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I've been using this recipe for close to 50 years. I'd tried making whole-wheat bread before, but it always failed. Then, I found this recipe for 'Mother's Favorite Bread' in [...]

Background: Breastfeeding has been reported to benefit visual development in children. A higher concentration of docosahexaneoic acid (DHA) in breast milk than in formula has been proposed as one explanation for this association and as a rationale for adding DHA to infant formula, but few long-term data support this possibility. Objective: The objectives of the study were, first, to test the hypothesis that breastfeeding benefits stereoscopic visual maturation and, second, if that benefit is shown, to ascertain whether it is mediated by the dietary intake of DHA. Design: Stereoacuity was measured by using the random dot E test (primary outcome), and visual acuity was measured by using the Sonksen-Silver acuity system (secondary outcome) in previously breastfed (n = 78) or formula-fed (n = 184) children aged 4- 6 y who had been followed prospectively from birth. In the formula-fed group, children were randomly assigned to receive formula with either DHA or arachidonic acid (n = 94) or a control formula (n = 90) for the first 6 mo. Results: Breastfed children had a significantly (P = 0.001) greater likelihood of foveal stereoacuity (high-grade or < 100 s/arc) than did formula-fed children (odds ratio: 2.5; 95% CI: 1.4, 4.5) independent of potential confounding (P = 0.005). Stereoacuity did not differ significantly between children randomly assigned to DHA-supplemented or control formula. None of the groups differed in Sonksen-Silver visual acuity. Conclusions: These findings support the hypothesis that breastfeeding benefits long-term stereoscopic development. An effect of DHA cannot be excluded, but the lack of difference in stereoacuity between infants randomly assigned to DHA-containing and those assigned to control formula raises the hypothesis that factors in breast milk other than DHA account for the observed benefits. KEY WORDS Polyunsaturated fatty acids, stereoacuity, vision, breastfeeding, randomized trial

Despite potential benefits, human milk may fail to meet preterm infants' nutrient requirements. We tested the hypothesis that fortified breast milk, fed alone or with preterm formula, would improve neurodevelopment and growth at 18-mo follow-up without adverse short-term clinical or biochemical consequences. Two hundred seventy-five preterm infants from two medical centers (birth weight < 1850 g; mean gestation 29.8 [+ or -] 2.7 wk) whose mothers chose to provide breast milk were randomly assigned to receive for a mean of 39 d a multinutrient fortifier or control supplement containing phosphate and vitamins. Breast milk comprised 47.6% and 46.4% of enteral intake in fortified and control groups, respectively; preterm formula supplements were used when insufficient breast milk was available. Overall, there were no significant growth advantages with fortification; although, when breast milk exceeded 50% of intake, fortification promoted faster weight gain (an advantage of 1.6 g.[kg.sup.-1].[d.sup.-1]; 95% CI: 0.1, 3.1; P < 0.05). Compared with control infants, the fortified group showed 1) higher plasma urea from week 2 (P = 0.04), 2) higher plasma calcium (mean 2.34 + 0.01 compared with 2.27 [+ or -] 0.02 mmol/L; P = 0.003), 3) a greater rise in alkaline phosphatase by week 6 (P = 0.04), 4) more clinical infections (suspected plus proven; 43% compared with 31%, P = 0.04), 5) a nonsignificantly increased incidence of necrotizing enterocolitis (5.8% compared with 2.2%, P = 0. 12), and 6) higher white cell and platelet counts. Developmental scores at 18 mo were slightly but not significantly higher in the fortified group. This study confirmed that breast milk fortifiers can improve short-term growth (when breast milk intakes are high); but beneficial effects on long-term development remained unproven. Future research is required to evaluate potential adverse consequences and explore more optimal fortification strategies.

Vitamin D deficiency and nutritional rickets are re-emerging as major pediatric health issues in Australia and New Zealand, with complications including hypocalcaemic seizures, rickets, limb pain and fracture. A review of the vitamin D metabolism includes the risk factors for, and features of, vitamin D deficiency in infants, children and adolescents as well as recommendations for treatment and subsequent prophylaxis.

