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Background: Existing evidence on the effects of race and ethnicity on pregnancy outcomes is restricted to individual studies done within specific countries and health systems. We aimed to assess the impact of race and ethnicity on perinatal outcomes in high-income and upper-middle-income countries, and to ascertain whether the magnitude of disparities, if any, varied across geographical regions. Methods: For this individual participant data (IPD) meta-analysis we used data from the International Prediction of Pregnancy Complications (IPPIC) Network of studies on pregnancy complications; the full dataset comprised 94 studies, 53 countries, and 4 539 640 pregnancies. We included studies that reported perinatal outcomes (neonatal death, stillbirth, preterm birth, and small-for-gestational-age babies) in at least two racial or ethnic groups (White, Black, south Asian, Hispanic, or other). For our two-step random-effects IPD meta-analysis, we did multiple imputations for confounder variables (maternal age, BMI, parity, and level of maternal education) selected with a directed acyclic graph. The primary outcomes were neonatal mortality and stillbirth. Secondary outcomes were preterm birth and a small-for-gestational-age baby. We estimated the association of race and ethnicity with perinatal outcomes using a multivariate logistic regression model and reported this association with odds ratios (ORs) and 95% CIs. We also did a subgroup analysis of studies by geographical region. Findings: 51 studies from 20 high-income and upper-middle-income countries, comprising 2 198 655 pregnancies, were eligible for inclusion in this IPD meta-analysis. Neonatal death was twice as likely in babies born to Black women than in babies born to White women (OR 2·00, 95% CI 1·44–2·78), as was stillbirth (2·16, 1·46–3·19), and babies born to Black women were at increased risk of preterm birth (1·65, 1·46–1·88) and being small for gestational age (1·39, 1·13–1·72). Babies of women categorised as Hispanic had a three-times increased risk of neonatal death (OR 3·34, 95% CI 2·77–4·02) than did those born to White women, and those born to south Asian women were at increased risk of preterm birth (OR 1·26, 95% CI 1·07–1·48) and being small for gestational age (1·61, 1·32–1·95). The effects of race and ethnicity on preterm birth and small-for-gestational-age babies did not vary across regions. Interpretation: Globally, among underserved groups, babies born to Black women had consistently poorer perinatal outcomes than White women after adjusting for maternal characteristics, although the risks varied for other groups. The effects of race and ethnicity on adverse perinatal outcomes did not vary by region. Funding: National Institute for Health and Care Research, Wellbeing of Women.

BACKGROUND: Maternal iron absorption during pregnancy can be evaluated using RBC incorporation of orally administered stable iron isotope. This approach underestimates true maternal absorption of iron as it does not account for absorbed iron that is transferred to the fetus or retained within the placenta. OBJECTIVE: Our objective was to re-evaluate maternal iron absorption after factoring in these losses and identify factors associated with iron partitioning between the maternal, neonatal, and placental compartments. METHODS: This study utilized data from stable iron isotope studies carried out in 68 women during the third trimester of pregnancy. Iron status indicators and stable iron isotopic enrichment were measured in maternal blood, umbilical cord blood, and placental tissue when available. Factors associated with iron isotope partitioning between the maternal, neonatal, and placental compartments were identified. RESULTS: On average, true maternal absorption of iron increased by 10% (from 19% to 21%) after accounting for absorbed iron present in the newborn (P

