The peripheral epigenome predicts white matter volume contingent on developmental stage: An ECHO study.

Epigenetic processes, including DNA methylation, are emerging as key areas of interest for their potential roles as biomarkers and contributors to the risk of neurodevelopmental, psychiatric, and other brain-based disorders. Despite this growing focus, there remains a notable gap in our understanding of how DNA methylation correlates with individual variations in brain function and structure. Additionally, the dynamics of these relationships during developmental periods, which are critical windows during which many disorders first appear, are still largely unexplored. The current study extends the field by examining if peripheral DNA methylation of myelination-related genes predicts white matter volume in a healthy pediatric population [N = 250; females = 113; age range 2 months-14 years; Mage = 5.14, SDage = 3.60]. We assessed if DNA methylation of 17 myelin-related genes predict white matter volume and if age moderates these relationships. Results highlight low variability in myelin-related epigenetic variance at birth, which rapidly increases non-linearly with age, and that DNA methylation, measured at both the level of a CpG site or gene, is highly predictive of white matter volume, in early childhood but not late childhood. These novel findings propel the field forward by establishing that DNA methylation of myelin-related genes from a peripheral tissue is a predictive marker of white matter volume in children and is influenced by developmental stage. The research underscores the significance of peripheral epigenetic patterns as a proxy for investigating the effects of environmental factors, behaviors, and disorders associated with white matter.

Parental perceptions of body weight and appetite in infants and toddlers with cystic fibrosis.

Nutritional status has clinical relevance and is a target of guidance to parents of children with cystic fibrosis (CF). Growth is routinely monitored in CF clinics but there is no standardized way of assessing appetitive behaviors or parents' perceptions of their children's appetite. Greater understanding of these factors could improve clinical guidance regarding parent feeding behaviors. We therefore aimed to assess parent perceptions of child weight, and parent reports of child appetite using the Baby Eating Behavior Questionnaire (BEBQ), in a sample of infants and toddlers with CF, compared with a community sample. We additionally assessed relationships of parent perceptions of child weight with parent feeding behaviors in the sample with CF. Anthropometric and questionnaire data were collected for 32 infants and toddlers with CF, as well as 193 infants and toddlers drawn from RESONANCE, a community cohort study. Parents perceived children with CF to be lower in weight than their actual weight, to a greater extent than was evident in the community sample. Parents who perceived their children with CF to be underweight vs. right weight reported greater slowness in eating on the BEBQ. Parents perceived children with CF to have greater slowness in eating and lower enjoyment of food, compared to parents of children in the community sample, independent of sample differences in child weight, age, and sex. Our results demonstrate the potential utility of the BEBQ in a clinical sample and suggest it may be helpful for clinicians to assess parents' perceptions of their child's weight and appetite to promote a fuller understanding of the child's nutritional status, facilitate appropriate feeding behaviors and alleviate unnecessary concerns.

Developmental characteristics and accuracy of autism screening among two-year-old toddlers in the ECHO program.

BACKGROUND: The Modified Checklist for Autism in Toddlers (M-CHAT) is a common pediatric screening tool with mixed accuracy findings. Prior evidence supports M-CHAT screening for developmental concerns, especially in toddlers born preterm. This study examined M-CHAT accuracy in a large, nationwide sample. METHODS: 3393 participants from the Environmental influences on Child Health Outcomes (ECHO) program were included. Harmonized M-CHAT (M-CHAT-H) results were compared with parent-reported autism diagnosis and autism-related characteristics to assess accuracy for term and preterm children, together and separately. Generalized estimating equations, clustering for ECHO cohort and controlling for demographic covariates, were used to examine associations between developmental and behavioral characteristics with M-CHAT-H accuracy. RESULTS: Sensitivity of the M-CHAT-H ranged from 36 to 60%; specificity ranged from 88 to 99%. Positive M-CHAT-H was associated with more developmental delays and behavior problems. Children with severe motor delays and more autism-related problems were more likely to have a false-negative M-CHAT-H. Children with fewer behavior problems and fewer autism-related concerns were more likely to have a false-positive screen. CONCLUSION: The M-CHAT-H accurately detects children at low risk for autism and children at increased risk with moderate accuracy. These findings support use of the M-CHAT-H in assessing autism risk and developmental and behavioral concerns in children. IMPACT: Previous literature regarding accuracy of the Modified Checklist for Autism in Toddlers (M-CHAT) is mixed but this study provides evidence that the M-CHAT performs well in detecting children at low risk for autism and consistently detects children with developmental delays and behavioral problems. The M-CHAT moderately detects children at increased risk for autism and remains a useful screening tool. This study examines M-CHAT accuracy in a large-scale, nationwide sample, examining associations between screening accuracy and developmental outcomes. These findings impact pediatric screening for autism, supporting continued use of the M-CHAT while further elucidating the factors associated with inaccurate screens.

