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Asthma is a common chronic disease in children. It is a dynamic condition-symptoms change over time, and the outcome of diagnostic tests can vary. Consequently, evaluating the onset of asthma at a single point in time, perhaps when patients are asymptomatic with limited impairment of the lung function, may result in false diagnostic conclusions. The absence of consistent gold-standard diagnostic criteria in children challenges the ability of any study to ascertain an effect of treatment on asthma prevention. A comprehensive review of the diagnostic criteria used for new-onset asthma in school-age children was conducted based on existing recommendations from published clinical guidance, alongside evidence from paediatric asthma prevention trials. Findings from the review were used to propose suggestions for diagnosing new-onset asthma in future asthma prevention trials. Despite an overall lack of consensus in the published clinical guidance, there are similarities between the various recommendations for diagnosing asthma in children, which typically involve assessing the variable symptoms and supplementing the medical history with objective measures of lung function. For future paediatric asthma prevention trials, we suggest that paediatric clinical trials should use a new-onset asthma definition that incorporates the concepts of "possible", "probable" and "confirmed" asthma. "Possible" asthma would capture self-reported features of chronic symptoms and symptom relief with ß2-agonist bronchodilator (suggesting reversibility). "Probable" asthma would include symptom chronicity, self-reported symptom relief with ß2-agonist bronchodilator, and objective features of asthma (reversibility or bronchial hyper-responsiveness). A "confirmed" diagnosis would be made only if there is a positive response to controller therapy. These suggestions aim to improve the diagnosis of new-onset childhood asthma in clinical trials, which will be useful in the design and conduct of future paediatric asthma prevention trials.
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INTRODUCTION: Knowledge on prevalence and association of human papillomavirus (HPV) in third trimester placentae and adverse pregnancy outcomes is limited. We investigated the prevalence of placental HPV at delivery, explored urine HPV characteristics associated with placental HPV and whether placental HPV increased the risk adverse pregnancy outcomes. METHODS: Pregnant women were enrolled in the Scandinavian PreventADALL mother-child cohort study at midgestation. Human papillomavirus genotyping was performed on placental biopsies collected at delivery (n = 587) and first-void urine at midgestation and delivery (n = 556). Maternal characteristics were collected by questionnaires at gestational week 18 and 34. Adverse pregnancy outcomes were registered from chart data including hypertensive disorders of pregnancy, gestational diabetes mellitus and newborns small for gestational age. Uni- and multivariable regression models were used to investigate associations. RESULTS: Placental HPV was detected in 18/587 (3 %). Twenty-eight genotypes were identified among the 214/556 (38 %) with midgestational urine HPV. Seventeen of the 18 women with placental HPV were midgestational HPV positive with 89 % genotype concordance. Midgestational high-risk-(HR)-HPV and high viral loads of Any- or HR-HPV were associated with placental HPV. Persisting HPV infection from midgestation to delivery was not associated with placental HPV. Adverse pregnancy outcomes were seen in 2/556 (0.4 %) of women with placental HPV. DISCUSSION: In this general cohort of pregnant women, the prevalence of placental HPV was 3 %, and midgestational urinary HPV 38 %. High HPV viral load increased the risk for placental HPV infections. We observed no increased risk for adverse pregnancy outcomes in women with placental HPV.
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Infecciones por Papillomavirus , Placenta , Complicaciones Infecciosas del Embarazo , Resultado del Embarazo , Humanos , Femenino , Embarazo , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/virología , Adulto , Placenta/virología , Complicaciones Infecciosas del Embarazo/epidemiología , Complicaciones Infecciosas del Embarazo/virología , Papillomaviridae/genética , Estudios de Cohortes , Tercer Trimestre del Embarazo , Adulto JovenRESUMEN
BACKGROUND: In the general population randomized controlled trial PreventADALL, frequent emollient bath additives from 2 weeks of age did not prevent atopic dermatitis, while the effect on skin barrier function throughout infancy is not established. OBJECTIVES: The primary aim of this exploratory substudy was to assess the effect of mineral-based oil baths on transepidermal water loss (TEWL) and dry skin through infancy, and secondarily to explore if filaggrin (FLG) mutations modified the effect. METHODS: Overall, 2153 infants were included and randomized to either the 'Skin intervention' (SI) group (n = 995) (oil bath 4 times weekly from 2 weeks through 8â months) or 'No skin intervention' (NSI) group (n = 1158), with TEWL measurements at 3, 6 and/or 12â months of age. Information on FLG mutation status was available for 1683 of these infants. Effects of the skin intervention on TEWL and dry skin through infancy were assessed by mixed-effects regression modelling. Background characteristics and protocol adherence were collected from electronic questionnaires, birth records and weekly diaries. RESULTS: The TEWL (95% confidence interval) was on average 0.42â g m-2 h-1 (0.13-0.70, P = 0.004) higher in the SI group compared with the NSI group through the first year of life, with significantly higher levels at 3â months [8.6 (8.3-9.0) vs. 7.6 (7.3-7.9)], but similar at 6 and 12â months. Dry skin was observed significantly more often in the NSI group compared with the SI group at 3â months (59% vs. 51%) and at 6â months of age (63% vs. 53%), while at 12â months of age, the difference was no longer significant. At 3â months, the TEWL of FLG mutation carriers was similar to the TEWL in the SI group. No interaction between SI and FLG mutation was found in the first year of life. CONCLUSIONS: Infants given frequent oil baths from 2 weeks of age had reduced skin barrier function through infancy compared with controls, largely attributed to higher TEWL at 3â months of age, while the skin at 3 and 6â months appeared less dry in infants subjected to the skin intervention.
