Prematurity, chorioamnionitis, and the development of recurrent wheezing: a prospective birth cohort study. Risk factors for respiratory morbidity in infancy after very premature birth Longitudinal follow-up of lung function from childhood to adolescence in prematurely born patients with neonatal chronic lung disease. Recurrent respiratory symptoms in the first year of life following preterm delivery Long-term pulmonary functional outcome of bronchopulmonary dysplasia and premature birth. Recurrent wheezing in very preterm infants. Pulmonary function in children with initial low birth weight. Environmental exposures and respiratory morbidity among very low birth weight infants at 1 year of life Prevalence, natural history, and relationship of wheezy bronchitis and asthma in children. An epidemiological study Association of birth weight with asthma-related outcomes at age 2 years. Reduced frequency of wheezing respiratory illness in infants with perinatal human immunodeficiency virus-type 1 infection: a model for immunologic and inflammatory mechanisms of airway obstruction?
BACKGROUND Prematurity ( < 37 weeks ) has been inconsistently associated with  asthma and wheezing .  Chorioamnionitis may promote both prematurity and inflammatory pathways in infants ' airways . OBJECTIVE To investigate the relationship of prematurity and chorioamnionitis with the development of early childhood recurrent wheezing .  METHODS The Boston Birth Cohort ( n = 1096 ) were followed prospect ively from birth to a mean age of 2.2 + /- 2 years . Perinatal and postnatal clinical data and placental pathology were collected . The primary outcome was recurrent wheezing ( > or = 2 physician documented episodes ) . Secondary outcomes included physician-diagnosed asthma , food allergy , and eczema . Preterm children were grouped by gestational age into moderately ( 33 - 36.9 weeks ) and very preterm ( < 33 weeks ) with and without chorioamnionitis , and compared with term children without chorioamnionitis ( reference group ) . Chorioamnionitis was diagnosed either by intrapartum fever or by placental histology findings . Logistic regression models were performed to investigate the independent and joint associations of degree of prematurity and chorioamnionitis . RESULTS Prematurity was associated with recurrent wheezing ( odds ratio [ OR ] , 1.7 ; 95 % CI , 1.2 - 2.6 ) . However , when subjects were grouped by degree of prematurity with or without chorioamnionitis , the highest risk of wheezing ( OR , 4.0 ; 95 % CI , 2.0 - 8.0 ) and physician-diagnosed asthma ( OR , 4.4 ; 95 % CI , 2.2 - 8.7 ) was present in the very preterm children with chorioamnionitis . The effect on both wheezing ( OR , 5.4 ; 95 % CI , 2.4 - 12.0 ) and asthma ( OR , 5.2 ; 95 % CI , 2.3 - 11.9 ) was greater in African Americans . Neither prematurity nor chorioamnionitis was associated with food allergy or eczema . CONCLUSION We found a strong joint effect of prematurity and chorioamnionitis on  early childhood wheezing .  This effect was stronger in African American subjects Objectives : To determine the occurrence of respiratory morbidity during infancy after very premature birth and to identify risk factors . Design : Prospect i ve follow up study . Setting : The United Kingdom oscillation study . Patients : 492 infants , all born before 29 weeks gestation . Interventions : Structured question naires were completed by local paediatricians when the infants were seen in out patients at 6 and 12 months of age corrected for prematurity . Main outcome measures : Cough , wheeze , and treatment requirements and the composite measure of respiratory morbidity ( cough , frequent cough , cough without infection , wheeze , frequent wheeze , wheeze without infection , and use of chest medicine ) and their relation to 13 possible explanatory variables . Results : At 6 and 12 months of corrected age , 27 % of the infants coughed and 6 % had frequent ( more than once a week ) cough , and 20 % and 3 % respectively had wheeze or frequent wheeze . At 6 and 12 months , 14 % of infants had taken bronchodilators and 8 % inhaled steroids . After adjustment for multiple outcome testing , four factors were associated with