The postnatal vitamin D status and bone health of women identified as vitamin D-deficient in pregnancy and of their infants are determined. It is found that pregnant women deficient in vitamin D transferred this deficiency to their infants and that these infants should receive vitamin D supplements.

In this study, bulk bone collagen carbon (δ13C) and nitrogen (δ15N) isotope data from 49 individuals, recovered from two Medieval burial grounds in Hereford, England, are coupled with incremental dentine data from five individuals with high δ15N bone values who survived into old age, to see whether the high δ15N values were consistent throughout their childhood and adolescence. There are statistically insignificant differences between mean bone δ13C and δ15N values from the two Hereford populations, exhumed at Cathedral Close and St. Guthlac's Priory, despite temporal and demographic differences (St Guthlac's mean: δ13C −19.4 ± 0.5‰ and δ15N 10.9 ± 1.2‰; Hereford Cathedral mean: δ13C −19.6 ± 0.4‰ and δ15N 10.4 ± 0.9‰, 1σ). In comparison to other contemporary urban populations, the Hereford individuals present significantly lower but more variable δ15N values, suggesting a diet low in protein from high trophic level foods such as meat and milk, possibly the result of differing social status or geographic factors. The approximately 23-year long incremental dentine profiles all show considerable fluctuation in stable isotope values during childhood and adolescence for all individuals until around age 20, suggesting possible influence by physiological processes related to growth and development.

Background: Small-for-gestational-age (SGA) term infants are at risk of long-term growth deficits. Objective: The objectives were to test the hypothesis that postnatal growth in SGA term infants can be altered by dietary intervention and to examine whether there is a critical window for nutritional programming of the growth trajectory during the first 9 mo postnatally. Design: Healthy term (gestation [is greater than or equal to] 37 wk) infants with birth weights below the 10th centile were randomly assigned to receive standard term formula (TF; n = 147) or nutrient-enriched formula (EF; n = 152) for the first 9 mo; 175 breast-fed SGA term infants formed a reference group. The main outcome measures were weight, length, and occipitofrontal head circumference (OFC) at 9 and 18 mo. Results: The infants fed the EF showed greater gains in length by 9 (1.1 cm; 95% CI: 0.38, 1.79) and 18 (1.0 cm; 0.25, 1.83) mo and in OFC by 9 (0.5 cm; 0.1, 0.9) and 18 (0.6 cm; 0.2, 1.1) mo than did infants fed the TF; the differences were larger in females. The dietary effects were independent of the pattern of growth retardation. Breast-fed infants showed greater gains in weight and OFC by 18 mo than did infants fed the TF; however, these differences disappeared after adjustment for age, parental size, and birth order. Conclusions: Linear growth and OFC gains in SGA term infants improve after nutritional intervention during the first 9 mo of life and the effects persist for [is greater than or equal to] 9 mo beyond the intervention period. Further information on whether catch-up growth is beneficial or detrimental to long-term outcomes is required before public health interventions can be recommended. KEY WORDS Term infants, small-for-gestational-age infants, catch-up growth, postnatal nutrition, randomized trial, infant formulas, United Kingdom

Background: Preterm children are at high risk of poor growth performance. In 2 randomized trials, preterm infants fed preterm formula grew better in the neonatal period than those fed banked donor breast milk or standard term formula. Objective: Our objective was to test the hypothesis that for preterm infants, the neonatal period is a critical one for programming growth performance and that early diet influences long-term growth. Design: A total of 926 preterm infants were recruited into 2 parallel, randomized trials of neonatal diet. In trial 1, infants were fed either banked donor breast milk or preterm formula whereas in trial 2, infants were fed either standard term formula or preterm formula. Within each trial, the allocated milk was the sole diet for some infants (study A), whereas for others it was a supplement to maternal breast milk, given when not enough expressed breast milk was available (study B). We followed up 781 of 833 survivors (94%) to age 7.5-8 y. Trained assessors obtained anthropometric measurements according to a standard protocol. Results: Despite significantly better neonatal growth performance in infants fed preterm formula (compared with either banked donor breast milk or standard formula), early diet had no influence on weight, height, head circumference, or skinfold thicknesses at 9 or 18 mo postterm or at age 7.5-8 y. Conclusions: These findings suggest that the preterm period is not a critical window for nutritional programming of growth, which contrasts with evidence from these trials showing that early diet influences later neurodevelopment. Am J Clin Nutr 2000;71:822-8. KEY WORDS Preterm infants, premature infants, infant nutrition, milk, human milk, breast milk, infant growth, growth, infant feeding, neonatal diet, preterm formula, term formula, standard infant formula

