The distinctive hypoxic environment of high-altitude regions has long been a key focus in perinatal medicine due to its impact on pregnancy and childbirth [1]. Prolonged exposure to low-pressure, low-oxygen environments at altitudes above 2500 meters can affect the mother, fetus, and newborn [2]. In the mother, this can lead to compensatory physiological changes, such as erythrocytosis and placental vascular remodeling. In the fetus, intrauterine growth patterns adapt, and the hypoxic environment may affect its development and health after birth [3]. As indigenous inhabitants of high-altitude regions, Tibetans have developed remarkable hypoxic adaptation capabilities through long-term natural selection and physiological adjustments [4]. However, it is not fully elucidated whether this adaptive mechanism affects the characteristics of their labor process during delivery (e.g., number of deliveries, duration of labor) and influences neonatal outcomes (e.g., birth weight, asphyxia).

Umbilical artery blood gas analysis (UABGA) is used to assess the oxygenation and acid-base status of neonates, as well as their respiratory response capacity. It has predictive value for adverse outcomes, including early identification of complications such as hypoxic injury and respiratory distress syndrome [5]. Key indicators of acid-base balance and oxygenation status in neonates include pH, base excess (BE), and lactate (LAC). A significant decrease in pH, a large negative BE deviation, and a significant increase in LAC levels suggest that the neonate may be experiencing acidosis [6]. Studies have shown that severe acidosis is strongly associated with increased neonatal mortality and neurological complications, while mild metabolic imbalance can also raise the risk of adverse outcomes in term neonates [7, 8]. Low [9] demonstrated that severe intrapartum hypoxic-ischemic events, reflected by marked metabolic acidosis at birth, strongly predict fetal brain injury. In high-altitude regions, the hypoxic environment can have a greater impact on these indicators and, consequently, on neonatal health [10]. Previous studies have primarily focused on complications of high-altitude pregnancy, such as preeclampsia and fetal growth restriction (FGR), with little attention given to the relationship between physiological labor processes, labor characteristics, and neonatal UABGA, particularly in indigenous Tibetan populations that have developed a hypoxic adaptation phenotype.

This study aims to systematically investigate the association between the delivery characteristics of Tibetan women in plateau regions, including parity, epidural analgesia, and the duration of the second stage of labor, and the blood gas parameters (pH, BE, and LAC) of their term newborns, through a retrospective analysis. This research will provide scientific evidence to inform obstetric clinical practice in plateau regions.

This study identified significant associations between labor characteristics and neonatal UABG parameters in low-risk Tibetan populations at high altitude. Our core finding is that the duration of the second stage of labor serves as a key modifiable factor, with prolonged duration independently predicting lower BE and higher LAC levels. Additionally, primiparity emerged as a major factor influencing umbilical cord blood gas values. Maternal height also showed a positive correlation with neonatal pH levels, although its predictive capability remains limited.

In this study, the median pH value of 7.28 (IQR: 7.22, 7.33) aligns closely with previous studies. For instance, it is comparable to the pH value of 7.25 $\pm$ 0.07 reported in 296 term newborns in Weifang [13] and the pH value of 7.25 $\pm$ 0.13 observed in 2121 newborns in Hulunbuir [14], indicating that pH values in healthy term neonates remain within a narrow range. In this study, the BE value of –8 (–10, –7) mmol/L was similar to the multicenter report of –7.66 $\pm$ 5.02 mmol/L [15], but lower than the –5.08 $\pm$ 2.53 mmol/L observed in 182 term newborns in Hainan [16]. The LAC value of 4.37 (3.47, 5.40) mmol/L in this study was comparable to the 3.91 $\pm$ 2.47 mmol/L reported by Weifang [13]. Similarly, our findings align with a study of healthy term newborns at 3500 meters in Yunnan [17], which reported UABG parameters of pH 7.29 (7.17–7.35), LAC 4.50 (3.40–5.73) mmol/L, and BE –7.20 (–9.70 to –4.70) mmol/L. However, specific statistical differences will require evaluation in future studies that compare high-altitude regions with lowland or other plateau areas. In our study, all neonates had a 1-minute Apgar score of $\ge$7, which may have limited the variability in clinical condition at birth. Notably, even in populations with lower Apgar scores, prior studies have reported a weak correlation between Apgar scores and umbilical cord blood gas parameters. For example, a study of newborns with Apgar scores 8 found only weak, though statistically significant, correlations between Apgar scores and pH or bicarbonate levels in umbilical vein blood. This finding suggests that Apgar scores and blood gas analysis provide complementary, rather than interchangeable, assessments of neonatal condition at birth [18]. This aligns with our findings that, even within a low-risk cohort, factors such as labor duration and parity exert more consistent influences on UABG parameters than Apgar score alone.

