Infant Iron Research Articles

Assessment of Risk Factors for Women with Iron Deficiency Anemia During Pregnancy

Background: Globally, iron insufficiency is the most common nutrient deficiency and the primary cause of anemia. Iron deficiency can result in maternal anemia and decreased infant iron reserves due to increased iron demand during pregnancy. Objective: The study was designed to assess the risk factors encountered during pregnancy among pregnant women with iron deficiency anemia. Materials and Methods: The study was conducted on one hundred pregnant women enrolled on the health care centers who were diagnosed as anemic. The data were obtained from all through direct interviews using a special questionnaire covering the sociodemographic characteristics, diet habits, and supplements taken during pregnancy. The one-way ANOVA test analysis was done to see the association of each variable with the anemia severity. The probability value <0.05 was considered statistically significant. Results: The results indicated that there was no statistically significant relation between iron deficiency anemia and all the socio-demographic characteristics which included; age, parity, educational level, occupation, family size, and gestational age. While there is a highly statistically significant relation between iron deficiency anemia and diet habit of pregnant women regarding the frequency of intake of meats, fishes, vegetables, and fruits at p-value = 0.001, intake pulse at p-value = 0.012, intake of nuts at p-value = 0.021, and drinking tea at p-value = 0.001. Conclusion: Educating pregnant women to eat iron-rich foods may be useful as a strategy for reducing iron deficiency anemia during pregnancy, also using of iron supplements, folic acid and vitamin B12 is regarded as a successful way to treat anemia.

Early life stress and iron metabolism in developmental psychoneuroimmunology

An estimated 250 million children face adverse health outcomes from early life exposure to severe or chronic social, economic, and nutritional adversity, highlighting/emphasizing the pressing concern about the link between ELS and long-term implications on mental and physical health. There is significant overlap between populations experiencing high levels of chronic stress and those experiencing iron deficiency, spotlighting the potential role of iron as a key mediator in this association. Iron, an essential micronutrient for brain development and immune function, is often depleted in stress conditions. Iron deficiency among the most common nutrient deficiencies in the world. Fetal and infant iron status may thus serve as a crucial intermediary between early chronic psychological stress and subsequent immune system changes to impact neurodevelopment. The review presents a hypothesized pathway between early life stress (ELS), iron deficiency, and neurodevelopment through the hypothalamic-pituitary-adrenocortical (HPA) axis and the IL-6-hepcidin axis. This hypothesis is derived from (1) evidence that stress impacts iron status (2) long-term neurodevelopmental outcomes that are shared by ELS and iron deficiency exposure, and (3) possible mechanisms for how iron may mediate the relation between ELS and iron deficiency through alterations in the developing immune system. The article concludes by proposing future research directions, emphasizing the need for rigorous studies to elucidate how stress and iron metabolism interact to modify the developing immune system. Understanding these mechanisms could open new avenues for improving human health and neurodevelopment for women and children globally, making it a timely and vital area of study in psychoneuroimmunology research.

Umbilical Cord Plasma Ferritin Concentration as a Proxy Measure of Infant Iron Status: An Exploratory Analysis Among Term and Preterm Infants Born in Vancouver, Canada

Umbilical Cord Plasma Ferritin Concentration as a Proxy Measure of Infant Iron Status: An Exploratory Analysis Among Term and Preterm Infants Born in Vancouver, Canada

Baby Food Pouches, Baby-Led Weaning, and Iron Status in New Zealand Infants: An Observational Study.

Iron deficiency in infants can impact development, and there are concerns that the use of baby food pouches and baby-led weaning may impair iron status. First Foods New Zealand (FFNZ) was an observational study of 625 New Zealand infants aged 6.9 to 10.1 months. Feeding methods were defined based on parental reports of infant feeding at "around 6 months of age": "frequent" baby food pouch use (five+ times per week) and "full baby-led weaning" (the infant primarily self-feeds). Iron status was assessed using a venepuncture blood sample. The estimated prevalence of suboptimal iron status was 23%, but neither feeding method significantly predicted body iron concentrations nor the odds of iron sufficiency after controlling for potential confounding factors including infant formula intake. Adjusted ORs for iron sufficiency were 1.50 (95% CI: 0.67-3.39) for frequent pouch users compared to non-pouch users and 0.91 (95% CI: 0.45-1.87) for baby-led weaning compared to traditional spoon-feeding. Contrary to concerns, there was no evidence that baby food pouch use or baby-led weaning, as currently practiced in New Zealand, were associated with poorer iron status in this age group. However, notable levels of suboptimal iron status, regardless of the feeding method, emphasise the ongoing need for paying attention to infant iron nutrition.

