Regional distribution and metabolic effect of PCSK9 insLEU and R46L gene mutations and apoE genotype.

BACKGROUND: Natural loss-of-function mutations in the proprotein convertase subtilisin/kexin type-9 gene (PCSK9) are associated with lower cholesterol and cardiovascular risk. Because a founder effect exists in French Canadians for many lipid-related genes, we sought to investigate PCSK9 mutations and associated variables in this population. We also investigated the combined effect of PCSK9 mutations and the apolipoprotein E (apoE) polymorphism on metabolic variables. METHODS: Gene sequencing and screening was carried out in 1745 healthy individuals ages 9, 13, and 16 years from a provincially representative population sample. In parallel, we measured related metabolic markers and used appropriate statistical methods. RESULTS: We report herein that the carrier rates of the R46L single-nucleotide polymorphism were higher in the French Canadian population (4.8%) than previously seen in Caucasian individuals (2.4%). This is second to the most common variant, insertion of leucine, at a carrier rate of 24%, making it the most common PCSK9 loss-of-function mutation in French Canadian individuals. In R46L carriers, the contribution of the apoE genotype better explains the cholesterol phenotype than the R46L mutation alone. Patients, with both the R46L and apoE3/E2 genotype also showed a tendency toward insulin resistance as indicated by a 2-fold increase in insulin, homeostasis model assessment of insulin resistance, and leptin concentrations, compared with those without apoE3/E2. CONCLUSIONS: R46L and insertion of leucine mutations were more frequent in French Canadian individuals and showed a specific geographic distribution. This might represent a gene selection to overcome clustering genes harbouring familial hypercholesterolemia and might suggest a founder effect. Subjects with the apoE3/E2 genotype and R46L have increased plasma insulin, homeostasis model assessment of insulin resistance, and leptin, an intriguing finding that warrants further investigation.

Is the obesity epidemic worsening the cardiovascular risk factor profile of children? Evidence from two Québec samples measured 10 years apart.

BACKGROUND: The impact of the obesity epidemic on cardiovascular health in young people is of increasing concern. However, data on secular trends in CVD indicators are outdated and mixed. METHODS: This study compared lipid profiles and insulin of 9-10 year olds in 2008 (n = 605) and 1999 (n = 779). Data were drawn from two population-based samples of youth: the 1999 Québec Child and Adolescent Health and Social Survey and the 2008 Québec Longitudinal Study of Child Development. RESULTS: Mean body mass index (BMI) Z-scores were higher in 2008 than in 1999 in both boys (0.37 vs 0.12, p = 0.004) and girls (0.32 vs 0.05, p = 0.0004). After adjusting for maturity stage, height, BMI Z-score, age and household income, high-density lipoprotein cholesterol was 0.12 mmol/L (p < 0.05) and 0.10 mmol/L (p < 0.05) higher in 2008 than 1999 in boys and girls, respectively. Total cholesterol, low density lipoprotein cholesterol and insulin were not significantly different between 2008 and 1999. CONCLUSIONS: Despite higher BMI Z-scores in 2008, differences in cardiometabolic indicators between 1999 and 2008 were small and may not be clinically meaningful. Surveillance to closely monitor trends in cardiometabolic indicators in Canadian youth is needed.

Association between different growth curve definitions of overweight and obesity and cardiometabolic risk in children.

BACKGROUND: Overweight and obesity in young people are assessed by comparing body mass index (BMI) with a reference population. However, two widely used reference standards, the Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO) growth curves, have different definitions of overweight and obesity, thus affecting estimates of prevalence. We compared the associations between overweight and obesity as defined by each of these curves and the presence of cardiometabolic risk factors. METHODS: We obtained data from a population-representative study involving 2466 boys and girls aged 9, 13 and 16 years in Quebec, Canada. We calculated BMI percentiles using the CDC and WHO growth curves and compared their abilities to detect unfavourable levels of fasting lipids, glucose and insulin, and systolic and diastolic blood pressure using receiver operating characteristic curves, sensitivity, specificity and kappa coefficients. RESULTS: The z scores for BMI using the WHO growth curves were higher than those using the CDC growth curves (0.35-0.43 v. 0.12-0.28, p < 0.001 for all comparisons). The WHO and CDC growth curves generated virtually identical receiver operating characteristic curves for individual or combined cardiometabolic risk factors. The definitions of overweight and obesity had low sensitivities but adequate specificities for cardiometabolic risk. Obesity as defined by the WHO or CDC growth curves discriminated cardiometabolic risk similarly, but overweight as defined by the WHO curves had marginally higher sensitivities (by 0.6%-8.6%) and lower specificities (by 2.6%-4.2%) than the CDC curves. INTERPRETATION: The WHO growth curves show no significant discriminatory advantage over the CDC growth curves in detecting cardiometabolic abnormalities in children aged 9-16 years.

