Very prematurely born infants wheezing at follow-up: lung function and risk factors.

OBJECTIVES: To determine whether abnormalities of lung volume and/or airway function were associated with wheeze at follow-up in infants born very prematurely and to identify risk factors for wheeze. DESIGN: Lung function data obtained at 1 year of age were collated from two cohorts of infants recruited into the UKOS and an RSV study, respectively. SETTING: Infant pulmonary function laboratory. PATIENTS: 111 infants (mean gestational age 26.3 (SD 1.6) weeks). INTERVENTIONS: Lung function measurements at 1 year of age corrected for gestational age at birth. Diary cards and respiratory questionnaires were completed to document wheeze. MAIN OUTCOME MEASURES: Functional residual capacity (FRC(pleth) and FRC(He)), airways resistance (R(aw)), FRC(He):FRC(pleth) and tidal breathing parameters (T(PTEF):T(E)). RESULTS: The 60 infants who wheezed at follow-up had significantly lower mean FRC(He), FRC(He):FRC(pleth) and T(PTEF):T(E), but higher mean R(aw) than the 51 without wheeze. Regression analysis demonstrated that gestational age, length at assessment, family history of atopy and a low FRC(He):FRC(pleth) were significantly associated with wheeze. CONCLUSIONS: Wheeze at follow-up in very prematurely born infants is associated with gas trapping, suggesting abnormalities of the small airways.     

Does a family history of atopy influence lung function at follow-up of infants born prematurely?

The aim of this study was to assess whether a family history of atopy influenced lung function at follow-up of infants born prematurely. Analysis was made of thoracic gas volume and airways resistance measurements performed at 1 year of age in 86 infants born at a median gestational age of 29 weeks. These measurements had been made during a prospective follow-up study. The 30 infants with a family history of atopy were found to have a higher airways resistance (median 35 cmH₂O/l/s) than the 56 infants without such a family history (median 30cmH₂O/l/s) ( p < 0.05). However, when the results from 18 infants with a family history of atopy were compared with 18 controls who were matched for requirement for neonatal ventilation, parental smoking and were within at least 1 week of gestational age, no significant difference in airways resistance was found between the two groups. Multiple regression analysis demonstrated that gestational age and birth weight explained the apparent relationship between a family history of atopy and an elevated airways resistance at follow-up.     

Diminished lung function, RSV infection, and respiratory morbidity in prematurely born infants

Background

Diminished lung function appears to be a risk factor for respiratory syncytial virus (RSV) infection/bronchiolitis in term born infants.

Aims

To determine if diminished lung function prior to neonatal unit discharge was associated with subsequent symptomatic RSV lower respiratory tract infection (LRTI) and respiratory morbidity in prematurely born infants.

Methods

Of 39 infants in a tertiary neonatal intensive care unit (median gestational age 28 weeks, range 23–31), 20 had bronchopulmonary dysplasia. Lung function (compliance and resistance of the respiratory system (C_rs and R_rs) and functional residual capacity (FRC)) was measured on the neonatal unit at 36 weeks postmenstrual age (PMA). Following neonatal unit discharge, nasopharyngeal aspirates were obtained on every occasion, at home or in hospital, an infant had an LRTI. RSV was identified by immunofluorescence and/or culture.

Results

The 15 infants who suffered a symptomatic RSV LRTI had a higher mean R_rs and suffered more wheeze at follow up than the rest of the cohort. Regression analysis showed that a high R_rs was significantly associated with a symptomatic RSV LRTI; significant factors for cough were a high R_rs and a symptomatic RSV LRTI, and for wheeze were a high R_rs.

Conclusion

Prematurely born infants, who had a symptomatic RSV LRTI and/or respiratory morbidity at follow up, had worse lung function prior to neonatal unit discharge.     

Respiratory function of very prematurely born infants at follow up: influence of sex

OBJECTIVE: To test the hypothesis that male compared with female prematurely born infants would have worse lung function at follow up. DESIGN: Prospective follow up study. SETTING: Tertiary neonatal intensive care units PATIENTS: Seventy six infants, mean (SD) gestational age 26.4 (1.5) weeks, from the United Kingdom oscillation study. INTERVENTIONS: Lung function measurements at a corrected age of 1 year. MAIN OUTCOME MEASURES: Airways resistance (Raw) and functional residual capacity (FRC(pleth)) measured by whole body plethysmography, specific conductance (sGaw) calculated from Raw and FRC(pleth), and FRC measured by a helium gas dilution technique (FRC(He)). RESULTS: The 42 male infants differed significantly from the 34 female infants in having a lower birth weight for gestation, requiring more days of ventilation, and a greater proportion being oxygen dependent at 36 weeks postmenstrual age and discharge. Furthermore, mean Raw and FRC(pleth) were significantly higher and mean sGaw significantly lower. After adjustment for birth and current size differences, the sex differences in FRC(pleth) and sGaw were 15% and 26% respectively and remained significant. CONCLUSION: Lung function at follow up of prematurely born infants is influenced by sex.     