Non Breast-Milk-Fed Very Preterm Infants Are at Increased Risk of Iron Deficiency at 4-6-Months Corrected Age: A Retrospective Population-Based Cohort Study.

Iron supplementation is routinely recommended for breast-milk-fed preterm infants. However, the Canadian Pediatric Society recommends no additional iron supplementation for preterm infants fed primarily with iron-rich formula. Other pediatric societies don't provide specific guidance on supplemental iron for formula-fed preterm infants. This study investigated how feeding type influences iron status of very preterm infants at 4-6-months corrected age (CA). A retrospective cohort study was conducted using a population-based database on all very preterm infants (<31 weeks gestational age) born in Nova Scotia, Canada from 2005-2018. Information about feeding type, iron intake from formula, supplemental iron therapy and iron status at 4-6-months CA was extracted. Iron deficiency (ID) was defined as serum ferritin <20 and <12 µg/L at 4-and 6-months CA, respectively. Of 392 infants, 107 were "breast-milk-fed" (exclusively or partially) and 285 were "not breast-milk-fed" (exclusively fed with iron-rich formula) at 4-6-months CA. Total daily iron intake was higher in the non-breast-milk-fed group (2.6 mg/kg/day versus 2.0 mg/kg/day). Despite this, 36.8% of non-breast-milk-fed infants developed ID versus 20.6% of breast-milk-fed infants. ID is significantly more prevalent in non-breast-milk-fed infants than breast-milk-fed infants despite higher iron intake. This suggests the need to revisit recommendations for iron supplementation in non-breast-milk-fed preterm infants.

RAPIDIRON Trial follow-up study — the RAPIDIRON-KIDS Study: protocol of a prospective observational follow-up study

BackgroundAnemia is a worldwide problem with iron deficiency being the most common cause. When anemia occurs in pregnancy, it increases the risk of adverse maternal, fetal, and postnatal outcomes. It induces preterm births and low birth weight (LBW) deliveries, long-term neurodevelopmental sequelae, and an increased risk of earlier onset of postnatal iron deficiency. Anemia rates are among the highest in South Asia, and India’s National Family Health Survey (NFHS-5) for 2019–2021 indicated that over half of pregnant women, and more than 65% of children, in the country are classified as anemic (Sciences IIfP, National Family Health Survey-5, 2019–21, India Fact Sheet). In 2021, the parent RAPIDIRON Trial (Derman et al., Trials 22:649, 2021) was initiated in two states in India, with the goal of assessing whether a dose of intravenous (IV) iron given to anemic women during early pregnancy results in a greater proportion of participants with normal hemoglobin concentrations in the third trimester and a lower proportion of participants with LBW deliveries compared to oral iron. As a follow-up to the RAPIDIRON Trial, the RAPIDIRON-KIDS Study will follow the offspring of previously randomized mothers to assess, neurobehavioral, hematological, and health outcomes.MethodsThis prospective observational cohort study will follow a subset of participants previously randomized as part of the RAPIDIRON Trial and their newborns. Study visits occur at birth, 6 weeks, 4 months, 12 months, 24 months, and 36 months and include blood sample collection with both maternal and infant participants and specific neurobehavioral assessments conducted with the infants (depending on the study visit). The primary outcomes of interest are (1) infant iron status as indicated by both hemoglobin and ferritin (a) at birth and (b) at 4 months of age and (2) the developmental quotient (DQ) for the cognitive domain of the Bayley Scales of Infant Development Version IV (BSID-IV) at 24 months of age.DiscussionThis RAPIDIRON-KIDS Study builds upon its parent RAPIDIRON Trial by following a subset of the previously randomized participants and their offspring through the first 3 years of life to assess neurodevelopmental and neurobehavioral (infants, children), hematological, and health outcomes.Trial registrationClinicalTrials.gov NCT05504863, Registered on 17 August 2022. Clinical Trials Registry – India CTRI/2022/05/042933. Registered on 31 May 2022.

