Early-Life Exposure to Air Pollution and Childhood Asthma Cumulative Incidence in the ECHO CREW Consortium.

Importance: Exposure to outdoor air pollution contributes to childhood asthma development, but many studies lack the geographic, racial and ethnic, and socioeconomic diversity to evaluate susceptibility by individual-level and community-level contextual factors. Objective: To examine early life exposure to fine particulate matter (PM2.5) and nitrogen oxide (NO2) air pollution and asthma risk by early and middle childhood, and whether individual and community-level characteristics modify associations between air pollution exposure and asthma. Design, Setting, and Participants: This cohort study included children enrolled in cohorts participating in the Children's Respiratory and Environmental Workgroup consortium. The birth cohorts were located throughout the US, recruited between 1987 and 2007, and followed up through age 11 years. The survival analysis was adjusted for mother's education, parental asthma, smoking during pregnancy, child's race and ethnicity, sex, neighborhood characteristics, and cohort. Statistical analysis was performed from February 2022 to December 2023. Exposure: Early-life exposures to PM2.5 and NO2 according to participants' birth address. Main Outcomes and Measures: Caregiver report of physician-diagnosed asthma through early (age 4 years) and middle (age 11 years) childhood. Results: Among 5279 children included, 1659 (31.4%) were Black, 835 (15.8%) were Hispanic, 2555 (48.4%) where White, and 229 (4.3%) were other race or ethnicity; 2721 (51.5%) were male and 2596 (49.2%) were female; 1305 children (24.7%) had asthma by 11 years of age and 954 (18.1%) had asthma by 4 years of age. Mean values of pollutants over the first 3 years of life were associated with asthma incidence. A 1 IQR increase in NO2 (6.1 µg/m3) was associated with increased asthma incidence among children younger than 5 years (HR, 1.25 [95% CI, 1.03-1.52]) and children younger than 11 years (HR, 1.22 [95% CI, 1.04-1.44]). A 1 IQR increase in PM2.5 (3.4 µg/m3) was associated with increased asthma incidence among children younger than 5 years (HR, 1.31 [95% CI, 1.04-1.66]) and children younger than 11 years (OR, 1.23 [95% CI, 1.01-1.50]). Associations of PM2.5 or NO2 with asthma were increased when mothers had less than a high school diploma, among Black children, in communities with fewer child opportunities, and in census tracts with higher percentage Black population and population density; for example, there was a significantly higher association between PM2.5 and asthma incidence by younger than 5 years of age in Black children (HR, 1.60 [95% CI, 1.15-2.22]) compared with White children (HR, 1.17 [95% CI, 0.90-1.52]). Conclusions and Relevance: In this cohort study, early life air pollution was associated with increased asthma incidence by early and middle childhood, with higher risk among minoritized families living in urban communities characterized by fewer opportunities and resources and multiple environmental coexposures. Reducing asthma risk in the US requires air pollution regulation and reduction combined with greater environmental, educational, and health equity at the community level.

Multi-omic association study identifies DNA methylation-mediated genotype and smoking exposure effects on lung function in children living in urban settings.

Impaired lung function in early life is associated with the subsequent development of chronic respiratory disease. Most genetic associations with lung function have been identified in adults of European descent and therefore may not represent those most relevant to pediatric populations and populations of different ancestries. In this study, we performed genome-wide association analyses of lung function in a multiethnic cohort of children (n = 1,035) living in low-income urban neighborhoods. We identified one novel locus at the TDRD9 gene in chromosome 14q32.33 associated with percent predicted forced expiratory volume in one second (FEV1) (p = 2.4x10-9; ßz = -0.31, 95% CI = -0.41- -0.21). Mendelian randomization and mediation analyses revealed that this genetic effect on FEV1 was partially mediated by DNA methylation levels at this locus in airway epithelial cells, which were also associated with environmental tobacco smoke exposure (p = 0.015). Promoter-enhancer interactions in airway epithelial cells revealed chromatin interaction loops between FEV1-associated variants in TDRD9 and the promoter region of the PPP1R13B gene, a stimulator of p53-mediated apoptosis. Expression of PPP1R13B in airway epithelial cells was significantly associated the FEV1 risk alleles (p = 1.3x10-5; ß = 0.12, 95% CI = 0.06-0.17). These combined results highlight a potential novel mechanism for reduced lung function in urban youth resulting from both genetics and smoking exposure.

