Risk of Infant Anemia Is Associated with Exclusive Breast-Feeding and Maternal Anemia in a Mexican Cohort1,2

he WHO recommends exclusive breast-feeding (EBF) for the first 6 mo of life to decrease the burden of infectious disease. However, some are concerned about the effect of EBF >6 mo on iron status of children in developing countries in which anemia is prevalent. This study examines the risk of anemia in relation to the duration of EBF and maternal anemia in a birth cohort studied between March 1998 and April 2003. All infant birth weights were ≥2.2 kg. All mothers received home-based peer counseling to promote EBF. Infant feeding data were collected weekly. Nurses measured hemoglobin (Hb) values every 3 mo. Hb was measured in 183 infants at 9 mo of age. Anemia at 9 mo was defined as a Hb value <100 g/L. EBF was defined by WHO criteria and ranged in duration from 0 to 31 wk. At 9 mo, Hb (mean ± SEM) was 114 ± 0.9 g/L; 23 children (12.5%) had Hb levels <100 g/L. EBF >6 mo, but not EBF 4-6 mo, was associated with increased risk of infant anemia compared with EBF <4 mo (odds ratio = 18.4, 95% CI = 1.9, 174.0). Maternal anemia was independently (P = 0.03) associated with a 3-fold increased risk of infant anemia. These associations were not explained by confounding with other maternal or infant factors. By linear regression, a lower infant Hb at 9 mo was associated with increased EBF duration among mothers who had a history of anemia (β = -0.07, P = 0.003), but not among mothers with no history of anemia. Infants who are exclusively breast-fed for >6 mo in developing countries may be at increased risk of anemia, especially among mothers with a poor iron status; greater attention to this issue is warranted. J. Nutr. 136: 452-458, 2006.
KEYWORDS: * infant anemia * maternal anemia * exclusive breast-feeding
Iron deficiency is the most common nutrient deficiency and cause of anemia in childhood (1). Although prevalence rates of anemia among healthy term infants 6-18 mo of age are reported to be as low as 2-6% in Western Europe and the United States (2-4), iron deficiency anemia was shown to affect more than half of the children in some developing countries (5). In Mexico, 27% of children <5 y old are anemic (6,7). A national probabilistic survey of Mexican children reported the prevalence of anemia to be 13% at 6-11 mo of age, but as high as 49% among children 12-24 mo old (8). Varying degrees of anemia in young children are associated with poor cognitive outcomes (9-13). Anemia diagnosed at 8 or 9 mo of age has been associated with significantly lower achievement scores in 2nd grade children (14) and impaired motor development at 18 mo (15). Iron deficiency anemia was also shown to be significantly associated with mental retardation (16), decreased activity, increased wariness or hesitance, and remaining in close proximity with caregivers (17).
Although the iron in human milk is highly bioavailable (~50% absorption) (18-21), the iron content is at its highest in early transitional milk and decreases steadily over the course of lactation (22). In general, infants born at term and with an adequate birth weight have sufficient iron stores for the first 4-6 mo of life. However, evidence suggests that infants with adequate birth weight born to anemic mothers have low iron stores and are more likely to develop anemia (23-26). By 6 mo, complementary foods are required to provide the iron and other nutrients necessary for infant development (27,28). A randomized trial conducted in Honduras concluded that at 6 mo, the risk of iron deficiency is low among exclusively breast-fed (EBF)4 infants with birth weights >3000 g (29), although infants who were exclusively breast-fed to 6 mo had significantly lower hemoglobin (Hb) levels (104 g/L) than infants who had received iron-fortified complementary foods (109 g/L). Simple iron-fortified complementary feedings before age 6 mo, however, were not sufficient to prevent anemia among the study infants. A second trial, conducted on micronutrient deficiencies during the period of EBF among term, low-birth-weight infants (1500-2500 g) in Honduras, found that infants who received iron supplements did not benefit from complementary foods at 4-6 mo. Dewey et al. (30) thus recommended that term, low-birth-weight infants be exclusively breast-fed for 6 mo with iron supplementation.