Developmental coupling of brain iron and intrinsic activity in infants during the first 150 days

Brain iron is vital for core neurodevelopmental processes including myelination and neurotransmitter synthesis and, accordingly, iron accumulates in the brain with age. However, little is known about the association between brain iron and neural functioning and how they evolve with age in early infancy. This study investigated brain iron in 48 healthy infants (22 females) aged 64.00 ± 33.28 days by estimating R2 * relaxometry from multi-echo functional MRI (fMRI). Linked independent component analysis was performed to examine the association between iron deposition and spontaneous neural activity, as measured by the amplitude of low frequency fluctuations (ALFF) by interrogating shared component loadings across modalities. Further, findings were validated in an independent dataset (n = 45, 24 females, 77.93 ± 26.18 days). The analysis revealed developmental coupling between the global R2 * and ALFF within the default mode network (DMN). Furthermore, we observed that this coupling effect significantly increased with age (r = 0.78, p = 9.2e-11). Our results highlight the importance of iron-neural coupling during early development and suggest that the neural maturation of the DMN may correspond to growth in distributed brain iron.

Maternal prenatal, with or without postpartum, vitamin D3 supplementation does not improve maternal iron status at delivery or infant iron status at 6 months of age: secondary analysis of a randomised controlled trial

BackgroundVitamin D may modify iron status through regulation of hepcidin and inflammatory pathways. This study aimed to investigate effects of maternal vitamin D supplementation on iron status in pregnancy and...

Alterations in Placental Inflammation-Related Gene Expression Partially Mediate the Effects of Prenatal Alcohol Consumption on Maternal Iron Homeostasis.

Prenatal alcohol exposure (PAE) is associated with alterations in maternal and infant iron homeostasis that are consistent with changes seen in the setting of inflammation. We hypothesized that PAE leads to alterations in the placental expression of genes related to iron metabolism and inflammation that play functional roles in the teratogenic effects of alcohol on iron homeostasis. A total of 126 heavy-drinking women (≥1 oz (30 mL) absolute alcohol/day (~1.67 standard drinks/day) or women reporting binge drinking (≥2 drinks/occasion)) and 80 control women (<0.5 oz AA per day, no binging) in Cape Town, South Africa were interviewed prenatally regarding demographics, and alcohol, smoking, and drug use around conception and during pregnancy. Prenatal/maternal and infant hemoglobin and ferritin were measured. Whole-transcriptome RNA sequencing analysis was performed on flash-frozen transplacental tissue samples. Gene sets related to iron metabolism (n = 398) and inflammation (n = 467) were constructed by searching the Molecular Signatures Database for related ontology terms. Principal component analysis (PCA) yielded 59 factors for each theme. In multivariable regression models, PAE was related to 2 iron metabolism PCA factors (PCs) and 5 inflammation PCs, among which 2 iron metabolism and 4 inflammation factors were related to at least 1 key maternal or infant iron outcome. In causal inference analyses based on marginal structural models and the product method, the alterations in the expression profile of genes with functions in immune cell regulation, cytokine activity, angiogenesis, hematopoiesis, and ubiquitous cell processes appeared to partially mediate the relation of prenatal drinking frequency (days/week) around conception to a lower maternal hemoglobin-to-log(ferritin) ratio (proportion mediation = 51.35%). These findings suggest that placental inflammation may be partly responsible for the differences in alcohol-related iron homeostasis patterns between pregnant and non-pregnant adults.

Protocol and statistical analysis plan for a randomized controlled trial of the effect of intravenous iron on anemia in Malawian pregnant women in their third trimester (REVAMP – TT)

Background: Anemia affects 40% of pregnant women globally, leading to maternal mortality, premature birth, low birth weight, and poor baby development. Iron deficiency causes over 40% of anemia cases in Africa. Oral iron supplementation is insufficient for Low-and-Middle-Income-Countries (LMICs) to meet current WHO targets. We hypothesized that a single intravenous dose of Ferric Carboxymaltose (FCM) may be more effective than oral iron treatment for anemia recovery, particularly in these settings where women present late for antenatal care. Methods: This is a two-arm parallel open-label individual-randomized controlled trial in third trimester, in malaria Rapid Diagnostic Test-negative pregnant women with moderate or severe anemia - capillary hemoglobin &lt;10 g/dL – who are randomized to receive either parenteral iron – with FCM – or standard-of-care oral iron for the remainder of pregnancy. This is the sister trial to the second-trimester REVAMP trial, funded by the Bill and Melinda Gates Foundation (trial registration ACTRN12618001268235, Gates Grant number INV-010612). In REVAMP-TT, recruitment and treatment are performed within primary health centers. The trial will recruit 590 women across Zomba district, Malawi. The primary outcome is the proportion of anemic women - venous hemoglobin &lt;11 g/dL - at 36 weeks’ gestation or delivery (whichever occurs first). Other pre-specified key secondary clinical and safety outcomes include maternal iron-status and hypophosphatemia, neonate birth weight, infant growth and infant iron and hematological parameters. Discussion: This study will determine whether FCM, delivered within primary health centers, is effective, safe and feasible for treating moderate to severe anemia in third-trimester pregnant Malawian women. This intervention could have long-term benefits for maternal and child health, resulting in improved survival and child development.