Green Space and Internalizing or Externalizing Symptoms Among Children.

Importance: Evidence suggests that living near green space supports mental health, but studies examining the association of green space with early mental health symptoms among children are rare. Objective: To evaluate the association between residential green space and early internalizing (eg, anxiety and depression) and externalizing (eg, aggression and rule-breaking) symptoms. Design, Setting, and Participants: Data for this cohort study were drawn from the Environmental Influences on Child Health Outcomes cohort; analysis was conducted from July to October 2023. Children born between 2007 and 2013 with outcome data in early (aged 2-5 years) and/or middle (aged 6-11 years) childhood who resided in 41 states across the US, drawing from clinic, hospital, and community-based cohorts, were included. Cohort sites were eligible if they recruited general population participants and if at least 30 children had outcome and residential address data to measure green space exposure. Nine cohorts with 13 sites met these criteria. Children diagnosed with autism or developmental delay were excluded, and 1 child per family was included. Exposures: Green space exposure was measured using a biannual (ie, summer and winter) Normalized Difference Vegetation Index, a satellite image-based indicator of vegetation density assigned to monthly residential history from birth to outcome assessment. Main Outcome and Measures: Child internalizing and externalizing symptoms were assessed using the Child Behavior Checklist for Ages 1½ to 5 or 6 to 18. The association between green space and internalizing and externalizing symptoms was modeled with multivariable linear regression using generalized estimating equations, adjusting for birthing parent educational level, age at delivery, child sex, prematurity, and neighborhood socioeconomic vulnerability. Models were estimated separately for early and middle childhood samples. Results: Among 2103 children included, 1061 (50.5%) were male; 606 (29.1%) identified as Black, 1094 (52.5%) as White, 248 (11.9%) as multiple races, and 137 (6.6%) as other races. Outcomes were assessed at mean (SD) ages of 4.2 (0.6) years in 1469 children aged 2 to 5 years and 7.8 (1.6) years in 1173 children aged 6 to 11 years. Greater green space exposure was associated with fewer early childhood internalizing symptoms in fully adjusted models (b = -1.29; 95% CI, -1.62 to -0.97). No associations were observed between residential green space and internalizing or externalizing symptoms in middle childhood. Conclusions and Relevance: In this study of residential green space and children's mental health, the association of green space with fewer internalizing symptoms was observed only in early childhood, suggesting a sensitive period for nature exposure. Policies protecting and promoting access to green space may help alleviate early mental health risk.

FTO variation and early frontostriatal brain development in children.

