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The purpose of this study was to assess the nutritional status and cognitive performance of women and their 5-year-old children using a cross-sectional design. Cognitive performance of mothers and children was assessed with Raven's Colored Progressive Matrices (CPM) and Kaufman Assessment Battery for Children-II (KABC-II). Demographic characteristics, food consumption patterns and anthropometry were also measured. Four rural districts in Sidama, southern Ethiopia served as the setting for this study. Subjects were one hundred women and their 5-year-old children. Mean ± standard deviation age of the mothers was 29 ± 6 years and family size was 7.0 ± 2.6. Maternal body mass index (BMI) ranged from 15.3 to 29.0 with 14% of the mothers having BMI < 18.5. Anthropometric assessment of children revealed 29% to be stunted (height-for-age z-score < -2) and 12% to be underweight (weight-for-age z-score < -2). Mothers' education significantly contributed to prediction of both mothers' and children's cognitive test scores. There were significant differences in mean cognitive test scores between stunted and non-stunted, and between underweight and normal-weight children. Height-for-age z-scores were correlated with scores for short-term memory (r = 0.42, P < 0.001), and visual processing (r = 0.42, P < 0.001) indices and weight-for-age z-scores were also correlated with scores of short-term memory (r = 0.41, P < 0.001) and visual processing (r = 0.43, P < 0.001) indices. Malnutrition in the community likely contributed to the cognitive performance of the subjects. Performance on memory and visual processing tasks was significantly lower in children with growth deficits suggesting that efficient and cost effective methods to alleviate malnutrition and food insecurity would impact not only child health but also cognitive function.

Male and female infants from rural Ethiopia were tested to investigate relations among hemoglobin (Hb), anthropometry, and attention. A longitudinal design was used to examine differences in attention performance from 6 (M = 24.9 weeks, n = 89) to 9 months of age (M = 40.6 weeks, n = 85), differences hypothesized to be related to changes in iron status and growth delays. Stunting (length-for-age z scores

OBJECTIVE: The goal was to determine the effect of training in newborn care and resuscitation on 7-day (early) neonatal mortality rates for very low birth weight (VLBW) infants. The study was designed to test the hypothesis that these training programs would reduce neonatal mortality rates for VLBW infants. METHODS: Local instructors trained birth attendants from 96 rural communities in 6 developing countries in protocol and data collection, the World Health Organization Essential Newborn Care (ENC) course, and a modified version of the American Academy of Pediatrics Neonatal Resuscitation Program (NRP), by using a train-the-trainer model. To test the impact of ENC training, data on infants of 500 to 1499 g were collected by using a before/after, active baseline, controlled study design. A cluster-randomized, controlled trial design was used to test the impact of the NRP. RESULTS: A total of 1096 VLBW (500–1499 g) infants were enrolled, and 98.5% of live-born infants were monitored to 7 days. All-cause, 7-day neonatal mortality, stillbirth, and perinatal mortality rates were not affected by ENC or NRP training. CONCLUSIONS: Neither ENC nor NRP training of birth attendants decreased 7-day neonatal, stillbirth, or perinatal mortality rates for VLBW infants born at home or at first-level facilities. Encouragement of delivery in a facility where a higher level of care is available may be preferable when delivery of a VLBW infant is expected.

The secretion of endogenous zinc (Zn) into the gut and subsequent excretion in the feces is understood to play a major role in maintaining Zn homeostasis in humans. Therefore, the measurement of endogenous Zn losses in the feces (EFZ) can be an important aspect of the study of Zn metabolism and homeostasis. The methods currently used to measure EFZ have the disadvantage of requiring complete fecal collections over multiple days. We have investigated the use of dysprosium (Dy), a nonabsorbable rare earth metal, in a method of determining EFZ that does not require complete fecal collections and permits the measurement of EFZ from several fecal samples. The method was evaluated using data from a study of free-living adult females in which Dy was administered 3-4 times/d over a period of 5 or 6 d to monitor completeness of fecal collections. The results did not differ from those obtained using an established isotope dilution method. We found that the measurement of the sample Dy:Zn ratio was useful for selecting samples for measurement. We conclude that the Dy method of determining EFZ is a valid and less burdensome alternative to current techniques.

BACKGROUND: Of the 3.7 million neonatal deaths and 3.3 million stillbirths each year, 98% occur in developing countries. An evaluation of community-based interventions designed to reduce the number of these deaths is needed. METHODS: With the use of a train-the-trainer model, local instructors trained birth attendants from rural communities in six countries (Argentina, Democratic Republic of Congo, Guatemala, India, Pakistan, and Zambia) in the World Health Organization Essential Newborn Care course (which focuses on routine neonatal care, resuscitation, thermoregulation, breast-feeding, "kangaroo" [skin-to-skin] care, care of the small baby, and common illnesses) and (except in Argentina) in a modified version of the American Academy of Pediatrics Neonatal Resuscitation Program (which teaches basic resuscitation in depth). The Essential Newborn Care intervention was assessed among 57,643 infants with the use of a before-and-after design. The Neonatal Resuscitation Program intervention was assessed as a cluster-randomized, controlled trial involving 62,366 infants. The primary outcome was neonatal death in the first 7 days after birth. RESULTS: The 7-day follow-up rate was 99.2%. After birth attendants were trained in the Essential Newborn Care course, there was no significant reduction from baseline in the rate of neonatal death from all causes in the 7 days after birth (relative risk with training, 0.99; 95% confidence interval [CI], 0.81 to 1.22) or in the rate of perinatal death; there was a significant reduction in the rate of stillbirth (relative risk with training, 0.69; 95% CI, 0.54 to 0.88; P=0.003). In clusters of births in which attendants had been randomly assigned to receive training in the Neonatal Resuscitation Program, as compared with control clusters, there was no reduction in the rates of neonatal death in the 7 days after birth, stillbirth, or perinatal death. CONCLUSIONS: The rate of neonatal death in the 7 days after birth did not decrease after the introduction of Essential Newborn Care training of community-based birth attendants, although the rate of stillbirths was reduced. Subsequent training in the Neonatal Resuscitation Program did not significantly reduce the mortality rates. (ClinicalTrials.gov number, NCT00136708.) Fil: Carlo, Waldemar A.. University of Alabama at Birmingahm; Estados Unidos Fil: Goudar, Shivaprasad S.. Instituto de Efectividad Clínica y Sanitaria; Argentina Fil: Jehan, Imtiaz. Aga Khan University; Pakistán Fil: Chomba, Elwyn. Instituto de Efectividad Clínica y Sanitaria; Argentina Fil: Tshefu, Antoinette. No especifíca; Fil: Garces, Ana. Universidad de San Carlos ; Guatemala Fil: Sailajanandan, Parida. Sriramchandra Bhanja Medical College; India Fil: Althabe, Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto de Efectividad Clínica y Sanitaria; Argentina Fil: McClure, Elizabeth M.. No especifíca; Fil: Derman, Richard J.. University of Missouri; Estados Unidos Fil: Goldenberg, Robert L.. Drexel University College of Medicine; Estados Unidos Fil: Bose, Carl. University of North Carolina; Estados Unidos Fil: Krebs, Nancy F.. University of Colorado; Estados Unidos Fil: Panigrahi, Pinaki. No especifíca; Fil: Buekens, Pierre. Tulane School of Public Health and Tropical Medicine; Estados Unidos Fil: Chakraborty, Hrishikesh. No especifíca; Fil: Hartwell, Tyler D.. No especifíca; Fil: Wright, Linda L.. National Institute of Child Health and Human Development; Estados Unidos

The quantity of total dietary zinc (Zn) and phytate are the principal determinants of the quantity of absorbed Zn. Recent estimates of Dietary Reference Intakes (DRI) for Zn by the Institute of Medicine (IOM) were based on data from low-phytate or phytate-free diets. The objective of this project was to estimate the effects of increasing quantities of dietary phytate on these DRI. We used a trivariate model of the quantity of Zn absorbed as a function of dietary Zn and phytate with updated parameters to estimate the phytate effect on the Estimated Average Requirement (EAR) and Recommended Daily Allowance for Zn for both men and women. The EAR predicted from the model at 0 phytate was very close to the EAR of the IOM. The addition of 1000 mg phytate doubled the EAR and adding 2000 mg phytate tripled the EAR. The model also predicted that the EAR for men and women could not be attained with phytate:Zn molar ratios > 11:1 and 15:1, respectively. The phytate effect on upper limits (UL) was predicted by first estimating the quantity of absorbed Zn corresponding to the UL of 40 mg for phytate-free diets, which is 6.4 mg Zn/d. Extrapolation of the model suggested, for example, that with 900 mg/d phytate, 100 mg dietary Zn is required to attain 6.4 mg absorbed Zn/d. Experimental studies with higher Zn intakes are required to test these predictions.