Justification of Universal Iron Supplementation for Infants 6-12 months in Regions with a High Prevalence of Thalassemia.

Many clinicians hesitate to adopt a universal infant iron supplementation program due to the risk of increased iron absorption for those with thalassemia. We aimed to determine thalassemia prevalence in 6- to 12-month-old infants, along with the iron status of those with and without thalassemia. We performed a cross-sectional descriptive study of infants attending the Well Baby Clinic at Thammasat University Hospital for routine checkups. Complete blood count, hemoglobin electrophoresis, iron parameters, and molecular genetics for common α- and β-thalassemia were evaluated. Overall, 97 of 206 (47%) participants had thalassemia minor, the majority having Hb E traits. None had thalassemia intermedia or major. Familial history of anemia or thalassemia presented an increased risk of detecting thalassemia minor in offspring (OR 5.18; 95% CI 2.60-10.33, p=0.001). There were no statistical differences in transferrin saturation, serum ferritin and hepcidin between iron-replete infants with thalassemia minor and those without. However, one-third of infants with thalassemia minor (31/97) also had iron deficiency anemia (IDA), with a similar risk of having iron deficiency to infants without thalassemia. There was no hepcidin suppression in our infants with thalassemia minor as compared to controls. Both thalassemia and IDA are endemic to Southeast Asia. Infants with thalassemia minor, particularly with Hb E and α-thalassemia traits, are at risk of IDA. Our short-term universal iron supplementation program for 6- to 12-month-old infants does not appear to increase the risk of those with thalassemia minor developing iron overload in the future.

Iron-Fortified Foods Are Needed To Meet the Estimated Average Requirement for Iron in Australian Infants Aged 6 to 12 Months

BackgroundMeeting iron intake recommendations is challenging for infants 6–12 mo, especially breastfed infants. Three-quarters of Australian infants 6–12 mo have iron intakes below the estimated average requirement (7 mg), placing them at risk of iron deficiency. After 6 mo, breastmilk is no longer sufficient to meet the increased demand for iron, and iron-rich complementary foods are recommended. Iron-fortified foods may be a means of improving iron intake in infants, particularly those that are breastfed. ObjectivesThe aims of the study were as follows: 1) to examine the effect of milk-type and fortified foods on iron intake and the prevalence of inadequacy in infants 6–12 mo; 2) to model the effect of fixed amounts of iron-fortified infant cereal (IFIC) at 6 levels of iron fortification on total iron intake and the prevalence of inadequacy; and 3) to assess the effect IFIC on the intake of other nutrients in the diet. DesignSecondary analysis of cross-sectional dietary intake data of infants 6–12 mo (n = 286) participating in the Australian Feeding Infants and Toddlers Study (OzFITS) 2021. ResultsMedian (interquartile range) iron intake was 8.9 (7.5, 10.3); 6.3 (4.5, 8.2); and 2.7 (1.5, 4.4) mg/d in formula-fed, combination-fed, and breastfed infants, respectively. The corresponding prevalence of inadequacy was 19%, 67%, and 96%. Infants who consumed fortified foods had higher median iron intakes than those who did not, 6.2 compared with 1.9 mg/d. Dietary modeling showed that consuming 18 g (300 kJ) of IFIC, fortified at 35 mg/100 g dry weight, reduces the prevalence of inadequacy for iron from 75% to 5% for all infants. ConclusionsIron intakes are low in Australian infants, especially for breastfed infants in the second half of infancy. Modeling shows that 300 kJ of IFIC, the current manufacturer-recommended serving, fortified at 35 mg/100 g dry weight, added to infant diets would be an effective means to reduce the prevalence of inadequacy for iron.

