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NCT Number: NCT07376616

Cardiovascular Research in EMbarazo and MAternity (EMMA). Study on Heart Rate Variability and Hemodynamic Adaptations During Pregnancy and Postpartum.

Heart rate variability (HRV) provides a non-invasive assessment of autonomic control of the nervous system over the heart. During pregnancy, the cardiovascular system adapts significantly, affecting HRV and hemodynamics. Studying the relationship between HRV and hemodynamic changes is critical to understanding and monitoring cardiovascular health during pregnancy and postpartum, and predicting potential complications.

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Key information

Age range

18 year and older

Sex eligibility

Female

Study type

Observational

Primary location

Hospital Alvaro Cunqueiro

Vigo, Pontevedra, 36312, Spain

Location status: Recruiting

Location contact

Emilio Couceiro Naveira

CONTACT

CONTACT

[email protected]

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Over 18 years of age
  • Pregnancy from the third month of gestation
  • No pre-existing cardiovascular disease
  • Good cognitive level
  • Sign informed consent

Exclusion criteria

  • Diabetes mellitus
  • Hyperthyroidism
  • Hypothyroidism
  • Chronic hypertension diagnosed before pregnancy
  • Heart failure
  • Ischemic heart disease or malignant ventricular arrhythmias (ventricular fibrillation, ventricular tachycardia, grade 2 or 3 AV block, atrial fibrillation in patients with Wolff-Parkinson- White syndrome, paroxysmal fibrillation or flutter with rapid ventricular response and hemodynamic deterioration, uncontrolled supraventricular tachycardia)
  • Exercise-induced ischaemia
  • Unstable angina
  • Disease not susceptible to revascularization
  • Associated valvular heart disease
  • Chronic kidney disease
  • Degenerative neurological condition
  • Brain aneurysms
  • Arteriovenous malformations
  • History of transient cerebral infarction (ICTUS)
  • Migraines diagnosed
  • Epilepsy
  • Brain or spinal cord injury
  • Tumors
  • Diseases of the respiratory tract
  • Diseases of lung tissue
  • Diseases of pulmonary circulation

Treatment and study plan

Assessment of HRV and blood pressure

Other

Assessment of Heart Rate Variation (HRV) and blood pressure

Primary outcomes

  1. RR (R-R range)

    Time frame: Pregnancy weeks 13, 27 and 41. Postpartum month, 3, 6 and 12 months.

    The RR interval is the time between successive R-waves of the QRS complex now electrocardiogram (ECG) expressed in milliseconds (ms). It is a fundamental unit in HRV analysis and represents the time between two consecutive heartbeats.

  2. RMSSD (Root Mean Square of Successive Differences)

    Time frame: Pregnancy weeks 13, 27 and 41. Postpartum month, 3, 6 and 12 months.

    RMSSD is a measure in the tempo domain that quantifies variability in the length of consecutive RR intervals expressed in milliseconds (ms). It reflects short-term HRV and is influenced by the parasympathetic nervous system.

  3. pNN50 (Percentage of successive RR intervals differing by more than 50 ms)

    Time frame: Pregnancy weeks 13, 27 and 41. Postpartum month, 3, 6 and 12 months.

    pNN50 is another measure in the time domain that represents a percentage (%) of RR intervals that differ by more than 50 ms. It is also indicative of short-term HRV and is related to parasympathetic activity.

  4. HF (High Frecuency)

    Time frame: Pregnancy weeks 13, 27 and 41. Postpartum month, 3, 6 and 12 months.

    HF is a measurement in the frequency domain that represents the power of heart rate variability in the high frequency range (typically 0.15 to 0.4 Hz). It is associated with parasympathetic (vagal) activity and is often analyzed by spectral analysis of the HRV signal. Expressed in milliseconds squared (ms^2).

  5. LF (low frequency)

    Time frame: Pregnancy weeks 13, 27 and 41. Postpartum month, 3, 6 and 12 months.

    LF is a measurement in the frequency domain that represents the power of heart rate variability at low frequencies (usually from 0.04 to 0.15 Hz). The LF is influenced by sympathetic and parasympathetic activity and the child analyzase xunto coa IC. Expressed in milliseconds to frame (ms^2).