ObjectiveTo assess the prevalence of zinc inadequacy based on dietary intakes and plasma zinc concentrations and, simultaneously, the prevalence of inadequate intakes of energy, protein, calcium and iron.DesignA cross-sectional study of a convenience sample of subsistence farming households in Sidama, Southern Ethiopia.SubjectsDietary intakes were calculated from 1-day weighed food records and 40 repeats from 99 pregnant women in the third trimester using analysed values of major staple foods for zinc, iron, calcium and phytate. The distribution of observed intakes was adjusted for usual intakes and the prevalence of inadequacy estimated using the estimated average requirement (EAR) cutpoint method. Prevalence of inadequacy for zinc, protein and iron intakes were compared with those based on biochemical measures.ResultsPrevalence of zinc inadequacy was very high: 99% for US FNB EAR and 100% for IZiNCG EAR compared to 72% based on low plasma zinc concentrations. Corresponding prevalence estimates for iron were much lower: 4% for inadequate intakes based on US FNB EAR vs. 8.7% for iron deficiency anaemia (haemoglobin < 110 g l−1; ferritin < 12 μg l−1) and 32.3% for low storage iron. Prevalence of inadequacy for protein was 100% for adjusted intakes and 91% for serum albumin < 32 g l−1. For calcium, 74% were at risk for inadequate intakes.ConclusionThe high prevalence of inadequate intakes of zinc and protein was reasonably consistent with those based on biochemical measures. Such dietary deficits could be overcome by regular consumption of cellular animal protein. In contrast, both dietary and biochemical measures of iron inadequacy were low.

The etiology of anemia during pregnancy in rural Southern Ethiopia is uncertain. Intakes of animal-source foods are low and infections and bacterial overgrowth probably coexist. We therefore measured the dietary intakes of a convenience sample of Sidama women in late pregnancy who consumed either maize (n = 68) or fermented enset (Enset ventricosum) (n = 31) as their major energy source. Blood samples were analyzed for a complete blood count, vitamin B-12 and folate status, plasma ferritin, retinol, zinc, albumin, and C-reactive protein (CRP). The role of infection and gravida was also examined. Dietary intakes were calculated from 1-d weighed records. No cellular animal products were consumed. Of the women, 29% had anemia, 13% had iron deficiency anemia, 33% had depleted iron stores, and 74 and 27% had low plasma zinc and retinol, respectively. Only 2% had low plasma folate ( 271 nmol/L). None had elevated plasma cystathionine or total homocysteine (tHcys). Women with enset-based diets had higher (P = 0.052) plasma vitamin B-12 concentration and lower (P or = 12 microg/L) status were major positive predictors of hemoglobin. Despite some early functional vitamin B-12 deficiency, there was no macrocytic anemia. Consumption of fermented enset may have increased vitamin B-12 levels in diet and plasma.

Speed of information processing and recognition memory can be assessed in infants using a visual information processing (VIP) paradigm. In a sample of 100 infants 6-8 months of age from Southern Ethiopia, we assessed relations between growth and VIP. The 69 infants who completed the VIP protocol had a mean weight z score of -1.12 ± 1.19 SD, and length z score of -1.05 ± 1.31. The age-appropriate novelty preference was shown by only 12 infants. When age was controlled, longest look duration during familiarization was predicted by weight (sr(2) = .16, p = .001) and length (sr(2) = .05, p =.058), and mean look duration during test phases was predicted by head circumference (sr(2) = .08, p = .018) implying that growth is associated with development of VIP. These data support the validity of VIP as a measure of infant cognitive development that is sensitive to nutritional factors and flexible enough to be adapted to individual cultures.

Background Iron deficiency (ID) is common in toddlers in developing countries. Iron fortified or meat-based complementary foods may be effective to prevent ID. Objective Our objective was to compare iron status at 18 months and growth from 6 to 18 months in rural poor toddlers fed 3 different complementary foods. Methods The study was nested within a larger trial in which 6-month-old infants were randomized to receive 50g/d meat (MG), an equi-caloric fortified cereal supplement (FG) or local cereal supplement (LG) for 1 year. Hb, sTfR, HsCRP, ferritin and AGP were measured in 410 blood samples collected by a random sampling (MG, 137; FG, 140; LG, 133); calprotectin was measured in feces. Body iron = -[log (sTfR ×1000/ferritin)-2.8229] /0.1207. ID = ferritin

Representative staple foods from Sidama, Southern Ethiopia, were analyzed for phytate using HPLC, and for Zn, Fe and Ca by flame atomic absorption spectrophotometry (AAS). Enset starchy foods had the lowest phytic acid content, followed by fermented injera prepared from tef. Oleaginous seeds (niger and sesame) had the highest phytate content (∼1600 mg/100 g). The iron content of raw tef and tef injera, unlike barley flour or corn bread, varied markedly, attributed to contaminant iron from soil. The foods prepared from enset and tef were also rich sources of calcium. Most of the fermented foods prepared from enset and tef had low Phy:Zn and Phy:Fe molar ratios, whereas corn bread (unleavened), kidney beans, sesame, and niger seeds had higher molar ratios. Absorption of intrinsic Zn, Fe, and Ca as well as any exchangeable contaminant iron is unlikely to be compromised by phytate in the fermented foods prepared from enset and tef, unless consumed together with high phytate foods such as corn bread, legumes, and oil seeds.

In the development and testing of programs designed to improve complementary feeding globally local nonfortified food-based solutions comprise an important strategy for the foreseeable future. These solutions are especially vital for the rural poor of less-developed countries. Zinc is notable among individual nutrients that have been designated as "problem" nutrients adequate intake of which is difficult from complementary foods without fortification. This article considers the potential role of meat ± liver in addressing this apparent problem. In a recent Colorado study beef and cereal have been determined to be equally acceptable between age 5-7 mo as first and regular complementary foods. Average intake and absorption of Zn from beef by 7 mo of age together with the modest intake/absorption of Zn from breast milk at that age were adequate to meet average dietary and physiologic zinc requirements respectively. Barriers to acceptability and availability of affordable meat are considered but these are neither universal nor irresolvable in all populations. (authors)

The quantities of zinc and phytate in the diet are the primary factors determining zinc absorption. A mathematical model of zinc absorption as a function of dietary zinc and phytate can be used to predict dietary zinc requirements and, potentially, enhance our understanding of zinc absorption. Our goal was to develop a model of practical and informative value based on fundamental knowledge of the zinc absorption process and then fit the model to selected published data to assess its validity and estimate parameter values. A model of moderate mathematical complexity relating total zinc absorption to total dietary zinc and total dietary phytate was derived and fit to 21 mean data from whole day absorption studies using nonlinear regression analysis. Model validity, goodness of fit, satisfaction of regression assumptions, and quality of the parameter estimates were evaluated using standard statistical criteria. The fit had an R(2) of 0.82. The residuals were found to exhibit a normal distribution, constant variance, and independence. The parameters of the model, A(MAX), K(R), and K(P), were estimated to have values of 0.13, 0.10, and 1.2 mmol/d, respectively. Several of these estimates had wide CI attributable in part to the small number and the scatter of the data. The model was judged to be valid and of immediate value for studying and predicting absorption. A version of the model incorporating a passive absorption mechanism was not supported by the available data.

Background Early initiation of breastfeeding after birth and exclusive breastfeeding through six months of age confers many health benefits for infants; both are crucial high impact, low-cost interventions. However, determining accurate global rates of these crucial activities has been challenging. We use population-based data to describe: (1) rates of early initiation of breastfeeding (defined as within 1 hour of birth) and of exclusive breastfeeding at 42 days post-partum; and (2) factors associated with failure to initiate early breastfeeding and exclusive breastfeeding at 42 days post-partum. Methods Prospectively collected data from women and their live-born infants enrolled in the Global Network’s Maternal and Newborn Health Registry between January 1, 2010-December 31, 2013 included women-infant dyads in 106 geographic areas (clusters) at 7 research sites in 6 countries (Kenya, Zambia, India [2 sites], Pakistan, Argentina and Guatemala). Rates and risk factors for failure to initiate early breastfeeding were investigated for the entire cohort and rates and risk factors for failure to maintain exclusive breastfeeding was assessed in a sub-sample studied at 42 days post-partum. Result A total of 255,495 live-born women-infant dyads were included in the study. Rates and determinants for the exclusive breastfeeding sub-study at 42 days post-partum were assessed from among a sub-sample of 105,563 subjects. Although there was heterogeneity by site, and early initiation of breastfeeding after delivery was high, the Pakistan site had the lowest rates of early initiation of breastfeeding. The Pakistan site also had the highest rate of lack of exclusive breastfeeding at 42 days post-partum. Across all regions, factors associated with failure to initiate early breastfeeding included nulliparity, caesarean section, low birth weight, resuscitation with bag and mask, and failure to place baby on the mother’s chest after delivery. Factors associated with failure to achieve exclusive breastfeeding at 42 days varied across the sites. The only factor significant in all sites was multiple gestation. Conclusions In this large, prospective, population-based, observational study, rates of both early initiation of breastfeeding and exclusive breastfeeding at 42 days post-partum were high, except in Pakistan. Factors associated with these key breastfeeding indicators should assist with more effective strategies to scale-up these crucial public health interventions. Trial registration Registration at the Clinicaltrials.gov website (ID# NCT01073475).