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

This study builds on a previous study by this group in which 6–11-month-old Peruvian infants who were fed bovine milk fat globule membrane (MFGM) containing complementary food had significantly fewer episodes of infection-related bloody diarrhea relative to those consuming a control food (skim milk powder). Micronutrient deficiencies including zinc deficiency were prevalent in this study population. To understand the mechanism behind the health benefits of consuming MFGM, the serum metabolome and cytokine levels, as markers for systemic immune responses, were evaluated using 1H nuclear magnetic resonance-based metabolomics and a multiplex system, respectively. Combined with data on micronutrient status and anthropometry, a comparative analysis was performed. Supplementation with MFGM tended to improve micronutrient status, energy metabolism, and growth reflected as increased levels of circulating amino acids and weight gain, particularly in female infants compared to controls. Decreased levels of the microbial choline metabolite trimethylamine-N-oxide in the MFGM-supplemented group (both male and female infants) suggest a functional perturbation in the intestinal microbiota. A cytokine shift toward a less T helper type 1 response was observed in those receiving the MFGM supplement, which was mainly attributed to decreases in interleukin-2 levels. Our findings suggest that consumption of MFGM with complementary food may reverse the metabolic abnormalities found in marginally nourished infants, thereby improving metabolic regulation, which may lead to enhanced immunity., Infant nutrition: milk fat globule membrane reverses metabolic abnormalities Bovine milk fat globule membrane (MFGM)-enriched complementary food has been recognized to be capable of reducing the episodes of bloody diarrhea in marginally nourished infants. However, the metabolic influence of MFGM remains unknown. Carolyn Slupsky from University of California-Davis and co-workers studied the impacts of bovine MFGM consumption on the levels of serum metabolome and immune markers. They found the supplements of MFGM improved the micronutrient status, energy metabolism, and growth, especially prominent for female infants. Moreover, MFGM complementary food lowered the level of the bacterial choline metabolite trimethylamine-N-oxide in the infants, indicating a functional perturbation to their intestinal microbiota. These findings suggest MFGM in complementary food can help to regulate the metabolic abnormalities of the infants with micronutrient deficiency, probably resulting in enhanced immunity.

OBJECTIVES: Iron (Fe) homeostasis must be tightly regulated during pregnancy to supply sufficient Fe to both the mother and her developing fetus. Stable isotopes have been utilized to understand Fe absorption during pregnancy by measuring maternal red blood cell incorporation. This measure, however, underestimates the true amount of Fe absorbed, as dietary Fe is transferred to the fetus and may be retained by the placenta. The objective of this study was to obtain a more accurate estimation of Fe absorption during pregnancy and determine factors associated with Fe partitioning between the mom, baby and placenta. METHODS: Sixty-eight women (6 carrying multiple fetuses (age 27–33), 20 carrying singletons from Rochester NY (age 16–32), and 42 carrying singletons from Peru (age 18–30)) were dosed with an oral stable Fe isotope during late pregnancy. Iron absorption was calculated as the sum of tracer recovered in maternal and umbilical cord red blood cells (RBC) and for isotope retained in placental tissue. The net amount of Fe in each compartment was calculated based on Hb concentration, body (or placental) weight and estimated blood volume. Hemoglobin (Hb), serum ferritin (SF), soluble transferrin receptor (sTfR), folate and vitamin B-12 were assessed in maternal and cord blood. RESULTS: The amount of maternally absorbed Fe was significantly greater when neonatal and placental uptake of tracer was accounted for (Table 1). While the majority (> 85%) of absorbed Fe tracer was utilized by the mother for RBC production, neglecting net Fe tracer transferred to the placenta and neonatal compartment underestimated true Fe absorption by 4%-20%. There was a significant positive association between the net amounts of Fe tracer recovered in the fetal compartment and the maternal compartment (R2 = 0.63, P

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.

Anemia in children younger than 3 years is a public health problem in Peru and worldwide. It is believed that one of the primary causes of anemia is iron deficiency. Numerous studies and reviews have reported that iron deficiency limited psychomotor development in children and that, despite the correction of anemia, children with iron deficiency experienced poorer long-term performance in cognitive, social, and emotional functioning. These outcomes were reported in observational studies, follow-up studies, and experimental studies with a control group. Anemia can decrease school performance, productivity in adult life, quality of life, and the general income of affected individuals. Here we describe possible mechanisms underlying the effect of iron deficiency, with or without anemia, on childhood development. The high rate of anemia in this age group is a cause for concern. Moreover, anemia should be prevented in the first year of life to avoid long-term negative effects on individual development.La anemia en niños menores de tres años es un problema de salud pública en el Perú y el mundo. Se estima que la causa principal de la anemia, aunque no la única, es la deficiencia de hierro. Existen muchos estudios y revisiones sobre cómo esta carencia en los infantes impacta negativamente en el desarrollo psicomotor y, a pesar de corregirse la anemia, los niños con este antecedente presentan, a largo plazo, un menor desempeño en las áreas cognitiva, social y emocional. Estos hallazgos se describen en estudios observacionales, de seguimiento, así como en experimentales con grupo control. La anemia puede disminuir el desempeño escolar, y la productividad en la vida adulta, afectando la calidad de vida, y en general la economía de las personas afectadas. Se describen algunos posibles mecanismos de cómo la deficiencia de hierro, con o sin anemia, podría afectar el desarrollo en la infancia; por ello, causa preocupación la alta prevalencia de anemia que se observa en este grupo de edad. La prevención de la anemia en el primer año de vida debe ser la meta para evitar consecuencias en el desarrollo de la persona a largo plazo.

