Instruct: Given a scientific claim, retrieve documents that support or refute the claim.
Query: Vitamin D deficiency effects birth weight.
OBJECTIVE To assess the effect of 25-hydroxyvitamin D (25-OHD) levels on pregnancy outcomes and birth variables. DESIGN Systematic review and meta-analysis. DATA SOURCES Medline (1966 to August 2012), PubMed (2008 to August 2012), Embase (1980 to August 2012), CINAHL (1981 to August 2012), the Cochrane database of systematic reviews, and the Cochrane database of registered clinical trials. STUDY SELECTION Studies reporting on the association between serum 25-OHD levels during pregnancy and the outcomes of interest (pre-eclampsia, gestational diabetes, bacterial vaginosis, caesarean section, small for gestational age infants, birth weight, birth length, and head circumference). DATA EXTRACTION Two authors independently extracted data from original research articles, including key indicators of study quality. We pooled the most adjusted odds ratios and weighted mean differences. Associations were tested in subgroups representing different patient characteristics and study quality. RESULTS 3357 studies were identified and reviewed for eligibility. 31 eligible studies were included in the final analysis. Insufficient serum levels of 25-OHD were associated with gestational diabetes (pooled odds ratio 1.49, 95% confidence interval 1.18 to 1.89), pre-eclampsia (1.79, 1.25 to 2.58), and small for gestational age infants (1.85, 1.52 to 2.26). Pregnant women with low serum 25-OHD levels had an increased risk of bacterial vaginosis and low birthweight infants but not delivery by caesarean section. CONCLUSION Vitamin D insufficiency is associated with an increased risk of gestational diabetes, pre-eclampsia, and small for gestational age infants. Pregnant women with low 25-OHD levels had an increased risk of bacterial vaginosis and lower birth weight infants, but not delivery by caesarean section.
Breast cancer may originate in utero. We reviewed the available evidence on the association between birthweight and the risk of breast cancer. To date, 26 research papers addressing this issue have been published. The majority of studies identified a positive link between birthweight and premenopausal, but not postmenopausal, breast cancer. The relative risk estimate for breast cancer comparing women with high birthweight to women with low birthweight combining all studies including both pre- and postmenopausal breast cancer was 1.23 (95% confidence interval 1.13-1.34). The mechanisms underlying this association likely include elevated levels of growth factors that may increase the number of susceptible stem cells in the mammary gland or initiate tumors through DNA mutations. Loss of imprinting (LOI) of growth hormone genes relevant for intrauterine growth, such as insulin-like growth factor 2 (IGF2), leads to abnormally high levels of these hormones evidenced by high birthweight. LOI of IGF2 has also been found in mammary tumor tissue. The role of environmental factors that stimulate such epigenetic regulation of gene expression remains to be elucidated.
BACKGROUND Calcium absorption is generally considered to be impaired under conditions of vitamin D deficiency, but the vitamin D status that fully normalizes absorption is not known for humans. OBJECTIVE To quantify calcium absorption at two levels of vitamin D repletion, using pharmacokinetic methods and commercially marketed calcium supplements. DESIGN Two experiments performed in the spring of the year, one year apart. In the first, in which participants were pretreated with 25-hydroxyvitamin D (25OHD), mean serum 25OHD concentration was 86.5 nmol/L; and in the other, with no pretreatment, mean serum concentration was 50.2 nmol/L. Participants received 500 mg oral calcium loads as a part of a standard low calcium breakfast. A low calcium lunch was provided at mid-day. Blood was obtained fasting and at frequent intervals for 10 to 12 hours thereafter. METHODS Relative calcium absorption at the two 25OHD concentrations was estimated from the area under the curve (AUC) for the load-induced increment in serum total calcium. RESULTS AUC(9) (+/- SEM), was 3.63 mg hr/dL +/- 0.234 in participants pretreated with 25OHD and 2.20 +/- 0.240 in those not pretreated (P < 0.001). In brief, absorption was 65% higher at serum 25OHD levels averaging 86.5 nmol/L than at levels averaging 50 nmol/L (both values within the nominal reference range for this analyte). CONCLUSIONS Despite the fact that the mean serum 25OHD level in the experiment without supplementation was within the current reference ranges, calcium absorptive performance at 50 nmol/L was significantly reduced relative to that at a mean 25OHD level of 86 nmol/L. Thus, individuals with serum 25-hydroxyvitamin D levels at the low end of the current reference ranges may not be getting the full benefit from their calcium intake. We conclude that the lower end of the current reference range is set too low.
