Ronald M. Lauer

We have examined the transmission frequencies of the methylenetetrahydrofolate reductase (MTHFR) 677 T and C alleles from heterozygous parents to children with Down syndrome (trisomy 21) in 202 Caucasian families. Our results indicated that the MTHFR 677T allele was transmitted to children with Down syndrome at a significantly higher rate than would be expected based on Mendelian inheritance patterns, and the C allele was transmitted at a significantly lower rate (P < 0.009). Transmission frequencies were also examined independently for maternally and paternally transmitted alleles to assess potential parent‐of‐origin effects. Because the vast majority of conceptions with trisomy 21 end in pregnancy loss, we questioned whether the observed preferential transmission of the T allele to this population of liveborn infants with Down syndrome could reflect a survival advantage. A plausible biochemical interpretation of these results is presented based on a maternal–fetal MTHFR 677T allele interaction in the context of the constitutive overexpression of three copies of the cystathionine beta synthase gene in the trisomy 21 fetus. Published 2002 Wiley‐Liss, Inc.

Background: Few studies have shown the efficacy and safety of lower-fat diets in children. Objective: Our objective was to assess the efficacy and safety of lowering dietary intake of total fat, saturated fat, and cholesterol to decrease LDL-cholesterol concentrations in children. Design: A 6-center, randomized controlled clinical trial was carried out in 663 children aged 8–10 y with LDL-cholesterol concentrations greater than the 80th and less than the 98th percentiles for age and sex. The children were randomly assigned to either an intervention group or a usual care group. Behavioral intervention promoted adherence to a diet providing 28% of energy from total fat, −1•d⁻¹ (not to exceed 150 mg/d). The primary efficacy measure was mean LDL cholesterol and the safety measures were mean height and serum ferritin concentration at 3 y. Results: At 3 y, dietary total fat, saturated fat, and cholesterol were lower in the intervention group than in the usual care group (all P < 0.001). LDL cholesterol decreased in the intervention and usual care groups by 0.40 mmol/L (15.4 mg/dL) and 0.31 mmol/L (11.9 mg/dL), respectively. With adjustment for baseline concentration, sex, and missing data, the mean difference between groups was −0.08 mmol/L (95% CI: −0.15, −0.01), or −3.23 mg/dL (95% CI: −5.6, −0.5) (P = 0.016). There were no significant differences between groups in adjusted mean height or serum ferritin. Conclusion: Dietary changes are effective in achieving modest lowering of LDL cholesterol over 3 y while maintaining adequate growth, iron stores, nutritional adequacy, and psychological well-being during the critical growth period of adolescence.

Beginning in 1971 children in grades kindergarten through the 12th grade were examined on alternate years until 1992 in Muscatine, Iowa, in these examinations the following variables were assessed: height, weight, skinfold thickness, lipids, lipoproteins, smoking behaviors, as well other variables. In order to lend relevance to risk factors in childhood a number strategies have been used. These include: 1) Examination of familial aggregation and mortality; 2) Segregation analysis of genetic mechanisms; 3) Relationship of obesity in childhood to other established risk factors; 4) Examination of the relationship of childhood obesity to the development of coronary artery calcification as assessed by electron beam computed tomography. In these studies we have shown that obese children's siblings, mothers, fathers, aunts and uncles have significant greater body mass indices than leaner children. Children who are obese have significantly higher systolic and diastolic blood pressure, higher plasma triglycerides and lower HDL-cholesterol levels. The first and second degree relatives of obese hypertensive children have a higher mortality rate from cardiovascular disease than leaner children's relatives. From complex segregation analyses about 35% of the population of Muscatine appear to carry a gene for obesity and 6% appear homozygous. Over the past decade we have observed that the children in Muscatine, Iowa have become more obese than previously. Our longitudinal observations indicate that obesity acquired in childhood is predictive of adult obesity and is also predictive of the development of coronary artery calcification. Thus obesity in childhood is not only an important risk factor in children but also a growing public health problem for children and adolescents.