[Importance of vitamin D in insulin resistance]. / L'importance de la vitamine D dans la résistance à I'insuline.

Beyond its classical role in bone metabolism, fundamental and epidemiological studies suggest that vitamin D is also involved in immunity and cell proliferation. Indeed, 25-hydroxyvitamin D 1alpha-hydroxylase and specific receptors for 1,25-dihydroxyvitamin D, the hormonal form of vitamin D, have been found in a variety of organs and tissues, such as the liver, epidermis, thymus, small intestine and pancreas. This brief review examines the results of in vitro, animal and clinical studies suggesting a role of vitamin D in glucose homeostasis. Epidemiological studies and meta-analyses have shown a weak association between vitamin D nutritional status and the risk of diabetes, but this does not justify the increasing demands for serum vitamin D assay. The latter should be restricted to disorders affecting the musculoskeletal system.

Vitamin D status is modestly associated with glycemia and indicators of lipid metabolism in French-Canadian children and adolescents.

In addition to its recognized role in bone health, recent studies point to vitamin D functions in other tissues, including the pancreas. We tested the association between the vitamin D status and glucose and lipid homeostasis in a school-based, cross-sectional survey of a representative sample of youth. We measured fasting plasma insulin, glucose, total cholesterol (TC), triglycerides (TG), HDL cholesterol (HDL-C) apolipoproteins (apo) A1 and B, and 25-hydroxyvitamin D [25(OH)D] concentrations in 878 boys and 867 girls. The 25(OH)D concentrations (mean +/- SD) were 45.9 +/- 12.2 nmol/L in boys and 45.9 +/- 13.0 nmol/L in girls. More than 93% of youth had suboptimal (<75 nmol/L) vitamin D concentrations. There was a slightly lower glycemia, -0.5% (P = 0.015) and -0.4% (P = 0.025), and homeostasis model assessment of insulin resistance, -2.8% (P = 0.043) and -2.3% (P = 0.050), for each 10-nmol/L increase in plasma 25(OH)D in boys and girls, respectively. In contrast, in girls only there were modest increases in plasma TC (1.1%; P = 0.017), TG (2.9%; P = 0.004), apoA1 (1.2%; P < 0.001), and apoB (1.5%; P = 0.023). We observed no association between the presence of at least 2 cardiometabolic risk factors (borderline/unfavorable fasting concentrations of apoB, HDL-C, TG, insulin, and glucose) and 25(OH)D concentrations in either boys or girls. Although the observed associations between 25(OH)D concentrations and fasting glucose, and variables of lipid metabolism are modest, they may have a potential long-term impact on cardiovascular risk.

Plasma PCSK9 is associated with age, sex, and multiple metabolic markers in a population-based sample of children and adolescents.

BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a protein convertase that posttranslationally promotes the degradation of the low-density lipoprotein receptor (LDLR) in hepatocytes and increases plasma LDL cholesterol (LDL-C). Heterozygote gain-of-function mutations of PCSK9 are associated with the familial hypercholesterolemia phenotype, whereas loss-of-function variants are associated with reduced LDL-C concentrations and lower coronary risk. Plasma PCSK9 correlates with body mass index, triglyceridemia, total cholesterol, and LDL-C in adults, but no data are available in youth. METHODS: We studied 1739 French Canadian youth ages 9, 13, and 16 years who participated in the Quebec Child and Adolescent Health and Social Survey, a province-wide school-based survey conducted in 1999. An ELISA assay was used to measure plasma PSCK9. RESULTS: The mean (SD) plasma PCSK9 concentration was 84.7 (24.7) microg/L in the sample. In boys, plasma PCSK9 decreased with age, whereas the inverse was true for girls. There were statistically significant positive associations between PCSK9 and fasting glucose, insulin, and HOMA-IR (homeostasis model assessment of insulin resistance). In multivariable analysis, a 10% higher fasting insulin was associated with a 1%-2% higher PCSK9 in both sexes. There were also positive associations between PCSK9 and total cholesterol, LDL-C, and triglycerides, as well as with HDL-C and apolipoproteins A1 and B. CONCLUSIONS: PCSK9 is associated with age, sex, and multiple metabolic markers in youth. A novel finding is that PCSK9 is associated with fasting insulinemia, which suggests that PCSK9 could play a role in the development of dyslipidemia associated with the metabolic syndrome. .