Atopic dermatitis (AD) affects approximately 20% of children in industrialized countries. AD causes dry, itchy skin and can increase the chance of infections. This study was a substudy of the large Scandinavian PreventADALL trial, including 2394 infants, recruited from the general population between 2014 and 2016. Children in this trial were allocated randomly to receive either a skin intervention, food intervention, combined intervention, or no intervention. Children were examined at 3, 6 and 12â months of age. The examinations involved an investigation of the skin, to evaluate dry skin and skin barrier function by transepidermal water loss (TEWL) in the outer layers of the skin (higher TEWL suggests decreased skin barrier function). The skin intervention consisted of oil baths at least 4 times per week from 2 weeks of age through 8â months of age, and have previously not been shown to prevent AD by 1 and 3â years of age. We aimed to investigate whether frequent oil baths had any effect on TEWL and dry skin. We found that the skin intervention increased TEWL in the first year of life, especially at 3â months of age. Dry skin was less common in the skin intervention groups compared with the groups with no skin intervention. Infants with mutations in the gene coding for a skin barrier protein, called filaggrin, were associated with increased TEWL; however, in the skin intervention group, TEWL was similar among the infants with or without filaggrin mutations. Our findings suggest that oil baths several times per week from early infancy transiently decreases skin barrier function.
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Baños , Dermatitis Atópica , Emolientes , Proteínas Filagrina , Proteínas de Filamentos Intermediarios , Mutación , Pérdida Insensible de Agua , Humanos , Pérdida Insensible de Agua/efectos de los fármacos , Baños/métodos , Lactante , Femenino , Dermatitis Atópica/prevención & control , Dermatitis Atópica/genética , Masculino , Emolientes/administración & dosificación , Proteínas de Filamentos Intermediarios/genética , Recién Nacido , Aceite Mineral/administración & dosificación , Cuidado del Lactante/métodos , Cuidados de la Piel/métodos , Piel/efectos de los fármacosRESUMEN
INTRODUCTION: Eosinophil-derived neurotoxin (EDN) is related to childhood asthma, while normal values are lacking. We aimed to document serum EDN levels at 1 and 3 years in general and in non-atopic children, and explore if EDN levels differed by sex or were associated with preschool asthma at 3 years. METHODS: From the PreventADALL birth cohort, we included 1233 children with EDN analysed using ImmunoCAP at 1 and/or 3 years. Non-atopic children had no history of wheeze, asthma, allergic sensitization or atopic dermatitis. Preschool asthma was defined as having ≥3 episodes of bronchial obstruction between 2 and 3 years, plus doctor diagnosed asthma and/or asthma medication use by 3 years. The upper limit of normal (ULN) of EDN was defined as the 95th percentile. With Youden Index we calculated EDN cut-off levels for risk of preschool asthma. RESULTS: The overall median (ULN) EDN levels were 27.4 (121) µg/L at 1 year (n = 787), and 20.1 (87.8) µg/L at 3 years (n = 857). Non-atopic children had EDN levels of 24.0 (107) µg/L at 1 year (n = 147), and 17.3 (84.6) µg/L at 3 years (n = 173). EDN levels were higher in boys compared to girls; 32.0 (133) versus 24.5 (97.0) µg/L at 1 year, and 20.9 (96.3) versus 19.0 (72.4) µg/L at 3 years. Preschool asthma was observed in 109/892 (12.2%) children. Higher EDN levels at 1 (>26.7 µg/L) and 3 (≥20.5 µg/L) years were associated with preschool asthma; adjusted OR (95% CI) 2.20 (1.09, 4.41) and 4.68 (2.29, 9.55), respectively. CONCLUSION AND CLINICAL RELEVANCE: We report EDN values in early childhood, demonstrating higher levels at 1 compared to 3 years and in boys compared to girls at both ages. Higher EDN levels at both ages were associated with preschool asthma. However, EDN cut-off levels for preschool asthma were overall lower than the ULN of non-atopic children, limiting translation into clinical practice.
