Mapping the Cellular Biogeography of Human Bone Marrow Niches Using Single-Cell Transcriptomics and Proteomic Imaging.

The bone marrow is the organ responsible for blood production. Diverse non-hematopoietic cells contribute essentially to hematopoiesis. However, these cells and their spatial organization remain largely uncharacterized as they have been technically challenging to study in humans. Here, we used fresh femoral head samples and performed single-cell RNA sequencing (scRNA-Seq) to profile 29,325 enriched non-hematopoietic bone marrow cells and discover nine transcriptionally distinct subtypes. We next employed CO-detection by inDEXing (CODEX) multiplexed imaging of 18 individuals, including both healthy and acute myeloid leukemia (AML) samples, to spatially profile over one million single cells with a novel 53-antibody panel. We discovered a relatively hyperoxygenated arterio-endosteal niche for early myelopoiesis, and an adipocytic, but not endosteal or perivascular, niche for early hematopoietic stem and progenitor cells. We used our atlas to predict cell type labels in new bone marrow images and used these predictions to uncover mesenchymal stromal cell (MSC) expansion and leukemic blast/MSC-enriched spatial neighborhoods in AML patient samples. Our work represents the first comprehensive, spatially-resolved multiomic atlas of human bone marrow and will serve as a reference for future investigation of cellular interactions that drive hematopoiesis.

No Difference in Perioperative Complications for Bilateral Total Knee Arthroplasty Staged at 1 Week Compared With Delayed Staging.

INTRODUCTION: Controversy exists regarding the safety of simultaneous bilateral total knee arthroplasty (TKA) versus two TKA procedures staged months apart in patients with bilateral knee arthritis. Here, we investigated a third option: bilateral TKA staged 1 week apart. In this study, we examined the rate of complications in patients undergoing bilateral TKA staged at 1 week compared with longer time intervals. METHODS: A retrospective review of 351 consecutive patients undergoing bilateral TKA at our institution was conducted. Patients underwent a 1-week staged bilateral procedure with planned interim transfer to a subacute rehabilitation facility (short-staged) or two separate unilateral TKA procedures within 1 year (long-staged). Binary logistic regression was used to compare outcomes while controlling for year of surgery, patient age, body mass index, and Charlson Comorbidity Index. RESULTS: Two hundred four short-staged and 147 long-staged bilateral TKA patients were included. The average interval between procedures in long-staged patients was 200.9 ± 95.9 days. Patients undergoing short-staged TKA had a higher Charlson Comorbidity Index (3.0 ± 1.5 versus 2.6 ± 1.5, P = 0.017) with no difference in preoperative hemoglobin ( P = 0.285) or body mass index ( P = 0.486). Regression analysis demonstrated that short-staged patients had a higher likelihood of requiring a blood transfusion (odds ratio 4.015, P = 0.005) but were less likely to return to the emergency department within 90 days (odds ratio 0.247, P = 0.001). No difference was observed in short-term complications ( P = 0.100), 90-day readmissions ( P = 0.250), or 1-year complications ( P = 0.418) between the groups. CONCLUSION: Bilateral TKA staged at a 1-week interval is safe with a comparable complication rate with delayed staged TKA, but allows for a faster total recovery time. LEVEL OF EVIDENCE: Level III.

Profound Impact of Insurance Payor and Socioeconomic Status in Total Hip Arthroplasty Outcomes: Results From a High Volume Tertiary Care Center.