BACKGROUND The International Lipid-Based Nutrient Supplements Project developed a small-quantity (20 g/d) lipid-based nutrient supplement (LNS) for pregnant and lactating women. OBJECTIVE We evaluated the effects of prenatal LNS supplementation on fetal growth. DESIGN In a community-based, partially double-blind, individually randomized controlled trial, 1320 women ≤20 wk pregnant received 60 mg Fe/400 μg folic acid (IFA), or 1-2 Recommended Dietary Allowances of 18 micronutrients, including 20 mg Fe (MMN), or LNS with the same micronutrients as the MMN group, plus 4 minerals and macronutrients contributing 118 kcal (LNS) daily until delivery. Fetal growth was compared across groups by using intention-to-treat analysis. The primary outcome was birth length. RESULTS This analysis included 1057 women (IFA = 349, MMN = 354, LNS = 354). Groups did not differ significantly in mean birth length, length-for-age z score (LAZ), head circumference, or percentage low birth length but differed in mean birth weight (P = 0.044), weight-for-age z score (WAZ; P = 0.046), and BMI-for-age z score (BMIZ; P = 0.040), with a trend toward differences in low birth weight (P = 0.069). In pairwise comparisons, the LNS group had greater mean birth weight (+85 g; P = 0.040), WAZ (+0.19; P = 0.045), and BMIZ (+0.21; P = 0.035) and a lower risk of low birth weight (RR: 0.61, 95% CI: 0.39, 0.96; P = 0.032) than did the IFA group. The other group differences were not significant. The effect of intervention was modified by mother's parity, age, height, baseline hemoglobin, household food insecurity, and child sex, with parity being the most consistent modifier. Among primiparous women (IFA = 131; MMN = 110; LNS = 128), the LNS group had greater mean birth length (+0.91 cm; P = 0.001), LAZ (+0.47; P = 0.001), weight (+237 g; P < 0.001), WAZ (+0.56; P < 0.001), BMIZ (+0.52; P < 0.001), head circumference (0.50 cm; P = 0.017), and head circumference-for-age z score (+0.40; P = 0.022) than did the IFA group; similar differences were found when comparing the LNS and MMN groups among primiparous women, and no group differences were found among multiparous women. CONCLUSION Prenatal LNS supplementation can improve fetal growth among vulnerable women in Ghana, particularly primiparous women. This trial was registered at clinicaltrials.gov as NCT00970866.
We evaluated oral 1,25-vitamin D3 for as long as 26 months in six prepubescent children with renal osteodystrophy previously treated with vitamin D2. Therapy was given at 14 to 41 ng per kilogram per day to correct hypocalcemia and reverse bone disease. Serum levels of 1,25-vitamin D3 were initially reduced at 15 +/- 5 pg per milliliter (mean +/- S.E.M.) and after treatment rose to 54 +/- 13. Serum calcium rose from 7.5 +/- 1.6 mg per deciliter (mean +/- S.D.) to 9.8 +/- 0.6 after one month (P less than 0.02). Alkaline phosphatase activity fell from 536 +/- 298 to 208 +/- 91 IU per liter after 12 months (P less than 0.05). Serum immunoreactive parathyroid levels fell from 900 +/- 562 microliter eq per milliliter 411 +/- 377. Healing of rickets and subperiosteal erosions was found. Remineralization of bone was demonstrated by the photon absorption technic. In four patients growth velocity, evaluated for 12 months before and after therapy, increased from 2.6 +/- 0.8 to 8.0 +/- 3.2 cm per year. Growth velocity per year increased from less than third percentile in each to the 10th to 97th percentile after therapy. Height increment ranged from 27 to 113 per cent of that expected for change in chronologic age and 40 to 114 per cent expected for change in bone age after therapy. This trial demonstrates that oral 1,25-vitamin D3 can reverse renal bone disease and increase growth in uremic children.
CONTEXT Adequate vitamin D status for optimum bone health has received increased recognition in recent years; however, the ideal intake is not known. Serum 25-hydroxyvitamin D is the generally accepted indicator of vitamin D status, but no universal reference level has been reached. OBJECTIVE To investigate the relative importance of high calcium intake and serum 25-hydroxyvitamin D for calcium homeostasis, as determined by serum intact parathyroid hormone (PTH). DESIGN, SETTING, AND PARTICIPANTS Cross-sectional study of 2310 healthy Icelandic adults who were divided equally into 3 age groups (30-45 years, 50-65 years, or 70-85 years) and recruited from February 2001 to January 2003. They were administered a semi-quantitative food frequency questionnaire, which assessed vitamin D and calcium intake. Participants were further divided into groups according to calcium intake (<800 mg/d, 800-1200 mg/d, and >1200 mg/d) and serum 25-hydroxyvitamin D level (<10 ng/mL, 10-18 ng/mL, and >18 ng/mL). MAIN OUTCOME MEASURE Serum intact PTH as determined by calcium intake and vitamin D.   RESULTS A total of 944 healthy participants completed all parts of the study. After adjusting for relevant factors, serum PTH was lowest in the group with a serum 25-hydroxyvitamin D level of more than 18 ng/mL but highest in the group with a serum 25-hydroxyvitamin D level of less than 10 ng/mL. At the low serum 25-hydroxyvitamin D level (<10 ng/mL), calcium intake of less than 800 mg/d vs more than 1200 mg/d was significantly associated with higher serum PTH (P = .04); and at a calcium intake of more than 1200 mg/d, there was a significant difference between the lowest and highest vitamin D groups (P = .04). CONCLUSIONS As long as vitamin D status is ensured, calcium intake levels of more than 800 mg/d may be unnecessary for maintaining calcium metabolism. Vitamin D supplements are necessary for adequate vitamin D status in northern climates.