OBJECTIVE: Common obesity-associated genetic variants at the fat mass and obesity-associated (FTO) locus have been associated with appetitive behaviors and altered structure and function of frontostriatal brain regions. The authors aimed to investigate the influence of FTO variation on frontostriatal appetite circuits in early life. METHODS: Data were drawn from RESONANCE, a longitudinal study of early brain development. Growth trajectories of nucleus accumbens and frontal lobe volumes, as well as total gray matter and white matter volume, by risk allele (AA) carrier status on FTO single-nucleotide polymorphism rs9939609 were examined in 228 children (102 female, 126 male) using magnetic resonance imaging assessments obtained from infancy through middle childhood. The authors fit functional concurrent regression models with brain volume outcomes over age as functional responses, and FTO genotype, sex, BMI z score, and maternal education were included as predictors. RESULTS: Bootstrap pointwise 95% CI for regression coefficient functions in the functional concurrent regression models showed that the AA group versus the group with no risk allele (TT) had greater nucleus accumbens volume (adjusted for total brain volume) in the interval of 750 to 2250 days (2-6 years). CONCLUSIONS: These findings suggest that common genetic risk for obesity is associated with differences in early development of brain reward circuitry and argue for investigating dynamic relationships among genotype, brain, behavior, and weight throughout development.

Association of maternal education, neighborhood deprivation, and racial segregation with gestational age at birth by maternal race/ethnicity and United States Census region in the ECHO cohorts.

Background: In the United States, disparities in gestational age at birth by maternal race, ethnicity, and geography are theorized to be related, in part, to differences in individual- and neighborhood-level socioeconomic status (SES). Yet, few studies have examined their combined effects or whether associations vary by maternal race and ethnicity and United States Census region. Methods: We assembled data from 34 cohorts in the Environmental influences on Child Health Outcomes (ECHO) program representing 10,304 participants who delivered a liveborn, singleton infant from 2000 through 2019. We investigated the combined associations of maternal education level, neighborhood deprivation index (NDI), and Index of Concentration at the Extremes for racial residential segregation (ICERace) on gestational weeks at birth using linear regression and on gestational age at birth categories (preterm, early term, post-late term relative to full term) using multinomial logistic regression. Results: After adjustment for NDI and ICERace, gestational weeks at birth was significantly lower among those with a high school diploma or less (-0.31 weeks, 95% CI: -0.44, -0.18), and some college (-0.30 weeks, 95% CI: -0.42, -0.18) relative to a master's degree or higher. Those with a high school diploma or less also had an increased odds of preterm (aOR 1.59, 95% CI: 1.20, 2.10) and early term birth (aOR 1.26, 95% CI: 1.05, 1.51). In adjusted models, NDI quartile and ICERace quartile were not associated with gestational weeks at birth. However, higher NDI quartile (most deprived) associated with an increased odds of early term and late term birth, and lower ICERace quartile (least racially privileged) associated with a decreased odds of late or post-term birth. When stratifying by region, gestational weeks at birth was lower among those with a high school education or less and some college only among those living in the Northeast or Midwest. When stratifying by race and ethnicity, gestational weeks at birth was lower among those with a high school education or less only for the non-Hispanic White category. Conclusion: In this study, maternal education was consistently associated with shorter duration of pregnancy and increased odds of preterm birth, including in models adjusted for NDI and ICERace.

Gut-resident microorganisms and their genes are associated with cognition and neuroanatomy in children.

Emerging evidence implicates gut microbial metabolism in neurodevelopmental disorders, but its influence on typical neurodevelopment has not been explored in detail. We investigated the relationship between the microbiome and neuroanatomy and cognition of 381 healthy children, demonstrating that differences in microbial taxa and genes are associated with overall cognitive function and the size of brain regions. Using a combination of statistical and machine learning models, we showed that species including Alistipes obesi, Blautia wexlerae, and Ruminococcus gnavus were enriched or depleted in children with higher cognitive function scores. Microbial metabolism of short-chain fatty acids was also associated with cognitive function. In addition, machine models were able to predict the volume of brain regions from microbial profiles, and taxa that were important in predicting cognitive function were also important for predicting individual brain regions and specific subscales of cognitive function. These findings provide potential biomarkers of neurocognitive development and may enable development of targets for early detection and intervention.

Impact of a Nutrient Formulation on Longitudinal Myelination, Cognition, and Behavior from Birth to 2 Years: A Randomized Clinical Trial.