Linear regression analysis indicates that the duration of the second stage of labor is an independent determinant of neonatal UABG parameters. Specifically, prolonged second stage of labor was significantly associated with lower BE and higher LAC levels, while exhibiting a negative correlation with pH. To assess the robustness of these associations, we further conducted robust regression analysis using the M-estimation method. The results confirmed that the duration of the second stage of labor remained significantly associated with BE and LAC, supporting the primary findings of the linear regression. At elevations above 2500 meters, the partial pressure of atmospheric oxygen decreases significantly, which affects umbilical artery blood gas levels [19]. Although the Tibetan population has developed adaptive features such as enhanced erythropoiesis and placental vascular remodeling, their fetuses remain in a state of relative hypoxia compared with those at sea level [20]. This hypoxic stress is exacerbated by the prolonged second stage of labor [21]. The increased frequency and intensity of uterine contractions reduce placental blood flow and thereby decrease oxygen delivery to the fetus. In order to sustain energy metabolism, fetal tissues shift towards anaerobic glycolysis, resulting in increased LAC production (manifested as an elevated LAC levels) and subsequent metabolic acidosis, reflected by more negative BE values [22]. Previous studies have found that healthy term newborns born at high altitude, up to 3600 meters above sea level, often exhibit pH and LAC levels in the UABGA that fall within the high-risk critical range [23, 24]. This phenomenon may relate to the hypoxic intrauterine environment (oxygen partial pressure of 16–27 mmHg). Under these conditions, the fetus relies mainly on glucose oxidation to maintain physiological functions [25]. In addition, most of the LAC in fetal UABGA is produced during the second stage of labor [26]. Meanwhile, mothers undergo a series of compensatory physiological adaptations to the chronic low-pressure hypoxic environment of high-altitude region. These changes may lead to an increase in placental blood flow [27], thus partially mitigating the effects of chronic hypoxia. Therefore, closer labor monitoring and neonatal assessment are needed for primiparous women in highland areas to identify and manage potential hypoxic and metabolic complications promptly, even during a physiologically normal labor period.

Additionally, this study found a weak positive association between maternal height and umbilical artery pH ($\beta$ = 0.002, p = 0.016). The mean height of mothers in the lower pH group ($\le$7.28) was 160.69 cm, significantly lower than the 161.56 cm observed in the higher pH group ($>$7.28) (p = 0.047). This effect may stem from shorter maternal stature being associated with smaller pelvic volumes, increasing resistance during fetal descent. In high-altitude environments, chronic hypoxia may modestly impair uterine contractions coordination [28]. This can further prolong labor duration (with a longer third stage duration in the lower pH group, p = 0.026), thereby exposing the fetus to intermittent hypoxia. Cumulative hypoxic stress disrupts fetal acid-base balance, leading to a modest yet measurable pH decrease. Notably, the adjusted coefficient of determination (R²) for the pH regression model was only 0.061. This unexpected association may reflect increased oxygen demand in longer fetuses or changes in fetal position during labor; however, the underlying mechanism requires further investigation.

