Taina Routi

Prospective randomised trial in 1062 infants of diet low in saturated fat and cholesterol

Interventions to avoid atherosclerosis might be more successful if launched early in life when eating and life-style patterns are formed, but dietary interventions have been limited by fears of diet-induced growth failure. We investigated the effects of a diet low in saturated fat and cholesterol on serum lipid concentrations and growth in 1062 healthy 7-month-old infants in a randomised study. Every 1-3 months, families in the intervention group received dietary advice aimed at adequate energy supply, with low fat intake (30-35% energy, polyunsaturated/monounsaturated/saturated fatty acid ratio 1/1/1, and cholesterol intake < 200 mg daily). Infants in control families consumed an unrestricted diet. 3-day food records were collected at ages 8 and 13 months. Growth was carefully monitored. Between 7 and 13 months serum cholesterol and non-high-density-lipoprotein cholesterol concentrations did not change significantly in the intervention group (mean change -0.03 [SD 0.72] mmol/L and 0.01 [0.67] mmol/L) but increased substantially in the control group (0.24 [0.64] mmol/L and 0.23 [0.60] mmol/L; p for difference in mean changes between groups < 0.001). Daily intakes of energy and saturated fat were lower in the intervention than in the control group at 13 months (4065 [796] vs 4370 [748] kJ, p = 0.033, and 9.3 [3.5] vs 14.5 [4.8] g, p < 0.001, respectively), and intake of polyunsaturated fat was higher (5.8 [2.2] vs 4.4 [1.4] g, p < 0.001). Growth did not differ between the groups and was as expected for children at this age. Serum cholesterol concentrations fell significantly in parents of intervention-group infants. The increases in serum cholesterol and non-high-density-lipoprotein cholesterol concentration that occur in infants between the ages of 7 and 13 months can be avoided by individualised diets, with no effect on the childrens growth.

Special Turku Coronary Risk Factor Intervention Project for Babies (STRIP)

BACKGROUND Introducing nutritional and lifestyle principles to children in late infancy may permanently improve their adherence to a low-saturated fat, low-cholesterol diet, thus reducing of coronary risk factors, but worries about possible effects on growth and development have hampered such an approach. OBJECTIVE The Special Turku Coronary Risk Factor Intervention Project for Babies (STRIP) aimed to decrease exposure to known environmental atherosclerosis risk factors in children 7-36 mo of age. DESIGN Repeated, individualized counseling aimed at promoting a fat intake of 30% of energy and a 1:1:1 ratio of saturated to monounsaturated to polyunsaturated fat intake was provided (n = 540 intervention children; 284 boys). Nutrition was discussed superficially with the families of the control children (n = 522; 266 boys) and food intake was recorded at 3-6-mo intervals by use of 3-4-d food diaries. Serum lipids were measured at 6-12-mo intervals and growth was monitored regularly. RESULTS Fat intake of the intervention (control) children provided 29.5% (29.4%) of energy at the age of 8 mo, 26.6% (28.5%) of energy at 13 mo, 30.5% (33.5%) of energy at 24 mo, and 31. 5% (33.5%) of energy at 36 mo. The intervention children consistently consumed less saturated fat than did the control children (P: <0.0001). Recommended intakes of other nutrients (except vitamin D and occasionally iron) were reached irrespective of the amount and type of dietary fat. Serum cholesterol, non-HDL cholesterol, and HDL-cholesterol concentrations were 3-6% lower in the intervention children than in the control children. The intervention had no effect on height, weight, or head circumference gain. Fat intake did not predict childrens growth patterns. CONCLUSION Repeated, individualized counseling in early childhood aimed at reducing consumption of saturated fat and cholesterol was effective and feasible and did not restrict growth in circumstances in which children were regularly monitored.

Cholesterol measurement by reflotron dry chemistry in infants, children and adults

Cholesterol values measured with the Reflotron dry chemistry (Boehringer Mannheim, Mannheim, Germany) and enzymatic (CHOD-PAP) routine method in 4150 venous blood samples from 580 infants aged 7 months, 1778 children aged 13 months to 19 years, and 1792 adults aged 18-63 years showed good correlation between the two assay systems (r > 0.92). However, the mean cholesterol concentrations were 4.5%, 3.7% and 2.3% lower in infants, children and adults, respectively, if measured with the Reflotron analyser as compared with values obtained with the CHOD-PAP method. These differences in the values were greater when cholesterol values were low (significance for the slope of regression line, p < 0.001). Values were below the detection limit of the Reflotron assay (2.59 mmol l-1) in 104 (4.4%) and 4 (0.2%) of all paediatric and adult samples, respectively. When measured with the CHOD-PAP method, 75 (72%) and 3 (75%) of these same samples showed values which exceeded the 2.59 mmol l-1 detection limit. We conclude that Reflotron dry chemistry analyser is precise in fast measurement of serum cholesterol both in all paediatric subjects and adults. A particular problem in paediatric age groups is that about 4% of children have values below the detection limit of the Reflotron analyser.