Tools to assess intake among children in Latin America are limited. We developed and assessed the reproducibility and validity of a semi-quantitative food frequency questionnaire (FFQ) administered to children, adolescents, and their caregivers in Lima, Peru. We conducted 24-h diet recalls (DRs) and focus groups to develop a locally-tailored FFQ prototype for children aged 0–14 years. To validate the FFQ, we administered two FFQs and three DRs to children and/or their caregivers (N = 120) over six months. We examined FFQ reproducibility by quartile agreement and Pearson correlation coefficients, and validity by quartile agreement and correlation with DRs. For reproducibility, quartile agreement ranged from 60–77% with correlations highest for vitamins A and C (0.31). Age-adjusted correlations for the mean DR and the second-administered FFQ were highest in the 0–7 age group, in which the majority of caregivers completed the FFQ on behalf of the child (total fat; 0.67) and in the 8–14 age group, in which both the child and caregiver completed the FFQ together (calcium, niacin; 0.54); correlations were

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.

It is well known that vitamin C is an important enhancer of nonheme iron bioavailability due to its high reducing capacity. Camu-camu, a fruit that grows in the jungle of Peru, contains high amount of vitamin C (2,780 mg per 100 g). In this study, we investigated the effect of camu-camu on nonheme iron bioavailability from two different meals (rice with lentils and wheat flour porridge) using an in vitro Caco-2 cell model. These two meals were treated with three different camu-camu juice concentrations (C 0 = 0 g, C 1 = typical consumption, and C 2 = 3X typical consumption). The results showed that camu-camu reduced rather than enhanced nonheme iron bioavailability. The inhibiting trend was significant (p

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.

Zinc is an essential micronutrient for the development of the fetal renal, cardiovascular and metabolic systems; however, there is limited evidence of its effects on the postnatal cardiometabolic function. In this study, we evaluated the effect of maternal zinc supplementation during pregnancy on the cardiometabolic profile of the offspring in childhood. A total of 242 pregnant women were randomly assigned to receive a daily supplement containing iron+folic acid with or without zinc. A follow-up study was conducted when children of participating mothers were 4.5 years of age to evaluate their cardiometabolic profile, including anthropometric measures of body size and composition, blood pressure, lipid profile and insulin resistance. No difference in measures of child cardiometabolic risk depending on whether mothers received supplemental zinc during pregnancy. Our results do not support the hypothesis that maternal zinc supplementation reduces the risk of offspring cardiometabolic disease.

Growth velocity patterns have the potential to signal unhealthy responses to environmental insults with long-term consequences. We aimed to investigate velocities in Peruvian infants (n = 259) in relation to attained anthropometric outcomes at 12 months and to identify determinants of velocities during critical periods of infancy. From 1995 to 1997, a randomised controlled trial of maternal zinc supplementation was conducted in a peri-urban slum area of Lima. Infants were followed monthly through 1 year on a range of anthropometric measures. Three types of velocity variables were studied: (1) incremental velocity (1 months and 3 months); (2) proportional changes (% of total size gained/month); and (3) individual velocity variability [standard deviation (SD) of individual child incremental velocities]. Mean individual child SD of weight velocity was 417 g (±126). In multivariate ordinary least squares regression analyses, growth velocities in month 1 and individual weight velocity variability positively predicted attained length and weight by 12 months. Panel regression by generalised least-squares with random effects of length and weight velocities confirmed the exponentially decelerating pace of growth through infancy and the importance of birth size in driving this trajectory. This study contributes evidence to support the importance of early growth velocities and greater degrees of weight gain plasticity for attained length and weight.

