Association of haemoglobin levels in the first trimester and at 26-30 weeks with fetal and neonatal outcomes: a secondary analysis of the Global Network for Women's and Children's Health's ASPIRIN Trial.

OBJECTIVE: Limited data are available from low- and middle-income countries (LMICs) on the relationship of haemoglobin levels to adverse outcomes at different times during pregnancy. We evaluated the association of haemoglobin levels in nulliparous women at two times in pregnancy with pregnancy outcomes. DESIGN: ASPIRIN Trial data were used to study the association between haemoglobin levels measured at 6+0 -13+6  weeks and 26+0 -30+0  weeks of gestation with fetal and neonatal outcomes. SETTING: Obstetric care facilities in Pakistan, India, Kenya, Zambia, The Democratic Republic of the Congo and Guatemala. POPULATION: A total of 11 976 pregnant women. METHODS: Generalised linear models were used to obtain adjusted relative risks and 95% CI for adverse outcomes. MAIN OUTCOME MEASURES: Preterm birth, stillbirth, neonatal death, small for gestational age (SGA) and birthweight <2500 g. RESULTS: The mean haemoglobin levels at 6+0 -13+6  weeks and at 26-30 weeks of gestation were 116 g/l (SD 17) and 107 g/l (SD 15), respectively. In general, pregnancy outcomes were better with increasing haemoglobin. At 6+0 -13+6  weeks of gestation, stillbirth, SGA and birthweight <2500 g, were significantly associated with haemoglobin of 70-89 g/l compared with haemoglobin of 110-129 g/l The relationships of adverse pregnancy outcomes with various haemoglobin levels were more marked at 26-30 weeks of gestation. CONCLUSIONS: Both lower and some higher haemoglobin concentrations are associated with adverse fetal and neonatal outcomes at 6+0 -13+6  weeks and at 26-30 weeks of gestation, although the relationship with low haemoglobin levels appears more consistent and generally stronger. TWEETABLE ABSTRACT: Both lower and some higher haemoglobin concentrations were associated with adverse fetal and neonatal outcomes at 6-13 weeks and 26-30 weeks of gestation.

Global Network for Women's and Children's Health Research: probable causes of stillbirth in low- and middle-income countries using a prospectively defined classification system.

OBJECTIVE: We sought to classify causes of stillbirth for six low-middle-income countries using a prospectively defined algorithm. DESIGN: Prospective, observational study. SETTING: Communities in India, Pakistan, Guatemala, Democratic Republic of Congo, Zambia and Kenya. POPULATION: Pregnant women residing in defined study regions. METHODS: Basic data regarding conditions present during pregnancy and delivery were collected. Using these data, a computer-based hierarchal algorithm assigned cause of stillbirth. Causes included birth trauma, congenital anomaly, infection, asphyxia, and preterm birth, based on existing cause of death classifications and included contributing maternal conditions. MAIN OUTCOME MEASURES: Primary cause of stillbirth. RESULTS: Of 109 911 women who were enrolled and delivered (99% of those screened in pregnancy), 2847 had a stillbirth (a rate of 27.2 per 1000 births). Asphyxia was the cause of 46.6% of the stillbirths, followed by infection (20.8%), congenital anomalies (8.4%) and prematurity (6.6%). Among those caused by asphyxia, 38% had prolonged or obstructed labour, 19% antepartum haemorrhage and 18% pre-eclampsia/eclampsia. About two-thirds (67.4%) of the stillbirths did not have signs of maceration. CONCLUSIONS: Our algorithm determined cause of stillbirth from basic data obtained from lay-health providers. The major cause of stillbirth was fetal asphyxia associated with prolonged or obstructed labour, pre-eclampsia and antepartum haemorrhage. In the African sites, infection also was an important contributor to stillbirth. Using this algorithm, we documented cause of stillbirth and its trends to inform public health programs, using consistency, transparency, and comparability across time or regions with minimal burden on the healthcare system. TWEETABLE ABSTRACT: Major causes of stillbirth are asphyxia, pre-eclampsia and haemorrhage. Infections are important in Africa.