Viral infections acquired during neonatal intensive care and lung function of preterm infants at follow-up

Yuksel B, Greenough A. Viral infections acquired during neonatal intensive care and lung function of preterm infants at follow-up. Acta Pzdiatr 1994;83:117–18. Stockholm. ISSN 0803–5253
Respiratory function was assessed at a median postnatal age of seven months in seven infants born prematurely who suffered from chronic lung disease and had a proven viral infection while on the neonatal unit (study group). The results were compared with those of seven infants with chronic lung disease who were gestational age- and gender-matched but who did not have a viral infection (controls). Six of the study group and two controls were symptomatic at follow-up. Airways resistance was significantly higher ( p < 0.04) and specific conductance significantly lower ( p < 0.05) in the study group compared with the controls. We conclude in premature infants with chronic lung disease that viral infections acquired in the neonatal nursery are associated with impaired lung function at follow-up.     

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??Abstract??The pathophysiology of wheezing in infants is yet to be fully understood, and approaches for a confirmatory diagnosis of this condition remain so far limited. Thus, a combination of medical history and laboratory investigations represents the most reliable source of clinical clues for diagnosis and differential diagnosis of infant wheezing.     

Sleeping position, oxygen saturation and lung volume in convalescent, prematurely born infants

OBJECTIVE: To determine whether the effects of sleeping position on lung volume and oxygenation are influenced by postmenstrual age (PMA) and oxygen dependency in convalescent prematurely born infants. DESIGN: Prospective study. SETTING: Tertiary neonatal unit. PATIENTS: 41 infants (21 oxygen dependent), median gestational age 28 weeks (range 24-31 weeks) and birth weight 1120 g (range 556-1780 g). INTERVENTION: Infants were studied both supine and prone at two-weekly intervals from 32 weeks' PMA until discharge. Each posture was maintained for 1 h. MAIN OUTCOME MEASURES: Pulse oximeter oxygen saturation (Spo(2)) was monitored continuously, and at the end of each hourly period functional residual capacity (FRC) was measured. RESULTS: Overall, lung volumes were higher in the prone position throughout the study period; there was no significant effect of PMA on lung volumes. Overall, Spo(2) was higher in the prone position (p = 0.02), and the effect was significant in the oxygen-dependent infants (p = 0.03) (mean difference in Spo(2) between prone and supine was 1.02%, 95% CI 0.11% to 1.92%), but not in the non-oxygen-dependent infants. There was no significant influence of PMA on Spo(2). CONCLUSION: In the present study, prone sleeping did not improve oxygenation in prematurely born infants, 32 weeks' PMA or older and with no ongoing respiratory problems. However, the infants were monitored in each position for an hour, thus it is recommended that oxygen saturation should continue to be monitored after 32 weeks' PMA to be certain that longer periods of supine sleeping are not associated with loss of lung volume and hypoxaemia.     

Human parechovirus type 3 infection: Cause of apnea in infants born prematurely

Four infants born prematurely presented with multiple apnea episodes caused by human parechovirus type 3 (HPeV3) infection. All patients required oxygen supplementation, and one patient required mechanical ventilation. HPeV3 infection might be included in the differential diagnosis of apnea in neonates and young infants, especially those born prematurely.     

Mortality and neurological morbidity in prematurely born infants and low birthweight infants born at term

In a follow-up study the fate and development of 245 prematures with a birthweight below 1,500 g and of 230 infants with a birth weight of 1,501-2,500 g are reported. The mortality of infants with a birthweight below 1,500 g was 29.8%, in the group of infants with higher birthweights 9.1%. The frequency of severe neurological sequelae in infants with very low birthweight was 8.2%, in the other group of infants 3.5%. Minor handicaps and developmental abnormalities were found in a frequency of 12.2%, and 4.7% respectively. These results meet the present international standard in centers for perinatal medicine. Prospective investigations are mandatory to recognize causal factors for later severe handicaps.     

Diminished lung function, RSV infection, and respiratory morbidity in prematurely born infants.