P07-041-23 Iron-Fortified Foods Are Needed To Meet the Estimated Average Requirement for Iron in Australian Infants 6– 12 Months

P07-041-23 Iron-Fortified Foods Are Needed To Meet the Estimated Average Requirement for Iron in Australian Infants 6– 12 Months

The Emerging Roles of Ferroptosis in Neonatal Diseases.

Ferroptosis is a novel type of programmed cell death involved in many diseases' pathological processes. Ferroptosis is characterized by lipid peroxidation, reactive oxygen species accumulation, and iron metabolism disorder. Newborns are susceptible to ferroptosis due to their special physiological state, which is prone to abnormal iron metabolism and the accumulation of reactive oxygen species. Recent studies have linked ferroptosis to a variety of diseases in the neonatal period (including hypoxic-ischemic encephalopathy, bronchopulmonary dysplasia, and necrotizing enterocolitis). Ferroptosis may become an effective target for the treatment of neonatal-related diseases. In this review, the ferroptosis molecular mechanism, metabolism characteristics of iron and reactive oxygen species in infants, the relationship between ferroptosis and common infant disorders, and the treatment of infant diseases targeted for ferroptosis are systematically summarized.

Comparison of two dosage regimens of iron in preterm infants for the prevention of iron deficiency: A prospective interventional study

Abstract BACKGROUND: The majority of infants born &lt;32 weeks of gestation develop anemia. The cause depends on multiple factors, most common being iron deficiency. Iron being a major nutrient, its deficiency may lead to irreversible neurodevelopment and cognitive impairment and overdose lead to neurodegeneration and gastrointestinal intolerance. Although the need for iron and outcome of iron deficiencies has been studied much, valid studies pertaining dosage for prevention of iron deficiency in preterm infants are insufficient. OBJECTIVE: To compare two dosage regimens of iron for the prevention of iron deficiency among preterm infants born &lt;32 weeks at 6 weeks of chronological age. MATERIALS AND METHODS: A prospective interventional study performed in a level III neonatal intensive care unit. A total of 64 infants with &lt;32 weeks of gestation were studied, were classified into two grouped, and initiated with iron at two different doses (2 and 4 mg/kg/day). The preintervention and postintervention hemoglobin and serum ferritin were compared at 6 weeks of chronological age. RESULTS: Of the 32 babies with iron initiated at 2 mg/kg/day, 21 babies had low hemoglobin level and 11 babies had normal hemoglobin level, and 10 babies had low ferritin level and 22 babies had normal ferritin level. Of the 32 babies with iron at 4 mg/kg/day, all babies had normal hemoglobin and ferritin levels. Conclusion: The incidence of anemia is lower in the infants receiving iron at 4 mg/kg/day compared with infants receiving iron at 2 mg/kg/day.

Iron and DHA in Infant Formula Purchased in the US Fails to Meet European Nutrition Requirements.

Requirements for iron and docosahexaenoic acid (DHA) content of infant formula varies by country. Powdered full-term infant formula purchase data from all major physical stores in the US between 2017-2019 were obtained from CIRCANA, Inc. Iron and DHA composition and scoop sizes for each formula were obtained from manufacturers. The equivalent liquid ounces of prepared formula were calculated. Average iron and DHA content were compared between formula types and to both US and European formula composition requirements. These data represent 55.8 billion ounces of formula. The average iron content of all formula purchased was: 1.80 mg/100 kcal. This iron concentration is within the FDA regulations. However, it exceeds the maximum allowable iron concentration of infant formula (Stage 1) set by the European Commission of 1.3 mg/100 kcal. A total of 96% of formula purchased had an iron concentration of >1.3 mg/100 kcal. DHA is not a required ingredient in US formulas. The average DHA content of all formula purchased was: 12.6 mg/100 kcal. This DHA concentration is far below the minimum required DHA concentrations of infant formula (Stage 1) and follow-on formula (Stage 2) set by the European Commission of 20 mg/100 kcal. These are novel insights into the iron and DHA intake of formula-fed infants in the US. As international infant formulas have entered the US market due to the formula shortage, parents and providers need to be aware of regulatory differences in formula nutrient composition.

