Maternal zinc supplementation during pregnancy affects autonomic function of Peruvian children assessed at 54 months of age

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.     

Maternal body weight and pregnancy outcome

Pregnancies that produced 56,857 children were analyzed to evaluate the relationship of the mothers' relative pregravid body weight to pregnancy outcome. Perinatal mortality rates progressively increased from 37 of 1000 in offspring of thin subjects to 121 of 1000 in the offspring of obese subjects (p less than 0.001). Nearly half of this mortality increase was due to preterm deliveries, particularly before 31 wk of gestation. More than half of the increase in preterm births was caused by acute chorioamnionitis. Other factors that made major contributions to the overall mortality increase were rises in the frequencies of older gravidas (ages 35-50 y), gravidas who had diabetes mellitus, children who had major congenital malformations, and dizygous twins.     

Iron supplementation during infancy--effects on expression of iron transporters, iron absorption, and iron utilization in rat pups

BACKGROUND: Studies conducted in human infants suggest developmental changes in the regulation of iron absorption; however, little is known about the molecular mechanisms regulating iron absorption during infancy. Two intestinal iron transporters, divalent metal transporter 1 (DMT1) and ferroportin 1 (FPN1), were recently identified. OBJECTIVE: The objective was to investigate at a molecular level the regulation of iron absorption during infancy in a rat pup model. We examined the developmental expression of DMT1 and FPN1 and the effects of iron supplementation on their expression and on iron absorption and utilization during infancy. DESIGN: Rat pups were given daily oral doses of 0, 30, or 150 microg Fe from day 2 to day 20 after birth. On days 10 and 20 after birth, (59)Fe absorption, tissue minerals, and intestinal DMT1, FPN1, and ferritin expression were examined. To assess developmental expression, DMT1 and FPN1 were examined in control rats from days 1 to 50 after birth. RESULTS: Intestinal DMT1 and FPN1 were significantly affected by age; expression increased dramatically by day 40. On day 10, no significant effect of iron supplementation on DMT1 and FPN1 gene expression or on iron absorption was observed. By day 20, DMT1 and FPN1 expression and iron absorption had decreased significantly with iron supplementation. CONCLUSIONS: During early infancy, rat pups are unable to down-regulate intestinal iron transporters or iron absorption in response to iron supplementation, whereas down-regulation occurs during late infancy. The current findings provide evidence of the developmental regulation of iron absorption, which emphasizes the need for caution when giving iron supplements to infants at an early age.     

Maternal zinc supplementation does not affect size at birth or pregnancy duration in Peru.

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; P > 0.05), 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.     

Chromium picolinate supplementation in women: effects on body weight, composition, and iron status

OBJECTIVE: This study tested the hypothesis that supplementation of chromium picolinate (CrPic), 200 microg Cr/d, compared with an equivalent amount of picolinic acid (1720 microg) in CrPic and placebo, decreases body weight, alters body composition, and reduces iron status of women fed diets of constant energy and nutrients. METHODS: We fed 83 women nutritionally balanced diets, used anthropometry and dual x-ray absorptiometry to assess body composition, and measured serum and urinary Cr and biochemical indicators of iron status before and serially every 4 wk for 12 wk in a double-blind, randomized trial. RESULTS: CrPic supplementation increased (P < 0.0001) serum Cr concentration and urinary Cr excretion compared with picolinic acid and placebo. CrPic did not affect body weight or fat, although all groups lost (P < 0.05) weight and fat; it did not affect fat-free, mineral-free mass or measurements of iron status. CONCLUSION: Under conditions of controlled energy intake, CrPic supplementation of women did not independently influence body weight or composition or iron status. Thus, claims that supplementation of 200 microg of Cr as CrPic promotes weight loss and body composition changes are not supported.     

Serum zinc changes due to iron supplementation in teen-age pregnancy

Serum zinc and iron concentrations in a group of pregnant teen-agers supplemented with a multivitamin were compared during pregnancy with a group supplemented with a multivitamin containing 18 mg Fe. Serum measurements were at 13 wk of gestational age (prestudy) and during supplementation at 20, 32, and 38 wk, delivery, and 4 and 12 wk postpartum. Hematocrit measurements were used to adjust the measured metal concentrations for the diluting effect of the normal blood-volume increase. The non-Fe-group mean, adjusted serum Zn concentrations showed no change, but the serum Fe decreased to 28% below prestudy concentrations at 38 wk. In contrast, the Fe-supplementation group showed a progressive increase in Fe concentrations to a maximum of 38% above prestudy concentrations at 4 wk postpartum and a 35% decrease from prestudy Zn concentrations during the third trimester. The results of this study suggest that 18 mg Fe/d is adequate supplementation for nonanemic teen-age pregnancy and depresses the serum Zn concentration.     

