Impact of maternal, antenatal and birth-associated factors on iron stores at birth: data from a prospective maternal–infant birth cohort

Background/Objectives: Low serum ferritin concentrations at birth, which reflect neonatal iron stores, track through to early childhood and have been associated with poorer neurodevelopmental outcomes. We aimed to identify maternal, antenatal and birth-associated factors that influence iron stores at birth in a prospective maternal–infant birth cohort. Subjects/Methods: In a population-based, longitudinal, birth cohort in Ireland, 413 maternal–infant dyads with prospectively collected lifestyle and clinical data from 15 weeks’ gestation had umbilical cord serum ferritin concentrations measured. Regression models were developed to identify independent factors associated with cord ferritin concentrations. Results: Median (IQR) cord ferritin concentrations were 185.7 (131.7, 385.5) μg/l, and 8% (n=33) of infants had low iron stores (ferritin <76 μg/l) at birth. Maternal obesity (BMI 30 kg/m2) at 15 weeks’ gestation (adj. estimate (95% confidence interval (CI)): −66.4 (−106.9, −25.9) μg/l, P<0.0001) and delivery by caesarean section (−38.8 (−70.2, −7.4) μg/l, P=0.016) were inversely associated with cord ferritin concentrations. In addition, maternal smoking at 15 weeks’ gestation (adj. odds ratio (95% CI): 2.9 (1.2, 7), P=0.020) and being born small-for-gestational age (3.4 (1.3, 8.9), P=0.012) were associated with an increased risk of low iron stores (ferritin <76 μg/l) at birth. Conclusions: We have identified a number of potentially modifiable lifestyle factors that influence iron stores at birth, with the important role of overall maternal health and lifestyle during pregnancy highlighted. Public health policies targeting women of child-bearing age to improve nutrition and health outcomes should be prioritised for the health of the next generation

Improvements in quality of life in children following epicutaneous immunotherapy (EPIT) for peanut allergy in the PEPITES and PEOPLE studies

Background: Food allergy quality of life (FAQL) is impaired in children with peanut allergy. Food Allergy Quality of Life Questionnaires (FAQLQs) provide disease-specific insight into the burden of peanut allergy and potential FAQL changes after peanut immunotherapy. Objective: To examine FAQL changes in children after treatment with epicutaneous immunotherapy for peanut allergy (250 μg, daily epicutaneous peanut protein; DBV712 250 μg). Methods: FAQL was prospectively measured using the FAQLQ parent proxy form (Food Allergy Quality of Life Questionnaire-Parent Proxy Form [FAQLQ-PF], for children aged ≤12 years) and child form (Food Allergy Quality of Life Questionnaire-Child Form [FAQLQ-CF], child rated if aged ≥8 years) during the 12-month double-blind, randomized, controlled Peanut EPIT Efficacy and Safety Study (PEPITES) trial and the initial 12 months of the open-label PEPITES Open Label Extension Study (PEOPLE) follow-up study. Data were analyzed for between-group differences after treatment unblinding. Results: FAQLQs from placebo participants (FAQLQ-PF: 96; FAQLQ-CF: 47) and treatment group participants (FAQLQ-PF: 209; FAQLQ-CF: 105) were analyzed. Twenty-four–month global FAQL scores (FAQLQ-PF/FAQLQ-CF) were significantly improved in the treatment group versus the placebo group (least squares mean, 0.34, P = .008, and 0.46, P = .023, respectively). At 24 months, there was significant FAQLQ-PF score improvement in participants initially randomized to treatment who met the efficacy primary end point (n = 74; least squares mean, 0.55; P < .001) and in participants with any eliciting dose increase (n = 127; least squares mean, 0.66; P < .001). FAQLQ-PF improvements were observed in social dietary limitations (P = .002), food-related anxiety (P = .029), and emotional impact (P = .048) domains. FAQLQ-CF improvements were observed in risk of accidental exposure (P = .002) and allergen avoidance (P = .04) domains. Nearly all outcomes met a nontreatment context minimal clinically important difference previously cited for FAQLQ. Conclusions: Epicutaneous immunotherapy treatment was observed to be associated with significant global and domain-specific FAQL improvement (FAQLQ-PF/FAQLQ-CF), largely driven by increases in eliciting dose, in children with peanut allergy

