Prenatal fever, occurring in approximately 11.4% of deliveries [1], is associated with adverse outcomes, such as contamination of the amniotic fluid, fetal distress, stillbirth, neonatal asphyxia [2], and an increased likelihood of cesarean sections [3, 4]. As awareness of the impact of intrauterine infection on both mothers and infants grows, clinical attention toward prenatal fever is increasing.

Distinguishing between infectious and non-infectious causes of prenatal fever poses challenges, particularly in cases presenting with elevated fetal heart rate, increased leukocyte count, and prolonged labor stages [5, 6]. The risks associated with short- and long-term complications of cesarean sections highlight the need for accurate diagnosis and enhanced clinical assessment of maternal fever to improve perinatal outcomes and ensure fetal intrauterine safety [7, 8].

Neonatal resuscitation guidelines emphasized the use of evidence-based medicine methods to promptly evaluate and support newborns after birth, including essential life support measures [9]. The American College of Obstetrics and Gynecology (ACOG) recommended umbilical artery blood gas analysis for all newborns with prenatal risk factors [10]. Umbilical cord blood gas analysis (UCBGA) serves as an objective and reliable adjunctive examination to assess newborns’ oxygenation metabolism at birth, with pH serving as a predictor of adverse neonatal outcomes. UCBGA is particularly advantageous for screening high-risk newborns [11, 12]. It provides a quantitative analysis to assess fetal stress reactions during delivery, recognized as the most objective basis for evaluating fetal and neonatal acid-base balance [13].

This retrospective study aimed to investigate the association between prenatal maternal fever and neonatal umbilical artery blood gas analysis. Specifically, it was attempted to assess whether the duration and degree of maternal fever during pregnancy would be correlated with neonatal blood gas parameters. This investigation could address the gap in understanding the impact of prenatal fever on neonatal acid-base balance and oxygenation metabolism at birth.

Fever refers to increased body temperature beyond the average value when the body is dysfunctional in the thermoregulation center caused by heat or various causes. Prenatal fever is a common complication during pregnancy [14]. Numerous studies have suggested that the intrauterine temperature of pregnant women is about 0.8 °C higher than that of the oral cavity and increases with maternal temperature [15]. Infection is a crucial factor contributing to prenatal fever, particularly retrograde infection resulting from artificial rupture of membranes. Premature rupture of membranes ranks foremost among the causes of prenatal fever [16, 17]. Fever in pregnant women during different periods of pregnancy can affect the progress of pregnancy and lead to various adverse pregnancy outcomes [18]. Even if the fetus has reached maturity during the prenatal period, maternal fever, particularly high fever, increases the risk of neonatal hypoxic-ischemic encephalopathy, fetal distress, neonatal septicemia, amniotic fluid contamination, cesarean section, and even fetal death [19]. Therefore, it is vital to carry out studies on the prevention of prenatal maternal fever.

In the present study, both high-risk and low-risk pregnant patients were included to assess the association between maternal pyrexia and postnatal umbilical artery blood gas analysis. Obstetric high-risk factors, such as intrauterine growth restriction (IUGR), placental abruption, and cord prolapse were assessed for each case. Additionally, the labor process was closely monitored, with particular attention to fetal heart rate monitoring and progress of labor. In this study, it was found that the incidence of the adverse delivery outcome of parturients with high prenatal fever and long duration of fever was significantly higher than that of low fever, short-term fever, and normal parturients. Consequently, clinical, scientific, and effective interventions should be given to prevent the occurrence of prenatal fever, reduce the duration of fever, and improve the maternal and pediatric outcomes. Pregnant women experiencing fever should prioritize its management, following medical advice to utilize antipyretic drugs or physiotherapy. Lowering body temperature promptly to normal level is crucial to mitigate adverse pregnancy outcomes. Additionally, comprehensive preventive health guidance regarding the various causes of prenatal fever should be provided to expectant mothers and their families. Beyond the direct effects of increased maternal metabolic demands, fever during pregnancy may lead to fetal hypoxia through multiple pathways. Inflammation-induced alterations in placental transport mechanisms could impair the delivery of oxygen from the maternal to fetal circulation. Additionally, fever-associated changes in maternal cytokine levels and vascular tone may disrupt uteroplacental blood flow, reducing oxygen delivery to the fetus. These mechanisms collectively highlight the multifaceted nature of the association between maternal fever and fetal hypoxia.

