Early initiation of short-term emollient use for the prevention of atopic dermatitis in high-risk infants-The STOP-AD randomised controlled trial.

BACKGROUND: Protecting the skin barrier in early infancy may prevent atopic dermatitis (AD). We investigated if daily emollient use from birth to 2 months reduced AD incidence in high-risk infants at 12 months. METHODS: This was a single-center, two-armed, investigator-blinded, randomized controlled clinical trial (NCT03871998). Term infants identified as high risk for AD (parental history of AD, asthma or allergic rhinitis) were recruited within 4 days of birth and randomised 1:1 to either twice-daily emollient application for the first 8 weeks of life (intervention group), using an emollient specifically formulated for very dry, AD-prone skin, or to standard routine skin care (control group). The primary outcome was cumulative AD incidence at 12 months. AD <6 months was diagnosed based on clinical presence of AD. The UK Working Party Diagnostic Criteria were applied when diagnosing AD between 6 and 12 months. RESULTS: Three hundred twenty-one were randomised (161 intervention and 160 control), with 61 withdrawals (41 intervention, 20 control). The cumulative incidence of AD at 12 months was 32.8% in the intervention group vs. 46.4% in the control group, p = 0.036 [Relative risk (95%CI): 0.707 (0.516, 0.965)]. One infant in the intervention group was withdrawn from the study following development of a rash that had a potential relationship with the emollient. There was no significant difference in the incidence of skin infections between the intervention and control groups during the intervention period (5.0% vs. 5.7%, p > 0.05). CONCLUSIONS: This study has demonstrated that early initiation of daily specialized emollient use until 2 months reduces the incidence of AD in the first year of life in high-risk infants.

Poor Quality Diets Characterized by Low-Nutrient Density Foods Observed in One-Quarter of 2-Year-Olds in a High Resource Setting.

BACKGROUND: Young children have high nutritional requirements relative to their body size, making healthy diets critical for normal growth and development. OBJECTIVE: We aimed to integrate analysis of dietary patterns among 2-y-old children with indicators of dietary quality, micronutrient status, and body weight status. METHODS: Data from the 2-y follow-up of the Cork BASELINE Birth Cohort included dietary assessment using a 2-d weighed food diary, vitamin D and iron status biomarkers, and anthropometry (n = 468). K-means cluster analysis identified predominant dietary patterns based on energy contributions and associations with nutrient intakes and status and body weight were investigated. RESULTS: Four dietary patterns emerged: "Cows' milk" (unmodified cows' milk: 32% of total energy (TE)); "Traditional" (wholemeal breads, butter, fresh meat, fruit); "Low Nutrient Density (LND) foods" (confectionary, processed meat, convenience foods) and "Formula" (young child formula: 23%TE). The LND pattern was associated with excessive free sugar intake (14%TE) and salt intake (153% of daily limit). No differences in patterns of overweight were observed between the 4 groups; however, the LND group had 3-fold higher odds of being underweight [aOR (95% CI): 3.2 (1.2, 8.5)]. Children consuming >400ml/d of cows' milk or formula exhibited lower dietary variety, fewer family-type meals, and continued use of feeding bottles (75% and 81%, respectively, vs. 35-37% in the other groups). CONCLUSIONS: Unhealthy eating habits are common among young children. Dietary guidance to support families to provide healthy diets needs to maintain currency with eating habits and focus on food choices for meals, snacks, and beverages.

Changes in parental smoking during pregnancy and risks of adverse birth outcomes and childhood overweight in Europe and North America: An individual participant data meta-analysis of 229,000 singleton births.

