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ARTICLES: Monica M. Lahra, Philip J. Beeby, and Heather E. Jeffery Intrauterine Inflammation, Neonatal Sepsis, and Chronic Lung Disease: A 13-Year Hospital Cohort Study Pediatrics 2009; 123: 1314-1319 [Abstract] [Full text] [PDF]

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Chorioamnionitis and chronic lung disease in preterm infants

Jasper V. Been, and Luc J. Zimmermann   (24 May 2009)

Author's Response

Monica M Lahra, Philip J. Beeby, Heather E. Jeffery   (1 July 2009)

Infections w coagulase-negative staphylococci & chronic lung disease in very-low-birth-weight infant

Dr. Christoph Härtel   (6 July 2009)

Chorioamnionitis and chronic lung disease in preterm infants 24 May 2009
Jasper V. Been, PhD student / Resident in training Pediatrics, Maastricht University Medical Centre, Maastricht, Netherlands, and Luc J. Zimmermann Send letter to journal: Re: Chorioamnionitis and chronic lung disease in preterm infants jasper.been{at}mumc.nl Jasper V. Been, et al.	Dear Editor, With great interest we read the article by Lahra and colleagues on the relationship between histological chorioamnionitis, neonatal sepsis and chronic lung disease in preterm infants [1]. Their findings underline the complexity of the associations between antenatal inflammation and adverse lung development [2]. Contrary to what the authors convey, we believe it would be quite informative to include mechanical ventilation in the multivariable model investigating the association between chorioamnionitis and CLD. In fact, the authors hypothesised that ‘intrauterine inflammation would decrease CLD as a consequence of reduced RDS and associated ventilation’. Although their findings may be suggestive of such a mechanism, comparing the models with and without addition of either RDS or mechanical ventilation could actually test this hypothesis. Would a reduction in mechanical ventilation have caused the negative association between chorioamnionitis and CLD, adjustment for this variable should diminish or even obliterate the association. In addition, adjustment for mechanical ventilation is crucial to rule out the possibility that the association between sepsis and CLD is merely the result of increased mechanical ventilation in infants with sepsis. Furthermore, inclusion of two-way interaction terms for the variables of interest may reveal informative subgroup-specific associations, as elegantly shown by Van Marter and colleagues [3]. We would be much interested to learn the effects of addition of mechanical ventilation / RDS to the model on the associations between chorioamnionitis, sepsis, and development of CLD. 1. Lahra MM, Beeby PJ, Jeffery HE. Intrauterine inflammation, neonatal sepsis, and chronic lung disease: a 13-year hospital cohort study. Pediatrics 2009;123(5):1314-19. 2. Been JV, Zimmermann LJ. Histological chorioamnionitis and respiratory outcome in preterm infants. Arch Dis Child Fetal Neonatal Ed 2009;94(3):F218-25. 3. Van Marter LJ, Dammann O, Allred EN, Leviton A, Pagano M, Moore M, Martin C. Chorioamnionitis, mechanical ventilation, and postnatal sepsis as modulators of chronic lung disease in preterm infants. J Pediatr 2002;140(2):171-6. Conflict of Interest: None declared
Author's Response 1 July 2009
Monica M Lahra, Medical Microbiologist, Research Fellow Department of Neonatal Medicine, Royal Prince Alfred Hospital, New South Wales, Australia; Faculty, Philip J. Beeby, Heather E. Jeffery Send letter to journal: Re: Author's Response monical{at}med.usyd.edu.au Monica M Lahra, et al.	Dear Editors We write in response to the letter of Been and Zimmerman1 . Since the sentinel paper by Avery et al2 which showed that neonatal units using less mechanical ventilation (MV) had less neonatal chronic lung disease (CLD), the strong association between MV and CLD has been demonstrated time and time again. In our study3, we hypothesized that babies exposed to intrauterine inflammation (IUI) would experience accelerated lung maturation, have less RDS, and therefore would need less MV and thus have less CLD. Clearly, this causal pathway places MV as an intermediate variable between the exposure (IUI) and the outcome in question (CLD). We also hypothesized that post-natal sepsis would be associated with an increased need for MV and therefore an increased risk of CLD. Again, MV can be regarded as an intermediate variable on the causal pathway between post-natal sepsis and CLD. Conventionally, intermediate variables such as MV are not be included in logistic regression models. However, Been and Zimmerman suggested that the inclusion of MV