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).

Infant colic and abdominal pain; associations with infant multimorbidity and maternal perceived stress up to 3 months postpartum-A cross-sectional/cohort study in the PreventADALL study.

AIMS AND OBJECTIVES: The primary aim was to explore whether infants with pain symptoms (colic, abdominal pain and visit to healthcare provider with pain or other discomforts) had increased multimorbidity (common infections, eczema and food sensitivity) compared with infants without these conditions. Secondarily, we aimed to determine whether infant pain symptoms were associated with maternal perceived stress in pregnancy and 3 months postpartum. BACKGROUND: Infant colic and abdominal pain are common concerns in early infancy. Nevertheless, to our knowledge, little research exists on the relationship between infant pain and common infant infections, eczema and food sensitization as comorbidities, and the impact of infant pain on the development of maternal perceived stress from pregnancy to infancy is inconsistent. DESIGN: This study was cross-sectional and partly prospective. METHODS: The sample consisted of mother-infant pairs (N = 1852); information regarding infant pain and multimorbidity was collected from the 3-month questionnaire and postpartum visits in the PreventADALL prospective cohort study. Chi-square tests and regression analyses were conducted. The STROBE checklist was followed. RESULTS: Our results showed a statistically significant higher proportion of respiratory and other infections in infants with pain symptoms. The odds of infant pain were higher for infants with multimorbidity compared to those with no comorbidity. Mothers of infants with colic and of infants visiting healthcare with pain and other discomforts reported statistically significant higher perceived stress by 3 months compared with mothers of infants with no reported pain. CONCLUSION: Our results indicate an association between infant pain symptoms and the presence of infections. Mothers of infants with colic and visiting healthcare had higher perceived stress compared to the no pain group. IMPLICATIONS FOR PRACTICE: Our study indicates that infant pain is associated with infant multimorbidity and maternal perceived stress, which may be useful when planning diagnostic, treatment and coping strategies in infant and family care. PATIENT OR PUBLIC CONTRIBUTION: The PreventADALL is a collaborative study with governmental and patient organisation representation. Selected infants with parents were also contributing during calibrating courses on eczema assessment for the data collectors. TRIAL REGISTRATION: The study was approved by the Regional Committee in Norway (2014/518) and Sweden (2014/2242-31/4) and registered at clinicaltrial.gov (NCT02449850). Link for clinical trials: https://clinicaltrials.gov/ct2/show/NCT02449850.

Prevalence and perinatal risk factors of parent-reported colic, abdominal pain and other pain or discomforts in infants until 3 months of age - A prospective cohort study in PreventADALL.

AIMS AND OBJECTIVES: To estimate the prevalence and perinatal risk factors associated with parent reported colic, abdominal pain and pain or other discomforts in infants until 3 months of age. BACKGROUND: Infant colic is a common concern for parents and clinicians. The prevalence varies in different studies and its symptoms overlap with other conditions like abdominal pain and discomfort. Diagnosis criteria are challenging, pathogenesis unclear and risk factors are conflicting. DESIGN: This was a prospective cohort study. METHODS: The 1852 mother-child pairs from the PreventADALL prospective birth-cohort answering the 3 months questionnaire were included. Information on perinatal risk factors was collected from the inclusion visit and questionnaires during pregnancy at 18 and 34 weeks, as well as birth charts. STROBE checklist was followed. RESULTS: The reported prevalence of colic was 3% (59/1852), abdominal pain 22% (415/1852) and pain or other discomfort 6% (119/1852), with a total of 26% (478/1852) infants. Mothers on sick leave in pregnancy and reporting any allergic diseases had a significantly higher odds of reporting infant colic, abdominal pain and pain or other discomforts. Mothers with higher perceived stress in pregnancy exhibited a trend towards higher odds for reporting infant pain. Mothers coming from Sweden were less likely to report infant abdominal pain compared to mothers from Norway. CONCLUSIONS: The prevalence of abdominal pain and pain or other discomforts was higher than the prevalence of colic. Perinatal risk factors connected to maternal health were associated with all three symptoms. RELEVANCE TO CLINICAL PRACTICE: Colic and abdominal pain are stressful, symptoms overlap and risk factors for both can be identified in pregnancy. Our study suggests that it is difficult for parents to distinguish among infant colic, abdominal pain and other pain or discomfort and some report two or all three symptoms. Identifying the perinatal risk factors associated with infant pain may help target and support parents.

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.

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.