Background Because large, prospective, population-based data sets describing maternal outcomes are typically not available in low- and middle-income countries, it is difficult to monitor maternal mortality rates over time and to identify factors associated with maternal mortality. Early identification of risk factors is essential to develop comprehensive intervention strategies preventing pregnancy-related complications. Our objective was to describe maternal mortality rates in a large, multi-country dataset and to determine maternal, pregnancy-related, delivery and postpartum characteristics that are associated with maternal mortality. Methods We collected data describing all pregnancies from 2010 to 2013 among women enrolled in the multi-national Global Network for Women’s and Children’s Health Research Maternal and Neonatal Health Registry (MNHR). We reported the proportion of mothers who died per pregnancy and the maternal mortality ratio (MMR). Generalized linear models were used to evaluate the relationship of potential medical and social factors and maternal mortality and to develop point and interval estimates of relative risk associated with these factors. Generalized estimating equations were used to account for the correlation of outcomes within cluster to develop appropriate confidence intervals. Results We recorded 277,736 pregnancies and 402 maternal deaths for an MMR of 153/100,000 live births. We observed an improvement in the total MMR from 166 in 2010 to 126 in 2013. The MMR in Latin American sites (91) was lower than the MMR in Asian (178) and African sites (125). When adjusted for study site and the other variables, no formal education (RR 3.2 [1.5, 6.9]), primary education only (RR 3.4 [1.6, 7.5]), secondary education only (RR 2.5 [1.1, 5.7]), lack of antenatal care (RR 1.8 [1.2, 2.5]), caesarean section delivery (RR 1.9 [1.3, 2.8]), hemorrhage (RR 3.3 [2.2, 5.1]), and hypertensive disorders (RR 7.4 [5.2, 10.4]) were associated with higher risks of death. Conclusions The MNHR identified preventable causes of maternal mortality in diverse settings in low- and middle-income countries. The MNHR can be used to monitor public health strategies and determine their association with reducing maternal mortality. Trial Registration clinicaltrials.gov NCT01073475

Background The Global Network for Women’s and Children’s Health Research is one of the largest international networks for testing and generating evidence-based recommendations for improvement of maternal-child health in resource-limited settings. Since 2009, Global Network sites in six low and middle-income countries have collected information on antenatal care practices, which are important as indicators of care and have implications for programs to improve maternal and child health. We sought to: (1) describe the quantity of antenatal care attendance over a four-year period; and (2) explore the quality of coverage for selected preventative, screening, and birth preparedness components. Methods The Maternal Newborn Health Registry (MNHR) is a prospective, population-based birth and pregnancy outcomes registry in Global Network sites, including: Argentina, Guatemala, India (Belgaum and Nagpur), Kenya, Pakistan, and Zambia. MNHR data from these sites were prospectively collected from January 1, 2010 – December 31, 2013 and analyzed for indicators related to quantity and patterns of ANC and coverage of key elements of recommended focused antenatal care. Descriptive statistics were generated overall by global region (Africa, Asia, and Latin America), and for each individual site. Results Overall, 96% of women reported at least one antenatal care visit. Indian sites demonstrated the highest percentage of women who initiated antenatal care during the first trimester. Women from the Latin American and Indian sites reported the highest number of at least 4 visits. Overall, 88% of women received tetanus toxoid. Only about half of all women reported having been screened for syphilis (49%) or anemia (50%). Rates of HIV testing were above 95% in the Argentina, African, and Indian sites. The Pakistan site demonstrated relatively high rates for birth preparation, but for most other preventative and screening interventions, posted lower coverage rates as compared to other Global Network sites. Conclusions Results from our large, prospective, population-based observational study contribute important insight into regional and site-specific patterns for antenatal care access and coverage. Our findings indicate a quality and coverage gap in antenatal care services, particularly in regards to syphilis and hemoglobin screening. We have identified site-specific gaps in access to, and delivery of, antenatal care services that can be targeted for improvement in future research and implementation efforts. Trial registration Registration at Clinicaltrials.gov (ID# NCT01073475)

Background During the post-partum period, most women wish to delay or prevent future pregnancies. Despite this, the unmet need for family planning up to a year after delivery is higher than at any other time. This study aims to assess fertility intention, contraceptive usage and unmet need for family planning amongst women who are six weeks postpartum, as well as to identify those at greatest risk of having an unmet need for family planning during this period. Methods Using the NICHD Global Network for Women’s and Children’s Health Research’s multi-site, prospective, ongoing, active surveillance system to track pregnancies and births in 100 rural geographic clusters in 5 countries (India, Pakistan, Zambia, Kenya and Guatemala), we assessed fertility intention and contraceptive usage at day 42 post-partum. Results We gathered data on 36,687 women in the post-partum period. Less than 5% of these women wished to have another pregnancy within the year. Despite this, rates of modern contraceptive usage varied widely and unmet need ranged from 25% to 96%. Even amongst users of modern contraceptives, the uptake of the most effective long-acting reversible contraceptives (intrauterine devices) was low. Women of age less than 20 years, parity of two or less, limited education and those who deliver at home were at highest risk for having unmet need. Conclusions Six weeks postpartum, almost all women wish to delay or prevent a future pregnancy. Even in sites where early contraceptive adoption is common, there is substantial unmet need for family planning. This is consistently highest amongst women below the age of 20 years. Interventions aimed at increasing the adoption of effective contraceptive methods are urgently needed in the majority of sites in order to reduce unmet need and to improve both maternal and infant outcomes, especially amongst young women. Study registration Clinicaltrials.gov (ID# NCT01073475)

BACKGROUND: To describe quantitative data quality monitoring and performance metrics adopted by the Global Network´s (GN) Maternal Newborn Health Registry (MNHR), a maternal and perinatal population-based registry (MPPBR) based in low and middle income countries (LMICs). METHODS: Ongoing prospective, population-based data on all pregnancy outcomes within defined geographical locations participating in the GN have been collected since 2008. Data quality metrics were defined and are implemented at the cluster, site and the central level to ensure data quality. Quantitative performance metrics are described for data collected between 2010 and 2013. RESULTS: Delivery outcome rates over 95% illustrate that all sites are successful in following patients from pregnancy through delivery. Examples of specific performance metric reports illustrate how both the metrics and reporting process are used to identify cluster-level and site-level quality issues and illustrate how those metrics track over time. Other summary reports (e.g. the increasing proportion of measured birth weight compared to estimated and missing birth weight) illustrate how a site has improved quality over time. CONCLUSION: High quality MPPBRs such as the MNHR provide key information on pregnancy outcomes to local and international health officials where civil registration systems are lacking. The MNHR has measures in place to monitor data collection procedures and improve the quality of data collected. Sites have increasingly achieved acceptable values of performance metrics over time, indicating improvements in data quality, but the quality control program must continue to evolve to optimize the use of the MNHR to assess the impact of community interventions in research protocols in pregnancy and perinatal health. Fil: Goudar, Shivaprasad S.. KLE University. Jawaharlal Nehru Medical College; India Fil: Stolka, Kristen B.. Research Triangle Institute International; Estados Unidos Fil: Koso Thomas, Marion. Eunice Kennedy Shriver National Institute of Child Health and Human Development; Estados Unidos Fil: Honnungar, Narayan V.. KLE University. Jawaharlal Nehru Medical College; India Fil: Mastiholi, Shivanand C.. KLE University. Jawaharlal Nehru Medical College; India Fil: Ramadurg, Umesh Y.. S. Nijalingappa Medical College; India Fil: Dhaded, Sangappa M.. KLE University. Jawaharlal Nehru Medical College; India Fil: Pasha, Omrana. Aga Khan University; Pakistán Fil: Patel, Archana. Indira Gandhi Government Medical College and Lata Medical Research Foundation; India Fil: Esamai, Fabian. University School of Medicine; Kenia Fil: Chomba, Elwyn. University of Zambia; Zambia Fil: Garces, Ana. Universidad de San Carlos; Guatemala Fil: Althabe, Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto de Efectividad Clínica y Sanitaria; Argentina Fil: Carlo, Waldemar A.. University of Alabama at Birmingahm; Estados Unidos Fil: Goldenberg, Robert L.. Columbia University; Estados Unidos Fil: Hibberd, Patricia L.. Massachusetts General Hospital for Children; Estados Unidos Fil: Liechty, Edward A.. Indiana University; Estados Unidos Fil: Krebs, Nancy F.. University of Colorado School of Medicine; Estados Unidos Fil: Hambidge, Michael K.. University of Colorado School of Medicine; Estados Unidos Fil: Moore, Janet L.. Research Triangle Institute International; Estados Unidos Fil: Wallace, Dennis D.. Research Triangle Institute International; Estados Unidos Fil: Derman, Richard J. Christiana Care Health Services; Estados Unidos Fil: Bhalachandra, Kodkany S.. KLE University. Jawaharlal Nehru Medical College; India Fil: Bose, Carl L.. University of North Carolina; Estados Unidos

