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The fatty acid composition of 48 samples of banked human milk for preterm infants and four standard infants formulas available in Finland were analysed by capillary gas liquid chromatography. The banked milk was collected from mothers who had given birth 0-8 weeks previously. Saturated fatty acids accounted for approximately 50% of the fatty acids in both human milk and the formulas, while the relative content of monoenoic fatty acids tended to be higher in human milk than in the formulas. The relative content of 18:2n-6 was higher in the formulas (range 14.7%-23.2%) than in human milk (median 9.1%, range 6.3%-13.4%). Fat of banked human milk contained 0.9% and 0.7% polyunsaturated fatty acids with 20 and 22 carbon atoms (LCP), respectively, which is comparable to that of fresh mature human milk. In contrast, LCP could not be detected in any of the formulas. Conclusion. Banked human milk is a good source of LCP and offers a good alternative to LCP containing formulas. [ABSTRACT FROM AUTHOR]

Aim: We tracked the body mass index (BMI) of children born to mothers with or without gestational diabetes mellitus (GDM) or type 1 diabetes from birth to 12 years of age and examined the trends in both diseases., Methods: Antenatal and postnatal health survey data were collected from 6909 Finnish children born at six time points between 1974 and 2004. We compared the BMI trajectory between the offspring of mothers with and without GDM or type 1 diabetes, and the association between GDM and overweight offspring was analysed., Results: The prevalence of GDM and type 1 diabetes increased markedly over the study period. The BMI trajectory in the GDM or type 1 diabetes offspring differed significantly from the nondiabetic offspring. The timing of adiposity rebound occurred significantly earlier in the GDM (4.8 years) and type 1 diabetes (4.4 years) groups than the nondiabetic group (5.5 years). GDM offspring were more likely to be overweight at five, seven and 12 years of age (24.6%, 28.1%, 29.4%) than nondiabetic offspring (15.6%, 18.3%, 18.1%)., Conclusion: Children born to mothers with GDM were significantly more likely to be overweight at an early age than those born to nondiabetic mothers., (©2016 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

In a previous study, we observed a higher incidence of dyslipidemia in pediatric renal recipients compared with liver recipients. In the present study, we measured common carotid artery intima-media thickness (IMT) in 13 pediatric renal recipients, 9 liver recipients, and 26 control individuals with median age of 11.4, 10.8, and 12.0 years, respectively. The patients were studied from 0.2 to 10.8 years after renal transplantation (RTx) or liver transplantation (LTx). An experienced radiologist (T.K.) blinded to the status of the children measured the IMT using a high-resolution B-mode ultrasonography method. In patients who underwent RTx or LTx, serum fasting lipid profile, estimates of renal and liver function, and glucose metabolism were determined. Children undergoing RTx or LTx more often had hypertension compared with the control individuals (P = .004). Before transplantation, dyslipidemia was greater in patients undergoing RTx compared with those undergoing LTx (P < .05). Children who underwent RTx, compared with those who underwent LTx or control individuals, had thicker mean IMT at the 6 sites measured (mean [SD], 0.57 [0.07], 0.51 [0.05], and 0.53 [0.06] mm, respectively; P = .02]. As a result of linear regression in renal recipients, variability of glomerular filtration rate (<60 mL/min/1.73 m(2) vs normal) accounted for 43.3% of variability of the mean of maximal IMT (B = 8.9; SE = 3.1; P = .01). Variability of pre-RTx serum triglyceride concentration (B = 1.6; SE = 0.6; P = .03) and actual triglyceride concentration (B = 10.3; SE = 2.2; P = .002) accounted for 82.2% of variability of maximal IMT. Our findings support previous data on the importance of maintenance of good graft function with sufficient but not overly efficient immunosuppression after transplantation in prevention of future cardiovascular disease.

Nineteen of 35 children (54%) with acute lymphoblastic leukemia receiving maintenance therapy consisting of daily oral 6-mercaptopurine and weekly oral methotrexate developed hypoglycemia (blood glucose level <2.7 mmol/L [50 mg/dL] or <2.9 mmol/L [54 mg/dL] with symptoms) during 16 hours of overnight fasting. In 15 of 15 re-studied children, fasting tolerance had improved, and in 67% (10/15), it had become normal a few months after cessation of therapy.