increased respiratory morbidity : male sex , oxygen dependency at 36 weeks postmenstrual age , having older siblings aged less than 5 years , and living in rented accommodation . Conclusions : Male infants are particularly vulnerable to respiratory morbidity in infancy after very premature birth . It is important to identify a safe and effective strategy to prevent chronic oxygen dependency We investigated whether early lung function abnormalities in prematurely born children with a history of chronic lung disease improve in late childhood and adolescence . We performed a prospect i ve , longitudinal evaluations of pulmonary function over an 8 year period . In seventeen patients from the age ( mean + /- SD ) of 8.2 + /- 1.2 years to the age of 15.1 + /- 1.6 years . They had been born at 29.1 + /- 1.9 weeks of gestation , with a birthweight of 1120 + /- 190 g , and they had received supplemental oxygen , with or without mechanical ventilation , for 40.4 + /- 23.8 days during the neonatal period . They all had radiographic evidence of chronic lung disease at 4 weeks of age . Annual measurements of lung volumes using the helium dilution technique , and of airway function with spirometry and maximal expiratory flow-volume curves over a 5 to 8 year period , were obtained . The results indicated that total lung capacity ( TLC ) and vital capacity ( VC ) were within the predicted normal range in all patients and increased over time . In contrast , the initially abnormal residual volume ( RV ) and RV/TLC ratio decreased over time , suggesting gradual resolution of air-trapping . The peak expiratory flow rate ( PEFR ) , forced expiratory volume in 1 second ( FEV1 ) , and the ratio FEV1/FVC remained at or above the predicted normal range in all patients . FEF25 - 75 , FEF50 , and FEF75 were within normal limits in eight patients and abnormally low ( more than 2 SD below the predicted normal value ) in the remaining nine patients , indicating small airway obstruction . Eight of the nine patients with lower airway obstruction showed significant response to inhaled bronchodilator , and four responded to a histamine challenge . None of the eight patients with normal airway function responded to histamine , but four responded to bronchodilators . The perinatal history , family history of asthma , and exposure to smoking were similar in patients with and without airway obstruction . The height and weight were and remained within the normal range . We conclude that gradual normalization of air-trapping continues well into adolescence in virtually all patients with a history of prematurity and chronic lung disease . in contrast , airflow obstruction may persist but does not get worse later in life . Although chronic airflow obstruction probably is the consequence of injury to the small airways during the neonatal period , it is present in only some of the children , and it does not appear to be directly related to the perinatal history . Finally , there is evidence that airway hyperresponsiveness may be a contributing factor to the development and /or persistence of airflow obstruction in chronic lung disease of prematurity Recurrent respiratory symptoms in the first year of life following preterm delivery were documented in two studies . In the first study a question naire was sent to all parents of preterm very low birth weight ( VLBW ) infants who had been admitted during a six-month period to the Neonatal Intensive Care Unit ( NICU ) at King 's College Hospital ( KCH ) and who lived within the local district . Question naires were also sent to parents of a control group of infants who were recruited by r and om selection . All the controls lived locally and were delivered at KCH in the same six-month period as the study group , but were born at 37 - 41 weeks of gestation and had had no neonatal problems . The question naire documented frequency of cough and wheeze , medication and hospital admissions . Recurrent respiratory symptoms ( wheeze or wheeze and cough ) occurred in 65 % of the preterm VLBW infants but only 33 % of the controls p less than 0.001 . Less than 10 % of infants in either group had received bronchodilator therapy . Admission to hospital