Background Determining cause of death is needed to develop strategies to reduce maternal death, stillbirth, and newborn death, especially for low-resource settings where 98% of deaths occur. Most existing classification systems are designed for high income settings where extensive testing is available. Verbal autopsy or audits, developed as an alternative, are time-intensive and not generally feasible for population-based evaluation. Furthermore, because most classification is user-dependent, reliability of classification varies over time and across settings. Thus, we sought to develop classification systems for maternal, fetal and newborn mortality based on minimal data to produce reliable cause-of-death estimates for low-resource settings. Results In six low-resource countries (India, Pakistan, Guatemala, DRC, Zambia and Kenya), we evaluated data which are collected routinely at antenatal care and delivery and could be obtained with interview, observation, or basic equipment from the mother, lay-health provider or family to inform causes of death. Using these basic data collected in a standard way, we then developed an algorithm to assign cause of death that could be computer-programmed. Causes of death for maternal (trauma, abortion, hemorrhage, infection and hypertensive disease of pregnancy), stillbirth (birth trauma, congenital anomaly, infection, asphyxia, complications of preterm birth) and neonatal death (congenital anomaly, infection, asphyxia, complications of preterm birth) are based on existing cause of death classifications, and compatible with the World Health Organization International Classification of Disease system. Conclusions Our system to assign cause of maternal, fetal and neonatal death uses basic data from family or lay-health providers to assign cause of death by an algorithm to eliminate a source of inconsistency and bias. The major strengths are consistency, transparency, and comparability across time or regions with minimal burden on the healthcare system. This system will be an important contribution to determining cause of death in low-resource settings.

The objective of the present study was to determine the effect of a whey-based nutritional supplement (WPS) on zinc and iron absorption from a plant-based diet (PBD) in Mexican children. Study 1 ev...

The EZP is the pool of rapidly exchanging, metabolically active zinc (Zn) in the human body. Its size is measured routinely in stable isotope tracer studies of Zn absorption, and it has been given ...

Longitudinal associations between dietary factors and growth patterns were examined in infants/toddlers from Zambia, DRC, Guatemala and Pakistan in a secondary analysis of a previously published large randomized efficacy trial of daily meat vs fortified cereal supplements as complementary foods. Growth (i.e. z-scores for length (LAZ), weight (WLZ)), diet (i.e. infant/young child feeding practices (IYCFP), food groups consumed), and SES data were collected from 929 breastfed children aged 6-18 mo (arms combined). Diet at 9 and 12 mo were correlated with growth measures at 12 and 18 mo, respectively, using adjusted IYCFP (terciles), multiple linear regression and logistic regression analyses. Significant findings (p

Reliable estimates of zinc requirements have assumed greater priority as the global public health importance of preventing zinc deficiency has gained increasing recognition. On a global public health basis, our first most evident goal is reliable estimates of average population requirements. Despite expectations of rapid advances towards simpler and more sophisticated strategies, estimations of zinc requirements continue to depend on a factorial approach. Since the Dietary Reference Intakes (DRIs) were published, there have been important advances in techniques for the factorial approach but also confusion resulting from the subsequent publication of conflicting 'international' estimates. The reasons for these differences have now been fully elucidated, removing an obstruction to continuing progress and refinements of our knowledge base. A key advance has been the development and validation of a model that can be simply applied to determine the inhibitory effects of phytate on zinc absorption. Better understanding of maternal and young child zinc requirements continues to present a challenge of special importance.

BACKGROUND Small-for-gestational-age (SGA) infants are susceptible to postnatal zinc deficiency, but whether this susceptibility is due to intrauterine factors or to high postnatal growth requirements is unknown. OBJECTIVE We hypothesized that the size of the exchangeable zinc pool (EZP), which reflects metabolically available zinc, would be smaller in SGA than in appropriate-for-gestational-age (AGA) infants born prematurely. DESIGN Intravenous 70Zn (45 microg/kg) was administered to 10 SGA infants (8 boys) with a mean (+/-SD) gestational age of 33.3 +/- 1.8 wk and to 11 AGA infants (8 boys) with a mean (+/-SD) gestational age of 32.4 +/- 1.2 wk within 24 h of birth. The EZP was determined from isotope enrichment in spot urine collections on days 3-7. RESULTS The mean birth weight of the SGA infants was 1.30 +/- 0.2 kg and of the AGA infants was 1.84 +/- 0.3 kg (P = 0.0001). The EZP size was significantly smaller in the SGA than in the AGA infants on an absolute basis (13.3 +/- 2.8 and 25.2 +/- 8.1 mg; P = 0.0002) and relative to body weight (10.3 +/- 2.5 and 13.9 +/- 4.5 mg/kg; P = 0.02). The difference remained significant after adjustment for gestational age and birth weight. CONCLUSION These data provide evidence for differential zinc status at birth between SGA and AGA infants born prematurely at similar stages of gestation and offer at least a partial explanation for the reported benefits of postnatal zinc supplementation.

Little is yet known about zinc absorption in late pregnancy, and no information on absorption from the total diet is available.The objective was to measure the fractional absorption of zinc (FAZ) and to estimate the total quantity of absorbed zinc (TAZ) each day during the third trimester of pregnancy in poor rural southern Ethiopian women.The participants (n = 17) were a convenience sample from a larger study population. The third stage of pregnancy was estimated from fundal height by the Bushulo Health Center prenatal outreach program. FAZ was determined with a dual-isotope tracer ratio technique that uses measurements of urine enrichment with zinc stable isotopes administered intravenously and orally, as an extrinsic label, with all meals in 1 d. Total dietary zinc (TDZ) was calculated from weighed diet records and Ethiopian food-composition tables supported by zinc and phytate analyses of major food items for individual meals. Plasma zinc and exchangeable zinc pool size were also estimated.Mean (+/-SD) FAZ was 0.35 +/- 0.11, TDZ was 6.0 +/- 3.2 mg/d, TAZ was 2.1 +/- 1.0 mg/d, phytate intake was 1033 +/- 843 mg/d, plasma zinc was 44.1 +/- 6.0 microg/dL, and the exchangeable zinc pool size was 142 +/- 39 mg. The molar ratio of phytate to zinc was 17:1.Women from a poor rural population who were dependent on a moderately high-phytate diet had low TDZ and low plasma zinc concentrations in the third trimester of pregnancy. TAZ was modestly higher than that predicted but did not meet physiologic requirements.

Zinc (Zn) nutrition is of special practical importance in infants and young children, however relatively little is known about maturation and comparative aspects of Zn absorption. The principal objective of this paper is to compare Zn absorption of term infants, preterm infants, and adults on low phytate diets. Existing data derived from using Zn stable isotopes as extrinsic labels for an entire day were modeled with saturation kinetic analysis (saturable response model). When adjusted for differences in length of small intestine, the efficiency of Zn absorption for both term (4 months) and preterm (33 weeks post-conception) infants was comparable with that for adults, suggesting early maturation of mechanisms that regulate absorption. However, infant intestinal lengths were shorter, and Zn absorptive capacity was proportionately less. Reduced capacity was matched by lower Zn requirements for normal term infants. This favorable match, however, did not occur in the preterm infant because of relatively high Zn requirements. Although intestinal conservation of endogenous Zn in these preterm infants was appropriate in relation to the quantity of Zn absorbed, it was not optimal for achieving the retention required. Normal homeostatic mechanisms in the premature infant prevented efficient absorption of the quantity of Zn required or/and optimal conservation of endogenous Zn.

