{"paper_id":"2a5338f6-542e-4add-8a3a-ab3db723ecdd","body_text":"Lactate values during labour and their correlation with maternal and foetal outcome: a prospective observational single-centre study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Lactate values during labour and their correlation with maternal and foetal outcome: a prospective observational single-centre study Barbara Milan, Giulia Fierro, Ilaria Roncagliolo, Francesca Graziano, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6375489/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Uterine contractions during labour are regulated by hormonal and metabolic processes, including oxytocin release, catecholamines modulation, and the hypoxia-induced force increase (HIFI) mechanism. This study investigates the relationship between lactate levels—produced during myometrial contraction and transient hypoxia—and maternal and foetal outcomes. In a cohort of 303 women receiving neuraxial analgesia, lactate was measured at three time points: at the time of diagnosis of the active phase of the first stage of labour (T0), at the beginning of active pushing (T1), and at delivery (T2). Lactate levels increased progressively, exceeding 2 mmol/L at T1 and T2. However, no significant correlation was found between lactate levels and postpartum haemorrhage or neonatal umbilical cord pH. Multiparous women exhibited lower lactate levels at T1 and T2 (p < 0.001), likely due to more efficient myometrial response and metabolic adaptation. Lactate, rather than solely indicating hypoxia, may act as an energy substrate. These findings suggest that lactate plays a physiological role in labour and should not be viewed exclusively as a marker of distress. Understanding its role could refine the clinical interpretation of maternal metabolic stress and improve labour management strategies. Biological sciences/Molecular biology Health sciences/Biomarkers Health sciences/Health care Health sciences/Medical research lactate labour physiology uterine contractions hypoxia-induced force increase postpartum haemorrhage maternal metabolism Figures Figure 1 Figure 2 Figure 3 Figure 4 Background Labour represents the physiological process whereby involuntary, rhythmic, and peristaltic contractions of the uterus lead to the effacement and dilation of the cervix, allowing the baby to pass through the birth canal. Rhythmic uterine contractions are controlled by several factors, including the release of catecholamines, oxytocin, and prostaglandins and a complex process called hypoxic-induced force increase (HIFI) (see Figure S2 in Supplementary Material) 1 – 4 . Endogenous catecholamine concentrations increase throughout labour due to stress, pain, and physical effort, modulating uterine smooth muscle contractions, increasing endorphin production, and promoting the release of oxytocin 3 . Adrenaline increases eightfold during labour compared to baseline levels and has a tocolytic effect, while norepinephrine has a uterotonic action 3 . Although both adrenaline and noradrenaline are increased, a tocolytic effect predominates; this effect is regulated by oxytocin 5 . Furthermore, oxytocin stimulates the production of prostaglandins, which enhances the myometrium's sensitivity to oxytocin 3 . The last crucial process that regulates uterine contractility is the mechanism of HIFI. The myometrium contraction induces a brief hypoxic state, resulting in elevated lactate levels, decreased pH, and relaxation of the smooth muscle fibroblasts 4 . During the hypoxic phase of HIFI, the pH and concentration of adenosine triphosphate (ATP) are reduced. The reduction of ATP concentration stimulates purinergic receptors (P2X7) that increase intracellular calcium levels and adenosine concentration. The adenosine increases calcium release from the sarcoplasmic reticulum and promotes actin-myosin binding. All these processes lead to an increase in force during subsequent uterine contractions 4 . This complex mechanism occurs only in the term-pregnant myometrium, with no analogous response (regarding enhanced contractile force) shown in the preterm or non-pregnant myometrium 4 . Therefore, labour is a complex and strenuous experience that leads to a hypermetabolic state and substantial energy production. Such production is predominantly facilitated by adrenaline, which induces glycogenolysis and enhances glucose availability. The increase of lactate levels during labour is a physiological response resulting from hypoxic events that inhibit the oxidative pathway of the Krebs cycle and from excessive glycolysis, which produces elevated pyruvate levels that exceed mitochondrial oxidative capacity, thus promoting lactic acid production 6 . The lactate standard threshold in healthy people is up to 2 mmol/l. During labour, lactate levels higher than 2 mmol/l are observed 7 . Currently, reference ranges for lactic acid levels during labour remain undefined. Lactic acid is hypothesised to play a role in the mechanisms regulating labour, which functions as an inflammation inhibitor 8 and it has been shown that high lactate levels and a low pH exert a tocolytic effect on the myometrium 9 . Postpartum haemorrhage (PPH) represents a significant cause of morbidity in the obstetric population, with a mortality rate of 140,000 women per year 10 , and the predominant cause of PPH (70%) is uterine atony 11 . As lactate levels may have an effect on the tone of the uterus, elevated levels during labour could influence maternal and foetal well-being. We decided to assess lactate concentrations during labour in women receiving neuraxial anaesthesia and evaluate the association between high lactate levels and adverse maternal and foetal outcomes. The primary aim of our study was to assess whether elevated lactate values during labour were associated with an increased risk of PPH. Our secondary aims were to assess lactate levels at different stages of labour and investigate whether there was any association between lactate concentrations and neonatal cord pH on delivery. Methods Study Design and Participants We conducted a prospective observational single-centre study involving women in active labour receiving neuraxial anaesthesia. Consecutive women in labour with neuraxial analgesia were recruited from May to September 2023 in the labour ward of ASST Papa Giovanni XXIII hospital (Bergamo, Italy), a tertiary care referral centre (Italian Ministerial Decree n. 70/2015) for obstetric care in the north of Italy. Before enrolment, all women received written information about the study, signed an informed consent form, and were informed about the processing of their personal or clinical data. Patients included in the study were ≥ 18 years old, had a single pregnancy with a gestational age of ≥ 36 weeks, were in active labour with a cervix dilation of 4 to 6 cm, received neuraxial analgesia and gave their informed consent to the study. Exclusion criteria were age < 18 years, twin pregnancy, gestational age < 36 weeks, women in labour without labour analgesia, cervix dilation > 6 cm at the moment of the placement of neuraxial analgesia, and women who did not informed consent to the study. The study design was approved by the ethical committee of ASST Papa Giovanni XXIII Hospital in May 2023 (REF: no. 751/2023, reg 56/23). ClinicalTrials.gov identifier NCT06807255. All methods were performed in conformity with the Declaration of Helsinki, and the study was designed and presented in accordance with the STROBE guidelines 12 . Study outcomes The primary aim of our study was to assess whether lactate levels at three specific time points are associated with postpartum haemorrhage. The secondary aims were to assess lactate levels at different stages of labour, compare them depending on parity and mode of labour onset, and assess whether there is any association between lactate concentrations and neonatal pH at delivery. Procedures – Labour analgesia Labour analgesia was placed at the beginning of active labour, which is considered to be between 4 and 6 cm of cervix dilatation 13 , 14 . The labour analgesia technique consisted of standard epidural or dural puncture epidural (DPE); analgesia was maintained by intermittent clinician boluses on maternal request. The chosen local anaesthetic was ropivacaine, whose concentration was increased (from 0.1% up to 0.15%, for a total volume of 15 to 20 ml) based on cervical dilatation and foetal head position at the time of the bolus administration. For each bolus, Sufentanil was added (10 − 5 mcg in epidural technique and 7,5 − 3,75 mcg in DPE). Data collection We recorded the following demographic and clinical information: age, pre-pregnancy and postpartum body mass index (BMI), gestational age, parity, mode of onset of labour (spontaneous vs. induction), duration of each stage of labour, total postpartum blood loss at the end of the third stage of labour, and umbilical artery foetal pH. Lactate levels were assessed by blood gas analysis on samples obtained from the women’s indwelling peripheral venous cannulae; subsequent analysis was conducted using the point-of-care emogasanalyser 500 Systems–Siemens (Siemens, Milano) at three time points. The three time points were as follows: T0: at the time of diagnosis of the active phase of the first stage of labour, T1: at the beginning of the active phase of the second stage of labour, at the beginning of active pushing, and T2: at the time of the delivery, before placenta expulsion. Postpartum haemorrhage (PPH) has been defined following the definition of the Royal College of Obstetricians and Gynaecologists as a total blood loss ≥ 500 ml 15 . Our population was divided into two groups: those with total blood loss < 500 ml and those with blood loss ≥ 500 ml. To measure umbilical cord pH, 1–2 ml of cord blood was taken from the umbilical artery one minute after birth, regardless of clamping. The analysis was conducted with the point-of-care emogasanalyser 500 Systems blood gas analyser, Siemens (Siemens, Milan). Statistical Analysis Baseline characteristics were described as mean (standard deviation, SD), median (I-III quartile), and absolute and relative frequencies, as appropriate. Differences between groups (e.g., nulliparous/multiparous) of lactate levels at each time point were assessed by t-tests or Mann-Whitney U, following the nature of the variable. To evaluate the variation of lactate over time, an initial exploratory analysis was conducted graphically using a spaghetti plot. Then, mixed-effects models were applied to evaluate the effect of postpartum haemorrhage and other clinically relevant variables on lactate variation. Finally, the relationships between lactate levels at each time point and the neonatal pH were also explored by the Pearson index (r) and its associated p-value. The tests were two-sided with a type I error set at a significance level