Prenatal iron supplementation is recommended to control anaemia during pregnancy. Low compliance and side effects have been claimed as the main obstacles for adequate impact of the supplementation. As part of a double-blind supplementation study carried out in a hospital located in a shantytown in Lima, Peru, we monitored compliance throughout pregnancy and evaluated factors associated with variation in compliance over time. Overall, 985 pregnant women were enrolled in a supplementation study that was administered through their prenatal care from 10 to 24 weeks of gestation until 4 weeks postpartum. They received 60 mg iron and 250 µg folate with or without 15 mg zinc. Women had monthly care visits and were also visited weekly to query regarding compliance, overall health status, and potential positive and negative effects of supplement consumption. Median compliance was 79% (inter-quartile range: 65-89%) over pregnancy, and the median number of tablets consumed was 106 (81-133). Primpara had lower average compliance; positive health reports were associated with greater compliance, and negative reports were associated with lower compliance. There was no difference by type of supplement. Women with low initial compliance did achieve high compliance by the end of pregnancy, and women who reported forgetting to take the supplements did have lower compliance. Compliance was positively associated with haemoglobin concentration at the end of pregnancy. In conclusion, women comply highly with prenatal supplementation within a prenatal care model in which supplies are maintained and reinforcing messages are provided.

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: To develop an indicator of maternal near miss as a proxy for maternal death and to study its association with maternalfactors and perinatal outcomes. METHODS: In a multicenter cross-sectional study, we collected maternal and perinatal data from the hospital records of a sample of women admitted for delivery over a period of two to three months in 120 hospitals located in eight Latin American countries. We followed a stratified multistage cluster random design. We assessed the intra-hospital occurrence of severe maternal morbidity and the latter's association with maternal characteristics and perinatal outcomes. FINDINGS: Of the 97 095 women studied, 2964 (34 per 1000) were at higher risk of dying in association with one or more of the following: being admitted to the intensive care unit (ICU), undergoing a hysterectomy, receiving a blood transfusion, suffering a cardiac or renal complication, or having eclampsia. Being older than 35 years, not having a partner, being a primipara or para > 3, and having had a Caesarean section in the previous pregnancy were factors independently associated with the occurrence of severe maternal morbidity. They were also positively associated with an increased occurrence of low and very low birth weight, stillbirth, early neonatal death, admission to the neonatal ICU, a prolonged maternal postpartum hospital stay and Caesarean section. CONCLUSION: Women who survive the serious conditions described could be pragmatically considered cases of maternal near miss. Interventions to reduce maternal and perinatal mortality should target women in these high-risk categories.

Background Previous growth studies of Peruvian children have featured high stunting rates and limited information about body composition. Objective We aimed to characterize anthropometric measures of Peruvian infants 0 to 12 months of age in relation to the international growth references and biological, environmental, and socioeconomic factors. Methods Infants ( n = 232) were followed longitudinally from birth through 12 months of age from a prenatal zinc supplementation trial conducted in Lima, Peru, between 1995 and 1997. Anthropometric measures of growth and body composition were obtained at enrollment from mothers and monthly through 1 year of age from infants. Weekly morbidity and dietary intake surveillance was carried out during the second half of infancy. Results The prevalence rates of stunting, underweight, and wasting did not exceed 4% based on the World Health Organization growth references. Infants of mothers from high-altitude regions had larger chest circumference ( p = .006) and greater length ( p = .06) by 12 months. Significant predictors of growth and body composition throughout infancy were age, sex, anthropometric measurements at birth, breastfeeding, maternal anthropometric measurements, primiparity, prevalence of diarrhea among children, and the altitude of the region of maternal origin. No associations were found for maternal education, asset ownership, or sanitation and hygiene factors. Conclusions Peruvian infants in this urban setting had lower rates of stunting than expected. Proximal and familial conditions influenced growth throughout infancy.