A prospective cause of death classification system for maternal deaths in low and middle-income countries: results from the Global Network Maternal Newborn Health Registry.

OBJECTIVE: To describe the causes of maternal death in a population-based cohort in six low- and middle-income countries using a standardised, hierarchical, algorithmic cause of death (COD) methodology. DESIGN: A population-based, prospective observational study. SETTING: Seven sites in six low- to middle-income countries including the Democratic Republic of the Congo (DRC), Guatemala, India (two sites), Kenya, Pakistan and Zambia. POPULATION: All deaths among pregnant women resident in the study sites from 2014 to December 2016. METHODS: For women who died, we used a standardised questionnaire to collect clinical data regarding maternal conditions present during pregnancy and delivery. These data were analysed using a computer-based algorithm to assign cause of maternal death based on the International Classification of Disease-Maternal Mortality system (trauma, termination of pregnancy-related, eclampsia, haemorrhage, pregnancy-related infection and medical conditions). We also compared the COD results to healthcare-provider-assigned maternal COD. MAIN OUTCOME MEASURES: Assigned causes of maternal mortality. RESULTS: Among 158 205 women, there were 221 maternal deaths. The most common algorithm-assigned maternal COD were obstetric haemorrhage (38.6%), pregnancy-related infection (26.4%) and pre-eclampsia/eclampsia (18.2%). Agreement between algorithm-assigned COD and COD assigned by healthcare providers ranged from 75% for haemorrhage to 25% for medical causes coincident to pregnancy. CONCLUSIONS: The major maternal COD in the Global Network sites were haemorrhage, pregnancy-related infection and pre-eclampsia/eclampsia. This system could allow public health programmes in low- and middle-income countries to generate transparent and comparable data for maternal COD across time or regions. TWEETABLE ABSTRACT: An algorithmic system for determining maternal cause of death in low-resource settings is described.

Routine antenatal ultrasound in low- and middle-income countries: first look - a cluster randomised trial.

OBJECTIVE: Ultrasound is widely regarded as an important adjunct to antenatal care (ANC) to guide practice and reduce perinatal mortality. We assessed the impact of ANC ultrasound use at health centres in resource-limited countries. DESIGN: Cluster randomised trial. SETTING: Clusters within five countries (Democratic Republic of Congo, Guatemala, Kenya, Pakistan, and Zambia) METHODS: Clusters were randomised to standard ANC or standard care plus two ultrasounds and referral for complications. The study trained providers in intervention clusters to perform basic obstetric ultrasounds. MAIN OUTCOME MEASURES: The primary outcome was a composite of maternal mortality, maternal near-miss mortality, stillbirth, and neonatal mortality. RESULTS: During the 24-month trial, 28 intervention and 28 control clusters had 24 263 and 23 160 births, respectively; 78% in the intervention clusters received at least one study ultrasound; 60% received two. The prevalence of conditions noted including twins, placenta previa, and abnormal lie was within expected ranges. 9% were referred for an ultrasound-diagnosed condition, and 71% attended the referral. The ANC (RR 1.0 95% CI 1.00, 1.01) and hospital delivery rates for complicated pregnancies (RR 1.03 95% CI 0.89, 1.20) did not differ between intervention and control clusters nor did the composite outcome (RR 1.09 95% CI 0.97, 1.23) or its individual components. CONCLUSIONS: Despite availability of ultrasound at ANC in the intervention clusters, neither ANC nor hospital delivery for complicated pregnancies increased. The composite outcome and the individual components were not reduced. TWEETABLE ABSTRACT: Antenatal care ultrasound did not improve a composite outcome that included maternal, fetal, and neonatal mortality.

Early infant adipose deposition is positively associated with the n-6 to n-3 fatty acid ratio in human milk independent of maternal BMI.

