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.