BACKGROUND Measurement of the major variables of zinc homeostasis is an essential prerequisite for estimating human zinc requirements, which currently require a factorial approach. The data required for this approach have not been available for toddlers, whose requirements have been estimated by extrapolation from other age groups. OBJECTIVE The objective of the study was to measure key variables of zinc homeostasis in rural and small-town Chinese toddlers. DESIGN Zinc stable-isotope tracers were administered intravenously and orally with all meals for 1 d to 43 toddlers. Subsequent metabolic collections in the homes included duplicate diets, quantitative fecal collections, and spot urine sampling. Fractional absorption of zinc (FAZ) was measured by a dual-isotope tracer ratio technique, and endogenous fecal zinc (EFZ) was measured by an isotope dilution technique. RESULTS No group or sex differences were found. Therefore, results were combined for 43 toddlers aged 19-25 mo whose major food staple was white rice. Selected results (x+/- SD) were 1.86 +/- 0.55 mg total dietary Zn/d; 0.35 +/- 0.12 FAZ; 0.63 +/- 0.24 mg total absorbed Zn/d; 0.67 +/- 0.23 mg EFZ/d; and 65.0 +/- 8.3 microg plasma Zn/dL. The molar ratio of dietary phytate to zinc was 2.7:1. CONCLUSIONS The mean intake and absorption of zinc in this population are low in comparison with estimated average dietary and physiologic requirements for zinc, and plasma zinc values are consistent with zinc deficiency. Intestinal losses of endogenous zinc exceed previous estimates for toddlers, and only modest evidence exists of conservation in response to low zinc intake and absorption.

Poor bioavailability of zinc from high-phytate diets is an important contributory factor to zinc deficiency in low-income populations.The objective of this study was to determine the effect of low-phytate maize consumption on zinc absorption.The participants were apparently healthy children from the Central Highlands of Guatemala. Sixty children (20 per group) were randomly assigned to be fed only the low-phytate maize or 1 of 2 control maizes, the isohybrid wild-type maize or a local maize, for a 10-wk period. During the final week, the fractional absorption of zinc for all meals was measured during 1 d with the use of zinc stable isotopes and a dual isotope ratio technique based on urine enrichment data.Mean (+/-SD) phytate intakes for the low-phytate, wild-type, and local maize groups were 1536 +/- 563, 2056 +/- 517, and 2253 +/- 687 mg/d, respectively. Corresponding zinc intakes were 8.6 +/- 2.5, 8.1 +/- 2.0, and 9.7 +/- 2.6 mg/d, and the dietary phytate:zinc molar ratios were 18 +/- 5, 26 +/- 6, and 23 +/- 5. Corresponding fractional absorptions of zinc were 0.32 +/- 0.07, 0.28 +/- 0.07, and 0.29 +/- 0.06. The respective values for total absorbed zinc were 2.72 +/- 0.88, 2.30 +/- 0.96, and 2.78 +/- 1.04 mg/d. No significant differences in either the fractional absorption of zinc or total absorbed zinc were seen between the maize groups.Under the conditions of the present study, zinc absorption was not increased by the long-term use of low-phytate maize in children whose major dietary staple is maize.

The objective was to compare the absorption of zinc from a micronutrient-fortified dried cow's milk, which is part of the Chilean National Complementary Food Program, with that from a standard nonfortified milk. Fortification included the addition of iron, zinc, copper, and ascorbic acid to provide total concentrations (in 100 g of powder) of 10, 5, 0.5, and 70 mg, respectively. Seven adults with normal plasma zinc concentrations (16.0 ± 0.9 μ mol/L) were studied. Fractional absorption of zinc was determined from single test meals using a stable isotope–based methodology. Mean (± SD) fractional absorption of zinc of the test meal containing nonfortified milk was 0.29 ± 0.09 compared with 0.30 ± 0.09 of the test meal with the fortified milk ( P = not significant). Absolute zinc absorptions from the test meals were 0.43 ± 0.14 vs 0.57 ± 0.16 mg, respectively ( P = .02). Micronutrient fortification of dried cow's milk, including zinc, was associated with increased total zinc absorption.

The focus of this paper is on the application of measurements of zinc absorption in human research, especially studies designed to assess the efficacy of intervention strategies to prevent and manage zinc deficiency in populations. Emphasis is given to the measurement of quantities of zinc absorbed rather than restricting investigations to measurements of fractional absorption of zinc. This is especially important when determining absorption of zinc from the diet, whether it be the habitual diet or an intervention diet under evaluation. Moreover, measurements should encompass all meals for a minimum of one day with the exception of some pilot studies. Zinc absorption is primarily via an active saturable transport process into the enterocytes of the proximal small intestine. The relationship between quantity of zinc absorbed and the quantity ingested is best characterized by saturable binding models. When applied to human studies that have sufficient data to examine dose-response relationships, efficiency of absorption is high until approximately 50–60% maximal absorption is achieved, even with moderate phytate intakes. This also coincides approximately with the quantity of absorbed zinc necessary to meet physiologic requirements. Efficiency of absorption with intakes that exceed this level is low or very low. These observations have important practical implications for the design and interpretation of intervention studies to prevent zinc deficiency. They also suggest the potential utility of measurements of the quantity of zinc absorbed when evaluating the zinc status of populations.

Calcium fortification of maize has been achieved for millennia in Central America by the process of nixtamalization. Bioavailability of calcium is, however, compromised by phytate, which is present in large quantities in maize kernels and is only modestly reduced by nixtamalization.The objective was to compare the absorption of calcium from tortilla meals prepared from low-phytate maize with that from meals prepared from maize with typical phytate content.At 1-mo intervals, 5 healthy adult women were fed 2 test meals of approximately 140 g tortillas in lieu of breakfast. On one occasion, the tortillas were prepared from maize with approximately 60% phytate reduction, and, on the other occasion, they were prepared from the matching isohybrid wild-type maize. Beginning midway through the test meal, (44)Ca (0.3 mg/kg body wt) was administered in water as an extrinsic label; (42)Ca (0.06 mg/kg body wt) was administered intravenously immediately after the test meal. Isotope ratios of (42)Ca to (43)Ca and of (44)Ca to (43)Ca were measured by inductively coupled plasma mass spectrometry in urine collected as an 8-h pool from the period 16-24 h after intravenous tracer administration and prepared by the oxalate precipitation method. Fractional absorption of calcium was determined by using a dual-isotope ratio technique.Mean fractional absorption of calcium from tortillas prepared from the low-phytate maize (0.50 +/- 0.03) was significantly (P = 0.003) greater than that from tortillas prepared from the control maize (0.35 +/- 0.07).The increase in the quantity of calcium absorbed could be of practical importance for calcium nutriture when the intake of dairy products is limited.

The objectives of this study were to compare zinc homeostasis in premature infants enterally fed with either preterm infant formula or fortified human milk; to examine interrelationships of variables of zinc homeostasis; and to examine the findings in relation to estimated zinc requirements of preterm infants. Zinc homeostasis was studied in 14 infants (8 male), with mean gestational age of 31 wk and birth weight appropriate for gestational age, who were exclusively fed either preterm formula (n = 9) or own mother's milk with human milk fortifier (n = 5). Zinc stable isotopes were administered intravenously ((70)Zn) and orally as an extrinsic label ((67)Zn) over multiple feeds for determination of fractional absorption by dual isotope tracer ratio in urine; endogenous fecal zinc was determined by isotope dilution; and exchangeable zinc pool (EZP) size was estimated from linear regression of log-transformed urine (70)Zn enrichment data. Results indicated no significant differences in the variables of zinc homeostasis between the feeding groups; data for all subjects were thus combined. Mean (+/- SD) fractional absorption was 0.26 +/- 0.07; net absorbed zinc 0.43 +/- 0.25 mg/d (0.31 +/- 0.19 mg/kg/d). Mean EZP was 20 +/- 10 mg/kg, and was positively correlated with total absorbed zinc and with net absorbed zinc. Feeding type and total absorbed zinc were significantly related to daily weight gain (p = 0.003). Current zinc intakes from fortified human milk or formula are associated with acceptable weight gain, but whether the observed net zinc absorption was optimal in the human milk group cannot be definitively determined from these data.

Three selected aspects of human zinc homeostasis and requirements are reviewed with special reference to studies undertaken by the author and his colleagues: 1) the implications for the calculation of physiologic requirements for zinc of the interrelationship between two key variables of zinc homeostasis, intestinal excretion of endogenous zinc and total absorbed zinc, are examined at levels of absorption below those necessary to meet physiologic requirements; 2) a method for deriving average dietary zinc requirements from zinc-stable isotope tracer/ metabolic studies is illustrated with examples of studies being conducted in developing countries; and 3) the effect of reduction of high intakes of phytic acid on zinc bioavailability is examined with test meals prepared from low-phytic-acid maize or isohybrid wild-type control maize.