Observation studies suggest differences in myelination in relation to differences in early life nutrition. This two-center randomized controlled trial investigates the effect of a 12-month nutritional intervention on longitudinal changes in myelination, cognition, and behavior. Eighty-one full-term, neurotypical infants were randomized into an investigational (N = 42) or a control group (N = 39), receiving higher versus lower levels of a blend of nutrients. Non-randomized breastfed infants (N = 108) served as a reference group. Main outcomes were myelination (MRI), neurodevelopment (Bayley-III), social-emotional development (ASQ:SE-2), infant and toddler behavior (IBQ-R and TBAQ), and infant sleep (BISQ) during the first 2 years of life. The full analysis set comprised N = 67 infants from the randomized groups, with 81 myelin-sensitive MRI sequences. Significantly higher myelination was observed in the investigational compared to the control group at 6, 12, 18, and 24 months of life, as well as significantly higher gray matter volume at 24 months, a reduced number of night awakenings at 6 months, increased day sleep at 12 months, and reduced social fearfulness at 24 months. The results suggest that brain development may be modifiable with brain- and age-relevant nutritional approaches in healthy infants and young children, which may be foundational for later learning outcomes.

Associations between area-level arsenic exposure and adverse birth outcomes: An Echo-wide cohort analysis.

BACKGROUND: Drinking water is a common source of exposure to inorganic arsenic. In the US, the Safe Drinking Water Act (SDWA) was enacted to protect consumers from exposure to contaminants, including arsenic, in public water systems (PWS). The reproductive effects of preconception and prenatal arsenic exposure in regions with low to moderate arsenic concentrations are not well understood. OBJECTIVES: This study examined associations between preconception and prenatal exposure to arsenic violations in water, measured via residence in a county with an arsenic violation in a regulated PWS during pregnancy, and five birth outcomes: birth weight, gestational age at birth, preterm birth, small for gestational age (SGA), and large for gestational age (LGA). METHODS: Data for arsenic violations in PWS, defined as concentrations exceeding 10 parts per billion, were obtained from the Safe Drinking Water Information System. Participants of the Environmental influences on Child Health Outcomes Cohort Study were matched to arsenic violations by time and location based on residential history data. Multivariable, mixed effects regression models were used to assess the relationship between preconception and prenatal exposure to arsenic violations in drinking water and birth outcomes. RESULTS: Compared to unexposed infants, continuous exposure to arsenic from three months prior to conception through birth was associated with 88.8 g higher mean birth weight (95% CI: 8.2, 169.5), after adjusting for individual-level confounders. No statistically significant associations were observed between any preconception or prenatal violations exposure and gestational age at birth, preterm birth, SGA, or LGA. CONCLUSIONS: Our study did not identify associations between preconception and prenatal arsenic exposure, defined by drinking water exceedances, and adverse birth outcomes. Exposure to arsenic violations in drinking water was associated with higher birth weight. Future studies would benefit from more precise geodata of water system service areas, direct household drinking water measurements, and exposure biomarkers.

Parent-reported child appetite moderates relationships between child genetic obesity risk and parental feeding practices.

Background: Food parenting practices are associated with child weight. Such associations may reflect the effects of parents' practices on children's food intake and weight. However, longitudinal, qualitative, and behavioral genetic evidence suggests these associations could, in some cases, reflect parents' response to children's genetic risk for obesity, an instance of gene-environment correlation. We tested for gene-environment correlations across multiple domains of food parenting practices and explored the role of parent-reported child appetite in these relationships. Materials and methods: Data on relevant variables were available for N = 197 parent-child dyads (7.54 ± 2.67 years; 44.4% girls) participating in RESONANCE, an ongoing pediatric cohort study. Children's body mass index (BMI) polygenic risk score (PRS) were derived based on adult GWAS data. Parents reported on their feeding practices (Comprehensive Feeding Practices Questionnaire) and their child's eating behavior (Child Eating Behavior Questionnaire). Moderation effects of child eating behaviors on associations between child BMI PRS and parental feeding practices were examined, adjusting for relevant covariates. Results: Of the 12 parental feeding practices, 2 were associated with child BMI PRS, namely, restriction for weight control (ß = 0.182, p = 0.011) and teaching about nutrition (ß = -0.217, p = 0.003). Moderation analyses demonstrated that when children had high genetic obesity risk and showed moderate/high (vs. low) food responsiveness, parents were more likely to restrict food intake to control weight. Conclusion: Our results indicate that parents may adjust their feeding practices in response to a child's genetic propensity toward higher or lower bodyweight, and the adoption of food restriction to control weight may depend on parental perceptions of the child's appetite. Research using prospective data on child weight and appetite and food parenting from infancy is needed to further investigate how gene-environment relationships evolve through development.