Age at Development of Type 1 Diabetes and Celiac Disease-Associated Antibodies and Clinical Disease in Genetically Susceptible Children Observed from Birth

OBJECTIVE To compare the ages and sequence in which antibodies associated with type 1 diabetes and celiac disease appear and overt diseases develop in children with an HLA-conferred susceptibility to both diseases. RESEARCH DESIGN AND METHODS We observed 2,052 children carrying genetic risks for both type 1 diabetes and celiac disease from birth until the median age of 5.7 years and analyzed diabetes- and celiac disease–associated antibodies in serum samples collected at 3- to 12-month intervals. Diabetes was confirmed by World Health Organization criteria and celiac disease by duodenal biopsies. RESULTS Altogether 342 children seroconverted to positivity for at least one diabetes-associated autoantibody and 88 to positivity for at least one celiac disease–associated antibody at the median ages of 3.0 and 1.5 years, respectively (P < 0.001). If only children with biochemically defined diabetes-associated autoantibodies against insulin, GAD, or IA-2A protein (n = 146) and children with tissue transglutaminase autoantibodies were compared (n = 86), the median seroconversion ages were 2.5 and 3.0 years (P = 0.011). Fifty-one children progressed to overt diabetes at 4.5 years and 44 children to celiac disease at 4.3 years (P = 0.257). Of the 19 children who developed both diabetes- and celiac disease–associated antibodies, 3 progressed to both diabetes and celiac disease. CONCLUSIONS Children with HLA-conferred susceptibility to type 1 diabetes and celiac disease develop celiac disease–associated antibodies mostly at a younger age or the same age at which they develop diabetes-associated autoantibodies. Clinical diabetes and celiac disease are commonly diagnosed at the same median age.

Serum cholesterol ester fatty acids in 7- and 13-month-old children in a prospective randomized trial of a low-saturated fat, low-cholesterol diet: the STRIP baby project

To evaluate changes that occur in serum cholesterol ester fatty acid composition during the transition from typical infant feeding to a more adult type of nutrition, this study compared the effects on serum cholesterol ester fatty acids of breast milk or formula at the age of 7 mo with effects caused by 6‐mo dietary intervention in 137 children. The intervention [Special Turku coronary Risk factor Intervention Project for children (STRIP baby project)] aimed at a reduction of saturated fat intake to 10% of energy after the age of 1 y without purposefully influencing total fat intake. Nutrient intakes were calculated from 3‐d food records. At the age of 7 mo, i.e. before dietary education began, milk type markedly influenced dietary and serum cholesterol ester fatty acid composition (mean serum cholesterol ester 16:0 in breastfed vs formula‐fed infants, 13.7% vs 12.0%, respectively, p < 0.001; serum cholesterol ester 18:2n‐6 50.6% vs 57.6%, p < 0.001). At the age of 13 mo the calculated fat intake of the intervention and control children differed markedly but serum cholesterol ester fatty acid compositions in all children resembled closely those measured in 7‐mo‐old breastfed infants, e.g. at the age of 13 mo the relative proportions of 18:2n‐6 were 49.9% and 51.1% in previously formula‐fed intervention and control children, respectively, and 50.3% and 50.1% in previously breastfed intervention and control children, respectively. In conclusion, serum cholesterol ester fatty acid composition reflected differences in dietary fat quality (breast milk or formula) at the age of 7 mo, whereas dietary intervention as applied in the STRIP baby project had only a minimal effect. □Cholesterol esters, dietary intervention, fatty acids, infant feeding

Correlation of toddlers' serum lipoprotein(a) concentration with parental values and grandparents' coronary heart disease: the STRIP baby study

The correlation between lipoprotein(a) (Lp(a)) concentrations in children aged 7‐24 months and their family members was determined and the association between the Lp(a) values of the children and a family history of coronary heart disease (CHD) was assessed. The Lp(a) values of the children correlated strongly with midparent Lp(a) values as early as at 7 months of age (r= 0.54 to 0.59, p < 0.0001). This correlation was stronger than the correlation of serum total cholesterol and total cholesterol corrected for Lp(a) ‐ cholesterol between children and parents. None of the parents had CHD. The median Lp(a) concentration of the parents with a family history of CHD was significantly higher than that of parents with no such history (111 vs 87 mg/l,p = 0.024). However. the childrens Lp(a) levels were not associated with CHD in their grandparents. The genetic dependence of the Lp(a) concentration is already evident in infancy. The Lp(a) concentration in young parents, but not in their 24‐month‐old children, is associated with CHD in grandparents. This may be explained by a dilution of the genetic influence on Lp(a) over two generations.