It is essential to note that while antipyretic medications may help alleviate maternal discomfort and prevent potential adverse effects on the fetus, they should be used judiciously and not as a substitute for identifying and treating the underlying cause of fever. Prompt and thorough evaluation to determine the etiology of maternal fever is essential, as it may indicate various conditions, such as infection, inflammation, or other medical issues. Treating the underlying cause of fever is crucial for optimizing maternal and neonatal outcomes. Clinicians should adopt a comprehensive approach to managing maternal fever during delivery, which includes not only the administration of antipyretic medications, but also investigation into the root cause of fever to develop appropriate treatment strategies. The management of maternal fever during delivery, including interventions, such as antipyretic medications or other treatments, may influence the pattern and severity of maternal fever, consequently affecting neonatal outcomes.

Under normal conditions, the mother supplies the fetus with blood rich in oxygen and nutrients through the umbilical vein. The umbilical artery transports blood rich in carbon dioxide and metabolic waste products from the fetus back to the placenta [20]. Therefore, umbilical artery blood provides a precise reflection of the fetal oxygenation metabolism. In cases of fetal or neonatal asphyxia and hypoxia, aerobic energy metabolism pathways are suppressed, leading to an increase in anaerobic metabolism. Consequently, there is elevated production and accumulation of lactic acid and other acidic metabolites [21]. In recent years, the international perinatal medical community has increasingly emphasized the significance of neonatal umbilical artery blood gas values [22]. At present, both domestically and internationally, umbilical artery blood gas analysis serves as an objective measure to assess newborns’ acid-base status and as a quality control index for delivery room management [23]. There is a consensus regarding the advantages of blood gas analysis, including its simplicity, minimal invasiveness, and swift results. This method facilitates a rapid understanding of the body’s acid-base balance and hypoxia, thereby playing a crucial role in diagnosing neonatal hypoxic conditions [24]. Scholars investigated whether umbilical artery pH $\le$7.00 and umbilical artery blood deficit $\ge$12.00 mmol/L could serve as reliable indicators of adverse neonatal outcomes. They found that infants with umbilical artery pH $\le$7.00 exhibited a 9.57-fold increased risk of 1-min Apgar score (AS) $\le$4, a 10.83-fold increased risk of 5-min AS $\le$7, and a 7.6-fold increased risk of adverse neonatal outcomes. Following multivariate analysis, umbilical artery pH $\le$7.00 persisted as a standalone predictor of adverse neonatal outcomes, entailing a 6.71-fold higher risk [25]. Prior research assessed the implementation of universal UCBGA in a secondary obstetric facility and a universal program for umbilical cord lactate analysis in primary and secondary units. The mentioned research demonstrated that following the introduction of universal UCBGA or lactate analysis, there were no notable alterations in the mean values of blood gas and lactate across any center. However, there was a non-significant decrease in arterial pH values below 7.10 observed at the secondary metropolitan center [26]. In the present study, it was revealed that the umbilical artery blood gas analysis was associated with maternal peak fever temperature and duration of fever. Under normal conditions, the fetus has a relatively coordinated acid-base disease and relatively stable hemodynamics. The pH value is typically above 7.20 [27]. When hypoxia and asphyxia occur, the hemodynamics adjust to prioritize blood supply to essential organs, ensuring their oxygenation. However, prolonged hypoxia leads to organ anoxia and damage, resulting in a decrease in the body’s pH value [28]. Consistently, the present study indicated that the pH of neonatal umbilical veins in the fever group was reduced compared with the control group, and it was positively correlated with maternal peak fever temperature and fever duration. Lac is the intermediate product of glycolysis. When the aerobic metabolism of sugar is limited, the tricarboxylic acid cycle is blocked, and the anaerobic glycolysis pathway is activated [29]. Lactate dehydrogenase converts pyruvate to Lac with the participation of coenzymes [30, 31]. The production and metabolism of Lac form a continuous cycle, with simultaneous metabolism occurring in the liver, kidney, skeletal muscle, and red blood cells, ensuring that the concentration of Lac is in the normal range [32, 33]. In the present study, it was revealed that the pH and BE of neonatal umbilical veins in the low and high fever groups were reduced compared with the control group. Remarkably, it has been recently demonstrated that the incidence of neonatal hypoxic-ischemic encephalopathy, neonatal intracranial hemorrhage, and neonatal respiratory failure significantly increased when pH 7.0 and/or BE –12.00 mmol/L and/or lactic acid level $\ge$6.00 mmol/L [34, 35]. The present study aimed to provide valuable insights into the clinical implications of maternal fever on neonatal outcomes. By examining the association between prenatal fever and umbilical artery blood gas analysis, actionable information could be provided for healthcare providers to optimize perinatal care practices. The findings of this study may contribute to the development of evidence-based guidelines for the management of maternal fever during pregnancy, ultimately improving the health outcomes of both mothers and newborns. This study indicated that the Lac of neonatal umbilical vein in the low fever and high fever groups was elevated compared with the control group. Therefore, for pregnant women with maternal fever, umbilical artery blood gas analysis results may predict the potential risk of poor neurological prognosis in their newborns. These objective indicators are conducive to doctors’ observations and early prediction of neonatal clinical diseases. Moreover, enhancing early detection and treatment of the condition improves the prognosis. To address potential biases and confounding factors inherent in retrospective case-control studies, rigorous methods were employed in data collection and analysis. Inclusion and exclusion criteria were clearly defined, and appropriate statistical methods were utilized to account for potential confounders. Strengths of this study include its large sample size and comprehensive analysis of neonatal outcomes in relation to maternal fever.