Cockroach allergen component analysis of children with or without asthma and rhinitis in an inner-city birth cohort.

BACKGROUND: Cockroach is one of the most important sources of indoor allergens and can lead to IgE sensitization and development of rhinitis and asthma. OBJECTIVE: We sought to perform a cockroach allergen component analysis to determine the allergens and antibody levels and patterns of sensitization associated with asthma and rhinitis. METHODS: Antibody (IgE, IgG, and IgG4) levels to total cockroach and 8 cockroach allergens were determined in 2 groups of cockroach-sensitized 10-year-old children with (n = 19) or without (n = 28) asthma and rhinitis. Allergen-specific antibody levels were measured in streptavidin ImmunoCAPs loaded with each of the recombinant allergens from groups 1, 2, 4, 5, 6, 7, 9, and 11, and total cockroach-specific IgE levels were measured with the i6 ImmunoCAP. RESULTS: IgE antibody levels to cockroach allergens and extract, but not IgG or IgG4 antibody levels, differed between subjects with and without asthma and rhinitis. Specifically, recognition of more cockroach allergens with higher allergen-specific IgE levels was associated with disease. Variable patterns of sensitization with no immunodominant allergens were found in both groups. There was a good correlation between the sum of allergen-specific IgE and total cockroach IgE levels (r = 0.86, P < .001). CONCLUSIONS: Component analysis of 8 cockroach allergens revealed significant differences in IgE reactivity associated with the presence of asthma and rhinitis. Allergen-specific IgE titers and sensitization profiles were associated with asthma and rhinitis.

Longitudinal Phenotypes of Respiratory Health in a High-Risk Urban Birth Cohort.

RATIONALE: Characterization of patterns of wheezing and allergic sensitization in early life may allow for identification of specific environmental exposures impacting asthma development. OBJECTIVES: To define respiratory phenotypes in inner-city children and their associations with early-life environmental exposures. METHODS: Data were collected prospectively from 442 children in the URECA (Urban Environment and Childhood Asthma) birth cohort through age 7 years, reflecting symptoms (wheezing), aeroallergen sensitization, pulmonary function, and body mass index. Latent class mixed models identified trajectories of wheezing, allergic sensitization, and pulmonary function. Cluster analysis defined nonoverlapping groups (termed phenotypes). Potential associations between phenotypes and early-life environmental exposures were examined. MEASUREMENTS AND MAIN RESULTS: Five phenotypes were identified and mainly differentiated by patterns of wheezing and allergic sensitization (low wheeze/low atopy; low wheeze/high atopy; transient wheeze/low atopy; high wheeze/low atopy; high wheeze/high atopy). Asthma was most often present in the high-wheeze phenotypes, with greatest respiratory morbidity among children with frequent wheezing and allergic sensitization. These phenotypes differentially related to early-life exposures, including maternal stress and depression, antenatal environmental tobacco smoke, house dust microbiome, and allergen content (all P < 0.05). Prenatal smoke exposure, maternal stress, and depression were highest in the high-wheeze/low-atopy phenotype. The high-wheeze/high-atopy phenotype was associated with low household microbial richness and diversity. Early-life aeroallergen exposure was low in high-wheeze phenotypes. CONCLUSIONS: Patterns of wheezing, allergic sensitization, and lung function identified five respiratory phenotypes among inner-city children. Early-life environmental exposure to stress, depression, tobacco smoke, and indoor allergens and microbes differentially associate with specific phenotypes.

Early-life home environment and risk of asthma among inner-city children.