  6. SD1 (standard deviation 1)

    Time frame: Pregnancy weeks 13, 27 and 41. Postpartum month, 3, 6 and 12 months.

    SD1 is xeometric measures derived from Poincaré graphs, which are graphical representations of RR intervals. SD1 represents the short-term variability perpendicular to the identity line in the Poincaré graphic and is influenced by parasympathetic activity.

  7. SD2 (standard deviation 2)

    Time frame: Pregnancy weeks 13, 27 and 41. Postpartum month, 3, 6 and 12 months.

    SD2 is a xeometric measure derived from Poincaré graphs, which are graphical representations of RR intervals. SD2 represents long-term variability along the identity line and is influenced by sympathetic and parasympathetic activity.

  8. DFAa1 (Trend Flotation Analysis, alpha-1)

    Time frame: Pregnancy weeks 13, 27 and 41. Postpartum month, 3, 6 and 12 months.

    DFA is a mathematical method used to evaluate fractal properties in time series, such as the HRV. DFAa1 centrase specifically in short-term floatation (alpha-1) in the HRV signal. It offers information about the properties of autosemellanza or long-range correlation of the signal.

  9. DFAa2 (Trend Flotation Analysis, alpha-2)

    Time frame: Pregnancy weeks 13, 27 and 41. Postpartum month, 3, 6 and 12 months.

    DFA is a mathematical method used to evaluate the fractal properties of time series, such as HRV. DFAa2 céntrase especially in long-term flotation (alpha-2) in the HRV signal.

  10. SampEn (Sample Entropy)

    Time frame: Pregnancy weeks 13, 27 and 41. Postpartum month, 3, 6 and 12 months.

    The show entropy is a modified algorithm less dependent on the duration of the time series. Used to evaluate the complexity of R-R intervals. A higher entropy value represents more complex dynamics and greater ability of the cardiovascular system to adapt to changes, which is associated with lower cardiovascular health.

  11. ApEn (approximate entropy)

    Time frame: Pregnancy weeks 13, 27 and 41. Postpartum month, 3, 6 and 12 months.

    ApEn is a measure used to evaluate the regularity and complexity of time series, such as HRV. ApEn quantifies the degree of unpredictability in the time series fluctuations, providing information about the structure of the signal and its irregularity. A lower value of ApEn indicates a more regular and predictable series, whereas a higher value reflects greater complexity and irregularity.

  12. MSE (Multiscale entropy)

    Time frame: Pregnancy weeks 13, 27 and 41. Postpartum month, 3, 6 and 12 months.

    MSE is an extension of SampEn that analyzes the complexity of time series on multiple time scales. The MSE allows to evaluate the structure of the signal at different levels of detail, providing a more complete view of its complexity.

  13. D2 (Correlation dimension)

    Time frame: Pregnancy weeks 13, 27 and 41. Postpartum month, 3, 6 and 12 months.

    The correlation dimension is a measure that estimates the minimum number of variables needed to build a model of the dynamics of a system. The greater the number of variables required to predict a time series, the greater its complexity. This measure provides information about the subcomplex and dynamic characteristics of the system.

  14. Heart rate turbulence (HRT)

    Time frame: Pregnancy weeks 13, 27 and 41. Postpartum month, 3, 6 and 12 months.

    The cardiac frequency turbulence and a baroreflex-mediated axus of the cardiac frequency that acts as a countermechanism for premature ventricular contraction. It consists of no brief acceleration of the heart rate, followed by a slow decrease at the reference rate.

  15. Heart rate (HR)

    Time frame: Pregnancy weeks 13, 27 and 41. Postpartum month, 3, 6 and 12 months.

    Number of heartbeats per minute during treatments performed during different trimesters of pregnancy and not postpartum (Lat/min).

  16. Systolic blood pressure (PAS)

    Time frame: Pregnancy weeks 13, 27 and 41. Postpartum month, 3, 6 and 12 months.

    Perform a systolic blood pressure record expressed in mmHg and measured in different locations.

  17. Diastolic blood pressure (DBP)

    Time frame: Pregnancy weeks 13, 27 and 41. Postpartum month, 3, 6 and 12 months.

