A carbohydrate-rich diet not only leads to incorporation of medium-chain fatty acids (6:0-14:0) in milk triglycerides but also in each milk-phospholipid subclass.

We isolated phospholipid (PL) subclasses from milk of women in Dominica and Belize. Fatty acid (FA) compositions of PLs and total lipids were determined. In the total-lipid fraction Dominican milk showed higher relative amounts of medium-chain saturated fatty acids (MC-SAFAs; 6:0-14:0) and 22:6n-3 and lower amounts of long-chain saturated fatty acids (LC-SAFAs) and monounsaturated fatty acids (MUFAs). There was a positive relationship between the MC-SAFA content in total lipids and total PLs. Incorporation of MC-SAFAs in PLs occurred at the expense of LC-SAFAs, MUFAs, polyunsaturated fatty acids (PUFAs), and long-chain PUFAs with greater than or equal to 20 carbon atoms (LC-PUFAs greater than or equal to C20). Previous studies from Western countries revealed low amounts of MCSAFAs and high amounts of PUFAs and LC-PUFAs greater than or equal to C20 in milk PLs. Our data show that carbohydrate-rich diets give rise to incorporation of MC-SAFAs in PLs at the expense of PUFAs and LC-PUFAs greater than or equal to C20. The data are discussed in relation to the presumed origin of fat-globule membrane phospholipids.

Vitamin E, lipid fractions, and fatty acid composition of colostrum, transitional milk, and mature milk: an international comparative study.

Triglycerides, cholesterol, fatty acid composition, and tocopherols were determined in colostrum, transitional milk, and mature milk in St Lucia. With progress of lactation, triglycerides and percentage medium-chain fatty acids increased whereas tocopherols, cholesterol, and percentage long-chain polyunsaturated fatty acids decreased. These changes reflect augmented de novo synthesis of fatty acids (8:0, 10:0, 12:0, and 14:0) in the mammary gland and a tendency of increasing fat-globule size as milk matures. Transitional and mature milks, but particularly colostrum, contained higher concentrations of components considered to be derived from the fat-globule membrane (cholesterol, tocopherols, percentage long-chain polyunsaturated fatty acids) compared with those reported for Western countries. Percentage medium-chain fatty acids in mature milk was two to three times higher than in developed countries. Differences from data from studies in Western countries are discussed in relation to analytical methods and possible consequences for lipid digestion, lipid absorption, growth, and brain development.

Influence of short-term dietary measures on dioxin concentrations in human milk.

Breast-feeding may expose infants to high levels of toxic chlorinated dioxins. To diminish intake of these lipophilic compounds by the baby, two diets were tested for their ability to reduce concentrations of dioxins in human milk. The diets were a low-fat/high- carbohydrate/low-dioxin diet. (about 20% of energy intake derived from fat) and a high fat /low-carbohydrate/low-dioxin diet. These diets were tested in 16 and 18 breast-feeding women, respectively. The test diets were followed for 5 consecutive days in the fourth week after delivery. Milk was sampled before and at the end of the dietary regimen, and dioxin concentrations and fatty acid concentrations were determined. Despite significant influences of these diets on the fatty acid profiles, no significant influence on the dioxin concentrations in breast milk could be found. We conclude that short-term dietary measures will not reduce dioxin concentration in human milk.

Effect of supplementation of arachidonic acid (AA) or a combination of AA plus docosahexaenoic acid on breastmilk fatty acid composition.

We investigated whether supplementation with arachidonic acid (20:4 omega 6; AA), or a combination of AA and docosahexaenoic acid (22:6 omega 3; DHA) would affect human milk polyunsaturated fatty acid (PUFA) composition. Ten women were daily supplemented with 300 mg AA, eight with 300 mg AA, 110 mg eicosapentaenoic acid (20:5 omega 3; EPA) and 400 mg DHA, for one week and eight women served as unsupplemented controls. Milk samples were collected on days 0, 1 and 7. The fatty acid composition of the milk was analyzed by capillary gas chromatography with flame ionisation detection. Supplementation with AA alone had no effect on breastmilk AA, but tended to reduce EPA and DHA levels. Administration of a combination of AA, EPA and DHA tended to increase both milk AA and long chain PUFA (LCPUFA)omega 3 content. A larger simultaneous increase of milk AA, DHA and EPA than observed in the present study can probably be accomplished by the use of a combination of a lower LCPUFA omega 6/LCPUFA omega 3 ratio and higher AA, EPA and DHA dosages.

