We read with great interest the paper by Combs et al who reported different degrees of intraamniotic inflammation in women with preterm labor and intact membranes that suggests that severe inflammation is related with a shorter latency to delivery and worse composite neonatal morbidity. This conclusion was based on a multivariable logistic regression analysis that was adjusted for gestational age at sampling.
Our group agrees with the idea of Combs et al that severe inflammation is associated with an earlier gestational age at delivery and a shorter latency to delivery. However, because gestational age at delivery is related to both inflammation and neonatal composite morbidity (the earlier the gestational age at delivery the higher the risk of inflammation and a worse neonatal outcome), we believe that composite neonatal morbidity results should be adjusted for gestational age at delivery and not at sampling. Women with low inflammation (even with a positive amniotic fluid culture) had a better neonatal prognosis because latency to delivery was longer and gestational age at delivery was later than women with severe inflammation or with infection. In line with that, women with severe inflammation showed worse neonatal outcome because gestational age at delivery was earlier and latency to delivery was shorter than women without inflammation. This affirmation is based on data from Combs et al. When they adjusted the gestational age at delivery in Table 6 (model 3 and 4 in the article), they found that severe inflammation did not have a negative effect. They found that severe inflammation had a protective effect (odds ratio, 0.2; 95% confidence interval, 0.0–0.8) on composite neonatal morbidity. Because they lost statistical significance when they excluded respiratory distress syndrome, one can hypothesize that the protective effect that was observed might be due to lung acceleration effect.
Therefore, according to the logistic regression models of Combs et al, it seems reasonable to refine or clarify the affirmation that intraamniotic inflammation is associated with worse perinatal outcome. The data suggest that gestational age at delivery is the main determinant of neonatal composite morbidity and not intraamniotic inflammation.
Because current clinical decisions are based mainly on the diagnosis of microbial invasion of amniotic cavity, the assessment of the inflammatory status in the amniotic cavity, mainly in undetected infection women, is particularly relevant in the current management of preterm labor with intact membranes or preterm prelabor with rupture of membranes. However, if women with inflammation could be targeted by appropriate treatment and if gestational age at delivery could be delayed remains unanswered.