Abstract Objectives To study the association between birth weight and blood pressure in children from multiple pregnancies (multiplets), mostly twins, to determine whether maternal or genetic factors are responsible for [...]

Background: The low sn-2 palmitate content of infant formulas results in formation of fatty acid calcium soaps in the stools and reduced calcium absorption. Objective: Our objective was to test the hypotheses that increasing the proportion of sn-2 palmitate in formula for term infants would result in greater skeletal mineral deposition and reduced stool hardness. Design: Healthy term neonates were randomly assigned to receive standard formula (n = 103) or formula containing 50% sn-2 palmitate (high-sn-2 formula; n = 100) for 12 wk. One hundred twenty breast-fed infants were also studied. The main outcome measures were 1) radial (single-photon absorptiometry) and whole-body (dual-energy X-ray absorptiometry) bone mineral content (WBBMC) at 12 wk and 2) stool frequency, volume, and consistency at 6 and 12 wk. Secondary outcome measures included stool fatty acid content. Results: Infants receiving high-sn-2 formula had higher WBBMC (128.1 [+ or -] 9.7 compared with 122.7 [+ or -] 10.1 g, adjusted for size and sex), softer stools at 6 and 12 wk, and a lower proportion of stool soap fatty acids than did infants receiving the control formula. Breast-fed infants had adjusted WBBMC values (128.3 [+ or -] 9.1 g) similar to those of infants fed high-sn-2 formula and significantly higher than those of infants fed the control formula. Conclusions: Changing the stereoisomeric structure of palmitate in infant formula resulted in higher WBBMC, reduced stool soap fatty acids, and softer stools more like those of breast-fed infants. The greater bone mass measured could be important if it persists beyond the trial period; this merits further investigation. Am J Clin Nutr 1999;70:920-7. KEY WORDS Term infants, full-term infants, synthetic triacylglycerol, palmitate, stool characteristics, stool biochemistry, bone mineralization, infant formula

An Australia study of vitamin D deficiency in dark-skinned and veiled pregnant women has found that this can be a problem and can be dealt with using supplements.

Complete data are needed EDITOR--Ten years ago Lucas et al reported a retrospective multicentre study determining whether asymptomatic neonatal hypoglycaemia results in neurological damage.[1] They found that moderate hypoglycaemia ([is [...]

Epigenetic events are crucial for early development, but can be influenced by environmental factors, potentially programming the genome for later adverse health outcomes. The insulin-like growth factor 2 (IGF2)/H19locus is crucial for prenatal growth and the epigenetic state at this locus is environmentally labile. Recent studies have implicated maternal factors, including folate intake and smoking, in the regulation of DNA methylation at this locus, although data are often conflicting in the direction and magnitude of effect. Most studies have focused on single tissues and on one or two differentially-methylated regions (DMRs) regulating IGF2/H19expression. In this study, we investigated the relationship between multiple shared and non-shared gestational/maternal factors and DNA methylation at four IGF2/H19DMRs in five newborn cell types from 67 pairs of monozygotic and 49 pairs of dizygotic twins. Data on maternal and non-shared supply line factors were collected during the second and third trimesters of pregnancy and DNA methylation was measured via mass spectrometry using Sequenom MassArray EpiTyper analysis. Our exploratory approach showed that the site of umbilical cord insertion into the placenta in monochorionic twins has the strongest positive association with methylation in all IGF2/H19DMRs (p < 0.05). Further, evidence for tissue- and locus-specific effects were observed, emphasizing that responsiveness to environmental exposures in utero cannot be generalized across genes and tissues, potentially accounting for the lack of consistency in previous findings. Such complexity in responsiveness to environmental exposures in utero has implications for all epigenetic studies investigating the developmental origins of health and disease.

