Er Boersma

PCB AND DIOXIN LEVELS IN PLASMA AND HUMAN MILK OF 418 DUTCH WOMEN AND THEIR INFANTS. PREDICTIVE VALUE OF PCB CONGENER LEVELS IN MATERNAL PLASMA FOR FETAL AND INFANT'S EXPOSURE TO PCBs AND DIOXINS.

Polychlorinated biphenyls (PCBs) as well as dioxins (polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs)) are potentially hazardous compounds in the environment for human beings. In order to investigate PCB and dioxin exposure of Dutch women and their neonates, levels were examined in 418 mother-infant pairs. Four non-planar PCB congener levels (PCB 118, 138, 153 and 180) were measured in maternal plasma and in umbilical cord plasma. The 209 mothers who breast-fed their infants collected human milk samples for the analysis of seventeen 2,3,7,8-substituted PCDD and PCDF congener levels, three planar PCB and twenty-three non-planar PCB congener levels. The dioxin and planar PCB levels we measured in human milk (mean 30 respectively 16 pg TEQ/g fat), belong to the highest background levels analysed all over the world but they are in the normal range for highly industrialised, densely populated countries in Western Europe. Correlation coefficients between PCB 118, 138, 153 and 180 congener levels in maternal plasma and PCB levels in cord plasma or PCB and dioxin levels in human milk are highly significant. However, the 95% predictive interval is too wide to predict accurately the PCB and dioxin levels to which an individual infant is exposed in utero or postnatally by breast-feeding, from the PCB levels in maternal plasma.

Neurological condition in 42-month-old children in relation to pre- and postnatal exposure to polychlorinated biphenyls and dioxins.

Adverse neurological effects of exposure to PCBs have been found up to 18 months of age. Now we report on the effect of pre- and postnatal exposure to PCBs and dioxins on the neurological condition at 42 months of age. For this purpose, PCB levels were determined in cord and maternal plasma, and used as a measure of prenatal exposure. Breast milk was analyzed for PCBs and dioxins. In addition, PCBs were determined in plasma sampled from the child at 42 months of age. We evaluated the neurological condition of 394 children using the Touwen/Hempel method. After adjustment for covariates, neither prenatal PCB exposure nor postnatal exposure to PCBs and dioxins was found to be related to the neurological condition at 42 months of age.

PERINATAL EXPOSURE TO POLYCHLORINATED BIPHENYLS AND DIOXINS THROUGH DIETARY INTAKE.

Polychlorinated biphenyls (PCBs) and dioxins (polychlorinated dibenzo-p-dioxins and dibenzofurans) are potentially hazardous compounds. Since food is the major source (> 90%) for the accumulation of PCBs and dioxins in the human body, food habits in women determine the degree of fetal exposure and levels in human milk. In order to investigate an association between dietary intake and PCB and dioxin levels in human milk and PCB levels in maternal and cord plasma, the food intake of 418 Dutch women during pregnancy was recorded using semi-quantitative food frequency questionnaires. After adjusting for covariates, a weak association was found between the estimated dietary intake of 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD), dioxins, and planar PCBs and their corresponding levels in breast milk. The estimated dietary intake of 2,3,7,8-TCDD, dioxins, and planar PCBs was also related to the PCB levels in maternal and cord plasma. Dairy products accounted for about half and industrial oils for about a quarter of the estimated 2,3,7,8-TCDD, dioxin, and the planar PCB intake. It is concluded that the contribution of a pregnancy related diet to PCB and dioxin levels in human milk and to PCB levels in maternal and cord plasma is relatively low. Decrease of exposure to PCBs and dioxins of the fetus and the neonate probably requires long-term reduction of the intake of these pollutants. Substitution of normal cheese by low-fat cheese and the use of vegetable oils instead of fish oils in the preparation of foodstuffs by the food industry could contribute to a reduced intake of PCBs and dioxins.

Long-chain polyunsaturated fatty acids and neurological developmental outcome at 18 months in healthy term infants

Aim: Previously, we found a beneficial effect of 2 mo supplementation of infant formula with long‐chain polyunsaturated fatty acids (LC‐PUFA) on neurological condition at 3 mo in healthy term infants. The aim of the present follow‐up study was to evaluate whether the effect on neurological condition persists until 18 mo. Methods: A prospective, double‐blind, randomized control study was conducted. Three groups were formed: a control (CF; n=169), an LC‐PUFA‐supplemented (LF; n=146) and a breastfed (BF; n=159) group. Information on potential confounders was collected at enrolment. At the age of 18 mo, neurodevelopmental condition was assessed by the age‐specific neurological examination of Hempel and the Bayley scales. The Hempel assessment resulted in a clinical neurological diagnosis, a total optimality score and a score on the fluency of motility. The Bayley scales resulted in mental and psychomotor developmental indices. Attrition at 18 mo was 5.5% and non‐selective. Multivariate regression analyses were carried out to evaluate the effect of type of feeding while adjusting for confounders. Results: None of the children had developed cerebral palsy and 23 (CF: n=8; LF: n=10; BF: n=5) showed minor neurological dysfunction. The groups did not show statistically significant differences in clinical neurological condition, neurological optimality score, fluency score, and the psychomotor and mental development indices. Multivariate analysis confirmed that there was no effect of type of feeding on neurological condition.