BACKGROUND: Dual eligible Medicare/Medicaid patients undergoing total hip arthroplasty (THA) have worse outcomes compared to other insurance payors. Prior literature fails to control for the heterogeneity of care provided amongst a large cohort of hospitals and surgeons as well as differences in patient populations treated. This study compares dual eligible THA patients and Medicaid and Medicare only THA patients at a single high volume tertiary center. METHODS: We retrospectively reviewed patients who underwent THA for aseptic osteoarthritis of the hip over a three-year period with either Medicaid or Medicare insurance. 3,329 THA patients were included, of which 439 were Medicaid payor, 182 were dual eligible, and 2,708 were Medicare payor. Groups were compared using appropriate tests for direct comparisons and regression analysis. RESULTS: Dual eligible patients were less likely to be white and married, and were more likely to be current smokers and have COPD, liver disease, renal disease, and human immunodeficiency virus (HIV) compared to Medicare patients. These patients also had a lower age-adjusted Charleson Comorbidity Index when compared to Medicare patients (2.4 vs 3.4, P < .001). When controlling for smoking status, age, BMI and major medical comorbidities, dual eligible and Medicaid patients had increased length of stay (LOS) (0.58, 0.66 days, P < .001), higher risk of discharge to subacute rehabilitation (RR 1.97, 3.19, P < .001), and dual eligible patients more often returned to the ED within 90 days (RR 2.74, P < .001) compared to Medicare patients. CONCLUSION: This study supports the implementation of socioeconomic risk stratification efforts to properly evaluate value-based healthcare metrics in total hip arthroplasty patients.

Does Dual-Eligible Medicare/Medicaid Insurance Status as a Surrogate for Socioeconomic Status Compromise Total Knee Arthroplasty Outcomes?

BACKGROUND: Medicare/Medicaid dual-eligible patients who undergo primary total knee arthroplasty (TKA) demonstrate poor outcomes when compared to patients with other payers. We compare Medicare/Medicaid dual-eligible patients vs Medicare and Medicaid only patients at a single hospital center. METHODS: All patients who underwent TKA for aseptic arthritis between August 9, 2016 and December 30, 2020 with either Medicare or Medicaid insurance were retrospectively reviewed. 4599 consecutive TKA (3749 Medicare, 286 Medicare/Medicaid dual eligibility, and 564 Medicaid) were included. Groups were compared using appropriate tests for direct comparisons and regression analysis. RESULTS: Patients with dual eligibility and Medicaid insurance were less likely to be white and married, more likely to be female and current smokers, and more likely to have COPD, mild liver disease, diabetes mellitus, malignancy, and HIV/AIDS, but had a lower age-adjusted Charleson Comorbidity Index when compared to Medicare patients. When controlling for smoking status and medical comorbidities, patients with dual eligibility and Medicaid insurance stayed in the hospital 0.64 and 0.39 additional days (P < .001), respectively, were more likely to be discharged to subacute rehab (RR 2.01, 1.49, P < .001) and acute rehab (RR 2.22, 2.46, P = .007, < .001), and were 2.14 and 1.73 times more likely to return to the ED within 90 days (P < .001) compared to Medicare patients. CONCLUSION: Value-based healthcare may disincentivize treating patients with low socioeconomic status, represented by Medicaid and dual-eligible insurance status, by their association with increased postoperative healthcare utilization, and less risky patients may be prioritized.

Promoting mother-infant relationships and underlying neural correlates: Results from a randomized controlled trial of a home-visiting program for adolescent mothers in Brazil.

Poverty and teenage pregnancy are common in low-and-middle-income countries and can impede the development of healthy parent-child relationships. This study aimed to test whether a home-visiting intervention could improve early attachment relationships between adolescent mothers and their infants living in poverty in Brazil. Analyses were conducted on secondary outcomes from a randomized controlled trial (NCT0280718) testing the efficacy of a home-visiting program, Primeiros Laços, on adolescent mothers' health and parenting skills and their infants' development. Pregnant youth were randomized to intervention (n = 40) or care-as-usual (CAU, n = 40) from the first trimester of pregnancy until infants were aged 24 months. Mother-infant attachment was coded during a mother-infant interaction when the infants were aged 12 months. Electrophysiological correlates of social processing (mean amplitude of the Nc component) were measured while infants viewed facial images of the mother and a stranger at age 6 months. Infants in the intervention group were more securely attached and more involved with their mothers than those receiving CAU at 12 months. Smaller Nc amplitudes to the mother's face at 6 months were associated with better social behavior at 12 months. Our findings indicate that the Primeiros Laços Program is effective in enhancing the development of mother-infant attachment.