Objective To determine if vitamin C and E supplementation in high-risk pregnant women with low nutritional status reduces pre-eclampsia. Design Multicentred, randomised, controlled, double-blinded trial. Setting Antenatal care clinics and Hospitals in four countries. Population Pregnant women between 14 and 22 weeks’ gestation. Method Randomised women received 1000 mg vitamin C and 400 iu of vitamin E or placebo daily until delivery. Main outcome measures Pre-eclampsia, low birthweight, small for gestational age and perinatal death. Results Six hundred and eighty-seven women were randomised to the vitamin group and 678 to the placebo group. Groups had similar gestational ages (18.1; SD 2.4 weeks), socio-economic, clinical and demographical characteristics and blood pressure at trial entry. Risk factors for eligibility were similar, except for multiple pregnancies: placebo group (14.7%), vitamins group (11.8%). Previous pre-eclampsia, or its complications, was the most common risk factor at entry (vitamins 41.6%, placebo 41.3%). Treatment compliance was 87% in the two groups and loss to follow-up was low (vitamins 2.0%, placebo 1.3%). Supplementation was not associated with a reduction of pre-eclampsia (RR: 1.0; 95% CI: 0.9–1.3), eclampsia (RR: 1.5; 95% CI: 0.3–8.9), gestational hypertension (RR: 1.2; 95% CI: 0.9–1.7), nor any other maternal outcome. Low birthweight (RR: 0.9; 95% CI: 0.8–1.1), small for gestational age (RR: 0.9; 95% CI: 0.8–1.1) and perinatal deaths (RR: 0.8; 95% CI: 0.6–1.2) were also unaffected. Conclusion Vitamins C and E at the doses used did not prevent pre-eclampsia in these high-risk women.

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.

Cluster-based studies involving aggregate units such as hospitals or medical practices are increasingly being used in healthcare evaluation. An important characteristic of such studies is the presence of intracluster correlation, typically quantified by the intracluster correlation coefficient (ICC). Sample size calculations for cluster-based studies need to account for the ICC, or risk underestimating the sample size required to yield the desired levels of power and significance. In this article, we present values for ICCs that were obtained from data on 97,095 pregnancies and 98,072 births taking place in a representative sample of 120 hospitals in eight Latin American countries. We present ICCs for 86 variables measured on mothers and newborns from pregnancy to the time of hospital discharge, including 'process variables' representing actual medical care received for each mother and newborn. Process variables are of primary interest in the field of implementation research. We found that overall, ICCs ranged from a minimum of 0.0003 to a maximum of 0.563 (median 0.067). For maternal and newborn outcome variables, the median ICCs were 0.011 (interquartile range 0.007-0.037) and 0.054 (interquartile range 0.013-0.075) respectively; however, for process variables, the median was 0.161 (interquartile range 0.072-0.328). Thus, we confirm previous findings that process variables tend to have higher ICCs than outcome variables. We demonstrate that ICCs generally tend to increase with higher prevalences (close to 0.5). These results can help researchers calculate the required sample size for future research studies in maternal and perinatal health.

OBJECTIVE: To set up a global system for monitoring maternal and perinatal health in 54 countries worldwide. METHODS: The WHO Global Survey for Monitoring Maternal and Perinatal Health was implemented through a network of health institutions, selected using a stratified multistage cluster sampling design. Focused information on maternal and perinatal health was abstracted from hospital records and entered in a specially developed online data management system. Data were collected over a two- to three-month period in each institution. The project was coordinated by WHO and supported by WHO regional offices and country coordinators in Africa and the Americas. FINDINGS: The initial survey was implemented between September 2004 and March 2005 in the African and American regions. A total of 131 institutions in seven African countries and 119 institutions in eight Latin American countries participated. CONCLUSION: This project has created a technologically simple and scientifically sound system for large-scale data management, which can facilitate programme monitoring in countries.

Objective To investigate optimal timing of elective repeat caesarean section among low-risk pregnant women with prior caesarean section in a multicountry sample from largely low- and middle-income countries. Design Secondary analysis of a cross-sectional study. Setting Twenty-nine countries from the World Health Organization Multicountry Survey on Maternal and Newborn Health. Population 29,647 women with prior caesarean section and no pregnancy complications in their current pregnancy who delivered a term singleton (live birth and stillbirth) at gestational age 37–41 weeks by pre-labour caesarean section, intra-partum caesarean section, or vaginal birth following spontaneous onset of labour. Methods We compared the rate of short-term adverse maternal and newborn outcomes following pre-labour caesarean section at a given gestational age, to those following ongoing pregnancies beyond that gestational age. Main Outcome Measures Severe maternal outcomes, neonatal morbidity, and intra-hospital early neonatal mortality. Results Odds of neonatal morbidity and intra-hospital early neonatal mortality were 0.48 (95% confidence interval [CI] 0.39–0.60) and 0.31 (95% CI 0.16–0.58) times lower for ongoing pregnancies compared to pre-labour caesarean section at 37 weeks. We did not find any significant change in the risk of severe maternal outcomes between pre-labour caesarean section at a given gestational age and ongoing pregnancies beyond that gestational age. Conclusions Elective repeat caesarean section at 37 weeks had higher risk of neonatal morbidity and mortality compared to ongoing pregnancy, however risks at later gestational ages did not differ between groups.