BACKGROUND: Environmental exposures in early life appear to play an important role in the pathogenesis of childhood asthma, but the potentially modifiable exposures that lead to asthma remain uncertain. OBJECTIVE: We sought to identify early-life environmental risk factors for childhood asthma in a birth cohort of high-risk inner-city children. METHODS: We examined the relationship of prenatal and early-life environmental factors to the occurrence of asthma at 7 years of age among 442 children. RESULTS: Higher house dust concentrations of cockroach, mouse, and cat allergens in the first 3 years of life were associated with lower risk of asthma (for cockroach allergen: odds ratio per interquartile range increase in concentration, 0.55; 95% CI, 0.36-0.86; P < .01). House dust microbiome analysis using 16S ribosomal RNA sequencing identified 202 and 171 bacterial taxa that were significantly (false discovery rate < 0.05) more or less abundant, respectively, in the homes of children with asthma. A majority of these bacteria were significantly correlated with 1 of more allergen concentrations. Other factors associated significantly positively with asthma included umbilical cord plasma cotinine concentration (odds ratio per geometric SD increase in concentration, 1.76; 95% CI, 1.00-3.09; P = .048) and maternal stress and depression scores. CONCLUSION: Among high-risk inner-city children, higher indoor levels of pet or pest allergens in infancy were associated with lower risk of asthma. The abundance of a number of bacterial taxa in house dust was associated with increased or decreased asthma risk. Prenatal tobacco smoke exposure and higher maternal stress and depression scores in early life were associated with increased asthma risk.

Individualized Household Allergen Intervention Lowers Allergen Level But Not Asthma Medication Use: A Randomized Controlled Trial.

BACKGROUND: Environmental exposures to indoor allergens are major contributors to asthma symptoms, particularly in inner cities. The effectiveness of household allergen reduction as an adjunct to National Asthma Education Prevention Program guideline-based pharmacologic therapy in asthma has not been prospectively studied. OBJECTIVE: To study the effect of individualized allergen reduction on ability to reduce asthma pharmacologic therapy over 40 weeks. METHODS: We performed a randomized controlled trial to determine the effect of multifaceted indoor allergen avoidance measures on the ability to reduce asthma controller therapy in adults and children residing in New York City who were both sensitized and exposed to at least 1 indoor allergen. Asthma treatment and control were optimized in all subjects before randomization. RESULTS: A total of 125 subjects were randomized to receive individualized household allergen reduction and 122 received a sham intervention. Subjects in the intervention group significantly reduced all measured allergen levels (cat, dog, dust mite allergens in the bedroom, cockroach and mouse allergens in the kitchen and bedroom); those in the control group reduced only dust mite and mouse allergens in the bedroom and cockroach allergen in the kitchen. Participants in the intervention arm reduced National Asthma Education Prevention Program-based therapy from step 4.4 at randomization to 3.50 postintervention (range, 0-6); participants in the control arm reduced medication from step 4.4 to 3.4 (P = .76). There were no differences in other measured asthma outcomes. CONCLUSIONS: Targeted allergen avoidance measures do not allow for reduction in asthma pharmacologic therapy compared with usual care in patients already receiving optimal controller therapy.

DNA methylation and childhood asthma in the inner city.

BACKGROUND: Epigenetic marks are heritable, influenced by the environment, direct the maturation of T lymphocytes, and in mice enhance the development of allergic airway disease. Thus it is important to define epigenetic alterations in asthmatic populations. OBJECTIVE: We hypothesize that epigenetic alterations in circulating PBMCs are associated with allergic asthma. METHODS: We compared DNA methylation patterns and gene expression in inner-city children with persistent atopic asthma versus healthy control subjects by using DNA and RNA from PBMCs. Results were validated in an independent population of asthmatic patients. RESULTS: Comparing asthmatic patients (n = 97) with control subjects (n = 97), we identified 81 regions that were differentially methylated. Several immune genes were hypomethylated in asthma, including IL13, RUNX3, and specific genes relevant to T lymphocytes (TIGIT). Among asthmatic patients, 11 differentially methylated regions were associated with higher serum IgE concentrations, and 16 were associated with percent predicted FEV1. Hypomethylated and hypermethylated regions were associated with increased and decreased gene expression, respectively (P < 6 × 10(-12) for asthma and P < .01 for IgE). We further explored the relationship between DNA methylation and gene expression using an integrative analysis and identified additional candidates relevant to asthma (IL4 and ST2). Methylation marks involved in T-cell maturation (RUNX3), TH2 immunity (IL4), and oxidative stress (catalase) were validated in an independent asthmatic cohort of children living in the inner city. CONCLUSIONS: Our results demonstrate that DNA methylation marks in specific gene loci are associated with asthma and suggest that epigenetic changes might play a role in establishing the immune phenotype associated with asthma.