of 0.05. All analyses were performed using R (version 4.3.1). Results Study population Between May and September 2023, we enrolled 381 women who were in active labour and had received neuraxial analgesia. Thirty-one cases were excluded from the analysis due to caesarean section delivery, and forty-seven were excluded due to incomplete data (the enrolment process is shown in Fig. S1 in the supplementary material). We conducted the final analysis on 303 women, 242 of whom were nulliparous and 61 were multiparous. The demographic, clinical, and labour characteristics of our study population are shown in Table 1 . The mean age was 32.02 (SD = 4.71) years, with a mean gestational age of 39.59 weeks, and the median pre-pregnancy BMI was equal to 21.8 (I-III quartile = 19.8–24.2). Table 1 Demographic and clinical data of the study population Overall n 303 Age, mean (SD) 32.02 (4.71) BMI prepregnancy, median (I-III quartile) 21.80 [19.80, 24.20] BMI post-pregnancy, median (I-III quartile) 26.60 [24.65, 29.45] Gestational age ≥ 40 weeks, n (%) 138 (45.5) Gestational age, weeks, mean (SD) 39.59 (1.19) Nulliparous n (%) 242 (79.9) Spontaneous labour n (%) 191 (63.0) Length of first stage, minutes, median (I-III quartile) 240.00 [137.50, 315.00] Length of the second stage, minutes, median (I-III quartile) 47.00 [25.50, 75.00] Abbreviations: BMI = body mass index Lactate levels over time Figure 1 illustrates the distribution of lactate levels at each time point measured. The mean at T0 was 1.83 (SD = 0.68), and it increased over time from the onset of labour to delivery. At T1 and T2, median lactate values are higher than 2 mmol/L (T1 = 2.84, SD = 1.32, and T2 = 3.80, SD = 1.56). Postpartum haemorrhage The median total postpartum blood loss was 400 ml (I-III quartile = 300–600). 110 (36.3%) patients had blood loss of less than 500 ml. No differences were found between the two groups ( ≥ 500 ml vs. < 500 ml) in lactate values at three time points and in changes over time from T0 (Table 2 A and B; Fig. 2 ). Considering the linear mixed models, both blood loss and the interaction term (time and blood loss) were not statistically significant (p = 0.574 and p = 0.211, respectively). Further analysis showed no statistically significant difference in lactate values even with blood losses > 1000 ml (p = 0.446) or > 1500 ml (p = 0.471). Lactate, parity and labour induction Of the 303 patients, 242 were nulliparous, and 61 were multiparous. Detailed results are illustrated in Table 3 . Table 2 - Mean differences between blood loss at each time point (A) and change from T0 of lactate value between the blood loss > 500 ml and < 500 ml (B). A. Mean (SD) Difference blood loss < 500 – blood loss > 500 (CI 95%) p-value Time point Blood loss < 500 Blood loss > 500 T0 1.85 (0.65) 1.78 (0.75) 0.07 (-0.09; 0.24) 0.406 T1 2.83 (1.38) 2.84 (1.22) 0.01 (-0.31; 0.29) 0.947 T2 3.84 (1.61) 3.98 (1.49) 0.14 (-0.50; 0.22) 0.439 B. T0 - T1 0.98 (1.35) 1.058 (1.26) 0.07 (-0.39; 0.22) 0.601 T0 - T2 1.99 (1.51) 2.19 (1.42) 0.21 (-0.56; 0.13) 0.223 Table 3 Lactate values at the three time points and lactate values change in time among the two groups (parity and mode of onset of labour) Mean (SD) Difference nulliparous - multiparous (CI 95%) p-value Time Nulliparous (n = 242) Multiparous (n = 61) T0 1.85 (0.62) 1.75 (0.88) 0.10 (-0.13; 0.35) 0.3721 T1 2.92 (1.36) 2.53 (1.10) 0.39 (0.06; 0.72) 0.019 T2 4.06 (1.58) 3.23 (1.30) 0.83 (0.45; 1.22) < 0.001 Changes in time T0-T1 1.06 (1.30) 0.77 (1.35) 0.29 (-0.09; 0.67) 0.141 T0-T2 2.21 (1.45) 1.47 (1.45) 0.80 (0.32; 1.14) < 0.001 Induction of labour (n = 112) Spontaneous labour (n = 191) Difference induced – spontaneous labour (CI 95%) p-value Time T0 1.80 (0.67) 1.85 (0.69) 0.05 (-0.11; 0.21) 0.511 T1 2.93 (1.49) 2.79 (1.22) 0.14 (-0.47; 0.19) 0.404 T2 3.89 (1.59) 3.90 (1.55) 0.01 (-0.36; 0.38) 0.959 Changes in time T0-T1 0.94 (1.18) 1.13 (1.51) 0.19 (-0.52; 0.14) 0.251 T0-T2 2.04 (1.43) 2.08 (1.55) 0.04 (-0.39; 0.31) 0.808 Data are expressed in Mean and Standard Deviation As shown, significant differences were found among nulliparous and multiparous women in the time points T1 and T2 (differences among groups 0.39, CI 95% = 0.06; 0.72, p = 0.019 and 0.83, CI 95% = 0.45; 1.22, p < 0.001, at T1 and T2, respectively). This result is confirmed considering the lactate change in time T2 - T0 (0.80, CI 95% = 0.32; 1.14, p < 0.001; Table 3 and Fig. 3 ) and in the linear mixed model (interaction term, p < 0.001). Regarding the mode of onset of labour, 191 women entered labour spontaneously, while 112 women underwent an induction of labour Among these two groups, the lactate trend did not show statistically significant differences at T0, T1, and T2 and in the change from T0 (Table 3 ). Lactate and foetal pH The mean value of foetal pH (umbilical artery sampling) was 7.268, SD = 0.10. There was no statistically significant correlation between lactate levels at any time point and foetal pH: at T0, the correlation index ® = -0.03, p = 0.566, at T1 r = 0.01, p = 0.914, and at T2 r = -0.1 and p = 0.073 (Fig. 4 ). Discussion It has been hypothesised that lactic acid acts as an inhibitor of inflammation and that low pH and high lactate levels may have a tocolytic effect on the myometrium 8 . Our study shows no statistically significant difference in lactate values at the three time points between women with blood losses less than or equal to or more than 500 ml (Table 2 ). Subsequent exploratory analysis reveals that this holds true with blood losses exceeding 1000 or 1500 ml. Lactate levels do not correlate with an increased incidence of PPH, and the correction with buffer substances 16 neither alters these levels nor mitigates the risk of PPH. Thus, lactate during labour should not be regarded exclusively as a biomarker of hypoxia and cellular damage. The tocolytic effect of lactate is modulated by oxytocin as demonstrated by in vitro studies 9 ; then, lactate production in labour is likely a typical physiological response of the organism. In the general population, plasma lactate levels remain up to 2 mmol/L in health 7 . In our population, at the onset of active labour (T0), the average lactate values were below 2 mmol/L, while at the start of the active phase of the second stage (T1) and at delivery (T2), the median lactate values were higher than 2 mmol/L (Fig. 1 ). This is in keeping with a meta-analysis by Baur et al. in 2018 7 that assessed lactate concentrations in healthy pregnant women during gestation and labour. They identified 22 studies involving 1193 patients to show that women have venous lactate levels below 2 mmol/L during pregnancy and between 2 and 4 mmol/L during active labour. During the second stage and at delivery, some studies reported lactate levels above 4 mmol/L. The limitation of this meta-analysis is that it includes studies whose populations analysed show significant heterogeneity. The role of neuraxial analgesia in modulating the neuroendocrine aspects of labour is well established. By modulating pain, neuroaxial analgesia diminishes catecholamine levels during labour, reduces endorphin production, and decreases oxytocin concentrations. These modifications make it challenging to compare women with analgesia with women without analgesia during labour 3 . As early as 1991, Piquard was among the first to recognise the significance of differentiating between women undergoing neuraxial analgesia and those not receiving analgesia 17 . Comparing our findings with Piquard’s, lactate levels at T2 in our population are almost 1 mmol higher than levels reported by Piquard in patients with neuraxial analgesia. This discrepancy may be attributed to the prevalence of multiparous patients compared to primiparous patients in the cohort examined by Piquard. Labour is a complex phenomenon influenced by numerous elements, including parity and the mode of onset of labour 13 , 18 . Our sub-analysis indicates that lactate generation during labour is diminished in multiparous women compared to nulliparous women, with statistically significant differences observed at T1 and T2 (p = 0.019 and p < 0.001, respectively; see Table 3 ). Our findings are echoed by the research conducted by Schneider et al. in 1990. However, the population analysed in that study did not receive neuraxial analgesia 19 . Multiparous women likely exhibit reduced metabolic exertion during the expulsion phase, which is typically more rapid and has more favourable outcomes, with a diminished risk of surgical intervention compared to nulliparous women 18 , 20 . Parity may affect activation levels of myometrial cells during labour; specifically, in multiparous women, the receptors for oxytocin are more sensitive and easily inducible 21 . Finally, various hormonal mechanisms are implicated, including a difference in beta-endorphin concentration between multiparous and nulliparous women 3 , 22 . All these characteristics likely lead to a less significant increase in lactate at the end of the second stage. This supports the role of lactic acid as a physiological marker of metabolic stress of labour. Clinicians could benefit from understanding the \"physiological\" lactate values after delivery to ensure the accurate interpretation of lactate, even in the event of complications in the immediate postpartum period. The literature reports that induced labour is more painful and prolonged 18 , 23 , 24 and associated with less favourable outcomes. However, our study (where all participants received neuraxial analgesia) did not observe any statistically significant differences in lactate levels between induced and non-induced labour (Table 3 ). Thus, we can assume that neuraxial analgesia effectively attenuates the increased metabolic stress seen during induction of labour but does not influence the metabolic stress in nulliparous women. To our knowledge, no previous study has compared lactate production in relation to the mode of labour onset. Intrapartum foetal hypoxia potentially increases the foetal risk of asphyxia, acidosis, neuronal damage, long-term morbidity, or even death 25 . Blood gas analysis of umbilical blood samples is the only method for objectively measuring the incidence of foetal acidosis or hypoxia 26 . Among the secondary endpoints, we studied the correlation between maternal venous lactate and foetal pH. We have shown no statistically significant correlation between lactate at the three distinct time points and foetal pH (Fig. 4 ). Our findings corroborate those previously published by Piquard et al. 17 . The authors observed that the lactate concentration in the mother's venous blood and cord arterial blood was in equilibrium at birth after elective caesarean sections. However, during labour, foetal and maternal lactate levels changed independently. The authors discovered that in hyporeactive newborns, the lactate concentration in cord blood