Early growth characteristics and the risk of reduced lung function and asthma: A meta-analysis of 25,000 children.

BACKGROUND: Children born preterm or with a small size for gestational age are at increased risk for childhood asthma. OBJECTIVE: We sought to assess the hypothesis that these associations are explained by reduced airway patency. METHODS: We used individual participant data of 24,938 children from 24 birth cohorts to examine and meta-analyze the associations of gestational age, size for gestational age, and infant weight gain with childhood lung function and asthma (age range, 3.9-19.1 years). Second, we explored whether these lung function outcomes mediated the associations of early growth characteristics with childhood asthma. RESULTS: Children born with a younger gestational age had a lower FEV1, FEV1/forced vital capacity (FVC) ratio, and forced expiratory volume after exhaling 75% of vital capacity (FEF75), whereas those born with a smaller size for gestational age at birth had a lower FEV1 but higher FEV1/FVC ratio (P < .05). Greater infant weight gain was associated with higher FEV1 but lower FEV1/FVC ratio and FEF75 in childhood (P < .05). All associations were present across the full range and independent of other early-life growth characteristics. Preterm birth, low birth weight, and greater infant weight gain were associated with an increased risk of childhood asthma (pooled odds ratio, 1.34 [95% CI, 1.15-1.57], 1.32 [95% CI, 1.07-1.62], and 1.27 [95% CI, 1.21-1.34], respectively). Mediation analyses suggested that FEV1, FEV1/FVC ratio, and FEF75 might explain 7% (95% CI, 2% to 10%) to 45% (95% CI, 15% to 81%) of the associations between early growth characteristics and asthma. CONCLUSIONS: Younger gestational age, smaller size for gestational age, and greater infant weight gain were across the full ranges associated with childhood lung function. These associations explain the risk of childhood asthma to a substantial extent.

E-health and health care behaviour of parents of young children: a qualitative study.

OBJECTIVE: Internet plays a huge role in providing information about health care problems. However, it is unknown how parents use and perceive the internet as a source of information and how this influences health care utilisation when it comes to common complaints in infants. The objective was to evaluate the perception parents have on the role of internet in providing health care information on common symptoms in infants and its effects on health care utilisation. DESIGN: A qualitative design was chosen. SETTING AND SUBJECTS: Parents were recruited from a population-based birth-cohort and selected purposefully. MAIN OUTCOME MEASURES: Semi-structured interviews were used to receive information of parents' ideas. Thematic coding and constant comparison were used for interview transcript analysis. RESULTS: Ten parents were interviewed. Parents felt anxious and responsible when their child displayed common symptoms, and appeared to be in need of information. They tried to obtain information from relatives, but more so from the internet, because of its accessibility. Nevertheless, information found on the internet had several limitations, evoked new doubts and insecurity and although parents compared information from multiple sources, only the physician was able to take away the insecurity. The internet did not interfere in the decision to consult the physician. CONCLUSIONS: Parents need information about their children's symptoms and the internet is a major resource. However, only physicians could take away their symptom-related doubts and insecurities and internet information did not play a role in parental decision making. Information gathered online may complement the information from physicians, rather than replace it. Key points Internet plays an increasing role in providing health care information but it is unknown how this influences health care utilisation. Our study suggests that: Parents need information about their children's symptoms and the internet is a major resource. However, only physicians could take away their symptom-related doubts and insecurities. Internet information did not play a role in parental decision making.

Preterm birth, infant weight gain, and childhood asthma risk: a meta-analysis of 147,000 European children.

BACKGROUND: Preterm birth, low birth weight, and infant catch-up growth seem associated with an increased risk of respiratory diseases in later life, but individual studies showed conflicting results. OBJECTIVES: We performed an individual participant data meta-analysis for 147,252 children of 31 birth cohort studies to determine the associations of birth and infant growth characteristics with the risks of preschool wheezing (1-4 years) and school-age asthma (5-10 years). METHODS: First, we performed an adjusted 1-stage random-effect meta-analysis to assess the combined associations of gestational age, birth weight, and infant weight gain with childhood asthma. Second, we performed an adjusted 2-stage random-effect meta-analysis to assess the associations of preterm birth (gestational age <37 weeks) and low birth weight (<2500 g) with childhood asthma outcomes. RESULTS: Younger gestational age at birth and higher infant weight gain were independently associated with higher risks of preschool wheezing and school-age asthma (P < .05). The inverse associations of birth weight with childhood asthma were explained by gestational age at birth. Compared with term-born children with normal infant weight gain, we observed the highest risks of school-age asthma in children born preterm with high infant weight gain (odds ratio [OR], 4.47; 95% CI, 2.58-7.76). Preterm birth was positively associated with an increased risk of preschool wheezing (pooled odds ratio [pOR], 1.34; 95% CI, 1.25-1.43) and school-age asthma (pOR, 1.40; 95% CI, 1.18-1.67) independent of birth weight. Weaker effect estimates were observed for the associations of low birth weight adjusted for gestational age at birth with preschool wheezing (pOR, 1.10; 95% CI, 1.00-1.21) and school-age asthma (pOR, 1.13; 95% CI, 1.01-1.27). CONCLUSION: Younger gestational age at birth and higher infant weight gain were associated with childhood asthma outcomes. The associations of lower birth weight with childhood asthma were largely explained by gestational age at birth.

