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OBJECTIVES: The objectives were to describe weight loss in a multiethnic population of first-born, predominantly breastfed, term infants and to identify potentially modifiable risk factors for excess weight loss (EWL). METHODS: Data on prenatal breastfeeding intentions, demographic characteristics, labor and delivery interventions and outcomes, breastfeeding behaviors, formula and pacifier use, onset of lactogenesis, and nipple type and pain were collected prospectively. Logistic regression analyses identified independent predictors of EWL (≥10% of birth weight) by using a preplanned theoretical model. RESULTS: EWL occurred for 18% of infants who received no or minimal (≤60 mL total since birth) formula (n = 229), including 19% of exclusively breastfed infants (n = 134) and 16% of infants who received minimal formula (n = 95). In bivariate analyses, EWL was associated (P < .05) with higher maternal age, education, and income levels, hourly intrapartum fluid balance, postpartum edema, delayed lactogenesis (>72 hours), fewer infant stools, and infant birth weight. In multivariate logistic regression analysis, only 2 variables predicted EWL significantly, namely, intrapartum fluid balance (adjusted relative risk for EWL of 3.18 [95% confidence interval [CI]: 1.35-13.29] and 2.80 [95% CI: 1.17-11.68] with net intrapartum fluid balance of >200 and 100-200 mL/hour, respectively, compared with <100 mL/hour) and delayed lactogenesis (adjusted relative risk: 3.35 [95% CI: 1.74-8.10]). CONCLUSIONS: EWL was more common in this population than reported previously and was independently related to intrapartum fluid balance. This suggests that intrapartum fluid administration can cause fetal volume expansion and greater fluid loss after birth, although other mechanisms are possible.

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Research tools that are comparable across ethnic groups are needed in order to understand sociodemographic disparities in breastfeeding rates. The Infant Feeding Intentions (IFI) scale provides a quantitative measure of maternal breastfeeding intentions. IFI score ranges from 0 (no intention to breastfeed) to 16 (very strong intentions to fully breastfeed for 6 months). The objective of this study was to examine intra- and inter-ethnic validity of the IFI scale. The IFI scale was administered to 218 white non-Hispanic, 75 African-American, 80 English-speaking Hispanic, 62 Spanish-speaking Hispanic and 64 Asian expectant primiparae. Participants were asked their planned duration of providing breast milk as the sole source of milk (full breastfeeding). The IFI scale was examined for intra-ethnic internal consistency and construct validity and for inter-ethnic comparability. For all five ethnic categories, principal component analysis separated the scale into the same two factors: intention to initiate breastfeeding and intention to continue full breastfeeding. Across ethnic categories, the range in Cronbach's alpha was 0.70-0.85 for the initiation factor and 0.90-0.93 for the continuation factor. Within each ethnic category, IFI score increased as planned duration of full breastfeeding increased (P < 0.0001 for all). Within the planned duration categories of <1, 1-3, 3-6 and ≥6 months, the median IFI score by ethnic category ranged from (low-high) 5-8, 9-10, 12-14 and 16-16, respectively. The IFI scale provides a valid measure of breastfeeding intentions in diverse populations of English- and Spanish-speaking primiparae, and may be a useful tool when researching disparities in breastfeeding practices.

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BACKGROUND: Delayed onset of lactogenesis (OL) is most common in primiparas and increases the risk of excess neonatal weight loss, formula supplementation, and early weaning. OBJECTIVE: We examined variables associated with delayed OL among first-time mothers who delivered at term and initiated breastfeeding (n = 431). DESIGN: We conducted in-person interviews during pregnancy and at days 0, 3, and 7 postpartum and extracted obstetric and newborn information from medical records. We defined OL as delayed if it occurred after 72 h and used chi-square analysis to examine its association with potential risk factors across 6 dimensions: 1) prenatal characteristics, 2) maternal anthropometric characteristics, 3) labor and delivery experience, 4) newborn characteristics, 5) maternal postpartum factors, and 6) infant feeding variables. We examined independent associations by using multivariable logistic regression analysis. RESULTS: Median OL was 68.9 h postpartum; 44% of mothers experienced delayed OL. We observed significant bivariate associations between delayed OL and variables in all 6 dimensions (P < 0.05). In a multivariate model adjusted for prenatal feeding intentions, independent risk factors for delayed OL were maternal age > or =30 y, body mass index in the overweight or obese range, birth weight >3600 g, absence of nipple discomfort between 0-3 d postpartum, and infant failing to "breastfeed well" > or =2 times in the first 24 h. Postpartum edema was significant in an alternate model excluding body mass index (P < 0.05). CONCLUSIONS: The risk factors for delayed OL are multidimensional. Public health and obstetric and maternity care interventions are needed to address what has become an alarmingly common problem among primiparas.