exceeded that in maternal venous blood, suggesting foetal lactate production. Further analyses are required to study the relationship between maternal lactate levels and foetal well-being. The women in our research represented a homogeneous population as they all received neuraxial analgesia. While this makes the outcome data reliable, it is also a limitation of the study, as the findings of the study are applicable only to women with neuraxial analgesia. Therefore, further research is necessary to investigate lactate levels in women without analgesia. Conclusion Labour is a complex physiological event with specific metabolic characteristics, unlike any other human experience. The absence of a correlation between maternal lactate and adverse maternal-foetal outcomes suggests that lactate is not exclusively a marker of cellular hypoxia. It has been hypothesised that elevated levels of lactate may represent a marker for the metabolic stress of labour and/or serve as a physiological source of energy produced and utilised by the uterus under stressful conditions, such as during labour. Identifying reference values of lactate levels at the different stages of labour could be used clinically in the future to evaluate the progress of labour whose dynamics are not fully understood. Further research is essential to clarify the role of lactate during labour. Declarations Data availability The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request. Authors Contributions BM and GF conceptualized the study and drafted the manuscript. IR drafted the manuscript and acquired the data. FG analysed and interpreted the data. VR drafted the manuscript. NS, EB, SMB acquired the data. FLL supervised the study. 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Allanson, E., Waqar, T., White, C., Tunçalp, Ö. & Dickinson, J. Umbilical lactate as a measure of acidosis and predictor of neonatal risk: a systematic review. BJOG 124, 584–594 (2017). Ayres‐de‐Campos, D. & Arulkumaran, S. FIGO consensus guidelines on intrapartum fetal monitoring: Physiology of fetal oxygenation and the main goals of intrapartum fetal monitoring. International Journal of Gynecology & Obstetrics 131, 5–8 (2015). Additional Declarations No competing interests reported. Supplementary Files Supplementarymaterialpdf.pdf Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {\"props\":{\"pageProps\":{\"initialData\":{\"identity\":\"rs-6375489\",\"acceptedTermsAndConditions\":true,\"allowDirectSubmit\":true,\"archivedVersions\":[],\"articleType\":\"Article\",\"associatedPublications\":[],\"authors\":[{\"id\":449389278,\"identity\":\"62dd7b64-9890-4aab-92b1-548c3095dc1f\",\"order_by\":0,\"name\":\"Barbara Milan\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"ASST Papa Giovanni XXIII\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Barbara\",\"middleName\":\"\",\"lastName\":\"Milan\",\"suffix\":\"\"},{\"id\":449389279,\"identity\":\"cf77862e-a6c1-41cb-a5ab-0f48d10b2c0d\",\"order_by\":1,\"name\":\"Giulia Fierro\",\"email\":\"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA+UlEQVRIiWNgGAWjYDAC5oMNIEoOxpeTZ2BswK+FLRGswBiIwUqNDRsYG/HrYUsAUyCNYC2JDQcIWCPvxtz4uHKPTXp///HnDxh31AKtYG5/gE+L4THGZsMzz9JyZ9zIATrpzHFmdgYCDjOc39gm2XDgcG7DDR7G5r9tx9gYCfnFsI2x/SdQS7r8+eMPGxjbjvEwHCCgRZ6NsY0RqCXB4EAC0GFtNRIEtRiwMTYDHZZmuBHolxmMZw4YGDYzNs7Aa0sb+8OPDQds5OXOH3/wgXFHXf189vYHH/DacgCZx9hwGJge8KkH2YLibMaGOgLqR8EoGAWjYCQCAPEjU8+0NqvWAAAAAElFTkSuQmCC\",\"orcid\":\"\",\"institution\":\"ASST Papa Giovanni XXIII\",\"correspondingAuthor\":true,\"prefix\":\"\",\"firstName\":\"Giulia\",\"middleName\":\"\",\"lastName\":\"Fierro\",\"suffix\":\"\"},{\"id\":449389280,\"identity\":\"21a8e56f-9425-43cb-8440-5d63f462ef9a\",\"order_by\":2,\"name\":\"Ilaria Roncagliolo\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"University College of London Hospital\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Ilaria\",\"middleName\":\"\",\"lastName\":\"Roncagliolo\",\"suffix\":\"\"},{\"id\":449389281,\"identity\":\"86f75d67-c04a-492f-af18-c40b95a9c3c9\",\"order_by\":3,\"name\":\"Francesca Graziano\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Fondazione IRCCS San Gerardo dei Tintori\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Francesca\",\"middleName\":\"\",\"lastName\":\"Graziano\",\"suffix\":\"\"},{\"id\":449389282,\"identity\":\"0422322f-b6de-4fc3-8d85-077ccd0a5278\",\"order_by\":4,\"name\":\"Vicky Rubini\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"University of Milan\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Vicky\",\"middleName\":\"\",\"lastName\":\"Rubini\",\"suffix\":\"\"},{\"id\":449389283,\"identity\":\"9eb9fd4c-809c-43f5-b38a-95131b686b11\",\"order_by\":5,\"name\":\"Nilaya Signori\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"ASST Bergamo EST\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Nilaya\",\"middleName\":\"\",\"lastName\":\"Signori\",\"suffix\":\"\"},{\"id\":449389284,\"identity\":\"7c69a0b4-ade7-4b21-ab18-b720286bf81d\",\"order_by\":6,\"name\":\"Elena Buelli\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"ASST Papa Giovanni XXIII\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Elena\",\"middleName\":\"\",\"lastName\":\"Buelli\",\"suffix\":\"\"},{\"id\":449389285,\"identity\":\"8f9c961b-3694-479a-86c1-06737e45a923\",\"order_by\":7,\"name\":\"Santa Maria Barresi\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"ASST Papa Giovanni XXIII\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Santa\",\"middleName\":\"Maria\",\"lastName\":\"Barresi\",\"suffix\":\"\"},{\"id\":449389286,\"identity\":\"47e0a41c-65d8-4e07-8eb8-5cc34f2b9c92\",\"order_by\":8,\"name\":\"Ferdinando L. Lorini\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"ASST Papa Giovanni XXIII\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Ferdinando\",\"middleName\":\"L.\",\"lastName\":\"Lorini\",\"suffix\":\"\"}],\"badges\":[],\"createdAt\":\"2025-04-04 10:53:11\",\"currentVersionCode\":1,\"declarations\":\"\",\"doi\":\"10.21203/rs.3.rs-6375489/v1\",\"doiUrl\":\"https://doi.org/10.21203/rs.3.rs-6375489/v1\",\"draftVersion\":[],\"editorialEvents\":[],\"editorialNote\":\"\",\"failedWorkflow\":false,\"files\":[{\"id\":82204657,\"identity\":\"e599c802-bf44-49e7-bd9a-a1ba20102430\",\"added_by\":\"auto\",\"created_at\":\"2025-05-07 16:56:23\",\"extension\":\"png\",\"order_by\":1,\"title\":\"Figure 1\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":186410,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003e\\u003cem\\u003e\\u003cstrong\\u003eLactate distribution value at each time point\\u003c/strong\\u003e\\u003c/em\\u003e\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"floatimage1.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-6375489/v1/f2636b7e9da19df5ce2b9e1f.png\"},{\"id\":82203622,\"identity\":\"606ece26-ddd3-4859-a3db-18f6c57adcef\",\"added_by\":\"auto\",\"created_at\":\"2025-05-07 16:48:23\",\"extension\":\"png\",\"order_by\":2,\"title\":\"Figure 2\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":216891,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003e\\u003cem\\u003e\\u003cstrong\\u003eLactate trend in the two groups with blood loss \\u0026lt; 500 or ≥ 500 ml\\u003c/strong\\u003e\\u003c/em\\u003e\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"floatimage2.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-6375489/v1/9ee9c26ac42befdd1dcfbab5.png\"},{\"id\":82203626,\"identity\":\"afaa90cd-f20b-4584-9cbb-8fe030cda4ec\",\"added_by\":\"auto\",\"created_at\":\"2025-05-07 16:48:23\",\"extension\":\"png\",\"order_by\":3,\"title\":\"Figure 3\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":223549,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003e\\u003cem\\u003e\\u003cstrong\\u003eLactate trend in labour according to parity\\u003c/strong\\u003e\\u003c/em\\u003e\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"floatimage3.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-6375489/v1/b68184950bb4bde1ba749040.png\"},{\"id\":82203629,\"identity\":\"82f80bd0-88ca-49cc-a12c-a3e979a726f0\",\"added_by\":\"auto\",\"created_at\":\"2025-05-07 16:48:24\",\"extension\":\"png\",\"order_by\":4,\"title\":\"Figure 4\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":287858,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003e\\u003cem\\u003e\\u003cstrong\\u003eCorrelation of lactate at T0, T1 and T2 with foetal pH values\\u003c/strong\\u003e\\u003c/em\\u003e\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"floatimage4.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-6375489/v1/5549aab378548539e5fdcfea.png\"},{\"id\":83979527,\"identity\":\"ebf3a8fb-6203-41d1-a527-9450d65a3965\",\"added_by\":\"auto\",\"created_at\":\"2025-06-05 09:39:04\",\"extension\":\"pdf\",\"order_by\":0,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"manuscript-pdf\",\"size\":1859475,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"manuscript.pdf\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-6375489/v1/7fb477aa-2cde-4ec4-a6da-80d290289f2c.pdf\"},{\"id\":82204658,\"identity\":\"55896260-6d4b-4674-857c-99f4f8e5852a\",\"added_by\":\"auto\",\"created_at\":\"2025-05-07 16:56:24\",\"extension\":\"pdf\",\"order_by\":0,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"supplement\",\"size\":292200,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"Supplementarymaterialpdf.pdf\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-6375489/v1/8f6c42d1ccf8d11e3cc11553.pdf\"}],\"financialInterests\":\"No competing interests reported.\",\"formattedTitle\":\"Lactate values during labour and their correlation with maternal and foetal outcome: a prospective observational single-centre study\",\"fulltext\":[{\"header\":\"Background\",\"content\":\"\\u003cp\\u003eLabour represents the physiological process whereby involuntary, rhythmic, and peristaltic contractions of the uterus lead to the effacement and dilation of the cervix, allowing the baby to pass through the birth canal.\\u003c/p\\u003e \\u003cp\\u003eRhythmic uterine contractions are controlled by several factors, including the release of catecholamines, oxytocin, and prostaglandins and a complex process called hypoxic-induced force increase (HIFI) (see Figure S2 in Supplementary Material)\\u003csup\\u003e\\u003cspan additionalcitationids=\\\"CR2 CR3\\\" citationid=\\\"CR1\\\" class=\\\"CitationRef\\\"\\u003e1\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR4\\\" class=\\\"CitationRef\\\"\\u003e4\\u003c/span\\u003e\\u003c/sup\\u003e.\\u003c/p\\u003e \\u003cp\\u003eEndogenous catecholamine concentrations increase throughout labour due to stress, pain, and physical effort, modulating uterine smooth muscle contractions, increasing endorphin production, and promoting the release of oxytocin\\u003csup\\u003e\\u003cspan citationid=\\\"CR3\\\" class=\\\"CitationRef\\\"\\u003e3\\u003c/span\\u003e\\u003c/sup\\u003e.