Hereditary tyrosinaemia type I is the most common of the diseases caused by defects in tyrosine metabolism. The underlying genetic defect is a mutation in the gene for fumarylacetate hydrolase (FAH), and more than 30 different mutations in this gene have been identified. The main clinical consequences of this defect include hepatic involvement, with a high risk for liver cancer, and renal tubular dysfunction. Restriction of phenylalanine and tyrosine from the diet along with supportive measures can ameliorate the symptoms, but cure has so far been possible only with liver transplantation. Recent discovery of a pharmacological treatment with a peroral inhibitor of tyrosine catabolic pathway, 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC), offers a new promising tool for the treatment of patients with hereditary tyrosinaemia type I. Mouse models of FAH deficiency have been successfully used in experimental gene therapy, and these studies indicate that future management of tyrosinaemia with a gene therapeutic approach may become feasible.

Many complications of prematurity have been suggested to result from free radical generation and an inadequacy of antioxidative capacity. We measured the plasma total peroxyl radical-trapping capability (TRAP) and concentrations of the main chain-breaking antioxidants contributing to it, i.e. uric acid, ascorbic acid, alpha-tocopherol, protein sulfhydryl groups and bilirubin, in 21 preterm infants with a mean birth weight of 1440 g and gestational age of 30 wk. The infants were divided into two groups according to their short-term outcome; the good outcome group (GOG) (N = 11) with no signs of morbidity and the poor outcome group (POG) (N = 10) with intraventricular haemorrhage and/or bronchopulmonary dysplasia and/or retinopathy. Arterial blood samples were obtained 3 and 10 days postpartum. TRAP was measured with a chemiluminescent method. As a comparison, venous blood samples from 13 adults (aged from 18 to 34) were used. At day 3 the poor outcome group had significantly higher TRAP than the good outcome or control group, mainly because of elevated uric acid concentration. Also the concentration of unidentified antioxidants was significantly lower in GOG. By day 10 the TRAP decreased substantially in both groups. However, from the components of TRAP, both ascorbate and the unidentified fraction decreased more in POG (p = 0.017 and 0.021, respectively). Furthermore in POG on day 10 urate concentration did not significantly differ from day 3 values. In conclusion, in preterm infants high TRAP was associated with high plasma uric acid concentration and a poor short-term prognosis.

Objective: The objective of this study was to evaluate the nutritional impact of therapeutic elimination diets and to identify risk factors predisposing infants with food allergy to poor growth., Study Design: We studied 100 children (mean age 7 months) with atopic dermatitis and challenge-proven cow's milk allergy and evaluated their growth during the symptomatic period before diagnosis and during the therapeutic elimination diet., Results: Clinical control of symptoms was achieved in all patients. The mean length SD score and weight-for-length index of patients decreased compared with those in healthy age-matched children, p < 0.0001 and p = 0.03, respectively. Low serum albumin was present in 6% of the patients, 24% had an abnormal urea concentration, and 8% had a low serum phospholipid docosahexaenoic acid. The delay in growth was more pronounced in a subgroup of patients with early onset than in those with later of symptoms (F = 6.665, p < 0.0001). The duration of breast-feeding correlated positively with the sum of n-3 polyunsaturated fatty acids (r = 0.39, p = 0.001) and with the relative amount of docosahexaenoic acid (r = 0.36, p = 0.002)., Conclusion: A delicate balance exists between the benefits and the risks of elimination diets.

Hereditary tyrosinaemia type 1 is a rare but serious metabolic disorder with an autosomal recessive mode of inheritance. We describe the prenatal diagnosis of an affected fetus performed by DNA-mutation analysis and a subsequent pregnancy with a healthy child in the same family.

Long-chain 3-hydroxyacyl-coenzyme A (CoA) dehydrogenase is one of three enzyme activities of the mitochondrial trifunctional protein. We report the clinical findings of 13 patients with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency. At presentation the patients had had hypoglycemia, cardiomyopathy, muscle hypotonia, and hepatomegaly during the first 2 years of life. Seven patients had recurrent metabolic crises, and six patients had a steadily progressive course. Two patients had cholestatic liver disease, which is uncommon in beta-oxidation defects. One patient had peripheral neuropathy, and six patients had retinopathy with focal pigmentary aggregations or retinal hypopigmentation. All patients were homozygous for the common mutation G1528C. However, the enoyl-CoA hydratase and 3-ketoacyl-CoA thiolase activities of the mitochondrial trifunctional protein were variably decreased in skin fibroblasts. Dicarboxylic aciduria was detected in 9 of 10 patients, and most patients had lactic acidosis, increased serum creatine kinase activities, and low serum carnitine concentration. Neuroradiologically there was bilateral periventricular or focal cortical lesions in three patients, and brain atrophy in one. Only one patient, who has had dietary treatment for 9 years, is alive at the age of 14 years; all others died before they were 2 years of age. Recognition of the clinical features of long-chain 3-hydroxyacyl-CoA deficiency is important for the early institution of dietary management, which may alter the otherwise invariably poor prognosis.