BACKGROUND: Diminished lung function appears to be a risk factor for respiratory syncytial virus (RSV) infection/bronchiolitis in term born infants. AIMS: To determine if diminished lung function prior to neonatal unit discharge was associated with subsequent symptomatic RSV lower respiratory tract infection (LRTI) and respiratory morbidity in prematurely born infants. METHODS: Of 39 infants in a tertiary neonatal intensive care unit (median gestational age 28 weeks, range 23-31), 20 had bronchopulmonary dysplasia. Lung function (compliance and resistance of the respiratory system (C(rs) and R(rs)) and functional residual capacity (FRC)) was measured on the neonatal unit at 36 weeks postmenstrual age (PMA). Following neonatal unit discharge, nasopharyngeal aspirates were obtained on every occasion, at home or in hospital, an infant had an LRTI. RSV was identified by immunofluorescence and/or culture. RESULTS: The 15 infants who suffered a symptomatic RSV LRTI had a higher mean R(rs) and suffered more wheeze at follow up than the rest of the cohort. Regression analysis showed that a high R(rs) was significantly associated with a symptomatic RSV LRTI; significant factors for cough were a high R(rs) and a symptomatic RSV LRTI, and for wheeze were a high R(rs). CONCLUSION: Prematurely born infants, who had a symptomatic RSV LRTI and/or respiratory morbidity at follow up, had worse lung function prior to neonatal unit discharge.     

Effect of caffeine on respiratory muscle strength and lung function in prematurely born,ventilated infants

The aims of this study were to determine whether caffeine administration increased respiratory muscle function and if this was associated with lung function improvement in prematurely born infants being weaned from mechanical ventilation. Respiratory muscle function was assessed by measurement of the maximum pressures generated during occlusions at end inspiration (Pemax) and end expiration (Pimax) and lung function by measurement of lung volume (functional residual capacity (FRC)) and respiratory system compliance (CRS) and resistance (RRS) in 18 infants with a median gestational age of 28 (range 24–36) weeks. Measurements were made immediately prior to caffeine administration (baseline) and 6 h later. Six hours after caffeine administration compared to baseline, the median Pemax (p = 0.017), Pimax (p = 0.004), FRC (p < 0.001), CRS (p = 0.002) and RRS (p = 0.004) had significantly improved. Our results suggest that caffeine administration facilitates weaning of prematurely born infants from mechanical ventilation by improving respiratory muscle strength.     

Risk factors for hyperinflation in young schoolchildren born prematurely

 Lung function abnormalities, including hyperinflation, are common in young children born prematurely. The aim of this study was, in such patients, to determine factors associated with hyperinflation, that is an elevated lung volume. Lung volume was estimated by measuring functional residual capacity (FRC) before and after bronchodilator therapy in 41 5-year-old children who had been born prematurely at a median of 30 weeks gestational age. Hyperinflation was defined as an FRC greater than 120% of that predicted for height and a positive bronchodilator response as a greater than or equal to 10% change in FRC. Twelve (29%) of the children were symptomatic at 5 years, their median FRC (132%) was significantly higher than that of the asymptomatic children (109%), P < 0.01. Twelve (29%) children were hyperinflated; a greater proportion of the hyperinflated compared to the non-hyperinflated patients were symptomatic at 5 years (7 or 58% versus 5 or 17%) (P < 0.05) and responded to bronchodilator therapy (9 or 75% versus 4 or 14%) (P < 0.01). Regression analysis demonstrated that hyperinflation related significantly only to current symptom status, but not perinatal variables. Conclusion Hyperinflation in young children born prematurely reflects current symptom status and not adverse neonatal events. Received: 19 January 1996 / Accepted: 1 July 1996     

Everyday memory and cognitive ability in children born very prematurely

In light of recent reports of episodic memory difficulties linked to early childhood hypoxia (Isaacs et al., 2000; Vargha-Khadem et al., 1997), preliminary findings of everyday memory function are reported for 20 children born at or before 32 weeks gestation, compared to 20 children born at term. Memory skills were assessed using the Rivermead Behavioural Memory Test for Children (Wilson, Ivani-Chalian, & Aldrich, 1991) at 5 years of age. Everyday memory problems were not found to be a general feature of children born prematurely, and performance was closely linked to receptive language ability but not general cognitive ability in both groups of children. Three children in the preterm group did obtain scores in the impaired range of the RBMT, and in two of these children memory impairment could not be predicted from their receptive language ability. This suggests an increased risk of everyday memory difficulties in populations of preterm children that may be enhanced in further studies by sampling children with greater risk of hypoxic insult.     