A multi-center ring trial of allergen analysis using fluorescent multiplex array technology.

BACKGROUND: Consistent performance of allergen assays is essential to ensure reproducibility of exposure assessments for investigations of asthma and occupational allergic disease. This study evaluated intra- and inter-laboratory reproducibility of a fluorescent multiplex array, which simultaneously measures eight indoor allergens in a single reaction well. METHODS: A multi-center study was performed in nine laboratories in the US and Europe to determine the inter-laboratory variability of an 8-plex array for dust mite, cat, dog, rat, mouse and cockroach allergens. Aliquots of 151 dust extract samples were sent to participating centers and analyzed by each laboratory on three separate occasions. Agreement within and between laboratories was calculated by the concordance correlation coefficient (CCC). RESULTS: Results were obtained for over 32,000 individual allergen measurements. Levels covered a wide range for all allergens from below the lower limit of detection (LLOD = 0.1-9.8 ng/ml) to higher than 6800 ng/ml for all allergens except Mus m 1, which was up to 1700 ng/ml. Results were reproducible within as well as between laboratories. Within laboratories, 94% of CCC were ≥ 0.90, and 80% of intra-laboratory results fell within a 10% coefficient of variance (CV%). Results between laboratories also showed highly significant positive correlations for all allergens (~0.95, p<0.001). Overall means of results were comparable, and inter-laboratory CV% for all allergens except Rat n 1 ranged between 17.6% and 26.6%. CONCLUSION: The data indicate that performance criteria for fluorescent multiplex array technology are reproducible within and between laboratories. Multiplex technology provides standardized and consistent allergen measurements that will streamline environmental exposure assessments in allergic disease.

Impact of hydroxyurea on perioperative management and outcomes in children with sickle cell anemia.

Hydroxyurea has enhanced the treatment for children with sickle cell anemia. The objectives of this study were to compare perioperative transfusions and outcomes for children taking hydroxyurea versus those not taking hydroxyurea. We retrospectively reviewed perioperative management and outcomes for 51 children with sickle cell anemia (HbSS genotype) who underwent surgery in our center between January 2003 and April 2008. Of the 51 patients, 30 (59%) were taking hydroxyurea and 21 (41%) were not taking hydroxyurea. Eight of 30 (27%) in the hydroxyurea group were not transfused preoperatively, 12 of 30 (40%) received a single transfusion and 10 of 30 (33%) received serial transfusions, compared with 1 of 21 (5%) children in the nonhydroxyurea group who was not transfused, 2 of 21 (10%) who received a single transfusion and 18 of 21 (85%) who received serial transfusions or pheresis (P=0.004; for comparison across groups). One patient not taking hydroxyurea developed a delayed hyperhemolytic transfusion reaction, and 2 children taking hydroxyurea developed acute chest syndrome. Overall, children taking hydroxyurea had substantially fewer transfusions compared with children not taking hydroxyurea. Both groups of children had a low complication rate. Further research should be done to optimize perioperative management of children taking hydroxyurea.

Differences in health-related quality of life in children with sickle cell disease receiving hydroxyurea.

