Neuropsychological Development in Patients with Long-Chain 3-Hydroxyacyl-CoA Dehydrogenase (LCHAD) Deficiency.

BACKGROUND: Reports on cognitive outcomes in long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) are scarce. We present results from neuropsychological assessments of eight patients diagnosed with LCHADD prior to newborn screening with regard to clinical disease severity. METHODS: Intellectual ability and adaptive and executive functions were assessed using age-appropriate Wechsler Scales, Adaptive Behavior Assessment Scales (ABAS), and Behavior Rating Inventory of Executive Function (BRIEF). RESULTS: Five patients performed in the normal range on IQ tests but with lower scores on verbal working memory. In addition, they had lower parent-rated adaptive and executive functions.Three patients had intellectual disabilities with IQs below normal and/or autism spectrum disorders. In addition, they had low results on parent-rated adaptive functions. (Two of these patients had epilepsy.) Conclusions: Patients with LCHADD seem to have a specific cognitive pattern, with presentation as intellectual disability and specific autistic deficiencies or a normal IQ with weaknesses in auditive verbal memory and adaptive and executive functions. Future studies are warranted to investigate whether newborn screening programs and early treatment may promote improved neuropsychological development and outcomes.

Fatty acid composition of diet, cord blood and breast milk in Chinese mothers with different dietary habits.

The influence of two different dietary patterns on maternal fatty acid (FA) intake on the composition of umbilical cord blood plasma phospholipids and transitional breast milk was investigated. A 7-day dietary record was completed in the last trimester of pregnancy by women living in an inland and a coastal area of south-eastern China. The FA composition in maternal diet was calculated using the 2002 Chinese food composition database. Cord blood and transitional breast milk samples were collected and their FA composition was analyzed by capillary gas-liquid chromatography. Mothers in the coastal area showed higher intake of long-chain polyunsaturated FA (LCPUFA) including docosahexaenoic acid (DHA, 22:6omega) and eicosapentaenoic acid (EPA,20:5omega3) but lower linoleic acid (LA, 18:2omega6) and alpha-linolenic acid (ALA, 18:3omega3) than the mothers in the inland area. The intake of arachidonic acid (AA, 20:4omega6) did not differ between the two areas. LA, ALA, AA and DHA in breast milk of day 5 reflected the maternal diet except that the EPA content in breast milk at day 5 was similar for the areas. LA, ALA and AA were lower and EPA higher in umbilical cord plasma phospholipids in infants from the costal compared to the inland area. There were significant differences in maternal intakes of FA confirming different dietary habits, which influenced the FA composition of cord plasma phospholipids and transitional breast milk. Since FA influence gene expression the found variation implies that the long-term follow-up of this cohort will be interesting.

Fatty acid composition in breast milk and serum phospholipids of healthy term Chinese infants during first 6 weeks of life.

AIM: To compare the fatty acid (FA) pattern in early and mature breast milk with that in plasma phospholipids of cord blood and breast-fed infants. METHODS: Forty-five mother-infant pairs from western Shanghai were studied. All infants, born at term with normal weight and length, were examined at birth and days 5 and 42. FA was analyzed by capillary gas-liquid chromatography. RESULTS: Cord blood showed higher concentration of long-chain polyunsaturated FA (LCPUFA) but lower saturated (SFA) and monounsaturated (MUFA) FA than postnatal infants' plasma. SFA decreased with age in the infants, but MUFA and linoleic acid (LA, 18:2omega6) increased. LCPUFA were lower in the plasma of 5-day-old infants than in cord blood, but LA was 80%, alpha-linolenic acid (ALA, 18:3omega3) 33% and the ratio omega-6/omega-3 42% higher. At day 42, LA increased further, LCPUFA remained similar, and was in breast milk lower than at day 5, while ALA and gamma-linolenic acid (18:3omega6) were higher. The activity index of desaturases indicated high Delta9 activity in breast milk and high activity of Delta5 desaturase in the infants. CONCLUSION: Breast milk FA composition changed markedly from day 5 to 42 with increasing correlation to infants' plasma. Calculation of desaturase activities suggested high capacity of LCPUFA synthesis.

