Discussion
Maternal intrapartum fever, a usual abnormal status during labor, result in most kinds of adverse outcomes affecting the health of mothers and newborns strongly4-8. However, in most cases, fever comes during birth time silently. In other words, intrapartum fever often occurs without obvious pathogens or symptoms. All these problems put clinicians in a dilemma and worth being noticed.
In present study, we focus on the influence of intrapartum fever to the whole labor. Before the delivery, the value of white blood cell (WBC), red blood cell (RBC), hemoglobin (Hb), and monocytes in mother with intrapartum fever were all higher than non-fever parturients. Though the difference reflected not obvious in value between two groups, the results demonstrated that women with intrapartum fever may have a manifestation in partial complete blood cell count (CBC) in the prenatal. On one hand, these phenomena could make clinicians stay alert. On the other hand, several of these cells play a key role in the development of fever. For example, WBC, one of the vital defense cells to protect the human body, could resist exogenous bacteria, fungal, and virus17, 18. Before suffering from the fever, heat-sensitive activators, including pathogens and elevated generation of IL-17, IL-1β, and IL-1α in intestinal tissue, increase the release of neutrophils from bone marrow and followed infiltration19. Besides, fever related soluble IL-6Rα for signal transduction may be supplied by monocytes20. As is well-known, monocytes and neutrophils were contained in WBC in the test of CBC. Hence, may be due to the pre-activation of the febrile stress response, monocytes and neutrophils, as well as other types of leukocyte, increased slightly and finally reflected in the change of the value of WBC. Moreover, another latest article demonstrated that the function of RBC not only limited in the oxygen transportation, but also contained the pathogen capture and presentation21(21). And this may attribute to its change in the blood. Additionally, literature reported that maternal Hb no more than 110 g/L was considered to be associated with maternal fever8. However, in our exploration, mean Hb of intrapartum fever parturients reached 119.75 g/L and even a little bit higher than afebrile subjects. This imparity needs to be deeply investigated by more large clinical trial.
Subsequently, we compared the relative parameter of prepartum and postpartum value for further investigation. Whether in intrapartum fever or afebrile group, almost all parameter demonstrated difference between prepartum and postpartum status except for lymphocytes in fever group. These results illustrated that delivery as a stress reaction changed the value of CBC through a set of immune responses. Pioneering studies suggested that delivery is an inflammatory process22-24 and our outcomes ulteriorly proved this view. Then, the results of the comparison of the CBC difference manifested that the fever further aggravated the change value of the WBC, RBC, Hb, and neutrophils and alleviated the change value of the PLT caused by parturition. In other words, the blood was concentrated after delivery, and more concentrated in intrapartum fever parturients. As for reduction in the value of RBC and Hb, it might be resulted from intra- or postpartum hemorrhage. All these consequences remind us that we need to pay close attention to the maternal situations after birth process.
In recent years, accumulating researches revealed that neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) could be employed as biomarkers, including prognostic markers for tumor therapy25, 26, diagnostic markers of cardiovascular disease27, 28(27, 28), predictor of certain disease mortality29, as well as in fever30. Previous study demonstrated that NLR and MLR could be applied as the diagnostic marker of bacterial infection30. Inspired by this practice, we planned to predict whether the maternity got a fever during the labor using NLR, PLR, and MLR. Regretfully, our data showed that these three ratios could not predict maternal intrapartum fever appropriately. This result may be due to that we considered fever and non-fever only, but not other relevant disease which might lead to the change of the ratio. This is also a question deserves further detailed research.
Vaginal secretion was cultured in fever subjects and 15.36% positive test rate in this paper. There was an article reported the positive blood and/or placental cultures were occurred in 13.9% women1. Though the site of the examination differs, both results declared that intrapartum fever during the labor might not primarily caused by infection. Combined with the characteristic data, we speculated that nulliparity may be a risk factor for intrapartum fever because of its longer labor time. And the longer labor time resulted in the maternal long-term touching of the external environment and this distracted the puerperae. Along with the fact that the childbirth was likely an inherently stress reaction, women were in a hypoimmunity state after long time labor and then fever came. In addition, more intrapartum hemorrhage, more oxytocin usage rate, and more cloudy amniotic fluid were found in intrapartum fever group. These findings also implied the fever parturients during labor in a poor state. After vaginal discharge examination, corresponding comparison of the CBC was implemented. And several differences were found among three groups. Then, post hoc analysis indicated the difference mainly existed in bacteria and fungus but not between gram positive and negative bacteria. These phenomena gave us a hint that we may develop a new marker to identify whether it is bacteria or fungus and thereby do more fundamental research to exploit the potential mechanism creating this result.
Generally speaking, intrapartum fever was defined as temperature greater than 38 ℃ during labor3, 31. But there were also studies set the temperature as over 37.4 ℃ or 37.5 ℃4, 32. And in our study, we defined the intrapartum fever as more than 37.5 ℃ because fever during labor were associated with neonatal morbidity, sepsis, and even to death and a series of other obstetric complications4, 32. Besides, for the most part, fetal heart rate would faster in pregnant women with temperature over 37.5 ℃. Given this, we were looking for better care for parturients and set the temperature of the intrapartum fever as 37.5 ℃.
Several shortages existed in this study. Firstly, all included parturients received epidural analgesia because of childbirth analgesia rate reached to 90% in our hospital. We had no control group without epidural analgesia, so we could not clarify whether the hematological indicators and converted NLR, PLR, and MLR increased during the delivery in those patients without epidural analgesia or not. Therefore, this research was difficult to reflect the situation of all populations combined with almost all of the included parturients were Chinese. And a large multi-center study deserved to be carried out for both maternal and fetal health. Besides, receiving epidural analgesia was a risk factor for intrapartum fever7, 33, 34 and its influence on the followed examination still unknown. Secondly, due to the limitation of conditions, we only designed this retrospective analysis but not randomized controlled study. And further large prospective clinical trials need to be carried out for the purpose of mother and child health. Thirdly, we measured the axillary temperature of maternity, which affected the accuracy of body temperature because of non-core temperature. Lastly, some data were not collected such as times of vaginal exams, internal fetal monitoring, duration of ruptured membranes, instrumental delivery, cesarean section, maternal and fetal umbilical vein serum IL-6 levels, which potentially affected the development of intrapartum fever.