Within-pair comparison of monozygotic (MZ) twins provides an ideal model for studying factors that regulate epigenetic profile, by controlling for genetic variation. Previous reports have demonstrated epigenetic variability within MZ pairs, but the contribution of early life exposures to this variation remains unclear. As epigenetic marks govern gene expression, we have used gene expression discordance as a proxy measure of epigenetic discordance in MZ twins at birth in two cell types. We found strong evidence of expression discordance at birth in both cell types and some evidence for higher discordance in twin pairs with separate placentas. Genes previously defined as being involved in response to the external environment showed the most variable expression within pairs, independent of cell type, supporting the idea that even slight differences in intrauterine environment can influence expression profile. Focusing on birthweight, previously identified as a predisposing factor for cardiovascular, metabolic and other complex diseases, and using a statistical model that estimated association based on within-pair variation of expression and birthweight, we found some association between birthweight and expression of genes involved in metabolism and cardiovascular function. This study is the first to examine expression discordance in newborn twins. It provides evidence of a link between birthweight and activity of specific cellular pathways and, as evidence points to gene expression profiles being maintained through cell division by epigenetic factors, provides a plausible biological mechanism for the previously described link between low birthweight and increased risk of later complex disease.

Sodium bisulfite treatment followed by PCR and DNA sequencing is widely considered the gold standard for the analysis of DNA methylation patterns. However, this technique generally requires substantial quantities of genomic DNA as starting material and is often associated with degradation of DNA. Here, we assess the feasibility of performing bisulfite sequencing on DNA isolated from 3-mm diameter punches of dried blood Guthrie spots. We demonstrate that it is possible to perform bisulfite sequencing from both freshly prepared and archived dried blood spots, using a combination of high purity DNA extraction and efficient bisulfite conversion. With the number of new technologies available for DNA methylation studies, we have extended this analysis and have successfully used a high-throughput mass spectrometry method for DNA methylation analysis on these samples. This provides a new source of material for epigenetic analysis of birth samples and provides an invaluable reference point to track temporal change in epigenetic profiles possibly linked with health and disease.

We hypothesized that cord blood erythropoietin (EPO), a marker of fetal hypoxia, relates to gestational factors and not solely those associated with delivery. We investigated the association between birth weight SD score (SDS) and cord blood EPO in 290 twins (145 pairs), assessing the influence of gestational versusperinatal factors by comparing the association in those who were delivered by elective cesarean (CS) with that in other delivery modes. Blood EPO values were skewed, so geometric means are presented and log EPO values were used in statistical models. The birth size–EPO association was estimated in mixed-effects models that included terms that represented difference in log EPO and mean log EPO for each twin pair. Within-pair estimates of the association were unconfounded by maternal factors (because these were perfectly controlled). Geometric mean EPO was higher in boys versusgirls (24.4 versus17.0 IU/L; p0.0001) and increased with gestational age (p0.0003) but was similar after elective CS versusother delivery modes. The negative birth size–EPO association was stronger in infants who were delivered by elective CS than by other delivery modes for log2EPO: −0.56 (95% CI, −0.77 to −0.36) versus−0.27 (−0.42 to −0.12), respectively; p0.02 for interaction). Because the association was seen after elective CS delivery, cord blood EPO must relate to factors during gestation, not just perinatal factors. There was no evidence of an association between birth weight SDS and pair mean log EPO, indicating that the association is entirely due to fetus-specific rather than pair-specific factors.

AbstractThere has been much interest in evidence that people with lower birthweight have higher risk of adult cardiovascular disease, but the causal pathways underlying such observations are uncertain. Study of twins offers an opportunity to shed light on these pathways, in three different ways. First, in a twin pregnancy maternal nutritional resources and the ?supply line? to the fetuses will be more ?stretched?. We hypothesise that study of twin pregnancies is a more efficient way to identify modifiable maternal factors that influence later health than studies of singleton pregnancies. Second, twins have lower birthweight than singletons. Comparison of cardiovascular disease risk in twins versus that in singletons will provide insight into whether birthweight per se is in the underlying causal pathway of interest, and whether factors constraining fetal growth of twins (versus singletons) affect later outcome. Third, twin cohorts provide an opportunity to investigate the role of ?shared? factors versus factors affecting each individual fetus, by comparing results of within-cohort versus within-pair analyses. Generalisability of findings in twins is debated. We suggest that findings in monochorionic twins (or in the absence of chorionicity data, those from monozygotic twins) need to be interpreted with caution.