in both groups was more common amongst children who had recurrent wheeze ( p less than 0.01 ) . In the second study all preterm VLBW infants admitted to the NICU in a six-month period were followed prospect ively over the first year of life . The nature and frequency of respiratory symptoms and frequency and length of re-admission was documented and related to the duration of neonatal ventilation . Twenty-three of the 44 preterm VLBW infants ( 53 % ) followed prospect ively had recurrent wheeze and /or cough . ( ABSTRACT TRUNCATED AT 250 WORDS Pulmonary function and exercise tolerance were evaluated in late childhood in two groups of prematurely born children : one group with bronchopulmonary dysplasia ( BPD ) [ n = 15 ; gestational age at birth ( GA ) : 29.6 + /- 2.8 weeks ; birth weight ( BW ) : 1,367 + /- 548 g ; age at test : 7.9 + /- 0.6 years ] , and a second group without significant neonatal lung disease [ pre-term ( PT ) ] ( n = 9 ; GA : 30.3 + /- 1.7 weeks ; BW : 1,440 + /- 376 g ; age at test : 7.8 + /- 0.22 years ) . The results were compared with a control group of children of similar ages and heights , born at term [ term born ( TB ) ] . We observed that total lung resistance ( RL ) was significantly higher in BPD ( 11 + /- 3 cmH2O/L/s ) , and in PT ( 9 + /- 2 ) than in TB [ 5 + /- 1 ; ( P < 0.001 and P < 0.05 , respectively ) ] . In BPD RL was higher than in PT ( P < 0.05 ) . Dynamic lung compliance ( CLdyn ) was decreased in BPD ( 43 + /- 11 mL/cmH2O ) and in PT ( 56 + /- 17 ) compared with TB ( 76 + /- 20 ) ( P < 0.001 and P < 0.05 ) , and also in BPD compared with PT ( P < 0.05 ) . Forced expiratory volume in 1 second ( FEV1 ) and FEV1/forced vital capacity ( FVC ) were lower in BPD ( 1.07 + /- 0.15 L and 72 + /- 7 % ) than in PT ( 1.29 + /- 0.23 L , and 80 + /- 7 % ) ( P < 0.05 ) . Exercise tests were performed in six boys with BPD . The ratio between minute ventilation at maximal workload ( VEmax ) and the predicted value of maximal voluntary ventilation ( MVV ) was elevated in the six BPD boys tested , compared with five boys of Group 2 and five TB boys ( 87 + /- 15 % vs. 62 + /- 14 % and 65 + /- 13 % ) ( P < 0.05 ) . We conclude that : 1 ) prematurity and BPD is followed by long-term airway obstruction and a mild degree of exercise intolerance and ; 2 ) premature birth without BPD may be followed by a milder degree of airway obstruction in childhood than in infants who developed BPD during the neonatal period AIMS : To document the prevalence of , and identify risk factors for ,  recurrent wheezing treated with bronchodilators in the first year of life . METHODS : Parental history and neonatal data were collected prospect ively in a regional cohort of very preterm infants ( < 33 weeks ) .  Data on maternal smoking , siblings at home , breast feeding , respiratory symptoms , and hospital re-admissions were documented at 12 months . RESULTS : Outcome data were available for 525/560 ( 95 % ) of survivors . The incidence of recurrent wheeze was 76/525 ( 14.5 % ) in very preterm infants and 20/657 ( 3 % ) in a cohort of term newborns . Significant risk factors for recurrent wheeze in very preterm infants were parental history of asthma , maternal smoking , siblings at home , neonatal oxygen supplementation at 28 days , 36 , and 40 weeks of gestation . CONCLUSIONS : Wheezing respiratory illnesses are common in very preterm infants . The factors involved are similar to those in more mature infants , with the addition of immaturity and neonatal lung injury The objective of this analysis was to examine the effect of low birth weight and prematurity on bronchial air-flow , bronchial reactivity , airway symptoms and asthma diagnosis at school age . A cross-sectional epidemiological study was performed in three small towns in the eastern part of Germany on 2470 school children aged 5 - 14 ( 89.1 % of eligible children ) . A 78 item question naire to determine risk factors at birth and in early childhood was employed . 7.8 % of the children were born before completing 38 gestational weeks ; 6.6 % had a birth weight less than 2500 g.  