Perinatal risk factors for wheezing phenotypes in the first 8 years of life.

BACKGROUND: A novel data-driven approach was used to identify wheezing phenotypes in pre-schoolchildren aged 0-8 years, in the Prevention and Incidence of Asthma and Mite Allergy (PIAMA) birth cohort. Five phenotypes were identified: never/infrequent wheeze, transient early wheeze, intermediate onset wheeze, persistent wheeze and late onset wheeze. It is unknown which perinatal risk factors drive development of these phenotypes. OBJECTIVE: The objective of the study was to assess associations of perinatal factors with wheezing phenotypes and to identify possible targets for prevention. METHODS: In the PIAMA study (n = 3963), perinatal factors were collected at 3 months, and wheezing was assessed annually until the age of 8 years. Associations between perinatal risk factors and the five wheezing phenotypes were assessed using weighted multinomial logistic regression models. Odds ratios were adjusted for confounding variables and calculated with 'never/infrequent wheeze' as reference category. RESULTS: Complete data were available for 2728 children. Risk factors for transient early wheeze (n = 455) were male gender, maternal and paternal allergy, low maternal age, high maternal body mass index, short pregnancy duration, smoking during pregnancy, presence of older siblings and day-care attendance. Risk factors for persistent wheeze (n = 83) were male gender, maternal and paternal allergy, and not receiving breastfeeding for at least 12 weeks. Intermediate onset wheeze (n = 98) was associated with a lower birth weight and late onset wheeze (n = 45) with maternal allergy. CONCLUSION AND CLINICAL RELEVANCE: We identified different risk factors for specific childhood wheezing phenotypes. Some of these are modifiable, such as maternal age and body mass index, smoking, day-care attendance and breastfeeding, and may be important targets for prevention programmes.

Childhood wheezing phenotypes and FeNO in atopic children at age 8.

BACKGROUND: Fractional exhaled Nitric Oxide (FeNO) is a surrogate biomarker of the degree of eosinophilic airway inflammation. Using longitudinal latent class analysis, five wheezing phenotypes have been identified, characterized by different ages of onset and prognosis. OBJECTIVES: To assess FeNO measured at 4 and 8 years in children with different phenotypes of wheeze and atopy. METHODS: Children participated in the Prevention and Incidence of Asthma and Mite Allergy (PIAMA) study, a prospective birth cohort in the Netherlands. Respiratory health was assessed yearly by questionnaires until the age of 8 years; these data were used to identify five wheezing phenotypes. Associations between FeNO and wheezing phenotypes were investigated using weighted linear regression. RESULTS: Data on wheezing phenotypes and FeNO at 4 and 8 years were available in 588 and 973 children respectively. Compared with the phenotype of never and transient wheeze, FeNO at 4 years was higher in intermediate onset and persistent wheeze. FeNO at 8 years of age differed significantly between all phenotypes, with highest FeNO values for persistent, intermediate onset, and late onset wheeze. Rise in FeNO from 4 to 8 years in intermediate and late onset wheezers was significantly higher compared to FeNO rise in never and transient wheezers. Stratified analyses showed that the increase in FeNO in persistent, intermediate, and late onset wheeze was only present in children with allergic sensitization at 8 years. CONCLUSIONS AND CLINICAL RELEVANCE: The FeNO measured at 8 years was associated with specific wheezing phenotypes, only among atopic children.

The transient value of classifying preschool wheeze into episodic viral wheeze and multiple trigger wheeze.

BACKGROUND: A recently proposed method for classifying preschool wheeze is to describe it as either episodic (viral) wheeze or multiple trigger wheeze. In research studies, phenotype is generally determined by retrospective questionnaire. AIM: To determine whether recently proposed phenotypes of preschool wheeze are stable over time. METHODS: In all, 132 two to six-year-old children with doctor diagnosed asthma on maintenance inhaled corticosteroids were classified as having episodic (viral) wheeze or multiple trigger wheeze at a screening visit and then followed up at three-monthly intervals for a year. At each follow-up visit, standardized questionnaires were used to determine whether the subjects wheezed only with, or also in the absence of colds. Stability of the phenotypes was assessed at the end of the study. RESULTS: Phenotype as determined by retrospective parental report at the start of the study was not predictive of phenotype during the study year. Phenotypic classification remained the same in 45.9% of children and altered in 54.1% of children. CONCLUSION: When children with preschool wheeze are classified into episodic (viral) wheeze or multiple trigger wheeze based on retrospective questionnaire, the classification is likely to change significantly within a 1-year period.

[Weighing before and after feeding: an unreliable method for estimating milk intake in infants]. / Wegen vóór en na de voeding: een onbetrouwbare methode om de hoeveelheid gedronken melk bij zuigelingen te bepalen.

OBJECTIVE: Weighing before and after feeding (test weighing) is commonly used to estimate the amount ofmilk intake in neonates. This study was designed to assess the reliability of test weighing in clinical practice, expressed as precision (scatter of measurements around the real value) and accuracy (the ability of a method to measure the real value). DESIGN: Method study. METHOD: Bottle-fed infants were weighed before and immediately after feeding by an investigator who was unaware of the amount of milk drunk by the infant. Actual milk intake was determined by reading the ml scale of the milk container before and after feeding. The accuracy and precision of test weighing were assessed by applying the method of Bland and Altman, by examining the frequency distribution of the difference between weight change and actual milk intake. The precision of the weighing scale used was assessed by calculating the standard deviation of repeated measurements of standard weights of 1.5 and 4 kg. RESULTS: Of 100 eligible infants, 6 were excluded because the measurements were taken with unknown scales. The accuracy of the test weighing was good (n = 94): mean difference between weight change and actual milk intake was 1.3 ml. The precision, however, was poor, with 95% of differences between weight change and actual milk intake ranging from -12.4 to +15 ml. The maximum difference was 30 ml. Imprecision was not influenced by the presence of monitor or oxygen saturation wires, intravenous lines, or vomiting or regurgitation ofthe infant. Based on the standard deviation of repeated measurements of the infant weighing scales, these instruments were not appropriate for assessing small changes in infants' weights after a single feed. CONCLUSION: Test weighing was an unreliable method for assessing milk intake in infants, because infant weighing scales are not sensitive enough to detect small changes in an infant's weight after feeding. Because of its unreliability, the use of test weighing should be abandoned.

Accuracy and precision of test weighing to assess milk intake in newborn infants.

BACKGROUND: Test weighing is commonly used to estimate milk intake in newborn infants. OBJECTIVE: To assess the accuracy and precision of test weighing in clinical practice. METHODS: Infants fed by bottle, cup, or nasogastric tube were weighed before and immediately after feeding by a blinded investigator. Actual milk intake was determined by reading the millilitre scale of the milk container before and after feeding. The accuracy and precision of test weighing was assessed by examining the frequency distribution of the difference between weight change and actual milk intake. RESULTS: Ninety four infants completed the study. The mean difference between weight change and actual milk intake was 1.3 ml, indicating good accuracy. The precision of test weighing, however, was poor: 95% of differences between weight change and actual milk intake ranged from -12.4 to 15 ml. The maximum difference was 30 ml. Imprecision was not influenced by the presence of monitor or oxygen saturation wires, intravenous lines, or vomiting of the infant. CONCLUSIONS: Test weighing is an imprecise method for assessing milk intake in young infants. This is probably because infant weighing scales are not sensitive enough to pick up small changes in an infant's weight after feeding. Because of its unreliability, test weighing should not be used in clinical practice.