\\u003c/p\\u003e \\u003cp\\u003eAdrenaline increases eightfold during labour compared to baseline levels and has a tocolytic effect, while norepinephrine has a uterotonic action\\u003csup\\u003e\\u003cspan citationid=\\\"CR3\\\" class=\\\"CitationRef\\\"\\u003e3\\u003c/span\\u003e\\u003c/sup\\u003e. Although both adrenaline and noradrenaline are increased, a tocolytic effect predominates; this effect is regulated by oxytocin\\u003csup\\u003e\\u003cspan citationid=\\\"CR5\\\" class=\\\"CitationRef\\\"\\u003e5\\u003c/span\\u003e\\u003c/sup\\u003e.\\u003c/p\\u003e \\u003cp\\u003eFurthermore, oxytocin stimulates the production of prostaglandins, which enhances the myometrium's sensitivity to oxytocin \\u003csup\\u003e\\u003cspan citationid=\\\"CR3\\\" class=\\\"CitationRef\\\"\\u003e3\\u003c/span\\u003e\\u003c/sup\\u003e.\\u003c/p\\u003e \\u003cp\\u003eThe last crucial process that regulates uterine contractility is the mechanism of HIFI. The myometrium contraction induces a brief hypoxic state, resulting in elevated lactate levels, decreased pH, and relaxation of the smooth muscle fibroblasts \\u003csup\\u003e\\u003cspan citationid=\\\"CR4\\\" class=\\\"CitationRef\\\"\\u003e4\\u003c/span\\u003e\\u003c/sup\\u003e.\\u003c/p\\u003e \\u003cp\\u003eDuring the hypoxic phase of HIFI, the pH and concentration of adenosine triphosphate (ATP) are reduced. The reduction of ATP concentration stimulates purinergic receptors (P2X7) that increase intracellular calcium levels and adenosine concentration. The adenosine increases calcium release from the sarcoplasmic reticulum and promotes actin-myosin binding.\\u003c/p\\u003e \\u003cp\\u003eAll these processes lead to an increase in force during subsequent uterine contractions\\u003csup\\u003e\\u003cspan citationid=\\\"CR4\\\" class=\\\"CitationRef\\\"\\u003e4\\u003c/span\\u003e\\u003c/sup\\u003e. This complex mechanism occurs only in the term-pregnant myometrium, with no analogous response (regarding enhanced contractile force) shown in the preterm or non-pregnant myometrium\\u003csup\\u003e\\u003cspan citationid=\\\"CR4\\\" class=\\\"CitationRef\\\"\\u003e4\\u003c/span\\u003e\\u003c/sup\\u003e.\\u003c/p\\u003e \\u003cp\\u003eTherefore, labour is a complex and strenuous experience that leads to a hypermetabolic state and substantial energy production. Such production is predominantly facilitated by adrenaline, which induces glycogenolysis and enhances glucose availability.\\u003c/p\\u003e \\u003cp\\u003eThe increase of lactate levels during labour is a physiological response resulting from hypoxic events that inhibit the oxidative pathway of the Krebs cycle and from excessive glycolysis, which produces elevated pyruvate levels that exceed mitochondrial oxidative capacity, thus promoting lactic acid production\\u003csup\\u003e\\u003cspan citationid=\\\"CR6\\\" class=\\\"CitationRef\\\"\\u003e6\\u003c/span\\u003e\\u003c/sup\\u003e.\\u003c/p\\u003e \\u003cp\\u003eThe lactate standard threshold in healthy people is up to 2 mmol/l. During labour, lactate levels higher than 2 mmol/l are observed\\u003csup\\u003e\\u003cspan citationid=\\\"CR7\\\" class=\\\"CitationRef\\\"\\u003e7\\u003c/span\\u003e\\u003c/sup\\u003e.\\u003c/p\\u003e \\u003cp\\u003eCurrently, reference ranges for lactic acid levels during labour remain undefined.\\u003c/p\\u003e \\u003cp\\u003eLactic acid is hypothesised to play a role in the mechanisms regulating labour, which functions as an inflammation inhibitor\\u003csup\\u003e\\u003cspan citationid=\\\"CR8\\\" class=\\\"CitationRef\\\"\\u003e8\\u003c/span\\u003e\\u003c/sup\\u003e and it has been shown that high lactate levels and a low pH exert a tocolytic effect on the myometrium\\u003csup\\u003e\\u003cspan citationid=\\\"CR9\\\" class=\\\"CitationRef\\\"\\u003e9\\u003c/span\\u003e\\u003c/sup\\u003e.\\u003c/p\\u003e \\u003cp\\u003ePostpartum haemorrhage (PPH) represents a significant cause of morbidity in the obstetric population, with a mortality rate of 140,000 women per year\\u003csup\\u003e\\u003cspan citationid=\\\"CR10\\\" class=\\\"CitationRef\\\"\\u003e10\\u003c/span\\u003e\\u003c/sup\\u003e, and the predominant cause of PPH (70%) is uterine atony\\u003csup\\u003e\\u003cspan citationid=\\\"CR11\\\" class=\\\"CitationRef\\\"\\u003e11\\u003c/span\\u003e\\u003c/sup\\u003e.\\u003c/p\\u003e \\u003cp\\u003eAs lactate levels may have an effect on the tone of the uterus, elevated levels during labour could influence maternal and foetal well-being.\\u003c/p\\u003e \\u003cp\\u003eWe decided to assess lactate concentrations during labour in women receiving neuraxial anaesthesia and evaluate the association between high lactate levels and adverse maternal and foetal outcomes.\\u003c/p\\u003e \\u003cp\\u003eThe primary aim of our study was to assess whether elevated lactate values during labour were associated with an increased risk of PPH.\\u003c/p\\u003e \\u003cp\\u003eOur secondary aims were to assess lactate levels at different stages of labour and investigate whether there was any association between lactate concentrations and neonatal cord pH on delivery.\\u003c/p\\u003e\"},{\"header\":\"Methods\",\"content\":\"\\u003cdiv id=\\\"Sec3\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eStudy Design and Participants\\u003c/h2\\u003e \\u003cp\\u003eWe conducted a prospective observational single-centre study involving women in active labour receiving neuraxial anaesthesia.\\u003c/p\\u003e \\u003cp\\u003e Consecutive women in labour with neuraxial analgesia were recruited from May to September 2023 in the labour ward of ASST Papa Giovanni XXIII hospital (Bergamo, Italy), a tertiary care referral centre (Italian Ministerial Decree n. 70/2015) for obstetric care in the north of Italy.\\u003c/p\\u003e \\u003cp\\u003e Before enrolment, all women received written information about the study, signed an informed consent form, and were informed about the processing of their personal or clinical data.\\u003c/p\\u003e \\u003cp\\u003ePatients included in the study were \\u0026ge;\\u0026thinsp;18 years old, had a single pregnancy with a gestational age of \\u0026ge;\\u0026thinsp;36 weeks, were in active labour with a cervix dilation of 4 to 6 cm, received neuraxial analgesia and gave their informed consent to the study.\\u003c/p\\u003e \\u003cp\\u003eExclusion criteria were age\\u0026thinsp;\\u0026lt;\\u0026thinsp;18 years, twin pregnancy, gestational age\\u0026thinsp;\\u0026lt;\\u0026thinsp;36 weeks, women in labour without labour analgesia, cervix dilation\\u0026thinsp;\\u0026gt;\\u0026thinsp;6 cm at the moment of the placement of neuraxial analgesia, and women who did not informed consent to the study.\\u003c/p\\u003e \\u003cp\\u003e The study design was approved by the ethical committee of ASST Papa Giovanni XXIII Hospital in May 2023 (REF: no. 751/2023, reg 56/23). ClinicalTrials.gov identifier NCT06807255.\\u003c/p\\u003e \\u003cp\\u003eAll methods were performed in conformity with the Declaration of Helsinki, and the study was designed and presented in accordance with the STROBE guidelines\\u003csup\\u003e\\u003cspan citationid=\\\"CR12\\\" class=\\\"CitationRef\\\"\\u003e12\\u003c/span\\u003e\\u003c/sup\\u003e.\\u003c/p\\u003e \\u003c/div\\u003e\\n\\u003ch3\\u003eStudy outcomes\\u003c/h3\\u003e\\n\\u003cp\\u003eThe primary aim of our study was to assess whether lactate levels at three specific time points are associated with postpartum haemorrhage.\\u003c/p\\u003e \\u003cp\\u003eThe secondary aims were to assess lactate levels at different stages of labour, compare them depending on parity and mode of labour onset, and assess whether there is any association between lactate concentrations and neonatal pH at delivery.\\u003c/p\\u003e\\n\\u003ch3\\u003eProcedures – Labour analgesia\\u003c/h3\\u003e\\n\\u003cp\\u003eLabour analgesia was placed at the beginning of active labour, which is considered to be between 4 and 6 cm of cervix dilatation\\u003csup\\u003e\\u003cspan citationid=\\\"CR13\\\" class=\\\"CitationRef\\\"\\u003e13\\u003c/span\\u003e,\\u003cspan citationid=\\\"CR14\\\" class=\\\"CitationRef\\\"\\u003e14\\u003c/span\\u003e\\u003c/sup\\u003e.\\u003c/p\\u003e \\u003cp\\u003eThe labour analgesia technique consisted of standard epidural or dural puncture epidural (DPE); analgesia was maintained by intermittent clinician boluses on maternal request. The chosen local anaesthetic was ropivacaine, whose concentration was increased (from 0.1% up to 0.15%, for a total volume of 15 to 20 ml) based on cervical dilatation and foetal head position at the time of the bolus administration. For each bolus, Sufentanil was added (10\\u0026thinsp;\\u0026minus;\\u0026thinsp;5 mcg in epidural technique and 7,5\\u0026thinsp;\\u0026minus;\\u0026thinsp;3,75 mcg in DPE).\\u003c/p\\u003e\\n\\u003ch3\\u003eData collection\\u003c/h3\\u003e\\n\\u003cp\\u003eWe recorded the following demographic and clinical information: age, pre-pregnancy and postpartum body mass index (BMI), gestational age, parity, mode of onset of labour (spontaneous vs. induction), duration of each stage of labour, total postpartum blood loss at the end of the third stage of labour, and umbilical artery foetal pH.\\u003c/p\\u003e \\u003cp\\u003eLactate levels were assessed by blood gas analysis on samples obtained from the women\\u0026rsquo;s indwelling peripheral venous cannulae; subsequent analysis was conducted using the point-of-care emogasanalyser 500 Systems\\u0026ndash;Siemens (Siemens, Milano) at three time points. The three time points were as follows: T0: at the time of diagnosis of the active phase of the first stage of labour, T1: at the beginning of the active phase of the second stage of labour, at the beginning of active pushing, and T2: at the time of the delivery, before placenta expulsion.\\u003c/p\\u003e \\u003cp\\u003ePostpartum haemorrhage (PPH) has been defined following the definition of the Royal College of Obstetricians and Gynaecologists as a total blood loss\\u0026thinsp;\\u003cspan type=\\\"Underline\\\" class=\\\"Underline\\\" name=\\\"Emphasis\\\"\\u003e\\u0026ge;\\u003c/span\\u003e\\u0026thinsp;500 ml\\u003csup\\u003e\\u003cspan citationid=\\\"CR15\\\" class=\\\"CitationRef\\\"\\u003e15\\u003c/span\\u003e\\u003c/sup\\u003e. Our population was divided into two groups: those with total blood loss\\u0026thinsp;\\u0026lt;\\u0026thinsp;500 ml and those with blood loss\\u0026thinsp;\\u003cspan type=\\\"Underline\\\" class=\\\"Underline\\\" name=\\\"Emphasis\\\"\\u003e\\u0026ge;\\u003c/span\\u003e\\u0026thinsp;500 ml.\\u003c/p\\u003e \\u003cp\\u003eTo measure umbilical cord pH, 1\\u0026ndash;2 ml of cord blood was taken from the umbilical artery one minute after birth, regardless of clamping. The analysis was conducted with the point-of-care emogasanalyser 500 Systems blood gas analyser, Siemens (Siemens, Milan).