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Asma , Dermatitis Atópica , Masculino , Niño , Femenino , Preescolar , Humanos , Neurotoxina Derivada del Eosinófilo , Eosinófilos , Biomarcadores , Asma/diagnóstico , Asma/epidemiología , Asma/etiologíaRESUMEN
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.
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Cólico , Eccema , Femenino , Embarazo , Lactante , Humanos , Cólico/epidemiología , Estudios Prospectivos , Estudios de Cohortes , Multimorbilidad , Estudios Transversales , Periodo Posparto , Madres , Dolor Abdominal , Estrés PsicológicoRESUMEN
Bacteroides and Phocaeicola, members of the family Bacteroidaceae, are among the first microbes to colonize the human infant gut. While it is known that these microbes can be transmitted from mother to child, our understanding of the specific strains that are shared and potentially transmitted is limited. In this study, we aimed to investigate the shared strains of Bacteroides and Phocaeicola in mothers and their infants. We analyzed fecal samples from pregnant woman recruited at 18 weeks of gestation from the PreventADALL study, as well as offspring samples from early infancy, including skin swab samples taken within 10 min after birth, the first available fecal sample (meconium), and fecal samples at 3 months of age. We screened 464 meconium samples for Bacteroidaceae, with subsequent selection of 144 mother-child pairs for longitudinal analysis, based on the presence of Bacteroidaceae, longitudinal sample availability, and delivery mode. Our results showed that Bacteroidaceae members were mainly detected in samples from vaginally delivered infants. We identified high prevalences of Phocaeicola vulgatus, Phocaeicola dorei, Bacteroides caccae, and Bacteroides thetaiotaomicron in mothers and vaginally born infants. However, at the strain level, we observed high prevalences of only two strains: a B. caccae strain and a P. vulgatus strain. Notably, the B. caccae strain was identified as a novel component of mother-child shared strains, and its high prevalence was also observed in publicly available metagenomes worldwide. Our findings suggest that mode of delivery may play a role in shaping the early colonization of the infant gut microbiota, in particular the colonization of Bacteroidaceae members. IMPORTANCE Our study provides evidence that Bacteroidaceae strains present on infants' skin within 10 min after birth, in meconium samples, and in fecal samples at 3 months of age in vaginally delivered infants are shared with their mothers. Using strain resolution analyses, we identified two strains, belonging to Bacteroides caccae and Phocaeicola vulgatus, as shared between mothers and their infants. Interestingly, the B. caccae strain showed a high prevalence worldwide, while the P. vulgatus strain was less common. Our findings also showed that vaginal delivery was associated with early colonization of Bacteroidaceae members, whereas cesarean section delivery was associated with delayed colonization. Given the potential for these microbes to influence the colonic environment, our results suggest that understanding the bacterial-host relationship at the strain level may have implications for infant health and development later in life.
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Bacteroidaceae , Cesárea , Lactante , Humanos , Femenino , Embarazo , Transmisión Vertical de Enfermedad Infecciosa , Bacteroides/genética , Heces , Relaciones Madre-HijoRESUMEN
BACKGROUND: Reduced lung function at birth has evident antenatal origins and is associated with an increased risk of wheezing and asthma later in life. Little is known about whether blood flow in the fetal pulmonary artery, may impact postnatal lung function. OBJECTIVE: Our primary aim was to investigate the potential associations between fetal Doppler blood flow velocity measures in the fetal branch pulmonary artery, and infant lung function by tidal flow-volume (TFV) loops at three months of age in a low-risk population. Our secondary aim was to explore the association between Doppler blood flow velocity measures in the umbilical and middle cerebral arteries, and the same lung function measures. METHODS: In 256 non-selected pregnancies from the birth cohort study Preventing Atopic Dermatitis and ALLergies in Children (PreventADALL) we performed fetal ultrasound examination with Doppler blood flow velocity measurements at 30 gestational weeks (GW). We recorded the pulsatility index, peak systolic velocity, time-averaged maximum velocity, acceleration time/ejection time ratio, and time velocity integral primarily in the proximal pulmonary artery close to the pulmonary bifurcation. The pulsatility index was measured in the umbilical and middle cerebral arteries and the peak systolic velocity in the middle cerebral artery. The cerebro-placental ratio (ratio between pulsatility index in the middle cerebral and umbilical arteries) was calculated. Infant lung function was assessed using TFV loops in awake, calmly breathing three months old infants. The outcome was the time to peak tidal expiratory flow to expiratory time ratio (tPTEF/tE), tPTEF/tE <25th percentile, and tidal volume per kg body weight (VT/kg). Potential associations between fetal Doppler blood flow velocity measures and infant lung function were assessed using linear and logistic regressions. RESULTS: The infants were born at median (min - max) 40.3 (35.6 - 42.4) GW, with a mean (SD) birth weight of 3.52 (0.46) kg, and 49.4% were females. The mean (SD) tPTEF/tE was 0.39 (0.1) and the 25th percentile was 0.33. Neither univariable nor multivariable regression models revealed any associations between fetal pulmonary blood flow velocity measures and tPTEF/tE, tPTEF/tE <25th percentile, or VT/kg at three months of age. Similarly, we did not observe associations between Doppler blood flow velocity measures in the umbilical and middle cerebral arteries and infant lung function measures. CONCLUSION: In a cohort of 256 infants from the general population, fetal third-trimester Doppler blood flow velocity measures in the branch pulmonary, umbilical, and middle cerebral arteries were not associated with infant lung function measures at three months of age.
