Feeding Practices and Dietary Diversity in the First Year of Life: PreventADALL, a Scandinavian Randomized Controlled Trial and Birth Cohort Study.

BACKGROUND: Breastmik is considered the optimal source of nutrition in early infancy. However, recommendations and practices for when and how complementary food should be introduced in the first year of life vary worldwide. Early introduction of allergenic foods may prevent food allergies, but if early food introduction influences infant feeding practices is less known. OBJECTIVES: We sought to assess infant feeding practices in the first year of life and to determine if early interventional food introduction influences breastfeeding and dietary diversity. METHODS: Dietary intake was assessed in infants from the population-based clinical trial Preventing Atopic Dermatitis and ALLergies (PreventADALL) in children study. A total of 2397 infants were cluster-randomized at birth into 4 different groups: 1) control, 2) skin intervention, 3) introduction to 4 allergenic foods between 3 and 4 mo of age: peanut, cow milk, wheat, and egg, as small tastings until 6 mo, and 4) combined skin and food interventions. Dietary data were available from at least one of the 3-, 6-, 9-, and 12-mo questionnaires in 2059 infants. In the present analysis, groups 1 and 2 constitute the No Food Intervention group, whereas groups 3 and 4 constitute the Food Intervention group. We used the log-rank test and Cox regression to assess the impact of food intervention on age of breastfeeding cessation. Mixed effects logistic regression was used to compare dietary diversity, defined as the number of food categories consumed, between intervention groups. RESULTS: At 3, 6, 9, and 12 mo, 95%, 88%, 67%, and 51% were breastfed, respectively, and breastfeeding duration was not affected by the food intervention. In the No Food Intervention group, mean age of complementary food introduction was 18.3 wk (confidence interval [CI]: 18.1, 18.5). In the Food Intervention group, the dietary diversity score was 1.39 units (CI: 1.16, 1.62) higher at 9 mo (P < 0.001) and 0.7 units (CI: 0.5, 0.9) higher at 12 mo (P < 0.001) compared to the No Food Intervention group. CONCLUSIONS: Early food intervention did not affect breastfeeding rates and increased dietary diversity at 9 and 12 mo.

Maternal food-avoidance diets and dietary supplements during breastfeeding.

AIMS: To identify maternal food-avoidance diets and dietary supplement use during breastfeeding, and to explore factors associated with food avoidance diets. DESIGN: A prospective mother-child birth cohort study. METHODS: Electronic questionnaires were answered by 1,462 breastfeeding mothers 6 months postpartum in the Preventing Atopic Dermatitis and Allergies in Children (PreventADALL) study from 2014-2016. Demographic and antenatal factors were analysed for associations with food avoidance diets in 1,368 women by multiple logistic regression. RESULTS: Overall, 289 breastfeeding women (19.8%) avoided at least one food item in their diet, most commonly cow's milk in 99 women (6.8%). Foods were most often avoided due to conditions in the child, maternal factors or lifestyle choice. The odds for food avoidance diets were 2.1 (95% CI: 1.3, 3.4) for food allergy (presumed or diagnosed) and 19.4 (5.4, 70.1) for celiac disease in the mother. Dietary supplements were reported by nearly 80%, most commonly cod liver oil.

Early food intervention and skin emollients to prevent food allergy in young children (PreventADALL): a factorial, multicentre, cluster-randomised trial.