However, it is important to acknowledge the limitations of this study. Firstly, its retrospective design might inherently introduce the potential for selection bias and confounding variables. Additionally, the reliance on medical records for data collection might introduce information bias. Secondly, the lack of detailed information on certain variables, such as the specific indications for extended labor in women with fever, could limit the interpretation of the findings. Thirdly, the relatively small sample size might also reduce the generalizability of the results. Finally, while the manuscript provides valuable insights into the association between maternal fever and fetal hypoxia, further research is needed to explore additional pathways through which fever may impact fetal wellbeing.

In conclusion, this retrospective study on prenatal fever mothers revealed that neonatal umbilical artery blood gas analysis was associated with the degree and duration of maternal fever. It was found that prenatal fever could influence the maternal delivery outcome, leading to adverse delivery outcomes. For high-risk pregnant women, especially those with prenatal fever, the umbilical artery blood gas analysis has high clinical application value and is worthy of further promotion in clinical application. It is imperative for future studies to explore the relationship between maternal fever management strategies and their effects on neonatal health, as understanding these dynamics can optimize perinatal care and improve neonatal outcomes.

The original contributions presented in the study are included in the article, and further inquiries can be directed to the corresponding author.

LL, XW, and TW designed the study. LL, XW, and YL performed the research. LH, LL, and TW analyzed the data. All authors contributed to editorial changes in the manuscript. All authors read and approved the final manuscript. All authors have participated sufficiently in the research and agreed to be accountable for all aspects of the research.

This study was approved by the Research Ethics Committee of Guangzhou Women and Children’s Medical Center Affiliated to Guangzhou Medical University (2021318B00). Written informed consent was signed by the parturients.

This research was funded by General Guidance Project of Guangzhou Health Commission (Name: Suiwei Science and Education [2021], Grant No. 20221A010021).

The authors declare no conflict of interest.