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Placenta , Arteria Pulmonar , Recién Nacido , Niño , Lactante , Humanos , Embarazo , Femenino , Masculino , Arteria Pulmonar/diagnóstico por imagen , Estudios de Cohortes , Velocidad del Flujo Sanguíneo/fisiología , Estudios Prospectivos , Pulmón/diagnóstico por imagen , Ultrasonografía Doppler , Arterias Umbilicales/fisiología , Ultrasonografía PrenatalRESUMEN
BACKGROUND: Early-life microbial colonization of the skin may modulate the immune system and impact the development of atopic dermatitis (AD) and allergic diseases later in life. To address this question, we assessed the association between the skin microbiome and AD, skin barrier integrity and allergic diseases in the first year of life. We further explored the evolution of the skin microbiome with age and its possible determinants, including delivery mode. METHODS: Skin microbiome was sampled from the lateral upper arm on the first day of life, and at 3, 6, and 12 months of age. Bacterial communities were assessed by 16S rRNA gene amplicon sequencing in 346 infants from the PreventADALL population-based birth cohort study, representing 970 samples. Clinical investigations included skin examination and skin barrier function measured as trans-epidermal water loss (TEWL) at the site and time of microbiome sampling at 3, 6, and 12 months. Parental background information was recorded in electronic questionnaires, and delivery mode (including vaginal delivery (VD), VD in water, elective caesarean section (CS) and emergency CS) was obtained from maternal hospital charts. RESULTS: Strong temporal variations in skin bacterial community composition were found in the first year of life, with distinct patterns associated with different ages. Confirming our hypothesis, skin bacterial community composition in the first year of life was associated with skin barrier integrity and later onsets of AD. Delivery mode had a strong impact on the microbiome composition at birth, with each mode leading to distinct patterns of colonization. Other possible determinants of the skin microbiome were identified, including environmental and parental factors as well as breastfeeding. CONCLUSION: Skin microbiome composition during infancy is defined by age, transiently influenced by delivery mode as well as environmental, parental factors and breastfeeding. The microbiome is also associated with skin barrier integrity and the onset of AD.
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Dermatitis Atópica , Hipersensibilidad , Microbiota , Lactante , Recién Nacido , Humanos , Embarazo , Femenino , Cesárea , ARN Ribosómico 16S/genética , Estudios de Cohortes , Piel/microbiología , Bacterias/genética , AguaRESUMEN
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.
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Hipersensibilidad a los Alimentos , Bovinos , Animales , Femenino , Embarazo , Estudios Prospectivos , Estudios de Cohortes , Hipersensibilidad a los Alimentos/prevención & control , Suplementos Dietéticos , Alérgenos , DietaRESUMEN
Background and aim: Physical activity (PA) in pregnancy is important for maternal and possibly offspring health. To study the early origins of lung function we aimed to determine whether PA in the first half of pregnancy is associated with lung function in healthy 3-month-old infants. Methods: From the general population-based Preventing Atopic Dermatitis and Allergies in Children birth cohort recruiting infants antenatally in Norway and Sweden, all 812 infants (48.8% girls) with available tidal flow-volume measures in the awake state at 3â months of age and mid-pregnancy data on PA were included. PA was self-reported by the mothers and, based on intensity, we categorised them as active or inactive during pregnancy. Furthermore, we defined active mothers as fairly or highly active. The main outcome was a ratio of time to peak tidal expiratory flow to expiratory time (t PTEF/t E) <0.25. Associations were analysed by logistic regression, adjusting for maternal age, education, parity, pre-pregnancy body mass index, in utero nicotine exposure and parental atopy. Results: The mean±sd t PTEF/t E was 0.391±0.08 and did not differ significantly according to maternal PA level in pregnancy. The 290 infants of inactive mothers had higher odds of having t PTEF/t E <0.25 compared to infants of all active mothers (OR 2.07, 95% CI 1.13-3.82; p=0.019) and compared to infants (n=224) of fairly active (OR 2.83, 95% CI 1.26-7.24; p=0.018) but not highly active mothers (n=298). Conclusion: Based on self-reported maternal PA in the first half of pregnancy, 3-month-old infants of inactive compared to active mothers had higher odds of a low t PTEF/t E.