\\u003c/p\\u003e \\u003cdiv id=\\\"Sec7\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eStatistical Analysis\\u003c/h2\\u003e \\u003cp\\u003eBaseline characteristics were described as mean (standard deviation, SD), median (I-III quartile), and absolute and relative frequencies, as appropriate.\\u003c/p\\u003e \\u003cp\\u003eDifferences between groups (e.g., nulliparous/multiparous) of lactate levels at each time point were assessed by t-tests or Mann-Whitney U, following the nature of the variable.\\u003c/p\\u003e \\u003cp\\u003eTo evaluate the variation of lactate over time, an initial exploratory analysis was conducted graphically using a spaghetti plot. Then, mixed-effects models were applied to evaluate the effect of postpartum haemorrhage and other clinically relevant variables on lactate variation.\\u003c/p\\u003e \\u003cp\\u003eFinally, the relationships between lactate levels at each time point and the neonatal pH were also explored by the Pearson index (r) and its associated p-value.\\u003c/p\\u003e \\u003cp\\u003eThe tests were two-sided with a type I error set at a significance level of 0.05. All analyses were performed using R (version 4.3.1).\\u003c/p\\u003e \\u003c/div\\u003e\"},{\"header\":\"Results\",\"content\":\"\\u003cdiv id=\\\"Sec9\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eStudy population\\u003c/h2\\u003e \\u003cp\\u003eBetween May and September 2023, we enrolled 381 women who were in active labour and had received neuraxial analgesia. Thirty-one cases were excluded from the analysis due to caesarean section delivery, and forty-seven were excluded due to incomplete data (the enrolment process is shown in Fig. \\u003cspan refid=\\\"MOESM1\\\" class=\\\"InternalRef\\\"\\u003eS1\\u003c/span\\u003e in the supplementary material). We conducted the final analysis on 303 women, 242 of whom were nulliparous and 61 were multiparous.\\u003c/p\\u003e \\u003cp\\u003eThe demographic, clinical, and labour characteristics of our study population are shown in Table\\u0026nbsp;\\u003cspan refid=\\\"Tab1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e. The mean age was 32.02 (SD\\u0026thinsp;=\\u0026thinsp;4.71) years, with a mean gestational age of 39.59 weeks, and the median pre-pregnancy BMI was equal to 21.8 (I-III quartile\\u0026thinsp;=\\u0026thinsp;19.8\\u0026ndash;24.2).\\u003c/p\\u003e \\u003cp\\u003e \\u003cdiv class=\\\"gridtable\\\"\\u003e\\u003ctable float=\\\"Yes\\\" id=\\\"Tab1\\\" border=\\\"1\\\"\\u003e \\u003ccaption language=\\\"En\\\"\\u003e \\u003cdiv class=\\\"CaptionNumber\\\"\\u003eTable 1\\u003c/div\\u003e \\u003cdiv class=\\\"CaptionContent\\\"\\u003e \\u003cp\\u003eDemographic and clinical data of the study population\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/caption\\u003e \\u003ccolgroup cols=\\\"2\\\"\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c1\\\" colnum=\\\"1\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c2\\\" colnum=\\\"2\\\"\\u003e\\u003c/div\\u003e \\u003cthead\\u003e \\u003ctr\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u0026nbsp;\\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e\\u003cem\\u003eOverall\\u003c/em\\u003e\\u003c/p\\u003e \\u003c/th\\u003e \\u003c/tr\\u003e \\u003c/thead\\u003e \\u003ctbody\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003en\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e303\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eAge, mean (SD)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e32.02 (4.71)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eBMI prepregnancy, median (I-III quartile)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e21.80 [19.80, 24.20]\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eBMI post-pregnancy, median (I-III quartile)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e26.60 [24.65, 29.45]\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eGestational age\\u0026thinsp;\\u0026ge;\\u0026thinsp;40 weeks, n (%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e138 (45.5)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eGestational age, weeks, mean (SD)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e39.59 (1.19)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eNulliparous n (%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e242 (79.9)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eSpontaneous labour n (%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e191 (63.0)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eLength of first stage, minutes, median (I-III quartile)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e240.00 [137.50, 315.00]\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eLength of the second stage, minutes, median (I-III quartile)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e47.00 [25.50, 75.00]\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003c/tbody\\u003e \\u003c/colgroup\\u003e \\u003ctfoot\\u003e \\u003ctr\\u003e\\u003ctd colspan=\\\"2\\\"\\u003eAbbreviations: BMI\\u0026thinsp;=\\u0026thinsp;body mass index\\u003c/td\\u003e\\u003c/tr\\u003e \\u003c/tfoot\\u003e \\u003c/table\\u003e\\u003c/div\\u003e \\u003c/p\\u003e \\u003c/div\\u003e\\n\\u003ch3\\u003eLactate levels over time\\u003c/h3\\u003e\\u003cp\\u003eFigure 1 illustrates the distribution of lactate levels at each time point measured. The mean at T0 was 1.83 (SD = 0.68), and it increased over time from the onset of labour to delivery. At T1 and T2, median lactate values are higher than 2 mmol/L (T1 = 2.84, SD = 1.32, and T2 = 3.80, SD = 1.56).\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003e \\u003c/p\\u003e \\u003cdiv id=\\\"Sec11\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003ePostpartum haemorrhage\\u003c/h2\\u003e \\u003cp\\u003eThe median total postpartum blood loss was 400 ml (I-III quartile\\u0026thinsp;=\\u0026thinsp;300\\u0026ndash;600). 110 (36.3%) patients had blood loss of less than 500 ml.\\u003c/p\\u003e \\u003cp\\u003eNo differences were found between the two groups (\\u003cspan type=\\\"Underline\\\" class=\\\"Underline\\\" name=\\\"Emphasis\\\"\\u003e\\u0026ge;\\u003c/span\\u003e\\u0026thinsp;500 ml vs. \\u0026lt; 500 ml) in lactate values at three time points and in changes over time from T0 (Table\\u0026nbsp;\\u003cspan refid=\\\"Tab3\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003eA and B; Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig2\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003e). Considering the linear mixed models, both blood loss and the interaction term (time and blood loss) were not statistically significant (p\\u0026thinsp;=\\u0026thinsp;0.574 and p\\u0026thinsp;=\\u0026thinsp;0.211, respectively).\\u003c/p\\u003e \\u003cp\\u003e \\u003c/p\\u003e \\u003cp\\u003e \\u003c/p\\u003e \\u003cp\\u003eFurther analysis showed no statistically significant difference in lactate values even with blood losses\\u0026thinsp;\\u0026gt;\\u0026thinsp;1000 ml (p\\u0026thinsp;=\\u0026thinsp;0.446) or \\u0026gt;\\u0026thinsp;1500 ml (p\\u0026thinsp;=\\u0026thinsp;0.471).\\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec12\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eLactate, parity and labour induction\\u003c/h2\\u003e \\u003cp\\u003eOf the 303 patients, 242 were nulliparous, and 61 were multiparous. Detailed results are illustrated in Table\\u0026nbsp;\\u003cspan refid=\\\"Tab2\\\" class=\\\"InternalRef\\\"\\u003e3\\u003c/span\\u003e.\\u003c/p\\u003e \\u003cp\\u003e\\u003cstrong\\u003eTable 2 - Mean differences between blood loss at each time point (A) and change from T0 of lactate value between the blood loss \\u003cu\\u003e\\u0026gt;\\u003c/u\\u003e 500 ml and \\u0026lt; 500 ml (B).\\u003c/strong\\u003e\\u003cstrong\\u003e\\u0026nbsp;\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003ctable border=\\\"1\\\" cellspacing=\\\"0\\\" cellpadding=\\\"0\\\" width=\\\"646\\\"\\u003e\\n \\u003ctbody\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 19.6594%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eA.\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 19.969%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eMean (SD)\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20.2786%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003e\\u0026nbsp;\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 30.031%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eDifference blood loss \\u0026lt; 500 \\u0026ndash; blood loss\\u0026nbsp;\\u003c/strong\\u003e\\u003cu\\u003e\\u0026gt;\\u003c/u\\u003e \\u003cstrong\\u003e500 (CI 95%)\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 10.0619%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003ep-value\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 19.6594%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eTime point\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 19.969%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eBlood loss \\u0026lt; 500\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20.2786%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eBlood loss\\u0026nbsp;\\u003c/strong\\u003e\\u003cu\\u003e\\u0026gt;\\u003c/u\\u003e 500\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 30.031%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003e\\u0026nbsp;\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 10.0619%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003e\\u0026nbsp;\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 19.6594%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eT0\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 19.969%;\\\"\\u003e\\n \\u003cp\\u003e1.85 (0.65)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20.2786%;\\\"\\u003e\\n \\u003cp\\u003e1.78 (0.75)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 30.031%;\\\"\\u003e\\n \\u003cp\\u003e0.07 (-0.09; 0.24)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 10.0619%;\\\"\\u003e\\n \\u003cp\\u003e0.406\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 19.6594%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eT1\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 19.969%;\\\"\\u003e\\n \\u003cp\\u003e2.83 (1.38)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20.2786%;\\\"\\u003e\\n \\u003cp\\u003e2.84 (1.22)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 30.031%;\\\"\\u003e\\n \\u003cp\\u003e0.01 (-0.31; 0.29)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 10.0619%;\\\"\\u003e\\n \\u003cp\\u003e0.947\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 19.6594%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eT2\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 19.969%;\\\"\\u003e\\n \\u003cp\\u003e3.84 (1.61)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20.2786%;\\\"\\u003e\\n \\u003cp\\u003e3.98 (1.49)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 30.031%;\\\"\\u003e\\n \\u003cp\\u003e0.14 (-0.50; 0.22)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 10.0619%;\\\"\\u003e\\n \\u003cp\\u003e0.439\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 19.6594%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eB.