Decreased lung function precedes severe respiratory syncytial virus infection and post-respiratory syncytial virus wheeze in term infants.

It is unknown why respiratory syncytial virus (RSV) causes mild disease in some children and severe disease, requiring hospitalisation, in others. We aimed to assess whether diminished premorbid lung function in healthy term infants predisposes to hospitalisation during RSV bronchiolitis, and to post-RSV wheeze. In a prospective birth cohort study of unselected term healthy children, neonatal lung function was measured before the age of 2 months (n=2133). From birth through the first year of life, respiratory symptoms were recorded in a diary, and general practitioner consultations and hospitalisations were documented. In a subgroup (n=417) repeated nose and throat swabs were collected for PCR to detect RSV infections. Median neonatal respiratory system compliance (Crs) was significantly lower (41.2 versus 47.4 mL · kPa(-1), p=0.03) and resistance (Rrs) was higher (8.2 versus 6.3 kPa · s · L(-1), p=0.10) in hospitalised RSV patients (n=18) compared with nonhospitalised RSV-positive infants (n=84). Every 10 mL · kPa(-1) increase in Crs was associated with 55% less post-RSV wheeze (OR 0.56, 95% CI 0.35-0.90), and each kPa · s · L(-1) increase in Rrs was associated with 42% more post-RSV wheeze, which was only marginally explained by pre-RSV wheeze or severity of the RSV disease. This unselected birth cohort study shows for the first time that decreased lung function at birth predisposes to severe RSV disease, and to post-RSV wheeze.

Reduced neonatal lung function and wheezing illnesses during the first 5 years of life.

Studies of reduced neonatal lung function and wheezing illnesses during childhood show conflicting results. The aim of our study was to assess the association between resistance (Rrs) and compliance (Crs) of the respiratory system by using the single occlusion technique (SOT) and prospectively collected wheezing illnesses during the first 5 years of life in a large birth cohort. SOT was performed during natural sleep before the age of 2 months. Information about wheezing illnesses was collected from the electronic patient file. 549 infants had a successful SOT measurement and complete medical records. Every kPa·L(-1)·s(-1) increase in Rrs was associated with 10% more consultations in the first 3 years of life. Every 10 mL·kPa(-1) increase in Crs was associated with a 14% reduction in consultations in the first 3 years of life, 27% in the fourth to fifth years of life, and a lower probability of having asthma at the age of 5 years (OR 0.66). Children with late-onset or persistent wheezing had significant lower Crs values than their peers. An increased neonatal resistance is associated with more wheezing illnesses during infancy, while a reduced neonatal compliance is associated with more wheezing illnesses during the first 5 years of life, a late-onset or persistent wheezing phenotype, and asthma.

Early life lung function and respiratory outcome in the first year of life.

Abnormal early life lung function is related to wheezing in childhood; however, data on the association with cough are not available. We determined the relationship between early life lung function and wheeze and cough during the first year of life, adjusted for other possible risk factors. Infants were participants of the Wheezing Illnesses Study Leidsche Rijn (WHISTLER). Lung function measurements were performed before the age of 2 months. Information on pre- and perinatal factors, general characteristics and anthropometrics were assessed by questionnaires. Follow-up data on respiratory symptoms were assessed by daily questionnaires. 836 infants had valid lung function measurements and complete follow-up data for respiratory symptoms at 1 yr of age. Multivariable Poisson analysis showed that higher values of respiratory resistance (R(rs)) and time constant (τ(rs)) were associated with an increased risk for wheeze and cough during the first year of life. Higher values of respiratory compliance (C(rs)) were associated with a decreased risk for wheeze and cough. R(rs), C(rs) and τ(rs) measured shortly after birth were independently associated with wheeze and cough during the first year of life. As the strength of the relationships were different for wheeze and cough, they should be used as two separate entities.

Effect of endotoxin and allergens on neonatal lung function and infancy respiratory symptoms and eczema.