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Background: Tidal flow-volume (TFV) loops are commonly recorded in infants during sleep, due to the more regular breathing patterns compared to the awake state. Standardised deselection of loops outside pre-specified ranges are based on periods of regular breathing, while criteria and available software for visual evaluation of TFV loops are lacking. We aimed to determine the reliability of standardised criteria for manual selection of infant TFV loops. Methods: Using a pre-defined set of criteria, three independent raters manually evaluated TFV loops among 57 randomly selected awake healthy 3-month-old infants with available TFV measurements in the Scandinavian Preventing Atopic Dermatitis and ALLergies in children (PreventADALL) study. The TFV loops were sampled using the Eco Medics Exhalyzer D. Criteria for selecting TFV loops included reproducible shape and volume with only one peak in tidal expiratory flow (PTEF), excluding loops with no clear or uneven flow towards PTEF. By intraclass coefficient (ICC), the reliability of agreement between raters was determined for the time to PTEF (t PTEF) to expiratory time (t E) and other TFV loop parameters. Results: Five infants had unsuccessful tests. Among the remaining 52 infants, the raters selected a median of 25, 26 and 15 loops per test. The ICCs (95% CI) were 0.97 (0.92-0.98) for t PTEF/t E, 0.99 (0.99-1.00) for respiratory rate, 0.98 (0.97-0.99) for tidal volume per kg and 0.98 (0.97-0.99) for expiratory volume, reflecting excellent agreement in all categories. Conclusion: Manual TFV loop selection using standardised criteria provides a reliable alternative for lung function measures in awake infants with interrupted breathing cycles in a real-life setting.
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Background: Infant lung function can be assessed with tidal flow-volume (TFV) loops. While TFV loops can be measured in both awake and sleeping infants, the influence of arousal state in early infancy is not established. The aim of the present study was to determine whether TFV loop parameters in healthy infants differed while awake compared to the sleeping state at 3â months of age. Methods: From the population-based Scandinavian Preventing Atopic Dermatitis and ALLergies in children (PreventADALL) birth cohort, 91 infants had reproducible TFV loops measured with Exhalyzer® D in both the awake and sleeping state at 3â months of age. The TFV loops were manually selected according to a standardised procedure. The ratio of time to peak tidal expiratory flow (t PTEF) to expiratory time (t E) and the corresponding volume ratio (V PTEF/V E), as well as tidal volume (V T) and respiratory rate were compared using nonparametric tests. Results: The mean (95% CI) t PTEF/t E was significantly higher while awake compared to the sleeping state: 0.39 (0.37-0.41) versus 0.28 (0.27-0.29); with the corresponding V PTEF/V E of 0.38 (0.36-0.40) versus 0.29 (0.28-0.30). The V T was similar, while the respiratory rate was higher while awake compared to the sleeping state: 53 (51-56) breaths·min-1 versus 38 (36-40) breaths·min-1. Conclusion: Higher t PTEF/t E, V PTEF/V E and respiratory rate, but similar V T while awake compared to the sleeping state suggests that separate normative TFV loop values according to arousal state may be required in early infancy.
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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 2â×â2 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).
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Hipersensibilidad al Huevo , Hipersensibilidad a los Alimentos , Hipersensibilidad al Cacahuete , Animales , Bovinos , Preescolar , Hipersensibilidad al Huevo/prevención & control , Emolientes/uso terapéutico , Femenino , Hipersensibilidad a los Alimentos/epidemiología , Hipersensibilidad a los Alimentos/prevención & control , Humanos , Lactante , Fenómenos Fisiológicos Nutricionales del Lactante , EmbarazoRESUMEN
BACKGROUND: Salivary cortisol (SC), a commonly used biomarker for stress, may be disrupted by negative events in pregnancy, at birth and in infancy. We aimed to explore if maternal perceived stress (PSS) in or after pregnancy and SC levels in pregnancy were associated with SC in early infancy, and, secondly, to identify early life factors associated with infants' SC levels (iSC). METHODS: At 3 months of age, SC was analyzed in 1057 infants participating in a Nordic prospective mother-child birth cohort study. Maternal PSS was available from questionnaires at 18- and 34-week gestational age (GA) and 3-month post-partum, and SC was analyzed at 18-week GA. Early life factors included sociodemographic and infant feeding from questionnaires, and birth data from medical charts. Associations to iSC were analyzed by Spearman correlation and multinomial logistic regression analyses. RESULTS: In this exploratory study neither PSS at any time point nor maternal SC (mSC) were associated with iSC. Higher birth weight was associated with higher levels of iSC, while inverse associations were observed in infants to a mother not living with a partner and mixed bottle/breastfeeding. CONCLUSIONS: Maternal stress was not associated with iSC levels, while birth weight, single motherhood and infant feeding may influence iSC levels.
