Staffan Berglund

Iron Supplements Reduce the Risk of Iron Deficiency Anemia in Marginally Low Birth Weight Infants

OBJECTIVE: Low birth weight infants are at risk for iron deficiency (ID). Most LBW infants have marginally low birth weight (MLBW, 2000–2500 g) and it is not known whether they benefit from iron supplements. The objective of this trial was to study the effects of iron supplementation in MLBW infants. METHOD: In a randomized controlled trial, we assigned 285 healthy, MLBW infants to receive iron supplements at a dose of 0 (placebo), 1, or 2 mg/kg per day between 6 weeks and 6 months of age. Hemoglobin levels, ferritin levels, transferrin saturation, mean cell volume, and transferrin receptor levels were analyzed at 6 months. Growth and morbidity were monitored. RESULTS: Iron supplementation resulted in significant dose-dependent effects on hemoglobin and all iron status indicators at 6 months. The prevalence of ID at 6 months was 36% in the placebo group, 8.2% in the 1 mg/kg per day group, and 3.8% in the 2 mg/kg per day group (P < .001). The prevalence rates of ID anemia (IDA) were 9.9%, 2.7%, and 0%, respectively (P = .004). Among infants who were exclusively breastfed at 6 weeks, the prevalence of IDA was 18% in the placebo group. There were no significant differences between groups in growth or morbidity. CONCLUSIONS: MLBW infants have relatively high risks of ID and IDA, especially if they are breastfed. Iron supplementation at 2 mg/kg per day from 6 weeks to 6 months reduces this risk effectively, with no short-term adverse effects on morbidity or growth.

SEXUAL ABUSE DURING CHILDHOOD AND ADOLESCENCE AMONG NICARAGUAN MEN AND WOMEN: A POPULATION-BASED ANONYMOUS SURVEY

AIMS The objective was to describe experiences of sexual abuse occurring before 19 years of age among men and women in León, Nicaragua and to explore the possible association to later sexual risk behavior. METHOD A sub-sample of literate urban men and women 25-44 years of age was selected from a representative sample of households in León. After an invitation to a public health event, 154 men (53% of the invited) and 213 women (66% of those invited) participated in giving written answers to an anonymous questionnaire. RESULTS Twenty percent of men and 26% of women reported that they had experienced sexual abuse. Women had been victims of attempted or completed rape twice as often as men, 15% as compared to 7%. Thirty-three percent of the abuse towards boys and 66% of the abuse towards girls was committed by family members. Women who had experienced attempted or completed rape were more likely to later have had a higher number of sexual partners compared to non-abused or moderately abused women. CONCLUSIONS Sexual abuse of children and adolescents of both sexes is common in Nicaragua. The results underscore the urgent need to address this serious problem more openly, and to make more resources available for the prevention of sexual abuse and for support to victims.

Effects of Iron Supplementation of LBW Infants on Cognition and Behavior at 3 Years

OBJECTIVE: Low birth weight (LBW) infants are at increased risk of cognitive and behavioral problems and at risk for iron deficiency, which is associated with impaired neurodevelopment. We hypothesized that iron supplementation of LBW infants would improve cognitive scores and reduce behavioral problems. METHODS: In a randomized controlled trial, 285 marginally LBW (2000–2500 g) infants received 0, 1, or 2 mg/kg/day of iron supplements from 6 weeks to 6 months of age. At 3.5 years of age, these infants and 95 normal birth weight controls were assessed with a psychometric test (Wechsler Preschool and Primary Scale of Intelligence) and a questionnaire of behavioral problems (Child Behavior Checklist; CBCL). RESULTS: There were no significant differences in IQ between the LBW groups or LBW infants versus controls. Mean (SD) full-scale IQ was 105.2 (14.5), 104.2 (14.7), and 104.5 (12.7) in the placebo, 1 mg, and 2 mg groups, respectively (P = .924). However, for behavioral problems, there was a significant effect of intervention. The prevalence of children with CBCL scores above the US subclinical cutoff was 12.7%, 2.9%, and 2.7% in the placebo, 1-mg, and 2-mg groups, respectively (P = .027), compared with 3.2% in controls. Relative risk (95% confidence interval) for CBCL score above cutoff in placebo-treated children versus supplemented was 4.5 (1.4–14.2). CONCLUSIONS: Early iron supplementation of marginally LBW infants does not affect cognitive functions at 3.5 years of age but significantly reduces the prevalence of behavioral problems. The study suggests a causal relation between infant iron deficiency and later behavioral problems.