We performed a meta-analysis of cross-sectional studies on serum 25(OH)D status globally. Serum 25(OH)D levels on average were 54 nmol/l, were higher in women than men, and higher in Caucasians than in non-Caucasians. There was no trend in serum 25(OH)D level with latitude. Vitamin D deficiency was widespread. We studied vitamin D status (expressed as serum 25-hydroxy-vitamin D [25(OH)D]) in native subjects worldwide. Meta-analysis and meta-regression of studies reporting on 25(OH)D in healthy subjects retrieved from Pubmed, Embase and Web of Science using the terms “serum”, “25-hydroxy-vitamin D”, “cholecalciferol”, and “human”. A total of 394 studies were included. The mean 25(OH)D level was 54 nmol/l (95% CI: 52–57 nmol/l). Women had borderline significantly higher 25(OH)D levels than men, and Caucasians had higher levels than non-Caucasians. 25(OH)D levels were higher in subjects aged >15 years than in younger subjects. Unadjusted there was no significant decrease in 25(OH)D with latitude (slope of curve −0.03 ± 0.12 nmol/l per degree latitude north or south of equator, p = 0.8). There was a significant decline with latitude for Caucasians (−0.69 ± 0.30 nmol/l per degree, p = 0.02), but not for non-Caucasians (0.03 ± 0.39 nmol/l per degree, p = 0.14). After adjustment for age, gender, and ethnicity, no overall correlation was present between 25(OH)D and latitude (−0.29 ± 0.24 nmol/l per degree, p = 0.23). There was no overall influence of latitude on 25(OH)D. However, in separate analyses 25(OH)D decreased with latitude in Caucasians but not in non-Caucasians. A widespread global vitamin D insufficiency was present compared with proposed threshold levels.
Birth weight is a significant predictor of breast cancer risk in adult life and mammary gland mass could be an intermediate stage in this long process. We have studied the association of birth size measurements with mammographic density, a marker of mammary gland mass. For a population-based sample of 893 postmenopausal women without previous cancer in Sweden, we retrieved information on birth size from birth records and their most recent mammography. Film mammograms of the medio-lateral oblique view were digitized and the Cumulus software was used for computer-assisted semi-automated thresholding of mammographic density. Results were analyzed using generalized linear models controlling for possible confounders. Mean percent mammographic density increased when comparing the extreme categories of birth weight (from 15.6% to 18.6%) and head circumference (from 15.5% to 20.4%), and the corresponding linear trends were statistically significant (p values 0.02 and 0.007, respectively). The associations were particularly strong when the cutoff for high versus low mammographic density was set at the relatively high value of 50%. Compared to women weighing 3001-3500 grams at birth, women with birth weights >4000g were at almost 3-fold risk of developing high mammographic density (odds ratio: 2.9, 95% confidence interval 1.1 to 7.9). No association with mammographic density was evident with respect to birth length which, however, is known to be less accurately measured. These results indicate that adult breast density, a powerful predictor of breast cancer risk, has intrauterine roots, as reflected in birth size.
CONTEXT Vitamin D deficiency is associated with many adverse health outcomes, yet little is known about the genetic epidemiology of vitamin D or its metabolites. OBJECTIVE Our objective was to examine the relationship among three vitamin D-related genes and levels of 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)2D] in Hispanics (HAs) and African Americans (AAs). DESIGN AND SETTING The cross-sectional Insulin Resistance Atherosclerosis Family Study recruited and examined subjects in: Los Angeles, California (AAs; 513 individuals from 42 families); San Luis Valley (SLV), Colorado (HAs; 513 individuals from 30 families); and San Antonio (SA), Texas (HAs; 504 individuals from 58 families). MAIN OUTCOME MEASURES Plasma levels of 25(OH)D and 1,25(OH)2D were measured. RESULTS Levels of 25(OH)D were highest in SLV-HAs [18.3 +/- 7.7 ng/ml (45.7 +/- 19.2 nmol/liter)], lower in SA-HAs [14.6 +/- 6.4 ng/ml (36.4 +/- 16.0 nmol/liter)], and lowest in AAs [11.0 +/- 5.4 ng/ml (27.5 +/- 13.5 nmol/liter)]. Levels of 1,25(OH)2D were similar in AAs [43.5 +/- 13.9 pg/ml (113.1 +/- 36.1 pmol/liter)] and SLV-HAs [43.2 +/- 13.3 pg/ml (112.3 +/- 34.6 pmol/liter)], but higher in SA-HAs [48.6 +/- 17.0 pg/ml (126.4 +/- 44.2 pmol/liter)]. After adjusting for gender and age within the site, two single nucleotide polymorphisms (SNPs) in the vitamin D binding protein gene (DBP), rs4588 and rs7041, were associated with 25(OH)D, and one SNP in the DBP, rs4588, was associated with 1,25(OH)2D at all three study centers. CONCLUSIONS SNPs in the DBP are associated with levels of 25(OH)D and 1,25(OH)2D in HA and AA participants in the Insulin Resistance Atherosclerosis Family Study.