OBJECTIVE: To report stillbirth and early neonatal mortality and to quantify the relative importance of different primary obstetric causes of perinatal mortality in 171 perinatal deaths from 7993 pregnancies that ended after 28 weeks in nulliparous women. METHODS: A review of all stillbirths and early newborn deaths reported in the WHO calcium supplementation trial for the prevention of pre-eclampsia conducted at seven WHO collaborating centres in Argentina, Egypt, India, Peru, South Africa and Viet Nam. We used the Baird-Pattinson system to assign primary obstetric causes of death and classified causes of early neonatal death using the International classification of diseases and related health problems, Tenth revision (ICD-10). FINDINGS: Stillbirth rate was 12.5 per 1000 births and early neonatal mortality rate was 9.0 per 1000 live births. Spontaneous preterm delivery and hypertensive disorders were the most common obstetric events leading to perinatal deaths (28.7% and 23.6%, respectively). Prematurity was the main cause of early neonatal deaths (62%). CONCLUSIONS: Advancements in the care of premature infants and prevention of spontaneous preterm labour and hypertensive disorders of pregnancy could lead to a substantial decrease in perinatal mortality in hospital settings in developing countries.

Iron and zinc deficiencies are common in developing countries and supplementation is one way of reversing these deficiencies. The objective of this randomized, placebo-controlled clinical trial was to identify the effect of daily supplementation with iron, zinc, and iron plus zinc on the morbidity experience of 855 children 0.5-15 years of age in Peru. Single nutrient supplementation with zinc reduced diarrhea morbidity by 23% in all children. In older children (more than five years of age), iron supplementation increased morbidity due to Plasmodium vivax and diarrhea. In younger children, iron combined with zinc provided protection against P. vivax malaria, but also interfered with some of the diarrhea protection associated with zinc supplementation. No statistically significant effect was observed of either supplement on incidence of respiratory infection or anthropometric indices. Iron and zinc deficiencies should be remedied, and combined supplementation may be a good option, particularly in younger children in P. vivax malaria-endemic areas, although local endemicity and species-specific prevalence should be considered carefully when designing any supplementation program involving iron in a malaria-endemic area.

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.

Our objective was to test whether intrauterine growth in the second half of pregnancy is associated with anthropometric and body composition measures in early childhood. We used data from a prenata...

Background: To ensure multiple micronutrient powders (MNP) for children have their intended effect, it is important to understand caregivers’ experiences. Objective: We aimed to assess perceptions, practices, and preferences relating to the use of MNP among caregivers of children enrolled in a study to compare different MNP dosing schemes in Cajamarca, Peru. Methods: Infants age 6-11 mo (n=400) were randomly assigned to 6 mo daily, 6 mo intermittent (every other day), 12 mo daily, or 12 mo intermittent MNP supplementation. MNP were provided monthly and field staff conducted home visits twice monthly. Unused MNP sachets were collected throughout and at endline (12 mo) all caregivers were asked about their experiences using MNP. Results: Most (94%) reported being very satisfied with MNP. One quarter (27%) reported difficulties remembering to give the MNP scheme as recommended. The most frequently reported strategies for remembering were keeping the MNP in the kitchen or bedroom. Most (98%) reported that giv...

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.

Fractional iron absorption from a breakfast meal was determined in Peruvian children employing stable iron isotopes as labels. Iron isotopic analysis was performed by the recently developed negative thermal ionization technique for high-precision iron isotope ratio measurements using FeF4– ions. By increasing the ascorbic acid content of the standard breakfast meal as served within the Peruvian school-breakfast program from 27 mg to 70 mg, it was possible to increase the geometric mean fractional iron absorption significantly from 5.1% (range 1.6–13.5%) to 8.2% (range 3.1–25.8%). Fractional iron absorption was calculated according to isotope dilution principles and by considering the non-monoisotopic character of the used spikes.

