Does Nicotine Influence the Risk of Preeclampsia? (PRE_Smoking)

Does Nicotine Influence the Risk of Preeclampsia? A Prospective Study

This prospective cohort study explores the long-term impact of pre-pregnancy smoking on vascular health in women predisposed to preeclampsia, conducted at the Medical University of Graz. The study specifically targets women at high risk for preeclampsia who are taking aspirin as a preventative measure.

The main question it aims to answer is:

Does smoking before pregnancy influence the development and severity of preeclampsia and its associated vascular changes in high-risk women?

Participants, divided into former smokers and non-smokers, underwent comprehensive assessments throughout their pregnancies. Measurements included hemodynamic parameters such as heart rate and blood pressure, assessed with an upper arm cuff, and arterial stiffness, evaluated using pulse wave velocity with the Vicorder device. Retinal microvasculature was examined through digital imaging, and the vascular health marker ADMA, nicotine exposure marker cotinine, blood pressure regulatory enzyme neprilysin, and cellular aging indicator telomere length were quantified from blood samples. Cortisol levels were also measured from hair samples to assess stress responses.

Study Overview

• Status: Completed
• Conditions: Endothelial Dysfunction; Hypertension in Pregnancy; Preeclampsia (PE)
• Intervention / Treatment: Other: This high-risk cohort underwent the same measurements during pregnancy: endothelial function, arterial stiffness, retinal microvasculature profile, measurement of Neprilysin, cotinine, telomere length

Detailed Description

The investigators collected extensive data on each participant, including age, BMI (body mass index), and medical history, to understand their baseline health. Routine laboratory tests were conducted to monitor the health status throughout the pregnancy. Preeclampsia biomarkers and Doppler ultrasound examinations of the uterine and umbilical arteries to assess fetal and placental blood flow were conducted. The investigators tracked the development of preeclampsia, gestational hypertension (GH), and gestational diabetes mellitus (GDM).

Outcomes for the babies, such as birth weight, delivery method, gender, and the gestational week at delivery, were meticulously recorded to evaluate the broader impacts of maternal smoking and vascular health on neonatal outcomes.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Austria
  • Steiermark
    • Graz, Steiermark, Austria, 8036
      • Medical University Graz

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• a positive preeclampsia screening or a history of preeclampsia, daily intake of 150mg aspirin , and age over 18 years

Exclusion Criteria:

