Investigating haemodynamic changes during vaginal delivery in low-risk pregnant women and the association between haemodynamic and adverse pregnancy outcomes: an ambispective cohort study protocol

Abstract

Introduction

The progressive adaptation of the maternal cardiovascular system throughout pregnancy is essential to maintaining adequate uteroplacental circulation and meeting maternal physiological demands. In recent years, maternal haemodynamic parameters have gained attention as useful indicators for screening and managing pregnancy, particularly for identifying women at high risk for complications and predicting adverse pregnancy outcomes. The aim of this study is to assess the trajectory of haemodynamic parameters during labour, establish reference ranges for different stages of labour and explore the association between haemodynamics and adverse pregnancy outcomes.

Methods and analysis

This is an ambispective observational cohort study conducted in a tertiary hospital in Chongqing, China. A total of 2800 pregnant women will be enrolled. After hospital admission and providing written informed consent, participants will complete a demographic questionnaire. Data collection will include maternal baseline characteristics, haemodynamic parameters at multiple stages of labour and maternal and newborn outcomes. These data will allow comprehensive analysis of haemodynamic changes during labour in women undergoing vaginal delivery.

Ethics and dissemination

This study has been approved by the Research Ethics Committee of the First Affiliated Hospital of Chongqing Medical University (ethics approval number: 2024–406-01). Participation is voluntary and initiated only after obtaining written informed consent. The findings will be disseminated through presentations at national and international conferences and through publications in peer-reviewed scientific journals.

Trial registration number

ChiCTR2500097643.

STRENGTHS AND LIMITATIONS OF THIS STUDY.

• Comprehensive collection of maternal demographics, phase-specific haemodynamic parameters, and detailed maternal and neonatal outcomes.

• To investigate advanced haemodynamic parameters and establish stage-specific reference ranges during labour.

• Despite efforts to standardise measurement conditions, substantial variability remains during the second stage of labour.

• No study has yet investigated the accuracy of regional impedance cardiography specifically in pregnant populations, therefore, all conclusions drawn from this study should be interpreted as relative comparisons based on NICaS (non-invasive haemodynamic monitoring system) measurements.

Introduction

Pregnancy is a unique physiological state, characterised by continuous maternal cardiovascular adaptations that begin at conception.¹ These progressive changes are essential for supporting fetal growth and development by maintaining adequate uteroplacental circulation and meeting the increasing functional demands of the maternal cardiovascular system throughout gestation.² Although substantial haemodynamic alterations occur during pregnancy, labour introduces additional physiological stressors—including uterine contractions, pain, Valsalva manoeuvres and physical exertion—that further intensify these changes. Consequently, haemodynamic patterns during childbirth may differ substantially from those observed during earlier stages of pregnancy.^{3 4}

In clinical practice, blood pressure (BP) and heart rate (HR) are commonly used as standard indicators for cardiovascular monitoring. However, these parameters are influenced by various physiological factors and may not accurately reflect the underlying causes of maternal cardiovascular dysfunction. Moreover, due to compensatory regulatory mechanisms, BP and HR have limited ability to detect early cardiovascular abnormalities. In recent years, alternative haemodynamic indicators such as cardiac output (CO) and peripheral vascular resistance have been increasingly used to assess maternal cardiovascular status. Several studies have demonstrated that abnormal cardiovascular adaptation is not only associated with pregnancy complications such as hypertensive disorders of pregnancy and fetal growth restriction, but also precedes measurable changes in BP.^{5 6} Therefore, relying solely on BP is insufficient for timely detection of haemodynamic changes, highlighting the need to develop and implement more comprehensive haemodynamic indicators. Large-scale studies have documented that CO increases progressively from early pregnancy, peaking at around 32–34 weeks of gestation, followed by a gradual decline towards term.^{7 8} Some researchers have reported that both CO and HR increase during the second stage of labour and subsequently decrease postpartum; however, these findings remain inconsistent and are subject to ongoing debate.⁹,¹³ The lack of consensus on haemodynamic trends during labour is largely attributed to the small sample sizes of previous studies and their reliance on techniques such as thermal dilution and ultrasound-based methods, which may be invasive, pose certain risks to participants or require highly specialised training to perform accurately.