BACKGROUND/OBJECTIVES: Excessive infant weight gain in the first 6-month of life is a powerful predictor of childhood obesity and related health risks. In mice, omega-6 fatty acids (FAs) serve as potent ligands driving adipogenesis during early development. The ratio of omega-6 relative to omega-3 (n-6/n-3) FA in human milk (HM) has increased threefold over the last 30 years, but the impact of this shift on infant adipose development remains undetermined. This study investigated how maternal obesity and maternal dietary FA (as reflected in maternal red blood cells (RBCs) composition) influenced HM n-6 and n-3 FAs, and whether the HM n-6/n-3 ratio was associated with changes in infant adipose deposition between 2 weeks and 4 months postpartum. SUBJECTS/METHODS: Forty-eight infants from normal weight (NW), overweight (OW) and obese (OB) mothers were exclusively or predominantly breastfed over the first 4 months of lactation. Mid-feed HM and maternal RBC were collected at either transitional (2 weeks) or established (4 months) lactation, along with infant body composition assessed using air-displacement plethysmography. The FA composition of HM and maternal RBC was measured quantitatively by lipid mass spectrometry. RESULTS: In transitional and established HM, docosahexaenoic acid (DHA) was lower (P=0.008; 0.005) and the arachidonic acid (AA)/DHA+eicosapentaenoic acid (EPA) ratio was higher (P=0.05; 0.02) in the OB relative to the NW group. Maternal prepregnancy body mass index (BMI) and AA/DHA+EPA ratios in transitional and established HM were moderately correlated (P=0.018; 0.001). Total infant fat mass was increased in the upper AA/DHA+EPA tertile of established HM relative to the lower tertile (P=0.019). The amount of changes in infant fat mass and percentage of body fat were predicted by AA/EPA+DHA ratios in established HM (P=0.038; 0.010). CONCLUSIONS: Perinatal infant exposures to a high AA/EPA+DHA ratio during the first 4 months of life, which is primarily reflective of maternal dietary FA, may significantly contribute to the way infants accumulate adipose.

Bioactive components in human milk are differentially associated with rates of lean and fat mass deposition in infants of mothers with normal vs. elevated BMI.

OBJECTIVE: To model breastfed infant growth and body composition patterns over the first 4 months with multiple bioactive components of human milk (HM) and clinical factors (including maternal BMI status), which are related to growth. METHODS: Longitudinal observation of infant growth and body composition from 0 to 4 months among 41 predominantly breastfed infants (25 mothers of Normal-weight and 16 mothers with overweight/obesity). Fasted morning HM samples were collected at 5 time-points. Macronutrients, leptin, adiponectin, ghrelin, insulin, cytokines and n-6:n-3 esterified fatty acid ratio were measured. Infant weight-for-length Z-score (WLZ) trajectory, fat-free mass (FFM) gain, fat mass gain and %fat gain were modelled controlling for clinical covariates. RESULTS: HM insulin negatively associated with WLZ trajectory among infants of NW mothers (P = 0.028), but not associated with WLZ trajectory among infants of OW/Ob mothers. HM glucose (P < 0.001) was associated with slower rates of infant FFM gain. Infants of mothers with OW/Ob exhibited slower rates of FFM gain. HM protein, adiponectin and insulin concentrations, and n-6:n-3 ratio were all significant predictors in the model of infant fat mass gain (P < 0.03). Any amount of formula supplementation was associated with faster fat gain (P = 0.002). The model of %fat gain was similar to that of fat mass gain, excepting HM adiponectin was not a significant covariate, and a trend for maternal OW/Ob to correlate with faster %fat gain (P = 0.056). CONCLUSIONS: Bioactive components in HM may contribute to regulation of partitioning of body composition, and these contributions may differ between mothers of normal-weight vs. with OW/Ob.

Human milk insulin is related to maternal plasma insulin and BMI: but other components of human milk do not differ by BMI.