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OBJECTIVES: Little is known regarding modifiable factors that may explain sociodemographic disparities in breastfeeding rates among women in the United States. Using a mediation model approach, we examined the relative contributions of breastfeeding and formula feeding psychosocial factors in explaining disparities in breastfeeding intentions. METHODS: We interviewed 532 expectant first-time mothers regarding exposure to breastfeeding by others (breastfeeding exposure), comfort with ideas of breastfeeding (breastfeeding comfort) and formula feeding (formula feeding comfort), and breastfeeding self-efficacy. We used logistic regression to evaluate the independent and mediating effects of these variables on strength of intention to fully breastfeed for 6 months (breastfeeding intention). RESULTS: The ethnic distribution of the sample was 41% white, non-Hispanic; 27% Hispanic; 14% African-American; 12% Asian; and 6% mixed or other ethnicity. In the overall sample, formula feeding comfort, breastfeeding comfort, and breastfeeding self-efficacy all independently predicted breastfeeding intention (p < 0.0001), but formula feeding comfort had the largest effect: adjusted odds of stronger breastfeeding intention increased threefold for each 1-level decrease (among four levels) in formula feeding comfort. The unadjusted odds (95% confidence interval) of stronger breastfeeding intention were 0.37 (0.24-0.58) for African-American versus non-African-American women; African-American women had higher formula feeding comfort (2.08 [1.32-3.29]) but similar breastfeeding comfort, breastfeeding self-efficacy, and breastfeeding exposure. Formula feeding comfort mediated 37% of the disparity in breastfeeding intentions between African-American and non-African-American women. CONCLUSIONS: Formula feeding comfort strongly predicted and substantially mediated ethnic disparity in breastfeeding intention. These results suggest that research and public health efforts aimed at increasing exclusive breastfeeding rates should include consideration of formula feeding attitudes.

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BACKGROUND: Iron deficiency (ID) can occur among exclusively breastfed infants before 6 mo of age. OBJECTIVE: The objective was to determine which subgroups of fully breastfed infants are at highest risk of ID. DESIGN: We assessed the prevalence of ID (ferritin < 12 mug/L) and iron deficiency anemia (IDA; ferritin < 12 mug/L and hemoglobin < 105 g/L) and risk factors associated with ID and IDA at 6 mo among 404 fully breastfed infants with a birth weight >2500 g from 6 studies in Ghana, Honduras, Mexico, and Sweden. Infants with an elevated C-reactive protein concentration (8%) were excluded. RESULTS: The percentages of infants with ID were 6% in Sweden, 17% in Mexico, 13-25% in Honduras, and 12-37% in Ghana. The percentages with IDA were 2% in Sweden, 4% in Mexico, 5-11% in Honduras, and 8-16% in Ghana. With data pooled, the key predictors of ID (20%) were male sex [adjusted odds ratio (AOR): 4.6; 95% CI: 2.5, 8.5] and birth weight 2500-2999 g (AOR: 2.4; 95% CI: 1.4, 4.3). The predictors of IDA (8%) were male sex (AOR: 7.6; 95% CI: 2.5, 23.0), birth weight of 2500-2999 g (AOR: 3.4; 1.5, 7.5), and weight gain above the median since birth (AOR: 3.4; 95% CI: 1.3, 8.6). The combination of birth weight 2500-2999 g or male sex had a sensitivity of 91% for identifying ID and of 97% for identifying IDA. CONCLUSIONS: Among fully breastfed infants with a birth weight >2500 g, IDA is uncommon before 6 mo, but male infants and those with a birth weight of 2500-2999 g are at higher risk of ID and IDA.