Maternal iron status influences iron transfer to the fetus during the third trimester of pregnancy

BACKGROUND: The effect of maternal iron status on fetal iron deposition is uncertain. OBJECTIVE: We used a unique stable-isotope technique to assess iron transfer to the fetus in relation to maternal iron status. DESIGN: The study group comprised 41 Peruvian women. Of these women, 26 received daily prenatal supplements containing iron and folate (n = 11; Fe group) or iron, folate, and zinc (n = 15; Fe+Zn group) from week 10-24 of pregnancy to 1 mo postpartum. The remaining 15 women (control group) received iron supplementation only during the final month of pregnancy. During the third trimester of pregnancy (+/- SD: 32.9 +/- 1.4 wk gestation) oral 57Fe (10 mg) and intravenous 58Fe (0.6 mg) stable iron isotopes were administered to the women, and isotope enrichment and iron-status indicators were measured in cord blood at delivery. RESULTS: The net amount of 57Fe in the neonates' circulation (from maternal oral dosing) was significantly related to maternal iron absorption (P < 0.005) and inversely related to maternal iron status during the third trimester of pregnancy: serum ferritin (P < 0.0001), serum folate (P < 0.005), and serum transferrin receptors (P < 0.02). Significantly more 57Fe was transferred to the neonates in non-iron-supplemented women: 0.112 +/- 0.031 compared with 0.078 +/- 0.042 mg in the control group (n = 15) and the Fe and Fe+Zn groups (n = 24), respectively (P < 0.01). In contrast, 58Fe tracer in the neonates' circulation was not significantly related to maternal iron status. CONCLUSION: The transfer of dietary iron to the fetus is regulated in response to maternal iron status at the level of the gut.     

孕期母体营养与胎儿出生体质量

孕期母体的营养状况对孕妇自身和胎儿均有重要的影响,胎儿出生体质量是评价营养对妊娠结局影响最重要的指标.现阶段评价孕妇营养的指标主要有人体测量学、血液学以及生物电阻抗分析,每一种评价手段各有所长.胎儿出生体质量受多种因素的影响,对异常出生体质量儿(如巨大JD)可能是有意义的指标.但对正常体质量儿不一定有意义,因而对于孕期母体营养与婴儿体质量的关系有待更深入的研究.     

Effects of iron supplementation on maternal hematologic status in pregnancy

OBJECTIVES: Prenatal iron supplementation has been the standard recommendation for reducing maternal anemia in developing countries for the past 30 years. This article reviews the efficacy of iron supplementation on hemoglobin levels in pregnant women in developing countries. METHODS: Data from randomized controlled trials published between 1966 and 1998 were pooled. Meta-analyses of the relative change in maternal hemoglobin associated with iron supplementation were stratified by initial hemoglobin levels, duration of supplementation, and daily gestational supplement dose and supplementation with other nutrients. RESULTS: Iron supplementation raises hemoglobin levels. Its effects are dose dependent and are related to initial hematologic status. The extent to which iron supplementation can reduce maternal anemia is unclear. CONCLUSIONS: The extent to which maternal hemoglobin levels can be increased by recommended prenatal supplementation is limited and has uncertain physiological benefits. Other approaches, including food fortification and prevention and treatment of other causes of anemia, require methodologically rigorous evaluation to find effective answers to this global problem.     

Effectiveness of iron supplementation compared to iron treatment during pregnancy

This study presents the evaluation of an iron supplementation program in a community by comparing 478 pregnant women who received iron supplementation from the 4th month of pregnancy, with 392 pregnant women who received iron treatment only if their Hb level was less than 12 gm/dl, and had no supplementation. In the supplementation group, no statistically significant associations were found between compliance with age, education, social class or parity. Pregnant women of European-American origin showed higher rates of good compliance than those of Asian-African origin. The mean decrease of haemoglobin (Hb) and haematocrit (Hct) between the second and third trimester of pregnancy was smaller in the supplementation group (-0.9 gm/dl Hb, -2.1% Hct) than in the treatment group (-1.1 gm/dl Hb; -3.3% Hct). The differences between the two groups were significant only for the Hct levels (P = 0.022). The mean Hb and Hct levels during the third trimester of pregnancy were higher for good compliers (11.7 gm/dl Hb; 33.6% Hct) than for poor compliers (11.4 gm/dl Hb, 32.6% Hct).     