\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 19.969%;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20.2786%;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 30.031%;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 10.0619%;\\\"\\u003e\\n \\u003cp\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 19.6594%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eT0 - T1\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 19.969%;\\\"\\u003e\\n \\u003cp\\u003e0.98 (1.35)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20.2786%;\\\"\\u003e\\n \\u003cp\\u003e1.058 (1.26)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 30.031%;\\\"\\u003e\\n \\u003cp\\u003e0.07 (-0.39; 0.22)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 10.0619%;\\\"\\u003e\\n \\u003cp\\u003e0.601\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 19.6594%;\\\"\\u003e\\n \\u003cp\\u003e\\u003cstrong\\u003eT0 - T2\\u003c/strong\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 19.969%;\\\"\\u003e\\n \\u003cp\\u003e1.99 (1.51)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 20.2786%;\\\"\\u003e\\n \\u003cp\\u003e2.19 (1.42)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 30.031%;\\\"\\u003e\\n \\u003cp\\u003e0.21 (-0.56; 0.13)\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd valign=\\\"top\\\" style=\\\"width: 10.0619%;\\\"\\u003e\\n \\u003cp\\u003e0.223\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003c/tbody\\u003e\\n\\u003c/table\\u003e\\u003cp\\u003e \\u003cdiv class=\\\"gridtable\\\"\\u003e\\u003ctable float=\\\"Yes\\\" id=\\\"Tab2\\\" border=\\\"1\\\"\\u003e \\u003ccaption language=\\\"En\\\"\\u003e \\u003cdiv class=\\\"CaptionNumber\\\"\\u003eTable 3\\u003c/div\\u003e \\u003cdiv class=\\\"CaptionContent\\\"\\u003e \\u003cp\\u003eLactate values at the three time points and lactate values change in time among the two groups (parity and mode of onset of labour)\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/caption\\u003e \\u003ccolgroup cols=\\\"5\\\"\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c1\\\" colnum=\\\"1\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c2\\\" colnum=\\\"2\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c3\\\" colnum=\\\"3\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c4\\\" colnum=\\\"4\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c5\\\" colnum=\\\"5\\\"\\u003e\\u003c/div\\u003e \\u003cthead\\u003e \\u003ctr\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u0026nbsp;\\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eMean (SD)\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003eDifference nulliparous - multiparous (CI 95%)\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e\\u003cem\\u003ep-value\\u003c/em\\u003e\\u003c/p\\u003e \\u003c/th\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cem\\u003eTime\\u003c/em\\u003e\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e\\u003cem\\u003eNulliparous (n\\u0026thinsp;=\\u0026thinsp;242)\\u003c/em\\u003e\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e\\u003cem\\u003eMultiparous\\u003c/em\\u003e\\u003c/p\\u003e \\u003cp\\u003e\\u003cem\\u003e(n\\u0026thinsp;=\\u0026thinsp;61)\\u003c/em\\u003e\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/th\\u003e \\u003c/tr\\u003e \\u003c/thead\\u003e \\u003ctbody\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eT0\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e1.85 (0.62)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e1.75 (0.88)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.10 (-0.13; 0.35)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.3721\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eT1\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e2.92 (1.36)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e2.53 (1.10)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.39 (0.06; 0.72)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003e0.019\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eT2\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e4.06 (1.58)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e3.23 (1.30)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.83 (0.45; 1.22)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003e\\u0026lt;\\u0026thinsp;0.001\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eChanges in time\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eT0-T1\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e1.06 (1.30)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e0.77 (1.35)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.29 (-0.09; 0.67)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.141\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eT0-T2\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e2.21 (1.45)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e1.47 (1.45)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.80 (0.32; 1.14)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003e\\u0026lt;\\u0026thinsp;0.001\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eInduction of labour\\u003c/b\\u003e\\u003c/p\\u003e \\u003cp\\u003e\\u003cb\\u003e(n\\u0026thinsp;=\\u0026thinsp;112)\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eSpontaneous labour\\u003c/b\\u003e\\u003c/p\\u003e \\u003cp\\u003e\\u003cb\\u003e(n\\u0026thinsp;=\\u0026thinsp;191)\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eDifference induced \\u0026ndash; spontaneous labour (CI 95%)\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003ep-value\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eTime\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eT0\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e1.80 (0.67)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e1.85 (0.69)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.05 (-0.11; 0.21)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.511\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eT1\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e2.93 (1.49)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e2.79 (1.22)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.14 (-0.47; 0.19)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.404\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eT2\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e3.89 (1.59)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e3.90 (1.55)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.01 (-0.36; 0.38)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.959\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eChanges in time\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eT0-T1\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e0.94 (1.18)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e1.13 (1.51)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.19 (-0.52; 0.14)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.251\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eT0-T2\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e2.04 (1.43)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e2.08 (1.55)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.04 (-0.39; 0.31)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.808\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003c/tbody\\u003e \\u003c/colgroup\\u003e \\u003ctfoot\\u003e \\u003ctr\\u003e\\u003ctd colspan=\\\"5\\\"\\u003eData are expressed in Mean and Standard Deviation\\u003c/td\\u003e\\u003c/tr\\u003e \\u003c/tfoot\\u003e \\u003c/table\\u003e\\u003c/div\\u003e \\u003c/p\\u003e \\u003cp\\u003eAs shown, significant differences were found among nulliparous and multiparous women in the time points T1 and T2 (differences among groups 0.39, CI 95% = 0.06; 0.72, p\\u0026thinsp;=\\u0026thinsp;0.019 and 0.83, CI 95% = 0.45; 1.22, p\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.001, at T1 and T2, respectively). This result is confirmed considering the lactate change in time T2 - T0 (0.80, CI 95% = 0.32; 1.14, p\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.001; Table\\u0026nbsp;\\u003cspan refid=\\\"Tab2\\\" class=\\\"InternalRef\\\"\\u003e3\\u003c/span\\u003e and Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig3\\\" class=\\\"InternalRef\\\"\\u003e3\\u003c/span\\u003e) and in the linear mixed model (interaction term, p\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.001).\\u003c/p\\u003e \\u003cp\\u003e \\u003c/p\\u003e \\u003cp\\u003e \\u003c/p\\u003e \\u003cp\\u003eRegarding the mode of onset of labour, 191 women entered labour spontaneously, while 112 women underwent an induction of labour\\u003c/p\\u003e \\u003cp\\u003eAmong these two groups, the lactate trend did not show statistically significant differences at T0, T1, and T2 and in the change from T0 (Table\\u0026nbsp;\\u003cspan refid=\\\"Tab2\\\" class=\\\"InternalRef\\\"\\u003e3\\u003c/span\\u003e).\\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec13\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eLactate and foetal pH\\u003c/h2\\u003e \\u003cp\\u003eThe mean value of foetal pH (umbilical artery sampling) was 7.268, SD\\u0026thinsp;=\\u0026thinsp;0.10. There was no statistically significant correlation between lactate levels at any time point and foetal pH: at T0, the correlation index \\u0026reg; = -0.03, p\\u0026thinsp;=\\u0026thinsp;0.566, at T1 r\\u0026thinsp;=\\u0026thinsp;0.01, p\\u0026thinsp;=\\u0026thinsp;0.914, and at T2 r = -0.1 and p\\u0026thinsp;=\\u0026thinsp;0.073 (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig4\\\" class=\\\"InternalRef\\\"\\u003e4\\u003c/span\\u003e).\\u003c/p\\u003e \\u003cp\\u003e \\u003c/p\\u003e \\u003cp\\u003e \\u003c/p\\u003e \\u003c/div\\u003e\"},{\"header\":\"Discussion\",\"content\":\"\\u003cp\\u003eIt has been hypothesised that lactic acid acts as an inhibitor of inflammation and that low pH and high lactate levels may have a tocolytic effect on the myometrium\\u003csup\\u003e\\u003cspan class=\\\"CitationRef\\\"\\u003e8\\u003c/span\\u003e\\u003c/sup\\u003e.\\u003c/p\\u003e\\n\\u003cp\\u003eOur study shows no statistically significant difference in lactate values at the three time points between women with blood losses less than or equal to or more than 500 ml (Table \\u003cspan class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003e). Subsequent exploratory analysis reveals that this holds true with blood losses exceeding 1000 or 1500 ml.\\u003c/p\\u003e\\n\\u003cp\\u003eLactate levels do not correlate with an increased incidence of PPH, and the correction with buffer substances\\u003csup\\u003e\\u003cspan class=\\\"CitationRef\\\"\\u003e16\\u003c/span\\u003e\\u003c/sup\\u003e neither alters these levels nor mitigates the risk of PPH. Thus, lactate during labour should not be regarded exclusively as a biomarker of hypoxia and cellular damage.