Multisite Study of Evoked Potentials in Rett Syndrome.

OBJECTIVE: The aim of the current study was to evaluate the utility of evoked potentials as a biomarker of cortical function in Rett syndrome (RTT). As a number of disease-modifying therapeutics are currently under development, there is a pressing need for biomarkers to objectively and precisely assess the effectiveness of these treatments. METHOD: Yearly visual evoked potentials (VEPs) and auditory evoked potentials (AEPs) were acquired from individuals with RTT, aged 2 to 37 years, and control participants across 5 sites as part of the Rett Syndrome and Related Disorders Natural History Study. Baseline and year 1 data, when available, were analyzed and the repeatability of the results was tested. Two syndrome-specific measures from the Natural History Study were used for evaluating the clinical relevance of the VEP and AEP parameters. RESULTS: At the baseline study, group level comparisons revealed reduced VEP and AEP amplitude in RTT compared to control participants. Further analyses within the RTT group indicated that this reduction was associated with RTT-related symptoms, with greater severity associated with lower VEP and AEP amplitude. In participants with RTT, VEP and AEP amplitude was also negatively associated with age. Year 1 follow-up data analyses yielded similar findings and evidence of repeatability of EPs at the individual level. INTERPRETATION: The present findings indicate the promise of evoked potentials (EPs) as an objective measure of disease severity in individuals with RTT. Our multisite approach demonstrates potential research and clinical applications to provide unbiased assessment of disease staging, prognosis, and response to therapy. ANN NEUROL 2021;89:790-802.

High Bundled Payment Costs Following Total Hip and Knee Arthroplasty in African Americans.

BACKGROUND: Concerns exist that minorities who utilize more resources in an episode-of-care following total hip (THA) and knee arthroplasty (TKA) may face difficulties with access to quality arthroplasty care in bundled payment programs. The purpose of this study is to determine if African American patients undergoing TKA or THA have higher episode-of-care costs compared to Caucasian patients. METHODS: We queried Medicare claims data for a consecutive series of 7310 primary TKA and THA patients at our institution from 2015 to 2018. We compared patient demographics, comorbidities, readmissions, and 90-day episode-of-care costs between African American and Caucasian patients. A multivariate regression analysis was performed to identify the independent effect of race on episode-of-care costs. RESULTS: Compared to Caucasians, African Americans were younger, but had higher rates of pulmonary disease and diabetes. African American patients had increased rates of discharge to a rehabilitation facility (20% vs 13%, P < .001), with higher subacute rehabilitation ($1909 vs $1284, P < .001), home health ($819 vs $698, P = .022), post-acute care ($5656 vs $4961, P = .008), and overall 90-day episode-of-care costs ($19,457 vs $18,694, P = .001). When controlling for confounding comorbidities, African American race was associated with higher episode-of-care costs of $440 (P < .001). CONCLUSION: African American patients have increased episode-of-care costs following THA and TKA when compared to Caucasian patients, mainly due to increased rates of home health and rehabilitation utilization. Further study is needed to identify social variables that can help reduce post-acute care resources and prevent reduction in access to arthroplasty care in bundled payment models.

Perception of Risk: A Poll of American Association of Hip and Knee Surgeons Members.