Effective haemodynamic monitoring during pregnancy requires non-invasive, simple and rapid methods. However, many existing monitoring devices are limited by invasiveness, long operation times and dependence on specialised personnel. To address these limitations, we used the non-invasive haemodynamic monitoring system (NICaS). Previous studies have shown that NICaS provides accurate, economical, repeatable and continuous assessments of cardiovascular status and correlates strongly with CO and stroke volume (SV) measurements obtained by thermodilution, Doppler echocardiography or cardiac MRI.^{14 15} In addition to conventional parameters, NICaS also offers advanced indices such as the Cardiac Power Index (CPI), Granff-Gower Index (GGI) and total body water (TBW), enabling a more comprehensive evaluation of maternal cardiovascular function. Furthermore, with minimal training, healthcare personnel can perform rapid and reliable measurements using the NICaS system.

Given the critical role of haemodynamics during labour and the current absence of large-scale studies examining novel haemodynamic indicators in this context, we use the NICaS system to monitor haemodynamic changes in healthy parturients. Monitoring could be conducted at multiple time points: before labour onset, during the first stage of labour (both before and after epidural anaesthesia), during the second stage and within 2 hours post partum. The aims of this study are to assess the trajectory of haemodynamic parameters throughout labour, establish reference ranges for different stages of labour and explore the association between haemodynamics and adverse pregnancy outcomes, with the ultimate goal of identifying potential windows for clinical intervention.

Methods and analysis

Study design

This ambispective cohort study is being conducted at the First Affiliated Hospital of Chongqing Medical University. The study protocol was approved by the Institutional Review Board of Chongqing Medical University in October 2024 (ethics approval number: 2024–406-01) and has been registered in the Chinese Clinical Trial Registry (registration number: ChiCTR2500097643). Written informed consent is obtained from all participants before enrolment.

Setting and participant recruitment

We recruit low-risk pregnant women planning vaginal delivery at the Department of Obstetrics, the First Affiliated Hospital of Chongqing Medical University from January 2024 to December 2026. Low-risk pregnant women are defined as those who meet all of the following criteria: (1) aged over 18 years; (2) body mass index at delivery <40 kg/m²; (3) confirmed normal singleton pregnancy on ultrasound examination; and (4) normal blood pressure during pregnancy according to the American College of Obstetricians and Gynecologists (ACOG) criteria. And without: (1) a history of hypertensive disorders of pregnancy (chronic hypertension with pregnancy, gestational hypertension, pre-eclampsia or eclampsia); (2) use of antihypertensive medications during pregnancy; (3) cardiovascular disease, autoimmune disorders (eg, systemic lupus erythematosus, antiphospholipid syndrome), chronic kidney disease (any stage), significant haematological disorders or hereditary diseases. These criteria form part of the study’s inclusion and exclusion protocol.

Patient and public involvement statement

Neither patients nor the public participated in the design, execution, reporting or dissemination of this research.

Inclusion and exclusion criteria

Inclusion criteria were as follows: (1) women aged over 18 years; (2) body mass index (BMI) at delivery <40 kg/m²; (3) confirmed normal singleton pregnancy on ultrasound; and (4) normal blood pressure during pregnancy according to ACOG criteria.

Exclusion criteria were: (1) history of hypertensive disorders of pregnancy (chronic hypertension with pregnancy, gestational hypertension, pre-eclampsia or eclampsia); (2) use of antihypertensive medication during pregnancy; (3) cardiovascular disease, autoimmune disorders (eg, systemic lupus erythematosus, antiphospholipid syndrome), chronic kidney disease (any stage), significant haematological disorders or hereditary diseases; (4) stillbirth or severe fetal malformations necessitating pregnancy termination; and (5) missing maternal or neonatal outcome data.

Eligible participants who meet the inclusion criteria and provide informed consent are asked to complete a baseline questionnaire, after which their haemodynamic parameters are systematically collected.

Withdrawal

All participants are free to withdraw from the study at any time, for any reason, without this affecting their subsequent medical care. If a participant chooses to withdraw before the study is completed, the reason for withdrawal will be recorded. If withdrawal occurs during data collection, any ongoing data collection will be stopped.

Study timeline and schedule

This cohort commenced in January 2024 and aims to enrol 2800 pregnant women. Data from 1 January 2024 to 31 October 2024 were collected retrospectively, while data from 1 November 2024 to 31 December 2026 will be collected prospectively. Retrospective data will be extracted from the hospital’s electronic medical record system, and prospective enrolment will begin after obtaining ethical and regulatory approval. The time points and specific details for participants are outlined in online supplemental table S1 and S2, respectively. During the study period, each participant will complete a demographic questionnaire before entering the delivery room. Haemodynamic data will be collected at multiple stages: before the onset of term labour, during the first stage of labour (both before and after labour analgesia), during the second stage and within 2 hours post partum, without interfering with the delivery process. In addition, fetal heart rate monitoring data during labour and relevant neonatal information after delivery will be collected for analysis.