The Environmental Influences on Child Health Outcomes (ECHO)-Wide Cohort.

The Environmental Influences on Child Health Outcomes (ECHO)-Wide Cohort Study (EWC), a collaborative research design comprising 69 cohorts in 31 consortia, was funded by the National Institutes of Health (NIH) in 2016 to improve children's health in the United States. The EWC harmonizes extant data and collects new data using a standardized protocol, the ECHO-Wide Cohort Data Collection Protocol (EWCP). EWCP visits occur at least once per life stage, but the frequency and timing of the visits vary across cohorts. As of March 4, 2022, the EWC cohorts contributed data from 60,553 children and consented 29,622 children for new EWCP data and biospecimen collection. The median (interquartile range) age of EWCP-enrolled children was 7.5 years (3.7-11.1). Surveys, interviews, standardized examinations, laboratory analyses, and medical record abstraction are used to obtain information in 5 main outcome areas: pre-, peri-, and postnatal outcomes; neurodevelopment; obesity; airways; and positive health. Exposures include factors at the level of place (e.g., air pollution, neighborhood socioeconomic status), family (e.g., parental mental health), and individuals (e.g., diet, genomics).

The Development of Appetite: Tracking and Age-Related Differences in Appetitive Traits in Childhood.

Appetitive traits are associated with body weight. Increased understanding of how appetitive traits evolve from early life could advance research on obesity risk and inform intervention development. We report on tracking and age-related differences in appetitive traits in childhood within the RESONANCE cohort. Parents of RESONANCE children aged 6.02 ± 2.99 years completed the Child Eating Behavior Questionnaire (CEBQ). Pearson correlations of appetitive traits and age were tested for all participants contributing at least one observation, using each participant's first observation (N = 335). Children's first and second observations of the CEBQ (n = 127) were used to test tracking (paired correlations) and age-related differences (paired t-tests) within individuals. CEBQ correlations with age suggested that satiety responsiveness, slowness in eating, emotional undereating, and desire to drink decreased with age (r = -0.111 to r = -0.269, all p < 0.05), while emotional overeating increased with age (r = 0.207, p < 0.001). Food fussiness demonstrated a quadratic relationship with age. Paired t-tests further supported an increase in emotional overeating with age (M: 1.55 vs. 1.69, p = 0.005). All CEBQ subscales demonstrated moderate to high tracking (r = 0.533 to r = 0.760, p < 0.001). Our initial findings within the RESONANCE cohort suggest that food avoidant traits are negatively related with age, while emotional overeating increases with age, and that appetitive traits track through childhood.

Protocol for a multicenter, double-blinded placebo-controlled randomized controlled trial comparing intravenous ferric derisomaltose to oral ferrous sulfate for the treatment of iron deficiency anemia in pregnancy: The IVIDA2 trial.