Iron Profile in Term Small for Gestational Age Infants at 10 Weeks of Age and Correlation With Maternal Iron Profile: A Prospective Cohort Study

Term small for gestational age (SGA) babies are at risk for developing iron deficiency anemia. The association between maternal and infant iron stores is not clear. To assess proportion of term SGA neonates developing iron deficiency anemia by 10 weeks of age, and measure correlation between iron profile and hepcidin of babies at birth and at 10 weeks of age with maternal iron profile. Prospective cohort study conducted from November, 2018 to April, 2020. 120 term SGA babies and their mothers. Hemogram, iron profile and serum hepcidin (every fourth case) estimated in mother, cord blood and baby at 10 weeks. Babies developing anemia at 6 weeks detected by hemogram and ferritin were started on iron supplementation and excluded from the study. Proportion of babies developing iron deficiency anemia at 10 weeks of age. 35 (29.2%) of 120 term SGA babies developed anemia (hemoglobin <9 g/dL) at 6 weeks. Proportion of infants who developed iron deficiency anemia (hemoglobin <9 g/dL and serum ferritin <40 µ/dL) at 6 and 10 weeks of age was 14.2% and 23.3%, respectively. No significant correlation was found bet-ween hemoglobin, iron and hepcidin of the baby in cord blood and at 10 weeks of age with that of mothers. Serum hepcidin in babies at birth (137.5 ng/mL) were higher than maternal values (128 ng/mL). A significant proportion of term SGA infants deve-loped anemia during early infancy, irrespective of maternal iron status.

Defining Anaemia across the Lifecycle in Healthy Reference Populations: An Analysis for Guideline Development

Background Detection of anaemia is critical for clinical medicine and public health in high and low income settings, but anaemia definitions are uncertain, causing discordance across different laboratories and guidelines. Current WHO anaemia definitions, set in 1968 using limited data, reflect the 5th centile of the haemoglobin distribution in apparently healthy populations. WHO is now reviewing these definitions. Haemoglobin concentration is sensitive to iron and other nutrient deficiencies, inflammation, renal impairment, and genetic conditions, and thus conservative criteria to obtain a healthy reference population is crucial in estimating the 5th centile. To support WHO definitions, this study estimated the 5th centile for haemoglobin in healthy reference populations derived from a secondary analysis of large cohorts. Methods We identified data sources from which sufficient clinical and laboratory data were available to identify an apparently healthy reference sample. These comprised the National Health and Nutrition Examination Survey (NHANES, USA, 8 survey years); Health Survey for England (HSE, England, 4 survey years); the Australian Health Survey (AHS), comprising 2 separate surveys: National Health Survey (NHS, Australia) and National Nutrition and Physical Activity Survey (NNPAS, Australia); TARGetKids! (prospective longitudinal cohort of children, Canada); BRISC (trial of oral iron in infants, Bangladesh); Generation R (prospective cohort of pregnant women, Netherlands). Markers or iron status and inflammation were available in all surveys, with exclusions for ferritin<15ug/L (or <12ug/L in children <5 years), or C-Reactive Protein (CRP) >5mg/L. Where possible, exclusions were applied based on renal function, folate, and active B12. Clinical data from all surveys (except Generation R) excluded individuals with pre-existing health conditions, use of medication (other than contraception), recent illness or hospital admission. In the pregnant Generation R group, those with pregnancy complications were excluded. In all groups, current smokers and those who consumed excess alcohol were excluded. Adults with BMI <18.5 or >30kg/m2 were excluded; children were excluded if growth z-scores were <-2 or >+2. In children <24months, those with birth complications or prematurity were excluded. Thresholds were defined in adult men (18-65 years), adult non-pregnant women (18-65 years), pregnant women (18-45 years, by trimester), and children (6-23 months, 24-59 months, 5-11 years, 12-17 years). Discrete 2.5th and 5th centiles were estimated along with two-sided 90% confidence intervals for each data set and estimates were combined across all data sources using a fixed-effect meta-analysis approach. Results In non pregnant adult men and women (total n=57,896 individuals), exclusions resulted in an apparently healthy group of 15-20% of each survey (less where survey years were missing required biochemistry). A broad range of self-reported ethnicities/ancestries were represented. For example in healthy adults: NHANES 17-33% of participants identified as White; HSE >90% identified as White; AHS 50-60% reported European ancestry. 5th centiles of the distribution of haemoglobin values in the derived reference samples were obtained (see Figure 1 for example in non-pregnant women). Pooled estimates for each sample are shown in Table 1. The results generally align with current WHO thresholds, other than adult men, where a 5th centile of 135.1g/L (90% CI 134.4-135.7) is above the WHO threshold of 130g/L, and in children 6-23 months where the 5th centile of 104.5g/L (90% CI 103.6-105.4) is lower than the current value of 110g/L. Our data support the current threshold in non-pregnant adult women of 120g/L. Sensitivity analyses suggest persons of Black race or ethnicity may have 5th centiles lower than values of White persons (predominantly within the US surveys), but presence of haemoglobinopathy as well as other contributing factors cannot be excluded. Conclusion In this analysis using stringent criteria to define healthy reference group at low risk of iron/ other nutrient deficiency, or inflammation, we have estimated statistical thresholds to define anaemia across the lifecycle. These data contribute to WHO guideline development, and provide a platform for harmonisation of thresholds across different laboratories and clinical guidelines. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Mediating and Moderating Effects of Iron Homeostasis Alterations on Fetal Alcohol-Related Growth and Neurobehavioral Deficits.