The emerging public health importance of zinc and selenium and the continuing public health challenges of iron and iodine draw attention to the unmet need for improved biomarkers of trace element status. Currently available biomarkers of these four trace elements are critiqued including the outstanding lack of satisfactory biomarkers for the assessment of zinc intake and status. Other trace elements are reviewed briefly including copper, for which human dietary deficiencies and excesses have been documented, and chromium, which is of possible but unconfirmed public health significance. Evolving strategies of considerable potential include molecular techniques such as the measurement of metallothionein mRNA in lymphocytes as a biomarker of zinc status, an assay that can now be performed with a dried blood spot. The judicious application of tracer techniques also has a role in advancing the quality of zinc biomarkers. Also of special current interest is full definition of the potential of plasma-soluble transferrin receptor concentrations as the biomarker of choice for the detection of early functional iron deficiency.

The poor indigenous population of the western highlands of Guatemala is notable for the high rate of stunting in infancy (1). Also notable in the Mayan population is the severity of the maternal short stature (2). The association between low maternal height and impaired linear growth in early childhood has been well documented (3), but there are more limited data for infancy, an age that is relevant to long-term growth (4). Data derived from a study of the Mayan population in the western highlands of Guatemala, the primary outcome of which has already been reported (1), has provided the opportunity to examine the association between maternal stature and linear growth, including incidence of stunting of offspring during mid- and late infancy; determine whether an association between maternal stature and linear growth velocity is detectable in late infancy; and evaluate the range of maternal heights over which there is an association with the length of older infants.

Zinc plays an integral role in numerous cellular processes including regulation of gene expression. This randomized placebo-controlled trial in adult women evaluated the effects of 20 mg Zn for 23 days. The mRNA abundance of zinc transporters ( ZnT1/ZIP3/ZIP4/ZIP8 ) and metallothionein ( MT1 ) from peripheral blood mononuclear cells was determined by real-time quantitative polymerase chain reaction. In paired samples ( n = 6-9), the ZIP4 ( P = 0.036) and ZIP8 ( P = 0.038) mRNA abundance decreased following zinc supplementation. ZnT1, ZIP3 , and MT1 mRNA abundance did not change significantly. The mean ± standard deviation plasma zinc concentration (by inductively coupled plasma mass spectrometry) at baseline was 680 ± 110 μg/L for the zinc group ( n = 24) and 741 ± 92 μg/L for the placebo group ( n = 23). At endpoint, plasma zinc in the zinc group increased to 735 ± 80 μg/L ( P < 0.01) while in the placebo group (717 ± 100 μg/L) it did not change significantly from baseline. The change in mRNA abundance highlights the importance of further investigating ZIP4 and ZIP8 mRNA abundance as potential zinc status biomarkers.

Background: Phytic acid reduction in cereal grains has been accomplished with plant genetic techniques. These low‐phytic acid grains provide a strategy for improving the mineral (eg, zinc) status in populations that are dependent on grains, including maize (Zea mays L.), as major dietary staples. Objective: The objective was to compare the fractional absorption of zinc from polenta prepared from maize low in phytic acid with that prepared from a wild-type isohybrid maize (control) after short-term consumption by adults whose habitual diet is low in phytic acid. Design: Healthy adults served as their own control subjects in a crossover design. All meals on 1 d consisted of polenta prepared from a low‐phytic acid maize homozygous for the recessive low phytic acid 1-1 (lpa1-1). On the preceding or following day, all meals consisted of polenta prepared from a sibling isohybrid homozygous wild-type maize with a “normal” phytic acid content. The low‐phytic acid maize contained � 60% less phytic acid than did the wild-type maize. All test meals were extrinsically labeled with zinc stable-isotope tracers. The fractional absorption of zinc was determined on the basis of fecal enrichment. Results: The molar ratios of phytic acid to zinc in the polenta prepared from lpa1-1 maize and the wild-type maize were 17:1 and 36:1, respectively. The corresponding fractional absorptions of zinc were 0.30 ± 0.13 and 0.17 ± 0.11, respectively (P < 0.005). Conclusion: Substitution of a low‐phytic acid grain in a maizebased diet is associated with a substantial increase in zinc absorption. Am J Clin Nutr 2002;76:556‐9.

Assessment of zinc status remains a challenge largely because serum/plasma zinc may not accurately reflect an individual’s zinc status. The comet assay, a sensitive method capable of detecting intracellular DNA strand breaks, may serve as a functional biomarker of zinc status. We hypothesized that effects of zinc supplementation on intracellular DNA damage could be assessed from samples collected in field studies in Ethiopia using the comet assay. Forty women, from villages where reported consumption of meat was less than once per month and phytate levels were high, received 20 mg zinc as zinc sulfate or placebo daily for 17 days in a randomized placebo-controlled trial. Plasma zinc concentrations were determined by inductively coupled plasma mass spectrometry (ICPMS). Cells from whole blood at the baseline and endpoint of the study were embedded in agarose, electrophoresed, and stained before being scored by an investigator blinded to the treatments. Although zinc supplementation did not significantly affect plasma zinc, mean (± SEM) comet tail moment measurement of supplemented women decreased from 39.7 ± 2.7 to 30.0 ± 1.8 (p

