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BackgroundAnemia is a term that describes low hemoglobin concentrations and can result from micronutrient deficiencies, infection, or low birth weight. Early-life anemia, particularly iron-deficiency anemia (IDA) is associated with several negative metabolic, developmental, and cognitive outcomes, some of which persist into adulthood.ObjectiveThe aim of this study was to investigate alterations in systemic metabolism and fecal microbial diversity and functionality associated with anemia and IDA in male and female infants from Iquitos, Peru.DesignCross-sectional stool and serum samples were collected from 95 infants (53 boys and 42 girls) at 12 mo of age. The fecal microbiome was assessed by using 16S ribosomal RNA gene sequencing, and the fecal and serum metabolomes were quantified using 1H-nuclear magnetic resonance.ResultsThe prevalence of anemia was 64%, with a greater proportion of anemia in male infants attributed to iron deficiency. Metabolically, anemia was associated with decreased concentrations of tricarboxylic acid cycle metabolites in both sexes (males: succinate, P=0.031; females: fumarate, P=0.028). In addition, anemic male infants exhibited significantly lower serum concentrations of several amino acids compared with nonanemic male infants. Although no specific structural or functional differences in the microbiota were observed with anemia in general, likely due the heterogeneity of its etiology, IDA affected the microbiome both structurally and functionally. Specifically, the abundance of butyrate-producing bacteria was lower in IDA subjects of both sexes than in nonanemic, non-iron-deficient subjects of the same sex (females: Butyricicoccus, P=0.041; males: Coprococcus, P=0.010; Roseburia, P=0.027). IDA male infants had higher concentrations of 4-hydroxyphenyllactate (P&nbsp

Objective To assess the accuracy of angiogenic biomarkers to predict pre-eclampsia. Design Prospective multicentre study. From 2006 to 2009, 5121 pregnant women with risk factors for pre-eclampsia (nulliparity, diabetes, previous pre-eclampsia, chronic hypertension) from Argentina, Colombia, Peru, India, Italy, Kenya, Switzerland and Thailand had their serum tested for sFlt-1, PlGF and sEng levels and their urine for PlGF levels at ⩽20, 23–27 and 32–35 weeks’ gestation (index tests, results blinded from carers). Women were monitored for signs of pre-eclampsia, diagnosed by systolic blood pressure ⩾140 mmHg and/or diastolic blood pressure ⩾90 mmHg, and proteinuria (protein/creatinine ratio ⩾0.3, protein ⩾1 g/l, or one dipstick measurement ⩾2+) appearing after 20 weeks’ gestation. Early pre-eclampsia was defined when these signs appeared ⩽34 weeks’ gestation. Main outcome measure Pre-eclampsia. Results Pre-eclampsia was diagnosed in 198 of 5121 women tested (3.9%) of whom 47 (0.9%) developed it early. The median maternal serum concentrations of index tests were significantly altered in women who subsequently developed pre-eclampsia than in those who did not. However, the area under receiver operating characteristics curve at ⩽20 weeks’ gestation were closer to 0.5 than to 1.0 for all biomarkers both for predicting any pre-eclampsia or at ⩽34 weeks’ gestation. The corresponding sensitivity, specificity and likelihood ratios were poor. Multivariable models combining sEng with clinical features slightly improved the prediction capability. Conclusions Angiogenic biomarkers in first half of pregnancy do not perform well enough in predicting the later development of pre-eclampsia.

A double-blind, randomized clinical trial was conducted to determine the effects of prevention of zinc deficiency on cognitive and sensorimotor development during infancy. At 6 mo of age, infants were randomly assigned to be administered a daily liquid supplement containing 10 mg/d of zinc (zinc sulfate), 10 mg/d of iron (ferrous sulfate), and 0.5 mg/d of copper (copper oxide), or an identical daily liquid supplement containing only 10 mg/d of iron and 0.5 mg/d of copper. Various controls were implemented to ensure adherence to the supplement protocol. A battery of developmental assessments was administered from 6 to 18 mo of age that included a visual habituation/recognition memory task augmented with heart rate at 6, 9, and 12 mo of age; the Bayley Scales of Infant Development, 2nd edition (BSID2) at 6, 12, and 18 mo; the A-not-B error task at 9 and 12 mo; and free-play attention tasks at 12 and 18 mo. Only infants supplemented with zinc had the normative decline in look duration from 6 to 12 mo during habituation and a normative decline in shifting between objects on free-play multiple-object attention tasks from 12 to 18 mo of age. The 2 groups did not differ on any of the psychophysiologic indices, the BSID2, or the A-not-B error task. The findings are consistent with zinc supplementation supporting a profile of normative information processing and active attentional profiles during the first 2 y of life. This trial was registered at clinicaltrials.gov as NCT00589264.