BACKGROUND: Fetal smoke exposure is a common and key avoidable risk factor for birth complications and seems to influence later risk of overweight. It is unclear whether this increased risk is also present if mothers smoke during the first trimester only or reduce the number of cigarettes during pregnancy, or when only fathers smoke. We aimed to assess the associations of parental smoking during pregnancy, specifically of quitting or reducing smoking and maternal and paternal smoking combined, with preterm birth, small size for gestational age, and childhood overweight. METHODS AND FINDINGS: We performed an individual participant data meta-analysis among 229,158 families from 28 pregnancy/birth cohorts from Europe and North America. All 28 cohorts had information on maternal smoking, and 16 also had information on paternal smoking. In total, 22 cohorts were population-based, with birth years ranging from 1991 to 2015. The mothers' median age was 30.0 years, and most mothers were medium or highly educated. We used multilevel binary logistic regression models adjusted for maternal and paternal sociodemographic and lifestyle-related characteristics. Compared with nonsmoking mothers, maternal first trimester smoking only was not associated with adverse birth outcomes but was associated with a higher risk of childhood overweight (odds ratio [OR] 1.17 [95% CI 1.02-1.35], P value = 0.030). Children from mothers who continued smoking during pregnancy had higher risks of preterm birth (OR 1.08 [95% CI 1.02-1.15], P value = 0.012), small size for gestational age (OR 2.15 [95% CI 2.07-2.23], P value < 0.001), and childhood overweight (OR 1.42 [95% CI 1.35-1.48], P value < 0.001). Mothers who reduced the number of cigarettes between the first and third trimester, without quitting, still had a higher risk of small size for gestational age. However, the corresponding risk estimates were smaller than for women who continued the same amount of cigarettes throughout pregnancy (OR 1.89 [95% CI 1.52-2.34] instead of OR 2.20 [95% CI 2.02-2.42] when reducing from 5-9 to ≤4 cigarettes/day; OR 2.79 [95% CI 2.39-3.25] and OR 1.93 [95% CI 1.46-2.57] instead of OR 2.95 [95% CI 2.75-3.15] when reducing from ≥10 to 5-9 and ≤4 cigarettes/day, respectively [P values < 0.001]). Reducing the number of cigarettes during pregnancy did not affect the risks of preterm birth and childhood overweight. Among nonsmoking mothers, paternal smoking was associated with childhood overweight (OR 1.21 [95% CI 1.16-1.27], P value < 0.001) but not with adverse birth outcomes. Limitations of this study include the self-report of parental smoking information and the possibility of residual confounding. As this study only included participants from Europe and North America, results need to be carefully interpreted regarding other populations. CONCLUSIONS: We observed that as compared to nonsmoking during pregnancy, quitting smoking in the first trimester is associated with the same risk of preterm birth and small size for gestational age, but with a higher risk of childhood overweight. Reducing the number of cigarettes, without quitting, has limited beneficial effects. Paternal smoking seems to be associated, independently of maternal smoking, with the risk of childhood overweight. Population strategies should focus on parental smoking prevention before or at the start, rather than during, pregnancy.

In vivo Raman spectroscopy discriminates between FLG loss-of-function carriers vs wild-type in day 1-4 neonates.

BACKGROUND: Carriers of loss-of-function mutations in the filaggrin gene (LoF FLG) have less natural moisturizing factor (NMF) in their stratum corneum (SC) and an increased risk of atopic dermatitis (AD). Natural moisturizing factor can be measured noninvasively by Raman spectroscopy. The use of Raman-derived NMF at birth to screen for FLG genotype could inform targeted AD prevention, but values in neonatal populations are largely unexplored. OBJECTIVE: To examine the associations between Raman-derived neonatal NMF measurements and FLG genotype. METHODS: Natural moisturizing factor was measured by Raman spectroscopy in the SC of the thenar eminence within 4 days of birth in 139 term neonates. Filaggrin genotyping was performed for 117 neonates (84%). RESULTS: The mean (SD) NMF was 0.37 (0.11) g/g protein, with values increasing across the first 3 days (day 1 vs 3: 0.29 [0.09] vs 0.43 [0.08, P < .001]). Twelve infants (10.3%) were carriers of LoF FLG, all heterozygous. Natural moisturizing factor was lower in LoF FLG carriers compared with wild-type (0.27 [0.08] vs 0.38 [0.11] g/g protein, P ≤ .001). Natural moisturizing factor had good discriminatory power for FLG genotype (area under the receiver operating curve [AUROC]: 0.79; 95% CI: 0.66, 0.91; P ≤ .001). This improved after correcting day 1 and 2 measurements to day 3 (AUROC: 0.83; 95% CI: 0.75, 0.92; P < .001). CONCLUSION: This study suggests that Raman-derived NMF measured in the early postnatal period may have the potential to classify by FLG genotype. The full translational value of this needs to be determined.

A longitudinal study of hymenoptera stings in preschool children.

BACKGROUND: Insect venom is the second most common cause of anaphylaxis outside of medical encounters. Stings cause over 20% of all anaphylactic deaths and 7% of anaphylaxis in children. To date, there have been no longitudinal studies of insect sting events or allergy in preschool children. METHODS: A prospective longitudinal nested observational study in the BASELINE Birth Cohort Study (n = 2137). Sting-related questions were asked at 6 and 12 months and 2 and 5 years. Skin prick testing (SPT) was performed at 2 and 5 years. SpIgE testing was performed on selected cases at 2 years. RESULTS: Seventy-seven children (6.8%) were stung by the age of 2. Of these, 25 (32.5%) reported adverse reactions (four systemic). Eleven (0.9%) had positive SPT at 2 years (eight bee, two wasp, one both). Four stung children had positive SPT. Two (one stung, one never stung) had positive spIgE to a venom component at 2 years. A total of 268 children (21.9%) were stung by 5 years, 144 (52.1%) reporting local reactions and none systemic. Four children (0.4%) had positive SPT at 5 years: one bee and three wasp. Of the 11 SPT-positive children at 2 years, none were still positive at 5 years. CONCLUSION: This is the first longitudinal study of the natural history of hymenoptera stings and allergy in preschool children. Hymenoptera venom allergy is less common in this cohort than in adults. Systemic reactions were not medically documented in this population, in keeping with previous literature. This study confirms the poor correlation of IgE sensitization to venom with sting allergy and does not support the common parental request to screen children for sting allergy.