Breast milk levels of zinc and omega-6 polyunsaturated fatty acids and growth of healthy Chinese infants.

AIM: To examine the concentrations of zinc and omega-6 polyunsaturated fatty acids (omega-6 PUFAs) in breast milk, the impact of zinc on omega-6 PUFA metabolism, and the growth rate of infants. METHODS: Forty-one mother-term infant pairs from a rural area of northern Beijing, China, who were 1 month (n = 18, group I) and 3 months (n = 23, group II) old and exclusively breastfed, were studied. The dietary records and the concentrations of zinc and omega-6 PUFAs in the milk of lactating women and the increase in weight and length of their infants during 1 and 3 postnatal months were analysed. RESULTS: The dietary intakes of mothers in the two groups were the same, i.e. high in carbohydrate and low in fat, protein and energy. The maternal zinc intake was 7.5mg/d and thus reached only 34.6% of the current Recommended Nutrient Intake (RNI). The levels of zinc and arachidonic acid (AA, C20:4 omega-6) in the milk of group I were significantly higher than those in group II. Furthermore, significant positive correlations were found between the concentrations of zinc and AA in the breast milk and between the level of milk AA and weight gain. CONCLUSION: Zinc may be a co-factor and essential for essential fatty acids (EFA) metabolism. Thus suboptimal zinc intake may cause EFA imbalance. Further studies of Chinese rural mother-infant pairs are necessary to determine whether zinc supplementation should be recommended when lactation exceeds 3 months.

Polychlorinated biphenyls in colostral milk and visual function at 12 months of life.

BACKGROUND AND AIMS: 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. MATERIAL: 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. METHODS: 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). RESULTS: 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). CONCLUSION: 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.

Ethical issues in research on control of the HIV/AIDS epidemic: report from a workshop of the world federation of scientists, Erice, Sicily, Italy, 22-24 August 2003.

In research on control of the HIV/AIDS epidemic there are many ethical issues to be considered. The problem of personal autonomy versus the interest of society to prevent the spread of the disease in various settings makes it difficult to follow the regulations of the Declaration of Helsinki in all respects. This is particularly clear in the evaluation of trials aimed at preventing mother-to-child transmission of HIV. The interest of the child does not always conform to the policy of avoiding stigmatization of the mother. Programmes for the implementation of antiretroviral therapy and vaccine trials may differ in countries with different mean incomes of the inhabitants, and are also influenced by local patterns. For this reason, the Declaration of Helsinki should be changed in such a way that it conforms with the ways in which it may be possible to combat such a disastrous epidemic as that caused by HIV.

Flawed reports of immunization complications: consequences for child health.

UNLABELLED: Flawed studies about complications in vaccination programmes may have serious consequences for community health, as illustrated by a previous report on the adverse effect of pertussis vaccination and a more recent report about a suspected link between MMR vaccination and autistic spectrum disorders. CONCLUSION: The Editorial Board of The Lancet has apologized for having published a paper which has misled its readers about the risk of MMR vaccination. Due to the important role of TV and newspapers in giving information about health promotion, these media should also be willing to correct false information.

Foetal growth of kidneys, liver and spleen in intrauterine growth restriction: "programming" causing "metabolic syndrome" in adult age.

