Abstract
ObjectiveTo explore the relationship between prematurity, gender and chorioamnionitis as determinants of early life lung function in premature infants.MethodsPlacenta and membranes were collected from preterm deliveries (<37 weeks gestational age) and evaluated for histological chorioamnionitis (HCA). Patients were followed and lung function was performed in the first year of life by Raised Volume-Rapid Thoracic Compression Technique.ResultsNinety-five infants (43 males) born prematurely (median gestational age 34.2 weeks) were recruited. HCA was detected in 66 (69%) of the placentas, and of these 55(58%) were scored HCA Grade 1, and 11(12%) HCA Grade 2. Infants exposed to HCA Grade 1 and Grade 2, when compared to those not exposed, presented significantly lower gestational ages, higher prevalence of RDS, clinical early-onset sepsis, and the use of supplemental oxygen more than 28 days. Infants exposed to HCA also had significantly lower maximal flows. There was a significant negative trend for z-scores of lung function in relation to levels of HCA; infants had lower maximal expiratory flows with increasing level of HCA. (p = 0.012 for FEF50, p = 0.014 for FEF25–75 and p = 0.32 for FEV0.5). Two-way ANOVA adjusted for length and gestational age indicated a significant interaction between sex and HCA in determining expiratory flows (p<0.01 for FEF50, FEF25–75 and p<0.05 for FEV0.5). Post-hoc comparisons revealed that female preterm infants exposed to HCA Grade 1 and Grade 2 had significant lower lung function than those not exposed, and this effect was not observed among males.ConclusionsOur findings show a sex-specific negative effect of prenatal inflammation on lung function of female preterm infants. This study confirms and expands knowledge upon the known association between chorioamnionitis and early life chronic lung disease.
Highlights
Premature birth can lead to a wide range of early life consequences for the immature lung and most of these are likely associated with increased respiratory morbidity in the first years of life
[9] The concept of exposure of the fetal lung to infection and inflammation, promoting in one direction accelerated maturation, and simultaneously, in an opposite direction, development of chronic lung disease (CLD) of prematurity has been previously demonstrated by a number of studies. [10,11,12,13,14] Several of these have shown an increased incidence of CLD or bronchopulmonary dysplasia (BPD) in infants with a previous diagnosis of histological chorioamnionitis, [15,16,17] or signs of systemic inflammatory responses. [18,19,20] In contrast, two large reports found no significant association between HCA and either CLD or BPD. [21,22] One potential limitation of most studies may be the use of a cut-off parameter of oxygen at 36 weeks post-menstrual age (PMA) as a surrogate for CLD
Infants exposed to HCA Grade 1 and Grade 2, when compared to those not exposed, presented significantly lower gestational ages, higher prevalence of Respiratory Distress Syndrome (RDS) and clinical early-onset sepsis, and the use of supplemental oxygen more than 28 days
Summary
Premature birth can lead to a wide range of early life consequences for the immature lung and most of these are likely associated with increased respiratory morbidity in the first years of life. One previous study from our group has shown that male preterm infants present up to 20% lower flows, as measured during the first three months of life, when compared to girls, at corresponding two full weeks of gestation. [4] This ventilatory disadvantage explains, at least in part, the increased frequency of obstructive respiratory morbidity among male preterm infants Another aspect that may influence respiratory morbidity in the first years of life is the fact that infant girls, who are more likely to be born with the benefit of larger airways compared to boys, seem to lose this advantage if exposed to pre-natal maternal smoking [5,6] or due to an inadequate breastfeeding scheme. The contribution of chorioamnionitis on lung development, through early life lung function measurements, should be investigated in the context of these intervening variables
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