BACKGROUND: Iron deficiency anemia (IDA) is common during pregnancy and associated with adverse maternal and neonatal outcomes. Treatment with iron supplementation is recommended during pregnancy, but the optimal delivery route is unclear. Oral iron risks has high risk of gastrointestinal side effects and low absorption. Intravenous iron is infused directly but is expensive. The American College of Obstetricians and Gynecologists currently recommends oral iron to treat IDA in pregnancy with intravenous iron reserved as second-line therapy, if needed. This approach is associated with persistent anemia, increasing the risk of peripartum blood transfusion. We aim to provide data on optimal route of iron repletion for IDA in pregnancy. METHODS: In IVIDA2, a double-blind, placebo controlled, multicenter randomized trial in the United States, 746 pregnant people with moderate-to-severe IDA (hemoglobin <10 g/dL and ferritin <30 ng/mL) at 24-28 weeks' gestation will be randomized 1:1 to either a single 1000 mg dose of intravenous ferric derisomaltose and oral placebo (1-3 times daily) or a single placebo infusion with 1-3 times daily 325 mg ferrous sulfate (65 mg elemental iron) tablet. The primary outcome is peripartum blood transfusion (blood transfusion from delivery to 7 days postpartum). Secondary outcomes include adverse medication reactions, maternal and neonatal hematologic indices, and offspring neurodevelopment. ETHICS AND DISSEMINATION: A central ethical review board-Advarra-granted ethical approval (Pro00060930). Participating centers-Women & Infants Hospital of Rhode Island, University of Michigan Medical Center, Washington University School of Ethics and dissemination: A central ethical review board-Advarra-granted ethical approval (Pro00060930). Participating centers-Women & Infants Hospital of Rhode Island, University of Michigan Medical Center, Washington University School of.

Development of a mobile low-field MRI scanner.

Magnetic resonance imaging (MRI) allows important visualization of the brain and central nervous system anatomy and organization. However, unlike electroencephalography (EEG) or functional near infrared spectroscopy, which can be brought to a patient or study participant, MRI remains a hospital or center-based modality. Low magnetic field strength MRI systems, however, offer the potential to extend beyond these traditional hospital and imaging center boundaries. Here we describe the development of a modified cargo van that incorporates a removable low-field permanent magnet MRI system and demonstrate its proof-of-concept. Using phantom scans and in vivo T2-weighted neuroimaging data, we show no significant differences with respect to geometric distortion, signal-to-noise ratio, or tissue segmentation outcomes in data acquired in the mobile system compared to a similar static system in a laboratory setting. These encouraging results show, for the first time, MRI that can be performed at a participant's home, community center, school, etc. Breaking traditional barriers of access, this mobile approach may enable imaging of patients and participants who have mobility challenges, live long distances from imaging centers, or are otherwise unable to travel to an imaging center or hospital.

A Nutrient Formulation Affects Developmental Myelination in Term Infants: A Randomized Clinical Trial.

BACKGROUND AND OBJECTIVES: Observational studies suggest differences between breast-fed and formula-fed infants in developmental myelination, a key brain process for learning. The study aims to investigate the efficacy of a blend of docosahexaenoic acid (DHA), arachidonic acid (ARA), iron, vitamin B12, folic acid, and sphingomyelin (SM) from a uniquely processed whey protein concentrate enriched in alpha-lactalbumin and phospholipids compared with a control formulation on myelination, cognitive, and behavioral development in the first 6 months of life. METHODS: These are 6-month results from an ongoing two-center, randomized controlled trial with a 12-month intervention period (completed for all participants). In this study, full term, neurotypical infants of both sexes (N = 81) were randomized into investigational (N = 42) or control groups (N = 39). In addition, non-randomized breast-fed children (N = 108) serve as a natural reference group. Main outcomes are myelination (MRI), cognitive (Bayley Scales of Infant and Toddler Development, 3rd edition [Bayley-III]), social-emotional development (Ages and Stages Questionnaires: Social-Emotional, 2nd edition [ASQ:SE-2]), sleep (Brief Infant Sleep Questionnaire [BISQ]), and safety (growth and adverse events [AEs]). RESULTS: The full analyses set comprises N = 66 infants. Significant differences in myelin structure, volume, and rate of myelination were observed in favor of the investigational myelin blend at 3 and 6 months of life. Effects were demonstrated for whole brain myelin and for cerebellar, parietal, occipital, and temporal regions, known to be functionally involved in sensory, motor, and language skills. No statistically significant differences were found for early behavior and cognition scores. CONCLUSIONS: This is the first study demonstrating the efficacy of a myelin nutrient blend in well-nourished, term infants on developmental myelination, which may be foundational for later cognitive and learning outcomes. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT03111927.