To quantify maternal, fetal and neonatal mortality in low- and middle-income countries, to identify when deaths occur and to identify relationships between maternal deaths and stillbirths and neonatal deaths.A prospective study of pregnancy outcomes was performed in 106 communities at seven sites in Argentina, Guatemala, India, Kenya, Pakistan and Zambia. Pregnant women were enrolled and followed until six weeks postpartum.Between 2010 and 2012, 214,070 of 220,235 enrolled women (97.2%) completed follow-up. The maternal mortality ratio was 168 per 100,000 live births, ranging from 69 per 100,000 in Argentina to 316 per 100,000 in Pakistan. Overall, 29% (98/336) of maternal deaths occurred around the time of delivery: most were attributed to haemorrhage (86/336), pre-eclampsia or eclampsia (55/336) or sepsis (39/336). Around 70% (4349/6213) of stillbirths were probably intrapartum; 34% (1804/5230) of neonates died on the day of delivery and 14% (755/5230) died the day after. Stillbirths were more common in women who died than in those alive six weeks postpartum (risk ratio, RR: 9.48; 95% confidence interval, CI: 7.97-11.27), as were perinatal deaths (RR: 4.30; 95% CI: 3.26-5.67) and 7-day (RR: 3.94; 95% CI: 2.74-5.65) and 28-day neonatal deaths (RR: 7.36; 95% CI: 5.54-9.77).Most maternal, fetal and neonatal deaths occurred at or around delivery and were attributed to preventable causes. Maternal death increased the risk of perinatal and neonatal death. Improving obstetric and neonatal care around the time of birth offers the greatest chance of reducing mortality.Quantifier la mortalité maternelle, foetale et néonatale dans les pays à revenus faible et intermédiaire pour identifier à quel moment survient le décès et pour analyser les relations entre les décès maternels et les mortinaissances/décès néonataux.Une étude prospective sur des grossesses a été effectuée dans 106 collectivités sur 7 sites: Argentine, Guatemala, Inde, Kenya, Pakistan et Zambie. Les femmes enceintes ont été inscrites et suivies jusqu'à 6 semaines après leur accouchement.Entre 2010 et 2012, 214 070 femmes inscrites sur 220 235 (97,2%) ont participé au suivi. Le taux de mortalité maternelle était de 168 pour 100 000 naissances d'enfants vivants, allant de 69 pour 100 000 en Argentine à 316 pour 100 000 au Pakistan. Dans l'ensemble, 29% (98/336) des décès maternels ont eu lieu au moment de la naissance: la plupart des décès ont été dus à une hémorragie (86/336), une prééclampsie ou une éclampsie (55/336), ou encore une septicémie (39/336). Environ 70% (4349/6213) des enfants sont mort-nés intrapartum; 34% (1804/5230) des nouveau-nés sont morts le jour de leur naissance et 14% (755/5230) le lendemain. Les mortinaissances étaient plus fréquentes chez les femmes qui ont aussi perdu la vie que chez celles qui ont survécu 6 semaines après l'accouchement (risque relatif, RR: 9,48; intervalle de confiance à 95%, IC: 7,97–11,27), pour les décès périnatals (RR: 4,30; IC à 95%: 3,26–5,67), à 7 jours (RR: 3,94; IC à 95%: 2,74–5,65), et à 28 jours (RR: 7,36; IC à 95%: 5,54–9,77).La plupart des cas de mortalité maternelle, foetale et néonatale se sont produits pendant ou peu avant ou après la naissance et ont été attribués à des causes évitables. La mortalité maternelle a augmenté le risque de mort périnatale et néonatale. L'amélioration des soins obstétricaux et néonatals au moment de la naissance offre les meilleures chances de réduire cette mortalité.Cuantificar la mortalidad materna, fetal y neonatal en países de ingresos bajos y medios a fin de identificar cuándo se producen muertes y las relaciones entre las muertes maternas y la mortalidad prenatal y neonatal.Se realizó un estudio prospectivo de los resultados del embarazo en 106 comunidades en siete lugares en Argentina, Guatemala, India, Kenya, Pakistán y Zambia. Se inscribieron mujeres embarazadas, de las que se hizo un seguimiento hasta seis semanas tras el parto.Entre 2010 y 2012, 214 070 de las 220 235 mujeres inscritas (97,2%) completaron el seguimiento. La tasa de mortalidad materna fue de 168 por 100 000 nacidos vivos, con una variación que va desde 69 por 100 000 en Argentina a 316 por 100 000 en Pakistán. En general, el 29% (98/336) de las muertes maternas se produjo en torno al momento del parto: la mayoría se atribuyó a hemorragias (86/336), preeclampsia o eclampsia (55/336), o sepsis (39/336). Alrededor del 70% (4349/6213) de las muertes prenatales se produjo probablemente en el parto; el 34% (1804/5230) de los recién nacidos murieron el día del parto y el 14% (755/5230), al día siguiente. Las muertes prenatales fueron más comunes en las mujeres que fallecieron que en aquellas con vida seis semanas después del parto (riesgo relativo, RR: 9,48; intervalo de confianza 95%, IC: 7,97–11,27), al igual que las muertes perinatales (RR: 4,30; IC del 95%: 3,26–5,67) y las muertes de neonatos a 7 días (RR: 3,94; IC del 95%: 2,74–5,65) y a 28 días (RR: 7,36; IC del 95%: 5,54–9,77).La mayoría de las muertes maternas, prenatales y neonatales ocurrieron en o en torno al parto y se atribuyeron a causas evitables. La muerte materna aumentó el riesgo de muerte perinatal y neonatal. Mejorar la atención obstétrica y neonatal en el momento del nacimiento ofrece las mayores posibilidades para reducir la mortalidad.قياس مقدار وفيات الأمومة والأجنة والولدان في البلدان المنخفضة والمتوسطة الدخل لتحديد أوقات حدوث الوفيات ولتحديد العلاقات بين وفيات الأمومة وحالات الإملاص ووفيات الولدان.تم إجراء دراسة استطلاعية عن حصائل الحمل في 106 مجتمعاً محلياً في سبعة مواقع في الأرجنتين وغواتيمالا والهند وكينيا وباكستان وزامبيا. وتم تسجيل النساء الحوامل ومتابعتهن حتى ستة أسابيع بعد الوضع.بين عامي 2010 و2012، أكملت 214070 سيدة من إجمالي 220235 سيدة مسجلة (97.2 %) المتابعة. وكانت نسبة وفيات الأمومة 168 لكل 100000 وليد حي، وتراوحت من 69 لكل 100000 وليد حي في الأرجنتين إلى 316 لكل 100000 وليد حي في باكستان. وبشكل عام، حدثت نسبة 29 % (98/336) من وفيات الأمومة في الفترة المحيطة بالولادة: يعزى معظم هذه الحالات إلى النزف (86/336) أو مقدمات الارتعاج أو الارتعاج (55/336) أو الإنتان (39/336). ومن المرجح أن حوالي 70 % من حالات الإملاص (4349/6213) كانت أثناء الوضع، وتوفيت نسبة 34 % من الولدان (1804/5230) في يوم الولادة وتوفيت نسبة 14 % من الولدان (755/5230) في اليوم الذي يليه. وكانت حالات الإملاص أكثر شيوعاً لدى النساء اللاتي لقين حتفهن عن اللواتي عشن ستة أسابيع بعد الوضع (نسبة الخطورة: 9.48؛ فاصل الثقة 95 %، فاصل الثقة: 7.97 - 11.27)، وهو نفس الوضع مع الوفيات في الفترة المحيطة بالولادة (نسبة الخطورة: 4.30؛ فاصل الثقة 95 %: 3.26 - 5.67) ووفيات الولدان في اليوم السابع (نسبة الخطورة: 3.94؛ فاصل الثقة 95 %: 2.74 - 5.65) ووفيات الولدان في اليوم الثامن والعشرين (نسبة الخطورة: 7.36؛ فاصل الثقة 95 %: 5.54–9.77).حدثت معظم وفيات الأمومة والأجنة والولدان عند الولادة أو في الفترة المحيطة بالولادة وتعزى إلى أسباب يمكن توقيها. وأدت وفيات الأمومة إلى زيادة خطورة وفيات الولدان والوفيات في الفترة المحيطة بالولادة. ويوفر تحسين الرعاية التوليدية والوليدية في الفترة المحيطة بالولادة أعظم فرصة لتقليل معدل الوفيات.量化中低收入国家孕产妇、胎儿和新生儿死亡率，确定发生死亡的时间以及孕产妇死亡、死产和新生儿死亡之间的关系。在阿根廷、危地马拉、印度、肯尼亚、巴基斯坦和赞比亚的七个地点106个社区进行妊娠结局的前瞻性研究。招募孕妇并随访至产后六周。在2010和2012年间，对纳入研究的220 235名女性中的214 070名（97.2%）完成随访。产妇死亡率为每10万例活产168例死亡，范围从阿根廷的每10万例69例到巴基斯坦的每10万例316例不等。整体而言，29%（98/336）的孕产妇死亡发生在分娩前后：大多数是因为出血（86/336）、子痫前期或子痫（55/336）或者败血症（39/336）。大约70%（4349/6213）的死产可能在分娩期发生；34%（1804/5230）的新生儿死亡发生在分娩当天，14%（755/5230）在第二天。与产后六周之后仍存活的女性相比，死产在死亡女性中更加普遍（风险比：RR：9.48；95%置信区间，CI：7.97–11.27），围产期死亡（RR：4.30；95% CI：3.26–5.67）和7天（RR：3.94；95% CI：2.74–5.65）和28天新生死亡（RR：7.36；95% CI：5.54–9.77）的情况也是如此。大多数孕产妇、胎儿和新生儿死亡发生在分娩或分娩前后，且都归因于可预防的原因。孕产妇死亡增加围产期和新生儿死亡的风险。改善分娩前后产科和新生儿护理是降低死亡率的最大机会。Определить уровень материнской, внутриутробной и неонатальной смертности в странах с низким и средним уровнем дохода, выяснить, когда происходят эти смерти и выявить связи между материнской смертностью, мертворождениями и неонатальной смертностью.Проспективное исследование исходов беременности было проведено в 106 общинах в семи районах Аргентины, Гватемалы, Индии, Кении, Пакистана и Замбии. Включение в исследование и наблюдение за беременными женщинами велось до шестинедельного послеродового периода.В 2010‒2012 годах наблюдение прошли 214 070 из 220 235 включенных в исследование женщин (97,2%). Коэффициент материнской смертности составлял 168 смертей на 100 000 живорождений, варьируясь в пределах от 69 смертей на 100 000 живорождений в Аргентине до 316 смертей на 100 000 живорождений в Пакистане. В общем, во время родов было зарегистрировано 29% (98/336) материнских смертей: причиной большинства из них были кровотечения (86/336), преэклампсия или эклампсия (55/336) или сепсис (39/336). Около 70% (4349/6213) мертворождений, вероятно, произошли во время родов; 34% (1804/5230) новорожденных умерли в день родов и 14% (755/5230) умерли на следующий день после родов. Мертворожденность чаще всего отмечалась у умерших в ходе родов женщин, чем у женщин, которые оставались в живых спустя шесть недель после родов (отношение рисков, ОР: 9,48; 95% доверительный интервал, ДИ: 7,97–11,27). То же самое касается перинатальной смертностности (ОР: 4,30; 95% ДИ: 3,26–5,67) и 7-дневной (ОР: 3,94; 95% ДИ: 2,74–5,65) и 28-дневной неонатальной смертности (ОР: 7,36; 95% ДИ: 5,54–9,77).Наибольшее число материнских, внутриутробных и неонатальных смертей зарегистрировано в момент родов или в дородовой или послеродовой период и объяснялись предотвратимыми причинами. Материнская смертность увеличивала риск перинатальной и неонатальной смерти. Совершенствование акушерской и неонатальной помощи во время родов открывает наилучшие возможности для снижения смертности.