Low vitamin D deficiency in Irish toddlers despite northerly latitude and a high prevalence of inadequate intakes.

PURPOSE: While reports of inadequate vitamin D intakes among young children are widespread, data on the prevalence of vitamin D deficiency are inconsistent. We aimed to quantify vitamin D intake and serum 25-hydroxyvitamin D [25(OH)D] concentrations in children aged 2 years in the prospective Cork BASELINE Birth Cohort Study. METHODS: Serum 25(OH)D was analysed using UPLC-MS/MS in 741 children living in Cork, Ireland (51°N). Two-day weighed food diaries were collected in 467 children, and 294 provided both a blood sample and a food diary. RESULTS: Mean (SD) 25(OH)D concentrations were 63.4 (20.4) nmol/L [winter: 54.5 (19.9), summer: 71.2 (17.5)]. The prevalence of vitamin D deficiency (<30 nmol/L) was 4.6, and 26.7% were <50 nmol/L [45.2% during winter (November-April) and 10.4% in summer (May-October)]. With a mean (SD) vitamin D intake of 3.5 (3.1) µg/day, 96% had intakes below 10 µg/day, the current IOM estimated average requirement and the SACN safe intake value for this age group. After adjustment for season, vitamin D intake (µg/day) was associated with higher 25(OH)D concentrations [adjusted estimate (95% CI) 2.5 (1.9, 3.1) nmol/L]. Children who did not consume vitamin D-fortified foods or supplements had very low vitamin D intakes (1.2 (0.9) µg/day), and during winter, 12 and 77% were <30 and <50 nmol/L, respectively, compared with 6 and 44% of fortified food consumers. CONCLUSION: There was a high prevalence of low vitamin D status during winter, especially among children who did not consume fortified foods or nutritional supplements. Our data indicate the need for dietary strategies to increase vitamin D intakes in this age group. This report provides further evidence that DRVs for vitamin D should be based on experimental data in specific population groups and indicates the need for dose-response RCTs in young children.

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

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.

Body Mass Index Trajectories in the First 5 Years and Associated Antenatal Factors.

Background: The increasing prevalence of childhood obesity is an important public health issue and the development of obesity in early life and associated risk factors need to be better understood. The aim of this study was to identify distinct body mass index trajectories in the first 5 years of life and to examine their associations with factors identified in pregnancy, including metabolic parameters. Methods: BMI measurements from 2,172 children in Ireland enrolled in the BASELINE cohort study with BMI assessments at birth, 2, 6, and 12 months, and 2 and 5 years were analyzed. Growth mixture modeling was used to identify distinct BMI trajectories, and multivariate multinomial logistic regression was used to assess the association between these trajectories and antenatal factors. Results: Three distinct BMI trajectories were identified: normal (89.6%); rapid gain in the first 6 months (7.8%); and rapid BMI after 12 months (2.6%). Male sex and higher maternal age increased the likelihood of belonging to the rapid gain in the first 6 months trajectory. Raised maternal BMI at 15 weeks of pregnancy and lower cord blood IGF-2 were associated with rapid gain after 1 year. Conclusion: Sex, maternal age and BMI, and IGF-2 levels were found to be associated with BMI trajectories in early childhood departing from normal growth. Further research and extended follow-up to examine the effects of childhood growth patterns are required to understand their relationship with health outcomes.

Variation in iodine food composition data has a major impact on estimates of iodine intake in young children.

BACKGROUND/OBJECTIVES: The reliability of an estimate of iodine intake is largely dependent on the quality of the food composition data. We aimed to assess the impact of variations in food composition data for iodine and season on the estimates of iodine intake in young children. SUBJECTS/METHODS: Cross-sectional dietary intake study of Irish 2-year-olds participating in the Cork BASELINE Birth Cohort Study (n=468; 30% of the cohort at the 2-year follow-up) were used to assess the impact of variation in iodine food composition data on estimates of iodine intake, dietary adequacy and risk of exceeding the tolerable upper intake level (UL). RESULTS: Mean (SD) iodine intakes calculated using UK (147 (71)) and Irish (177 (93)) food composition data were significantly different (P < 0.001) (mean difference (95% confidence interval) = 30 (26-33) µg/day) and largely adequate (7-14% below the estimated average requirement). Intakes at the 95th percentile were 138% and 173% of the UL using UK and Irish food composition data, respectively, of which milk accounted for 106% and 150% of the UL. This translated into 22% and 35% of toddlers exceeding the UL, using UK and Irish composition data, respectively. The mean (SD) daily intake of cow's milk among the 91% of consumers was 309 (208) ml. Intakes of cow's milk at the 75th and 95th percentiles were 452 and 706 ml, respectively. Using Irish composition data for iodine in cows' milk, a daily intake of 450 ml could result in a toddler exceeding the UL from milk alone. CONCLUSIONS: Variability in food composition has a large impact on assessments of iodine intake, particularly among young children for whom milk contributes a large proportion of their daily nutrient intake. Although this is unlikely to result in long-term adverse effects, our study highlights the need for development of valid biomarkers of individual iodine status.