Polychlorinated Biphenyls in Adipose Tissue, Liver, and Brain from Nine Stillborns of Varying Gestational Ages

We analyzed polychlorinated biphenyls (PCBs) in s.c. adipose tissue, liver, and brain of nine fetuses who died in utero. Their median(range) gestational ages and birth weights were 34 (17-40) wk and 2050(162-3225) g. Three fetuses were small for gestational age. The levels of PCB congener nos. 118, 138, 153, and 180, and the sum of these (ΣPCB), were calculated in terms of tissue total fat content (ng/g fat). The median(range) ΣPCB (in ng/g fat) amounted to adipose tissue 235 (97-768), liver 198 (67-362), and brain 50 (22-122). Median (range) ΣPCB levels in liver and brain were 0.8 (0.4-0.9) and 0.2 (0.1-0.3) times, respectively, as high as the ΣPCB levels in adipose tissue. There were strong relations between ΣPCB in adipose tissue and ΣPCB in liver(r = 0.98; p < 0.01), and between ΣPCB in adipose tissue and ΣPCB in brain (r = 0.91;p < 0.01). Adipose tissue, liver, and brain did not show differences in the distribution of congeners 118, 138, 153, and 180, and there was no statistically significant association between tissue PCB levels and gestational age (r varied between 0.22 and 0.47). MedianΣPCB levels in fetal adipose tissue proved to be comparable with our previously established ΣPCB levels in mature breast milk of 93 Dutch women (median 414; range 158-969 ng/g of fat). The PCB congeneric distribution of fetal adipose tissue was not different from that of human milk. We conclude that maternal PCBs have a tendency to accumulate notably in fetal tissues with high triglyceride contents. They are easily transferred across the placenta and seem to become equilibrated among the apolar parts of maternal and fetal lipids.

Relationship between umbilical cord essential fatty acid content and the quality of general movements of healthy term infants at 3 months

Prenatal essential fatty acid (EFA) status might be an important factor in the development of the central nervous system (CNS). The aim of the present study was to evaluate the relationship between the fatty acid compositions of the umbilical blood vessels at birth, used as a proxy of prenatal EFA status, and quality of general movements (GMs) at 3 mo. Umbilical artery and vein fatty acid compositions were investigated in a mixed group of breastfed infants and infants fed with formula with or without long-chain polyunsaturated fatty acid (LCPUFA) supplementation. At the age of 3 mo, video assessment of the quality of GMs was performed to evaluate neurologic condition. The quality of GMs was scored by assessing the degree of variation, complexity, and fluency. Outcomes were classified as normal-optimal, normal suboptimal, mildly abnormal, and definitely abnormal movements. Information on potential confounders, including the type of postnatal feeding, was collected prospectively. Associations between fatty acid status at birth and quality of GMs were investigated, and multinomial logistic regression analyses were carried out. None of the infants showed definitely abnormal movements. Infants with mildly abnormal GMs had a lower EFA index, lower arachidonic acid (AA) content, higher total n-9 fatty acid, and higher total monounsaturated fatty acid (MUFA) content in the umbilical artery compared with infants with normal GMs. Multivariate analyses confirmed these findings. We conclude that mildly abnormal GMs are associated with a less favorable EFA status in the umbilical artery.

Estimation of 24-hour polyamine intake from mature human milk

It has been suggested that milk polyamines stimulate GI tract proliferation and maturation in newborns. We determined human milk polyamine concentrations and estimated 24-h outputs on days 16 +/- 4 (n = 98), 44 +/- 3 (n = 97) and 91 +/- 6 (n = 25) after delivery. Median concentrations in micromolars were, respectively, putrescine 0.77, 0.63, and 0.63; spermidine 4.54, 3.07, and 2.73; spermine 3.76, 2.90, and 2.22; and total polyamines 9.82, 6.83, and 5.71. Concentrations of spermidine, spermine, and total polyamines decreased during the observation period. Putrescine, spermidine, and spermine milk/maternal plasma ratios were estimated to be 16-19, 14-24, and 44-75, respectively. It would appear that milk polyamines are derived from the high polyamine contents in the mammary gland and that they may be important in infant nutrition.