妊娠期铁营养评价

该文介绍了评价妊娠期妇女铁营养的指标.从体内铁储备减少、细胞内缺铁、红细胞生成时缺铁发展到缺铁性贫血,概述了孕妇缺铁性贫血的原因及铁营养与缺铁性贫血进程关系的各种状态,并详细阐述了相应的诊断标志(如血红蛋白、平均红细胞体积、铁蛋白、锌原卟啉、网织红细胞、血红蛋白含量、血清铁、可溶性转铁蛋白受体)、其单项检查的优缺点及多项复合检查对铁营养诊断的意义,同时讨论了孕期生理代谢改变对这些铁生物标志物的影响,以预防因铁营养不足所致的缺铁性贫血及缺铁对母婴的危害.     

Insufficient evidence supporting iron supplementation in anaemia during pregnancy

The Royal Dutch Organization of Midwives (KNOV) recently presented their practice guideline 'Anaemia in midwifery practice'. The guideline identified available evidence on diagnosis, prognosis and treatment of anaemia in pregnancy. Anaemia based on iron deficiency and subsequent treatment with iron supplementation are probably the most frequent aspects of care for pregnant women. However, there is surprisingly enough no evidence of the efficacy of iron supplementation treatment on relevant clinical outcomes in pregnant women with anaemia. We plead to make the next guideline a multidisciplinary one. Such a guideline may lead to a large pragmatic trial evaluating the efficacy of iron supplementation treatment for patients with anaemia.     

Maternal growth during pregnancy and decreased infant birth weight

We used stature and measurement of knee height to measure continued maternal growth during adolescent pregnancy in a sample of young gravidas (primigravidas and multiparas) and mature pregnant control subjects. Growth during pregnancy has been masked by a tendency of all gravidas to shrink while pregnant (approximately 0.5 cm over 6 mo of observation). Consequently, growth of many adolescent gravidas has not been clinically apparent. There was no effect on maternal growth during a first pregnancy in adolescence but this may be a result of the relatively good prepregnant nutrition status of the young gravidas in developed countries. Maternal growth during pregnancy, however, is associated with significantly decreased (-282 g, p less than 0.05) birth weight for infants when maternal growth continues during a subsequent adolescent pregnancy. This observation is consistent with the hypothesized competition between the metabolic demands of the growing adolescent mother and the nutrient needs of her developing fetus.     

孕前体重、孕期体重增长与妊娠结局的关系

目的:研究孕妇孕前及孕期体重指数变化对妊娠结局的影响。方法:分析732例孕妇孕前体重指数(BMI)、整个妊娠期体重指数增长幅度(△BMI)对妊娠结局的影响。结果:高BMI组妊娠期高血压疾病明显高于正常BMI组;低BMI组胎盘功能不良明显高于正常BMI组;低BMI组、高BMI组糖代谢异常、剖宫产率明显高于正常BMI组,差异有统计学意义。当△BMI6时妊娠期高血压疾病、糖代谢异常、巨大儿和剖宫产率明显高于△BMI=4～6组;当△BMI4时胎盘功能不良、早产率明显高于△BMI=4～6组。结论:孕前体重指数及孕期体重指数变化对妊娠结局有很大影响,孕前、孕期进行营养咨询和体重控制非常必要。     

妊娠期妇女的能量摄入、营养状况和体重变化

胎儿期是人生的特殊阶段,胎儿在子宫内的生长发育要依赖于母体的营养状况和生理状态.孕期母体体重的适宜性增长是胎儿正常发育和孕妇孕期健康状况的重要指标之一.孕期妇女通过膳食摄入能量来维持胎儿的发育和母体的适应性变化,表现在母体即是孕妇体重于妊娠期的进行性增加.孕期妇女撮入多少能量的问题也就是其体重增长多少的问题,同时也反映了其营养状况问题.孕期母体营养不良可导致胎儿宫内营养不良,引起低出生体重并将进一步导致一系列成年痰病的发生.该文综述了孕期母体的能量需要及母体的营养状况、体重变化和胎儿生长发育间的关系.     