Gender and social differences in adolescent sexuality and reproduction in Nicaragua

PURPOSE The aim of this research was to study gender and social differences in adolescent sexuality and reproduction, as reflected in age at first intercourse and age at first pregnancy, as a basis for future interventions in the municipality of León, Nicaragua. METHODS In a community-based cross-sectional study including 7789 households, all women aged 15-49 years (n = 10,867) were interviewed about socioeconomic, sexual, and reproductive issues. A random subsample of men (n = 388) and women (n = 413) aged 15-49 years was interviewed in more detail about sexual patterns and reproduction. RESULTS The median age at first intercourse for women and men was 17.8 and 16.2 years, respectively. Womens average latency period to end of first pregnancy was 22 months. There was a significant tendency to start active sexual life later among todays girls aged 15-20 years, compared to the groups 21-27, 28-35, and 36-49 years old. A similar trend was found in age at first pregnancy. These secular trends were not found among men. Age at first pregnancy for current adolescents was lower among those having less formal education. CONCLUSIONS The short latency period between first sexual intercourse and end of first pregnancy, probably reflecting lack of access to counseling and contraception, is worrying in light of the growing sexually transmitted disease/human immunodeficiency virus threat. The secular trend of later start of reproduction, however, is a positive sign which partly may be an effect of increasing education in the Nicaraguan society.

Effects of iron supplementation on serum hepcidin and serum erythropoietin in low-birth-weight infants

BACKGROUND The iron-regulatory hormone hepcidin has not been studied in infants, who experience large physiologic changes in iron status. OBJECTIVE The objective was to study hepcidin and erythropoietin and their correlation with iron status in iron-replete and iron-deficient low-birth-weight (LBW) infants-a group at particular risk of iron deficiency (ID). DESIGN We randomly assigned 285 otherwise healthy LBW infants to receive, from 6 wk to 6 mo of age, 3 doses of iron supplements: 0 (placebo), 1, or 2 mg/kg daily. Hepcidin, erythropoietin, hemoglobin, and variables of iron status were analyzed. RESULTS Serum hepcidin did not change over time in the placebo group, despite a rapid decrease in serum ferritin. In iron-supplemented infants, hepcidin increased significantly, reaching a mean (±SD) concentration of 19.2 ± 2.5 ng/mL in the 2-mg/kg group compared with 13.0 ± 2.6 ng/mL in the placebo group at age 6 mo (P < 0.001). The difference was even larger between iron-deficient and iron-replete infants. Hepcidin was independently positively correlated with ferritin at all ages and was negatively correlated with the transferrin receptor concentration at age 6 wk and with transferrin at age 6 mo. Erythropoietin was initially similar between groups but decreased significantly in iron-supplemented infants. In addition to being negatively correlated with hemoglobin, it was also independently negatively correlated with indicators of iron status. CONCLUSIONS Hepcidin is closely associated with iron status and may be a useful indicator of iron stores and ID in infants. Erythropoietin is negatively correlated with iron status, which suggests a feedback mechanism that needs further study. This trial is registered at clinicaltrials.gov as NCT00558454.

Meeting iron needs for infants and children.

Purpose of review Iron deficiency early in life is associated with impaired neurological development. This study reviews the latest research on how to best meet iron requirements in infants and children. Recent findings There is concurrent evidence that delayed cord clamping is well tolerated and improves infant iron stores. Iron supplements or enriched complementary foods starting before 6 months of life do not reduce iron deficiency prevalence in low-risk populations. However, for low birth weight infants, iron supplements before 6 months of life have long-term benefits. Iron deficiency anaemia (IDA) during the second half year of life is rare in countries with high compliance to iron-rich complementary foods, but remains a major problem globally. In high-risk populations, iron supplementation reduces IDA and possibly improves growth. However, increased risk of infections is a concern and optimal preventive strategies have not yet been determined. Finally, there is concurrent evidence that iron supplementation of anaemic school-aged children reduces IDA and possibly improves neuropsychological outcomes. Summary Interventions for prevention of iron deficiency should be prioritized in risk groups. However, the unclear long-term benefits and possible risk of adverse effects, particularly increased infections in developing countries, prompt further large-scale, double-blinded trials.

Iron supplementation until 6 months protects marginally low-birth-weight infants from iron deficiency during their first year of life.