• twin pregnancies, fetal anomalies, maternal chronic renal diseases and discontinued aspirin intake.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: previous smokers; All women at high risk for developing preeclampsia were divided into two groups based on reported smoking status: previous smokers who quit by the positive pregnancy test, and non-smokers.	Other: This high-risk cohort underwent the same measurements during pregnancy: endothelial function, arterial stiffness, retinal microvasculature profile, measurement of Neprilysin, cotinine, telomere length; This high-risk cohort underwent the same measurements during pregnancy: endothelial function, arterial stiffness, retinal microvasculature profile, measurement of Neprilysin, cotinine, telomere length, and routine laboratory parameters.
Other: non smokers; All women at high risk for developing preeclampsia were divided into two groups based on reported smoking status: previous smokers who quit by the positive pregnancy test, and non-smokers.	Other: This high-risk cohort underwent the same measurements during pregnancy: endothelial function, arterial stiffness, retinal microvasculature profile, measurement of Neprilysin, cotinine, telomere length; This high-risk cohort underwent the same measurements during pregnancy: endothelial function, arterial stiffness, retinal microvasculature profile, measurement of Neprilysin, cotinine, telomere length, and routine laboratory parameters.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of Pulse wave velocity	Pulse Wave Velocity (PWV): A measure of how fast the blood pressure pulse travels through the arteries, used to assess arterial stiffness. Higher PWV indicates stiffer arteries, linked to increased cardiovascular risk.	Measurements were conducted at three stages of pregnancy: (V1: 11-16 weeks), second trimester (V2: 24-28 weeks), and third trimester (V3: 34-37 weeks).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of Endothelial function	Endothelial Function Assessed through ADMA: Measurement of asymmetric dimethylarginine (ADMA), an inhibitor of nitric oxide production, provides insights into endothelial health and its capacity to regulate vascular function.	Measurements were conducted at three stages of pregnancy: (V1: 11-16 weeks), second trimester (V2: 24-28 weeks), and third trimester (V3: 34-37 weeks).
Change of retinal microvasculature profile	Retinal Microvasculature Profile Assessed through CRAE and CRVE: Central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE) are used to gauge the caliber of retinal blood vessels, reflecting systemic microvascular health.	Measurements were conducted at three stages of pregnancy: (V1: 11-16 weeks), second trimester (V2: 24-28 weeks), and third trimester (V3: 34-37 weeks).
Change of Neprilysin level	Neprilysin levels are analyzed to understand its role in modulating vasoactive peptides, which affect blood pressure and fluid balance.	Measurements were conducted at three stages of pregnancy: (V1: 11-16 weeks), second trimester (V2: 24-28 weeks), and third trimester (V3: 34-37 weeks).
Change of Cotinine level	Measured to determine exposure to nicotine, providing a reliable indicator of smoking status or secondhand smoke exposure.	Measurements were conducted at three stages of pregnancy: (V1: 11-16 weeks), second trimester (V2: 24-28 weeks), and third trimester (V3: 34-37 weeks).
Change of Telomere length	Telomere Length: The measurement of telomere length serves as a biomarker of cellular aging and an indicator of potential health risks and longevity.	Measurements were conducted at three stages of pregnancy: (V1: 11-16 weeks), second trimester (V2: 24-28 weeks), and third trimester (V3: 34-37 weeks).
Blood parameters for high-risk pregnancy monitor	Blood parameters for high-risk pregnancy monitor kidney, liver, inflammation, blood count, electrolytes, enzymes, coagulation, proteins, and placental function. Kidney: Creatinine, urea, uric acid, eGFR. Liver: Bilirubin, GGT, AST, ALT. Inflammation: CRP. Blood count: Leukocytes, erythrocytes, hemoglobin, hematocrit, MCV, MCH, MCHC, platelets, MPV. Electrolytes: Na, K, Cl, Ca, Mg. Enzymes: CK, LDH, glucose. Coagulation: PT, INR, aPTT, fibrinogen, antithrombin. Proteins: Total protein, albumin. Placental markers: sFlt-1, PlGF. These help assess maternal-fetal health, detect conditions like preeclampsia, gestational diabetes, and monitor complications in high-risk pregnancies.	Measurements were conducted at three stages of pregnancy: (V1: 11-16 weeks), second trimester (V2: 24-28 weeks), and third trimester (V3: 34-37 weeks).

Collaborators and Investigators

• Sponsor: Medical University of Graz

Study record dates

Study Major Dates

• Study Start (Actual): November 2, 2019
• Primary Completion (Actual): September 30, 2022
• Study Completion (Actual): December 17, 2023

Study Registration Dates

• First Submitted: October 15, 2024
• First Submitted That Met QC Criteria: October 15, 2024
• First Posted (Actual): October 16, 2024

Study Record Updates

• Last Update Posted (Actual): October 23, 2024
• Last Update Submitted That Met QC Criteria: October 21, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Endothelial Function; Smoking; Arterial Stiffness; Retinal Microvasculature; Preeclampsia Risk
• Additional Relevant MeSH Terms: Urogenital Diseases; Vascular Diseases; Cardiovascular Diseases; Female Urogenital Diseases and Pregnancy Complications; Pregnancy Complications; Hypertension; Pre-Eclampsia; Hypertension, Pregnancy-Induced
• Other Study ID Numbers: EK-Nr.: 31-541 ES 18/19

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No