We evaluated changes in the status of iron, zinc, and copper in non-anemic Peruvian infants who were receiving daily supplements of 10 mg of iron and 0.5 mg of copper with or without 10 mg of zinc from 6 to 18 mo of age.Overall, 251 infants were randomized to receive one of two daily supplements. Venous blood draws at 6, 12, and 18 mo of age were taken to characterize hemoglobin, plasma ferritin, zinc, and copper concentrations. The urinary excretion of zinc was also measured at each time point. Repeated measures analysis of variance was used to evaluate changes over time and by supplement type.Both hemoglobin and copper concentrations increased significantly and plasma ferritin decreased from 6 to 12 mo of age (P0.05). Mean plasma zinc concentrations in the zinc treatment group were maintained over time, whereas zinc concentrations in the control group declined; differences by treatment were found at 12 and 18 mo of age (P0.05). Urinary zinc concentration was increased in the zinc group at 12 mo only. There was evidence that zinc treatment improved the hemoglobin level at 18 mo of age (P = 0.09). Compliance with supplementation was high, with 81% of the intended dose consumed over the 12-mo period.Daily mineral supplementation over the course of 1 y appears to be feasible and acceptable in this population. A combined supplement can improve the status of iron, zinc, and copper in infants at the same time.

Maternal prenatal zinc supplementation improved fetal autonomic regulation in a nutrient-deficient population in Peru. To evaluate whether differences in autonomic regulation existed in early childhood, we studied 165 children from a zinc supplementation trial (80% of original sample) as part of a comprehensive evaluation at age 54 mo. Electrocardiogram (ECG) data were collected from the children at rest and while they underwent a cognitive testing battery following a standardized protocol. Of these, 79 were born to mothers receiving 25 mg/d zinc in addition to 60 mg/d iron and 250 μg/d folic acid during pregnancy, and 86 were born to mothers receiving iron and folic acid only. Derived cardiac measures included heart period (HP), range, HP variability (HPV), mean square of successive differences (MSSD), and a measure of vagal tone (V). Children in the zinc supplementation group had greater HP (i.e. slower heart rate), greater range, higher time-independent (HPV) and time-dependent (MSSD) variability in HP, and higher V (P < 0.05) during baseline. Analyses conducted across the cognitive testing period revealed similar effects of prenatal zinc supplementation on cardiac patterns. Concurrent child zinc plasma concentration was also associated with longer HP, greater variability, and marginally higher range and V (P < 0.10). Differences in cardiac patterns due to prenatal zinc supplementation were detectable in children at 54 mo of age during conditions of both rest and challenge, indicating that supplementing zinc-deficient pregnant women has beneficial long-term consequences for neural development associated with autonomic regulation.

Objective We describe the levels and patterns of change in red blood cell (RBC) metallothionein (MT) during pregnancy and the neonate and relate RBCMT to other indicators of zinc and iron status. Methods As part of a double-masked controlled trial of prenatal zinc supplementation among 242 Peruvian pregnant women, we determined RBCMT at enrollment (10–16 wk), at 28 and 36 wk of gestation, and in the cord blood at delivery in 158 women (86 who received daily supplements containing 60 mg of iron and 250 μg of folic acid and 72 whose supplements also contained 25 mg of zinc). In addition, we measured plasma and urinary zinc concentrations, hemoglobin and serum ferritin, and, on a limited sample, RBC zinc and placental MT. Results RBCMT increased during pregnancy, and levels in the cord blood approximated maternal values at 36 wk. Only RBC zinc at 36 wk differed by supplement type ( P Conclusion Changes in RBCMT throughout pregnancy were consistent with the hypothesized role of MT in regulating zinc homeostasis. RBCMT appears to not be responsive during pregnancy to changes in zinc status achieved with supplements.

Background: Maternal zinc deficiency is relatively common in developing countries, but its consequences for fetal growth are not established. Objective: The goal was to examine whether improvement in maternal gestational zinc status is positively associated with fetal growth as assessed by ultrasonography. Design: We conducted a double-masked, randomized trial among 242 pregnant Peruvian women in an impoverished shantytown in Lima, Peru. At 10 –16 wk of gestation, the women were randomly assigned to receive daily supplements containing 60 mg Fe and 250 g folic acid, with or without 25 mg Zn. We measured fetal head circumference, biparietal diameter, abdominal circumference, and femur diaphysis length at 20, 24, 28, 32, 36, and 38 wk of gestation. Fetal measures were analyzed longitudinally to evaluate differences in trends of fetal growth by supplement type, and within-subject correlations were taken into account. Results: Femur diaphysis length was greater in fetuses whose mothers received zinc supplements (P 0.05), and the difference tended to increase with gestational age. No significant differences by supplement type were observed for the other anatomical sites measured. Conclusions: The observed positive effect of prenatal zinc on fetal femur diaphysis length is consistent with the results of experimental studies in animals and in vitro. The supplementation effect represents an upward shift in mean femur diaphysis length at term of about one-quarter of the reference SD. These findings suggest the potential importance of maternal zinc status for fetal bone growth in humans and illustrate the value of ultrasonography for evaluating the effect of prenatal nutritional interventions on components of fetal growth. Am J Clin Nutr 2004;79:826 –30.