Type I tyrosinemia (HTI) is an autosomally recessively inherited disease caused by deficiency of fumarylacetoacetate hydrolase. The disease manifests with liver failure, renal tubular defects, and neurologic crises. Currently orthotopic liver transplantation (OLT) enables patients to survive. However, renal fumarylacetoacetate hydrolase deficiency is not corrected by OLT, and the long-term prognosis of the nephropathy is not known. We investigated tyrosine metabolism, GFR, renal tubular function, and histopathology before and 18-36 mo after OLT in eight patients with HTI. Progressive renal dysfunction was not documented despite continuing, although diminished, urinary succinylacetone excretion in all patients. The mean GFR was 82 mL/min/1.73 m2 before and 102 mL at 18 mo and 93 mL at 36 mo after OLT. All patients showed tubular dysfunction before OLT. At 18 mo, glucosuria occurred in one, amino aciduria and phosphaturia in three, and hypercalciuria in six patients. Only hypercalciuria was seen at 36 mo. Renal biopsies showed mild nonspecific changes caused either by minimal progression of the renal disease or by mild cyclosporine nephrotoxicity. In conclusion, patients with HTI had normal GFR, but showed signs of tubular dysfunction 18-36 mo after OLT. Renal function and histopathology should be monitored after OLT for HTI.

Using capillary gas chromatography, we analyzed the fatty acid composition of human milk from 23 women who had delivered prematurely and 16 women who had delivered at term. Milk samples were obtained at 1, 2, 4, 12, and 26 weeks after delivery. The relative amounts of saturated and monounsaturated fatty acids in preterm and term milk remained stable throughout the 6 months of lactation. The proportions of linoleate (18:2n-6) and alpha-linolenate (18:3n-3) were similar in preterm and term milk and showed an increasing trend from transitional (8.7-9.9% and 0.9-1.1% of total fatty acids, respectively) to mature milk (9.9-11.8% and 1.2-1.5%, respectively). The proportions of the major long-chain polyunsaturated fatty acids (LCP), 20:3n-6, 20:4n-6, 22:5n-3 and 22:6n-3, were highest at 1 week and decreased thereafter in both types of milk. In term milk, the proportion of LCP continued to decrease from 1 month to 6 months, whereas in preterm milk it was fairly constant. Consequently, at 6 months of lactation, the relative content of arachidonate (20:4n-6) was 1.5 times (p < 0.05) and that of docosahexaenoate (22:6n-3) was two times higher (p < 0.01) in preterm than in term milk. We conclude that in long-term lactation, preterm human milk provides a significantly higher relative supply of LCP than term human milk. This higher LCP content may be of special benefit to the development of a preterm infant.

Hereditary tyrosinemia type I (HTT-I) is an inherited metabolic disorder with severe liver disease and a high risk for hepatic malignancy. Patients with HTT-I are monitored with repeated analyses of serum amino acids, urine succinylacetone, and serum alpha-fetoprotein (AFP). Oncofetal markers CA 125 and CA 19-9 are elevated in serum of patients with various gastrointestinal diseases and malignancy. To study the biology of oncofetal antigens in tyrosinemia and to assess the possible usefulness of these markers in HTT-I, we studied serum concentrations of CA 125 (n = 160) and CA 19-9 (n = 188), together with AFP (n = 337), in serial samples from 10 patients. At early stages of the disease, most children with an acute type of disease had a remarkably elevated serum CA 125 concentration (153-1560 IU/L) that normalized gradually after the institution of therapy. Serum CA 125 levels may thus reflect acute metabolic imbalance in fulminant HTT-I. The patients with a chronic type of disease showed CA 125 levels within the normal range at diagnosis that slowly increased as the liver condition worsened. These concentrations, however, never reached values seen in acute HTT-I. Serum concentration CA 19-9 in HTT-I was mostly normal. Serum AFP levels fluctuated in all patients and positively correlated with tests for metabolic state and biliary function. A distinct increase in the serum AFP level was recorded in association with the detection of massive hepatocellular carcinoma and also preceded metabolic imbalance leading to porphyria crises.(ABSTRACT TRUNCATED AT 250 WORDS)