BACKGROUND/OBJECTIVES: The impact of maternal BMI and insulin sensitivity on bioactive components of human milk (HM) is not well understood. As the prevalence of obesity and diabetes rises, it is increasingly critical that we understand how maternal BMI and hormones associated with metabolic disease relate to concentrations of bioactive components in HM. SUBJECTS/METHODS: This longitudinal cohort design followed 48 breastfeeding mothers through the first four months of lactation, collecting fasting morning HM samples at 2-weeks and 1, 2, 3 and 4-months, and fasting maternal blood at 2-weeks and 4-months. Insulin, glucose, adipokines leptin and adiponectin, appetite regulating hormone ghrelin, marker of oxidative stress 8OHdG and inflammatory cytokines (IL-6, IL-8, and TNF-a) were measured in HM and maternal plasma. RESULTS: A total of 26 normal weight (NW) (BMI=21.4±2.0 kg/m2) and 22 overweight/obese (OW/Ob) (BMI=30.4±4.2 kg/m2) were followed. Of all HM analytes measured, only insulin and leptin were different between groups - consistently higher in the OW/Ob group (leptin: P<0.001; insulin: P<0.03). HM insulin was 98% higher than maternal plasma insulin at 2-weeks and 32% higher at 4-months (P<0.001). Maternal fasting plasma insulin and HOMA-IR were positively related to HM insulin at 2-weeks (P<0.001, R2⩾0.38, n=31), and 4-months (P⩽0.005, R2⩾0.20, n=38). CONCLUSIONS: The concentrations of insulin in HM are higher than in maternal plasma and are related to maternal BMI and insulin sensitivity. With the exception of leptin, there were minimal other differences observed in HM composition across a wide range in maternal BMI.

Zinc supplementation during lactation.

The requirements for zinc during lactation are greater than those during pregnancy, especially during the early weeks postpartum. Therefore, lactation poses a significant threat to maternal zinc homeostasis, particularly in populations with chronically low dietary zinc intakes. The current knowledge of maternal zinc status in lactation, particularly in developing countries, is reviewed herein with emphasis on the effects of zinc supplementation trials. The studies that have examined the zinc status of breast-fed infants are also reviewed.

Zinc requirements and zinc intakes of breast-fed infants.

Longitudinal changes in dietary zinc requirements for infants at different levels of net absorption were estimated using a factorial approach. Apart from variations in net absorption, the zinc needed for new lean body mass is the major determinant of requirements. As growth velocity declines progressively, estimated zinc requirements for growth and for replacement of urine and sweat losses decrease from a high for male infants of 780 micrograms/day at 1 mo to 480 micrograms/day in the 5th mo and then remain quite constant through the 1st yr. Calculated percentage absorption of zinc from human milk necessary to meet estimated requirements increases with duration of lactation. For infants of mothers whose zinc intake approximated 25 mg/day the calculated percentage absorption remained within plausible limits. It is suggested that the progressive decrease in milk zinc concentrations provides a mechanism for conserving maternal zinc while meeting infant needs.

PIP: This study aims to estimate longitudinal changes in dietary zinc requirements of infants with a factorial approach, and to use these estimates to evaluate the adequacy of calculated zinc intakes of the fully breast fed infant. Rates calculated are growth velocity, zinc concentration of lean body mass, zinco excretion is urine and sweat, milk zinc concentrations and milk volume. Apart from variations in net absorption, the zinc needed for new lean body mass is the major determinant of infant zinc requirements. Hence these requirements are relatively high in the very young infant and decrease with increasing age of the infant. As growth velocity declines progressively, estimated zinc requirements for growth and for replacement of urine and sweat losses decrease from a high for male infants of 780 ug/day at 1 month to 480 ug/day in the 5th month and then remain quite constant through the 1st year. Calculated % absorption of zinc from human milk necessary to meet estimated requirements increases with duration of lactation. For infants of mothers whose zinc intake approximated 25mg/day the calculated % absorption remained within plausible limits. It is suggested that the progressive decrease in milk zinc concentrations provides a mechanism for conserving material zinc while meeting infant needs.

Evaluation of zinc metabolism with use of stable-isotope techniques: implications for the assessment of zinc status.

Zinc stable isotopes can be applied to the identification of populations at risk for zinc deficiency and to monitoring the effects of zinc intervention studies designed to improve zinc nutriture. Techniques using these isotopes can provide information on how effectively the intestine is absorbing exogenous dietary zinc and conserving endogenous zinc. They can also yield estimates of the quantity of readily exchangeable zinc in the body. Data derived from stable-isotope studies can provide extensive information on zinc status and the bioavailability of dietary zinc, allowing researchers to relate zinc intake to physiologic and pathologic conditions. Application of these techniques in longitudinal studies can provide quantitative data on the effectiveness of prevention programs such as simple community measures aimed at reducing dietary phytate and zinc fortification and supplementation programs. Further, judicious application of zinc stable-isotope techniques could make an important contribution to progress toward the eradication of zinc deficiency in infants and young children in the developing world.