INTRODUCTION Various perinatal factors, including birth weight, birth order, maternal age, gestational age, twin status, and parental smoking, have been postulated to affect breast cancer risk in daughters by altering the hormonal environment of the developing fetal mammary glands. Despite ample biologic plausibility, epidemiologic studies to date have yielded conflicting results. We investigated the associations between perinatal factors and subsequent breast cancer risk through meta-analyses. METHODS We reviewed breast cancer studies published from January 1966 to February 2007 that included data on birth weight, birth order, maternal age, gestational age, twin status, and maternal or paternal smoking. Meta-analyses using random effect models were employed to summarize the results. RESULTS We found that heavier birth weights were associated with increased breast cancer risk, with studies involving five categories of birth weight identifying odds ratios (ORs) of 1.24 (95% confidence interval [CI] 1.04 to 1.48) for 4,000 g or more and 1.15 (95% CI 1.04 to 1.26) for 3,500 g to 3,999 g, relative to a birth weight of 2,500 to 2,599 g. These studies provided no support for a J-shaped relationship of birthweight to risk. Support for an association with birthweight was also derived from studies based on three birth weight categories (OR 1.15 [95% CI 1.01 to 1.31] for > or =4,000 g relative to <3,000 g) and two birth weight categories (OR 1.09 [95% CI 1.02 to 1.18] for > or =3,000 g relative to <3,000 g). Women born to older mothers and twins were also at some increased risk, but the results were heterogeneous across studies and publication years. Birth order, prematurity, and maternal smoking were unrelated to breast cancer risk. CONCLUSION Our findings provide some support for the hypothesis that in utero exposures reflective of higher endogenous hormone levels could affect risk for development of breast cancer in adulthood.
Recent evidence suggests that vitamin D intakes above current recommendations may be associated with better health outcomes. However, optimal serum concentrations of 25-hydroxyvitamin D [25(OH)D] have not been defined. This review summarizes evidence from studies that evaluated thresholds for serum 25(OH)D concentrations in relation to bone mineral density (BMD), lower-extremity function, dental health, and risk of falls, fractures, and colorectal cancer. For all endpoints, the most advantageous serum concentrations of 25(OH)D begin at 75 nmol/L (30 ng/mL), and the best are between 90 and 100 nmol/L (36-40 ng/mL). In most persons, these concentrations could not be reached with the currently recommended intakes of 200 and 600 IU vitamin D/d for younger and older adults, respectively. A comparison of vitamin D intakes with achieved serum concentrations of 25(OH)D for the purpose of estimating optimal intakes led us to suggest that, for bone health in younger adults and all studied outcomes in older adults, an increase in the currently recommended intake of vitamin D is warranted. An intake for all adults of > or =1000 IU (25 microg) [DOSAGE ERROR CORRECTED] vitamin D (cholecalciferol)/d is needed to bring vitamin D concentrations in no less than 50% of the population up to 75 nmol/L. The implications of higher doses for the entire adult population should be addressed in future studies.
In this paper we review the associations between maternal and child undernutrition with human capital and risk of adult diseases in low-income and middle-income countries. We analysed data from five long-standing prospective cohort studies from Brazil, Guatemala, India, the Philippines, and South Africa and noted that indices of maternal and child undernutrition (maternal height, birthweight, intrauterine growth restriction, and weight, height, and body-mass index at 2 years according to the new WHO growth standards) were related to adult outcomes (height, schooling, income or assets, offspring birthweight, body-mass index, glucose concentrations, blood pressure). We undertook systematic reviews of studies from low-income and middle-income countries for these outcomes and for indicators related to blood lipids, cardiovascular disease, lung and immune function, cancers, osteoporosis, and mental illness. Undernutrition was strongly associated, both in the review of published work and in new analyses, with shorter adult height, less schooling, reduced economic productivity, and--for women--lower offspring birthweight. Associations with adult disease indicators were not so clear-cut. Increased size at birth and in childhood were positively associated with adult body-mass index and to a lesser extent with blood pressure values, but not with blood glucose concentrations. In our new analyses and in published work, lower birthweight and undernutrition in childhood were risk factors for high glucose concentrations, blood pressure, and harmful lipid profiles once adult body-mass index and height were adjusted for, suggesting that rapid postnatal weight gain--especially after infancy--is linked to these conditions. The review of published works indicates that there is insufficient information about long-term changes in immune function, blood lipids, or osteoporosis indicators. Birthweight is positively associated with lung function and with the incidence of some cancers, and undernutrition could be associated with mental illness. We noted that height-for-age at 2 years was the best predictor of human capital and that undernutrition is associated with lower human capital. We conclude that damage suffered in early life leads to permanent impairment, and might also affect future generations. Its prevention will probably bring about important health, educational, and economic benefits. Chronic diseases are especially common in undernourished children who experience rapid weight gain after infancy.