Sample size

Based on the reference interval precision principle, the formula used is:

$${\displaystyle {\displaystyle \begin{array}{c}n=\left(1+0.5z_{(1+q)/2}^2\right)\left(\frac{{\left(\varphi Z_{(1+q)/2}.Z_{(1+\varphi )/2}\right)}^2}{\delta }\right)\end{array}}}$$

where q=0.95 (confidence level), η=0.9 (statistical power) and δ=0.003 (tolerance error). This method has shown that a sample of 1688 women achieves a precision of 0.003 SD at the 2.5th or 97.5th centile.¹⁶ We also accounted for an estimated 10% of women who will meet exclusion criteria, as well as 30% of haemodynamic data collected during labour that may fail to be effectively gathered for various reasons. Therefore, we plan to recruit 2800 women. Among these, 1200 will be retrospective samples extracted from the electronic medical record system, and 1600 will be prospective samples. Furthermore, longitudinal studies require approximately half the sample size of cross-sectional studies to estimate a given centile with the same precision.^{17 18} Consequently, our cohort of 2800 women contributing 6720 measurements has statistical power equivalent to that of 13 440 measurements in a cross-sectional study.

Data collection

Through in-depth training and supervision of the data collection personnel in the research team, overall data quality will be ensured. All retrospective data will be collected by trained researchers from the electronic medical record system and NICaS devices, and prospective data will be collected by the same group of researchers using standardised questionnaires and NICaS devices.

Maternal data

Maternal data included demographic characteristics (maternal age, height, BMI at delivery and gestational weight gain), medical history (pre-existing conditions such as autoimmune disease and diabetes mellitus) and obstetrical history (gravidity, parity, mode of conception, previous pregnancy complications and history of caesarean section).

Data of the delivery process

Data collected after admission to the delivery room included physical examination findings (uterine height, temperature, pulse, respiratory rate and blood pressure), basic delivery information (delivery method, indication for caesarean section, method of placental removal, placenta-related disorders, intrapartum complications, umbilical cord abnormalities and records of the labour process), epidural anaesthesia, postpartum haemorrhage and blood transfusion-related information.

Haemodynamic data

Haemodynamic data were collected at multiple time points: (1) before the onset of term labour—from admission until the appearance of regular contractions, monitored by tocodynamometry (TOCO); (2) first stage of labour—from the beginning of cervical dilation to full dilation, accompanied by painful contractions; (3) second stage of labour—from full cervical dilation to delivery of the fetus; and (4) within 2 hours post partum—from delivery to 2 hours after placental expulsion.

To ensure data accuracy and reproducibility, all haemodynamic measurements were performed under strictly standardised conditions. Measurements were obtained with the participant in the supine position, except during the second stage of labour when the lithotomy position was used. During labour, measurements were taken exclusively during the inter-contraction interval (at least 30 s after the end of a contraction and before the onset of the next contraction). All measurements were confirmed in real-time using TOCO, the participant’s subjective sensation and abdominal palpation. Measurements were performed while the participant was relatively at rest and were avoided during breath-holding, bearing down or urgent interventions. For women receiving epidural analgesia, post-analgesia measurements were obtained 60 min after the initial dose.

All retrospective haemodynamic measurements were obtained using the same device (NICaS) as the prospective cohort, with measurements performed by trained labour ward nurses. The timing of measurements within each labour stage was consistent between the two cohorts.

For women who converted to caesarean section, only haemodynamic data collected up to the point of the decision for caesarean were included in the longitudinal analysis of labour trajectories.

The recorded haemodynamic parameters included: basic indices—systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP) and heart rate (HR); preload indices—CO, Cardiac Index (CI), SV, stroke volume per kilogram (SV/kg) and Stroke Index (SI); afterload indices—total peripheral resistance (TPR) and Total Peripheral Resistance Index (TPRI); myocardial contractility indices—CPI and GGI; and other indicators—TBW and TBW/kg. All haemodynamic indicators were collected using the NICaS system.