\\u003c/p\\u003e\\n\\u003cp\\u003eThe tocolytic effect of lactate is modulated by oxytocin as demonstrated by in vitro studies\\u003csup\\u003e\\u003cspan class=\\\"CitationRef\\\"\\u003e9\\u003c/span\\u003e\\u003c/sup\\u003e; then, lactate production in labour is likely a typical physiological response of the organism.\\u003c/p\\u003e\\n\\u003cp\\u003eIn the general population, plasma lactate levels remain up to 2 mmol/L in health\\u003csup\\u003e\\u003cspan class=\\\"CitationRef\\\"\\u003e7\\u003c/span\\u003e\\u003c/sup\\u003e.\\u003c/p\\u003e\\n\\u003cp\\u003eIn our population, at the onset of active labour (T0), the average lactate values were below 2 mmol/L, while at the start of the active phase of the second stage (T1) and at delivery (T2), the median lactate values were higher than 2 mmol/L (Fig.\\u0026nbsp;\\u003cspan class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e).\\u003c/p\\u003e\\n\\n\\u003cp\\u003eThis is in keeping with a meta-analysis by Baur et al. in 2018\\u003csup\\u003e7\\u003c/sup\\u003e that assessed lactate concentrations in healthy pregnant women during gestation and labour. They identified 22 studies involving 1193 patients to show that women have venous lactate levels below 2 mmol/L during pregnancy and between 2 and 4 mmol/L during active labour. During the second stage and at delivery, some studies reported lactate levels above 4 mmol/L.\\u003c/p\\u003e\\n\\u003cp\\u003eThe limitation of this meta-analysis is that it includes studies whose populations analysed show significant heterogeneity.\\u003c/p\\u003e\\n\\u003cp\\u003eThe role of neuraxial analgesia in modulating the neuroendocrine aspects of labour is well established. By modulating pain, neuroaxial analgesia diminishes catecholamine levels during labour, reduces endorphin production, and decreases oxytocin concentrations. These modifications make it challenging to compare women with analgesia with women without analgesia during labour\\u003csup\\u003e\\u003cspan class=\\\"CitationRef\\\"\\u003e3\\u003c/span\\u003e\\u003c/sup\\u003e.\\u003c/p\\u003e\\n\\u003cp\\u003eAs early as 1991, Piquard was among the first to recognise the significance of differentiating between women undergoing neuraxial analgesia and those not receiving analgesia\\u003csup\\u003e\\u003cspan class=\\\"CitationRef\\\"\\u003e17\\u003c/span\\u003e\\u003c/sup\\u003e.\\u003c/p\\u003e\\n\\u003cp\\u003eComparing our findings with Piquard\\u0026rsquo;s, lactate levels at T2 in our population are almost 1 mmol higher than levels reported by Piquard in patients with neuraxial analgesia. This discrepancy may be attributed to the prevalence of multiparous patients compared to primiparous patients in the cohort examined by Piquard.\\u003c/p\\u003e\\n\\u003cp\\u003eLabour is a complex phenomenon influenced by numerous elements, including parity and the mode of onset of labour \\u003csup\\u003e\\u003cspan class=\\\"CitationRef\\\"\\u003e13\\u003c/span\\u003e,\\u003cspan class=\\\"CitationRef\\\"\\u003e18\\u003c/span\\u003e\\u003c/sup\\u003e.\\u003c/p\\u003e\\n\\u003cp\\u003eOur sub-analysis indicates that lactate generation during labour is diminished in multiparous women compared to nulliparous women, with statistically significant differences observed at T1 and T2 (p\\u0026thinsp;=\\u0026thinsp;0.019 and p\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.001, respectively; see Table\\u0026nbsp;\\u003cspan class=\\\"InternalRef\\\"\\u003e3\\u003c/span\\u003e). Our findings are echoed by the research conducted by Schneider et al. in 1990. However, the population analysed in that study did not receive neuraxial analgesia\\u003csup\\u003e\\u003cspan class=\\\"CitationRef\\\"\\u003e19\\u003c/span\\u003e\\u003c/sup\\u003e.\\u003c/p\\u003e\\n\\u003cp\\u003eMultiparous women likely exhibit reduced metabolic exertion during the expulsion phase, which is typically more rapid and has more favourable outcomes, with a diminished risk of surgical intervention compared to nulliparous women\\u003csup\\u003e\\u003cspan class=\\\"CitationRef\\\"\\u003e18\\u003c/span\\u003e,\\u003cspan class=\\\"CitationRef\\\"\\u003e20\\u003c/span\\u003e\\u003c/sup\\u003e.\\u003c/p\\u003e\\n\\u003cp\\u003eParity may affect activation levels of myometrial cells during labour; specifically, in multiparous women, the receptors for oxytocin are more sensitive and easily inducible\\u003csup\\u003e\\u003cspan class=\\\"CitationRef\\\"\\u003e21\\u003c/span\\u003e\\u003c/sup\\u003e.\\u003c/p\\u003e\\n\\u003cp\\u003eFinally, various hormonal mechanisms are implicated, including a difference in beta-endorphin concentration between multiparous and nulliparous women\\u003csup\\u003e\\u003cspan class=\\\"CitationRef\\\"\\u003e3\\u003c/span\\u003e,\\u003cspan class=\\\"CitationRef\\\"\\u003e22\\u003c/span\\u003e\\u003c/sup\\u003e.\\u003c/p\\u003e\\n\\u003cp\\u003eAll these characteristics likely lead to a less significant increase in lactate at the end of the second stage. This supports the role of lactic acid as a physiological marker of metabolic stress of labour.\\u003c/p\\u003e\\n\\u003cp\\u003eClinicians could benefit from understanding the \\u0026quot;physiological\\u0026quot; lactate values after delivery to ensure the accurate interpretation of lactate, even in the event of complications in the immediate postpartum period.\\u003c/p\\u003e\\n\\u003cp\\u003eThe literature reports that induced labour is more painful and prolonged\\u003csup\\u003e\\u003cspan class=\\\"CitationRef\\\"\\u003e18\\u003c/span\\u003e,\\u003cspan class=\\\"CitationRef\\\"\\u003e23\\u003c/span\\u003e,\\u003cspan class=\\\"CitationRef\\\"\\u003e24\\u003c/span\\u003e\\u003c/sup\\u003e and associated with less favourable outcomes. However, our study (where all participants received neuraxial analgesia) did not observe any statistically significant differences in lactate levels between induced and non-induced labour (Table\\u0026nbsp;\\u003cspan class=\\\"InternalRef\\\"\\u003e3\\u003c/span\\u003e).\\u003c/p\\u003e\\n\\u003cp\\u003eThus, we can assume that neuraxial analgesia effectively attenuates the increased metabolic stress seen during induction of labour but does not influence the metabolic stress in nulliparous women.\\u003c/p\\u003e\\n\\u003cp\\u003eTo our knowledge, no previous study has compared lactate production in relation to the mode of labour onset.\\u003c/p\\u003e\\n\\u003cp\\u003eIntrapartum foetal hypoxia potentially increases the foetal risk of asphyxia, acidosis, neuronal damage, long-term morbidity, or even death\\u003csup\\u003e\\u003cspan class=\\\"CitationRef\\\"\\u003e25\\u003c/span\\u003e\\u003c/sup\\u003e. Blood gas analysis of umbilical blood samples is the only method for objectively measuring the incidence of foetal acidosis or hypoxia\\u003csup\\u003e\\u003cspan class=\\\"CitationRef\\\"\\u003e26\\u003c/span\\u003e\\u003c/sup\\u003e.\\u003c/p\\u003e\\n\\u003cp\\u003eAmong the secondary endpoints, we studied the correlation between maternal venous lactate and foetal pH.\\u003c/p\\u003e\\n\\u003cp\\u003eWe have shown no statistically significant correlation between lactate at the three distinct time points and foetal pH (Fig.\\u0026nbsp;\\u003cspan class=\\\"InternalRef\\\"\\u003e4\\u003c/span\\u003e).\\u003c/p\\u003e\\n\\u003cp\\u003eOur findings corroborate those previously published by Piquard et al. \\u003csup\\u003e\\u003cspan class=\\\"CitationRef\\\"\\u003e17\\u003c/span\\u003e\\u003c/sup\\u003e. The authors observed that the lactate concentration in the mother\\u0026apos;s venous blood and cord arterial blood was in equilibrium at birth after elective caesarean sections. However, during labour, foetal and maternal lactate levels changed independently. The authors discovered that in hyporeactive newborns, the lactate concentration in cord blood exceeded that in maternal venous blood, suggesting foetal lactate production.\\u003c/p\\u003e\\n\\u003cp\\u003eFurther analyses are required to study the relationship between maternal lactate levels and foetal well-being.\\u003c/p\\u003e\\n\\u003cp\\u003eThe women in our research represented a homogeneous population as they all received neuraxial analgesia.\\u003c/p\\u003e\\n\\u003cp\\u003eWhile this makes the outcome data reliable, it is also a limitation of the study, as the findings of the study are applicable only to women with neuraxial analgesia.\\u003c/p\\u003e\\n\\u003cp\\u003eTherefore, further research is necessary to investigate lactate levels in women without analgesia.\\u003c/p\\u003e\"},{\"header\":\"Conclusion\",\"content\":\"\\u003cp\\u003eLabour is a complex physiological event with specific metabolic characteristics, unlike any other human experience.\\u003c/p\\u003e \\u003cp\\u003eThe absence of a correlation between maternal lactate and adverse maternal-foetal outcomes\\u003c/p\\u003e \\u003cp\\u003esuggests that lactate is not exclusively a marker of cellular hypoxia. It has been hypothesised that elevated levels of lactate may represent a marker for the metabolic stress of labour and/or serve as a physiological source of energy produced and utilised by the uterus under stressful conditions, such as during labour.\\u003c/p\\u003e \\u003cp\\u003eIdentifying reference values of lactate levels at the different stages of labour could be used clinically in the future to evaluate the progress of labour whose dynamics are not fully understood. Further research is essential to clarify the role of lactate during labour.\\u003c/p\\u003e \"},{\"header\":\"Declarations\",\"content\":\"\\u003ch2\\u003e\\u003cstrong\\u003eData availability\\u003c/strong\\u003e\\u003c/h2\\u003e\\n\\u003cp\\u003e\\u0026nbsp;The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.\\u003c/p\\u003e\\n\\u003cp\\u003eAuthors Contributions\\u003c/p\\u003e\\n\\u003cp\\u003eBM and GF conceptualized the study and drafted the manuscript. IR drafted the manuscript and acquired the data. FG analysed and interpreted the data. VR drafted the manuscript. NS, EB, SMB acquired the data. FLL supervised the study. All authors read and approved the final version of the manuscript for publication.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u0026nbsp;\\u003cstrong\\u003eCompeting interests\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThe authors declare no competing interests.\\u0026nbsp;\\u003c/p\\u003e\"},{\"header\":\"References\",\"content\":\"\\u003col\\u003e\\n\\u003cli\\u003eArrowsmith, S., Kendrick, A., Hanley, J., Noble, K. \\u0026amp; Wray, S. Myometrial physiology \\u0026ndash; time to translate? \\u003cem\\u003eExp Physiol\\u003c/em\\u003e 99, 495\\u0026ndash;502 (2014).\\u003c/li\\u003e\\n\\u003cli\\u003eArrowsmith, S. \\u0026amp; Wray, S. Oxytocin: Its Mechanism of Action and Receptor Signalling in the Myometrium. \\u003cem\\u003eJ Neuroendocrinol\\u003c/em\\u003e 26, 356\\u0026ndash;369 (2014).