Estimated biological variation of the mature human milk fatty acid composition.

We estimated the biological variation (CV(biol)) of 28 fatty acids (FA) in 465 mature human milk samples from The Netherlands, Caribbean, Jerusalem, Tanzania and Pakistan, by using data from the observed variation (CV(obs)) and analytical variation (CV(anal)). CV(biol) of the various regions was remarkably similar. The average CV(biol) of 455 samples, Pakistan excluded, ranged from 12.7% for 16:0 and 18.9% for 18:1 omega 9 to 68% for 22:6 omega 3 and about 100% for 20:5 omega 3. Those of 20:4 omega 6, 18:2 omega 6 and 18:3 omega 3 were 28.0, 33.0 and 37.3%, respectively. Because of the large CV(biol) and the many dietary changes in recent history, it seems impossible to consider the present human milk FA composition as the 'gold standard' for infant formula. Optimal human milk FA composition should rather derive from populations that consume traditional diets or from the scientific data that show the function of the individual FAs in neonatal development.

Assessment of essential fatty acid and omega3-fatty acid status by measurement of erythrocyte 20:3omega9 (Mead acid), 22:5omega6/20:4omega6 and 22:5omega6/22:6omega3.

BACKGROUND: Early suspicion of essential fatty acid deficiency (EFAD) or omega3-deficiency may rather focus on polyunsaturated fatty acid (PUFA) or long-chain PUFA (LCP) analyses than clinical symptoms. We determined cut-off values for biochemical EFAD, omega3-and omega3/22:6omega3 [docosahexaenoic acid (DHA)]-deficiency by measurement of erythrocyte 20:3omega9 (Mead acid), 22:5omega6/20:4omega6 and 22:5omega6/22:6omega3, respectively. METHODS: Cut-off values, based on 97.5 percentiles, derived from an apparently healthy omnivorous group (six Dominica breast-fed newborns, 32 breast-fed and 27 formula+LCP-fed Dutch low-birth-weight infants, 31 Jerusalem infants, 33 Dutch 3.5-year-old infants, 69 omnivorous Dutch adults and seven Dominica mothers) and an apparently healthy group with low dietary LCP intake (81 formula-fed Dutch low-birth-weight infants, 12 Dutch vegans). Cut-off values were evaluated by their application in an EFAD suspected group of 108, mostly malnourished, Pakistani children, three pediatric patients with chronic fat-malabsorption (abetal-ipoproteinemia, congenital jejunal and biliary atresia) and one patient with a peroxisomal beta-oxidation disorder. RESULTS: Erythrocyte 20:3omega9, 22:5omega6/20:4omega6 and 22:5omega6/22:6omega3 proved age-dependent up to 0.2 years. Cut-off values for ages above 0.2 years were: 0.46mol% 20:3omega9 for EFAD, 0.068mol/mol 22:5omega6/20:4omega6 for omega3-deficiency, 0.22mol/mol 22:5omega6/22:6omega3 for omega3/DHA-marginality and 0.48mol/mol 22:5omega6/22:6omega3 for omega3/DHA-deficiency. Use of RBC 20:3omega9 and 22:5omega6/20:4omega6 cut-off values identified 20.4% of the Pakistani subjects as EFAD+omega3-deficient, 12.9% as EFAD+omega3-sufficient, 38.9% as EFA-sufficient+omega3-deficient and 27.8% as EFA-sufficient+omega3-sufficient. The patient with the peroxisomal disorder was classified as EFA-sufficient, omega3-sufficient (based on RBC 22:5omega6/20:4omega6) and omega3/DHA-deficient (based on RBC 22:5omega6/22:6omega3). The three other pediatric patients were classified as EFAD, omega3-deficient and omega3/DHA-deficient. CONCLUSION: Use of the combination of the present cut-off values for EFA, omega3 and omega3/DHA status assessment, as based on 97.5 percentiles, may serve for PUFA supplement intervention until better concepts have emerged.

Functional aspects of developmental toxicity of polyhalogenated aromatic hydrocarbons in experimental animals and human infants.