BACKGROUND: Primary prevention of food allergy by early introduction of allergenic foods seems promising. We aimed to determine whether early food introduction or the application of regular skin emollients in infants from a general population reduced the risk of food allergy. METHODS: This 2 × 2 factorial, cluster-randomised trial was done at Oslo University Hospital and Østfold Hospital Trust, Oslo, Norway, and Karolinska University Hospital, Stockholm, Sweden. Infants of women recruited antenatally at the routine 18-week ultrasound examination were cluster-randomised at birth to the following groups: (1) no intervention group; (2) the skin intervention group (skin emollients; bath additives and facial cream; from age 2 weeks to <9 months, both at least four times per week); (3) the food intervention group (early complementary feeding of peanut, cow's milk, wheat, and egg from age 3 months); or (4) combined intervention group (skin and food interventions). Participants were randomly assigned (1:1:1:1) using computer-generated randomisation based on clusters of 92 geographical areas and eight 3-month time blocks. Study personnel performing clinical assessments were masked to group allocation. The primary outcome was allergy to any interventional food at 36 months of age. The primary efficacy analysis was done by intention-to-treat analysis, which included all participants who were randomly assigned, apart from three individuals who withdrew their consent. This was a study performed within ORAACLE (the Oslo Research Group of Asthma and Allergy in Childhood; the Lung and Environment). This study is registered as ClinicalTrials.gov, NCT02449850. FINDINGS: We recruited 2697 women with 2701 pregnancies, from whom 2397 newborn infants were enrolled between April 14, 2015, and April 11, 2017. Of these infants, 597 were randomly assigned to the no intervention group, 575 to the skin intervention group, 642 to the food intervention group, and 583 to the combined intervention group. One participant in each of the no intervention, food intervention, and skin intervention groups withdrew consent and were therefore not included in any analyses. Food allergy was diagnosed in 44 children; 14 (2·3%) of 596 infants in the non-intervention group, 17 (3·0%) of 574 infants in the skin intervention group, six (0·9%) of 641 infants in the food intervention group, and seven (1·2%) of 583 infants in the combined intervention group. Peanut allergy was diagnosed in 32 children, egg allergy in 12 children, and milk allergy in four children. None had allergy to wheat. Prevalence of food allergy was reduced in the food intervention group compared with the no food intervention group (risk difference -1·6% [95% CI -2·7 to -0·5]; odds ratio [OR] 0·4 [95% CI 0·2 to 0·8]), but not compared with the skin intervention group (0·4% [95% CI -0·6 to 1· 5%]; OR 1·3 [0·7 to 2·3]), with no significant interaction effect (p=1·0). Preventing food allergy in one child required early exposure to allergenic foods in 63 children. No serious adverse events were observed. INTERPRETATION: Exposure to allergenic foods from 3 months of age reduced food allergy at 36 months in a general population. Our results support that early introduction of common allergenic foods is a safe and effective strategy to prevent food allergy. FUNDING: Full funding sources listed at end of paper (see Acknowledgments).

Fecal Microbiota Nutrient Utilization Potential Suggests Mucins as Drivers for Initial Gut Colonization of Mother-Child-Shared Bacteria.

The nutritional drivers for mother-child sharing of bacteria and the corresponding longitudinal trajectory of the infant gut microbiota development are not yet completely settled. We therefore aimed to characterize the mother-child sharing and the inferred nutritional utilization potential for the gut microbiota from a large unselected cohort. We analyzed in depth gut microbiota in 100 mother-child pairs enrolled antenatally from the general population-based Preventing Atopic Dermatitis and Allergies in Children (PreventADALL) cohort. Fecal samples collected at gestational week 18 for mothers and at birth (meconium), 3, 6, and 12 months for infants were analyzed by reduced metagenome sequencing to determine metagenome size and taxonomic composition. The nutrient utilization potential was determined based on the Virtual Metabolic Human (VMH, www.vmh.life) database. The estimated median metagenome size was ∼150 million base pairs (bp) for mothers and ∼20 million bp at birth for the children. Longitudinal analyses revealed mother-child sharing (P < 0.05, chi-square test) from birth up to 6 months for 3 prevalent Bacteroides species (prevalence, >25% for all age groups). In a multivariate analysis of variance (ANOVA), the mother-child-shared Bacteroides were associated with vaginal delivery (1.7% explained variance, P = 0.0001). Both vaginal delivery and mother-child sharing were associated with host-derived mucins as nutrient sources. The age-related increase in metagenome size corresponded to an increased diversity in nutrient utilization, with dietary polysaccharides as the main age-related factor. Our results support host-derived mucins as potential selection means for mother-child sharing of initial colonizers, while the age-related increase in diversity was associated with dietary polysaccharides.IMPORTANCE The initial bacterial colonization of human infants is crucial for lifelong health. Understanding the factors driving this colonization will therefore be of great importance. Here, we used a novel high-taxonomic-resolution approach to deduce the nutrient utilization potential of the infant gut microbiota in a large longitudinal mother-child cohort. We found mucins as potential selection means for the initial colonization of mother-child-shared bacteria, while the transition to a more adult-like microbiota was associated with dietary polysaccharide utilization potential. This knowledge will be important for a future understanding of the importance of diet in shaping the gut microbiota composition and development during infancy.