Hydroxyurea is a safe and efficacious medication for children with sickle cell disease (SCD). Our objective was to compare health-related quality of life (HRQL) between children taking hydroxyurea and those not taking hydroxyurea. We conducted a retrospective cohort study of children with SCD who had completed the PedsQL 4.0 at Duke University Medical Center or the Midwest Sickle Cell Center. Our primary outcome was HRQL in children receiving hydroxyurea therapy compared with those not receiving hydroxyurea. One hundred and ninety-one children with SCD were included in the study. Children in the hydroxyurea group had higher self-reported Total PedsQL median scores than children in the no hydroxyurea group (P=0.04). Child self-reported physical functioning scores were significantly higher for children in the hydroxyurea group (P=0.01). In conclusion, children with SCD who received hydroxyurea therapy reported better overall HRQL and better physical HRQL than children who did not receive this therapy despite disease severity. Further research assessing the impact of hydroxyurea therapy on HRQL, such as prospective assessment over time, would aid in our understanding of the effectiveness of hydroxyurea for individual children. Ultimately, this may aid in decreasing the barriers to the use of hydroxyurea.

Randomized trial of omalizumab (anti-IgE) for asthma in inner-city children.

BACKGROUND: Research has underscored the effects of exposure and sensitization to allergens on the severity of asthma in inner-city children. It has also revealed the limitations of environmental remediation and guidelines-based therapy in achieving greater disease control. METHODS: We enrolled inner-city children, adolescents, and young adults with persistent asthma in a randomized, double-blind, placebo-controlled, parallel-group trial at multiple centers to assess the effectiveness of omalizumab, as compared with placebo, when added to guidelines-based therapy. The trial was conducted for 60 weeks, and the primary outcome was symptoms of asthma. RESULTS: Among 419 participants who underwent randomization (at which point 73% had moderate or severe disease), omalizumab as compared with placebo significantly reduced the number of days with asthma symptoms, from 1.96 to 1.48 days per 2-week interval, a 24.5% decrease (P<0.001). Similarly, omalizumab significantly reduced the proportion of participants who had one or more exacerbations from 48.8 to 30.3% (P<0.001). Improvements occurred with omalizumab despite reductions in the use of inhaled glucocorticoids and long-acting beta-agonists. CONCLUSIONS: When added to a regimen of guidelines-based therapy for inner-city children, adolescents, and young adults, omalizumab further improved asthma control, nearly eliminated seasonal peaks in exacerbations, and reduced the need for other medications to control asthma. (Funded by the National Institute of Allergy and Infectious Diseases and Novartis; ClinicalTrials.gov number, NCT00377572.).

Prenatal maternal stress and cord blood innate and adaptive cytokine responses in an inner-city cohort.

RATIONALE: Stress-elicited disruption of immunity begins in utero. OBJECTIVES: Associations among prenatal maternal stress and cord blood mononuclear cell (CBMC) cytokine responses were prospectively examined in the Urban Environment and Childhood Asthma Study (n = 557 families). METHODS: Prenatal maternal stress included financial hardship, difficult life circumstances, community violence, and neighborhood/block and housing conditions. Factor analysis produced latent variables representing three contexts: individual stressors and ecological-level strains (housing problems and neighborhood problems), which were combined to create a composite cumulative stress indicator. CBMCs were incubated with innate (lipopolysaccharide, polyinosinic-polycytidylic acid, cytosine-phosphate-guanine dinucleotides, peptidoglycan) and adaptive (tetanus, dust mite, cockroach) stimuli, respiratory syncytial virus, phytohemagglutinin, or medium alone. Cytokines were measured using multiplex ELISAs. Using linear regression, associations among increasing cumulative stress and cytokine responses were examined, adjusting for sociodemographic factors, parity, season of birth, maternal asthma and steroid use, and potential pathway variables (prenatal smoking, birth weight for gestational age). MEASUREMENTS AND MAIN RESULTS: Mothers were primarily minorities (Black [71%], Latino [19%]) with an income less than $15,000 (69%). Mothers with the highest cumulative stress were older and more likely to have asthma and deliver lower birth weight infants. Higher prenatal stress was related to increased IL-8 production after microbial (CpG, PIC, peptidoglycan) stimuli and increased tumor necrosis factor-alpha to microbial stimuli (CpG, PIC). In the adaptive panel, higher stress was associated with increased IL-13 after dust mite stimulation and reduced phytohemagglutinin-induced IFN-gamma. CONCLUSIONS: Prenatal stress was associated with altered innate and adaptive immune responses in CBMCs. Stress-induced perinatal immunomodulation may impact the expression of allergic disease in these children.