A scientific evaluation was made of functional aspects of developmental toxicity of polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) in experimental animals and in human infants. Persistent neurobehavioral, reproductive and endocrine alterations were observed in experimental animals, following in utero and lactational exposure to PCBs, PCDDs and PCDFs. The lowest observable adverse effect levels (LOAELs) for developmental neurobehavioral and reproduction endpoints, based on body burden of TCDD-toxic equivalents (TEQs) in animals, are within the range of current background human body burdens. Relatively subtle adverse effects on neurobehavioral development and thyroid hormone alterations have also been observed in infants and children exposed to background levels. Exclusive use of the toxic equivalency factor (TEF) approach may underestimate the risk of neurodevelopmental effects, because both Ah receptor dependent and independent mechanisms may be involved in these effects. The use of marker congeners and/or bioassays based on Ah receptor mediated mechanisms are rapid, low cost pre-screening alternatives for expensive and time consuming gas chromatographic-mass spectrometric analysis.

Urinary steroid profile of a newborn suffering from pseudohypoaldosteronism.

A case is described of a newborn, admitted to hospital because of severe salt loss at the age of 1 month. Subsequent analysis of urinary steroid excretion, by gas chromatography and gas chromatography-mass spectrometry, revealed that the patient suffered from pseudohypoaldosteronism. However, it was difficult to interpret the results unambiguously, since the first urinary analysis appeared to suggest 21-hydroxylase- or 18-hydroxylase deficiency. The final diagnosis was possible only after detecting high urinary levels of aldosterone and tetrahydroaldosterone. It is concluded that neonatal urinary steroid profiles should be interpreted cautiously in order to arrive at the correct diagnosis.

Triglycerides, fatty acids, sterols, mono- and disaccharides and sugar alcohols in human milk and current types of infant formula milk.

OBJECTIVE: To investigate differences in the fatty acid composition, sterols, minor carbohydrates and sugar alcohols between human and formula milk. DESIGN: We analyzed the concentrations of triglycerides, sterols, di- and monosaccharides and sugar alcohols, as well as the fatty acid composition of 10 currently available types of formula milk for term babies. Results were compared with mature human milk from 99 exclusively breast-feeding Dutch women, who collected 24-hour samples in the second week (n = 99), sixth week (n = 99) and 3 months (n = 25) after delivery. Infant formula milk data were considered different if they fell outside the mean +/- 2s.d. range of corresponding human milk data. RESULTS: The triglyceride concentrations in human milk were lower than those of the formula milk, possibly due to an incomplete collection of fat-rich hindmilk. Formula milks tended towards a higher proportion of medium chain fatty acids and lower proportions of longer-chain polyunsaturated fatty acids. Formulas had cholesterol concentrations 3-35 times lower, and much higher phytosterol concentrations, compared with the human milk. In the formula milk types the glucose, sorbitol and myoinositol concentrations were generally lower, whereas the fucose and erythreitol concentrations were in the lower mean +/- 2s.d. human milk range. The galactose concentrations in the formulas were generally higher. CONCLUSIONS: Formula milk and human milk differ considerably in fatty acid composition and concentrations of cholesterol, phytosterols, monosaccharides and sugar alcohols. The biological consequences of these differences in composition are uncertain.

Weight loss in full-term negroid infants: relationship to body water compartments at birth?

The possible influence of the body fluid compartments at birth on postnatal weight loss was studied in normal term negroid infants when on a standardized oral fluid, sodium and energy regimen during the first three days of life. Measurements of plasma volume (PV), total body water (TBW), and extracellular water (ECW) were performed simultaneously on vaginally-born infants on the first day of life, by using a triple indicator (Evans blue, deuterium oxide and sucrose) single injection dilution technique. PV was 54 +/- 7 ml/kg (N = 9), TBW was 751 +/- 50 ml/kg (N = 13) and ECW was 311 +/- 61 ml/kg (N = 13) (mean +/- S.D.). Postnatal weight loss (3.7% of birth weight) occurred during the first two days. The postnatal weight loss was not related to any of the body water compartments. However, there was a highly significant correlation with the (cumulative) urine water excretion (r = 0.833, P less than 0.001 on day 1, with similar values for days 1 and 2).

Indicators of long chain polyunsaturated fatty acid status of exclusively breastfed infants at delivery and after 20-22 days.