Recurrent wheezing in preterm infants: Prevalence and risk factors

ObjectiveTo evaluate the prevalence and risk factors associated with progression to recurrent wheezing in preterm infants.MethodsThe cross-sectional study was carried out in 2014 and 2015 and analyzed preterm infants born between 2011 and 2012. The search for these children was performed in a university maternity hospital and a Special Immunobiological Reference Center. The evaluation was performed through a questionnaire applied during a telephone interview.ResultsThe study included 445 children aged 39 (18–54) months. In the univariate analysis, the risk factors with the greatest chance of recurrent wheezing were birth weight <1000 g, gestational age <28 weeks, living with two or more siblings, food allergy, and atopic dermatitis in the child, as well as food allergy and asthma in the parents. In the multivariate analysis, there was a significant association between recurrent wheezing and gestational age at birth <28 weeks, food allergy and atopic dermatitis in the child, and living with two or more children. Of the 445 analyzed subjects, 194 received passive immunization against the respiratory syncytial virus, and 251 preterm infants were not immunized. There was a difference between the gestational age of these subgroups (p < 0.001). The overall prevalence of recurrent wheezing was 27.4% (95% CI: 23.42–31.70), whereas in the children who received passive immunization it was 36.1% (95% CI: 29.55–43.03).ConclusionsPersonal history of atopy, lower gestational age, and living with two or more children had a significant association with recurrent wheezing. Children with lower gestational age who received passive immunization against the respiratory syncytial virus had a higher prevalence of recurrent wheezing than the group with higher gestational age.     

Assessment of pulmonary function in resolving chronic lung disease of prematurity

AIM—To investigate the longitudinal changes of interstitial and airways disease in resolving chronic lung disease of prematurity (CLD).METHODS—Thirty three infants were studied between 35 and 40 weeks of postconceptional age, and then at three monthly intervals throughout their first year. Measurements of mean arterial oxygen saturation (MSaO₂) and its variability (δMSaO₂) were recorded. PaCO₂ and PaO₂ were determined while the infants breathed steady state 50% oxygen via a hood. From these, the alveolar arterial difference (A-a) Do₂⁵⁰ was calculated. Airway disease was assessed by the measurement of partial forced expiratory flow volume curves (PEFC) to give V?_max Frc.RESULTS—The cohort mean +/- 95% confidence intervals measured between 35 and 40 weeks were for MSaO₂ (89·25 +/- 1·87%, range 75-96·5%) and δMSaO₂ (4·79 +/- 0·8%, range 0·16-9·64%), PaCO₂ (5·89 +/- 0·56 kpa, range 4·2-10·11 kpa), (A-a) Do₂⁵⁰ (22·7 +/- 2·56 kpa, range 6·67-31·4 kpa) and V?_maxFrc (41·5 +/- 8·65 mls/second, range 8·5-103·7 ml/second). The most significant improvement in all measurements occurred within the first three months (P = 0·05). An MSaO₂ of less than 90% in room air at 1 year of age was predicted between 35 and 40 weeks postconceptional age by an (A-a) Do₂⁵⁰ of greater than 29 kpa, with a sensitivity of 0·85 and a specificity of 0·88, and a PaCO₂ greater than 7 kpa predicted a specificity of 0·78 and a sensitivity of 0·88. Predictions were strengthened by combining the above criteria and these then gave a sensitivity and specificity of 1.CONCLUSION—Measurements of (A-a) Do₂⁵⁰ and PaCO₂ taken between 35 and 40 weeks can be used to assess the degree of pulmonary dysfunction at 1 year. Quantification of the severity of CLD could be used as a measurable end point for early neonatal intervention studies.     

Respiratory morbidity in preschool children born prematurely. Relationship to adverse neonatal events

Respiratory morbidity, recurrent cough and/or wheeze and lung function abnormalities are common even outside infancy in preschool children born prematurely. Throughout the first 5 years of life, adverse neonatal events such as immaturity at birth and a requirement for prolonged respiratory support are significantly associated with positive symptom status. In the older preschool child, however, there is some evidence to suggest that other factors, such as a family history of atopy, may be equally important. The development of recurrent symptoms even at 4 years of age can be predicted accurately from the results of lung function measurements made in infancy, and hopefully such data will facilitate the introduction of effective intervention strategies. Lung function abnormalities are more marked in symptomatic patients and, in older children, seem to reflect increased airway responsiveness rather than having a significant relationship to adverse neonatal events. The hospital readmission rate for respiratory disorders, however, is certainly adversely affected by extremely low birthweight and neonatal chronic lung disease, as well as current symptom status. These data highlight that strategies to reduce extremely premature delivery and its consequences should favourably influence respiratory morbidity in preschool children.