would further test our hypothesis. We included MV (days) in our first logistic regression model, and as expected it was a highly significant risk factor for CLD (OR 1.08, CI 1.05 -1.11, p < 0.001) The inclusion of MV removed IUI as a risk factor for CLD (p = 0.68), but not post-natal infection overall (p = 0.002). Interestingly, the effect of CoNS was little changed (OR 2.5, CI 1.5-3.9), but other bacteria and yeasts were no longer significant. These findings are consistent with IUI being associated with CLD by a simple reduction in MV, thus adding weight to our original hypothesis. Further, the finding that CONS septicaemia remains an independent significant risk factor for CLD suggests the likelihood of mechanisms of lung injury beyond those caused by MV. 1. Been JV, Zimmerman LJ. Chorioamnionitis and chronic lung disease in preterm infants. Pediatric eLetters 24 May 2009. 2. Avery ME, Tooley WH, Keller JB, Hurd SS, et al. Is Chronic Lung Disease in Low Birth Weight Infants Preventable? A Survey of Eight Centers. Pediatrics 1987; 79: 26-30. 3. Lahra MM, Beeby PJ, Jeffery HE. Intrauterine inflammation, neonatal sepsis, and chronic lung disease: a 13-year hospital cohort study. Pediatrics 2009; 123(5): 1314-19. Conflict of Interest: None declared
Infections w coagulase-negative staphylococci & chronic lung disease in very-low-birth-weight infant 6 July 2009
Dr. Christoph Härtel, New Born Intensive Care University of Lübeck Medical School Send letter to journal: Re: Infections w coagulase-negative staphylococci & chronic lung disease in very-low-birth-weight infant haertel{at}paedia.ukl.mu-luebeck.de Dr. Christoph Härtel	Infections with coagulase-negative staphylococci and chronic lung disease in very-low-birth-weight infants Christoph Härtel, Egbert Herting and Wolfgang Göpel for the German Neonatal Network (GNN)University of Lübeck, Department of Pediatrics, Ratzeburger Allee 160, 23538 Lübeck, Germany Dear Editor, With great interest we read the article by Lahra and colleagues on the relationship between sepsis with coagulase-negative staphylococci (CoNS) and the development of chronic lung disease (CLD) in preterm infants (1). Given the fact that CoNS are often interpreted as microorganisms with less clinical significance, the authors’ findings are remarkable and are supported by the data from our recently founded German Neonatal Network (GNN). From October 2003 until April 2008, 14 tertiary care centers in Germany prospectively enrolled 2327 very-low-birth-weight (VLBW) infants (gestational age: 28.8 ± 2.7 weeks, birth weight: 1075 ± 294 g, mean ± SD). 190/2327 (8.2%) VLBW infants developed blood-culture proven CoNS sepsis, 236/2327 (10.1%) infants had sepsis from other organisms, and 21/2327 (0.9%) infants suffered from Candida sepsis. In our cohort, 69/2327 (3.0%) infants died, CLD (oxygen demand at 36 weeks postmenstrual age) was diagnosed in 306/2327 (13.1%) infants, while 132/2327 (5.6%) infants required supplemental oxygen when discharged. VLBW infants with CoNS sepsis were found to have an increased risk for CLD compared to those without CoNS sepsis (31.1 % vs. 11.6%, p<0.001). In a stepwise logistic regression model, gestational age (per week), birth weight at < 10th percentile, and neonatal sepsis (reference: no blood- culture proven sepsis; CoNS sepsis; sepsis from other bacteria than CoNS; candida sepsis) were selected for analysis (table 1). CoNS sepsis was proven to be an independent risk factor for both, CLD and the combined outcome parameter CLD/death. Effective prevention strategies against CoNS infections may therefore have a significant impact on the incidence of CLD in the highly susceptible population of VLBW infants. Variables adjusted CLD or death CLD Oxygen at discharge Gestational age, wk OR 1.65 (95 % CI: 1.55-1.75; p<0.0001) OR 1.6 (95 % CI: 1.5-1.7; p<0.0001) OR 1.59 (95 % CI: 1.46-1.74; p<0.0001) Birth weight at < 10th percentile OR 2.92 (95 % CI: 2.08-4.08; p<0.0001) OR 2.69 (95 % CI: 1.89-3.83; p<0.0001) OR 2.64 (95 % CI: 1.68-4.16; p<0.0001) CoNS sepsis OR 1.59 (95 % CI: 1.09-2.31; p=0.014) OR 1.83 (95 % CI: 1.26-2.67; p=0.002) OR 1.25 (95 % CI: 0.75-2.09; p=0.39) Sepsis other bacteria OR 1.52 (95 % CI: 1.06-2.18; p=0.022) OR 1.32 (95 % CI: 0.9-1.94; p=0.146) OR 1.62 (95 % CI: 0.99-2.64; p=0.053) Candida sepsis OR 2.79 (95 % CI: 1.01-7.76; p=0.048) OR 2.45 (95 % CI: 0.91-6.56; p=0.07) OR 2.78 (95 % CI: 1.003-7.7; p=0.049) Reference 1 Lahra MM, Beeby PJ, Jeffery HE. Intrauterine Inflammation, Neonatal Sepsis, and Chronic Lung Disease: A 13-year Hospital Cohort Study. Pediatrics 2009; 123: 1314-1319. Conflict of Interest: None declared