There is increasing emphasis on the need to practise evidence-based medicine and the strongest evidence comes from well designed and well-conducted randomized controlled trials. Every component is important for the success of a clinical trial; if the design or sample size is inappropriate, then the results of the study will be unreliable, however well the study is conducted. Conversely a well-designed study may founder because of poor outcome measurement or unacceptably high subject loss. The advantages of a well-designed trial apply equally to studies with short term outcomes and to those requiring long-term follow up. This paper therefore focuses on general methodological issues with a discussion, where appropriate, of the special considerations associated with long-term follow-up. This emphasis is motivated by the belief that a trial with methodological weaknesses is both a waste of resources and unethical. Anyone planning to undertake a randomized controlled trial should consult a more comprehensive text [1–4]. Here, some selected issues are highlighted with the choice of topics reflecting the experience and interests of the authors.

A number of studies have shown that children born by cesarean section have lower blood pressure during the neonatal period. The aim of this study was to investigate whether mode of delivery influenced childhood blood pressure: at age 7.5 to 8 y in a cohort of 756 children born preterm, at 7 to 9 y in a pilot study of 166 children born at term in the United Kingdom, and in a cohort of 650 Tasmanian children born at term. In the preterm cohort, systolic blood pressure was significantly lower in children born by cesarean section rather than delivered vaginally (99.3 ± 10.0 versus 101.4 ± 9.4 mm Hg; 95% confidence interval, -0.69 to -3.46;p = 0.003), with a significant trend to having a higher pressure in those born by breech versus forceps versus spontaneous vaginal delivery versus cesarean section. These findings were not replicated in the term cohorts. This raises the hypothesis that there is a sensitive period for programming later blood pressure by factors associated with mode of delivery and that this period does not extend to full-term.

The author states the reasons for organising summer schools in Great Britain in 2010. She says that it is a privilege to take part in the activities at the Scottish International Flute Summer School, where students try to enhance their skills and musicianship and witness the growing friendships between people. She notes that the nature of summer schools reflect the potential of students to stimulate their creative energy. Information on the schedule of summer school classes in the region is provided.

This article presents letters to the editor in response to articles in previous issues, including a letter in response to "Road Runner to Trail Runner (Batteries Required)," in the May/June 2007 issue, a response to an article entitled "Comrades in South Africa," in the Jan/Feb 2007 issue, a letter from Adam Gould about running events in Wisconsin and other states, and a letter from Robert Frary about training quality.

AbstractWe tested the hypothesis that energy intake among women with twin pregnancies decreases in late gestation, as the uterus enlarges and they become increasingly uncomfortable. We asked women to recall dietary intake for the previous 24 hours, every 2 weeks from around 29 weeks of gestation, using a photographic atlas and other strategies to estimate portion size. Eighty women provided data at around 29, 31, 33 and 35 weeks of gestation. We calculated total energy intake, and energy intake from carbohydrate, fat and protein. Data were log transformed to reduce skewness. Using mixed effects linear regression models, we found minimal evidence that total energy intake changed over this time period, either before or after adjustment for potential confounding factors (95% confidence interval for relative change per week: ?1.4%, 0.6%). There was weak evidence of a small decline in carbohydrate intake over time, both before and after controlling for energy intake. We cannot exclude change in energy intake or diet composition before 29 weeks or after 35 weeks of twin gestation.

Presents letters to the editor referencing articles and topics discussed in previous issues. "The History of the Marathon in Canada," which featured marathons in Canada; Praises for the content of each issue of the magazine; Information on the Bagram Airfield Minefield Marathon in Afghanistan.