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BACKGROUND: Factors predicting allergic sensitization in the first 6 months of life are poorly understood. We aimed to determine whether eczema, dry skin, and high transepidermal water loss (TEWL) at 3 months were associated with allergic sensitization at 6 months of age and, secondarily, to establish whether these characteristics predicted sensitization from 3 to 6 months of age. METHODS: At 3 months of age, 1,994 infants from the population-based PreventADALL birth cohort in Norway and Sweden were assessed for eczema and dry skin on the cheeks and/or extensors; impaired skin barrier function, defined as TEWL in the upper quartile (>9.4 g/m2 /h), and allergen-specific IgE levels <0.1 kUA /L, available in 830. At 6 months, we assessed allergic sensitization to any food (egg, cow's milk, peanut, wheat, soy) or inhalant (birch, timothy grass, dog, and cat) allergen by a skin prick test wheal diameter ≥2 mm larger than negative control. RESULTS: Any sensitization was found in 198 of the 1,994 infants (9.9%), the majority to food allergens (n = 177, 8.9%). Eczema, dry skin, and high TEWL at 3 months increased the risk of sensitization at 6 months; adjusted odds ratios 4.20 (95% CI 2.93-6.04), 2.09 (95% CI 1.51-2.90) and 3.67 (95% CI 2.58-5.22), respectively. Eczema predicted sensitization with 55.6% sensitivity and 68.1% specificity; dry skin with 65.3% sensitivity and 57.3% specificity; and high TEWL with 61.7% sensitivity and 78.1% specificity. CONCLUSION: Eczema, dry skin, and high TEWL at 3 months predicted allergic sensitization at 6 months of age.
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Eccema , Hipersensibilidad a los Alimentos , Alérgenos , Animales , Bovinos , Perros , Eccema/epidemiología , Eccema/etiología , Femenino , Hipersensibilidad a los Alimentos/diagnóstico , Hipersensibilidad a los Alimentos/epidemiología , Humanos , Inmunoglobulina E , Lactante , Pruebas CutáneasRESUMEN
OBJECTIVE: Research on early origins of lung disease suggests the need for studying the relationships of thoracic and lung size with fetal size and pulmonary circulation. The primary aim of this study is therefore to explore the associations between fetal thoracic circumference, lung volume, and fetal size. We also aim to assess if lung volume and thoracic circumference are associated with fetal pulmonary artery blood flow velocity measures. METHODS: Cross-sectional assessment of singleton pregnancies from the general population (n = 447) at 30 gestational weeks (GW) was performed using ultrasound measurement of fetal thoracic circumference, lung volume, head and abdominal circumference, and femur length. We obtained Doppler blood flow velocity measures from the proximal branches of the fetal pulmonary artery. Associations between variables were studied using Pearson's correlation and multiple linear regression analyses. RESULTS: Both thoracic circumference and lung volume correlated with fetal size measures, ranging from r = 0.64 between thoracic circumference and abdominal circumference, to r = 0.28 between lung volume and femur length. Adjustment for gestational age, maternal nicotine use, pre-pregnancy body mass index, and fetal sex marginally influenced the associations with abdominal circumference. The correlations of thoracic circumference and lung volume with pulmonary artery blood flow velocity measures were weak (r ≤ 0.17). CONCLUSION: We found moderate to low correlation between thoracic circumference, lung volume, and fetal size at 30 GW. The closest relationship was with the abdominal circumference. We found low correlations of thoracic circumference and lung volume with pulmonary artery blood flow velocity measures.