Fatty acid composition of serum cholesterol esters as a reflector of low-saturated-fat, low-cholesterol diet in young children: the STRIP project.

STRIP (the Special Turku coronary Risk factor Intervention Project) is an ongoing intervention trial which aims at a permanent reduction in the intake of saturated fat and cholesterol starting in childhood. A total of 75 intervention and 63 control children was studied consecutively at the ages of 7 and 13 mo, and 2, 3 and 5 y to evaluate the influence of such intervention on serum cholesterol ester (CE) fatty acid composition, a widely used biomarker of fatty acid intake. Analysis of 4‐d food records showed that total intake of fat and of saturated fat increased with age in both groups of children but was constantly lower in intervention than in control children, e.g. at the age of 5 y the mean intakes of total fat and of saturated fatty acids were 31.1 E% and 33.9 E% and 12.1 E% and 14.6E% in intervention and control children, respectively (p = 0.009 and 0.0001, respectively). Serum CE fatty acid compositions did not differ between the 2 groups at any age; the mean proportion of CE linoleic acid was 52.4% and 52.0% in 5‐y‐old intervention and control children, respectively. Correlation analysis showed, however, that the percentage of linoleic acid and of polyunsaturated fatty acids in CE reflected well the respective dietary intakes (r= 0.36; p = 0.0001 for both coefficients).

Tracking of Serum Lipoprotein (a) Concentration and Its Contribution to Serum Cholesterol Values in Children from 7 to 36 Months of Age in the STRIP Baby Study

We investigated the tracking phenomenon of serum lipoprotein (a) concentrations and assessed the impact of serum concentration of lipoprotein (a) cholesterol on total cholesterol concentrations in children from 7 to 36 months of age. Serum samples for lipoprotein (a) and cholesterol determinations at 7, 13, 24 and 36 months were prospectively obtained from 430 children. Serum lipoprotein (a) was determined using immunoradiometric assay. A strong correlation was observed between lipoprotein (a) concentrations at 7 and 36 months of age (r = 0.88, P < 0.001). Seventy-eight per cent to 86% of the children in the lowest and highest lipoprotein (a) quintiles at 13 months remained in the respective quintiles at 36 months. The average contribution of lipoprotein (a) cholesterol to total cholesterol varied from 0.5% to 3.2% (individual variation 0.13-32.39%) depending on the type of milk received and the age of the children. At 7 months the contribution was 0.44% in breast-fed and 0.93% in formula-fed infants (P < 0.0001). The tracking phenomenon of serum lipoprotein (a) concentrations is strong already in early childhood. The contribution of lipoprotein (a) cholesterol to serum total cholesterol concentration should be taken into account when the changes in serum cholesterol levels are interpreted in the first year of life.

Effect of weaning on serum lipoprotein(a) concentration: the STRIP baby study.

Risk for coronary heart disease is increased in adult Caucasians with high serum lipoprotein(a) [Lp(a)J concentration. In adults the concentration is mainly regulated by genetic factors. Our previous study suggests that breast milk has a beneficial effect on serum Lp(a) concentration in infants. Now we analyzed the influence of weaning by measuring serum Lp(a) and cholesterol in 414 infants at 7, 13, 24, and 36 mo of age. At 7 mo the infants received, in addition to solid food, only breast milk (n = 148), breast milk and formula (n = 74), or formula only (n = 191). Median (range) serum Lp(a) concentrations were then 25 (≤ 12-743) mg/L, 35 (≤ 12-1188) mg/L, and 45 (≤ 12-577) mg/L in the three feeding groups, respectively (p = 0.0013). Breast milk and formula were changed to cows milk in all infants before 12 mo of age. At 13 mo serum Lp(a) concentration had increased more in infants who were weaned from breast milk than in those who had been fed both breast milk and formula, or formula only (median increases 37, 26, and 20 mg/L, respectively; p = 0.0062). Thus the serum Lp(a) concentration was similar in all feeding groups at 13 mo. This finding was also observed at 24 and 36 mo. The increase in serum Lp(a) concentration was independent of the baseline Lp(a) level, apolipopro-tein E phenotype, gender, and weight gain of the infants between 7 and 13 mo. The results imply that weaning from breast milk influences markedly serum Lp(a) concentration, suggesting the presence of a Lp(a) lowering factor in breast milk.

Effect of Diet and Apolipoprotein E Phenotype on Serum Lipoprotein(a) Concentration in Children at 5 Years of Age

Effect of Diet and Apolipoprotein E Phenotype on Serum Lipoprotein(a) Concentration in Children at 5 Years of Age