Remote and at-home data collection: Considerations for the NIH HEALthy Brain and Cognitive Development (HBCD) study.

The NIH HEALthy Brain and Cognitive Development (HBCD) study aims to characterize the impact of in utero exposure to substances, and related environmental exposures on child neurodevelopment and health outcomes. A key focus of HBCD is opioid exposure, which has disproportionately affected rural areas. While most opioid use and neonatal abstinence syndrome has been reported outside of large cities, rural communities are often under-represented in large-scale clinical research studies that involve neuroimaging, in-person assessments, or bio-specimen collections. Thus, there exists a likely mismatch between the communities that are the focus of HBCD and those that can participate. Even geographically proximal participants, however, are likely to bias towards higher socioeconomic status given the anticipated study burden and visit frequency. Wearables, 'nearables', and other consumer biosensors, however, are increasingly capable of collecting continuous physiologic and environmental exposure data, facilitating remote assessment. We review the potential of these technologies for remote in situ data collection, and the ability to engage rural, affected communities. While not necessarily a replacement, these technologies offer a compelling complement to traditional 'gold standard' lab-based methods, with significant potential to expand the study's reach and importance.

Intravenous versus Oral Iron for Iron-Deficiency Anemia in Pregnancy (IVIDA): A Randomized Controlled Trial.

OBJECTIVE: Iron-deficiency anemia (IDA) can have serious consequences for mothers and babies. Iron supplementation is recommended, but the administration route is controversial. We sought to conduct a randomized controlled trial (RCT) testing the effectiveness and safety of intravenous (IV) iron compared with oral iron on perinatal outcomes in pregnant women with IDA. STUDY DESIGN: This open-label RCT randomized patients with IDA (hemoglobin [hgb] <10 g/dL and ferritin <30 ng/mL) at 24 to 34 weeks' to oral iron or single 1,000-mg dose of IV low-molecular weight iron dextran over one hour. The primary outcome was maternal anemia at delivery (hgb < 11 g/dL). Secondary outcomes were mild/moderate or severe adverse reactions, maternal hgb and ferritin at delivery, blood transfusion, gestational age at delivery, birth weight, neonatal hgb and ferritin, and composite neonatal morbidity. Analysis was as per protocol. RESULTS: The trial was stopped early for logistical reasons, and the data analyzed as preliminary data to inform a larger, potentially externally funded, definitive trial. Of 55 patients approached, 38 consented. Of these, 15 were withdrawn: 5 received IV iron from their primary obstetrician after being randomized to oral iron and 10 declined to receive IV iron. Of the remaining 23 patients, who were included in the analytic population, 13 received oral iron and 10 received IV iron. The rate of maternal anemia at delivery (hgb < 11 g/dL) was high overall but significantly reduced with IV iron (40 vs. 85%, p = 0.039). Rates of maternal hgb < 10 g/dL were significantly lower in the IV iron group (10 vs. 54%, p = 0.029). There were no severe adverse reactions and similar rates of mild/moderate reactions between groups. CONCLUSION: IV iron reduces rates of anemia at the time of admission for delivery, supporting a larger RCT comparing IV versus oral iron for the treatment of IDA of pregnancy powered for definitive clinical outcomes. However, issues uncovered in this RCT suggest that patient, clinician, and systems-level barriers associated with different IDA treatment modalities must be considered prior to conducting a larger RCT. This study is registered with clinicaltrials.gov with identifier no.: NCT03438227. KEY POINTS: · IV iron decreases rates of anemia on admission for delivery compared with oral iron.. · In an unblinded randomized trial, a significant proportion of patients preferred alternate therapy.. · Future RCTs should incorporate double-blinded technique to reduce risk of patient crossover.. · Results from feasibility trial support a larger RCT comparing IV to oral iron for IDA in pregnancy..