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OBJECTIVE: Formula-fed infants gain weight faster than breastfed infants. This study evaluated whether encouraging formula-feeding caregivers to be sensitive to infant satiety cues would alter feeding practices and reduce infant formula intake and weight gain. DESIGN: Double-blind, randomized educational intervention, with intake and growth measured before (at 1 to 2 months) and after (4 to 5 months) the intervention. SETTING: Women, Infants, and Children (WIC) clinics in Sacramento, California. PARTICIPANTS: 836 caregivers of young infants were screened; 214 were eligible, and 104 agreed to participate. INTERVENTION: Intervention subjects received education promoting awareness of satiety cues and discouraging bottles containing more than 6 ounces before 4 months of age; intervention and control groups received education regarding introduction and feeding of solid food after 4 months of age. MAIN OUTCOME MEASURES: Formula intake (mL/24 hours) and weight gain (g/week). ANALYSIS: Differences between groups evaluated using 2-way analysis of covariance (ANCOVA). RESULTS: Sixty-one subjects completed baseline records, 44 attended class, and 38 completed the study. Despite a positive response to the educational intervention, there was no change in bottle-feeding behaviors (formula intake at 4 to 5 months was more than 1100 mL/day in both groups). Infant growth in the intervention group was greater than in the control group (P < .01), contrary to the hypothesis. CONCLUSIONS AND IMPLICATIONS: The intervention improved knowledge of the key messages, but further research is needed to understand barriers to modifying bottle-feeding behaviors.

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BACKGROUND: Efforts to develop global programs for the control of iron deficiency require simple, low-cost, and accurate indicators of iron status. OBJECTIVE: We aimed to compare estimates of body iron (BI) stores, as calculated from either plasma ferritin concentration alone (BI-ferritin) or the ratio of plasma transferrin receptor (TfR) to ferritin (BI-TfR/ferritin). DESIGN: Data were analyzed from 4 previously completed, randomized intervention trials that enrolled infants, schoolchildren, or pregnant women (total n = 1189, after excluding subjects with elevated C-reactive protein). RESULTS: The correlation coefficients between BI-ferritin and BI-TfR/ferritin were >0.95 for all studies. The kappa index ranged from 0.5 to 1.0. All of the sensitivities of BI-ferritin for identifying persons with low iron stores (defined as BI-TfR/ferritin < 0 mg/kg body wt) were >0.90. All of the specificities were >0.90 except the study of pregnant women (specificity = 0.66). The effect sizes of iron intervention trials were significantly greater for change in iron reserves estimated by BI-TfR/ferritin than by BI-ferritin in 2 studies with larger effect sizes (1.11 compared with 1.00 and 1.56 compared with 1.44, respectively; P < 0.05) and 1 study with medium effect size (0.70 compared with 0.57; P < 0.05). However, there were no significant differences between estimates of these effect sizes for 1 study with a medium effect size and 1 study with a smaller effect size (0.78 compared with 0.83 and 0.37 compared with 0.35, respectively; P > 0.2). CONCLUSION: Plasma ferritin concentration alone provides a good approximation of total BI reserves, as estimated by BI-TfR/ferritin, on the basis of high correlation, sensitivity, and specificity among nonpregnant persons with unelevated C-reactive protein.

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Using data from 242 exclusively breastfeeding mother-infant pairs, newborn elimination patterns were analyzed. Sensitivity (Se) and Specificity (Sp) of day 4 (72-96 hours) wet and soiled output, in addition to the timing of onset of lactation, in identifying cases of breastfeeding inadequacy (defined as neonatal weight loss >or= 10% of birth weight) were examined. The usefulness of 2 measures in parallel was also explored. Median number of diapers (wet, soiled) on days 1, 4, and 7, respectively, was 2, 3; 5, 4; and 7, 6. The most efficient day 4 predictor of breastfeeding inadequacy was soiled diaper output or= 72 hours); Se = .86 (95% confidence interval, .73-.99) and Sp = .59 (.55-.63). Fewer than 4 soiled diapers on day 4 when used in conjunction with delayed onset of lactation may be indicative of breastfeeding inadequacy, but low specificity will result in many false positives.