\\u003c/li\\u003e\\n\\u003cli\\u003eBuckley, S. J. Executive Summary of \\u003cem\\u003eHormonal Physiology of Childbearing: Evidence and Implications for Women, Babies, and Maternity Care\\u003c/em\\u003e. \\u003cem\\u003eJ Perinat Educ\\u003c/em\\u003e 24, 145\\u0026ndash;153 (2015).\\u003c/li\\u003e\\n\\u003cli\\u003eAlotaibi, M., Arrowsmith, S. \\u0026amp; Wray, S. Hypoxia-induced force increase (HIFI) is a novel mechanism underlying the strengthening of labor contractions, produced by hypoxic stresses. \\u003cem\\u003eProceedings of the National Academy of Sciences\\u003c/em\\u003e 112, 9763\\u0026ndash;9768 (2015).\\u003c/li\\u003e\\n\\u003cli\\u003eSegal, S., Csavoy, A. N. \\u0026amp; Datta, S. The Tocolytic Effect of Catecholamines in the Gravid Rat Uterus. \\u003cem\\u003eAnesth Analg\\u003c/em\\u003e 87, 864\\u0026ndash;869 (1998).\\u003c/li\\u003e\\n\\u003cli\\u003eMarik, P. \\u0026amp; Bellomo, R. Lactate clearance as a target of therapy in sepsis: A flawed paradigm. \\u003cem\\u003eOA Critical Care\\u003c/em\\u003e 1, (2013).\\u003c/li\\u003e\\n\\u003cli\\u003eBauer, M. E. \\u003cem\\u003eet al.\\u003c/em\\u003e Normal Range for Maternal Lactic Acid during Pregnancy and Labor: A Systematic Review and Meta-Analysis of Observational Studies. \\u003cem\\u003eAm J Perinatol\\u003c/em\\u003e 36, 898\\u0026ndash;906 (2019).\\u003c/li\\u003e\\n\\u003cli\\u003eMadaan, A. \\u003cem\\u003eet al.\\u003c/em\\u003e Lactate produced during labor modulates uterine inflammation via GPR81 (HCA1). \\u003cem\\u003eAm J Obstet Gynecol\\u003c/em\\u003e 216, 60.e1-60.e17 (2017).\\u003c/li\\u003e\\n\\u003cli\\u003eHanley, J., Weeks, A. \\u0026amp; Wray, S. Physiological increases in lactate inhibit intracellular calcium transients, acidify myocytes and decrease force in term pregnant rat myometrium. \\u003cem\\u003eJ Physiol\\u003c/em\\u003e 593, 4603\\u0026ndash;4614 (2015).\\u003c/li\\u003e\\n\\u003cli\\u003eGraham, W. \\u003cem\\u003eet al.\\u003c/em\\u003e Diversity and divergence: the dynamic burden of poor maternal health. \\u003cem\\u003eThe Lancet\\u003c/em\\u003e 388, 2164\\u0026ndash;2175 (2016).\\u003c/li\\u003e\\n\\u003cli\\u003eSolomon, C., Collis, R. E. \\u0026amp; Collins, P. W. Haemostatic monitoring during postpartum haemorrhage and implications for management. \\u003cem\\u003eBr J Anaesth\\u003c/em\\u003e 109, 851\\u0026ndash;863 (2012).\\u003c/li\\u003e\\n\\u003cli\\u003evon Elm, E. \\u003cem\\u003eet al.\\u003c/em\\u003e The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement: Guidelines for reporting observational studies. \\u003cem\\u003eInternational Journal of Surgery\\u003c/em\\u003e 12, 1495\\u0026ndash;1499 (2014).\\u003c/li\\u003e\\n\\u003cli\\u003e\\u003cem\\u003eIntrapartum Care for Healthy Women and Babies\\u003c/em\\u003e. (2022).\\u003c/li\\u003e\\n\\u003cli\\u003eACOG Committee Opinion No. 766: Approaches to Limit Intervention During Labor and Birth. \\u003cem\\u003eObstetrics \\u0026amp; Gynecology\\u003c/em\\u003e 133, e164\\u0026ndash;e173 (2019).\\u003c/li\\u003e\\n\\u003cli\\u003ePrevention and Management of Postpartum Haemorrhage. \\u003cem\\u003eBJOG\\u003c/em\\u003e 124, (2017).\\u003c/li\\u003e\\n\\u003cli\\u003eMusaba, M. W. \\u003cem\\u003eet al.\\u003c/em\\u003e Effect of pre-operative bicarbonate infusion on maternal and perinatal outcomes among women with obstructed labour in Mbale hospital: A double blind randomized controlled trial. \\u003cem\\u003ePLoS One\\u003c/em\\u003e 16, e0245989 (2021).\\u003c/li\\u003e\\n\\u003cli\\u003ePiquard, F., Schaefer, A., Dellenbach, P. \\u0026amp; Haberey, P. Is fetal acidosis in the human fetus maternogenic during labor? A reanalysis. \\u003cem\\u003eAmerican Journal of Physiology-Regulatory, Integrative and Comparative Physiology\\u003c/em\\u003e 261, R1294\\u0026ndash;R1299 (1991).\\u003c/li\\u003e\\n\\u003cli\\u003eSpandrio R, R. A. B. G. \\u003cem\\u003eFisiologia Della Nascita. Dai Prodromi al Post-Partum. \\u003c/em\\u003e. (2014).\\u003c/li\\u003e\\n\\u003cli\\u003eSchneider, H., Pr\\u0026ouml;gler, M., Ziegler, W. H. \\u0026amp; Huch, R. Biochemical changes in the mother and the fetus during labor and its significance for the management of the second stage. \\u003cem\\u003eInternational Journal of Gynecology \\u0026amp; Obstetrics\\u003c/em\\u003e 31, 117\\u0026ndash;126 (1990).\\u003c/li\\u003e\\n\\u003cli\\u003eAshwal, E. \\u003cem\\u003eet al.\\u003c/em\\u003e Contemporary patterns of labor in nulliparous and multiparous women. \\u003cem\\u003eAm J Obstet Gynecol\\u003c/em\\u003e 222, 267.e1-267.e9 (2020).\\u003c/li\\u003e\\n\\u003cli\\u003eCoad J, P. K. D. M. \\u003cem\\u003eAnatomy and Physiology for Midwives E-Book: Anatomy and Physiology for Midwives\\u003c/em\\u003e. (2019).\\u003c/li\\u003e\\n\\u003cli\\u003eWeissberg, N. \\u003cem\\u003eet al.\\u003c/em\\u003e The relationship between beta‐endorphin levels and uterine muscle contractions during labor. \\u003cem\\u003eInternational Journal of Gynecology \\u0026amp; Obstetrics\\u003c/em\\u003e 33, 313\\u0026ndash;316 (1990).\\u003c/li\\u003e\\n\\u003cli\\u003eChestnut, W. T. \\u003cem\\u003eChestnut\\u0026rsquo;s Obstetric Anesthesia: Principles and Practice\\u003c/em\\u003e. (2019).\\u003c/li\\u003e\\n\\u003cli\\u003eJacobsen, L., Haslund, H., Brock, C. \\u0026amp; Laursen, B. Medically induced labor: Epidural analgesia and women\\u0026rsquo;s perceptions of pain in early labor. \\u003cem\\u003eEur J Midwifery\\u003c/em\\u003e 2, (2018).\\u003c/li\\u003e\\n\\u003cli\\u003eAllanson, E., Waqar, T., White, C., Tun\\u0026ccedil;alp, \\u0026Ouml;. \\u0026amp; Dickinson, J. Umbilical lactate as a measure of acidosis and predictor of neonatal risk: a systematic review. \\u003cem\\u003eBJOG\\u003c/em\\u003e 124, 584\\u0026ndash;594 (2017).\\u003c/li\\u003e\\n\\u003cli\\u003eAyres‐de‐Campos, D. \\u0026amp; Arulkumaran, S. FIGO consensus guidelines on intrapartum fetal monitoring: Physiology of fetal oxygenation and the main goals of intrapartum fetal monitoring. \\u003cem\\u003eInternational Journal of Gynecology \\u0026amp; Obstetrics\\u003c/em\\u003e 131, 5\\u0026ndash;8 (2015).\\u003c/li\\u003e\\n\\u003c/ol\\u003e\"}],\"fulltextSource\":\"\",\"fullText\":\"\",\"funders\":[],\"hasAdminPriorityOnWorkflow\":false,\"hasManuscriptDocX\":true,\"hasOptedInToPreprint\":true,\"hasPassedJournalQc\":\"\",\"hasAnyPriority\":false,\"hideJournal\":true,\"highlight\":\"\",\"institution\":\"\",\"isAcceptedByJournal\":false,\"isAuthorSuppliedPdf\":false,\"isDeskRejected\":\"\",\"isHiddenFromSearch\":false,\"isInQc\":false,\"isInWorkflow\":false,\"isPdf\":false,\"isPdfUpToDate\":true,\"isWithdrawnOrRetracted\":false,\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"researchsquare\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":true,\"externalIdentity\":\"\",\"sideBox\":\"\",\"snPcode\":\"\",\"submissionUrl\":\"/submission\",\"title\":\"Research Square\",\"twitterHandle\":\"researchsquare\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"\",\"reportingPortfolio\":\"\",\"inReviewEnabled\":false,\"inReviewRevisionsEnabled\":true},\"keywords\":\"lactate, labour physiology, uterine contractions, hypoxia-induced force increase, postpartum haemorrhage, maternal metabolism\",\"lastPublishedDoi\":\"10.21203/rs.3.rs-6375489/v1\",\"lastPublishedDoiUrl\":\"https://doi.org/10.21203/rs.3.rs-6375489/v1\",\"license\":{\"name\":\"CC BY 4.0\",\"url\":\"https://creativecommons.org/licenses/by/4.0/\"},\"manuscriptAbstract\":\"\\u003cp\\u003eUterine contractions during labour are regulated by hormonal and metabolic processes, including oxytocin release, catecholamines modulation, and the hypoxia-induced force increase (HIFI) mechanism. This study investigates the relationship between lactate levels\\u0026mdash;produced during myometrial contraction and transient hypoxia\\u0026mdash;and maternal and foetal outcomes. In a cohort of 303 women receiving neuraxial analgesia, lactate was measured at three time points: at the time of diagnosis of the active phase of the first stage of labour (T0), at the beginning of active pushing (T1), and at delivery (T2). Lactate levels increased progressively, exceeding 2 mmol/L at T1 and T2. However, no significant correlation was found between lactate levels and postpartum haemorrhage or neonatal umbilical cord pH. Multiparous women exhibited lower lactate levels at T1 and T2 (p\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.001), likely due to more efficient myometrial response and metabolic adaptation. Lactate, rather than solely indicating hypoxia, may act as an energy substrate. These findings suggest that lactate plays a physiological role in labour and should not be viewed exclusively as a marker of distress. Understanding its role could refine the clinical interpretation of maternal metabolic stress and improve labour management strategies.\\u003c/p\\u003e\",\"manuscriptTitle\":\"Lactate values during labour and their correlation with maternal and foetal outcome: a prospective observational single-centre study\",\"msid\":\"\",\"msnumber\":\"\",\"nonDraftVersions\":[{\"code\":1,\"date\":\"2025-05-07 16:48:19\",\"doi\":\"10.21203/rs.3.rs-6375489/v1\",\"editorialEvents\":[{\"type\":\"communityComments\",\"content\":0}],\"status\":\"published\",\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"researchsquare\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":true,\"externalIdentity\":\"\",\"sideBox\":\"\",\"snPcode\":\"\",\"submissionUrl\":\"/submission\",\"title\":\"Research Square\",\"twitterHandle\":\"researchsquare\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"\",\"reportingPortfolio\":\"\",\"inReviewEnabled\":false,\"inReviewRevisionsEnabled\":true}}],\"origin\":\"\",\"ownerIdentity\":\"0331d895-e98c-4905-821c-2c0765e471b2\",\"owner\":[],\"postedDate\":\"May 7th, 2025\",\"published\":true,\"recentEditorialEvents\":[],\"rejectedJournal\":[],\"revision\":\"\",\"amendment\":\"\",\"status\":\"posted\",\"subjectAreas\":[{\"id\":47819963,\"name\":\"Biological sciences/Molecular biology\"},{\"id\":47819964,\"name\":\"Health sciences/Biomarkers\"},{\"id\":47819965,\"name\":\"Health sciences/Health care\"},{\"id\":47819966,\"name\":\"Health sciences/Medical research\"}],\"tags\":[],\"updatedAt\":\"2025-06-05T09:38:21+00:00\",\"versionOfRecord\":[],\"versionCreatedAt\":\"2025-05-07 16:48:19\",\"video\":\"\",\"vorDoi\":\"\",\"vorDoiUrl\":\"\",\"workflowStages\":[]},\"version\":\"v1\",\"identity\":\"rs-6375489\",\"journalConfig\":\"researchsquare\"},\"__N_SSP\":true},\"page\":\"/article/[identity]/[[...version]]\",\"query\":{\"redirect\":\"/article/rs-6375489\",\"identity\":\"rs-6375489\",\"version\":[\"v1\"]},\"buildId\":\"8U1c8b4HqxoKbykW_rLl7\",\"isFallback\":false,\"isExperimentalCompile\":false,\"dynamicIds\":[84888],\"gssp\":true,\"scriptLoader\":[]}","source_license":"CC-BY-4.0","license_restricted":false}