    Perform a diastolic blood pressure record expressed in mmHg and measured in different locations.

  18. Mean arterial pressure (MAP)

    Time frame: Pregnancy weeks 13, 27 and 41. Postpartum month, 3, 6 and 12 months.

    MAP is the constant blood pressure value that, wedge same peripheral resistance would produce the same flow rate (minute cardiac volume) as xera a variable blood pressure (systolic and diastolic pressure) expressed in mmHg.

  19. Pulse pressure (BP)

    Time frame: Pregnancy weeks 13, 27 and 41. Postpartum month, 3, 6 and 12 months.

    BP is an index of arterial distensibility expressed in mmHg obtained from the difference between systolic and diastolic blood pressure and measured in different locations.

  20. O2 saturation

    Time frame: Pregnancy weeks 13, 27 and 41. Postpartum month, 3, 6 and 12 months.

    Oxygen saturation measures, in different locations, the percentage of hemoglobin in red blood cells currently transporting oxygen, indicating how well the lungs and heart are oxygenating body tissues. The following are measured: Regional O2 saturation (StO2) using near-infrared spectroscopy (NIRS), Arterial O2 saturation (SpO2) uses standard pulse oximetry, Venous O2 saturation (SjvO2) requires invasive catheterization.

  21. Cardiac output (CO)

    Time frame: Pregnancy weeks 13, 27 and 41. Postpartum month, 3, 6 and 12 months.

    Cardiac output is the total volume of blood pumped by the heart's left ventricle in one minute, serving as a critical indicator of cardiovascular health and tissue perfusion. It is measured in L/min multiplying the stroke volume (blood ejected per beat) by the heart rate (beats per minute) using an echocardiogram.

  22. Stroke volume (SV)

    Time frame: Pregnancy weeks 13, 27 and 41. Postpartum month, 3, 6 and 12 months.

    Stroke volume is the volume of blood pumped from the left ventricle per beat. It is measured in mL using a volumetric formula whose values are obtained from cardiac imaging and hemodynamic monitoring techniques, such as echocardiography.

  23. Systemic vascular resistance (SRV)

    Time frame: Pregnancy weeks 13, 27 and 41. Postpartum month, 3, 6 and 12 months.

    Systemic vascular resistance is measured by calculating the opposition to blood flow in the left ventricle using a formula. The essential values are mean arterial pressure (MAP), central venous pressure (CVP), and cardiac output (CO), usually obtained through invasive catheterization (Swan-Ganz catheter) or advanced hemodynamic monitoring methods. It is measured in dyn*s/cm^5

  24. Vasodilation / Constriction (VDCx)

    Time frame: Pregnancy weeks 13, 27 and 41. Postpartum month, 3, 6 and 12 months.

    Vasodilation (widening) and vasoconstriction (narrowing) of blood vessels (VDCx), which reflect vascular function and muscle tone, are measured in mm using non-invasive techniques that assess how an artery reacts to a stimulus. The standard method is Flow-Mediated Dilation (FMD) using ultrasound.

  25. Cerebral vascular flow (CBF)

    Time frame: Pregnancy weeks 13, 27 and 41. Postpartum month, 3, 6 and 12 months.

    Cerebral blood flow is the net amount of blood delivered to the brain's capillary bed per unit of time and tissue mass, typically measured in mL/min/100g using various imaging and functional monitoring techniques, mainly classified into non-invasive methods (ultrasound, MRI) and perfusion techniques by tomography or nuclear medicine, intended to assess the amount and speed of blood reaching brain tissue.

  26. Cardiac Index (CI)

    Time frame: Pregnancy weeks 13, 27 and 41. Postpartum month, 3, 6 and 12 months.

    The Cardiac Index is a hemodynamic parameter representing the heart's pumping efficiency, calculated as the cardiac output divided by the body surface area. It measures blood flow (liters per minute) relative to a person's size L/min/m^2 using Doppler Echocardiography.

  27. Central Venous Pressure (CVP)

    Time frame: Pregnancy weeks 13, 27 and 41. Postpartum month, 3, 6 and 12 months.