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This review addresses the question of whether a short birth interval is associated with adverse nutritional outcomes for the mother or the child. Indices of anthropometric status (maternal weight or body mass index; child growth) and micronutrient status (e.g. iron or vitamin A) were included as outcomes. A computerized search of all relevant papers published since 1966 was completed, and the 'snowball' method was used to identify additional relevant published or unpublished papers. In total, 57 papers were found to contain data regarding the relationship between birth spacing and nutritional outcomes (35 for child nutrition, 11 for maternal anthropometric status, and 11 for maternal anaemia or micronutrient status). Of these, 23 papers were excluded from further consideration because they did not include any multivariate analysis, leaving 34 papers that met the criteria for the review (22 for child nutrition, eight for maternal anthropometric status, and four for maternal anaemia or micronutrient status). The studies on child nutrition outcomes indicate that a longer birth interval is associated with a lower risk of malnutrition in some populations, but not all. In those countries in which the relationship was significant, the reduction in stunting associated with a previous birth interval >or=36 months ranged from approximately 10% to 50%. Some of this reduction may be due to residual confounding, i.e. to factors not included in the analysis (such as breastfeeding and maternal height). The studies on maternal anthropometric outcomes yielded mixed results. Because the nutritional burden on the mother between pregnancies depends on the extent of breastfeeding, the interpregnancy interval is not the best measure of whether the mother has had a chance to recover from the pregnancy, in terms of repleting her nutritional status. Therefore, some studies examined the 'recuperative interval' (duration of the non-pregnant, non-lactating interval) instead. Taken as a whole, the studies do not provide clear evidence of a link between interpregnancy or recuperative interval and maternal anthropometric status. This may be due, in part, to changes in the hormonal regulation of nutrient partitioning between the mother and the fetus when a mother is malnourished. Only four papers were identified that related to micronutrient status, three of which examined maternal anaemia. One study showed an increased risk for maternal anaemia when the interpregnancy interval was <6 months, but the analysis did not control for iron supplementation during pregnancy. The other two studies did not show a significant association between interpregnancy interval and maternal anaemia. One study of micronutrient status indicated no significant relationship between interpregnancy interval and maternal serum zinc, copper, magnesium, ferritin, folate or thyroid-stimulating hormone. Important methodological limitations were apparent in most of the studies. Thus, further research with more comprehensive control of potentially confounding variables is needed.

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AIM: To investigate whether iron supplements compromise copper status in infants. METHODS: 214 healthy, term, breastfed Swedish and Honduran infants were randomized to (1) iron supplements (1 mg/kg/d) from 4-9 mo of age, (2) iron supplements from 6-9 mo, or (3) placebo. Blood samples were obtained at 4, 6, and 9 mo and analyzed for plasma copper (p-Cu) and, at 9 mo, for copper/zinc-dependent superoxide dismutase (CuZn-SOD) activity. RESULTS: P-Cu increased with infant age. At 9 mo, Honduran infants had significantly higher p-Cu (1.40+/-0.29 vs 1.09+/-0.22 mg/l, p<0.001) and CuZn-SOD activity (1.09+/-0.29 vs 0.93+/-0.21 U/mg Hb, p<0.001) than Swedish infants. Infants receiving iron supplements from 4-9 mo had significantly lower CuZn-SOD at 9 mo of age (0.95+/-0.27 vs 1.08+/-0.24 U/mg Hb, p=0.023) than those receiving placebo. CONCLUSION: There is a physiologic increase in p-Cu during the first 9 mo of life. Differences in copper status between Swedish and Honduran infants may be due to genetic or nutritional differences. Iron supplementation decreases CuZn-SOD activity, probably due to a negative effect on copper status. Possible clinical implications remain to be elucidated.