Longitudinal evaluation of externalizing and internalizing behavior problems following iron deficiency in infancy.

OBJECTIVE: This study examined externalizing and internalizing behavior problem trajectories as a function of both iron status in infancy and infant characteristics. METHODS: A sample of 185 healthy Costa Rican children who either had chronic, severe iron deficiency or good iron status in infancy were followed for 19 years. RESULTS: Mother ratings of externalizing and internalizing problems from age 5 to 11-14 years were higher for the chronic iron deficiency group compared with those with the good iron status. Iron deficiency in infancy predicted persisting externalizing problems over this time period, especially for those with low physical activity in infancy. Beyond adolescence, youth in the chronic iron deficiency group did not report more problems than those in the good iron group. CONCLUSIONS: These findings underscore the importance of considering infant iron status along with early behavioral characteristics to better identify those children at greatest risk for persisting long-term behavior problems.

A pilot study of hydroxyurea to prevent chronic organ damage in young children with sickle cell anemia.

BACKGROUND: Hydroxyurea improves laboratory parameters and prevents acute clinical complications of sickle cell anemia (SCA) in children and adults, but its effects on organ function remain incompletely defined. METHODS: To assess the safety and efficacy of hydroxyurea in young children with SCA and to prospectively assess kidney and brain function, 14 young children (mean age 35 months) received hydroxyurea at a mean maximum tolerated dose (MTD) of 28 mg/kg/day. RESULTS: After a mean of 25 months, expected laboratory effects included significant increases in hemoglobin, MCV and %HbF along with significant decreases in reticulocytes, absolute neutrophil count, and bilirubin. There was no significant increase in glomerular filtration rate by DTPA clearance or Schwartz estimate. Mean transcranial Doppler (TCD) velocity changes were -25.6 cm/sec (P < 0.01) and -26.8 cm/sec (P < 0.05) in the right and left MCA vessels, respectively. At study exit, no child had conditional or abnormal TCD values, and none developed brain ischemic lesions or vasculopathy progression by MRI/MRA. Growth and neurocognitive scores were preserved and Impact-on-Family scores improved. CONCLUSIONS: These pilot data indicate hydroxyurea at MTD is well-tolerated by both children and families, and may prevent chronic organ damage in young children with SCA.

Iron status of inner-city African-American infants.

The iron status of African-American infants continues to be subject to debate. We characterized the iron status of 198 9-month-old inner-city infants (94% fed iron-fortified formula) using a comprehensive panel of measures and assessing lead and inflammation markers. The proportion with iron deficiency was calculated based on three approaches (> or = 2 abnormal iron measures with or without anemia for MCV model--NHANES II, ferritin model--NHANES III, or Sweden/Honduras study) and a promising new measure-body iron, calculated from ferritin and transferrin receptor (TfR). There were no sex differences for any iron measure. Hb < 110 g/l was observed in 25%; Hb < or = 105 g/l in 10.1%. Free erythrocyte protoporphyrin (FEP) values were elevated without elevated lead concentrations or an inflammatory response: mean FEP = 86.6 microg/dl red blood cells [75.5 micromol/mol heme]; 52.3% were > 80 microg/dl (1.42 micromol/l), almost half of which were accompanied by a second abnormal iron measure. The estimated prevalence of iron deficiency was 14.4, 5.3, and 2.5% for the MCV model, ferritin model, and Sweden/Honduras cutoffs, respectively, and 4.1% for body iron < 0 mg/kg. Regulation of iron storage is immature at < 1 year of age, making estimates of iron deficiency that depend on ferritin, including body iron, suspect in this age period. Thus, the "true" prevalence of iron deficiency could not be established with confidence due to major differences in the results, depending on the guidelines used. Functional indicators of poor iron status in young infants are urgently needed.