The fatty acid composition of plasma cholesterol esters (CE), erythrocytes (RBC) and mature milk from seven lactating/women and their exclusively breastfed newborns, living on Dominica, were studied. Blood samples were taken from umbilical cord and mother at birth. A sample of breastmilk was collected on day 20-22 postpartum, together with a blood sample from the baby. At birth, cord blood plasma CE and RBC total long chain polyunsaturated fatty acid (LC-PUFA) contents were higher, and linoleic (18:2c, omega 6) and alpha-linolenic (18:3c, omega 3) acid contents lower, than in corresponding maternal compartments. Cord blood RBC LC-PUFA omega 3 content was lower and LC-PUFA omega 6 content higher than in maternal RBC. After birth, feeding with human milk led to a drop in LC-PUFA content in the plasma CE fraction, whereas RBC LC-PUFA content remained virtually constant. Current understanding of the origin and relative affinity of fatty acids incorporated in plasma CE and RBC suggests that RBC LC-PUFA content is a more reliable parameter for LC-PUFA status than plasma CE LC-PUFA content. The RBC LC-PUFA data suggest therefore that at birth the newborn has a lower LC-PUFA omega 3 status than the mother, and that this does not change during three weeks of exclusive breastfeeding.

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 and its effect on neonatal neurological development.

Polychlorinated biphenyls (PCBs) and dioxins (polychlorinated dibenzo-p-dioxins (PCDDs), and dibenzofurans (PCDFs)) are widespread environmental contaminants which are neurotoxic in animals. Perinatal exposure to PCBs, PCDDs, and PCDFs occurs prenatally via the placenta and postnatally via breast milk. To investigate whether such an exposure affects the neonatal neurological condition, the neurological optimality of 418 Dutch newborns was evaluated with the Prechtl neurological examination. Half of the infants were breast-fed, the other half were formula-fed, representing a relatively high against a relatively low postnatally exposed group, respectively. As an index of prenatal exposure, four non-planar PCBs in cord and maternal plasma were used. These PCB levels were not related to neurological function. As measures of combined pre- and early neonatal exposure, 17 dioxin congeners, three planar, and 23 non-planar PCB congeners were determined in human milk in the second week after delivery. Higher levels of PCBs, PCDDs, and PCDFs in breast milk were related to reduced neonatal neurological optimality. Higher levels of planar PCBs in breast milk were associated with a higher incidence of hypotonia. This study confirms previous reports about the neurotoxic effects of these compounds on the developing brain of newborn infants.

Neurological condition in 18-month-old children perinatally exposed to polychlorinated biphenyls and dioxins.

The neurological optimality of 418 Dutch children was evaluated at the age of 18 months, in order to determine whether prenatal and breast milk mediated exposure to polychlorinated biphenyls (PCBs) and dioxins affected neurological development. Half of the infants were breast-fed, the other half were formula-fed. PCB concentrations in cord and maternal plasma were used as a measure of prenatal exposure to PCBs. To measure postnatal exposure, PCB and dioxin congeners were determined in human milk and in formula milk. After adjusting for covariates, transplacental PCB exposure was negatively related to the neurological condition at 18 months. Although greater amounts of PCBs and dioxins are transferred via nursing than via placental passage, an effect of lactational exposure to PCBs and dioxins could not be detected. We even found a beneficial effect of breast-feeding on the fluency of movements. We conclude that transplacental PCB passage has a small negative effect on the neurological condition in 18-month-old toddlers.

Environmental exposure to polychlorinated biphenyls (PCBs) and dioxins. Consequences for longterm neurological and cognitive development of the child lactation.