Association between insulin, leptin, adiponectin and blood pressure in youth.

OBJECTIVE: To examine whether insulin, leptin and adiponectin are independent correlates of blood pressure (BP) in a large population-based sample of children and adolescents. METHODS: We studied 655 boys and 667 girls aged 9, 13 and 16 years who participated in the Quebec Child and Adolescent Health and Social Survey, a province-wide school-based survey conducted in 1999. RESULTS: Strong, positive univariate associations between BMI, insulin and leptin Z-scores, and both systolic and diastolic BP were found in both sexes. Adiponectin Z-scores were negatively associated with systolic BP in girls only. In multivariate analyses only BMI and insulin Z-scores were significantly associated with systolic BP. In boys, each 1 SD increase in BMI was associated with a 4 mmHg increase in mean systolic BP; each 1 SD increase in insulin was associated with a 1 mmHg increase in mean systolic BP. Only insulin Z-scores were independently associated with diastolic BP in both sexes. For each 1 SD increase in insulin, there was a 1 mmHg increase in mean diastolic BP in boys. Similar to systolic BP, the magnitude of the effect of insulin Z-scores on diastolic BP increased as a function of BMI Z-scores in girls. CONCLUSION: Independently of BMI, insulin is a strong correlate of systolic and diastolic BP in youth. Although animal studies support a role for leptin and adiponectin in controlling BP, they are not independently associated with BP in youth.

13C-labeled mixed triglyceride breath test (13C MTG-BT) in healthy children and children with cystic fibrosis (CF) under pancreatic enzyme replacement therapy (PERT): a pilot study.

The MTG-BT estimates the hydrolysis of triacyl-glycerols by pancreatic lipase, and appears attractive for monitoring exogenous lipase requirements in patients with exocrine pancreatic insufficiency. To assess the test's discrimination capacity and repeatability, 9 CF patients with PERT and 10 healthy children underwent the (13)C-MTG-BT twice, at a 2- to 4-week interval. The test distinguished well between patients with severe exocrine pancreatic insufficiency (SEPI) and healthy subjects. However, within-subject variability for postprandial per thousand(13)C-enrichment and postprandial % dose recovery (PDR) was high in both groups. Therefore, the (13)C-MTG-BT seems useful to distinguish between SEPI and normal exocrine pancreatic function, but requires further development to improve its repeatability.

Prevalence of cardiometabolic risk factors by weight status in a population-based sample of Quebec children and adolescents.

BACKGROUND: There are few data on the prevalence of cardiometabolic risk factors in population-based samples of overweight and obese youth. OBJECTIVES: To compare the prevalence of individual and multiple cardiometabolic risk factors across body mass index (BMI) categories in a population-based sample of youth. METHODS: In 1999, a school-based survey of a provincially representative sample of youth nine, 13 and 16 years of age was conducted in Quebec (1778 boys, 1835 girls). Overweight was defined as BMI in the 85th percentile or higher and lower than the 95th percentile of the Centers for Disease Control and Prevention 2000 growth charts, and obesity was defined as BMI in the 95th percentile or higher. Levels of total cholesterol, low-density lipoprotein cholesterol, apolipoprotein B, high-density lipoprotein cholesterol, triglycerides, insulin, glucose, C-reactive protein and systolic blood pressure were categorized as desirable, borderline or unfavourable. RESULTS: The proportions of overweight and obese participants were 14% and 10% in boys, and 14% and 7% in girls, respectively. With the exception of total cholesterol and low-density lipoprotein cholesterol in girls, and glucose in both sexes, the prevalence of all investigated risk factors (borderline or unfavourable) was significantly higher among overweight and obese participants. Almost one-third of obese participants had unfavourable levels of at least two of seven risk factors (apolipoprotein B, high-density lipoprotein cholesterol, triglycerides, insulin, glucose, C-reactive protein and systolic blood pressure) compared with 3% of normal weight participants (adjusted OR 15 and 18 in boys and girls, respectively). Thirty-four per cent of obese youth did not have unfavourable levels of any risk factor. CONCLUSION: There is marked heterogeneity in the association between excess weight and cardiometabolic risk factors. Nonetheless, the present study highlights a high prevalence of multiple risk factors in a population-based sample of overweight and obese youth.