Bone mineral density changes during lactation: maternal, dietary, and biochemical correlates.

The objectives of this study were to characterize the effects of lactation and weaning on maternal bone mineral density (BMD) and on biochemical markers of bone turnover, and to determine the effects of dietary intake, milk output, and other maternal factors on changes in BMD. Twenty-six fully lactating and eight nonlactating women were followed longitudinally through 7 mo postpartum; the lactating women were followed through postweaning. Maternal dietary and supplement intake data, infant milk intake measurements, blood and urine samples, and midradius and L2-L4 vertebral BMD measurements were obtained 0.5, 3, 5, and 7 mo postpartum. Biochemical analyses included measurements of calciotropic hormones, 24-h urinary excretion of calcium, markers of bone formation and resorption, estradiol, and prolactin. Estimated maternal demands for calcium excretion in milk were met by a combination of high calcium intake (from diet and supplements, 1500 +/- 460 mg/d at 0.5 mo for lactating women) and a decline of approximately 4% in vertebral BMD between 0.5 and 3 mo postpartum. Postweaning BMD (n = 15) at this site approximated initial values. Two factors were positively associated with vertebral BMD, estradiol (P < 0.001) and calcium intake (P = 0.03), whereas two factors were negatively associated, parity (P = 0.03) and protein intake (P = 0.01). In these well-nourished women, the results suggest that the extent of bone loss associated with lactation and its recovery postweaning are negatively influenced by parity. The results also suggest that the bone loss may be attenuated by a generous dietary ratio of calcium to protein.

Linear growth of low income preschool children receiving a zinc supplement.

The effects of a zinc supplement on growth velocity were assessed in a double-blind, pair-matched controlled study in 40 children with low growth percentiles. Participants were low-income Spanish-American children, 2 to 6 yr of age with heights below the 10th percentile and nutritional or biochemical evidence of zinc deficiency. After 1 yr, the mean height velocity of the zinc-supplemented children was slightly, but significantly (p less than 0.005), greater than that of control children. This effect was primarily due to a greater height achievement of the zinc-supplemented boys. Increases in height-for-age z-scores were also significant for the supplemented males (p less than 0.001) and for the combined sexes (p less than 0.05). This study indicates the existence of a growth-limiting syndrome of mild zinc deficiency in children.

The effects of a dietary zinc supplement during lactation on longitudinal changes in maternal zinc status and milk zinc concentrations.

Dietary zinc intakes, selected biochemical indices of zinc status, and milk zinc concentrations were determined at monthly intervals throughout lactation for 53 middle-income lactating women, 14 of whom received a daily supplement of 15 mg zinc. Overall mean dietary zinc intake for the non-supplemented group (NZS) was 10.7 +/- 4.1 mg/day (mean +/- SD). The mean dietary zinc intake of the zinc supplemented group (ZS) was 12.2 +/- 3.5 mg/day, with an additional 12.8 +/- 1.5 mg/day from the supplement. For the NZS group, the highest mean plasma zinc concentration of 79 +/- 10 mu/dl, which occurred at month 4, was significantly less than the mean for non-lactating control women (86 +/- 10 micrograms/dl). ZS plasma zinc levels had a pattern similar to that of the NZS group for months 1-7. The rate of decline in milk zinc during lactation was significantly less for the ZS group compared to that of the NZS group (p = 0.02). It is concluded that milk zinc concentrations are influenced by maternal zinc intake within a physiological range and that the effects of low maternal intakes are most apparent with prolonged lactation.

Zinc supplementation during lactation: effects on maternal status and milk zinc concentrations.

