The aim of this study was to investigate the correlation between the cytokine levels in the amniotic fluid (AF) and the histological stage of chorioamnionitis (CAM) in premature labor. AF of 6 cases (7 samples of AF were obtained as one was a twin pregnancy) in whom CAM was diagnosed histologically, and 12 cases without CAM were included in this study. Amniotic fluid was obtained within 24 hours prior to delivery. Cytokine levels (IL-2, -4, -6, TNF-alpha, IFN-gamma) in AF were measured by an ELISA method. Levels of IL-2 and -6 in the CAM-positive group (mean +/-S.E., 52.9 +/- 83.9 pg/ml, and 20,537.9 +/- 8853.7 pg/ml, respectively) were higher than those in the CAM-negative group (i.e. undetectable, and 65.6 +/- 27.5, respectively) with a statistical significance of p < 0.05, p < 0.001, respectively. There was a positive linear relationship between IL-6 levels of AF and the placental histological inflammatory stages of Blanc in the CAM-positive group. From these results it would appear that the IL-6 level in AF is the most sensitive test in the detection of extraamniotic infection or intraamniotic infection in preterm labor with intact membranes and also indicates the severity infection.
PMID 9120746 9120746 DOI 10.1515/jpme.1996.24.6.633 10.1515/jpme.1996.24.6.633 Negishi et al. 1996, Negishi 1996
Cite this article
Negishi, H., Yamada, H., Mikuni, M., Kishida, T., Okuyama, K., Sagawa, T., Makinoda, S., & Fujimoto, S. (1996). Correlation between cytokine levels of amniotic fluid and histological chorioamnionitis in preterm delivery. Journal of perinatal medicine, 24(6), 633-639. https://doi.org/10.1515/jpme.1996.24.6.633
Negishi H, Yamada H, Mikuni M, Kishida T, Okuyama K, Sagawa T, et al. Correlation between cytokine levels of amniotic fluid and histological chorioamnionitis in preterm delivery. J Perinat Med. 1996;24(6):633-639. doi:10.1515/jpme.1996.24.6.633
Negishi, H., et al. "Correlation between cytokine levels of amniotic fluid and histological chorioamnionitis in preterm delivery." Journal of perinatal medicine, vol. 24, no. 6, 1996, pp. 633-639.
C-reactive protein (CRP) levels were evaluated during spontaneous labour, in imminent premature parturition (IPP) and after preterm rupture of oocyst membranes (PROM). Increasing CRP level during spontaneous labour was found in 16.6% parturients. Elevated CRP level in patients with IPP makes it impossible to predict premature labour. In parturients with PROM, increase in CRP level makes further infection predictable only in a few cases.
The role of subclinical intrauterine infection in preterm labor was evaluated prospectively in 40 patients and appropriate control subjects. The 24 preterm labor patients (60%) with a negative C-reactive protein value responded to tocolysis 95.8% of the time, with a mean delay of delivery of 35.5 days and a mean gestational age of 36.9 weeks. The 16 patients (40%) with a positive C-reactive protein value responded to tocolysis only 37.5% of the time, with a mean delay of delivery of 14.4 days and a mean gestational age of 33.2 weeks. Pathologic evidence of chorioamnionitis was present in 32.9% of 310 preterm deliveries as compared to only 22.3% of 1631 term deliveries. The presence of subclinical infection must be considered in cases of preterm labor, especially among patients for whom tocolytic therapy is unsuccessful.