Iron status, body size, and growth in the first 2years of life

Rapid growth in infancy has been shown to adversely affect iron status up to 1 year; however the effect of growth on iron status in the second year of life has been largely unexplored. We aimed to investigate the impact of growth and body size in the first 2 years on iron status at 2 years. In the prospective, maternal‐infant Cork BASELINE Birth Cohort Study, infant weight and length were measured at birth, 2, 6, 12, and 24 months and absolute weight (kg) and length (cm) gain from 0 to 2, 0 to 6, 0 to 12, 6 to 12, 12 to 24, and 0 to 24 months were calculated. At 2 years (n = 704), haemoglobin, mean corpuscular volume, and serum ferritin (umbilical cord concentrations also) were measured. At 2 years, 5% had iron deficiency (ferritin < 12 μg/L) and 1% had iron deficiency anaemia (haemoglobin < 110 g/L + ferritin < 12 μg/L). Weight gain from 6 to 12, 0 to 24, and 12 to 24 months were all inversely associated with ferritin concentrations at 2 years but only the association with weight gain from 12 to 24 months was robust after adjustment for potential confounders including cord ferritin (adj. estimate 95% CI: −4.40 [−8.43, −0.37] μg/L, p = .033). Length gain from 0 to 24 months was positively associated with haemoglobin at 2 years (0.42 [0.07, 0.76] g/L, p = .019), only prior to further adjustment for cord ferritin. To conclude, weight gain in the second year was inversely associated with iron stores at 2 years, even after accounting for iron status at birth. Further examinations of iron requirements, dietary intakes, and growth patterns in children in the second year of life in high‐resource settings are warranted

Antenatal vitamin D status is not associated with standard neurodevelopmental assessments at age 5 Years in a well-characterized prospective maternal-infant cohort

Background: Although animal studies show evidence for a role of vitamin D during brain development, data from human studies show conflicting signals. Objective: We aimed to explore associations between maternal and neonatal vitamin D status with childhood neurodevelopmental outcomes. Methods: Comprehensive clinical, demographic, and lifestyle data were collected prospectively in 734 maternal-infant dyads from the Cork BASELINE Birth Cohort Study. Serum 25-hydroxyvitamin D [25(OH)D] concentrations were quantified at 15 weeks of gestation and in umbilical cord sera at birth via a CDC-accredited liquid chromatography-tandem mass spectrometry method. Children were assessed at age 5 y through the use of the Kaufman Brief Intelligence Test (2nd Edition, KBIT-2) and the Child Behaviour Checklist (CBCL). Linear regression was used to explore associations between 25(OH)D and neurodevelopmental outcomes. Results: 25(OH)D concentrations were <30 nmol/L in 15% of maternal and 45% of umbilical cord sera and <50 nmol/L in 42% of mothers and 80% of cords. At age 5 y, the mean ± SD KBIT-2 intelligence quotient (IQ) composite score was 104.6 ± 8.6; scores were 107.2 ± 10.0 in verbal and 99.8 ± 8.8 in nonverbal tasks. Developmental delay (scores <85) was seen in <3% of children across all domains. The mean ± SD CBCL total problem score was 21.3 ± 17.5; scores in the abnormal/clinical range for internal, external, and total problem scales were present in 12%, 4%, and 6% of participants, respectively. KBIT-2 and CBCL subscale scores at 5 y were not different between children exposed to low antenatal vitamin D status, either at 30 or 50 nmol/L 25(OH)D thresholds. Neither maternal nor cord 25(OH)D (per 10 nmol/L) were associated with KBIT-2 IQ composite scores [adjusted β (95% CI): maternal –0.01 (−0.03, 0.02); cord 0.01 (−0.03, 0.04] or CBCL total problem scores [maternal 0.01 (−0.04, 0.05); cord 0.01 (−0.07, 0.09)]. Conclusion: In this well-characterized prospective maternal-infant cohort, we found no evidence that antenatal 25(OH)D concentrations are associated with neurodevelopmental outcomes at 5 y. The BASELINE Study was registered at www.clinicaltrials.gov as NCT01498965; the SCOPE Study was registered at http://www.anzctr.org.au as ACTRN1260700055149

Iron intakes and status of 2-year-old children in the Cork BASELINE Birth Cohort Study