Family SES Is Associated with the Gut Microbiome in Infants and Children.

BACKGROUND: While early life exposures such as mode of birth, breastfeeding, and antibiotic use are established regulators of microbiome composition in early childhood, recent research suggests that the social environment may also exert influence. Two recent studies in adults demonstrated associations between socioeconomic factors and microbiome composition. This study expands on this prior work by examining the association between family socioeconomic status (SES) and host genetics with microbiome composition in infants and children. METHODS: Family SES was used to predict a latent variable representing six genera abundances generated from whole-genome shotgun sequencing. A polygenic score derived from a microbiome genome-wide association study was included to control for potential genetic associations. Associations between family SES and microbiome diversity were assessed. RESULTS: Anaerostipes, Bacteroides, Eubacterium, Faecalibacterium, and Lachnospiraceae spp. significantly loaded onto a latent factor, which was significantly predicted by SES (p < 0.05) but not the polygenic score (p > 0.05). Our results indicate that SES did not predict alpha diversity but did predict beta diversity (p < 0.001). CONCLUSIONS: Our results demonstrate that modifiable environmental factors influence gut microbiome composition at an early age. These results are important as our understanding of gut microbiome influences on health continue to expand.

Accessible pediatric neuroimaging using a low field strength MRI scanner.

Magnetic resonance imaging (MRI) has played an increasingly relevant role in understanding infant, child, and adolescent neurodevelopment, providing new insight into developmental patterns in neurotypical development, as well as those associated with potential psychopathology, learning disorders, and other neurological conditions. In addition, studies have shown the impact of a child's physical and psychosocial environment on developing brain structure and function. A rate-limiting complication in these studies, however, is the high cost and infrastructural requirements of modern MRI systems. High costs mean many neuroimaging studies typically include fewer than 100 individuals and are performed predominately in high resource hospitals and university settings within high income countries (HICs). As a result, our knowledge of brain development, particularly in children who live in lower and middle income countries (LMICs) is relatively limited. Low field systems, with magnetic fields less than 100mT offer the promise of lower scanning costs and wide-spread global adoption, but routine low field pediatric neuroimaging has yet to be demonstrated. Here we present the first pediatric MRI data collected on a low cost and assessable 64mT scanner in children 6 weeks to 16 years of age and replicate brain volumes estimates and developmental trajectories derived from 3T MRI data. While preliminary, these results illustrate the potential of low field imaging as a viable complement to more conventional high field imaging systems, and one that may further enhance our knowledge of neurodevelopment in LMICs where malnutrition, psychosocial adversities, and other environmental exposures may profoundly affect brain maturation.

Functional connectivity correlates of infant and early childhood cognitive development.

Childhood is defined by the development of cognitive abilities as well as brain growth and function. While prior neuroimaging studies have investigated early development fragmentally, we studied the typical development of functional network connectivity continuously from infancy to childhood (average of 24 months) in 196 singleton term born children, as well as their emergence with age and visual, motor, and language abilities as assessed using the Mullen Scales of Early Learning. We demonstrate a cross-age shift to networks linked to higher-order cognitive processes, paralleling previous findings about developmental courses of functional connectivity networks. When investigating skill associations with functional connectivity independent of age, we revealed distinct network connectivity patterns for visual, motor, and language skills as each of them become more and more refined along childhood development. Specifically, the amount of functional networks recruited increases with skill complexity, with an exceeding involvement of higher order networks enabling daily maintenance and coordination of cognitive functions. Further, both motor and language network connectivity patterns overlapped in network connectivity patterns for the default mode, visual, salience, and dorsal attention networks, possibly implicating their overarching contribution to each other's and higher cognitive development.