BACKGROUND: Exposure to endotoxin and allergens in house dust has been found to be associated with childhood wheeze and asthma. Neonatal lung function is rarely examined in relation to this exposure. OBJECTIVES: To assess the association between exposure to endotoxin, house dust mite and cat allergens and neonatal lung function, and respiratory symptoms and eczema in infancy. METHODS: In the Wheezing Illnesses Study Leidsche Rijn (WHISTLER) birth cohort study, levels of endotoxin, house dust mite allergens, and cat allergen have been measured in dust samples collected in the child's home. Lung function was measured before age 2 months, and respiratory symptoms and eczema were recorded in a daily diary during the first year of life. Associations of lung function (N = 302), respiratory symptoms (N = 361), and eczema (N = 342) with endotoxin and allergen levels have been studied by means of linear and logistic regression, respectively. RESULTS: Mattress dust endotoxin was associated with a significant increase in neonatal respiratory compliance [adjusted mean difference (95% confidence interval) 2.31 (0.33; 4.29) ml/kPa per interquartile range increase in exposure] and a non-significant decrease in neonatal airway resistance [0.32 (-0.77; 0.14) kPa/l/s]. There were no associations between allergen exposure and neonatal lung function and respiratory symptoms. CONCLUSIONS: Environmental exposure to endotoxin may have an important role in the development of lung function.

E-health and consultation rates for respiratory illnesses in infants: a randomised clinical trial in primary care.

BACKGROUND: It is assumed that clear and complete information on the internet can reduce healthcare consumption. AIM: We assessed in a randomised clinical trial whether a personalised online parent information program on infant respiratory symptoms can reduce primary care utilisation. DESIGN AND SETTING: Randomised clinical trial in primary healthcare centres in a new residential area in the Netherlands. METHOD: A web-based program (WHISTLER-online) was developed for parents that offered general information on childhood respiratory disease and personalised risk assessments. Parents of infants who enrolled from June 2009 to June 2012 in WHISTLER, an ongoing population-based birth cohort, were randomly allocated to 'WHISTLER-online' or 'usual care'. Information about, first, consultations and, second, associated prescriptions for respiratory symptoms during the first year of life was collected from the electronic patient files. RESULTS: A total of 323 infants were randomly assigned to WHISTLER-online and 322 to usual care, and 314 and 305, respectively, were analysed. Of the parents, 70% used WHISTLER-online, and 99% of them judged it to be clear and useful information. There were differences neither in consultation rates for respiratory symptoms (incidence rate ratio 0.96 [95% CI = 0.85 to 1.09, P = 0.532]) nor in associated drug prescriptions. CONCLUSION: Although parents greatly appreciate the provided facilities, a personalised e-support program on respiratory illnesses in infants does not substantially reduce healthcare utilisation.

Life-course of cardio-respiratory associations.

BACKGROUND: Several studies have shown that raised cardiovascular risk factors are associated with an impaired lung function in adulthood. Whether this association also exists in the young is unknown. Our aim was to study the relation between blood pressure and lung function from neonatal to elderly age. STUDY DESIGN: This was a cross-sectional study in a general population cohort. METHODS: Within the Utrecht Health Project (UHP) 6673 adults (aged 18-91 years) had spirometry and blood pressure measurements taken. In the WHeezing Illnesses STudy LEidsche Rijn (WHISTLER) study, a satellite birth cohort of the UHP, blood pressure and respiratory mechanics were measured using the single occlusion technique in 755 newborns and spirometry in 382 5-year-old participants. Linear regression analyses were performed with lung function as an independent variable and blood pressure as a dependent variable in different age groups. The analyses were adjusted for age, sex, weight and height. RESULTS: In infancy a more favorable lung function (higher compliance and lower resistance) was associated with higher blood pressure. In 5-year-old children and young adults higher forced expiratory volume in 1 second (FEV1) was associated with higher systolic blood pressure (p-values < 0.05). At the age of 5 the adjusted regression coefficient for systolic blood pressure was 4.8 mmHg/L (95% confidence interval (95% CI) -0.3-9.98). The association decreased with increasing age and reversed in the age groups above 40 years to -7.3 mmHg/L (95% CI -15.5-0.9) in those aged over 70 years of age. The association with pulse pressure showed a similar pattern. CONCLUSIONS: A positive association between the mechanical properties of the respiratory system and blood pressure in childhood and young adulthood reverses in later adulthood.

Parent-reported symptoms of acute otitis media during the first year of life: what is beneath the surface?