Hereditary tyrosinemia type I is a metabolic disease caused by a deficiency of fumarylacetoacetate hydrolase (FAH, EC 3.7.1.2), the last enzyme in the catabolic pathway of tyrosine. The molecular basis of FAH deficiency was examined in five Finnish patients suffering from this severe metabolic disease. No immunoreactive FAH nor enzymatic activity were found in their liver. Direct sequencing of the 14 exons of the FAH gene showed a G to A transition, which predicts a change from tryptophan to a stop codon (TGG-->TGA) at position 262 (W262X). Four of the five patients examined were homozygous for the mutation. Allele specific oligonucleotide hybridization showed a predominance of the W262X mutation in Finland (9 of 10 alleles) and the absence of this mutant allele in patients from other parts of the world. The loss of a BsaJI restriction site in those patients may be used for diagnosis.

This report describes the general outline and progress of a multicentre study on risk factors of coronary heart disease and their determinants in children and adolescents. "Cardiovascular Risk in Young Finns" comprises a cross-sectional study of 3 to 18-year old subjects in 1980, and follow-up studies in 1983 and 1986 in various parts of Finland, and in 1989 in one of the study areas (Turku). The number of participants in 1980 was 3596 (83.1%) of those invited. In 1983 and 1986 83.2% and 77.8% of them, respectively, participated. The study programme has comprised questionnaire data on, for example, general health and living conditions, physical activity, eating habits, smoking, and psychological variables. The physical examination covered height, weight, skinfold thickness, pubertal stages and blood pressure. Blood specimens were obtained to assess concentrations of serum lipids and insulin, and in 1986 also for possible genetic markers of hypercholesterolemia. A 48 hour recall on nutrient intake was obtained from some of the subjects. The follow-up studies have enabled a study of the tracking phenomenon. Other important questions under study include, for example, the possible clustering of risk factors and their determinants. The cohorts studied provide a valuable research basis for the future, with emphasis on enabling a long-term follow-up of the subjects.

A multicentre study on atherosclerosis precursors in young Finns aged three to 18 years was started in 1980 (3596 subjects) serum lipid concentrations (cholesterol, HDL (high density lipoprotein) cholesterol and triglycerides) were determined (n = 3554) and the apolipoproteins A-I and B measured (n = 1355). Two follow-up studies were carried out in 1983 (n = 2851) and 1986 (n = 2489), when HDL-subfractions (HDL-2-cholesterol and HDL-3-cholesterol) were also determined. Apolipoproteins A-I and B were measured again in 1986 (n = 1202). Serum total cholesterol concentration has fallen by about 1% annually during the 1980's from 5.07 mmol/l (1980) to 4.79 mmol/l (1986) in 9- to 18-year old children and adolescents. Mean values of serum triglycerides have slightly increased during the follow-up from 0.79 mmol/l to 0.84 mmol/l, respectively. In children and young adults (3-24 years) the mean cholesterol concentration was highest at the age of six and lowest during puberty. Concentrations of serum cholesterol, LDL (low density lipoprotein) cholesterol apoprotein B and triglycerides were higher in eastern than in western Finland in 1980 and 1983, but these differences were smaller in 1986, with the exception of serum triglycerides. Both in 1983 and in 1986 HDL-2-cholesterol was lower in the west than in the east, whereas HDL-3-cholesterol was higher in the former. The favourable changes in lipid levels should be reflected in future morbidity and mortality rates from coronary heart disease in Finland.

We wanted to determine the levels of fasting serum insulin during growth, the tracking of serum insulin, and the correlation of serum insulin with other coronary heart disease risk indicators in children and young adults. In 1986 2433 subjects, aged nine to 24 were studied, and insulin data were available from the same population in 1980 and 1983. Serum insulin levels showed a peak during puberty in both sexes and the decline in insulin continued after the age of 21. Tracking of serum insulin was only moderate, especially in females and young boys. Serum insulin correlated positively with body mass index, concentrations of serum triglycerides, and blood pressure, and inversely with the concentration of high density lipoprotein cholesterol. High triglycerides, high systolic blood pressure, and low level of high density lipoprotein cholesterol clustered among subjects within the highest insulin quartile. Our results suggest that the insulin resistance phenomenon, caused mainly by obesity and leading to unfavourable levels of other coronary heart disease risk indicators, is already developing in children and young adults. This suggests that preventing obesity in early life is important.