Objectives: Low-birth-weight (LBW) infants (<2500 g) have an increased risk of iron deficiency (ID) during their first 6 months of life. The optimal dose and duration of iron supplementation to LBW infants are, however, unknown. The objective of the present study was to investigate the long-term effect on iron status and growth in marginally LBW (2000–2500 g) infants, of iron supplements given until 6 months of life. Methods: In a randomized controlled trial, 285 healthy marginally LBW infants received 0, 1, or 2 mg · kg−1 · day−1 of iron supplements from 6 weeks to 6 months of age. At 12 months and 3.5 years of life we measured length, weight, head circumference, and indicators of iron status (hemoglobin, ferritin, mean corpuscular volume, and transferrin saturation) and assessed the prevalence of iron depletion, functional ID, and ID anemia. Results: At 12 months of age, there was a significant difference in ferritin between the groups (P = 0.006). Furthermore, there was a significant difference in the prevalence of iron depletion (23.7%, 10.6%, and 6.8%, respectively, in the placebo, 1-mg, and 2-mg groups, P = 0.009) and similar nonsignificant trends for functional ID and ID anemia. At 3.5 years of life there were no significant differences in iron status and the mean prevalence of iron depletion was 3.2%. Anthropometric data were not affected by the intervention. Conclusions: Iron supplements with 2 mg · kg−1 · day−1 until 6 months of life effectively reduces the risk of ID during the first 12 months of life and is an effective intervention for preventing early ID in marginally LBW infants.

Effects of iron supplementation on auditory brainstem response in marginally LBW infants.

LBW infants are at risk of iron deficiency (ID), which is associated with impaired nervous system development and may lead to prolonged auditory brainstem response (ABR) latencies. We hypothesized that iron supplementation shortens ABR latencies in marginally LBW (MLBW, 2000-2500 g) infants. In a randomized, controlled trial, 285 healthy MLBW infants received 0, 1, or 2 mg iron/kg/d of iron supplements from 6 wk to 6 mo of age. ABR absolute wave V latencies and central conduction time (CCT) were measured at the endpoint. There were no significant differences between groups in ABR wave V latencies (n = 218). Furthermore, there were no significantly prolonged ABR latencies in infants with ID (n = 32). CCT was significantly higher in the 2 mg group than in the placebo group (n = 126). However, there were no significant correlations between CCT and iron intake or any iron status variable, suggesting that differences in CCT were not caused by iron. We conclude that iron supplements did not improve ABR latencies, and iron-deficient MLBW infants did not have impaired ABR latencies at 6 mo, suggesting that ABR is not a sensitive measure of impaired neurological development or that mild/moderate ID causes no such impairment in MLBW infants.

Iron deficiency in the first 6 months of age in infants born between 32 and 37 weeks of gestational age

Background/objectives:Preterm infants are at risk of iron deficiency (ID). In the Netherlands, preterm infants born after 32 weeks of gestational age (GA) do not receive iron supplementation on a routine basis. We hypothesized that dietary iron intake in these infants might not be sufficient to meet the high iron requirements during the first 6 months of life.Subjects/methods:In a prospective cohort study, we analyzed the prevalence and risk factors of ID in 143 infants born between 32+0 and 36+6 weeks GA who did not receive iron supplementation.Results:ID at the age of 4 and 6 months was present in 27 (18.9%) and 7 (4.9%) infants. Results of a multivariable logistic regression analysis showed that ID was associated with lower birth weight, a shorter duration of formula feeding, more weight gain in the first 6 months of life and lower ferritin concentrations at the age of 1 week.Conclusions:Preterm infants born after 32 weeks GA have an increased risk of ID compared with those born at term, supporting the need of iron supplementation. Our results suggests that measurement of ferritin at the age of 1 week might be useful to identify those infants at particular risk and could be used in populations without general supplementation programs. However, the efficacy and safety of individualized iron supplementation, based on ferritin concentrations at the age of 1 week, together with other predictors of ID, needs to be further investigated, preferably in a randomized controlled trial.

Effects of iron supplementation of low-birth-weight infants on cognition and behavior at 7 years: a randomized controlled trial

BackgroundLow-birth-weight infants (LBW) are at an increased risk of iron deficiency that has been associated with impaired neurodevelopment. We hypothesized that iron supplementation of LBW infants improves cognitive scores and reduces behavioral problems until school age.MethodsWe randomized 285 marginally LBW (2,000–2,500 g) infants to receive 0, 1, or 2 mg/kg/day of iron supplements from 6 weeks to 6 months of age. At 7 years of age, 205 participants were assessed regarding cognition using Wechsler Intelligence Scale for Children (WISC-IV) and behavior using the parental questionnaires Child Behavior Checklist (CBCL) and Five to Fifteen (FTF).ResultsThere were no significant differences between the intervention groups in WISC-IV or FTF. However, the CBCL scores for externalizing problems were significantly different, in favor of supplemented children (P=0.045). When combining the supplemented groups, they had significantly lower scores for externalizing behavior compared with placebo (median (interquartile range): 44 [34;51] vs. 48.5 [41;56] P=0.013), and their risk ratio (95% confidence interval) for a total behavioral score above the cutoff for clinical problems was 0.31 (0.09–1.0), P=0.054.ConclusionLower scores of externalizing behavior in supplemented children support our previous findings at 3 years, and suggest that iron supplementation may have long-lasting effects on behavioral functions.