Low vitamin D status in a representative sample of youth from Québec, Canada.

BACKGROUND: Adequate vitamin D status is important for bone growth and mineralization and has been implicated in the regulation of autoimmunity, metabolic function, and cancer prevention. There are no reports of population-based studies on the vitamin D status of Canadian youth, a population with mandatory fortification of foods. METHODS: We measured plasma 25-hydroxyvitamin D [25(OH)D], the best indicator of vitamin D status, in a school-based cross-sectional sample of representative French Canadian youth (n = 1753) ages 9, 13, and 16 years living in Québec (latitude: 45 degrees-48 degrees N). Blood samples were collected from January to May 1999. We defined 25(OH)D deficiency as < or = 27.5 nmol/L, hypovitaminosis as < or = 37.5 nmol/L, and optimal as > 75.0 nmol/L. RESULTS: More than 93% of youth in each age and sex group had suboptimal 25(OH)D concentrations. The prevalence of 25(OH)D deficiency increased with age in both sexes (P < 0.0001). It was 2%, 3%, and 13% in 9-, 13-, and 16-year-old boys and 2%, 8%, and 10% in 9-, 13-, and 16-year-old girls. Girls with higher body mass index and girls from households with lower income had lower 25(OH)D concentrations. These effects were not observed in boys. CONCLUSIONS: Inadequate vitamin D status is a potentially serious public health problem among children and adolescents in Québec. Youth living at high latitudes in countries with and without mandatory fortification of vitamin D are likely at heightened risk of 25(OH)D deficiency. These results call for renewed efforts to ensure adequate vitamin D intake among growing children and adolescents.

Association between cigarette smoking and C-reactive protein in a representative, population-based sample of adolescents.

Although related to inflammatory markers in adults, little is known about the association between cigarette smoking and C-reactive protein (CRP) in adolescent smokers. We examined the association between high-sensitivity CRP (hs-CRP) concentrations and smoking in youth. We used data from a cross-sectional, province-wide survey of a representative sample of youth conducted in Quebec, Canada, in 1999. Data were collected in self-report questionnaires completed by participants and their parents. Participants provided a fasting blood sample, and anthropometric measures were undertaken by trained technicians. The present analysis pertains to 1,501 adolescents aged 13 and 16 years who completed questionnaires and for whom blood samples were available. The independent association between a six-category indicator of smoking status and elevated hs-CRP, defined as a value at least in the 90th percentile of the age- and sex-specific CRP distribution, was assessed in multiple logistic regression analyses controlling for potential confounders. Relative to never-smokers, the odds ratios (95% confidence intervals) for puffers (i.e., never smoked a whole cigarette), those who smoked but not in the past month, light past-month smokers, moderate past-month smokers, and heavy past-month smokers were 1.04 (0.55-1.98), 1.76 (1.06-2.94), 1.39 (0.70-2.76), 2.07 (0.96-4.42), and 2.40 (1.18-4.88), respectively. Our data suggest a positive association between smoking status and elevated CRP in adolescents, and in particular among heavier past-month smokers. Damage related to cigarette smoking may begin soon after tobacco use initiation, reinforcing the preventive message that no level of smoking is safe in youth.

Gap analysis of pediatric reference intervals related to thyroid hormones and the growth hormone-insulin growth factor axis.

Efficacy of laboratory medicine in assisting attending physicians in their diagnostic and follow-up endeavors is intimately linked to an access to meaningful and reliable reference values. Pediatrics is particularly sensitive to this problem as the processes, associated with growth and development, are imposing rapid discontinuous changes on the physiology of the individuals. Some developmental stages are more critical than others. The neonatal and the pubertal periods, for which we lack reference ranges, are two such examples. Beyond biological considerations, we realize that, over the last 2 decades, technology has evolved, both at the analytical and reagent levels. This technological evolution inexorably leads to the need in redefining reference values. It is for this reason that a group of clinical and medical biochemists have joined their efforts in creating the Canadian Laboratory Initiative in Paediatric Reference (CALIPER) which objective is to define a pan-Canadian set of reference values from birth to late adolescence. To illustrate the need of such a venture, a brief gap analysis for biochemical variables related to the thyroid function, and the growth hormone-insulin-like growth factors axis follows.