The effects of a zinc supplement on maternal zinc status and milk zinc concentrations through > or = 7 mo of lactation were examined. Seventy-one lactating women received either a daily 15-mg zinc supplement (ZS, n = 40) or placebo (NZS, n = 31) started by 2 wk postpartum in a double-blind, randomized design. Overall mean zinc intakes were 13.0 +/- 3.4 mg/d for the NZS group and 25.7 +/- 3.9 mg/d (including supplement) for the ZS group. Plasma zinc concentrations of the ZS group were significantly higher than those of the NZS group (P = 0.05). Milk zinc concentrations declined significantly over the course of the study for all subjects but were not affected by zinc supplementation. The mean dietary zinc intake observed in the nonsupplemented group was adequate to maintain normal maternal zinc status and milk zinc concentrations through > or = 7 mo lactation. Similar controlled intervention trials in less well-nourished populations will be required to assess the impact of lower zinc intakes on milk zinc concentrations.

Zinc absorption and intestinal losses of endogenous zinc in young Chinese women with marginal zinc intakes.

The objective of this study was to determine fractional absorption of exogenous zinc and intestinal excretion of endogenous zinc in women of childbearing age whose habitual dietary zinc intake was marginal. The target population (L group) comprised residents of a remote farming village in northeast China and the control subjects (M group) were residents of Beijing. Mean (+/-SE) calculated dietary zinc intakes were 5.2 +/- 0.2 and 8.1 +/- 0.2 mg/d, respectively. The phytate-zinc molar ratio in the diet of both groups was approximately 10:1. 70Zn was administered intravenously before breakfast and 67Zn orally with three main meals in 1 d. Subsequently, all feces were collected quantitatively until the second visible marker had been excreted and 12-h urine samples were collected on days 3-9. Fractional absorption was determined by measuring cumulative fecal excretion of nonabsorbed 67Zn and endogenous fecal zinc by isotope-dilution technique (70Zn). Fractional absorption values for L and M groups, respectively, were 0.31 +/- 0.03 and 0.34 +/- 0.03 (P=0.45). Corresponding figures for endogenous fecal zinc were 1.30 +/- 0.07 and 2.34 +/- 0.20 mg Zn/d (P<0.001). Both the estimated total size of the pools of zinc that exchange with zinc in plasma within 2 d (r=0.762, P<0.001) and the excretion of endogenous zinc in the feces (r=0.706, P<0.0001) were positively correlated with calculated total daily zinc absorption. We conclude that fractional absorption of zinc does not differ between women consuming marginal and adequate quantities of zinc in their diets, but endogenous zinc is conserved effectively by the intestine in women whose habitual dietary zinc is marginal.

Zinc nutritional status during pregnancy: a longitudinal study.

Dietary zinc (Zn) intake and selected biochemical indices of Zn status were studied longitudinally at monthly intervals in 46 pregnant middle-income women, 10 of whom received a daily supplement of 15 mg Zn. Mean dietary Zn intake for the nonsupplemented subjects (group A) was 11.3 +/- 4.1 mg/day (56% of the Recommended Dietary Allowances), and for the Zn-supplemented subjects (group B) was 21.7 mg/day (109% of the Recommended Dietary Allowance), including an average intake of 11.1 mg/day as supplemental Zn. The mean plasma Zn concentration of group A at 2 months gestation, 71.4 +/- 9.8 micrograms/dl, was 17% lower than that of nonpregnant control women, and continued to decline significantly (p less than 0.01) between 2 and 10 months gestation. Plasma Zn of group B did not differ significantly from group A at any stage of gestation. Mean serum alkaline phosphatase activity of group B was higher than that of group A at 7 of 8 months studied (p less than 0.05). The level of prenatal iron supplementation in group A was negatively correlated with alkaline phosphatase activity and plasma Zn in the 2nd and 3rd trimesters, respectively. It is concluded that an early and progressive decline in plasma Zn which is not influenced by Zn intake occurs during gestation. Tentative standards for lower limits of normal at monthly intervals have been suggested. The higher alkaline phosphatase activity of group B compared with group A suggested that the dietary Zn intake of the latter was suboptimal. Prenatal supplemental iron may adversely affect maternal Zn status.

American Academy of Pediatrics. Committee on Nutrition. Calcium requirements of infants, children, and adolescents.