Zinc deficiency in pregnancy probably is common all over the world but especially in developing countries and where women eat a diet based on cereals, vegetables, and legumes. It has been estimated that approximately 80% of pregnant women worldwide may consume an inadequate amount of zinc. Whether maternal zinc deficiency impedes fetal growth is not clear. This double-blind, randomized trial related maternal zinc status during pregnancy to fetal growth as measured sonographically. The subjects were 242 Peruvian women living in an impoverished area of Lima. At 10 to 16 weeks gestation, they were assigned to receive daily supplements of 60 mg iron and 250 μg folic acid with or without 25 mg of zinc. Fetal head circumference, biparietal diameter, abdominal circumference, and length of the femoral diaphysis were measured every 4 weeks from 20 to 38 weeks gestation. Compliance with taking supplements was estimated at 87%. Women took their assigned supplements a median of 6 days a week. There were no significant differences between the 2 groups in duration of pregnancy, neonatal size, head circumference, biparietal diameter, or abdominal circumference. Femoral diaphysial length, however, was greater in zinc-supplemented women than in those taking only iron and folic acid. The effect of zinc on femoral length appeared to increase with advancing gestational age. It approximated one fourth of the reference standard deviation. The positive effect of supplemental zinc on fetal femoral length observed in this study is consistent with experimental animal and in vitro studies that have demonstrated a stimulatory effect of zinc on bone growth. Previous studies also have shown an adverse effect of maternal zinc deficiency on bone growth and fetal bone metabolism. The present findings endorse the use of zinc supplements when dietary zinc intake is inadequate.

BACKGROUND: Effects of prenatal iron supplementation on maternal postpartum iron status and early infant iron homeostasis remain largely unknown. OBJECTIVE: We examined iron absorption and growth in exclusively breastfed infants in relation to fetal iron exposure and iron status during early infancy. DESIGN: Longitudinal paired iron-absorption ((5)(8)Fe) studies were conducted in 59 exclusively breastfed Peruvian infants at 2-3 mo of age (2M) and 5-6 mo of age (5M). Infants were born to women who received >/= 5100 or

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

Growth velocity patterns have the potential to signal unhealthy responses to environmental insults with long‐term consequences. We aimed to investigate velocities in Peruvian infants (n = 259) in relation to attained anthropometric outcomes at 12 months and to identify determinants of velocities during critical periods of infancy. From 1995 to 1997, a randomised controlled trial of maternal zinc supplementation was conducted in a peri‐urban slum area of Lima. Infants were followed monthly through 1 year on a range of anthropometric measures. Three types of velocity variables were studied: (1) incremental velocity (1 months and 3 months); (2) proportional changes (% of total size gained/month); and (3) individual velocity variability [standard deviation (SD) of individual child incremental velocities]. Mean individual child SD of weight velocity was 417 g (±126). In multivariate ordinary least squares regression analyses, growth velocities in month 1 and individual weight velocity variability positively predicted attained length and weight by 12 months. Panel regression by generalised least‐squares with random effects of length and weight velocities confirmed the exponentially decelerating pace of growth through infancy and the importance of birth size in driving this trajectory. This study contributes evidence to support the importance of early growth velocities and greater degrees of weight gain plasticity for attained length and weight.

OBJECTIVE: The aim of the present study was to evaluate the efficacy of a milkfat globule membrane (MFGM)-enriched protein fraction in a complementary food on diarrhea anemia and micronutrient status. SUBJECTS AND METHODS: A randomized double-blind controlled design to study 550 infants 6 to 11 months old who received daily for 6 months a complementary food (40 g/day) with the protein source being either the MFGM protein fraction or skim milk proteins (control). Health and nutritional status of infants were examined monthly in the outpatient clinic; product intake food patterns and diarrhea morbidity were assessed by home visits twice per week. Hemoglobin and micronutrient status were measured at 0 and 6 months of intervention. Results are presented as the entire group and as 6 to 8 and 9 to 11 months subgroups. RESULTS: A total of 499 infants completed the study. Global prevalence of diarrhea was 3.84% and 4.37% in the MFGM group and control group respectively (P < 0.05). Consumption of the MFGM protein fraction reduced episodes of bloody diarrhea (odds ratio 0.54; 95% confidence interval 0.31-0.93 P = 0.025) adjusting for anemia and potable water facilities as covariates. There were no differences between groups in anemia serum ferritin zinc or folate. CONCLUSIONS: Addition of an MFGM-enriched protein fraction to complementary food had beneficial effects on diarrhea in infants and may thus help to improve the health of vulnerable populations.