Young children are at risk of iron deficiency and subsequent anaemia, resulting in long‐term consequences for cognitive, motor and behavioural development. This study aimed to describe the iron intakes, status and determinants of status in 2‐year‐old children. Data were collected prospectively in the mother–child Cork BASELINE Birth Cohort Study from 15 weeks' gestation throughout early childhood. At the 24‐month assessment, serum ferritin, haemoglobin and mean corpuscular volume were measured, and food/nutrient intake data were collected using a 2‐day weighed food diary. Iron status was assessed in 729 children (median [IQR] age: 2.1 [2.1, 2.2] years) and 468 completed a food diary. From the food diary, mean (SD) iron intakes were 6.8 (2.6) mg/day and 30% had intakes < UK Estimated Average Requirement (5.3 mg/day). Using WHO definitions, iron deficiency was observed in 4.6% (n = 31) and iron deficiency anaemia in five children (1.0%). Following an iron series workup, five more children were diagnosed with iron deficiency anaemia. Twenty‐one per cent had ferritin concentrations <15 µg/L. Inadequate iron intakes (OR [95% CI]: 1.94 [1.09, 3.48]) and unmodified cows' milk intakes ≥ 400 mL/day (1.95 [1.07, 3.56]) increased the risk of low iron status. Iron‐fortified formula consumption was associated with decreased risk (0.21 [0.11, 0.41] P < 0.05). In this, the largest study in toddlers in Europe, a lower prevalence of low iron status was observed than in previous reports. Compliance with dietary recommendations to limit cows' milk intakes in young children and consumption of iron‐fortified products appears to have contributed to improved iron status at two years

Microcytosis is associated with low cognitive outcomes in healthy 2-year-olds in a high-resource setting

Fe deficiency in early childhood is associated with long-term consequences for cognitive, motor and behavioural development; however explorations in healthy children from low risk, high-resource settings have been limited. We aimed to explore associations between Fe status and neurodevelopmental outcomes in low risk, healthy 2-year-olds. This study was a secondary analysis of a nested case–control subgroup from the prospective, maternal-infant Cork Babies after Screening for Pregnancy Endpoints: Evaluating the Longitudinal Impact using Neurological and Nutritional Endpoints (BASELINE) Birth Cohort Study. At 2 years, serum ferritin, Hb and mean corpuscular volume (MCV) were measured and neurodevelopment was assessed using the Bayley Scales of Infant and Toddler Development (n 87). Five children had Fe deficiency (ferritin <12 µg/l) and no child had Fe deficiency anaemia (Hb<110 g/l+ferritin<12 µg/l). Children with microcytosis (MCV<74 fl, n 13) had significantly lower mean cognitive composite scores (88·5 (sd 13·3) v. 97·0 (sd 7·8), P=0·04, Cohen’s d effect size=0·8) than those without microcytosis. The ferritin concentration which best predicted microcytosis was calculated as 18·4 µg/l (AUC=0·87 (95% CI 0·75, 0·98), P<0·0001, sensitivity 92 %, specificity 75 %). Using 18·5 µg/l as a threshold, children with concentrations <18·5 µg/l had significantly lower mean cognitive composite scores (92·3 (sd 10·5) v. 97·8 (sd 8·1), P=0·012, Cohen’s d effect size=0·6) compared with those with ferritin ≥18·5 µg/l. All associations were robust after adjustment for potential confounding factors. Despite a low prevalence of Fe deficiency using current diagnostic criteria in this healthy cohort, microcytosis was associated with lower cognitive outcomes at 2 years. This exploratory study emphasises the need for re-evaluation of the diagnostic criteria for Fe deficiency in young children, with further research in adequately powered studies warranted

Skin microbiome prior to development of atopic dermatitis:early colonization with commensal staphylococci at 2 months is associated with a lower risk of atopic dermatitis at 1 year

Background: Disease flares of established atopic dermatitis (AD) are generally associated with a low-diversity skin microbiota and Staphylococcus aureus dominance. The temporal transition of the skin microbiome between early infancy and the dysbiosis of established AD is unknown. Methods: We randomly selected 50 children from the Cork Babies After SCOPE: Evaluating the Longitudinal Impact Using Neurological and Nutritional Endpoints (BASELINE) longitudinal birth cohort for microbiome sampling at 3 points in the first 6 months of life at 4 skin sites relevant to AD: the antecubital and popliteal fossae, nasal tip, and cheek. We identified 10 infants with AD and compared them with 10 randomly selected control infants with no AD. We performed bacterial 16S ribosomal RNA sequencing and analysis directly from clinical samples. Results: Bacterial community structures and diversity shifted over time, suggesting that age strongly affects the skin microbiome in infants. Unlike established AD, these patients with infantile AD did not have noticeably dysbiotic communities before or with disease and were not colonized by S aureus. In comparing patients and control subjects, infants who had affected skin at month 12 had statistically significant differences in bacterial communities on the antecubital fossa at month 2 compared with infants who were unaffected at month 12. In particular, commensal staphylococci were significantly less abundant in infants affected at month 12, suggesting that this genus might protect against the later development of AD. Conclusions: This study suggests that 12-month-old infants with AD were not colonized with S aureus before having AD. Additional studies are needed to confirm whether colonization with commensal staphylococci modulates skin immunity and attenuates development of AD