Women with symptoms of iron deficiency while pregnant can anticipate adverse effects on both their own and their infant's health. Premature births and low birth weight are more frequent, and the risk of death at delivery and perinatally is increased. Previous studies done to determine how maternal iron deficiency affects the ability of the fetus to accumulate iron have given mixed results. The present study used a stable-isotope technique to quantify iron transfer in 41 pregnant Peruvian women, 26 of whom received daily supplements of iron and folate, with or without zinc, from week 10 to 24 of pregnancy up to I month postoperatively. At an average of 33 weeks gestation, the women were given 10 mg of 5 7 Fe orally and 0.6 mg of 5 8 Fe intravenously. Isotope enrichment and markers of iron status were estimated in cord blood samples at the time of delivery. Isotope ratios were measured by a mass spectrometric method. The net amount of 5 7 Fe in the neonatal circulation, a result of maternal supplementation, correlated directly with maternal iron absorption and inversely with maternal iron status in the third trimester as reflected by serum levels of ferritin, folate, and transferrin receptor. As expected, the women given supplements had significantly better iron status than did those in the control group. When women did not receive supplements, significantly more 5 7 Fe was transferred to their infants. This was the case whether or not iron supplementation was accompanied by zinc. In contrast, the amount of the 5 8 Fe tracer in the neonatal circulation was not significantly related to the mother's iron status. There were no significant differences in birth weight or length between the 2 groups. These findings demonstrate that the transfer of maternal iron to the fetus is regulated by the prevailing maternal iron status. The fact that transfer of intravenously administered iron was not a function of maternal iron status suggests that iron transfer takes place chiefly in the gastrointestinal tract. The fetal need for iron appears to take priority over maternal needs.

To estimate the effect of maternal zinc deficiency on pregnancy outcomes, we conducted a zinc supplementation trial in an urban shantytown in Lima, Peru, a population with habitual low zinc intakes. Beginning at 10-24 wk gestation, 1295 mothers were randomly assigned to receive prenatal supplements containing 60 mg iron and 250 (g folate, with or without 15 mg zinc. Women were followed up monthly during pregnancy. At birth, newborn weight was recorded, and crownheel length, head circumference and other circumferences and skinfold thicknesses were assessed on d 1. At delivery, 1016 remained in the study; duration of pregnancy was known for all women, and birth weight information was available for 957 newborns. No differences were noted in duration of pregnancy (39.4 +/- 2.2 vs. 39. 5 +/- 2.0 wk) or birth weight (3267 +/- 461 vs. 3300 +/- 498 g) by prenatal supplement type (iron + folate + zinc vs. iron + folate; P0.05), and there were no differences in the rates of preterm (37 wk) or post-term (42 wk) delivery, low birth weight (2500 g) or high birth weight (4000 g). Finally, there were no differences by prenatal supplement type in newborn head circumference, crownheel length, chest circumference, mid-upper arm circumference, calf circumference or skinfold thickness at any of three sites. Adjustment for covariates and confounding factors did not alter these results. Adding zinc to prenatal iron and folate tablets did not affect duration of pregnancy or size at birth in this population.

The factors regulating concentrations of iron and iron-binding proteins in milk are incompletely known. Since anemic women usually are given iron supplements, we have evaluated the effect of this practice on iron and lactoferrin levels in milk. Lactating Peruvian mothers (n = 29) were studied during the first month of lactation. Lactoferrin and iron in milk were analyzed at 2 and 30 days post-partum. Mothers who were anemic (Hgb

Objective The objective of the study was to examine whether blood pressure in early pregnancy and its rise in the second half of gestation are associated with spontaneous preterm birth in healthy, normotensive, nulliparous women. Study Design We included 5167 women with singleton gestation who participated in the World Health Organization Calcium Supplementation for the Prevention of Preeclampsia Trial. Systolic, diastolic, and mean arterial blood pressure and pulse pressure at baseline (12-19 weeks of gestation) and at the midthird trimester (30-34 weeks) were calculated. Rise in blood pressure was the difference between the midthird trimester and baseline. Preterm birth was defined as early preterm (less than 34 completed weeks) and late preterm birth (34-36 weeks). Results Women experiencing early or late preterm birth had over 10 mm Hg and 3 mm Hg higher rise, respectively, in systolic, diastolic, and mean arterial blood pressure than women delivering at term. A rise in systolic pressure over 30 mm Hg or diastolic pressure over 15 mm Hg was associated with a statistically significant 2- to 3-fold increase in risk of spontaneous preterm birth. Conclusion An excessive rise in either systolic or diastolic blood pressures from early pregnancy to the midthird trimester is associated with spontaneous preterm birth in a dose-response pattern.