CONTEXT Maternal depressive symptoms during pregnancy have been reported in some, but not all, studies to be associated with an increased risk of preterm birth (PTB), low birth weight (LBW), and intrauterine growth restriction (IUGR). OBJECTIVE To estimate the risk of PTB, LBW, and IUGR associated with antenatal depression. DATA SOURCES AND STUDY SELECTION We searched for English-language and non-English-language articles via the MEDLINE, PsycINFO, CINAHL, Social Work Abstracts, Social Services Abstracts, and Dissertation Abstracts International databases (January 1980 through December 2009). We aimed to include prospective studies reporting data on antenatal depression and at least 1 adverse birth outcome: PTB (<37 weeks' gestation), LBW (<2500 g), or IUGR (<10th percentile for gestational age). Of 862 reviewed studies, 29 US-published and non-US-published studies met the selection criteria. DATA EXTRACTION Information was extracted on study characteristics, antenatal depression measurement, and other biopsychosocial risk factors and was reviewed twice to minimize error. DATA SYNTHESIS Pooled relative risks (RRs) for the effect of antenatal depression on each birth outcome were calculated using random-effects methods. In studies of PTB, LBW, and IUGR that used a categorical depression measure, pooled effect sizes were significantly larger (pooled RR [95% confidence interval] = 1.39 [1.19-1.61], 1.49 [1.25-1.77], and 1.45 [1.05-2.02], respectively) compared with studies that used a continuous depression measure (1.03 [1.00-1.06], 1.04 [0.99-1.09], and 1.02 [1.00-1.04], respectively). The estimates of risk for categorically defined antenatal depression and PTB and LBW remained significant when the trim-and-fill procedure was used to correct for publication bias. The risk of LBW associated with antenatal depression was significantly larger in developing countries (RR = 2.05; 95% confidence interval, 1.43-2.93) compared with the United States (RR = 1.10; 95% confidence interval, 1.01-1.21) or European social democracies (RR = 1.16; 95% confidence interval, 0.92-1.47). Categorically defined antenatal depression tended to be associated with an increased risk of PTB among women of lower socioeconomic status in the United States. CONCLUSIONS Women with depression during pregnancy are at increased risk for PTB and LBW, although the magnitude of the effect varies as a function of depression measurement, country location, and US socioeconomic status. An important implication of these findings is that antenatal depression should be identified through universal screening and treated.
BACKGROUND Knowledge gaps have contributed to considerable variation among international dietary recommendations for vitamin D.   OBJECTIVE We aimed to establish the distribution of dietary vitamin D required to maintain serum 25-hydroxyvitamin D [25(OH)D] concentrations above several proposed cutoffs (ie, 25, 37.5, 50, and 80 nmol/L) during wintertime after adjustment for the effect of summer sunshine exposure and diet. DESIGN A randomized, placebo-controlled, double-blind 22-wk intervention study was conducted in men and women aged 20-40 y (n = 238) by using different supplemental doses (0, 5, 10, and 15 microg/d) of vitamin D(3) throughout the winter. Serum 25(OH)D concentrations were measured by using enzyme-linked immunoassay at baseline (October 2006) and endpoint (March 2007). RESULTS There were clear dose-related increments (P < 0.0001) in serum 25(OH)D with increasing supplemental vitamin D(3). The slope of the relation between vitamin D intake and serum 25(OH)D was 1.96 nmol x L(-1) x microg(-1) intake. The vitamin D intake that maintained serum 25(OH)D concentrations of >25 nmol/L in 97.5% of the sample was 8.7 microg/d. This intake ranged from 7.2 microg/d in those who enjoyed sunshine exposure, 8.8 microg/d in those who sometimes had sun exposure, and 12.3 microg/d in those who avoided sunshine. Vitamin D intakes required to maintain serum 25(OH)D concentrations of >37.5, >50, and >80 nmol/L in 97.5% of the sample were 19.9, 28.0, and 41.1 microg/d, respectively. CONCLUSION The range of vitamin D intakes required to ensure maintenance of wintertime vitamin D status [as defined by incremental cutoffs of serum 25(OH)D] in the vast majority (>97.5%) of 20-40-y-old adults, considering a variety of sun exposure preferences, is between 7.2 and 41.1 microg/d.
BACKGROUND Multiple studies have been carried out to assess the effect of zinc supplementation on children's growth. The results of these studies are inconsistent, and the factors responsible for these varied outcomes are unknown. OBJECTIVE Meta-analyses of randomized controlled intervention trials were therefore completed to assess the effect of zinc supplementation on the physical growth and serum zinc concentrations of prepubertal children. DESIGN A total of 33 acceptable studies with appropriate data were identified by MEDLINE (National Library of Medicine, Bethesda, MD) searches and other methods. Weighted mean effect sizes (expressed in SD units) were calculated for changes in height, weight, weight-for-height, and serum zinc concentration by using random-effects models; factors associated with effect sizes were explored by meta-regression techniques. RESULTS Zinc supplementation produced highly significant, positive responses in height and weight increments, with effect sizes of 0.350 (95% CI: 0.189, 0.511) and 0.309 (0.178, 0.439), respectively. There was no significant effect of zinc on weight-for-height indexes [weighted mean effect size: -0.018 (-0.132, 0.097)]. Zinc supplementation caused a large increase in the children's serum zinc concentrations, with an effect size of 0.820 (0.499, 1.14). Growth responses were greater in children with low initial weight-for-age z scores and in those aged >6 mo with low initial height-for-age z scores. CONCLUSIONS Interventions to improve children's zinc nutriture should be considered in populations at risk of zinc deficiency, especially where there are elevated rates of underweight or stunting. The population mean serum zinc concentration is a useful indicator of the successful delivery and absorption of zinc supplements in children.
