Vanadium in Late-onset Preeclampsia

Preeclampsia Clinical Trial

— Vanadium PE  

Official title:

Analyses of Maternal Plasma Cadmium, Lead and Vanadium Levels in the Diagnosis and Severity of Late-onset Preeclampsia; A Prospective and Comparative Study From Turkey

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04200222
• Other study ID #: CengizGWCH1
• Status: Completed
• Start date: March 1, 2018
• Est. completion date: August 30, 2019

Study information

• Verified date: December 2019
• Source: Cengiz Gokcek Women's and Children's Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Introduction: Cadmium, lead and vanadium important pollutants produced from anthropogenic activities, has been suggested to be embryotoxic and fetotoxic in a lot of studies. However, the causes of preeclampsia are little known and heavy metals merit further investigation. We tested whether late-onset preeclampsia (L-PrE) was associated with exposure to these metals.

Methods: This study was designed to determine maternal plasma cadmium, lead and vanadium concentrations in women with L-PrE (n=46) compared to those of normotensive women (n=46). These three heavy metals concentrations measured using inductively coupled plasma-mass spectrometry were compared.

Description:

This observational case-control study was conducted at the Department of Obstetrics and Gynecology, Cengiz Gokcek Public Hospital, Gaziantep, Turkey, between March 2018 and June 2019. The protocol was approved by the Ethics Committee for Clinical Research of Gaziantep University (reference no: 2019/36). The study strictly adhered to the principles of the Declaration of Helsinki. All subjects included in the study gave oral and written informed consent. Ninety-two women were enrolled in the study in two groups.

Data collection and Study intervention:

The diagnosis of L-PrE, as defined by the Committee on Terminology of the American College of Obstetricians and Gynecologists (ACOG), is established based on the presence of proteinuria (urinary excretion of protein ≥300 mg in a 24-h urine specimen, or proteinüria ≥1+ in dipstick) and a blood pressure level of ≥90/140 mmHg (two blood pressure measurements 6 h apart) that occurs after 34 weeks of gestation in a previously normotensive woman. The diastolic and/or systolic blood pressure <110/160 mm Hg, it was accepted as mild; and in case these values exceeded this level, it was accepted as severe. Every women in the study population underwent obstetric ultrasound examination and fetal-maternal assesment was carried out by one of the authors. The obstetric anamnesis were obtained from all subjects. The dempograhic data like age, gravidity, parity, body mass index (BMI) and gestational age were recorded. The gestational age was determined by calculation from the last menstrual period and supported by the ultrasonography measurements at first trimester of gestation. Maternal venous plasma samples were taken for measurement of cadmium, lead and vanadium levels after the diagnosis of L-PrE in outpatient clinic. These samples quickly centrifuged at 1,500 g for 10 min, plasma samples were seperated and stored at -80 C until the day of measurement. All patients with L-PrE were also hospitalized and their pregnancies were terminated. The samples of the control groups were obtained during the routine obstetrical care examination in the third trimester of pregnancy. Then, these pregnant women were followed-up until the delivery. Both groups were compared in terms of maternal age, BMI, week of gestation, gravida, parity, live born, systolic/diastolic blood pressure, total protein in spot urine sample, hemoglobin, hematocrit, platelet count, white blood cell count, urea, uric acid, albümin, blood urea nitrogen, creatinine, liver function tests (AST, ALT), lactic acid dehydrogenase, cadmium, lead and vanadium concentrions and infant weight at delivery. Small for gestational age (SGA) neonate was defined as birth weight <10th percentile for gestational age with Turkey's national nomogram as the reference for fetal growth. The samples were transferred within boxes in ice molds to Yozgat Bozok University Science and Technology Application and Research Center (Occupational and Environmental Toxicology Laboratory) for measuring heavy metal and trace element levels. The frequency of seafood consumption was divided into four categories: 2-3 per week, 1-2 per week, 1-2 per month, and rare. Smoking was classified into 3 groups (none, formerly smoker, and active smoking). Passive smoking was also categorized into 2 groups (no and yes). The education levels was classified into 4 groups (illiterate, primary education, high school, and university). The residences of women was classified as rural and urban. Furthermore, the residences of women have divided either living near a busy street (around 100 metres) or not.Small for gestational age (SGA) neonate was defined as birth weight <10th percentile for gestational age with Turkey's national nomogram as the reference for fetal growth.

The method developed by Aliyev et al. was used for preparing the samples for analysis One milliliter of plasma samples was placed into high-temperature-resistant Teflon tubes in a microwave oven, and 5 mL Suprapur® (Merck, Darmstadt, Germany) nitric acid (HNO3) and 5 mL ultra-pure water was added. All plasma samples were digested using a microwave digestion system (Start D; Milestone, MD, USA). After digestion, each sample was made to a total volume of 20 mL with 9 mL ultra-pure water in a 50 mL polypropylene tube. Nitric acid (Suprapur®, 65%) was used for digestion of samples and standard reference material. Ultra-pure water (Direct-Q®; Millipore, Darmstadt, Germany) was used for dilution of the standard (multi-element standard Chem-Lab, Zedelgem, Belgium) and sample preparations.