BACKGROUND: Providers of total hip and knee replacements are being judged regarding quality/cost by payers using competition-based performance measures with poor medical and no socioeconomic risk adjustment. Providers might assume that other providers shed risk and the perception of added risk can influence practice. A poll was collected to examine such perceptions. METHODS: In 2019 a poll was sent to the 2800 surgeon members of the American Association of Hip and Knee Surgeons using Survey Monkey while protecting respondent anonymity/confidentiality. The questions asked whether the perception of poorly risk-adjusted medical comorbidities and socioeconomic risk factors influence surgeons to selectively offer surgery. RESULTS: There were 474 surgeon responses. Prior to elective total hip arthroplasty/total knee arthroplasty, 95% address modifiable risk factors; 52% require a body mass index <40, 64% smoking cessation, 96% an adequate hemoglobin A1C; 82% check nutrition; and 63% expect control of alcohol 2. Due to lack of socioeconomic risk adjustment, 83% reported feeling pressure to avoid/restrict access to patients with limited social support, specifically the following: Medicaid/underinsured, 81%; African Americans, 29%; Hispanics/ethnicities, 27%; and low socioeconomic status, 73%. Of the respondents, 93% predicted increased access to care with more appropriate risk adjustment. CONCLUSION: Competition-based quality/cost performance measures influence surgeons to focus on medical risk factors in offering lower extremity arthroplasty. The lack of socioeconomic risk adjustment leads to perceptions of added risk from such factors as well. This leads to marginal loss of access for patients within certain medical and socioeconomic classes, contributing to existing healthcare disparities. This represents an unintended consequence of competition-based performance measures.

African American Patients Have Improved Functional Gains and Comparable Clinical Outcomes to Caucasian Patients After Total Hip and Knee Arthroplasty.

BACKGROUND: With the increasing popularity of alternative payment models, minorities who use more postacute care resources may face difficulties with access to quality total hip arthroplasty (THA) and total knee arthroplasty (TKA) care. The purpose of this study is to compare differences in perioperative complications and functional outcomes between African American and Caucasian patients undergoing THA and TKA. METHODS: We reviewed a consecutive series of all primary THA and TKA patients at our institution from 2015 to 2018. Demographics, comorbidities, 90-day complications, readmissions, Veterans Rand 12-Item Health Survey (VR-12), Hip disability Osteoarthritis Outcome Score (HOOS), and Knee injury and Osteoarthritis Outcome Scores (KOOS) were compared between African American and Caucasian patients. A multivariate analysis was performed to control for confounding variables. RESULTS: Of the 5284 patients included in the study, 1041 were African American (24.5%). Although African American patients had lower preoperative HOOS/KOOS (33.5 vs 45.1, P < .001) and mental VR-12 scores (37.8 vs 51.5, P < .001) compared with Caucasian patients, there was no clinical difference at 1 year in HOOS/KOOS (50.2 vs 50.4), mental VR-12 (55.0 vs 52.6), or physical VR-12 scores (39.5 vs 39.8). When controlling for demographics and medical comorbidities, African American race was associated with increased rehabilitation facility discharge (odds ratio, 1.69; P < .001) but no difference in readmissions or complications. CONCLUSION: Although African American patients had lower preoperative functional scores, they made improved postoperative gains when compared with Caucasian patients. Although there was no difference in postoperative complications, further studies should assess social causes for the increase in rehabilitation utilization rates in minority patients.

The influence of maternal anxiety and depression symptoms on fNIRS brain responses to emotional faces in 5- and 7-month-old infants.

Greater relative right (versus left) frontal cortical activation to emotional faces as measured with alpha power in the electroencephalogram (EEG), has been considered a promising neural marker of increased vulnerability to psychopathology and emotional disorders. We set out to explore multichannel fNIRS as a tool to investigate infants' frontal asymmetry responses (hypothesizing greater right versus left frontal cortex activation) to emotional faces as influenced by maternal anxiety and depression symptoms during the postnatal period. We also explored activation differences in fronto-temporal regions associated with facial emotion processing. Ninety-one typically developing 5- and 7-month-old infants were shown photographs of women portraying happy, fearful and angry expressions. Hemodynamic brain responses were analyzed over two frontopolar and seven bilateral cortical regions subdivided into frontal, temporal and parietal areas, defined by age-appropriate MRI templates. Infants of mothers reporting higher negative affect had greater oxyhemoglobin (oxyHb) activation across all emotions over the left inferior frontal gyrus, a region implicated in emotional communication. Follow-up analyses indicated that associations were driven by maternal depression, but not anxiety symptoms. Overall, we found no support for greater right versus left frontal cortex activation in association with maternal negative affect. Findings point to the potential utility of fNIRS as a method for identifying altered neural substrates associated with exposure to maternal depression in infancy.