In 2001, the WHO issued the recommendation for EBF for the 1st 6 mo of life (31). EBF reduces infant mortality due to common childhood illnesses such as diarrhea or pneumonia, and is associated with shorter recovery time during illness (32). There is some concern, however, about the potential for increased risk of anemia associated with longer duration of EBF in populations with a high prevalence of maternal and infant anemia. Between 1998 and 2003, we conducted a cohort study of breast-feeding mother-infant pairs in Mexico City. Following the protocol of our previous community-based efficacy trial of breast-feeding support (33), we provided peer breast-feeding counseling to all study mothers in this cohort with the goal of achieving the WHO recommendations for EBF for 6 mo. This counseling was associated with a median duration of 3-4 mo exclusive breast-feeding, much longer than previously seen in this population. To determine the effect of this new pattern, we examined the association between EBF, maternal anemia, and other factors in relation to the prevalence of anemia among infants in our cohort.
SUBJECTS AND METHODS
Population. From March 1998 to April 2003, .306 infants in San Pedro Martir, Mexico City, were enrolled and monitored prospectively from birth to 2 y of age as part of an ongoing NIH-funded study of human milk immune protection against diarrheal diseases. The geographic and socioeconomic characteristics of this community were described previously (34,35). All enrolled infants were healthy, full-term infants born without congenital defects, whose mothers agreed to breast-feed. Potential subjects were excluded if consent was refused, the mother did not plan to breast-feed, or the infant was low birth weight, premature, or had a congenital malformation that might affect their ability to breast-feed. Mother-infant pairs received 3 home-based peer counseling visits to support exclusive breast-feeding (33), once in the 3rd trimester, and twice in the first few weeks postpartum. In addition, mothers were visited in their homes weekly by a trained study worker to collect standardized data on infant feedings and occurrence of diarrhea in the past 24 h. Weight and length of the infants were recorded monthly. This study was approved by the institutional review boards of the Institute Nacional de Ciencas Medicas y Nutricion and Cincinnati Children's Hospital Medical Center. Written informed consent was obtained from the parents of study children.

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Risk of Infant Anemia Is Associated with Exclusive Breast-Feeding and Maternal Anemia in a Mexican Cohort1,2

he WHO recommends exclusive breast-feeding (EBF) for the first 6 mo of life to decrease the burden of infectious disease. However, some are concerned about the effect of EBF >6 mo on iron status of children in developing countries in which anemia is prevalent. This study examines the risk of anemia in relation to the duration of EBF and maternal anemia in a birth cohort studied between March 1998 and April 2003. All infant birth weights were ≥2.2 kg. All mothers received home-based peer counseling to promote EBF. Infant feeding data were collected weekly. Nurses measured hemoglobin (Hb) values every 3 mo. Hb was measured in 183 infants at 9 mo of age. Anemia at 9 mo was defined as a Hb value <100 g/L. EBF was defined by WHO criteria and ranged in duration from 0 to 31 wk. At 9 mo, Hb (mean ± SEM) was 114 ± 0.9 g/L; 23 children (12.5%) had Hb levels <100 g/L. EBF >6 mo, but not EBF 4-6 mo, was associated with increased risk of infant anemia compared with EBF <4 mo (odds ratio = 18.4, 95% CI = 1.9, 174.0). Maternal anemia was independently (P = 0.03) associated with a 3-fold increased risk of infant anemia. These associations were not explained by confounding with other maternal or infant factors. By linear regression, a lower infant Hb at 9 mo was associated with increased EBF duration among mothers who had a history of anemia (β = -0.07, P = 0.003), but not among mothers with no history of anemia. Infants who are exclusively breast-fed for >6 mo in developing countries may be at increased risk of anemia, especially among mothers with a poor iron status; greater attention to this issue is warranted. J. Nutr. 136: 452-458, 2006.