Effects of iron deficiency in infancy on patterns of motor development over time.

This longitudinal study of the effects of iron deficiency in infancy assessed motor development over time in 185 healthy Costa Rican children who varied in iron status at 12-23 months. Longitudinal analyses (hierarchical linear modeling) used the Bayley Psychomotor Index before and both 1 week and 3 months after iron treatment in infancy and the Bruninks-Oseretsky Test of Motor Proficiency - long form at 5 years and short form at 11-14 years. Children with chronic severe iron deficiency in infancy had lower motor scores at the beginning of the study and a lower but parallel trajectory for motor scores through early adolescence. Thus, there was no evidence of catch-up in motor development, despite iron therapy in infancy that corrected iron deficiency anemia in all cases.

Iron deficiency in infancy predicts altered serum prolactin response 10 years later.

Serum prolactin may reflect CNS dopaminergic function. Because iron deficiency (ID) alters brain dopamine in rats, serum prolactin levels were previously investigated in infants with varied iron status. High serum prolactin levels correlated with behaviors typical of chronic ID. The objective of this study was to determine the effect of infant iron status on serum prolactin levels after a stressor in early adolescence. One hundred fifty-nine of 191 children enrolled in infancy (chronic ID, n = 46; good iron comparison group, n = 113) had serum prolactin measurements after catheter placement at 11-14 y of age. Serum prolactin levels were compared by sex, pubertal status and infant iron status and the pattern of change over time was compared by infant iron status controlling for pubertal stage and background factors. Males and less mature adolescents had lower serum prolactin concentrations than females and more mature adolescents. Controlling for these factors, the serum prolactin response pattern differed significantly by infant iron status. Serum prolactin declined earlier for the chronic ID group. In conclusion, an altered serum prolactin response pattern was observed 10 y after chronic ID in infancy and may suggest a long-lasting effect of ID on the regulation of prolactin.

Diet-induced iron deficiency anemia and pregnancy outcome in rhesus monkeys.

BACKGROUND: Iron deficiency anemia (IDA) is relatively common in the third trimester of pregnancy, but causal associations with low birth weight and compromised neonatal iron status are difficult to establish in human populations. OBJECTIVE: The objective was to determine the effects of diet-induced IDA on intrauterine growth and neonatal iron status in an appropriate animal model for third-trimester IDA in women. DESIGN: Hematologic and iron-status measures, pregnancy outcomes, and fetal and neonatal evaluations were compared between pregnant rhesus monkeys (n = 14) fed a diet containing 10 microg Fe/g diet from the time of pregnancy detection (gestation days 28-30) and controls (n = 24) fed 100 microg Fe/g diet. RESULTS: By the third trimester, 79% of the iron-deprived dams and 29% of the control monkeys had a hemoglobin concentration <11 g/dL. There were also significant group differences in hematocrit, mean corpuscular volume, transferrin saturation, serum ferritin, and serum iron. At birth, the newborns of monkeys iron-deprived during pregnancy had significantly lower hemoglobin, mean corpuscular volume, and mean corpuscular hemoglobin values and a lower ratio of erythroid to total colony-forming units in bone marrow than did the control newborns. Pregnancy weight gain did not differ significantly between the iron-deprived and control dams, and the fetuses and newborns of the iron-deprived dams were not growth retarded relative to the controls. Gestation length, the number of stillbirths, and neonatal neurobehavioral test scores did not differ significantly by diet group. CONCLUSION: These data indicate that an inadequate intake of iron from the diet during pregnancy in rhesus monkeys can lead to compromised hematologic status of the neonate without indications of growth retardation or impaired neurologic function at birth.