BACKGROUND/AIMS: Epidemiological studies in humans link adult disease to abnormal growth in utero. In addition to general malnutrition of the foetus, preferential blood flow to the brain and heart may furthermore deprive organs such as the liver, spleen and kidneys of oxygen and macro- and micronutrients. As a consequence, these organs may not develop normally, which predisposes the individual to the so-called metabolic syndrome (syndrome X) in later life. The effects of foetal undernutrition on the growth of some abdominal organs were investigated by comparing the volume of the kidneys, spleen and liver in small-for-gestational-age (SGA) newborn infants with that in appropriate-for-gestational-age (AGA) newborn infants. METHODS: In 25 randomly selected AGA infants and 25 SGA infants, who were subdivided into three gestational age groups (<30, 30-36 and 37-40 wk) the volumes of the liver, kidneys and spleen were determined by ultrasonography. Organ volumes were estimated using the standard ellipsoid formula (longitudinal x anteroposterior x transverse diameter x pi/6). Liver/kidney, liver/spleen and kidney/spleen volume ratios were also determined. RESULTS: The volumes of the kidneys and liver differed significantly between AGA and SGA infants in all three gestational age groups (p < 0.0018 and p < 0.029, respectively). The fact that the spleen volume differed only in the 37-40 wk group (p = 0.0002) may indicate that there is a graded relationship across the whole range of normal birthweight. The correlation between the liver volume and birthweight differed significantly between SGA and AGA infants (r = 0.56 vs 0.84, p = 0.04). On the other hand, the volume ratios between the three organs were the same in all groups (p > 0.15). CONCLUSION: In intrauterine growth retarded infants, foetal growth of the liver and kidneys is more impaired than the body as a whole. Retarded foetal development of these organs may cause metabolic dysfunction, which predisposes to the group of diseases included in the so-called metabolic syndrome or syndrome X.

Industrial and agricultural pollution: a threat to the health of children living in the Arctic region.

UNLABELLED: Various environmental pollutants of industrial or agricultural origin such as persistent organic pollutants (POCs) are causing great concern owing to their toxicity to humans and animals. At the Stockholm Convention on POCs in 2001, 12 of these pollutants, i.e. dioxins, PCBs (polychlorinated biphenyls) and DDT were referred to as "the dirty dozen". CONCLUSION: Collaborative studies by scientists from Canada, Russia, Scandinavia and other countries representing different fields such as environmental chemistry, ecology and medical sciences may increase our knowledge about the present threat of toxic chemicals to ecology and human health in the Arctic region. It is hoped that improved understanding will promote preventive political decisions.

Initiation of breastfeeding.

UNLABELLED: Breastfeeding is a biological process that is highly influenced by various physiological and environmental factors such as the plans for infant feeding of pregnant women, their education and work situation, family support and nutrition. CONCLUSION: The way in which breastfeeding is initiated in the early postnatal period is of importance both for how long the process is likely to continue and for the growth of the infant.

Vertical transmission of HIV-1 infection and dilemma of infant feeding.

UNLABELLED: The problem of giving proper recommendations on early feeding of infants of HIV-1-positive mothers in countries with deficient hygienic conditions is discussed. Even in exclusive breastfeeding, which is associated with a lower risk of HIV transmission than when supplements are given, the risk that the infant will acquire HIV-1 has to be balanced against the risk of formula feeding. Furthermore, it also has to be stressed that exclusive breastfeeding is a rarity in many poor countries. CONCLUSION: The dilemma of recommending appropriate early feeding to HIV-1-positive mothers will persist until further studies of the type performed by the Coutsoudis group in South Africa have been performed.

Concentrations of dioxins and other organochlorines (PCBs, DDTs, HCHs) in human milk from Seveso, Milan and a Lombardian rural area in Italy: a study performed 25 years after the heavy dioxin exposure in Seveso.