The three metals (cadmium, lead and vanadium) were measured using inductively coupled plasma-mass spectrometry (Thermo Scientific ICAPQc, USA). The operating parameters were set as follows: radiofrequency power 1550 W, nebulizer gas 0.96 L/min, plasma gas 0.88 L/min, nebulizer pressure 3.01 bar, dwell time 0.01 milliseconds, and spray chamber temperature 3.7°C. The sampler probe was washed between injections by rinsing with ultrapure water for 30 s, followed by washing with 2% HNO3 for 45 s, and finally rinsing with ultrapure water for 45 s. After the washing steps, the instrument automatically ran the next sample. An 11-point calibration curve (0.5-500 µg/L) was used to measure the level of each element. The r2 values of the calibration curves of all metals were calculated, and the minimum value was 0.9994. To ensure the accuracy of the results, each measurement of the samples and standards was repeated three times. The results of these measurements showed that the relative standard deviation (RSD) did not exceed 5%. Certified Reference Material (CRM-Seronorm™ Trace Elements Whole Blood L-2, Sero AS, Billingstad, Norway) was used for the validation method. To check the stability and sensitivity of the instrument, a mixture of internal standards (Hf) was used, and the mean and RSD values of metals were also calculated. The variations of each measurement of the quality controls was <15%. The relative percentage differences in replicate analyses were <5% in the samples and standards.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: August 30, 2019
• Est. primary completion date: June 30, 2019
• Gender: Female
• Age group: 18 Years to 40 Years

Eligibility

Inclusion Criteria:

• preeclampsia

• healthy pregnancy

Exclusion Criteria:

1. pregnant women with any systemic condition (such as chronic hypertension, renal disease and )

2. using any kind of medication/supplement intake throughout pregnancy (such as heparin)

3. history of medication for PE treatment at the time of first admission

4. smoking

5. drug user

6. patients who had fetal congenital abnormalities or genetic syndromes

7. multiple-gestation pregnancies

8. pregnancies resulting from in vitro fertilization

9. intrauterine fetal death

10. having family history of preeclampsia

Related Conditions & MeSH terms

• Pre-Eclampsia
• Preeclampsia

Intervention

Diagnostic Test:
• cadmium, lead and vanadium measurements and compare
The method developed by Aliyev et al. was used for preparing the samples for analysis (1). The three metals (cadmium, lead and vanadium) were measured using inductively coupled plasma-mass spectrometry (Thermo Scientific ICAPQc, USA). 1. Ovayolu A, Ovayolu G, Karaman E, Yuce T, Ozek MA, Turksoy VA. Amniotic fluid levels of selected trace elements and heavy metals in pregnancies complicated with neural tube defects. Congenit Anom (Kyoto). 2019:10.1111/cga.12363.

Locations

Country	Name	City	State
Turkey	Cengiz Gokcek Women's and Child's hospital	Gaziantep

Sponsors (1)

Lead Sponsor	Collaborator
Cengiz Gokcek Women's and Children's Hospital

Country where clinical trial is conducted

Turkey, 

References & Publications (5)

Gruzewska K, Michno A, Pawelczyk T, Bielarczyk H. Essentiality and toxicity of vanadium supplements in health and pathology. J Physiol Pharmacol. 2014 Oct;65(5):603-11. Review. — View Citation

Ovayolu A, Ovayolu G, Karaman E, Yuce T, Ozek MA, Turksoy VA. Amniotic fluid levels of selected trace elements and heavy metals in pregnancies complicated with neural tube defects. Congenit Anom (Kyoto). 2019 Nov 19. doi: 10.1111/cga.12363. [Epub ahead of print] — View Citation

Poropat AE, Laidlaw MAS, Lanphear B, Ball A, Mielke HW. Blood lead and preeclampsia: A meta-analysis and review of implications. Environ Res. 2018 Jan;160:12-19. doi: 10.1016/j.envres.2017.09.014. Epub 2017 Sep 21. — View Citation

Wang F, Fan F, Wang L, Ye W, Zhang Q, Xie S. Maternal Cadmium Levels During Pregnancy and the Relationship with Preeclampsia and Fetal Biometric Parameters. Biol Trace Elem Res. 2018 Dec;186(2):322-329. doi: 10.1007/s12011-018-1312-3. Epub 2018 Apr 12. — View Citation

Zhang Q, Huang Y, Zhang K, Huang Y, Yan Y, Wang F, Wu J, Wang X, Xu Z, Chen Y, Cheng X, Li Y, Jiao J, Ye D. Cadmium-induced immune abnormality is a key pathogenic event in human and rat models of preeclampsia. Environ Pollut. 2016 Nov;218:770-782. doi: 10.1016/j.envpol.2016.07.073. Epub 2016 Aug 7. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Tertiary outcome was to compare the cadmium, lead and vanadium levels in SGA group and non-SGA group.	Tertiary outcome was to compare the cadmium, lead and vanadium levels in SGA group and non-SGA group.	1 day
Primary	The primary outcome in these analyses was to compare cadmium, lead and vanadium levels in L-PrE group and control group.	The primary outcome in these analyses was to compare cadmium, lead and vanadium levels in L-PrE group and control group.	3 months
Secondary	The secondary outcome was to compare the cadmium, lead and vanadium levels in mild L-PrE group and severity L-PrE group.	The secondary outcome was to compare the cadmium, lead and vanadium levels in mild L-PrE group and severity L-PrE group.	1 day