▪ Abstract Currently, estimates of human zinc requirements depend primarily on a factorial approach. The availability of tracer techniques employing zinc stable isotopes has facilitated the acquisition of data on major variables of zinc homeostasis in addition to those that can be measured with careful metabolic balance techniques. These data have promising potential to facilitate and improve the factorial approach. The thesis proposed in this paper is that realistic estimations of dietary zinc requirements by a factorial approach require attention to the dynamic interrelationships between major variables of zinc homeostasis. This applies especially to the positive relationship between endogenous fecal zinc and total absorbed zinc, which is the essential starting point in estimating physiologic and, from there, dietary requirements.

Objective: We investigated whether previous reports of reduced bone mineral density after management for childhood acute lymphoblastic leukemia (chALL) were confirmed in a more recently treated cohort. Study design: In a cross-sectional study 75 subjects who were given the diagnosis of chALL between January 1, 1991, and December 31, 1997 (69% standard, 31% high risk), at Denver Children's Hospital and who were 11 to 82 months post-diagnosis with no history of relapse, secondary malignancy, or transplant underwent whole body areal bone mineral densitometry (BMD A expressed as age- and sex-standardized z scores), a food frequency questionnaire, and a weight-bearing activity survey. Results: Overall, the mean whole body BMD A z score was normal (+0.22 ± 0.96). A significant positive association was found with whole body BMD A z score and years elapsed since the beginning of maintenance (linear regression coefficient=+0.2 Δ z score/year; 95% CI=0.09 to 0.3) after adjustment was done for risk status/age category, history of cranial radiation, and total days hospitalized. No association was found with high risk/older age at diagnosis, nutrient intake, chemotherapy dosage, or weight-bearing activity. Conclusion: Contrary to previous reports in which cranial radiation and longer hospitalizations were prominent components of therapy, our study suggests that more recently treated patients with chALL do not have persistent abnormalities of bone mineral density after completion of therapy. (J Pediatr 2001;138:898-904)

Tracer kinetic techniques based on zinc stable isotopes have a vital role in advancing knowledge of human zinc physiology and homeostasis. These techniques have demonstrated the complexity of zinc metabolism, and have been critical to estimating the size and interrelationships of those pools of zinc that exchange rapidly with zinc in plasma and which are likely to be especially important for zinc dependent biology. This paper presents findings from recent research linking a steady state compartmental model with non-steady state post-prandial sampling from the intestine, utilizing a combination of intestinal intubation/perfusion and stable isotope tracer kinetic techniques. The gastrointestinal tract has a central role in maintaining whole body zinc homeostasis. While the fractional absorption of zinc from a meal depends on the quantity of exogenous zinc and on such dietary factors as phytic acid, the fractional absorption does not appear to be dependent on the size of the rapidly exchanging pool of the host. In contrast, the quantity of endogenous zinc excreted via the intestine is positively correlated with both the amount of absorbed zinc and the zinc ‘status’ of the host, and thus this process has an equally critical role in maintaining zinc homeostasis. The observed alterations in zinc metabolism in some disease states can be understood in the context of known homeostatic processes. In other conditions, however, such alterations as inflammation-associated hyperzincuria and zinc redistribution, the links between homeostatic perturbation and cellular biology are yet to be explained. Thus the challenge remains for research at the whole body level to carefully characterize zinc distribution and exchange under diverse circumstances, while research at the cellular level must elucidate the regulatory processes and the factors to which they respond.

Current knowledge of the metabolism of zinc is summarized in relation to the clinical and public health importance of human zinc deficiency. Zinc metabolism is considered in relation to estimations of zinc requirements. Special attention is focused on the role and limitations of regulation of intestinal absorption of exogenous dietary zinc and of intestinal excretion of endogenous zinc in the maintenance of zinc homeostasis. The dynamic interrelationships between these variables and between each of these and readily exchangeable pools of body zinc are highlighted, as is the impact of dietary phytate on zinc requirements. Measurements of these variables utilizing zinc stable isotope techniques can provide quantitative information on zinc homeostasis and dietary zinc requirements in different communities, as well as facilitating assessment of alternative strategies for preventing zinc deficiency.

High dietary phytate content that compromises zinc nutriture is thought to be a major problem among children of the developing world. Zinc stable isotope techniques permit the quantitative assessment of the effect of phytate reduction on zinc homeostasis. We tested the hypothesis that zinc absorption would be increased in Malawian children fed a reduced-phytate corn-plus-soy diet compared with a standard high phytate diet. Twenty-three children hospitalized in Blantyre, Malawi, were enrolled. Children were selected from those recovering from tuberculosis and from well children (those with minor injuries, those awaiting elective surgery or healthy siblings). Children received a diet of corn-plus-soy porridge (either low phytate or high phytate) for a period of 3-7 d and then participated in a zinc stable isotope study. The study included the administration of oral and intravenous zinc stable isotopes and 7-d collections of urine and stool. The diet was maintained throughout the duration of specimen collection. Zinc isotopic enrichments in urine and stool were measured, and zinc fractional absorption, total zinc absorption, endogenous fecal zinc, net zinc retention and size of the exchangeable zinc pool were calculated. Among the 14 children recovering from tuberculosis, dietary phytate reduction resulted in higher fractional absorption (0.41 +/- 0.14 versus 0.24 +/- 0.09, mean +/- SD, P:0.05) and total zinc absorption (169 +/- 55 versus 100 +/- 46 microg/(kg. d), P:0.05). No effect of phytate reduction was seen in the well children (n = 9). Phytate reduction did not decrease the absolute endogenous fecal zinc, but it did decrease it relative to total absorbed zinc. These preliminary results indicate that phytate reduction may be beneficial in improving zinc nutriture in groups with increased zinc requirements who consume a cereal-based diet.

A compartmental model of zinc metabolism has been developed from stable isotope tracer studies of five healthy adults. Multiple isotope tracers were administered orally and intravenously, and the resulting enrichment was measured in plasma, erythrocytes, urine, and feces for as long as 3 wk. Data from total zinc measurements and model-independent calculations of various steady-state parameters were also modeled with the kinetic data. A structure comprised of 14 compartments and as many as 25 unknown kinetic parameters was developed to adequately model the data from each of the individual studies. The structural identifiability of the model was established using the GLOBI2 identifiability analysis software. Numerical identifiability of parameter estimates was evaluated using statistical data provided by SAAM. A majority of the model parameters was estimated with sufficient statistical certainty to be considered well determined. After the fitting of the model and data from the individual studies using SAAM/CONSAM, results were submitted to SAAM extended multiple studies analysis for aggregation into a single set of population parameters and statistics. The model was judged to be valid based on criteria described elsewhere.

The objective of this paper is to provide a current overview of the significance of zinc in human nutrition. To achieve this, the following issues are addressed: (1) the biochemistry and biology of zinc in the context of their relevance to zinc in human nutrition and to our understanding of the complexity and practical importance of human zinc deficiency; (2) the history of our understanding of human zinc deficiency with an emphasis both on its brevity and on notable recent progress; (3) the clinical spectrum of severe zinc deficiency; (4) the lack of ideal biomarkers for milder zinc deficiency states, with the consequent dependence on randomized, placebo-controlled intervention studies to ascertain their prevalence and clinical consequences, including growth delay, diarrhea, pneumonia, other infections, disturbed neuropsychological performance and abnormalities of fetal development; (5) the public health significance of human zinc deficiency in the developing world; (6) reasons for concern and unanswered questions about zinc nutriture in the United States; (7) the need for better understanding of human zinc metabolism and homeostasis (including its limitations) at a molecular, cellular, organ-system and whole body level and of factors that affect zinc bioavailability; and (8) potential strategies for the prevention and management of human zinc deficiency. This review concludes with an emphasis on the immediate need for expanded research in directions that have become increasingly well demarcated and impelling as a result of recent progress, which is summarized in this overview.

The intestine is the major route of excretion of endogenous zinc (Zn) and has a key role in maintaining Zn homeostasis. The principal objective of this paper is to provide an interpretative report of quantities of endogenous fecal Zn (EFZ) excreted by rural Guatemalan school children fed either normal or low phytate maize as their principal food staple. EFZ was measured by a Zn stable isotope technique. EFZ did not differ between control and low phytate maize groups. The overall EFZ (n = 53) was (mean +/- SD) 1.56 +/- 0.69 mg Zn/d or 0.07 +/- 0.03 mg Zn x kg body wt(-1) x d(-1). EFZ was not correlated with the quantity of Zn absorbed. The estimated EFZ at the level of absorption that matched the physiologic requirement (EFZ(PR)) did not differ from the above mean value. The EFZ(PR) of 0.07 +/- 0.03 mg Zn/kg body wt is twice the value currently used in the estimation of Dietary Reference Intakes. Supported by other recent childhood data, these results suggest that the current estimates of EFZ(PR) used in the calculation of Zn requirements for children are misleadingly low.