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Several studies have documented that length gain often lags behind weight gain during infancy and early childhood, suggesting that linear growth is partly regulated by initial body mass or fatness. To investigate this hypothesis, we analysed data from four longitudinal studies on growth of infants in the first 12 months: (1) U.S. breast-fed and formula-fed infants (n = 89); (2) breast-fed infants in Ghana (n = 190); (3) normal birthweight, breast-fed infants in Honduras (n = 108); and (4) term, low-birthweight breast-fed infants in Honduras (n = 119). The dependent variable was length gain during each 3-month interval (1- 4, 2-5, 3-6, 4-7, 5-8, 6-9, 7-10, 8-11 and 9-12 months). Three main independent variables were examined: initial weight-for-length z-score (W/L), weight change during the prior 3 months, and initial skinfold thickness. Controlling for maternal height, infant sex, and initial length-for-age z-score, length gain was positively correlated with initial W/L and prior weight change during all age intervals and with initial skinfold thickness at 3 and 4 months (r = 0.15-0.36; P < 0.01). There was no evidence of a threshold effect. These associations were evident in all four populations, in both boys and girls, and in breast-fed and formula-fed infants. The consistency of this relationship across studies supports the hypothesis that linear growth is partly regulated by initial body mass or fatness in infants.

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The World Health Organization (WHO) Multicentre Growth Reference Study (MRGS) North American site was Davis, California. For the longitudinal cohort (0-24 months), 208 infants were enrolled between January and December 1999 from five area hospitals at which nearly all Davis women give birth. The target sample size was lower in the United States than in the other sites, because recruitment in the United States was restricted to mothers who were willing to exclusively breastfeed for at least 4 months and continue breastfeeding for at least 12 months. For the cross-sectional component, a mixed-longitudinal design was used, which required approximately 500 subjects. The subjects were recruited by going door-to-door, with the sampling scheme based on the distribution of the subjects of the longitudinal study within the city. The cross-sectional sample was recruited between January and July 2001. Major challenges during implementation were maintaining daily communication with hospital personnel and scheduling home visits.

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There is little information on the risk of micronutrient deficiencies during the period of exclusive breast-feeding. We evaluated this among term, low-birthweight (LBW; 1500-2500 g) infants in Honduras. Mother-infant pairs were recruited in the hospital and assisted with exclusive breast-feeding during the first 4 mo. At 4 mo, infants were randomly assigned to either continue exclusive breast-feeding to 6 mo (EBF; n = 59) or be given iron-fortified complementary foods (rice, chicken, fruits, and vegetables) from 4 to 6 mo while continuing to breast-feed (SF, n = 60). Blood samples were collected at 2, 4, and 6 mo and analyzed for hemoglobin (Hb), hematocrit, plasma ferritin, % transferrin saturation, vitamin A, vitamin B-12, folate, zinc, and erythrocyte folate. Infants with Hb < 100 g/L at 2 or 4 mo were given medicinal iron supplements for 2 mo; the proportion administered iron drops did not differ significantly between groups. There was no significant effect of complementary foods on indices of vitamin A, B-12, folate, or zinc status. Among infants not given medicinal iron at 4-6 mo, iron status was higher in the SF group than the EBF group. In those given medicinal iron at 4-6 mo, iron status was higher in the EBF group, suggesting that complementary foods interfered with iron utilization. About half of the infants were anemic by 2 mo, before the age when complementary foods would be recommended. This supports the recommendation that LBW infants should receive iron supplementation in early infancy. Given that infants given iron supplements did not benefit from complementary foods at 4-6 mo, we conclude that exclusive breast-feeding for 6 mo (with iron supplementation) can be recommended for term, LBW infants.