Physical activity in pregnancy: a Norwegian-Swedish mother-child birth cohort study.

BACKGROUND: Physical activity during pregnancy is important for maternal and offspring health. Optimal conditions during pregnancy may help reduce the burden of noncommunicable diseases. National and international guidelines recommend at least 150 minutes of physical activity of at least moderate intensity per week. To optimize physical activity in pregnant women, it is important to identify factors associated with higher levels of physical activity. OBJECTIVE: This study aimed to explore types and levels of physical activity in midpregnancy in Norway and Sweden and to identify factors associated with higher levels of physical activity. MATERIALS AND METHODS: From the population-based mother-child cohort Preventing Atopic Dermatitis and Allergies in Children study recruiting 2697 women in Norway and Sweden from 2014 to 2016, we included 2349 women who answered an electronic questionnaire at enrollment in midpregnancy. Women were asked about regular physical activity in the last 2 weeks of pregnancy and afterward for types and levels of physical activity in pregnancy and before pregnancy and socioeconomic status, lifestyle, and maternal health. Logistic regression analyses were used to identify factors associated with higher levels of physical activity in pregnancy, defined as >30 minutes per session of ≥2 times per week of moderate- or high-intensity brisk walking, strength training, jogging, and bicycling. RESULTS: No regular physical activity during the last 2 weeks before answering the questionnaire at midpregnancy was reported by 689 women (29%). In this study, 1787 women (76%) reported weekly strolling during pregnancy. Regular physical activity at least twice weekly in the first half of pregnancy was reported as brisk walking by 839 women (36%), bicycling by 361 women (15%), strength training by 322 women (14%), and other activities by <10% of women. Among the 1430 women with regular moderate- or high-intensity physical activity, the estimated median duration per week was 120 minutes. Higher physical activity levels were achieved in 553 women (23.5%) by brisk walking, 287 women (12.2%) by strength training, 263 women (11.2%) by bicycling, and 114 women (4.9%) by jogging. Higher physical activity levels were positively associated with regular physical activity before pregnancy, dog ownership, and atopic dermatitis and negatively associated with higher body mass index, study location in Østfold, previous pregnancy or pregnancies, non-Nordic origin, suburban living, and sick leave. CONCLUSION: At midpregnancy, 29% of women were inactive, and less than 50% of women had at least 2 hours of moderate-intensity physical activity weekly. Awareness of physical activity in pregnancy should be discussed at pregnancy follow-up visits, particularly among women with higher body mass index, sick leave, previous pregnancy or pregnancies, and non-Nordic origin.

De novo species identification using 16S rRNA gene nanopore sequencing.

Nanopore sequencing is rapidly becoming more popular for use in various microbiota-based applications. Major limitations of current approaches are that they do not enable de novo species identification and that they cannot be used to verify species assignments. This severely limits applicability of the nanopore sequencing technology in taxonomic applications. Here, we demonstrate the possibility of de novo species identification and verification using hexamer frequencies in combination with k-means clustering for nanopore sequencing data. The approach was tested on the human infant gut microbiota of 3-month-old infants. Using the hexamer k-means approach we identified two new low abundant species associated with vaginal delivery. In addition, we confirmed both the vaginal delivery association for two previously identified species and the overall high levels of bifidobacteria. Taxonomic assignments were further verified by mock community analyses. Therefore, we believe our de novo species identification approach will have widespread application in analyzing microbial communities in the future.

Butyrate Levels in the Transition from an Infant- to an Adult-Like Gut Microbiota Correlate with Bacterial Networks Associated with Eubacterium Rectale and Ruminococcus Gnavus.