Outcomes

Primary outcome: The longitudinal dataset of repeatedly measured haemodynamic parameters. These include the following measurements taken at predefined time points: SBP, DBP, MAP, HR; preload indices: CO, CI, SV, SV/kg, SI; afterload indices: TPR, TPRI; myocardial contractility indices: CPI, GGI; and other indicators: TBW, TBW/kg. These parameters will be analysed as continuous variables in the primary analysis.

Exploratory outcomes: (1) intrapartum caesarean delivery or operative vaginal delivery (forceps or vacuum) indicated by pathological cardiotocographic patterns or meconium-stained amniotic fluid; (2) postpartum haemorrhage (blood loss ≥500 mL within 24 hours after delivery); and (3) neonatal admission to the intensive care unit.

Sample bank establishment

All maternal demographic and haemodynamic data will be securely stored in the Real-World Data Platform (RWD; https://rwdmp.cqmu.edu.cn/eproPad/html/index.html). Access to this database is strictly controlled through rigorous data protection protocols, requiring unanimous approval from the principal investigators to ensure participant confidentiality and compliance with all applicable privacy regulations.

Sample analysis

Handling of missing data

First, the proportion of missing values will be reported for all parameters. Any parameter with >30% missing values will be excluded from subsequent analyses to ensure robustness. For parameters with ≤30% missing values, the missing data pattern will be assessed. If the data are missing at random, multiple imputation will be performed, followed by sensitivity analyses using the imputed datasets. If the data are missing not at random, sensitivity analyses will be conducted by excluding participants with non-random missing data to evaluate the potential impact of such missingness.

Comparability of retrospective and prospective data

First, the retrospective cohort is required to match the prospective cohort in terms of measurement device, timing and clinical conditions; therefore, data will be independently verified by two researchers. Second, baseline characteristics will be compared with ensure demographic comparability. Third, data completeness will be assessed; variables with a missing rate exceeding 30% in the retrospective cohort will be excluded from the primary analysis.

Covariate strategy

Covariates were selected based on clinical relevance and prior literature, including maternal age, parity, pre-pregnancy BMI, gestational weight gain, cohort type, epidural anaesthesia use, smoking status and others.

Data analysis

Descriptive analysis

Normality will be assessed to determine whether variables follow a normal distribution. Continuous variables will be summarised using observed values, number of missing values, mean, SD, median and range. Categorical variables will be presented as frequencies and percentages.

Analysis of the primary outcome

Linear mixed models will be used to assess the effects of haemodynamic parameters during labour. The dependent variables are the primary haemodynamic indices. Fixed effects include time point (pre-labour, first stage (before vs after epidural anaesthesia), second stage and 2 hours postpartum), BMI at delivery, age, parity, cohort type and labour analgesia. Patient ID is included as a random effect. Likelihood ratio tests will be used to define the best-fitting multilevel model. Estimated marginal means for each haemodynamic parameter by labour stage will be presented, with pairwise comparisons adjusted using Tukey’s Honestly Significant Difference. Generalised Additive Models for Location, Scale and Shape will be used to explore the relationship between haemodynamic parameters and labour stage. Missing values for haemodynamic parameters will be handled by multiple imputation using chained equations. From these models, percentile reference ranges (2.5th, 10th, 25th, 50th, 75th, 90th and 97.5th percentiles) will be generated.

Analysis of the exploratory outcome

Generalised estimating equations with modified Poisson regression will be used to compare haemodynamic differences among pregnant women according to secondary outcomes.

Sensitivity analysis

To assess robustness, we performed the following sensitivity analyses: (1) complete-case analysis; (2) analysis excluding adverse maternal and neonatal outcomes; (3) analysis without handling of missing data; and (4) analysis restricted to the 1200 retrospective cohort, to evaluate whether each conclusion remained consistent with the results from the total 2800-case dataset.

All statistical analyses will be conducted using SPSS V.27.0 (IBM) and R V.4.4.2. The study flow is shown in figure 1.

Figure 1. Flowchart of the study. CQMU, Chongqing Medical University; GAMLSS, Generalised Additive Models for Location, Scale and Shape; GEE, Generalised estimating equations; HSD, Honestly Significant Difference; LMM, linear mixed models; NICaS, non-invasive haemodynamic monitoring system; RDW, Real-World Data Platform.