BACKGROUND: Most estimates of the incidence of acute otitis media (AOM) are based on general practitioner (GP) or pediatrician diagnoses. It is likely that these figures underestimate the community incidence of AOM since parents do not visit their doctor every time their child suffers from acute ear symptoms. The impact of these symptom episodes may be substantial since they affect the child's quality of life and parents' productivity. METHODS: To determine AOM symptoms in the community, we measured parent-reported AOM symptoms daily for 12 consecutive months in 1,260 children participating in a prospective birth cohort in the Netherlands. The mean age of these children was at study enrollment 0.9 months (standard deviation 0.6). A parent-reported AOM symptom episode was defined as fever (temperature 38˚C or above) plus at least one of the following symptoms: ear pain and ear discharge. These febrile AOM symptom episodes were linked to GP-consultations and diagnoses in the GP electronic health records. RESULTS: With an estimated 624 parent-reported symptom episodes per 1,000 child-years (95% CI: 577 to 674) incidence of febrile AOM symptoms during the child's first year is high. The GP was consulted in half of these symptom episodes and AOM was diagnosed in 49% of these consultations. CONCLUSIONS AND RELEVANCE: The incidence of febrile AOM symptoms in the first year of life is high in Dutch children and leads to a GP-consultation in only half of the cases. This suggests that AOM symptomatology in the community is underestimated when focusing on GP-diagnosed AOM episodes alone, since a considerable proportion of febrile AOM symptom episodes are treated symptomatically by parents at home and do not come to the attention of the GP. Having data on community AOM symptomatology available for each country is important when the potential impact of preventive and therapeutic interventions for AOM are studied.

Human rhinovirus and wheezing: short and long-term associations in children.

OBJECTIVES: Human rhinoviruses (HRVs) have been suggested to play a role in the development of childhood wheezing. However, whether HRV is causally related to the development of wheezing or HRV-associated wheeze is merely an indicator of disease susceptibility is unclear. Our aim was to study the role of HRV during infancy in the development of lower respiratory disease during infancy and childhood. METHODS: In a population-based birth cohort, during the 1st year of life, nose and throat swabs were collected on a monthly basis, regardless of any symptoms. Polymerase chain reaction was used to detect an extensive panel of respiratory pathogens. Lung function was measured before 2 months of age. Information on respiratory symptoms was collected by daily questionnaires and electronic patient files. RESULTS: 1425 samples were collected in 140 infants. Both the presence of (single or multiple) pathogens (HRV equal to other pathogens) and increased respiratory system resistance were significantly associated with lower respiratory symptoms during infancy. HRV presence during infancy was not associated with the risk of wheezing at age 4, but every HRV episode with wheezing increased the risk of wheezing at age 4 (odds ratio 1.9, 1.1-3.5). This association weakened after adjustment for lung function (odds ratio 1.4, 0.7-2.9). CONCLUSIONS: HRV and other viruses are associated with lower respiratory symptoms during infancy, as well as a high presymptomatic respiratory system resistance. HRV presence during infancy is not associated with childhood wheezing, but wheeze during a HRV episode is an indicator of children at high risk for childhood wheeze, partly because of a reduced neonatal lung function.

Referrals for recurrent respiratory tract infections including otitis media in young children.

OBJECTIVE: (a) To establish whether disease-related, child-related, and physician-related factors are independently associated with specialist referral in young children with recurrent RTI, and (b) to evaluate whether general practitioners (GPs) follow current guidelines regarding these referrals. METHODS: Electronic GP records of children under 24 month of age, born 2002-2008, were reviewed for RTI episodes using ICPC codes. Child-related factors were extracted from the prospective WHISTLER birth-cohort in which a considerable part of children had been enrolled. To evaluate guideline adherence, referral data were compared to national guideline recommendations. RESULTS: Consultations for 2532 RTI episodes (1041 children) were assessed. Seventy-eight children were referred for recurrent RTI (3.1% of RTI episodes; 7.5% of children). Disease factors were the main determinants of referral: number (OR 1.7 [CI 1.7-1.7]) and severity of previous RTI episodes (OR 2.2 [CI 1.6-2.8]), and duration of RTI episode (OR 1.7 [CI 1.7-1.8]). The non-disease factors daycare attendance (OR 1.3 [CI 1.0-1.7]) and 5-10 years working experience as a GP compared with <5 years (OR 0.37 [CI 0.27-0.50]) were also associated. Fifty-seven percent of referrals for recurrent RTI were made in accordance with national guidelines. CONCLUSIONS: Referral of children for recurrent RTI was primarily determined by frequency, severity, and duration of RTIs; the influence of non-disease factors was limited. Just over half of referrals were made in accordance with guidelines.