Congenital hypothyroidism: from paracelsus to molecular diagnosis.

Endemic cretinism was noted in alpine Europe as early as the 13th century. However, it was only in 1848 that a commission, sponsored by the King of Sardinia, first formally demonstrated its link to goiter. An important landmark was the publication of a report in 1871 describing several cases of nongoitrous hypothyroidism that were clearly distinguished from the endemic form of the disease, for which the author suggested the designation of "sporadic cretinism." Classification of the hypothyroid status was for a long time solely based on clinical observation. In the second half of the 20th century, the use of radionuclides (iodine radioisotope and technetium pertechnetate) allowed a more precise diagnosis and taxonomy into thyroid dysgenesis and dyshormonogenesis. This brief review summarizes the progress that has been achieved during the last 40 years in diagnosing the multiple variants of congenital hypothyroidism (CH). It becomes evident that while accurate diagnosis for CH is readily available, its exact etiology requires a precise molecular investigation as different genes are implicated in the differentiation, migration and growth of the thyroid gland.

WITHDRAWN: Clinical Chemistry: 50 years of stimulating changes and more to come.

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Adiponectin, adiposity, and insulin resistance in children and adolescents.

CONTEXT: Determinants of adiponectin and its association with insulin resistance (IR) are less well studied in youth than in adults. OBJECTIVES: The objective of the study was to describe, in youth, the age- and sex-specific distribution of adiponectin concentrations and the association with demographic, anthropometric, and lifestyle factors, parental diabetes, and markers of IR. DESIGN, SETTING, PARTICIPANTS: We studied 1632 French Canadian youth aged 9, 13, and 16 yr who participated in the Québec Child and Adolescent Health and Social Survey, a province-wide, school-based survey conducted in 1999. RESULTS: Boys had lower adiponectin concentrations than girls by 17% (P < 0.0001). At age 16 yr, mean adiponectin concentrations were 27.7% (boys, P < 0.0001) and 13.3% (girls, P < 0.0001) lower than at age 9 yr (p(interaction) = 0.009). Mean adiponectin decreased for every unit increase in body mass index (BMI) Z-score by 8.1% in boys and 11.2% in girls (P < 0.0001). Growth-related change in BMI explained half the age effect in boys and all the age effect in girls. Self-reported pubertal status, physical activity, smoking, and parental diabetes were not independently associated with adiponectin. Fasting insulin and homeostasis model assessment-IR were not associated with adiponectin concentration. However, the interaction of adiponectin and BMI Z-score was significant in a multiple regression model of fasting insulin. CONCLUSIONS: Male sex and changes in body fat may be major determinants of the decreasing adiponectin concentrations of growing youth, which are accompanied by a dissociation of adiponectin and markers of IR. The relationship between adiposity and markers of IR is attenuated in those with higher adiponectin concentrations, making adiponectin a potential intervention target or risk marker.

Newborn screening for sickle cell disease: A 1988-2003 Quebec experience.

BACKGROUND: Sickle cell disease (SCD) is associated with significant mortality and morbidity that can be decreased by neonatal diagnosis. Although 44 American states have implemented such programs, there are no provincially funded universal or targeted newborn screening programs for SCD in Canada. OBJECTIVE: To report a critical appraisal of a hospital-based neonatal screening program targeting at-risk infants over a 15-year period. METHODS: The cord blood of infants born at Sainte-Justine University Health Centre (Sainte-Justine UHC, Montreal, Quebec) whose mother or father was black was collected at birth and analyzed for the presence of hemoglobin (Hb) S by liquid chromatography or isoelectric focusing. Samples with positive results underwent confirmatory testing. RESULTS: A total of 9619 infants were screened: 8142 (84.6%) had a normal phenotype, 1012 (10.5%) had sickle cell trait and 386 (4.0%) had HbC trait. Seventy-two infants were diagnosed with SCD: 37 (0.4%) were classified as HbSS or HbS-beta-thalassemia and 35 (0.4%) had HbSC disease. Of these 72 infants, 67 (93.1%) were immediately enrolled in a multidisciplinary SCD follow-up clinic. The five remaining children not initially enrolled were later referred to the clinic. A chart study revealed that six patients with SCD born at Sainte-Justine UHC were not identified by neonatal screening. CONCLUSIONS: The screening program was clinically effective because it identified 92.3% of at-risk patients born at Sainte-Justine UHC. These infants received appropriate medical care before 10 weeks of age as opposed to a median of 12 months for infants not identified by the screening program. It is proposed that either a targeted or a universal neonatal screening for SCD should be available in Canada.