Cognitive Development of Infants Exposed to the Zika Virus in Puerto Rico.

Importance: Existing research has established a causal link between Zika virus (ZIKV) infection and severe birth defects or consequent health impairments; however, more subtle cognitive impairments have not been explored. Objective: To determine whether infants of mothers with at least 1 positive ZIKV test show differences in cognitive scores at ages 3 to 6 months and ages 9 to 12 months. Design, Setting, and Participants: This cross-sectional study recruited infants enrolled in existing ZIKV study cohorts associated with the Maternal-Infant Studies Center and the Puerto Rico Clinical and Translational Research Consortium at the University of Puerto Rico and from the broader San Juan metropolitan area. The study took place at the Puerto Rico Clinical and Translational Research Consortium at the University of Puerto Rico. Participants were recruited through convenience sampling if their mothers underwent ZIKV testing prenatally and were at the target ages during the study period. Infants who were born preterm (<36 weeks' gestational age), with low birth weight (<2500 g), or with a known genetic disorder were excluded. Infants were tested from ages 3 to 6 months or ages 9 to 12 months from May 2018 to April 2019. Data analysis was performed from March to April 2019. Exposures: Zika virus status was measured prenatally and in the early postnatal period using real-time polymerase chain reaction or a ZIKV IgM antibody capture enzyme-linked immunosorbent assay. Main Outcomes and Measures: The infants' development was assessed using the Mullen Scales of Early Learning (translated to Spanish and adapted for Puerto Rico), and assessors were blinded to each infant's ZIKV status. Results: A total of 65 study participants were included. The mean (SD) age of the infants at the time of cognitive testing was 8.98 (3.19) months. Most of the infants were white (55 [84.6%]) and Puerto Rican (64 [98.5%]); 38 of the infants were male (58.5%). General cognitive and domain-specific scores did not differ significantly between prenatally ZIKV-positive and ZIKV-negative infants except for receptive language score (mean difference = 5.52; t = 2.10; P = .04). Exposure to ZIKV (B = -5.69; ß = -0.26 [95% CI -11.01 to -0.36]; P = .04) and a measure of Hurricane Maria exposure (time without water, B = -0.05; ß = -0.27 [95% CI, -0.10 to -0.01]; P = .03) were both independently and significantly associated with receptive language scores after adjusting for key confounders. Conclusions and Relevance: Although infants exposed to ZIKV prenatally showed unaffected motor and visually mediated cognitive development, they did show deficits in receptive language scores. Receptive language skills were also associated with the degree of exposure to Hurricane Maria, with those who spent more time without water after the hurricane having lower receptive language scores.

Effects of Maternal Psychopathology and Education Level on Neurocognitive Development in Infants of Adolescent Mothers Living in Poverty in Brazil.

BACKGROUND: Adolescent motherhood remains common in developing countries and is associated with risk factors that adversely impact infant neurodevelopment, including poverty, low maternal education, and increased maternal psychopathology. Yet, no published work has assessed how these factors affect early brain development in developing countries. METHODS: This pilot study examined effects of maternal psychopathology and education on early neurocognitive development in a sample of adolescent mothers (N = 50, final n = 31) and their infants living in poverty in São Paulo, Brazil. Maternal symptoms of anxiety, depression, and attention-deficit/hyperactivity disorder and education level were assessed during pregnancy. Infant neurocognitive development was assessed at 6 months of age, with oscillatory power and functional connectivity in the theta (4-6 Hz), alpha (6-9 Hz), and gamma (30-50 Hz) frequencies derived from resting-state electroencephalography; temperament (negative affect, attention, and regulation); and cognitive, language, and motor skills. Cluster-based permutation testing and graph-theoretical methods were used to identify alterations in oscillatory power and connectivity that were associated with maternal psychopathology and education. Correlations between power and connectivity alterations were examined in relation to infants' overt cognitive behavioral abilities. RESULTS: Increased maternal anxiety and lower maternal education were associated with weaker oscillatory connectivity in alpha-range networks. Infants with the weakest connectivity in the alpha network associated with maternal anxiety also showed the lowest cognitive ability. Greater maternal anxiety and attention-deficit/hyperactivity disorder were associated with increased absolute and relative theta power. CONCLUSIONS: Our findings highlight the importance of addressing maternal psychopathology and improving education in poor adolescent mothers to prevent negative effects on infant neurodevelopment.

