Fetal Membrane Histology in Preterm Premature Rupture of Membranes: Comparison to Controls, and between Antibiotic and Placebo Treatment

Abstract

The objectives of this study were to test the hypotheses that antibiotic therapy will alter the histologic appearance of fetal membranes in preterm premature rupture of membranes (pPROM), and that the membrane histology will demonstrate distinct differences between term and preterm rupture of membranes. We also wished to test interobserver variability of pathologists. Placental membranes were sampled from 268 women participating in a randomized placebo-controlled trial of antibiotic therapy for pPROM at 24-32 weeks of gestation (cases) and from 4 control groups who were not in the randomized trial: (1) preterm labor without pPROM (n = 21), (2) term labor (n = 65), (3) term PROM (n = 21), and (4) term cesarean section (n = 27). The cases and controls were scored for 40 histologic features by pathologists blinded to the identity of each sample (case or control). pPROM histology of samples from patients receiving antibiotics and those receiving placebo was compared using a chi-squared test and with control groups using logistic regression. There were no histological differences between pPROM cases treated with antibiotic and those receiving placebo, nor with respect to duration of membrane rupture greater or less than 48 h. Concordance among pathologists was low for features other than acute inflammation. Logistic regression analysis controlled for race and pathologist, and demonstrated that all of the control groups had significantly fewer common markers of acute inflammation when compared with the pPROM cases. This study suggests that histopathologic evidence of infection is seen more frequently with pPROM than in preterm or term controls. The histologic features used in this study cannot be used to determine the effectiveness of antibiotic therapy.

A new anti-microbial combination prolongs the latency period, reduces acute histologic chorioamnionitis as well as funisitis, and improves neonatal outcomes in preterm PROM

“…This benefit occurred in patients with demonstrable intra-amniotic infection/inflammation at the beginning of the therapy, but not in patients without this condition. Our findings are in contrast to those previously reported, indicating that a combination of amoxicillin and erythromycin for a short period of time did not reduce the frequency of acute histologic chorioamnionitis [96,202,203]. Of interest, in a randomized clinical trial in which the efficacy of cefazolin, cefazolin plus erythromycin, or cefazolin plus clarithromycin for seven days was compared, the use of cefazolin with clarithromycin was associated with a reduction in the percentage of patients with severe funisitis.…”

A new antibiotic regimen treats and prevents intra-amniotic inflammation/infection in patients with preterm PROM

“…Studies in humans have suggested an association between acute chorioamnionitis and neurodevelopmental disorders [136,151–159]. The observation that the administration of ampicillin and erythromycin in the randomized clinical trial conducted by Mercer et al [100] did not result in a lower rate of funisitis (compared to the placebo group) [160] indicates that short-term antimicrobial therapy did not reduce the likelihood of a fetal inflammatory response [79]. This observation is consistent with a subsequent report indicating that there was no change in the concentrations of inflammatory cytokines in umbilical cord blood after the administration of antibiotics [161].…”

The antibiotic treatment of PPROM study: systemic maternal and fetal markers and perinatal outcomes

“…Consistent with our findings regarding maternal systemic inflammatory markers, we have previously found that antibiotic treatment during conservative management of preterm PROM does not significantly impact histological findings in the placenta and membranes. (25) It is plausible that the inflammatory cascade cannot be stopped once initiated. Alternatively it may also be possible that intrapartum events obscure the effects of antibiotics on placental and cytokine findings regardless of extended latency and absence of overt intrauterine infection until near the time of delivery.…”