Maternal zinc supplementation and growth in Peruvian infants

BACKGROUND: Little is known about how maternal zinc intake influences growth in utero and in postnatal life in humans. OBJECTIVE: We aimed to assess the effect of maternal zinc supplementation during pregnancy on infant growth through age 1 y. DESIGN: A double-blind, randomized controlled trial of prenatal zinc supplementation was conducted from 1995 to 1997 in Lima, Peru. Women (n = 1295) were enrolled at 15.6 +/- 4.6 wk gestation and assigned to receive daily supplements with zinc (15 mg Zn + 60 mg Fe + 250 microg folic acid) or without zinc (60 Fe + 250 microg folic acid) through pregnancy to 1 mo after delivery. At birth, 546 infants were followed for 12 mo to assess growth. Anthropometric measures of body size and composition were collected monthly, and morbidity and dietary intake surveillance was carried out weekly. RESULTS: No differences in maternal socioeconomic characteristics by treatment group or follow-up period were found. Infants born to mothers prenatally supplemented with zinc had significantly (P < 0.05) larger average growth measures beginning in month 4 and continuing through month 12. In longitudinal regression modeling, prenatal zinc was associated with greater weight (by 0.58 +/- 0.12 kg; P < 0.001), calf circumference (by 1.01 +/- 0.21 cm; P < 0.001), chest circumference (by 0.60 +/- 0.20 cm; P = 0.002), and calf muscle area (by 35.78 +/- 14.75 mm(2); P = 0.01) after adjustment for a range of covariates. No effect was observed for linear growth. CONCLUSION: Maternal zinc supplementation in this population was associated with offspring growth, which is suggestive of lean tissue mass accretion.     

Zinc supplementation reduces iron absorption through age-dependent changes in small intestine iron transporter expression in suckling rat pups

Zinc (Zn) supplementation negatively affects iron (Fe) absorption; however, the molecular mechanisms are not understood. We determined effects of Zn supplementation during mid- and late infancy on intestinal Fe transport mechanisms using a suckling rat model. Suckled rat pups were supplemented with 0 (control), 300 (low), or 750 (high) microg Zn/d until weaning at postnatal day (PN) 20. At mid-(PN10) and late (PN20) infancy, tissue Fe distribution, Fe absorption, intestine DMT1, ferroportin-1 (FPN) and hephaestin expression, and localization and liver hepcidin expression were measured. During early infancy, DMT1 and FPN were localized intracellularly. Negative effects of Zn supplementation on Fe absorption were associated with increased small intestine Fe retention, decreased hephaestin, and increased FPN expression. During late infancy, both DMT1 and FPN were appropriately localized to the apical and basolateral membrane, respectively, and negative effects of Zn supplementation on Fe absorption were absent. Although FPN protein level was lower in Zn-supplemented pups, hephaestin protein level was increased, which may have facilitated enhanced Fe efflux. These results indicate that Zn supplementation reduced Fe absorption during early infancy as a consequence of increased intestinal Fe retention due to reduced hephaestin levels. These effects were age-dependent, further demonstrating that Fe transport regulation is not fully developed until weaning, which may have important implications regarding the safety and efficacy of Zn supplementation programs for infants.     

Changes in iron status during pregnancy in peruvian women receiving prenatal iron and folic acid supplements with or without zinc

BACKGROUND: Iron deficiency anemia is the most prevalent nutrient deficiency during pregnancy, yet there are few data on the effect of prenatal iron supplementation in women in developing countries. OBJECTIVE: Our objective was to describe the effect of iron supplementation on hematologic changes during pregnancy, and the effect on those changes of adding zinc to the supplements. DESIGN: Pregnant women were enrolled in a randomized, double-masked study conducted at a hospital in a shantytown in Lima, Peru. Women were supplemented daily from 10-24 wk gestation to 4 wk postpartum with 60 mg Fe and 250 microg folic acid with or without 15 mg Zn. Hemoglobin and ferritin concentrations were measured in 645 and 613 women, respectively, at enrollment, at 28-30 and 37-38 wk gestation, and in the cord blood of 545 neonates. RESULTS: No differences in iron status were detected by supplement type, but hematologic changes were related to initial hemoglobin status. Women with anemia (hemoglobin <110 g/L) showed steady increases in hemoglobin concentration throughout pregnancy whereas women with relatively higher initial hemoglobin concentrations had declining values during mid pregnancy, then rising values by 37-38 wk gestation. Women with an initial hemoglobin concentration >95 g/L showed increases in serum ferritin by the end of the pregnancy. Despite supplementation, women with poorer hematologic status; who were younger, single, and multiparous; and who consumed fewer supplements were more likely to have anemia at the end of pregnancy. CONCLUSIONS: These hematologic changes are congruent with the effects of iron supplementation reported in placebo-controlled trials and the addition of zinc did not significantly affect them.