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BACKGROUND: Little is known about the regulation of iron, zinc, and copper in breast milk and the transport of these minerals across the mammary gland epithelium. OBJECTIVE: The objective was to study associations between breast-milk concentrations of iron, zinc, and copper and maternal mineral status. DESIGN: Milk samples from 191 Swedish and Honduran mothers were collected at 9 mo postpartum. Iron, zinc, and copper concentrations were measured by atomic absorption spectrometry. Blood samples from mothers were analyzed for plasma zinc and copper and 4 indexes of iron status: hemoglobin, plasma ferritin, soluble transferrin receptors, and zinc protoporphyrin. Complementary food energy (CFE) intake was used as an inverse proxy for breast-milk intake. RESULTS: Mean (+/-SD) breast-milk concentrations of iron were lower in the Honduran than in the Swedish mothers (0.21 +/- 0.25 compared with 0.29 +/- 0.21 mg/L; P < 0.001), and mean breast-milk concentrations of zinc and copper were higher in the Honduran than in the Swedish mothers [0.70 +/- 0.18 compared with 0.46 +/- 0.26 mg/L (P < 0.001) and 0.16 +/- 0.21 compared with 0.12 +/- 0.22 mg/L (P = 0.001), respectively]. Milk iron was positively correlated with CFE intake (r = 0.24, P = 0.001) but was not significantly correlated with any iron-status variable. Milk zinc was negatively correlated with CFE intake (r = -0.24, P = 0.001) but was not significantly correlated with maternal plasma zinc. Milk copper was not significantly correlated with CFE intake or maternal plasma copper. CONCLUSIONS: Milk iron, zinc, and copper concentrations at 9 mo postpartum are not associated with maternal mineral status, which suggests active transport mechanisms in the mammary gland for all 3 minerals. Milk iron concentrations increase and milk zinc concentrations decrease during weaning [corrected]

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OBJECTIVE: Some mothers have difficulty initiating lactation even when highly motivated to breastfeed. The purpose of this study was to determine the incidence of and risk factors for suboptimal infant breastfeeding behavior (SIBB), delayed onset of lactation, and excess neonatal weight loss among mother-infant pairs in a population with high educational levels and motivation to breastfeed. METHODS: All mothers residing in Davis, California, who gave birth to a healthy, single, term infant at 1 of 5 area hospitals during the 10-month recruitment period in 1999 were invited to participate if they were willing to attempt to breastfeed exclusively for at least 1 month. Lactation guidance was provided and data were collected in the hospital (day 0) and on days 3, 5, 7, and 14. Infant breastfeeding behavior was evaluated by trained lactation consultants using the Infant Breastfeeding Assessment Tool. Onset of lactation was defined based on maternal report of changes in breast fullness. Infant weight loss was considered excessive if it was >or=10% of birth weight by day 3. RESULTS: Of the 328 eligible mothers, 280 (85%) participated in the study. The prevalence of SIBB was 49% on day 0, 22% on day 3, and 14% on day 7. SIBB was significantly associated with primiparity (days 0 and 3), cesarean section (in multiparas, day 0), flat or inverted nipples, infant status at birth (days 0 and 3), use of nonbreast milk fluids in the first 48 hours (days 3 and 7), pacifier use (day 3), stage II labor >1 hour (day 7), maternal body mass index >27 kg/m(2) (day 7) and birth weight <3600 g (day 7). Delayed onset of lactation (>72 hours) occurred in 22% of women and was associated with primiparity, cesarean section, stage II labor >1 hour, maternal body mass index >27 kg/m(2), flat or inverted nipples, and birth weight >3600 g (in primiparas). Excess weight loss occurred in 12% of infants and was associated with primiparity, long duration of labor, use of labor medications (in multiparas), and infant status at birth. The risk of excess infant weight loss was 7.1 times greater if the mother had delayed onset of lactation, and 2.6 times greater if the infant had SIBB on day 0. CONCLUSIONS: Early lactation success is strongly influenced by parity, but may also be affected by potentially modifiable factors such as delivery mode, duration of labor, labor medications, use of nonbreast milk fluids and/or pacifiers, and maternal overweight. All breastfeeding mother-infant pairs should be evaluated at 72 to 96 hours' postpartum.