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Arteria Pulmonar , Circulación Pulmonar , Velocidad del Flujo Sanguíneo , Estudios Transversales , Femenino , Edad Gestacional , Humanos , Mediciones del Volumen Pulmonar , Embarazo , Arteria Pulmonar/diagnóstico por imagen , Ultrasonografía PrenatalRESUMEN
OBJECTIVE: To compare Doppler blood flow velocity measures in the right and left proximal branch of the fetal pulmonary artery at 30 gestational weeks. METHODS: Doppler blood flow velocity waveforms were recorded in both fetal proximal pulmonary artery branches in 62 healthy fetuses at 30 gestational weeks. Pulsatility index, peak systolic velocity, time averaged maximum velocity, time velocity integral, fetal heart rate, acceleration- and ejection time with their ratio, time of one heart cycle and time velocity integral were recorded. Paired-samples t-test was used to compare measures from the right and left pulmonary branch. RESULTS: We observed significantly higher peak systolic velocity, time averaged maximum velocity, time velocity integral, acceleration time and acceleration time/ejection time ratio in the right compared to the left pulmonary artery (p < .001). Sampling angle, pulsatility index, fetal heart rate, ejection time and time of one heart cycle were similar in both pulmonary branches. CONCLUSION: Our study conducted at 30 weeks gestational age found significantly different blood flow velocity waveform measures in the right and left pulmonary artery branches in contrast to previous reports of similar velocities.
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Arteria Pulmonar , Ultrasonografía Prenatal , Velocidad del Flujo Sanguíneo , Femenino , Feto/diagnóstico por imagen , Feto/fisiología , Edad Gestacional , Hemodinámica , Humanos , Embarazo , Arteria Pulmonar/diagnóstico por imagen , Ultrasonografía DopplerRESUMEN
BACKGROUND: Eczema and food allergy are common health conditions that usually begin in early childhood and often occur together in the same people. They can be associated with an impaired skin barrier in early infancy. It is unclear whether trying to prevent or reverse an impaired skin barrier soon after birth is effective in preventing eczema or food allergy. OBJECTIVES: Primary objective To assess effects of skin care interventions, such as emollients, for primary prevention of eczema and food allergy in infants Secondary objective To identify features of study populations such as age, hereditary risk, and adherence to interventions that are associated with the greatest treatment benefit or harm for both eczema and food allergy. SEARCH METHODS: We searched the following databases up to July 2020: Cochrane Skin Specialised Register, CENTRAL, MEDLINE, and Embase. We searched two trials registers and checked reference lists of included studies and relevant systematic reviews for further references to relevant randomised controlled trials (RCTs). We contacted field experts to identify planned trials and to seek information about unpublished or incomplete trials. SELECTION CRITERIA: RCTs of skin care interventions that could potentially enhance skin barrier function, reduce dryness, or reduce subclinical inflammation in healthy term (> 37 weeks) infants (0 to 12 months) without pre-existing diagnosis of eczema, food allergy, or other skin condition were included. Comparison was standard care in the locality or no treatment. Types of skin care interventions included moisturisers/emollients; bathing products; advice regarding reducing soap exposure and bathing frequency; and use of water softeners. No minimum follow-up was required. DATA COLLECTION AND ANALYSIS: This is a prospective individual participant data (IPD) meta-analysis. We used standard Cochrane methodological procedures, and primary analyses used the IPD dataset. Primary outcomes were cumulative incidence of eczema and cumulative incidence of immunoglobulin (Ig)E-mediated food allergy by one to three years, both measured by the closest available time point to two years. Secondary outcomes included adverse events during the intervention period; eczema severity (clinician-assessed); parent report of eczema severity; time to onset of eczema; parent report of immediate food allergy; and allergic sensitisation to food or inhalant allergen. MAIN RESULTS: This review identified 33 RCTs, comprising 25,827 participants. A total of 17 studies, randomising 5823 participants, reported information on one or more outcomes specified in this review. Eleven studies randomising 5217 participants, with 10 of these studies providing IPD, were included in one or more meta-analysis (range 2 to 9 studies per individual meta-analysis). Most studies were conducted at children's hospitals. All interventions were compared against no skin care intervention or local standard care. Of the 17 studies that reported our outcomes, 13 assessed emollients. Twenty-five studies, including all those contributing data to meta-analyses, randomised newborns up to age three weeks to receive a skin care intervention or standard infant skin care. Eight of the 11 studies contributing to meta-analyses recruited infants at high risk of developing eczema or food allergy, although definition of high risk varied between studies. Durations of intervention and follow-up ranged from 24 hours to two years. We assessed most of this review's evidence as low certainty or had some concerns of risk of bias. A rating of some concerns was most often due to lack of blinding of outcome assessors or significant missing data, which could have impacted outcome measurement but was judged unlikely to have done so. Evidence for the primary food allergy outcome was rated