Neonate capillary blood gas reference values.

OBJECTIVES: Because biological data are instrument-dependent and because technology has evolved over the last two decades, the published capillary blood reference values for blood gases, lactate, ionized calcium (iCa) and glucose may not reflect the present day situation. Hence, we report such values for healthy term neonates at 48 +/- 12 h of life. DESIGN AND METHODS: The Institution Ethics Review Board for Research on Human Subjects has accepted the protocol. Extra blood sample was obtained at the time heel-pricks were performed in the frame of the Quebec genetic screening program. One hundred twenty-six term neonates (39.6 +/- 1.2 weeks of gestation) were included in the study. pH, pO2, pCO2, lactate, ionized calcium and glucose were simultaneously measured with selective electrodes on the ABL 735 blood gas analyzer (Radiometer). RESULTS: All variables exhibited a Gaussian distribution. Since there was no gender effect, all data were pooled.

Distribution of LDL particle size in a population-based sample of children and adolescents and relationship with other cardiovascular risk factors.

BACKGROUND: Smaller, denser LDL particles are associated with an increased risk for cardiovascular diseases (CVD). In youths, data on the distribution of LDL particle size and on its association with other CVD risk factors are limited. METHODS: We determined LDL peak particle size by nondenaturing 2%-16% gradient gel electrophoresis in a representative sample of 2249 youths 9, 13, and 16 years of age who participated in a school-based survey conducted in 1999 in the province of Quebec, Canada. Standardized clinical measurements and fasting plasma lipid, glucose, and insulin concentrations were available. RESULTS: The LDL peak particle size distribution was gaussian. The 5th, 50th (median), and 95th percentiles by age and sex were 255.5-258.6, 262.1-263.2, and 268.1-269.5 A, respectively. The prevalence of the small, dense LDL phenotype (LDL peak particle size

Oral vitamin A, E and D supplementation of pre-term newborns either breast-fed or formula-fed: a 3-month longitudinal study.

BACKGROUND: In contrast to the studies of vitamin A and E status in children, adolescents and adults, information on preterm infants is scarce. In the present investigation we examined the vitamin A, D and E status of pre-term infants at birth, and verified whether, at 1 and 3 months, breast or formula feeding affected the plasma concentration of those vitamins while being supplemented with Uvesterol ADEC. PATIENTS AND METHODS: In this prospective study, 2 groups of consecutively recruited preterm newborns fed either breast milk or formula received 3000 IU of vitamin A, 5 IU of vitamin E and 1000 IU of vitamin D daily. Vitamin A and E were measured by high performance liquid chromatography and spectrophotometry. 25-hydroxyvitamin D, a surrogate marker for vitamin D status, was measured by radioimmunoassay, and retinol binding-protein concentration was measured by immunonephelometry. RESULTS: At birth, formula-fed and breast-milk fed infants had similar plasma concentrations of vitamin A (0.75 +/- 0.20 and 0.64 +/- 0.21 micromol/L, ns), 25-hydroxyvitamin D (34.4 +/- 25.6 and 47.5 +/- 26.7 nmol/L, ns) and vitamin E (9.5 +/- 3.2 and 8.4 +/- 3.3 micromol/L, ns). Vitamins A and E, and retinol binding-protein concentrations steadily increased with time in both groups of infants without attaining, at 3 months, values considered normal in term infants and in young children. At 3 months of age, concentrations of 25-hydroxyvitamin D reached values comparable to those observed in term infants. CONCLUSION: Plasma concentrations of vitamins A and E and of retinol binding-protein steadily increased during the the study without reaching full repletion values. At the conclusion of the study, the type of nutrition did not affect plasma vitamin concentrations.