Pulmonary function analysis were done by a mobile plethysmography at the school . There were only weak restrictions in lung volume in term low birth weight ( LBW ) children ( 100 ml lower TLC , p = 0.107 ) , and flow ( 257 ml lower PEFR , p = 0.108 ) , were low . However , bronchial hyper-responsiveness indicated by 292 ml lower FEV1.0 after cold air bronchial provocation , was significantly increased compared to term normal birth weight children ( p < 0.001 ) . The effect of LBW was less in older children , only slightly stronger in girls and increased in children mechanically ventilated during the postnatal period . Correspondingly , there was a higher prevalence of diagnosed asthma in term LBW children ( OR 1.6 , 95%-confidence interval 1.0 - 2.6 ) , however these were without an increased risk for any allergic sensitization . LBW , therefore , seems to be a risk factor for smaller lungs and hyperreactive airways primarily in term born children , whereas in preterm children the immature bronchial system seems to be recover by school age Introduction : Preterm infants have a substantially increased risk of developing respiratory illnesses . The goal of this study was to consider the impact of modifiable postnatal exposures on respiratory morbidity among a cohort of very low birth weight ( VLBW ) infants . Objectives : ( 1 ) Assess the rates of respiratory morbidity and exposure to indoor respiratory triggers in a population of VLBW infants at 1 year ; ( 2 ) determine the association between exposures and respiratory morbidity . Methods : We enrolled 124 VLBW infants into a prospect i ve cohort study . Parents were called at 1 year to assess respiratory outcomes and environmental exposures . We used bivariate and multivariate analyses to assess the relationship between environmental exposures and acute care for respiratory illnesses . Results : At 1 year , 9 % of infants had physician-diagnosed asthma , 47 % required ⩾1 acute visit and 11 % required hospitalisation for respiratory illness . The majority of infants ( 82 % ) were exposed to at least one indoor respiratory trigger . Infants living with a smoker ( 61 % vs 40 % ) and infants exposed to pests ( 62 % vs 39 % ) were more likely than unexposed infants to require acute care for respiratory problems . In a multivariate regression controlling for demographics , birth weight , bronchopulmonary dysplasia , and family history of asthma or allergies , both living with a smoker ( OR 2.62 ; CI 1.09 to 6.29 ) and exposure to pests ( OR 4.41 ; CI 1.22 to 15.94 ) were independently associated with the need for acute care for respiratory illnesses . Conclusions : In this sample , respiratory morbidity and exposure to triggers were common . VLBW infants may benefit from interventions that decrease exposure to respiratory triggers Three r and omly selected groups of 7-year-old schoolchildren in Melbourne with mild wheezy bronchitis , with moderate wheezy bronchitis , and with asthma were compared with a control group  , and the patients followed up until 10 years of age . Comparison showed that if there was any significant difference between the study groups and the controls it was usually present in all these study groups . It was considered that children with wheezy bronchitis and asthma were from the same population with the same underlying basic disorder , and that there was a wide spectrum in various aspects of the natural history of the disorder . About 11 % of all children aged 10 years had had some asthmatic episodes . Seventy per cent . of these children ceased having asthma before 10 years of age , while about 30 % ( 3·7 % of the whole community ) continued to have episodes . There was a highly significant correlation between early age of onset , the frequency of episodes in the first year of symptoms , and the persistence of asthmatic episodes up to 10 years of age . Ten per cent . of all children with asthmatic episodes continued to have symptoms as severely at 10 years as at an earlier period . In this group the onset of symptoms was almost always before 3 years of age , there was a high frequency of episodes in the first year of symptoms , and boys and girls were affected in the ratio of 7:3 BACKGROUND Although lower birth weight associated with prematurity raises the risk of asthma