leptin concentrations to investigate whether leptin acts as a satiety factor. Venous blood samples were obtained from 18 healthy lactating women aged from 17-42 years and their 3-120 day-old infants. Breast milk samples were collected just before and immediately after suckling, when the infant had self-terminated sucking. Leptin mean values in breast milk were lower than in maternal plasma (p<0.001). Breast milk log leptin concentrations positively correlated with both maternal and infant plasma log leptin concentrations (p<0.001 and p=0.001, respectively) and negatively correlated with maternal serum total cholesterol and low-density lipoprotein cholesterol levels (p<0.001 and p<0.01, respectively), but did not correlate with maternal and infant adiposity, serum glucose and insulin levels, maternal serum HDL-C, triglyceride levels and infants' lipid and lipoprotein concentrations (p>0.05). Using stepwise multiple regression analysis, maternal plasma log leptin and serum HDL-C concentrations were related to breast milk log leptin concentration (R2=0.82; p<0.0001 and p<0.001, respectively). There was no significant difference between initial and terminal milk leptin levels (p>0.05). We concluded that maternal leptin may be transferred to the infant via milk and may exert biological effects; there may be factors other than adiposity affecting breast milk leptin levels, and that leptin might not contribute to the development of satiation at the end of suckling.

Effect of docosahexaenoic acid supplementation of lactating women on the fatty acid composition of breast milk lipids and maternal and infant plasma phospholipids

To determine whether docosahexaenoic acid (DHA) supplementation of breast-feeding mothers increases the DHA contents of breast milk and infant plasma phospholipids (PPs), breast-feeding women were randomly assigned to 3 DHA-supplementation groups (170-260 mg/d) or a control group. Group 1 (n = 6) consumed an algae-produced high-DHA triacylglycerol; group 2 (n = 6) consumed high-DHA eggs; group 3 (n = 6) consumed a high-DHA, low-eicosapentaenoic acid marine oil; and group 4 (n = 6) received no supplementation. From before to after supplementation (2 and 8 wk postpartum), mean (+/-SD) maternal PP DHA increased in groups 1, 2, and 3 by 1.20 +/- 0.53, 0.63 +/- 0.82, and 0.76 +/- 0.35 mol% of fatty acids, respectively (23-41%), but decreased in group 4 by 0.44 +/- 0.34 mol% (15%). Breast-milk DHA of groups 1, 2, and 3 increased by 0.21 +/- 0.16, 0.07 +/- 0.11, and 0. 12 +/- 0.07 mol%, respectively (32-91%) but decreased in group 4 by 0.03 +/- 0.04 mol% (17%). Mean infant PP DHA in groups 1, 2, and 3 increased by 1.63 +/- 0.79, 0.40 +/- 1.0, and 0.98 +/- 0.61 mol%, respectively (11-42%), but only by 0.18 +/- 0.74 mol% (5%) in group 4. Correlations between the DHA contents of maternal plasma and breast milk and of milk and infant PPs were significant. Breast-milk and maternal and infant PP 22:5n-6 concentrations were lowest in group 2. DHA supplementation increases the plasma and breast-milk DHA concentrations of lactating women, resulting in higher PP DHA concentrations in infants.

Trans Fatty acids in human milk are inversely associated with concentrations of essential all-cis n−6 and n−3 fatty acids and determine trans, but not n−6 and n−3, fatty acids in plasma lipids of breast-fed infants

Human milk fatty acids vary with maternal dietary fat composition. Hydrogenated dietary oils with trans fatty acids may displace cis n-6 and n-3 unsaturated fatty acids or have adverse effects on their metabolism. The effects of milk trans, n-6, and n-3 fatty acids in breast-fed infants are unclear, although n-6 and n-3 fatty acids are important in infant growth and development. We sought to determine the relations between trans and cis unsaturated fatty acids in milk and plasma phospholipids and triacylglycerols of breast-fed infants, and to identify the major maternal dietary sources of trans fatty acids. We collected milk from 103 mothers with exclusively breast-fed 2-mo-old infants, blood from 62 infants, and 3-d dietary records from 21 mothers. Mean (+/-SEM) percentages of trans fatty acids were as follows: milk, 7.1 +/- 0.32%; infants' triacylglycerols, 6.5 +/- 0. 33%; and infants' phospholipids, 3.7 +/- 0.16%. Milk trans fatty acids, alpha-linolenic acid (18:3n-3), arachidonic acid (20:4n-6), docosahexaenoic acid (22:6n-3) (P < 0.001), and linoleic acid (18:2n-6) (P = 0.007) were each related to the same fatty acid in infant plasma phospholipids. Milk trans fatty acids were inversely related to milk 18:2n-6 and 18:3n-3, but not to milk or infant plasma 20:4n-6 or 22:6n-3. trans Fatty acids represented 7.7% of maternal total fat intake (2.5% of total energy); the major dietary sources were bakery products and breads (32%), snacks (14%), fast foods (11%), and margarines and shortenings (11%). There were comparable concentrations of trans fatty acids in the maternal diet, breast milk, and plasma triacylglycerols of breast-fed infants. Prepared foods were the major dietary source of trans fatty acids.