Caregiving Disruptions Affect Growth and Pubertal Development in Early Adolescence in Institutionalized and Fostered Romanian Children: A Randomized Clinical Trial.

OBJECTIVES: To determine the effects of foster care vs institutional care, as well as disruptions in the caregiving environment on physical development through early adolescence. STUDY DESIGN: This was a randomized controlled trial of 114 institutionalized, though otherwise healthy, children from 6 orphanages and 51 never institutionalized control children living in birth families (family care group) in Bucharest, Romania. Children were followed from baseline (21 months, range 5-31) through age 12 years for caregiving disruptions and growth trajectories and through age 14 years for pubertal development. RESULTS: Children randomized to the foster care group showed greater rates of growth in height, weight, and body mass index (BMI) through age 12 years than institutionalized group. Tanner development was delayed in institutionalized group boys compared with foster care group and family care group boys at 12 but not 14 years. There were no differences in Tanner development and age of menarche among foster care group, institutionalized group, and family care group girls at ages 12 and 14 years. More disruptions in caregiving between 30 months and 12 years moderated decreases in growth rates of height in foster care group and weight in foster care group and institutionalized group across age. institutionalized group boys with ≥2 disruptions showed lower Tanner scores at age 12 vs institutionalized group and foster care group boys with <2 disruptions. foster care group girls with ≥2 disruptions had higher Tanner scores at age 14 vs foster care group girls with <2 disruptions. Age of menarche was not affected by caregiving disruptions. CONCLUSIONS: For children who experienced early institutionalization, stable placement within family care is essential to ensuring the best outcomes for physical developmental. TRIAL REGISTRATION: clinicaltrials.gov: NCT00747396.

Behavioral and neural correlates of emotional development: typically developing infants and infants of depressed and/or anxious mothers / Bases neurais e comportamentais do desenvolvimento emocional: lactentes com desenvolvimento típico e lactentes filhos de mães deprimidas e/ou ansiosas

ABSTRACT Objectives: To describe the main findings of studies of behavioral and neural correlates regarding the development of facial emotion processing during the first year of life in typically developing infants and infants of depressed and/or anxious mothers. Sources: Comprehensive, non-systematic review of the literature on studies about individual differences in facial emotion processing by newborns and infants over the first year of life. Summary of the findings: Maternal stress related to depression and anxiety has been associated to atypical emotional processing and attentional behaviors in the offspring. Recent neurophysiological studies using electroencephalogram and event-related potentials have begun to shed light on the possible mechanisms underlying such behaviors. Conclusions: Infants of depressed and/or anxious mothers have increased risk for several adverse outcomes across the lifespan. Further neurobehavioral investigations and the promotion of clinical and developmental research integration might eventually contribute to refining screening tools, improving treatment, and enabling primary prevention interventions for children at risk.