Breastfeeding and neurological outcome at 42 months

This study investigated the effect of early feeding mode on the neurological condition at 42 months. For this purpose, healthy pregnant women were recruited in Groningen and Rotterdam, The Netherlands. Children were healthy and born at term. At 42 months, the children were neurologically examined by means of the Touwen/Hempel technique. In addition to the clinical diagnosis, the neurological findings were interpreted in terms of optimality. Special attention was paid to the quality of movements in terms of fluency. In total, 200 (51%) exclusively breastfed (for ≥ 6 weeks) and 194 (49%) formula‐fed children were studied. Twelve (3%) 42‐month‐old children were considered to be neurologically mildly abnormal and 1 child was diagnosed as abnormal. No effect of the type of feeding was found on the clinical diagnosis or the neurological optimality. After adjustments for study centre and social, obstetric, perinatal and neonatal neurological differences, a beneficial effect of breastfeeding on the fluency of movements was found (odds ratio for non‐optimal fluency 0.56; 95% confidence interval 0.37‐0.85). The prolongation of full breastfeeding beyond 6 weeks did not influence the quality of movements. In conclusion, among Dutch preschool children, there was a small advantageous effect of full breastfeeding during the first 6 weeks of life on the fluency of movements.

Fatty acids in formulae for term infants: compliance of present recommendations with the actual human milk fatty acid composition of geographically different populations.

Aim: Recommendations for formula fatty acids (FA) are largely based on the mature human milk FA composition. This study aimed to investigate whether current recommendations for formula FA for term infants comply with the actual breast‐milk FA composition of geographically distinct populations and to provide more realistic grounds for future recommendations. Methods: 455 mature breast‐milk samples were collected in different countries over 25 y. Recommendations of different organizations were projected on their FA data. FA interrelationships were calculated with Spearmans rank tests. FA compositions of 30 formulae were compared with those of breast milk. Results: Many samples from non‐Western communities did not meet the recommendations for formula 12:0, 14:0 and 18:2ω6, since these are mainly based on breast milk of mothers living in Western countries. Recommendations for 18:3ω3, 18:2ω6/18:3ω3, 20:4ω6 and 22:6ω3 were not met by many milk samples, which may point to the poorly developed recommendations for long‐chain polyunsaturated FA. Most of the investigated breast‐milk FA (12:0, 14:0, 16:0, 18:0, 18:3ω3, 22:6ω3, 18:2ω6, 20:4ω6, 18:lω9) were either positively or negatively interrelated. Many formulae had FA compositions that were not consistent with the physiological interrelationships of FA in breast milk. Conclusion: Future recommendations, if based on human milk, should derive from its FA balance, as indicated by the FA interrelationships. A “humanized” formula FA composition would in this sense be any composition that cannot be distinguished from that of breast milk by techniques such as principal component analysis.

Oral administration of deuterium-labelled polyamines to sucking rat pups : luminal uptake, metabolic fate and effects on gastrointestinal maturation

Non-physiological amounts of oral polyamines have been reported to induce precocious gut maturation in rat pups. The aim of the present study was to investigate organ distribution and metabolic fate of orally administered stable-isotopically labelled polyamines in rat pups. Pups received tetradeuterium-labelled putrescine (Pu-d4; 3 mumol), spermidine (Sd-d4; 5 mumol), spermine (Sp-d4; 3 mumol), or physiological saline twice daily on postnatal days 7-10 or 12-15. They were killed on days 10 and 15. We determined activities of ileal lactase (EC 3.2.1.23), maltase (EC 3.2.1.20), sucrase (EC 3.2.1.48) and diamine oxidase (EC 1.4.3.6) and established villus and crypt lengths. Polyamines and their labelling percentages in organs were determined by GC and mass fragmentography. Treatments did not affect growth rate, but caused lower weights of liver, kidneys and heart. Maltase activity increased, lactase decreased, whereas sucrase and diamine oxidase did not change. Villus and crypt lengths increased. Organ polyamine pools were labelled to different extents. Irrespective of the orally administered polyamine, all organs contained Pu-d4, SD-d4 and Sp-d4. Administered Pu-d4 and Sd-d4 were recovered mainly as Sd-d4, whereas Sp-d4 was recovered as Sp-d4 and Sd-d4. Total polyamines in a caecum, colon and erythrocytes increased, but increases were only to a minor extent with regard to labelled polyamines. Our data confirm precocious gut maturation by exogenous polyamines. Putrescine appears to be limiting factor. The exogenous polyamines were distributed among all investigated organs. They are not only used for the synthesis of higher polyamines, but also retroconverted to their precursors. Changes in erythrocyte polyamine contents suggest precocious stimulation of erythropoiesis.