Chorioamnionitis is diagnosed clinically by fever, maternal or fetal tachycardia, uterine pressure, vaginal discharge or foul odor of amniotic fluid, and maternal leukocytosis [6, 23]. In contrast, histological chorioamnionitis is usually clinically asymptomatic, with a minimal maternal inflammatory response [24, 25], the diagnosis cannot be confirmed by routine physical signs and laboratory tests, but only by postpartum pathology of the placenta.
A recent study found significantly higher levels of interleukin 6 (IL-6), metalloproteinase matrix 8 (MMP-8) and tumor necrosis factor alpha (TNF-α) in amniotic fluid obtained vaginally in patients with HCA compared to non-HCA patients . However, the diagnostic efficacy of these indicators is not good enough to be used in clinical applications. The lack of effective detection methods can easily lead to the underdiagnosis of pregnant women with HCA who do not have clinical symptoms and eventually cause serious fetal complications. Thus, we wanted to discover a valid diagnostic index for HCA.
In this study, the reference range of HBP concentration in normal maternal amniotic fluid was established, and the diagnostic value of HBP in the prediction of HCA was evaluated. Our results showed that HBP in amniotic fluid was significantly lower in normal and non-HCA pregnant women than in those with HCA. Both the reference range established by normal pregnant women and the ROC evaluation results of abnormal pregnant women had a sensitivity of 84.20% and specificity of 96.90% for predicting HCA. In addition, there was no statistical difference in HBP in umbilical artery and umbilical vein, nor was there a statistical difference in HBP between HCA and non-HCA in umbilical artery or umbilical vein. This result suggests that HBP in amniotic fluid may not be related to umbilical artery and umbilical vein.
Overall, HBP is an excellent predictor of HCA. However, 3 of the 19 pregnant women with HCA in the study had test values < 5.9 ng/mL, which is a clear departure from the test values of other pregnant women and leads us to consider whether there are some factors influencing these results. HCA, as a manifestation of placental inflammation, is usually caused by pathogens invading the amniotic cavity, but we note recent evidence that "sterile" intra-amniotic inflammation is frequently associated with HCA . In the original study design, we did not consider sterile HCA, which may explain the HBP values of < 5.9 ng/ml in the three HCA pregnant women. In addition, we found only one case of non-HCA pregnant women with HBP > 82.67 ng/ml, whose value was 95.45 ng/ml. This value is relatively low compared to the value for HCA pregnant women, perhaps due to other factors affecting this value.
Current studies suggest that the secretion of HBP in the blood activates monocytes rolling along the endothelial cells, causing monocyte stagnation. Monocytes will move across the endothelial cells and migrate to the injured site after adhesion. The pro-inflammatory effect of HBP is mainly the activation of monocytes, which play an important role in antimicrobial action, and it is a potential biomarker with diagnostic properties . At present, there is no study on the relationship between HBP in amniotic fluid and HCA, but there are many studies on the relationship between HBP and infection, and HBP is considered as a reliable index for predicting severe infection. A meta-analysis of HBP in predicting sepsis in critically ill patients showed that the sensitivity and specificity of HBP in the diagnosis of sepsis were 0.85 and 0.91, respectively ; Another study on the relationship between HBP and sepsis also found that it has high diagnostic value. In addition, the study pointed out that the secretory granules secreting HBP were first mobilized after neutrophil activation, so the rise of HBP was prior to other infection indicators (WBC, C-reactive protein, procalcitonin, lactic acid) ; Furthermore, elevated CSF levels of HBP can distinguish patients with acute bacterial meningitis from patients with other central nervous system infections . The relationship between HBP in amniotic fluid and infection has not been studied at present, so it is necessary to further study the source of HBP in amniotic fluid.
Previous studies suggested that neutrophils in amniotic fluid originated from the mother, but subsequent experiments showed that neutrophils in amniotic fluid may also come from the fetus [30–33]. A DNA fingerprinting study on the origin of neutrophils in amniotic fluid of pregnant women with intrauterine infection pointed out that neutrophils in amniotic fluid are effective markers of inflammation, mainly from the fetus or the mother or both, because both the fetus and the mother can participate in the immune mechanism of intra amniotic infection . Since there was no significant difference in HBP in the umbilical cord vessels of HCA and non-HCA pregnant women, we speculate that HBP in amniotic fluid may not be derived from the umbilical cord vessels because neutrophils infiltrate the umbilical cord and fetus only in severe chorioamnionitis .
The results of this study suggest the value of HBP in the diagnosis of HCA is positive, but there are some drawbacks in our study. Due to the unique nature of pregnant women and fetuses, we encountered many difficulties in obtaining samples, resulting in a limited number of subjects that could be included. Secondly, this is the first study on the value of HBP in amniotic fluid for the diagnosis of HCA and thus may not be standard in the way the sample was collected. Finally, we did not consider HCA caused by non-bacterial infections during the experimental design phase, which prevented us from fully excluding their effect. We will continue to study the diagnostic value of HBP in the group of pregnant women with PROM, which is a high risk factor for HCA or a clinical condition caused by HCA.