as high risk of bias due to inclusion of only one trial where findings varied when different assumptions were made about missing data. Skin care interventions during infancy probably do not change risk of eczema by one to two years of age (risk ratio (RR) 1.03, 95% confidence interval (CI) 0.81 to 1.31; moderate-certainty evidence; 3075 participants, 7 trials) nor time to onset of eczema (hazard ratio 0.86, 95% CI 0.65 to 1.14; moderate-certainty evidence; 3349 participants, 9 trials). It is unclear whether skin care interventions during infancy change risk of IgE-mediated food allergy by one to two years of age (RR 2.53, 95% CI 0.99 to 6.47; 996 participants, 1 trial) or allergic sensitisation to a food allergen at age one to two years (RR 0.86, 95% CI 0.28 to 2.69; 1055 participants, 2 trials) due to very low-certainty evidence for these outcomes. Skin care interventions during infancy may slightly increase risk of parent report of immediate reaction to a common food allergen at two years (RR 1.27, 95% CI 1.00 to 1.61; low-certainty evidence; 1171 participants, 1 trial). However, this was only seen for cow's milk, and may be unreliable due to significant over-reporting of cow's milk allergy in infants. Skin care interventions during infancy probably increase risk of skin infection over the intervention period (RR 1.34, 95% CI 1.02 to 1.77; moderate-certainty evidence; 2728 participants, 6 trials) and may increase risk of infant slippage over the intervention period (RR 1.42, 95% CI 0.67 to 2.99; low-certainty evidence; 2538 participants, 4 trials) or stinging/allergic reactions to moisturisers (RR 2.24, 95% 0.67 to 7.43; low-certainty evidence; 343 participants, 4 trials), although confidence intervals for slippages and stinging/allergic reactions are wide and include the possibility of no effect or reduced risk. Preplanned subgroup analyses show that effects of interventions were not influenced by age, duration of intervention, hereditary risk, FLG mutation, or classification of intervention type for risk of developing eczema. We could not evaluate these effects on risk of food allergy. Evidence was insufficient to show whether adherence to interventions influenced the relationship between skin care interventions and risk of developing eczema or food allergy. AUTHORS' CONCLUSIONS: Skin care interventions such as emollients during the first year of life in healthy infants are probably not effective for preventing eczema, and probably increase risk of skin infection. Effects of skin care interventions on risk of food allergy are uncertain. Further work is needed to understand whether different approaches to infant skin care might promote or prevent eczema and to evaluate effects on food allergy based on robust outcome assessments.
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Eccema/prevención & control , Emolientes/uso terapéutico , Hipersensibilidad a los Alimentos/prevención & control , Cuidados de la Piel/métodos , Sesgo , Femenino , Proteínas Filagrina , Hipersensibilidad a los Alimentos/inmunología , Humanos , Hipersensibilidad Inmediata/inmunología , Inmunoglobulina E/inmunología , Lactante , Recién Nacido , Masculino , Hipersensibilidad a la Leche/etiología , Enfermedades Cutáneas Infecciosas/epidemiología , JabonesRESUMEN
OBJECTIVE: Eczema and food allergy start in infancy and have shared genetic risk factors that affect skin barrier. We aimed to evaluate whether skincare interventions can prevent eczema or food allergy. DESIGN: A prospectively planned individual participant data meta-analysis was carried out within a Cochrane systematic review to determine whether skincare interventions in term infants prevent eczema or food allergy. DATA SOURCES: Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase and trial registries to July 2020. ELIGIBILITY CRITERIA FOR SELECTED STUDIES: Included studies were randomized controlled trials of infants <1 year with healthy skin comparing a skin intervention with a control, for prevention of eczema and food allergy outcomes between 1 and 3 years. RESULTS: Of the 33 identified trials, 17 trials (5823 participants) had relevant outcome data and 10 (5154 participants) contributed to IPD meta-analysis. Three of seven trials contributing to primary eczema analysis were at low risk of bias, and the single trial contributing to primary food allergy analysis was at high risk of bias. Interventions were mainly emollients, applied for the first 3-12 months. Skincare interventions probably do not change risk of eczema by age 1-3 years (RR 1.03, 95% CI 0.81, 1.31; I2 =41%; moderate certainty; 3075 participants, 7 trials). Sensitivity analysis found heterogeneity was explained by increased eczema in a trial of daily bathing as part of the intervention. It is unclear whether skincare interventions increase risk of food allergy by age 1-3 years (RR 2.53, 95% CI 0.99 to 6.47; very low certainty; 996 participants, 1 trial), but they probably increase risk of local skin infections (RR 1.34, 95% CI 1.02, 1.77; I2 =0%; moderate certainty; 2728 participants, 6 trials). CONCLUSION: Regular emollients during infancy probably do not prevent eczema and probably increase local skin infections.
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Dermatitis Atópica/prevención & control , Emolientes/uso terapéutico , Hipersensibilidad a los Alimentos/prevención & control , Humanos , Lactante , Recién Nacido , Cuidados de la Piel , Enfermedades Cutáneas Infecciosas/epidemiología , Jabones , Ablandamiento del AguaRESUMEN
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 â¼150 million base pairs (bp) for mothers and â¼20 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.