Background The widely observed association between birth size and risk of later coronary heart disease (CHD) has not been examined in an impoverished pre-20th century birth cohort. Methods Birth weights and maternal characteristics, for births between 1857 and 1900 in a charity hospital, were recorded from preserved ledgers. Names were linked to death certificates to determine age and cause of death. Death with CHD was coded using specific criteria, and survival analysis methods were used to relate risk of CHD to birth weight, allowing for competing causes of death and adjusting for potentially confounding maternal factors. Results Death certificates were traced for 8584 (53%) of 16 272 registered live-births. Survival analyses were confined to 2938 subjects (1572 male, 1366 female) who survived beyond age 40, since none of the 486 CHD cases was recorded earlier. CHD risk increased with time, but there was no evidence that it was related to birth weight, in men or women. Conclusions We did not replicate findings in more recent cohorts. This may represent a true lack of association in a historical cohort who we believe remained impoverished through their early life. However, we acknowledge the strong possibility of misclassification of cause of death by the person filling in the death certificate and/or our coding criteria, and temporal change in diagnostic criteria for CHD. We cannot exclude the possibility that low birth weight babies ‘programmed’ in utero for later CHD were more likely to die in infancy, in this cohort with a high infant mortality rate.

Twin studies have long been recognized for their value in learning about the aetiology of disease and specifically for their potential for separating genetic effects from environmental effects. The recent upsurge of interest in life-course epidemiology and the study of developmental influences on later health has provided a new impetus to study twins as a source of unique insights. Twins are of special interest because they provide naturally matched pairs where the confounding effects of a large number of potentially causal factors (such as maternal nutrition or gestation length) may be removed by comparisons between twins who share them. The traditional tool of epidemiological ‘risk factor analysis’ is the regression model, but it is not straightforward to transfer standard regression methods to twin data, because the analysis needs to reflect the paired structure of the data, which induces correlation between twins. This paper reviews the use of more specialized regression methods for twin data, based on generalized least squares or linear mixed models, and explains the relationship between these methods and the commonly used approach of analysing within-twin-pair difference values. Methods and issues of interpretation are illustrated using an example from a recent study of the association between birth weight and cord blood erythropoietin. We focus on the analysis of continuous outcome measures but review additional complexities that arise with binary outcomes. We recommend the use of a general model that includes separate regression coefficients for within-twin-pair and between-pair effects, and provide guidelines for the interpretation of estimates obtained under this model.

Background There is evidence that maternal calcium supplementation may result in lower offspring blood pressure. We hypothesized that maternal calcium supplementation also influences other cardiovascular risk factors. Methods In the Tasmanian Infant Health Study, supplements reportedly taken in pregnancy were recorded. Twin children of 147 participating mothers were seen at mean age 9 years. Blood pressure was measured in all 294 children and fasting blood samples taken from 230 (78%) for glucose and insulin, triacylglycerol, total cholesterol (T-C) and HDL cholesterol (HDL-C). LDL cholesterol (LDL-C) was calculated. Results Children of supplemented mothers (n = 110, 77 had venipuncture) had lower geometric mean triacylglycerol, T-C, and LDL-C than other children. After adjustment for potential confounding factors, geometric mean ratios were 0.86 (95% CI: 0.75, 0.98), 0.94, (95% CI: 0.90, 0.99) and 0.90, (95% CI: 0.83, 0.98) respectively. The association with T-C and LDL-C was seen principally among children with BMI > 17.5: estimated ratios 0.85 (95% CI: 0.79, 0.92) for total cholesterol and 0.79 (95% CI: 0.70, 0.90) for LDL cholesterol (P for interaction 0.001 and 0.009 respectively). There was no significant association between maternal calcium supplementation and child size at birth and follow up, blood pressure, fasting glucose or insulin or HDL-C. Conclusions Maternal calcium supplementation may confer health benefits on twin offspring, especially if they are relatively fat. Calcium availability could permanently programme lipid metabolism during fetal life, directly or by influencing maternal lipid profile. Our findings need to be replicated in other studies and in singletons. If confirmed, our findings could have important implications for population health.