Preterm birth is the leading cause of neonatal morbidity and mortality. The recurrence rate of spontaneous preterm birth is high, and additional preventive measures are required. Our objective was to assess the effectiveness of low-dose aspirin compared to placebo in the prevention of preterm birth in women with a previous spontaneous preterm birth. Findings: We performed a parallel multicentre, randomised, double-blinded, placebo-controlled trial (the APRIL study). The study was performed in 8 tertiary and 26 secondary care hospitals in the Netherlands. We included women with a singleton pregnancy and a history of spontaneous preterm birth of a singleton between 22 and 37 weeks. Participants were randomly assigned to aspirin 80 mg daily or placebo initiated between 8 and 16 weeks of gestation and continued until 36 weeks or delivery. Randomisation was computer generated, with allocation concealment by using sequentially numbered medication containers. Participants, their healthcare providers, and researchers were blinded for treatment allocation. The primary outcome was preterm birth <37 weeks of gestation. Secondary outcomes included a composite of poor neonatal outcome (bronchopulmonary dysplasia, periventricular leukomalacia > grade 1, intraventricular hemorrhage > grade 2, necrotising enterocolitis > stage 1, retinopathy of prematurity, culture proven sepsis, or perinatal death). Analyses were performed by intention to treat. From May 31, 2016 to June 13, 2019, 406 women were randomised to aspirin (n = 204) or placebo (n = 202). A total of 387 women (81.1% of white ethnic origin, mean age 32.5 ± SD 3.8) were included in the final analysis: 194 women were allocated to aspirin and 193 to placebo. Preterm birth <37 weeks occurred in 41 (21.2%) women in the aspirin group and 49 (25.4%) in the placebo group (relative risk (RR) 0.83, 95% confidence interval (CI) 0.58 to 1.20, p = 0.32). In women with ≥80% medication adherence, preterm birth occurred in 24 (19.2%) versus 30 (24.8%) women (RR 0.77, 95% CI 0.48 to 1.25, p = 0.29). The rate of the composite of poor neonatal outcome was 4.6% (n = 9) versus 2.6% (n = 5) (RR 1.79, 95% CI 0.61 to 5.25, p = 0.29). Among all randomised women, serious adverse events occurred in 11 out of 204 (5.4%) women allocated to aspirin and 11 out of 202 (5.4%) women allocated to placebo. None of these serious adverse events was considered to be associated with treatment allocation. The main study limitation is the underpowered sample size due to the lower than expected preterm birth rates. In this study, we observed that low-dose aspirin did not significantly reduce the preterm birth rate in women with a previous spontaneous preterm birth. However, a modest reduction of preterm birth with aspirin cannot be ruled out. Further research is required to determine a possible beneficial effect of low-dose aspirin for women with a previous spontaneous preterm birth. Dutch Trial Register (NL5553, NTR5675) https://www.trialregister.nl/trial/5553.
Preterm birth complicates 8-10% of all pregnancies in the United States and is the leading cause of infant morbidity and mortality. Neonatal morbidity and mortality is concentrated among very low-birthweight and extremely premature infants, particularly those delivered prior to 30 weeks' gestational age. In addition to the contribution of preterm birth to neonatal morbidity and mortality, the economic costs associated with this pregnancy complication are staggering. Efforts to reduce the preterm birth rate have been largely focused on prevention and early intervention with treatment for preterm labor. Mixed results regarding the success of prematurity prevention programs have been reported, and controversy continues to surround the efficacy of tocolytic therapy in the treatment of preterm labor. Although neonatal survival for infants born at early gestational ages has steadily improved in recent years, survival of infants delivered prior to 24 weeks' gestation remains very poor. Additionally, despite this decline in neonatal mortality, the United States still lags behind most industrialized nations in infant mortality, and no change in the rate of low birthweight has occurred in recent decades. Multiple lines of evidence support a role for infection as an etiologic factor in preterm labor. Although this association has been well known for many years, a wealth of new data is emerging, linking subclinical genital tract infection with spontaneous preterm birth, particularly among pregnancies that result in birth prior to 30 weeks' gestational age as a result of spontaneous preterm labor or preterm, premature rupture of membranes. Conversely, preterm birth that occurs closer to term is less likely to be associated with genital tract infection. Improved understanding of the link between genital tract infection and preterm birth now provides an exciting potential for the development of sensitive new markers to identify women at risk and effective interventions to prevent preterm birth. A review and comment on this growing literature is provided.