Evidence of Excess Cancer Mortality in a Cohort of Workers Exposed to Polychlorinated Biphenyls

Evidence of Excess Cancer Mortality in a Cohort of Workers Exposed to Polychlorinated Biphenyls

Plasma vitamin A levels in the very low birthweight infant — relationship to respiratory outcome

To examine the association between plasma vitamin A levels and outcome measures in very low birthweight (VLBW) infants, including meta-analysis of all observational studies. A prospective observational longitudinal study of plasma vitamin A levels measured in the cord blood; maternal blood in the first 48 h after delivery; and the infants' blood at 48 h, 7 days and 28 days of age and correlated with antenatal and postnatal events. A meta-analysis of all published observational studies on the association of vitamin A with respiratory outcome in the VLBW infant was undertaken. Fifty-seven infants (88% of all eligible) VLBW infants (< 1500 g) admitted from January through October 1993 to one of two regional neonatal intensive care units in the South Island of New Zealand. Exposure to antenatal steroids led to a significant increase in infant cord plasma vitamin A levels (P = 0.003), but no influence on infant plasma vitamin A levels at any other time. Exposure to postnatal steroids produced a significant rise in infant plasma vitamin A levels between 7 and 28 days (P = 0.008). After controlling for gestational age, antenatal and postnatal steroid exposure, low vitamin A levels at 48 h increased the risk of developing chronic lung disease (odds ratio for 50 microg/l decrease: 2.04, 95% CI 1.19-5.77) and bronchopulmonary dysplasia (odds ratio 1.96, 95% CI 1.14-6.87). On combining our results in meta-analysis with those of other published prospective observational studies, infants with chronic lung disease had lower plasma vitamin A levels at all times. Our results support an association between low plasma vitamin A levels and adverse outcome in the VLBW infant.

Effects of Dietary Long-Chain Polyunsaturated Fatty Acids on Plasma Amino Acids and Indices of Protein Metabolism in Infants: Results from a Randomized Clinical Trial

Background/Aim: Previous studies in vitro and in animals in vivo found that α-linolenic acid (C18:3ω3) may enhance oxidative damage of essential amino acids. We investigated whether the addition of the long-chain polyunsaturated fatty acids (LCPUFA) arachidonate (C20:4ω-6; AA) and docosahexaenoate (C22:6-ω3; DHA) in the form of egg phospholipids to infant formula affects plasma amino acid concentrations and indices of protein metabolism in term infants. Methods: In a double-blind, randomized clinical trial, healthy infants were fed from day 5 of life formula with or without preformed LCPUFA (n = 10 and 12, respectively). At the age of 5 days and 1, 2, 3 and 4 months, blood samples were obtained and analyzed for plasma amino acids by high-performance liquid chromatography and for plasma phospholipid fatty acid composition by gas chromatography. Results: At the age of 3 months, plasma threonine concentrations were significantly lower in infants receiving dietary LCPUFA than in controls (124 ± 16 vs. 216 ± 28 µmol/l, p < 0.05). Values of other plasma essential amino acids, total protein, albumin, creatinine and urea nitrogen did not differ between the two feeding groups throughout the study. At the age of 5 days, plasma phospholipid AA and DHA concentrations were inversely correlated with histidine concentrations (AA: r = –0.60, p = 0.01; DHA: r = –0.53, p < 0.05). At the age of 3 months, DHA concentrations were inversely related to plasma histidine, methionine and threonine concentrations (r = –0.66, –0.62, and –0.64, respectively, p < 0.05). Conclusions: The dietary LCPUFA supplementation of infant formula used in this study has no adverse effects on infant plasma amino acid concentrations and indicators of protein metabolism. Nonetheless, the apparent interaction of LCPUFA with some amino acids in formula-fed infants warrants further investigation.