All vertebrates, including humans, obtain most of their daily vitamin D requirement from casual exposure to sunlight. During exposure to sunlight, the solar ultraviolet B photons (290-315 nm) penetrate into the skin where they cause the photolysis of 7-dehydrocholesterol to precholecalciferol. Once formed, precholecalciferol undergoes a thermally induced rearrangement of its double bonds to form cholecalciferol. An increase in skin pigmentation, aging, and the topical application of a sunscreen diminishes the cutaneous production of cholecalciferol. Latitude, season, and time of day as well as ozone pollution in the atmosphere influence the number of solar ultraviolet B photons that reach the earth's surface, and thereby, alter the cutaneous production of cholecalciferol. In Boston, exposure to sunlight during the months of November through February will not produce any significant amounts of cholecalciferol in the skin. Because windowpane glass absorbs ultraviolet B radiation, exposure of sunlight through glass windows will not result in any production of cholecalciferol. It is now recognized that vitamin D insufficiency and vitamin D deficiency are common in elderly people, especially in those who are infirm and not exposed to sunlight or who live at latitudes that do not provide them with sunlight-mediated cholecalciferol during the winter months. Vitamin D insufficiency and deficiency exacerbate osteoporosis, cause osteomalacia, and increase the risk of skeletal fractures. Vitamin D insufficiency and deficiency can be prevented by encouraging responsible exposure to sunlight and/or consumption of a multivitamin tablet that contains 10 micrograms (400 IU) vitamin D.
BACKGROUND Birth size, perhaps a proxy for prenatal environment, might be a correlate of subsequent breast cancer risk, but findings from epidemiological studies have been inconsistent. We re-analysed individual participant data from published and unpublished studies to obtain more precise estimates of the magnitude and shape of the birth size-breast cancer association. METHODS AND FINDINGS Studies were identified through computer-assisted and manual searches, and personal communication with investigators. Individual participant data from 32 studies, comprising 22,058 breast cancer cases, were obtained. Random effect models were used, if appropriate, to combine study-specific estimates of effect. Birth weight was positively associated with breast cancer risk in studies based on birth records (pooled relative risk [RR] per one standard deviation [SD] [= 0.5 kg] increment in birth weight: 1.06; 95% confidence interval [CI] 1.02-1.09) and parental recall when the participants were children (1.02; 95% CI 0.99-1.05), but not in those based on adult self-reports, or maternal recall during the woman's adulthood (0.98; 95% CI 0.95-1.01) (p for heterogeneity between data sources = 0.003). Relative to women who weighed 3.000-3.499 kg, the risk was 0.96 (CI 0.80-1.16) in those who weighed < 2.500 kg, and 1.12 (95% CI 1.00-1.25) in those who weighed > or = 4.000 kg (p for linear trend = 0.001) in birth record data. Birth length and head circumference from birth records were also positively associated with breast cancer risk (pooled RR per one SD increment: 1.06 [95% CI 1.03-1.10] and 1.09 [95% CI 1.03-1.15], respectively). Simultaneous adjustment for these three birth size variables showed that length was the strongest independent predictor of risk. The birth size effects did not appear to be confounded or mediated by established breast cancer risk factors and were not modified by age or menopausal status. The cumulative incidence of breast cancer per 100 women by age 80 y in the study populations was estimated to be 10.0, 10.0, 10.4, and 11.5 in those who were, respectively, in the bottom, second, third, and top fourths of the birth length distribution. CONCLUSIONS This pooled analysis of individual participant data is consistent with birth size, and in particular birth length, being an independent correlate of breast cancer risk in adulthood.
Vitamin D insufficiency is common, however within individuals, not all manifest the biochemical effects of PTH excess. This further extends to patients with established osteoporosis. The mechanism underlying the blunted PTH response is unclear but may be related to magnesium (Mg) deficiency. The aims of this study were to compare in patients with established osteoporosis and differing degrees of vitamin D and PTH status : (1) the presence of Mg deficiency using the standard Mg loading test (2) evaluate the effects of Mg loading on the calcium-PTH endocrine axis (3) determine the effects of oral, short term Mg supplementation on the calcium-PTH endocrine axis and bone turnover. 30 patients (10 women in 3 groups) were evaluated prospectively measuring calcium, PTH, Mg retention (Mg loading test), dietary nutrient intake (calcium, vitamin D, Mg) and bone turnover markers (serum CTX & P1CP). Multivariate analysis controlling for potential confounding baseline variable was undertaken for the measured outcomes. All subjects, within the low vitamin D and low PTH group following the magnesium loading test had evidence of Mg depletion [mean(SD) retention 70.3%(12.5)] and showed an increase in calcium 0.06(0.01) mmol/l [95% CI 0.03, 0.09, p=0.007], together with a rise in PTH 13.3 ng/l (4.5) [95% CI 3.2, 23.4, p=0.016] compared to baseline. Following oral supplementation bone turnover increased: CTX 0.16 (0.06) mcg/l [95%CI 0.01, 0.32 p=0.047]; P1CP 13.1 (5.7) mcg/l [95% CI 0.29, 26.6 p=0.049]. In subjects with a low vitamin D and raised PTH mean retention was 55.9%(14.8) and in the vitamin replete group 36.1%(14.4), with little change in both acute markers of calcium homeostasis and bone turnover markers following both the loading test and oral supplementation. This study confirms that in patients with established osteoporosis, there is also a distinct group with a low vitamin D and a blunted PTH level and that Mg deficiency (as measured by the Mg loading test) is an important contributing factor.
Multiple sclerosis (MS) shows a multifold increase in prevalence with an increase in latitudes, both north and south of the equator. One of the potential factors related to the difference of the prevalence is vitamin D, because the strength of ambient ultraviolet light, which is essential for vitamin D production, decreases with increasing latitude. It is known that vitamin D has immunomodulatory functions and suppresses an animal model of MS. It is also considered that vitamin D-related genes are critical susceptible genes for MS. An approach from environmental and genetic aspects is needed to investigate the association between vitamin D and MS.