Relatively little is known about the ecological forces shaping the gut microbiota composition during infancy. Therefore, the objective of the present study was to identify the nutrient utilization- and short-chain fatty acid (SCFA) production potential of gut microbes in infants during the first year of life. Stool samples were obtained from mothers at 18 weeks of pregnancy and from infants at birth (first stool) at 3, 6, and 12-months of age from the general population-based PreventADALL cohort. We identified the taxonomic and SCFA composition in 100 mother-child pairs. The SCFA production and substrate utilization potential of gut microbes were observed by multiomics (shotgun sequencing and proteomics) on six infants. We found a four-fold increase in relative butyrate levels from 6 to 12 months of infant age. The increase was correlated to Eubacterium rectale and its bacterial network, and Faecalibacterium prausnitzii relative abundance, while low butyrate at 12 months was correlated to Ruminococcus gnavus and its associated network of bacteria. Both E. rectale and F. prausnitzii expressed enzymes needed for butyrate production and enzymes related to dietary fiber degradation, while R. gnavus expressed mucus-, fucose, and human milk oligosaccharides (HMO)-related degradation enzymes. Therefore, we believe that the presence of E. rectale, its network, and F. prausnitzii are key bacteria in the transition from an infant- to an adult-like gut microbiota with respect to butyrate production. Our results indicate that the transition from an infant- to an adult-like gut microbiota with respect to butyrate producing bacteria, occurs between 6 and 12 months of infant age. The bacteria associated with the increased butyrate ratio/levels were E. rectale and F. prausnitzii, which potentially utilize a variety of dietary fibers based on the glycoside hydrolases (GHs) expressed. R. gnavus with a negative association to butyrate potentially utilizes mucin, fucose, and HMO components. This knowledge could have future importance in understanding how microbial metabolites can impact infant health and development.

Skin emollient and early complementary feeding to prevent infant atopic dermatitis (PreventADALL): a factorial, multicentre, cluster-randomised trial.

BACKGROUND: Skin emollients applied during early infancy could prevent atopic dermatitis, and early complementary food introduction might reduce food allergy in high-risk infants. The study aimed to determine if either regular skin emollients applied from 2 weeks of age, or early complementary feeding introduced between 12 and 16 weeks of age, reduced development of atopic dermatitis by age 12 months in the general infant population. METHODS: This population-based 2×2 factorial, randomised clinical trial was done at Oslo University Hospital and Østfold Hospital Trust, Oslo, Norway; and Karolinska University Hospital, Stockholm, Sweden. Infants of women recruited antenatally at the routine ultrasound pregnancy screening at 18 weeks were cluster-randomised at birth from 2015 to 2017 to the following groups: (1) controls with no specific advice on skin care while advised to follow national guidelines on infant nutrition (no intervention group); (2) skin emollients (bath additives and facial cream; skin intervention group); (3) early complementary feeding of peanut, cow's milk, wheat, and egg (food intervention group); or (4) combined skin and food interventions (combined intervention group). Participants were randomly assigned (1:1:1:1) using computer- generated cluster randomisation based on 92 geographical living area blocks as well as eight 3-month time blocks. Carers were instructed to apply the interventions on at least 4 days per week. Atopic dermatitis by age 12 months was the primary outcome, based on clinical investigations at 3, 6 and 12 months by investigators masked to group allocation. Atopic dermatitis was assessed after completing the 12-month investigations and diagnosed if either of the UK Working Party and Hanifin and Rajka (12 months only) diagnostic criteria were fulfilled. The primary efficacy analyses was done by intention-to-treat analysis on all randomly assigned participants. Food allergy results will be reported once all investigations at age 3 years are completed in 2020. This was a study performed within ORAACLE (the Oslo Research Group of Asthma and Allergy in Childhood; the Lung and Environment). The study is registered at clinicaltrials.gov, NCT02449850. FINDINGS: 2697 women were recruited between Dec 9, 2014, and Oct 31, 2016, from whom 2397 newborn infants were enrolled from April 14, 2015, to April 11, 2017. Atopic dermatitis was observed in 48 (8%) of 596 infants in the no intervention group, 64 (11%) of 575 in the skin intervention group, 58 (9%) of 642 in the food intervention group, and 31 (5%) of 583 in the combined intervention group. Neither skin emollients nor early complementary feeding reduced development of atopic dermatitis, with a risk difference of 3·1% (95% CI -0·3 to 6·5) for skin intervention and 1·0% (-2·1 to 4·1) for food intervention, in favour of control. No safety concerns with the interventions were identified. Reported skin symptoms and signs (including itching, oedema, exanthema, dry skin, and urticaria) were no more frequent in the skin, food, and combined intervention groups than in the no intervention group. INTERPRETATION: Neither early skin emollients nor early complementary feeding reduced development of atopic dermatitis by age 12 months. Our study does not support the use of these interventions to prevent atopic dermatitis by 12 months of age in infants. FUNDING: The study was funded by several public and private funding bodies: The Regional Health Board South East, The Norwegian Research Council, Health and Rehabilitation Norway, The Foundation for Healthcare and Allergy Research in Sweden-Vårdalstiftelsen, Swedish Asthma and Allergy Association's Research Foundation, Swedish Research Council-the Initiative for Clinical Therapy Research, The Swedish Heart-Lung Foundation, SFO-V at the Karolinska Institute, Freemason Child House Foundation in Stockholm, Swedish Research Council for Health, Working Life and Welfare-FORTE, Oslo University Hospital, the University of Oslo, and Østfold Hospital Trust.