We have previously demonstrated prenatal alcohol exposure (PAE)-related alterations in maternal and infant iron homeostasis. Given that early iron deficiency and PAE both lead to growth restriction and deficits in recognition memory and processing speed, we hypothesized that PAE-related iron homeostasis alterations may mediate and/or moderate effects of PAE on growth and neurobehavior. We examined this hypothesis in a prenatally recruited, prospective longitudinal birth cohort [87 mother-infant pairs with heavy prenatal alcohol exposure (mean = 7.2 drinks/occasion on 1.4 days/week); 71 controls], with serial growth measures and infant neurobehavioral assessments. PAE was related to growth restriction at 2 weeks and 5 years, and, in infancy, poorer visual recognition memory, slower processing speed, lower complexity of symbolic play, and higher emotionality and shyness on a parental report temperament scale. Lower maternal hemoglobin-to-log(ferritin) ratio, which we have shown to be associated with PAE, appeared to exacerbate PAE-related 2-week head circumference reductions, and elevated maternal ferritin, which we have shown to be associated with PAE, appeared to exacerbate PAE-related visual recognition memory deficits. In causal inference analyses, PAE-related elevations in maternal ferritin and hemoglobin:log(ferritin) appeared to statistically mediate 22.6–82.3% of PAE-related growth restriction. These findings support potential mechanistic roles of iron homeostasis alterations in fetal alcohol spectrum disorders (FASD).

A hybrid type I, multi-center randomized controlled trial to study the implementation of a method for Sustained cord circulation And VEntilation (the SAVE-method) of late preterm and term neonates: a study protocol

BackgroundAn intact umbilical cord allows the physiological transfusion of blood from the placenta to the neonate, which reduces infant iron deficiency and is associated with improved development during early childhood. The implementation of delayed cord clamping practice varies depending on mode of delivery, as well as gestational age and neonatal compromise. Emerging evidence shows that infants requiring resuscitation would benefit if respiratory support were provided with the umbilical cord intact. Common barriers to providing intact cord resuscitation is the availability of neonatal resuscitation equipment close to the mother, organizational readiness for change as well as attitudes and beliefs about placental transfusion within the multidisciplinary team. Hence, clinical evaluations of cord clamping practice should include implementation outcomes in order to develop strategies for optimal cord management practice.MethodsThe Sustained cord circulation And Ventilation (SAVE) study is a hybrid type I randomized controlled study combining the evaluation of clinical outcomes with implementation and health service outcomes. In phase I of the study, a method for providing in-bed intact cord resuscitation was developed, in phase II of the study the intervention was adapted to be used in multiple settings. In phase III of the study, a full-scale multicenter study will be initiated with concurrent evaluation of clinical, implementation and health service outcomes. Clinical data on neonatal outcomes will be recorded at the labor and neonatal units. Implementation outcomes will be collected from electronic surveys sent to parents as well as staff and managers within the birth and neonatal units. Descriptive and comparative statistics and regression modelling will be used for analysis. Quantitative data will be supplemented by qualitative methods using a thematic analysis with an inductive approach.DiscussionThe SAVE study enables the safe development and evaluation of a method for intact cord resuscitation in a multicenter trial. The study identifies barriers and facilitators for intact cord resuscitation. The knowledge provided from the study will be of benefit for the development of cord clamping practice in different challenging clinical settings and provide evidence for development of clinical guidelines regarding optimal cord clamping.Trial registrationClinicaltrials.gov, NCT04070560. Registered 28 August 2019.