RESUMO Objetivos: Descrever os principais achados de estudos de correlação entre o comportamento e as bases neurais em relação ao processamento de emoções faciais durante o primeiro ano de vida de lactentes com desenvolvimento típico e lactentes de mães deprimidas e/ou ansiosas. Fontes: Análise abrangente e não sistemática da literatura de estudos sobre diferenças individuais no processamento de emoções faciais de neonatos e lactentes ao longo do primeiro ano de vida. Resumo dos achados: O estresse materno relacionado à depressão e ansiedade tem sido associado a alterações no processamento emocional e na alocação da atenção da prole. Estudos neurofisiológicos recentes utilizando electroencefalograma e potenciais relacionados a eventos começam a esclarecer os possíveis mecanismos inerentes a esses comportamentos. Conclusões: Lactentes filhos de mães deprimidas e/ou ansiosas têm maior risco de problemas de saúde física e mental durante toda vida. O avanço de estudos neurocomportamentais e a promoção de integração entre a pesquisa clínica e de desenvolvimento poderão contribuir para refinar as ferramentas de triagem, melhorar o tratamento e permitir intervenções de prevenção primária para crianças em risco.

Behavioral and neural correlates of emotional development: typically developing infants and infants of depressed and/or anxious mothers.

OBJECTIVES: To describe the main findings of studies of behavioral and neural correlates regarding the development of facial emotion processing during the first year of life in typically developing infants and infants of depressed and/or anxious mothers. SOURCES: Comprehensive, non-systematic review of the literature on studies about individual differences in facial emotion processing by newborns and infants over the first year of life. SUMMARY OF THE FINDINGS: Maternal stress related to depression and anxiety has been associated to atypical emotional processing and attentional behaviors in the offspring. Recent neurophysiological studies using electroencephalogram and event-related potentials have begun to shed light on the possible mechanisms underlying such behaviors. CONCLUSIONS: Infants of depressed and/or anxious mothers have increased risk for several adverse outcomes across the lifespan. Further neurobehavioral investigations and the promotion of clinical and developmental research integration might eventually contribute to refining screening tools, improving treatment, and enabling primary prevention interventions for children at risk.

Motor outcomes in children exposed to early psychosocial deprivation.

OBJECTIVES: To determine the effect of psychosocial deprivation early in life on motor development, assess the impact of a foster care intervention on improving motor development, and assess the association between motor and cognitive outcomes in children with a history of institutional care. STUDY DESIGN: In a randomized controlled trial, children living in Romanian institutions were randomly assigned to care as usual in the institution or placed in family-centered foster care as part of the Bucharest Early Intervention Project. The average age at placement into foster care was 23 months. At age 8 years, the Bruininks-Oseretsky Test of Motor Proficiency, Second Edition, Short Form (BOT2-SF) was applied to assess the motor proficiency of children in both groups, as well as a never-institutionalized group from the Romanian community. RESULTS: Children in the never-institutionalized group did significantly better on the BOT2-SF than children who had ever been institutionalized (P < .001). There was no significant difference in performance between children in the care as usual group and the foster care group. This finding also held true for all individual items on the BOT2-SF except sit-ups. Regression analyses revealed that the between-group and within-group differences in BOT2-SF scores were largely mediated by IQ. CONCLUSION: Early deprivation had a negative effect on motor development that was not resolved by placement in foster care. This effect was predominantly mediated by IQ. This study highlights the importance of monitoring for and addressing motor delays in children with a history of institutionalization, particularly those children with low IQ.

Iron-deficiency anemia in infancy and poorer cognitive inhibitory control at age 10 years.

AIM: The aim of this study was to assess the effects of iron-deficiency anemia (IDA) in infancy on executive functioning at age 10 years, specifically inhibitory control on the Go/No-Go task. We predicted that children who had IDA in infancy would show poorer inhibitory control. METHOD: We assessed cognitive inhibitory control in 132 Chilean children (mean [SD] age 10 y [1 mo]): 69 children had IDA in infancy (45 males, 24 females) and 63 comparison children who did not have IDA (26 males, 37 females). Participants performed the Go/No-Go task with event-related potentials. Group differences in behavioral (accuracy, reaction time) and electrophysiological outcomes (N2 and P300 components) were analyzed using repeated-measures analyses of variance. N2 and P300 are interpreted to reflect attention and resource allocation respectively. RESULTS: Relative to comparison participants, children who had IDA in infancy showed slower reaction time (mean [SE], 528.7 ms [14.2] vs 485.0 ms [15.0], 95% confidence interval [CI] for difference between groups 0.9-86.5); lower accuracy (95.4% [0.5] vs 96.9% [0.6], 95% CI -3.0 to -0.1); longer latency to N2 peak (378.9 ms [4.9] vs 356.9 ms [5.0], 95% CI 7.5-36.6); and smaller P300 amplitude (4.5 µV [0.8] vs 7.6 µV [0.9], 95% CI-5.5 to -0.5). INTERPRETATION: IDA in infancy was associated with slower reaction times and poorer inhibitory control 8 to 9 years after iron therapy. These findings are consistent with the long-lasting effects of early IDA on myelination and/or prefrontal-striatal circuits where dopamine is the major neurotransmitter.