UNLABELLED: Polychlorinated biphenyls (PCBs) and dioxins are environmental pollutants. Prenatally, as well as postnatally through breast feeding, large amounts are transferred from mother to the child. Formula is free of these substances. Considering their potential developmental neurotoxicity, we investigated long term effects of perinatal exposure to PCBs and dioxins on neurological and cognitive development. Given the evidence that PCBs exert oestrogenic effects, and oestrogens are known to suppress lactation, we investigated the effect of maternal PCB body load on lactation performances as well. METHODS: A group of 418 infants were followed from birth up to 6 years of age. Half of them were fully breast fed (BF) for at least 6 weeks. Prenatal PCB exposure was measured from cord and maternal blood. Postnatal exposure was reflected by PCB and dioxin levels in breast and formula milk and plasma PCB levels at 42 months of age. Both neurological and cognitive development were taken as outcome variable at 18, 42 months and at 6 years of age. At 18 and 42 months of age neurological condition was evaluated according to Hempel and at 6 years of age according to Touwen. Condition was evaluated in terms of optimality. Separately, the fluency of movements was scored. Cognitive abilities were measured at 18 months by the Bayley Scales of Infant Development, at 42 months of age by the Kaufman Assessment Battery for Children (K-ABC) and at 6 years of age by the McCarthy Scales. Daily breast milk volume and milk fat content in relation to PCB body load was evaluated in 102 mothers. Multivariate regression models were applied to analyse associations of measured exposure variables with independent variables adjusted for confounders. RESULTS: At 18 months of age cognitive development was not affected by either pre- or postnatal exposure to the measured PCBs and dioxins. However, neurological examination showed an adverse effect of prenatal exposure to the measured pollutants on neurological optimality score. At 42 months of age we found negative associations between prenatal PCB exposure on cognitive development. However no effect was demonstrated on postnatal exposure to the measured pollutants. Neurological development was not affected by either pre- or postnatal exposure to PCBs and dioxins. At 6 years of age the preliminary results revealed evidence that cognitive development is affected by prenatal exposure to these pollutants in children from young mothers. An adverse effect of prenatal exposure on neurological outcome was also demonstrated in the formula fed group but not in the breast fed group. Despite a higher PCB exposures from breast milk we found at 18 months, 42 months of age, and at 6 years of age a beneficial effect of breast feeding on the quality of movements, in terms of fluency, and on the cognitive development tests. Maternal PCB body load was inversely related to 24-h breast milk volume and milk fat content. CONCLUSION: These data give evidence that prenatal exposure to PCBs do have subtle negative effects on neurological and cognitive development of the child up to school-age. Human breast milk volume and fat content is adversely affected by the presently encountered PCB levels in W. Europe. Our studies showed evidence that breast feeding counteracts the adverse developmental effects of PCBs and dioxins.

The Dutch PCB/Dioxin Study. Contents of dioxins, planar and other PCBs in human milk from the Rotterdam and Groningen area.

In two areas (Groningen and Rotterdam): individual human milk samples (24 hr.) were obtained 10 and 42 days after delivery from about 200 mothers. In all samples non-planar PCBs, including some monoorthochlorine substituted PCBs were determined. All first samples, and a smaller number of the second samples were analysed for dioxins and coplanar PCBs. The obtained results are in the same order of magnitude as earlier Dutch results and do in general not differ from the situation in neighbouring countries. No differences could be observed between the analytical results of both areas.

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.

Dioxin and PCB levels in blood and human milk in relation to living areas in The Netherlands.

Dioxins and polychlorinated biphenyls (PCBs) are ubiquitous toxic compounds in the environment. Negative influences of these compounds on the health status of human beings have been described. Especially susceptible might be the fetus, which is exposed in utero, and the newborn breast-fed infant, since both are exposed to relatively high levels of dioxins and PCBs during a critical period of organ growth and development. We investigated PCB levels in 406 maternal plasma samples as well as PCB and dioxin levels in 172 human milk samples with relation to living area of women living for at least five years in the western industrialized part of the Netherlands or the northern more rural part. The western part was further subdivided into one urban and two highly industrialized areas. After correction for covariates, we found significantly higher levels of PCB 118 in maternal plasma as well as significantly higher levels of the dioxin-TEQ and of ten individual dioxin and PCB congener levels in human milk in the western more industrialized areas of the Netherlands compared to the northern more rural part. We did not find significant differences in planar, mono-ortho or di-ortho PCB-TEQ levels in human milk between all different areas. We conclude that significantly higher levels of a number of dioxin and PCB congeners are found in women living in industrialized areas compared to women living in rural areas in the Netherlands.

Conjoined twins and abdominal pregnancy.

Abdominal pregnancy is rare; conjoined twins are also rare. The diagnosis of abdominal pregnancy is easily missed and often not made until near full-term. Similarly conjoined twins are not diagnosed until late in gestation or during parturition. In this case, the diagnosis of conjoined twins and abdominal pregnancy was only made during laparotomy.

Neonatal neurological morbidity in relation to obstetrical and social conditions in Grenada (Caribbean).

Neonatal morbidity, in particular neurological morbidity is a more relevant measure of the effectiveness of obstetrical care than perinatal mortality. Neurological morbidity was assessed in a birth cohort in Grenada, and appeared to be lower than in a reference group examined in Groningen, the Netherlands, in 1975-1978. Perinatal mortality, however, was higher. The results support the thesis that some children may have died who, if they would have survived, would have been neurologically abnormal. It is concluded that whereas a decrease in perinatal deaths is an essential goal in Grenada, a concomitant increase in morbidity should be carefully avoided.