    Central Venous Pressure is measured by connecting a central venous catheter to a manometer or electronic transducer, aligning the equipment with the phlebostatic point (level of the right atrium), and reading the fluid column (cm H2O) or the figure in mmHg that indicates the hydroelectrolytic balance and function of the right side of the heart, reflecting intravascular volume and cardiac preload.

  28. Jugular venous distensibility (JVDx/JYI-DI)

    Time frame: Pregnancy weeks 13, 27 and 41. Postpartum month, 3, 6 and 12 months.

    Jugular venous distensibility is an index given by a formula whose data is obtained from ultrasound measurement to evaluate the response in the change of diameter of the veins to fluids and the volemia status.

  29. The Ankle-Brachial Index with Doppler (ABI-D or ITB)

    Time frame: Pregnancy weeks 13, 27 and 41. Postpartum month, 3, 6 and 12 months.

    The Ankle-Brachial Index with Doppler is a non-invasive diagnostic test used to evaluate peripheral arterial disease (PAD) by comparing systolic blood pressure at the ankle with that in the arm. It is measured by dividing the highest systolic pressure obtained at the ankle by the highest systolic pressure in the arms.

  30. The Cardio-Ankle Vascular Index (CAVI)

    Time frame: Pregnancy weeks 13, 27 and 41. Postpartum month, 3, 6 and 12 months.

    The Cardio-Ankle Vascular Index is measured non-invasively using a specialized device, commonly the VaSera (Fukuda Denshi, Japan), which automatically calculates stiffness from the origin of the aorta to the ankle. The procedure is based on pulse wave velocity (PWV) and blood pressure.

  31. The Acoustic Index Derived (AI-D)

    Time frame: Pregnancy weeks 13, 27 and 41. Postpartum month, 3, 6 and 12 months.

    The Acoustic Index Derived is a new metric in cardiology that is measured using AI-assisted automated echocardiography to assess cardiac function in real time. It is calculated by automatically analyzing ultrasound images to provide a comprehensive view of heart health.

  32. PEP (Pre-Ejection Period)

    Time frame: Pregnancy weeks 13, 27 and 41. Postpartum month, 3, 6 and 12 months.

    The PEP (Pre-Ejection Period) in hemodynamics is a parameter measured in milliseconds (ms) that evaluates the time that elapses from the beginning of the electrical activation of the ventricle until the beginning of the ejection of blood towards the aorta. It is measured by calculating the time interval between the start of ventricular depolarization (Q wave of the ECG) and the beginning of aortic blood ejection (point B of impedance cardiography).

  33. Ejection Time (ET)

    Time frame: Pregnancy weeks 13, 27 and 41. Postpartum month, 3, 6 and 12 months.

    Ejection Time (ET) is the duration of systolic flow, measuring (in milliseconds) the time interval from aortic valve opening to closure when the left ventricle ejects blood into the aorta. Using Spectral Doppler (Pulsed or Continuous Wave) the time is measured from the start of the flow (valve opening) to the end of the aortic flow (valve closing).

Secondary outcomes

  1. Age

    Time frame: Basal assessment

    Age expressed in years

  2. Race

    Time frame: Basal assessment

    Caucasian, Black or of African descent, Arab or North African, Asian, Native American, Latin American, Other

  3. Births

    Time frame: Basal assessment

    Nulliparous, primiparous, multiparous

  4. Fertilization

    Time frame: Basal assessment

    Spontaneous, Conventional IVF, ICSI, FET (frozen embryos), Mini IVF, Ovodonation, ROPA Method

  5. Risk of pre-eclampsia

    Time frame: Basal assessment

    High, Medium, Low

  6. Previous pregnancies

    Time frame: Basal assessment

    Number of pregnancies

  7. Previous spontaneous abortions

    Time frame: Basal assessment

    Number of pregnancies

  8. Type of childbirth

    Time frame: Basal assessment

    Spontaneuos vaginal, assisted vaginal, scheduled cesarean, urgent cesarean

  9. Time of childbirth

    Time frame: Basal assessment

    Pre-term, at term, post-term

  10. Level of education

    Time frame: Basal assessment

    No studies, primary education, secondary, baccalaureate, vocational training, university studies