This statement is intended to provide pediatric caregivers with advice about the nutritional needs of calcium of infants, children, and adolescents. It will review the physiology of calcium metabolism and provide a review of the data about the relationship between calcium intake and bone growth and metabolism. In particular, it will focus on the large number of recent studies that have identified a relationship between childhood calcium intake and bone mineralization and the potential relationship of these data to fractures in adolescents and the development of osteoporosis in adulthood. The specific needs of children and adolescents with eating disorders are not considered.

Growth of breast-fed infants deviates from current reference data: a pooled analysis of US, Canadian, and European data sets. World Health Organization Working Group on Infant Growth.

OBJECTIVE: To compare growth patterns of a large sample of breast-fed infants with the current World Health Organization (WHO)/Centers for Disease Control and Prevention (CDC) reference data. METHODS: Data from seven longitudinal studies of infant growth in North America and northern Europe were pooled (n = 453 breast-fed infants). Weight, length and head circumference were compared with the WHO/CDC reference, and repeated-measures analysis of variance was used to examine associations between growth patterns and breast-feeding duration, age of introduction of solid foods, and use of other milks. RESULTS: In comparison with WHO/CDC reference data, infants breast-fed for at least 12 months (n = 226) grew more rapidly in the first 2 months and less rapidly (particularly in weight) from 3 to 12 months; the mean z score at 12 months was -0.53 for weight for age, -0.29 for length for age, and -0.32 for weight for length. In contrast, mean head circumference was well above the WHO/CDC median throughout the first year of life. These patterns were generally consistent across studies. In the full sample (n = 453), a longer duration of breast-feeding was associated with a greater decline in weight for age and weight for length but not length for age. CONCLUSION: These results suggest that if growth charts are to reflect patterns consistent with those of infants following WHO feeding recommendations, new reference data based on breast-fed infants are needed.

Acute effects of iron therapy on zinc status during pregnancy.

The acute effects of iron therapy on zinc status during pregnancy were investigated. The 20 subjects studied were healthy and had unremarkable obstetric histories. The mean stage of gestation was 27 weeks (range 21-33 weeks). Initial hematologic indices (mean +/- SEM) were: hematocrit 36.5 +/- 0.4%, serum ferritin 32.6 +/- 6.1 ng/mL, and serum iron 117 +/- 13 micrograms/dL. Iron therapy, prescribed by the obstetric caregivers, provided a total average daily elemental iron intake of 261 mg (range 164-395 mg) from therapy and routine supplements. Laboratory studies of zinc status were obtained immediately before iron therapy and at one and four weeks thereafter. Initial plasma zinc was 62.9 +/- 2.1 micrograms/dL. A mean decline in plasma zinc of 4.0 +/- 1.8 micrograms/dL (P less than .05) was observed from baseline to one week. The decline remained statistically significant after adjustment for the expected physiologic decline over the same interval of gestation. No further decline occurred from one to four weeks. No significant treatment-related effects were observed for neutrophil zinc, mononuclear leukocyte zinc, or serum alkaline phosphatase activity. These results indicate that iron therapy in doses typically prescribed by obstetric caregivers in this country has an acute, measurable effect on maternal zinc status.

Human zinc metabolism: advances in the modeling of stable isotope data.

Compartmental modeling is a useful tool for investigating metabolic systems and processes. We and others have applied it to the study of zinc metabolism in humans. Because existing models could not be accurately fitted to our data, we have developed a new model of human zinc metabolism based on stable isotope tracer data from studies of five healthy adults. Multiple isotope tracers were administered orally and intravenously and the resulting enrichment measurement in plasma, erythrocytes, urine, and feces. These tracer kinetic data, along with other measured and calculated tracee and steady-state data, were used to develop the model. A single model structure composed of fourteen compartments was found to be suitable for all subjects. Model development and fitting of data and model for each subject were accomplished using the SAAM/CONSAM computer programs. The model development and fiting processes are described and exemplified using data from one of the subjects. While identifiability could not be demonstrated a priori due to the model's complexity, parameter statistics for the fitted models did show most parameters to be adequately identified a posteriori.