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Diagnostic criteria for iron deficiency (ID) and iron deficiency anemia (IDA) in infants are poorly defined. Our aim was to establish appropriate cut-off values for hemoglobin (Hb), plasma ferritin, erythrocyte mean cell volume (MCV), zinc protoporphyrin (ZPP) and soluble transferrin receptors (TfR) in infancy. Exclusively breast-fed infants (n = 263) in Honduras and Sweden were randomly assigned to receive iron supplementation or placebo, and blood samples were obtained at 4, 6 and 9 mo of age. Reference ranges were determined using three different approaches for defining iron-replete infants. The usefulness of several variables for predicting the Hb response to iron was evaluated. We found the following 2 SD cut-off values in iron-replete infants: Hb <105 g/L at 4-6 mo and <100 g/L at 9 mo; ZPP >75 micro mol/mol heme at 4-6 mo and >90 micro mol/mol heme at 9 mo; ferritin <20 micro g/L at 4 mo, <9 micro g/L at 6 mo and <5 micro g/L at 9 mo; and TfR >11 mg/L at 4-9 mo. The Hb response to iron was not a useful definition of IDA at 4 mo of age. Hb, MCV and ZPP at 6 mo as well as growth variables predicted the Hb response at 6-9 mo, but ferritin and TfR at 6 mo did not. We conclude that there is need for a reevaluation of the definitions of ID and IDA in infants.

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Iron supplements are often prescribed during infancy but their benefits and risks have not been well documented. We examined whether iron supplements affect growth or morbidity of breast-fed infants. Full-term infants in Sweden (n = 101) and Honduras (n = 131) were randomly assigned to three groups at 4 mo of age: 1) placebo from 4 to 9 mo; 2) placebo from 4 to 6 mo and iron supplements [1 mg/(kg. d)] from 6 to 9 mo; or 3) iron supplements from 4 to 9 mo. All infants were exclusively or nearly exclusively breast-fed to 6 mo and continued to be breast-fed to at least 9 mo. Growth was measured monthly and morbidity data were collected every 2 wk. Among the Swedish infants, gains in length and head circumference were significantly lower in those who received iron than in those given placebo from 4 to 9 mo. The same effect on length was seen in Honduras, but only at 4-6 mo among those with initial hemoglobin (Hb) > or =110 g/L. There was no significant main effect of iron supplementation on morbidity, nor any significant interaction between iron supplementation and site, but for diarrhea (with both sites combined), there was an interaction between iron supplementation and initial Hb. Among infants with Hb < 110 g/L at 4 mo, diarrhea was less common among those given iron than in those given placebo from 4-9 mo, whereas the opposite was true among those with Hb > or = 110 g/L (P < 0.05). We conclude that routine iron supplementation of breast-fed infants may benefit those with low Hb but may present risks for those with normal Hb.

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BACKGROUND: It is commonly assumed that there is no difference in iron status between male and female infants, despite a lack of studies addressing this question. OBJECTIVE: To study sex differences in different measures of iron status in infants. METHODS: At 4 months of age, 263 term, breastfed infants (121 Swedish and 142 Honduran) were randomized to receive iron supplements or placebo until 9 months of age. Blood samples at 4, 6, and 9 months of age were analyzed for hemoglobin (Hb), mean cell volume (MCV), zinc protoporphyrin (ZPP), plasma ferritin, and transferrin receptors (TfR). RESULTS: At 4, 6, and 9 months, boys had significantly lower Hb, MCV, and ferritin and higher ZPP and TfR than girls. At 9 months, boys had a 10-fold higher risk of being classified as having iron deficiency anemia. The differences at 9 months in MCV (71.6 vs 75.1 fL) and ZPP (59 vs 49 micro mol/mol heme) remained significant after controlling for iron supplementation, site, growth variables, and other possible confounders. For ferritin, there was a remaining sex difference at 9 months among Swedish (29 vs 53 micro g/L) but not Honduran infants. For Hb and TfR, sex differences at 9 months were larger in unsupplemented infants, especially in those with a birth weight of <3500 g. CONCLUSIONS: There are substantial sex differences in Hb and other indicators of iron status during infancy. Some of these may be genetically determined, whereas others seem to reflect an increased incidence of true iron deficiency in boys.

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