  11. Employment status

    Time frame: Basal assessment

    Full-time paid employment, part-time paid employment, self employed, unemployed, dedication to the home

  12. Concomitant medication

    Time frame: Basal assessment

    Without medication, Analgesics, Antibiotics, Antivirals, Antifungals, Antiparasitics, Anti-inflammatory drugs, Antihistamines, Antihypertensive drugs, Hypoglycemic agents, Antidepressants, Anxiolytics, Antipsychotics, Diuretics, Anticoagulants, Nutritional supplementation, Antiemetics, Hormone treatment before pregnancy, Hormone treatment in pregnancy, Other

  13. Smoking habit

    Time frame: Basal assessment

    Non-smoker, Ex-smoker more than one year, Ex-smoker less than a year, Non-smoker during pregnancy, Smoker

  14. Consumption of alcohol

    Time frame: Basal assessment

    Non-consumer, Ex-consumer, Not consuming during pregnancy, Occasional consumer, Daily consumer

  15. Family history of disease

    Time frame: Basal assessment

    No background, High blood pressure, Type 2 diabetes mellitus (T2DM), Hypertensive disorders during pregnancy, Other

  16. Weight

    Time frame: Basal assessment

    Kg

  17. Height

    Time frame: Basal assessment

    Cm

  18. Pregnancy-associated plasma A protein (PAPP-A)

    Time frame: Pregnancy weeks 13, 27 and 41. Postpartum month, 3, 6 and 12 months.

    Biomarker of preeclampsia expressed in MoM

  19. Placental growth factor (PlGF)

    Time frame: Pregnancy weeks 13, 27 and 41. Postpartum month, 3, 6 and 12 months.

    Biomarker of preeclampsia expressed in pg/mL

  20. Ratio sFlt-1/PlGF

    Time frame: Pregnancy weeks 13, 27 and 41. Postpartum month, 3, 6 and 12 months.

    Biomarker of preeclampsia

  21. Postpartum physical activity habits (IPAQ)

    Time frame: Postpartum month, 3, 6 and 12 months.

    Low, moderate, high

  22. Physical activity habits in pregnancy (PPAQ)

    Time frame: Pregnancy weeks 13, 27 and 41

    METS-h/week

  23. Postpartum specific anxiety scale (PSAS - ES)

    Time frame: Postpartum month, 3, 6 and 12 months.

    Minimal anxiety, Mild anxiety, Moderate anxiety, Severe anxiety

  24. Edinburgh Scale for Postnatal Depression (EPDS - ES)

    Time frame: Postpartum month, 3, 6 and 12 months.

    No postnatal depression, Mild symptoms, Moderate symptoms, Significant symptoms

  25. Maternal-fetal complications in pregnancy

    Time frame: Pregnancy weeks 13, 27 and 41

    No complications, Severe nausea and vomiting, Pre-eclampsia, Gestational hypertension, Gestational diabetes, Infections, Anemia, Detachment of placenta, Restriction of intrauterine growth, Placenta previa, Other

  26. Postpartum complications

    Time frame: Postpartum month, 3, 6 and 12 months.

    No complications, Postpartum hypertension, Postpartum hemorrhage, Postpartum infections, Postpartum depression, Deep vein thrombosis or pulmonary embolism, Perineal pain, Other

  27. Hospitalizations pregnancy

    Time frame: Pregnancy weeks 13, 27 and 41

    Number

  28. Reason hospitalization

    Time frame: Pregnancy weeks 13, 27 and 41

    No hospitalization, Severe nausea and vomiting, Infections, Abnormal vaginal bleeding, Postpartum bleeding, Postpartum infections, Complications from cesarean section, Mood disorders, Cardiorespiratory complications, Other

Study contacts

Contact information is provided by the study sponsor or research team.

Alicia González Represas

CONTACT

[email protected]

616044977

Sponsors and collaborators

Lead sponsor

Fundacin Biomedica Galicia Sur

Other

Registry information

Acronym: EMMA

Important dates

Study start
2025
Primary completion
2027
Study completion
2027
First posted
Jan 29, 2026
Registry last updated
Feb 17, 2026

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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