in childhood , few prospect i ve studies have examined higher birth weight , and few have separated the two components of birth weight , fetal growth and length of gestation . OBJECTIVE To examine the associations of fetal growth and length of gestation with asthma-related outcomes by age 2 years . METHODS We studied 1,372 infants and toddlers born after 34 weeks ' gestation in Project Viva , a prospect i ve cohort study of pregnant mothers and their children . The main outcome measures were parent report of ( 1 ) any wheezing ( or whistling in the chest ) from birth to age 2 years , ( 2 ) recurrent wheezing during the first 2 years of life , and ( 3 ) doctor 's diagnosis of asthma , wheeze or reactive airway disease ( " asthma " ) by age 2 . We calculated gestational age from the last menstrual period or ultrasound examination , and determined birth weight for gestational age z-value ( " fetal growth " ) using US national reference data . RESULTS  Infants ' mean birth weight  was 3,527 ( SD , 517 ; range , 1,559 - 5,528 ) grams . By age 2 years , 34 % of children had any wheezing , 14 % had recurrent wheezing , and 16 % had doctor-diagnosed asthma . After adjusting for several parent , child , and household characteristics in logistic regression models , we found that infants with birth weight > or = 4,000 g were not more likely to have any wheezing ( odds ratio ( OR ) , 0.91 ; 95 % confidence interval ( CI ) : 0.62 , 1.34 ) or doctor-diagnosed asthma ( OR , 0.80 ; 95 % CI : 0.49 , 1.31 ) than infants with birth weight 3,500 - 3,999 g. In models examining length of gestation and fetal growth separately , neither the highest nor the lowest groups of either predictor were associated with the three outcomes . Boys had a higher incidence of asthma-related outcomes than girls , and exposure to passive smoking , parental history of asthma , and exposure to older siblings were all associated with greater risk of recurrent wheeze or asthma-related outcomes at age 2 years . CONCLUSION Although male sex , exposure to smoking , parental history of asthma , and exposure to older siblings were associated with increased risk of wheezing and asthma-related outcomes in this prospect i ve study of children born after 34 weeks gestation , fetal growth and length of gestation were not A multivariate analysis using a logistic regression model evaluated odds ratio ( OR ) and 95 % confidence limits ( 95 % CL ) of pediatrician-diagnosed wheezing respiratory illness in 75 infants with perinatal human immunodeficiency virus-type 1 ( HIV-1 ) infection , 205 uninfected infants of HIV-1 infected mothers , and 1780 infants of HIV-1 uninfected mothers . Infants were prospect ively followed-up for the first 2 years of life . Covariates were risk factors for wheezing respiratory illness ( preterm delivery , low birth weight , maternal smoking , formula feeding , and neonatal respiratory disorders ) . Maternal use of illicit drugs in pregnancy  ,  antiretroviral treatment in pregnancy , maternal HIV-1-related clinical condition at the time of delivery were also included in the models when infants of HIV-1 infected mothers were taken into account . Although the frequency of risk factors for wheezing respiratory illness was higher in infants of HIV-1 infected than in those of uninfected mothers , HIV-1 infection emerged as a protective factor [ OR : 0.001 ( 95 % CL : 0.0001 - 0.01 ) ; p < 0.001 ] . The frequency of risk factors was similarly high among infants of infected mothers , but OR was lower in HIV-1 infected than in uninfected infants of infected mothers ( 0.005 ; 95 % CL : 0.0004 - 0.06 ; p < 0.001 ) . Finally , OR was higher in uninfected infants of HIV-1 infected mothers ( who evidence d a higher frequency of risk factors ) than in infants of HIV-1 uninfected mothers ( 9.97 ; 95 % CL : 4.87 - 20.40 ; p < 0.001 ) . Underst and ing the reason why HIV-1 protects against wheezing respiratory illness could shed light on the immunologic and inflammatory mechanisms of airway obstruction
We aim ed to provide a summary of the existing published knowledge on the association between adverse birth outcomes  and the development of wheezing during the first two years of life .