AIM: To investigate whether those who were exposed to high levels of the dioxin TCDD 25 years ago in Seveso, northern Italy still have higher than the expected levels of dioxins in their fat stores, and to investigate the concentrations of dioxins in the breast milk of mothers in Seveso and in two other regions in Italy. The load of vertically transmitted dioxins to the next generation, if being breastfed, was also investigated. METHODS: As there may be a synergistic effect of mixtures of organic chlorines, the concentrations of pesticides such as DDTs and PCBs have also been studied in the same human milk samples. Breast milk from 12 mothers from Seveso, Central Milan and a Lombardian village was collected for analysis during the first week and 1 and 3 mo after delivery. Individual samples were used for the analysis of pesticides and PCBs, whereas dioxins were analysed in pooled samples from all 12 mothers on each occasion. RESULTS: In human milk from Seveso, the TCDD concentration in fat calculated on a fresh weight basis was more than twice as high as the level in the other two regions, whereas the concentrations of investigated other toxins were lower in Seveso possible due to induction of the enzyme cytochrome P4501A, which means that the total level of dioxins was the same in all three locations. The congener profile, measured as mean toxic equivalency (TEQ) values, was the same in the Italian samples as previously reported from Stockholm. The calculations are based on the most recent WHO TCDD equivalency factors (TEF). The DDE concentration was higher in the samples from Milan than in the samples from the other two Italian regions, which may be due to the fact that, to a greater extent than in the other regions, Milanese food is imported from countries where DDT is still used as a pesticide. CONCLUSION: Twenty-five years after the dioxin catastrophe, human milk from mothers in Seveso has concentrations of the highly toxic dioxin congener TCDD that are more than twice as high as those in central Milan and a Lombardian village. This means that breastfed infants in Seveso still store an appreciable amount of TCDD in their body fat. The health consequences of this fact remain to be elucidated. The effect of the high load of DDTs in central Milan also has to be considered

Hospitalization in Sweden of children born to immigrants.

AIM: To study whether excess hospitalization occurs among certain groups of children born in Sweden to immigrant parents. METHODS: The study was based on linkage of the Swedish Medical Birth Register 1987-1997 and the Swedish Hospital Discharge Register 1987-1998. RESULTS: Among children whose parents were of Swedish nationality excess hospitalization was found for children of young mothers, parity 3 or more, and if the mother smoked in early pregnancy. These factors were controlled for in the further analysis. Ten years after birth, a large percentage of children born to parents with foreign nationality could not be followed owing to death or emigration (19.9% vs 1.77% of children with Swedish parents). An excess hospitalization of immigrant children up to the age of about 5 y was seen but after that, if anything, these children were hospitalized less. For the whole group of children born to parents of non-Swedish nationality there was no difference in hospitalization rate after stratification for risk factors and age. When analysis was performed for specific nationalities significantly reduced rates were found for several western European countries while significantly increased rates were seen for the Middle East, north Africa and especially sub-Saharan Africa (odds ratio 1.57, 95% confidence interval 1.49-1.64). CONCLUSION: A moderately increased rate of child hospitalization was only observed for some selected immigrant groups.

Bibliometric data: a disaster for many non-American biomedical journals.

UNLABELLED: Bibliometric data published by the Institute of Scientific Information in Philadelphia (ISI), and which was previously discussed in Acta Paediatrica, has increasingly been used despite all the relevant and severe criticism that has been raised against this method of evaluating individual research results and grading scientific journals. It is obvious that the present trend regarding the use of bibliometric data as a basis for priorities and funding of research and for the promotion of individual scientists favours American-oriented research projects at the expense of those that are based on concepts of predominantly European relevance. CONCLUSION: For the future of non-American research, it is important that no single super-power, i.e. the USA, should dominate scientific priorities. The condition for efficient European competition is that European Centres with high levels of competence for creative research and training of scientists from all over the world are established. In addition, it is important that the results of European research are published in prestigious European journals, as was the situation before World War II.

Prospects of vaccination as a means of preventing mother-to-child transmission of HIV-I.

Although short-course antiretroviral therapy is efficient in reducing mother-to-child transmission (MTCT) of HIV-1, it does not prevent transmission during the breastfeeding period. There is therefore an urgent need to test various approaches, including HIV-1 vaccination, to try to prevent postnatal transmission of HIV-1 in breastfeeding populations in developing countries.