Predicting Skin Barrier Dysfunction and Atopic Dermatitis in Early Infancy.

BACKGROUND: Dry skin is associated with increased transepidermal water loss (TEWL), which has been found to precede atopic dermatitis (AD) in childhood. OBJECTIVE: We aimed to identify parental, prenatal, and perinatal predictive factors of dry skin, high TEWL, and AD at 3 months of age, and to determine if dry skin or high TEWL at 3 months can predict AD at 6 months. METHODS: From the Preventing Atopic Dermatitis and Allergies in children prospective birth cohort study, we included 1150 mother-child pairs. Dry skin, TEWL, and eczema were assessed at 3- and 6-month investigations. Eczema, used as a proxy for AD, was defined as the presence of eczematous lesions, excluding differential diagnoses to AD. High TEWL was defined as TEWL >90th percentile, equaling 11.3 g/m2/h. Potential predictive factors were recorded from electronic questionnaires at 18- and 34-week pregnancy and obstetric charts. RESULTS: Significant predictive factors (P < .05) for dry skin at 3 months were delivery >38 gestational weeks and paternal age >37 years; for high TEWL, male sex, birth during winter season, and maternal allergic disease; and for eczema, elective caesarean section, multiparity, and maternal allergic diseases. Dry skin without eczema at 3 months was predictive for eczema at 6 months (adjusted odds ratio: 1.92, 95% confidence interval: 1.21-3.05; P = .005), whereas high TEWL at 3 months was not. CONCLUSION: In early infancy, distinct parental- and pregnancy-related factors were predictive for dry skin, high TEWL, and AD. Dry skin at 3 months of age was predictive for AD 3 months later.

Food and nutrient intake and adherence to dietary recommendations during pregnancy: a Nordic mother-child population-based cohort.

BACKGROUND: A woman's food intake during pregnancy has important implications not only for herself but also for the future health and well-being of her child. Suboptimal dietary quality has been consistently reported in many high-income countries, reflecting poor adherence to dietary guidelines. OBJECTIVE: This study aimed to explore the intake of food and nutrients in a cohort of pregnant women in Norway and their adherence to Nordic Nutrition Recommendations (NNR) and Norwegian food-based guidelines (NFG). DESIGN: We investigated the dietary intake in 1,674 pregnant women from the mother-child birth cohort, PreventADALL, recruited at approximately 18-week gestational age. Dietary intake was assessed by an electronic validated food frequency questionnaire (PrevFFQ) in the first half of pregnancy. RESULTS: Total fat intake was within the recommended intake (RI) range in most women; however, the contribution of saturated fatty acids to the total energy intake was above RI in the majority (85.2%) of women. Carbohydrate intake was below RI in 43.9% of the women, and 69.5% exceeded the RI of salt. Intakes of fiber, vegetables, and fish were high in a large part of the population. Many women had a high probability of inadequate intakes of the following key micronutrients during pregnancy: folate (54.4%), iron (49.6%), calcium (36.2%), vitamin D (28.7%), iodine (24.4%), and selenium (41.3%). A total of 22.8% women reported an alcohol intake of >1 g/day, and 4.4% reported an alcohol intake of >10 g/day. Women with higher educational levels showed a tendency towards healthier eating habits, except for higher intakes of alcohol and coffee, compared to women with lower educational level. DISCUSSION: Excessive saturated fat intake and limited intake of many important micronutrients during pregnancy were common, potentially increasing the risk for adverse pregnancy and birth outcomes. CONCLUSIONS: This study highlights the need for improved nutritional guidance to pregnant women across all educational levels.