Plasma apolipoprotein B (apo B) concentrations were determined in 178 randomly selected 40-49-year-old men from Eastern and Southwestern Finland and compared with the concentrations of plasma lipids and the fatty acid composition of plasma and adipose tissue determined previously from the same populations. The plasma apo B concentrations ranged from 50 to 209 mg/dl. Although men from the two regions had similar mean concentrations of plasma triglyceride, total cholesterol and high density lipoprotein (HDL)-cholesterol, men from Eastern Finland had significantly higher mean apo B levels (139 +/- 25 mg/dl) and a lower ratio of total cholesterol to apo B (1.85 +/- 0.25) than the Southwestern men (125 +/- 33 mg/dl and 2.05 +/- 0.40, respectively). In the whole population, apo B and total cholesterol had significant negative correlations with the percentages of linoleate in the fatty acids of plasma and adipose tissue, which are known to reflect the quality of dietary fat. As the percentages of linoleate have previously been shown to be lower in the Eastern population, part of the regional difference in apo B is obviously explained by differences in the quality of dietary fat. On the other hand, men (n = 59) who had high plasma apo B (greater than 130 mg/dl) but low density lipoprotein (LDL)-cholesterol within the reference values (less than 5.17 mmol/l) showed no correlation between linoleate and apo B. This suggests that other factors than dietary fat determine the concentration of apo B in this group of men.

The fatty acid composition of cholesteryl esters (CE), triglycerides (TG) and phospholipids (PL) was analysed with gas chromatography before and after 3 years' storage of EDTA plasmas at -20 degrees C. In the three lipid fractions the proportion of polyunsaturated fatty acids (PUFA) with 3 or more double bonds decreased by 14% to 46%, while the proportions of saturated and monounsaturated fatty acids and also of linoleate (18:2 omega 6) showed an increasing trend. The changes tended to be relatively greatest in TG and smallest in PL. The initial concentration of vitamin A correlated negatively with reductions of all 20- to 22-carbon PUFA in CE and with that of arachidonate (20:4 omega 6) and docosahexaenoate (22:6 omega 3) in TG. The change in CE-18:2 omega 6 tended to be inversely correlated with vitamin A. The initial concentration of beta-carotene and the change in CE- and TG-18:3 omega 3 and CE-22:6 omega 3 showed also inverse correlations. Vitamin C, alpha-tocopherol and selenium had only occasional and mostly insignificant associations with the fatty acid alterations. In freshly analysed samples the concentration of vitamin A correlated negatively with the percentage of 18:2 omega 6 in plasma CE, TG and PL and with that of 20:4 omega 6 in platelets, and beta-carotene and alpha-tocopherol had positive correlations with 18:2 omega 6 in most plasma lipid fractions and platelets. Vitamin C and selenium correlated positively with 22:6 omega 3 in plasma, and selenium also with that in platelets.(ABSTRACT TRUNCATED AT 250 WORDS)

Rats were given a cod liver oil supplemented diet and a standard diet for 4 months. The cod liver oil supplementation resulted in a marked increase in the 20:5(n-3) and 22:6(n-3) fatty acids and a marked decrease in the 20:4(n-6) fatty acid in phosphatidylcholine and ethanolamine of the atrial membrane. Atria from the cod liver oil treated rats showed a marked decrease in contractile force, heart rate and cyclic AMP (cAMP) levels under basal conditions. Stimulation with noradrenaline (1 X 10(-6) M) during high oxygen saturation and reoxygenation resulted in an equal increase in the mechanical responses of the two groups in spite of the significantly different levels of cAMP, whereas in hypoxia, both the cAMP level and the contractile force were significantly lower in the cod liver oil treated group. These results indicate that changes in the fatty acid composition of heart membrane phospholipids is associated with changes in adenylate cyclase activity and physiological function of the rat heart and that an increase in the n-3/n-6 fatty acid ratio in membrane phospholipids of the heart results, when oxygen is abundant in enhanced cAMP-independent contractile activity.