ARIA 2016: Care pathways implementing emerging technologies for predictive medicine in rhinitis and asthma across the life cycle

The Allergic Rhinitis and its Impact on Asthma (ARIA) initiative commenced during a World Health Organization workshop in 1999. The initial goals were (1) to propose a new allergic rhinitis classification, (2) to promote the concept of multi-morbidity in asthma and rhinitis and (3) to develop guidelines with all stakeholders that could be used globally for all countries and populations. ARIA—disseminated and implemented in over 70 countries globally—is now focusing on the implementation of emerging technologies for individualized and predictive medicine. MASK [MACVIA (Contre les Maladies Chroniques pour un Vieillissement Actif)-ARIA Sentinel NetworK] uses mobile technology to develop care pathways for the management of rhinitis and asthma by a multi-disciplinary group and by patients themselves. An app (Android and iOS) is available in 20 countries and 15 languages. It uses a visual analogue scale to assess symptom control and work productivity as well as a clinical decision support system. It is associated with an inter-operable tablet for physicians and other health care professionals. The scaling up strategy uses the recommendations of the European Innovation Partnership on Active and Healthy Ageing. The aim of the novel ARIA approach is to provide an active and healthy life to rhinitis sufferers, whatever their age, sex or socio-economic status, in order to reduce health and social inequalities incurred by the disease

Allergic Rhinitis and its Impact on Asthma (ARIA) Phase 4 (2018) : Change management in allergic rhinitis and asthma multimorbidity using mobile technology

Allergic Rhinitis and its Impact on Asthma (ARIA) has evolved from a guideline by using the best approach to integrated care pathways using mobile technology in patients with allergic rhinitis (AR) and asthma multimorbidity. The proposed next phase of ARIA is change management, with the aim of providing an active and healthy life to patients with rhinitis and to those with asthma multimorbidity across the lifecycle irrespective of their sex or socioeconomic status to reduce health and social inequities incurred by the disease. ARIA has followed the 8-step model of Kotter to assess and implement the effect of rhinitis on asthma multimorbidity and to propose multimorbid guidelines. A second change management strategy is proposed by ARIA Phase 4 to increase self-medication and shared decision making in rhinitis and asthma multimorbidity. An innovation of ARIA has been the development and validation of information technology evidence-based tools (Mobile Airways Sentinel Network [MASK]) that can inform patient decisions on the basis of a self-care plan proposed by the health care professional.Peer reviewe

Next-generation ARIA care pathways for rhinitis and asthma : a model for multimorbid chronic diseases

Background In all societies, the burden and cost of allergic and chronic respiratory diseases are increasing rapidly. Most economies are struggling to deliver modern health care effectively. There is a need to support the transformation of the health care system into integrated care with organizational health literacy. Main body As an example for chronic disease care, MASK (Mobile Airways Sentinel NetworK), a new project of the ARIA (Allergic Rhinitis and its Impact on Asthma) initiative, and POLLAR (Impact of Air POLLution on Asthma and Rhinitis, EIT Health), in collaboration with professional and patient organizations in the field of allergy and airway diseases, are proposing real-life ICPs centred around the patient with rhinitis, and using mHealth to monitor environmental exposure. Three aspects of care pathways are being developed: (i) Patient participation, health literacy and self-care through technology-assisted "patient activation", (ii) Implementation of care pathways by pharmacists and (iii) Next-generation guidelines assessing the recommendations of GRADE guidelines in rhinitis and asthma using real-world evidence (RWE) obtained through mobile technology. The EU and global political agendas are of great importance in supporting the digital transformation of health and care, and MASK has been recognized by DG Sante as a Good Practice in the field of digitally-enabled, integrated, person-centred care. Conclusion In 20 years, ARIA has considerably evolved from the first multimorbidity guideline in respiratory diseases to the digital transformation of health and care with a strong political involvement.Peer reviewe