BACKGROUND The growing appreciation of the multi-faceted importance of optimal maternal nutrition to the health and development of the infant and young child is tempered by incompletely resolved strategies for combatting challenges. OBJECTIVE To review the importance of maternal nutrition and strategies being employed to optimize outcomes. METHODS Selected data from recent literature with special focus on rationale for and currently published results of maternal nutrition supplements, including lipid based nutrition supplements. RESULTS 1) An impelling rationale for improving the maternal and in utero environment of low resource populations has emerged to achieve improved fetal and post-natal growth and development. 2) Based partly on population increases in adult height over one-two generations, much can be achieved by reducing poverty. 3) Maternal, newborn and infant characteristics associated with low resource environments include evidence of undernutrition, manifested by underweight and impaired linear growth. 4) Apart from broad public health and educational initiatives, to date, most specific efforts to improve fetal growth and development have included maternal nutrition interventions during gestation. 5) The relatively limited but real benefits of both iron/folic acid (IFA) and multiple micronutrient (MMN) maternal supplements during gestation have now been reasonably defined. 6) Recent investigations of a maternal lipid-based primarily micronutrient supplement (LNS) have not demonstrated a consistent benefit beyond MMN alone. 7) However, effects of both MMN and LNS appear to be enhanced by commencing early in gestation. CONCLUSIONS Poor maternal nutritional status is one of a very few specific factors in the human that not only contributes to impaired fetal and early post-natal growth but for which maternal interventions have demonstrated improved in utero development, documented primarily by both improvements in low birth weights and by partial corrections of impaired birth length. A clearer definition of the benefits achievable by interventions specifically focused on correcting maternal nutrition deficits should not be limited to improvements in the quality of maternal nutrition supplements, but on the cumulative quantity and timing of interventions (also recognizing the heterogeneity between populations). Finally, in an ideal world these steps are only a prelude to improvements in the total environment in which optimal nutrition and other health determinants can be achieved.
OBJECTIVE To compare contemporary pregnancy outcomes in women with and without type 1 diabetes, and to examine the effects of obesity and glycaemic control on these outcomes. DESIGN AND SETTING Historical cohort study in a specialist diabetes and maternity network in Victoria. PARTICIPANTS All singleton births (at least 20 weeks' gestation), 2010-2013, were analysed: 107 pregnancies to women with type 1 diabetes and 27 075 pregnancies to women without diabetes. Women with type 2 diabetes or gestational diabetes were excluded. METHODS Data were extracted from the Birthing Outcomes System database; associations between type 1 diabetes and pregnancy outcomes were analysed by multivariable regression. MAIN OUTCOME MEASURES Mode of birth; maternal and neonatal outcomes. RESULTS The mean body mass index was higher for women with type 1 diabetes than for women without diabetes (mean, 27.3 kg/m(2) [SD, 5.0] v 25.7 kg/m(2) [SD, 5.9]; P = 0.01); the median gestation period for their babies was shorter (median, 37.3 weeks [IQR, 34.6-38.1] v 39.4 weeks [IQR, 38.4-40.4]; P < 0.001) and they were more likely to be large for gestational age (LGA) (adjusted odds ratio [aOR], 7.9; 95% CI, 5.3-11.8). Women with type 1 diabetes were more likely to have had labour induced (aOR, 3.0; 95% CI, 2.0-4.5), a caesarean delivery (aOR, 4.6; 95% CI, 3.1-7.0), or a pre-term birth (aOR, 6.7; 95% CI, 4.5-10.0); their babies were more likely to have shoulder dystocia (aOR, 8.2; 95% CI, 3.6-18.7), hypoglycaemia (aOR, 10.3; 95% CI, 6.8-15.6), jaundice (aOR, 5.1; 95% CI, 3.3-7.7), respiratory distress (aOR, 2.5; 95% CI, 1.4-4.4) or to suffer perinatal death (aOR, 4.3; 95% CI, 1.9-9.9). In women with type 1 diabetes, greater obesity was associated with increased odds for an LGA baby or congenital malformation, and increased HbA1c levels were associated with pre-term birth and perinatal death. CONCLUSION Women with type 1 diabetes, even when managed in a specialist setting, still experience adverse obstetric and neonatal outcomes. Poor glycaemic control is not wholly responsible for adverse outcomes, reinforcing the importance of other risk factors, such as obesity and weight gain.