Primiparity and premature rupture of membranes are additional factors associated with UABG parameters. Primiparous women were more likely to exhibit decreased BE values (172/331 cases in the low BE group, vs. 53/193 in the high BE group, p = 0.001) and elevated LAC values (87/262 primiparas in the low LAC group vs. 138/262 in the high LAC group, p = 0.001). In both linear and robust regression analyses, parity showed a significant association with BE levels. Linear regression revealed parity as a positive predictor. Primiparas exhibit poorer uterine contraction coordination and slower cervical dilation [29], leading to prolonged first and second stages of labor. The median duration of the first stage was 320.00 minutes in the low BE group, significantly longer than 240.00 minutes in the high BE group (p 0.001). Prolonged labor exacerbates fetal hypoxia, resulting in LAC accumulation and reduced BE values [30]. Premature rupture of membranes correlates with elevated LAC levels, observed in 69 of 262 cases in the high LAC group compared with 46 of 262 in the lower LAC group (p = 0.015). This effect occurs because premature rupture of membranes compromises the integrity of the amniotic cavity, potentially reducing amniotic fluid volume and impairing both fetal buffering capacity and placental oxygen exchange efficiency [31]. In the oxygen-limited environment of high altitude, premature rupture of membranes may further exacerbate fetal hypoxic stress, leading to elevated LAC levels.

This study identified significant differences in umbilical artery blood pH, BE, and LAC levels between newborns of primiparous and multiparous mothers in high-altitude regions. These findings are consistent with multiple studies conducted in lowland areas, indicating that parity is an important determinant of UABG parameters. A large-scale, multicenter study conducted across six Chinese hospitals, comprising 20,191 newborns, demonstrated that parity significantly impacts UABG values [15]. Notably, in this study, epidural anesthesia affected only BE values, without significantly altering pH or LAC levels. This suggests that the acid-base balance changes induced by epidural anesthesia are primarily metabolic in nature and relatively mild, not reaching the threshold required to cause significant alterations in pH and LAC levels. This study exhibits both similarities and differences compared with the Tehran, Iran study regarding the effects of epidural anesthesia on neonatal acid-base balance [32]. Both studies observed a shift toward more negative BE values in the epidural group. However, a key discrepancy lies in the impact on pH: the Iranian study reported a significant pH decrease in the epidural group, whereas no such change was observed in the high-altitude setting of the present study. This discrepancy may result from variations in anesthetic management strategies between locations (e.g., blood pressure maintenance, oxygen therapy application). Additionally, differences in study population characteristics or statistical power may also be contributing factors. Overall, these findings suggest that although epidural anesthesia exerts a relatively consistent effect on fetal metabolic status, its impact on overall acid-base balance may be modulated by regional environmental factors, clinical practices, and population characteristics.

In conclusion, the present study revealed the relationship between labor and delivery characteristics and neonatal UABGs in secular Tibetan mothers living in the plateau region. In this low-risk population, factors influencing pH include maternal height, the duration of the second stage of labor, and neonatal length. Factors influencing BE include parity and the duration of the second stage of labor. The duration of the second stage of labor is a factor influencing LAC.

All data reported in this paper will be shared by the corresponding author upon request.

ZDo: conceptualization, investigation, formal analysis, data curation, writing—original draft preparation. BC: conceptualization, methodology, investigation, writing—original draft preparation. QG: investigation, data curation, writing—review and editing. LY, ZDa, LC, and ZC: investigation, writing—review and editing. PZ: formal analysis, writing—review and editing. ZY: data curation, writing—review and editing. JF: conceptualization, methodology, investigation, supervision, writing—original draft preparation, writing—review and editing. All authors contributed to editorial changes in the manuscript. All authors read and approved the final manuscript. All authors have participated sufficiently in the work and agreed to be accountable for all aspects of the work.

The research adheres to the Declaration of Helsinki. Ethical approval was obtained from the medical ethics committee of Lhasa People’s Hospital (No. SYLL22250108). This is a retrospective study utilising anonymised routine clinical data; no interventions were performed on patients, nor was there any contact with individual patients. Given the retrospective design of this study and the analysis of anonymised data, the Ethics Committee has waived the requirement for informed consent.

Thanks to all the peer reviewers for their opinions and suggestions.

This research received no external funding.

The authors declare no conflict of interest.