KEYWORDS: * infant anemia * maternal anemia * exclusive breast-feeding
Iron deficiency is the most common nutrient deficiency and cause of anemia in childhood (1). Although prevalence rates of anemia among healthy term infants 6-18 mo of age are reported to be as low as 2-6% in Western Europe and the United States (2-4), iron deficiency anemia was shown to affect more than half of the children in some developing countries (5). In Mexico, 27% of children <5 y old are anemic (6,7). A national probabilistic survey of Mexican children reported the prevalence of anemia to be 13% at 6-11 mo of age, but as high as 49% among children 12-24 mo old (8). Varying degrees of anemia in young children are associated with poor cognitive outcomes (9-13). Anemia diagnosed at 8 or 9 mo of age has been associated with significantly lower achievement scores in 2nd grade children (14) and impaired motor development at 18 mo (15). Iron deficiency anemia was also shown to be significantly associated with mental retardation (16), decreased activity, increased wariness or hesitance, and remaining in close proximity with caregivers (17).
Although the iron in human milk is highly bioavailable (~50% absorption) (18-21), the iron content is at its highest in early transitional milk and decreases steadily over the course of lactation (22). In general, infants born at term and with an adequate birth weight have sufficient iron stores for the first 4-6 mo of life. However, evidence suggests that infants with adequate birth weight born to anemic mothers have low iron stores and are more likely to develop anemia (23-26). By 6 mo, complementary foods are required to provide the iron and other nutrients necessary for infant development (27,28). A randomized trial conducted in Honduras concluded that at 6 mo, the risk of iron deficiency is low among exclusively breast-fed (EBF)4 infants with birth weights >3000 g (29), although infants who were exclusively breast-fed to 6 mo had significantly lower hemoglobin (Hb) levels (104 g/L) than infants who had received iron-fortified complementary foods (109 g/L). Simple iron-fortified complementary feedings before age 6 mo, however, were not sufficient to prevent anemia among the study infants. A second trial, conducted on micronutrient deficiencies during the period of EBF among term, low-birth-weight infants (1500-2500 g) in Honduras, found that infants who received iron supplements did not benefit from complementary foods at 4-6 mo. Dewey et al. (30) thus recommended that term, low-birth-weight infants be exclusively breast-fed for 6 mo with iron supplementation.
In 2001, the WHO issued the recommendation for EBF for the 1st 6 mo of life (31). EBF reduces infant mortality due to common childhood illnesses such as diarrhea or pneumonia, and is associated with shorter recovery time during illness (32). There is some concern, however, about the potential for increased risk of anemia associated with longer duration of EBF in populations with a high prevalence of maternal and infant anemia. Between 1998 and 2003, we conducted a cohort study of breast-feeding mother-infant pairs in Mexico City. Following the protocol of our previous community-based efficacy trial of breast-feeding support (33), we provided peer breast-feeding counseling to all study mothers in this cohort with the goal of achieving the WHO recommendations for EBF for 6 mo. This counseling was associated with a median duration of 3-4 mo exclusive breast-feeding, much longer than previously seen in this population. To determine the effect of this new pattern, we examined the association between EBF, maternal anemia, and other factors in relation to the prevalence of anemia among infants in our cohort.
SUBJECTS AND METHODS
Population. From March 1998 to April 2003, .306 infants in San Pedro Martir, Mexico City, were enrolled and monitored prospectively from birth to 2 y of age as part of an ongoing NIH-funded study of human milk immune protection against diarrheal diseases. The geographic and socioeconomic characteristics of this community were described previously (34,35). All enrolled infants were healthy, full-term infants born without congenital defects, whose mothers agreed to breast-feed. Potential subjects were excluded if consent was refused, the mother did not plan to breast-feed, or the infant was low birth weight, premature, or had a congenital malformation that might affect their ability to breast-feed. Mother-infant pairs received 3 home-based peer counseling visits to support exclusive breast-feeding (33), once in the 3rd trimester, and twice in the first few weeks postpartum. In addition, mothers were visited in their homes weekly by a trained study worker to collect standardized data on infant feedings and occurrence of diarrhea in the past 24 h. Weight and length of the infants were recorded monthly. This study was approved by the institutional review boards of the Institute Nacional de Ciencas Medicas y Nutricion and Cincinnati Children's Hospital Medical Center. Written informed consent was obtained from the parents of study children.

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