Vitamin D may play a role in glucose metabolism. A low vitamin D level has been associated with increased risk of diabetes mellitus, but the association has not been confirmed in Asians. Our objective was to examine the association of serum 25-hydroxyvitamin D [25(OH)D] levels with insulin resistance and diabetes mellitus in Korean adults based on a large population-based survey. Cross-sectional analyses were carried out on 5787 Korean adults (2453 men and 3334 women) who were 20 y or older and participated in the Fourth Korea NHANES conducted in 2008. Diabetes mellitus was defined as fasting plasma glucose ≥7 mmol/L or current use of oral hypoglycemic agents or insulin. Insulin resistance was estimated by homeostatic model assessment for insulin resistance (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI). Compared to individuals with a sufficient serum 25(OH)D concentration ≥75 nmol/L, the OR (95% CI) for diabetes mellitus were 1.73 (1.09-2.74), 1.30 (0.91-1.84), and 1.40 (0.99-1.98) for serum 25(OH)D concentrations <25, 25 to <50, and 50 to <75 nmol/L, respectively, after multiple adjustments (P-trend < 0.0001). Furthermore, the serum 25(OH)D level was inversely associated with HOMA-IR (β = -0.061; P = 0.001) and positively associated with QUICKI (β = 0.059; P = 0.001) in overweight or obese participants. In conclusion, a low serum vitamin D concentration is associated with a high risk of diabetes mellitus in Korean adults and the concentration is inversely associated with insulin resistance in those who are overweight or obese.
BACKGROUND Emerging evidence suggests an association between female prenatal experience and her subsequent risk of developing breast cancer. Potential underlying mechanisms include variation in amounts of maternal endogenous sex hormones and growth hormones, germ-cell mutations, formation of cancer stem-cells, and other genetic or epigenetic events. We reviewed and summarised quantitatively the available data on intrauterine exposures and risk of breast cancer. METHODS We systematically searched for studies that assessed association between perinatal factors and risk of breast cancer. We reviewed separately each of the perinatal factors, including birthweight, birth length, parental age at delivery, gestational age, intrauterine exposure to diethylstilbestrol, twin membership, maternal pre-eclampsia or eclampsia, and other factors. FINDINGS We identified 57 studies published between Oct 1, 1980, and June 21, 2007. Increased risk of breast cancer was noted with increased birthweight (relative risk [RR] 1.15 [95% CI 1.09-1.21]), birth length (1.28 [1.11-1.48]), higher maternal age (1.13 [1.02-1.25]), and paternal age (1.12 [1.05-1.19]). Decreased risk of breast cancer was noted for maternal pre-eclampsia and eclampsia (0.48 [0.30-0.78]) and twin membership (0.93 [0.87-1.00]). No association was noted between risk of breast cancer and gestational age at birth (0.95 [0.71-1.26]) or maternal diethylstilbestrol treatment (1.40 [0.86-2.28]). INTERPRETATION The intrauterine environment contributes to the predisposition of women to breast cancer in adulthood. The in-utero mechanisms responsible for such predisposition need to be elucidated.
Maternal diabetes mellitus is a significant risk factor for structural birth defects, including congenital heart defects and neural tube defects. With the rising prevalence of type 2 diabetes mellitus and obesity in women of childbearing age, diabetes mellitus-induced birth defects have become an increasingly significant public health problem. Maternal diabetes mellitus in vivo and high glucose in vitro induce yolk sac injuries by damaging the morphologic condition of cells and altering the dynamics of organelles. The yolk sac vascular system is the first system to develop during embryogenesis; therefore, it is the most sensitive to hyperglycemia. The consequences of yolk sac injuries include impairment of nutrient transportation because of vasculopathy. Although the functional relationship between yolk sac vasculopathy and structural birth defects has not yet been established, a recent study reveals that the quality of yolk sac vasculature is related inversely to embryonic malformation rates. Studies in animal models have uncovered key molecular intermediates of diabetic yolk sac vasculopathy, which include hypoxia-inducible factor-1α, apoptosis signal-regulating kinase 1, and its inhibitor thioredoxin-1, c-Jun-N-terminal kinases, nitric oxide, and nitric oxide synthase. Yolk sac vasculopathy is also associated with abnormalities in arachidonic acid and myo-inositol. Dietary supplementation with fatty acids that restore lipid levels in the yolk sac lead to a reduction in diabetes mellitus-induced malformations. Although the role of the human yolk in embryogenesis is less extensive than in rodents, nevertheless, human embryonic vasculogenesis is affected negatively by maternal diabetes mellitus. Mechanistic studies have identified potential therapeutic targets for future intervention against yolk sac vasculopathy, birth defects, and other complications associated with diabetic pregnancies.
OBJECTIVE In 1989 the St. Vincent declaration set a five-year target for approximating outcomes of pregnancies in women with diabetes to those of the background population. We investigated and quantified the risk of adverse pregnancy outcomes in pregnant women with type 1 diabetes (T1DM) to evaluate if the goals of the 1989 St. Vincent Declaration have been obtained concerning foetal and neonatal complications. METHODS Twelve population-based studies published within the last 10 years with in total 14,099 women with T1DM and 4,035,373 women from the background population were identified. The prevalence of four foetal and neonatal complications was compared. RESULTS In women with T1DM versus the background population, congenital malformations occurred in 5.0% (2.2-9.0) (weighted mean and range) versus 2.1% (1.5-2.9), relative risk (RR) = 2.4, perinatal mortality in 2.7% (2.0-6.6) versus 0.72% (0.48-0.9), RR = 3.7, preterm delivery in 25.2% (13.0-41.7) versus 6.0% (4.7-7.1), RR = 4.2 and delivery of large for gestational infants in 54.2% (45.1-62.5) versus 10.0%, RR = 4.5. Early pregnancy HbA1c was positively associated with adverse pregnancy outcomes. CONCLUSION The risk of adverse pregnancy outcomes was two to five times increased in women with T1DM compared with the general population. The goals of the St. Vincent declaration have not been achieved.