Iron deficiency in infancy is associated with altered neural correlates of recognition memory at 10 years.

OBJECTIVE: To determine the long-term effects of iron deficiency on the neural correlates of recognition memory. STUDY DESIGN: Non-anemic control participants (n=93) and 116 otherwise healthy formerly iron-deficient anemic Chilean children were selected from a larger longitudinal study. Participants were identified at 6, 12, or 18 months as iron-deficient anemic or non-anemic and subsequently received oral iron treatment. This follow-up was conducted when participants were 10 years old. Behavioral measures and event-related potentials from 28 scalp electrodes were measured during an new/old word recognition memory task. RESULTS: The new/old effect of the FN400 amplitude, in which new words are associated with greater amplitude than old words, was present within the control group only. The control group also showed faster FN400 latency than the formerly iron-deficient anemic group and larger mean amplitude for the P300 component. CONCLUSIONS: Although overall behavioral accuracy is comparable in groups, the results show that group differences in cognitive function have not been resolved 10 years after iron treatment. Long-lasting changes in myelination and energy metabolism, perhaps especially in the hippocampus, may account for these long-term effects on an important aspect of human cognitive development.

Inequality in early childhood: risk and protective factors for early child development.

Inequality between and within populations has origins in adverse early experiences. Developmental neuroscience shows how early biological and psychosocial experiences affect brain development. We previously identified inadequate cognitive stimulation, stunting, iodine deficiency, and iron-deficiency anaemia as key risks that prevent millions of young children from attaining their developmental potential. Recent research emphasises the importance of these risks, strengthens the evidence for other risk factors including intrauterine growth restriction, malaria, lead exposure, HIV infection, maternal depression, institutionalisation, and exposure to societal violence, and identifies protective factors such as breastfeeding and maternal education. Evidence on risks resulting from prenatal maternal nutrition, maternal stress, and families affected with HIV is emerging. Interventions are urgently needed to reduce children's risk exposure and to promote development in affected children. Our goal is to provide information to help the setting of priorities for early child development programmes and policies to benefit the world's poorest children and reduce persistent inequalities.

Electrophysiologic evidence of impaired cross-modal recognition memory in 8-month-old infants of diabetic mothers.

OBJECTIVES: Previous studies have shown deficits in auditory and visual recognition memory in infants of diabetic mothers. The purpose of this study was to further investigate memory development in infants of diabetic mothers (IDMs) by evaluating cross-modal recognition memory followed by behavioral memory testing at 8 months of age. STUDY DESIGN: Cross-modal (tactile to vision) recognition memory was evaluated using event related potentials. Control and IDMs palpated an object without seeing it and were then tested on their ability to recognize that object visually. Infants were then tested behaviorally on their ability to recognize and discriminate faces. The Bayley Scales of Infant Development was administered at 12 months of age. RESULTS: Control infants showed typical event-related potential patterns indicative of intact cross-modal recognition memory, whereas the IDMs did not show any evidence of recognition of the palpated object. Neither group showed behavioral evidence of visual recognition memory. Both groups had Bayley scores in the normal range, although controls had slightly higher mental development index scores than IDMs. CONCLUSIONS: IDMs showed neurophysiologic evidence of persistent subtle impairments in hippocampally-based recognition memory, despite having normal one-year developmental scores.