Ethics and dissemination

This study was approved by the Institutional Review Board of Chongqing Medical University in October 2024 (ethics approval number: 2024–406-01) and has been registered in the Chinese Clinical Trial Registry (registration number: ChiCTR2500097643). The Clinical Research Management Committee of the First Affiliated Hospital of Chongqing Medical University will oversee data and safety monitoring. All committee members are independent of the study team and are responsible for supervising ethical and safety matters in accordance with the regulations, policies and guidelines issued by the National Health Commission of the People’s Republic of China regarding clinical research.

The researchers or designated members of the research team will ensure that all participating pregnant women receive a copy of the participant information sheet. The details of the study have been explained to them, and their questions have been answered. Participants will have sufficient time to decide whether to take part. If they agree, the researcher and the participant will jointly sign and date the informed consent form before participation. One copy of the consent form will be kept by the participant, and the other will be stored by the researcher in a locked cabinet.

The data will be securely archived on RWD and analysed by qualified researchers. Study findings will be disseminated widely through conference presentations and publications in peer-reviewed journals.

Discussion

Given that haemodynamics may change during labour, we use a longitudinal study design to systematically collect haemodynamic information from parturients at multiple time points: before the onset of term labour, during the first stage of labour (both before and after epidural anaesthesia), during the second stage and within 2 hours post partum. This design enables a comprehensive assessment of haemodynamic trends throughout the labour process and allows reference ranges to be established accordingly. Moreover, given the potential link between haemodynamic alterations and adverse pregnancy outcomes, we will analyse haemodynamic differences among parturients with varying delivery outcomes to support early identification of those at increased risk of complications.

Theoretically, several factors during labour may induce maternal haemodynamic changes, including increased heart rate, preload and circulating catecholamines due to painful uterine contractions, as well as the return of 300–500 mL of blood from the uterus to the systemic circulation immediately after each contraction. Additional factors such as blood loss during delivery, labour analgesia and changes in maternal position (supine vs left lateral) may also elicit secondary cardiovascular effects.^{3 4} Using techniques such as thermodilution, echocardiography, tissue Doppler and lung ultrasound, several investigators have monitored haemodynamics in women undergoing vaginal delivery and found that CO and HR increase significantly until the second stage of labour, followed by a gradual decrease post partum.⁹,¹¹ Conversely, other studies have reported a progressive decline in CO throughout the entire labour process.^{12 13} However, findings in this field remain inconclusive, and large-sample studies are lacking. Moreover, several studies have indicated that alternative haemodynamic indicators such as CO, CI and TPR provide a more accurate assessment of maternal cardiovascular status.^{19 20}

Haemodynamic alterations during labour have been closely associated with adverse obstetrical outcomes, highlighting the importance of early prediction. Studies have demonstrated that women with low CO and increased systemic vascular resistance have an 8-fold to 10-fold increased risk of labour-related complications.¹⁹ Current research suggests that specific haemodynamic thresholds—such as CO ≤5.8 L/min, CI ≤2.9 L/min/m² and TPR >1069 dynes×s/cm⁵—may serve as predictive markers for adverse pregnancy outcomes.¹⁹ Similar findings were reported by Kalafat et al in women undergoing labour induction.²⁰ However, these studies were limited by small sample sizes and relied primarily on univariate analyses, which may not adequately account for confounding factors. As a result, larger-scale studies incorporating multifactorial models are urgently needed to refine prediction thresholds and enhance the clinical utility of haemodynamic monitoring. Such efforts will support earlier and more accurate identification of women at risk for adverse outcomes, ultimately improving maternal and neonatal care.

Strengths and limitations of this study

To achieve our research objectives, the study follows a rigorous design and implementation process to ensure scientific integrity in sample selection, data collection and statistical analysis. Beyond the benefits of a large-sample longitudinal study, it offers several key strengths: (1) comprehensive collection of maternal demographics, phase-specific haemodynamic parameters and detailed maternal and neonatal outcomes; and (2) investigation of advanced haemodynamic parameters to establish stage-specific reference ranges during labour. However, the study also has limitations. First, despite attempts to standardise measurement conditions, substantial variability remains during the second stage of labour. Second, NICaS has been widely used in women undergoing caesarean section or vaginal delivery,^{21 22} but no study has yet investigated the accuracy of NICaS specifically in pregnant populations; therefore, all conclusions drawn from this study should be interpreted as relative comparisons based on NICaS measurements. Notwithstanding these limitations, the study is expected to enhance the reliability and validity of the findings and provide meaningful insights for improving maternal and neonatal health in China. Of note, the scale and complexity of the study require substantial time, effort and resource investment.