Vitamin D and Angiogenic Markers in Odense Child Cohort 1 (VITAM)

May 5, 2015 updated by: Henrik Christesen, Odense University Hospital

Vitamin D and Angiogenic Markers in Odense Child Cohort 1: A Prospective Cohort Study on Their Role in Early Pregnancy Adverse Outcome

The Vitamin D and Angiogenic Marker Study 1:

Vitamin D and angiogenic markers in early pregnancy. Epidemiology and associations to early-pregnancy miscarriage

Study Overview

Status

Active, not recruiting

Conditions

Detailed Description

Overall: The Odense Child Cohort Study (OCC) is a population-based cohort study, comprising pregnant women recruited between January 1st 2010 and December 31st 2012. All women who were pregnant in the municipality of Odense during this time were eligible for participation, and 6,707 women were approached directly with recruitment material.

The study complied with the Helsinki declaration and was approved by the Regional Scientific Ethical Committee for Southern Denmark, no. S-20090130. All participants gave informed consent. From a population base of 6,707 pregnant women, 2,874 (42.9%) enrolled in the OCC up to December 31st, 2012. The children will be followed until 18 years of age.

Serum samples were taken in early pregnancy (GA 2-25 weeks), late pregnancy (GA 26-30 weeks), maternal serum and cord blood at birth, and from the children along with general examinations at ages 3 months, 1 year, 3 years.

Questionnaires were completed by the families in early pregnancy, late pregnancy, after birth, and at the times of clinical examination of the children.

Register data on health variables were further available from the Danish registries.

Objective: The Vitamin D and Angiogenic Marker Study 1 examines the relationship between serum biomarkers 25(OH)D and soluble Fms-like kinase 1 (sFlt-1) and placental growth factor (PlGF) in pregnancy and risk of miscarriage as an adverse outcome in early pregnancy.

Method:

  • 25(OH)D analysis: Serum was stored at -80º Celsius until analysis, which was performed by liquid chromatography mass spectrometry (LC-MS/MS). Triple deuterium marked 25(OH)vitamin D3 was added to serum samples as internal standard and deproteinized with ZnSO4 in methanol, centrifuged at 2750 g for 10 minutes, and 100 μl was injected on the TurboFlow column (Thermo Scientific) on the LC-MS/MS. The LC-MS/MS consisted of a Thermo Scientific TLX1 system connected to a Thermo Scientific Vantage TSQ. 25(OH)D2 and 25(OH)D3 were concentrated on a Thermo Scientific Cyclone P 50 x 1.0 mm column and back-flushed on the analytical column, Phenomenex Gemini C18 50 x 3.0 mm and eluted from the analytical column by a gradient. Mobile phases were A: 10 mM NH4Ac in water and B: 10 mM NH4Ac in methanol. Human serum was spiked with appropriate amounts of 25(OH)D2 and 25(OH)D3 in order to produce six point calibration curves (weighed 1/x2) and 3 levels of QC samples (low, mid, high). The method was calibrated against NIST standard 972.25 The C3 epimer of D3 was detected along with D3 and the two were not distinguishable from one another. Lowest detectable concentrations were 0.15 nM for both D2 and D3. Values of D2 and D3 were only considered if above 6.5 nM.
  • Measurements for BRAHMS sFlt-1 and PIGF KRYPTOR assays were performed on the fully automated KRYPTOR compact Plus system (KRYPTOR PlGF and KRYPTOR sFlt-1; Thermo Fisher Scientific) according to the manufacturer's instructions. The BRAHMS sFlt-1 and PlGF KRYPTOR assays are homogeneous sandwich immunoassays based on the Trace technology24. The total duration of the assays are 9 minutes (sFlt-1) and 29 minutes (PlGF) and the sample volume is 9 µl, and 70 μl, respectively. The assays are calibrated with recombinant human sFlt-1 and PIGF and standardized against the Quantikine PIGF ELISA (R&D Systems Europe Ltd, Abingdon, UK) and against the sFlt-1 Elecsys assay (Elecsys, Penzberg, Germany). According to the manufacturer's instructions for use, the KRYPTOR sFlt-1 assay covered a measuring range of 22-90,000 pg/ml. The limit of detection is 22 pg/ml and the limit of quantization (functional sensitivity) is 29 pg/ml. The intra- and inter-assay variations at an sFlt-1 concentration of 1540 pg/ml are 0.3% and 0.8%, respectively; at 2988 pg/ml 0.5% and 1.1%; and at 9666 pg/ml 0.5% and 1.0%, respectively. The KRYPTOR PlGF assay covers a measuring range of 3.6-7.000 pg/ml. The limit of detection is 3.6 pg/ml and the limit of quantitation is 6.9 pg/ml. The intra- and inter-assay variations at a PlGF concentration of 35 pg/ml are 4.6% and 7.3%, respectively; at 103 pg/ml 2.1% and 3.1%, and at 430 pg/ml 0.9% and 2.3%, respectively.
  • Measurements for Elecsys sFlt-1 and PIGF assays were performed on the fully automated Elecsys system (Elecsys, Penzberg, Germany) according to the manufacturer's instructions. The Elecsys assays are sandwich immunoassays based on the electrochemiluminescence technology. The total duration of the assays is 18 minutes and the sample volume is 20 µl for sFlt-1 and 50 µl for PIGF. The assays are calibrated with recombinant human PIGF and sFlt-1 and standardized against the Quantikine PIGF and vascular endothelial growth factor-R1 ELISAs (R&D Systems, Minneapolis, MN). According to the manufacturer's instructions for use, the Elecsys sFlt-1 assay covers a measuring range from 10-85,000 pg/ml, the Elecsys PIGF assay from 3-10,000 pg/ml. The limit of detection is 10 pg/ml (sFlt-1) and 3 pg/ml (PIGF). The limit of quantization is 15 pg/ml for sFlt-1 and 10 pg/ml for PIGF.

The Vitamin D and Angiogenic Marker Study 1:

Vitamin D and angiogenic markers in early pregnancy. Epidemiology and associations to early-pregnancy miscarriage

  • In 1728 serum samples collected in early pregnancy, the levels of serum 25(OH)D were investigated by LC-MS/MS and levels of sFlt-1 and PlGF were determined by immunoassays in 1720 samples. Questionnaire and medical file information was used to determine the factors which were influential on 25(OH)D levels and sFlt/PlGF in early pregnancy by multiple linear regression and logistic regression.
  • In 1675 serum samples collected before gestational age 22+0 weeks, analysis was performed to evaluate the predictive properties of sFlt-1 and PlGF levels as biomarkers of miscarriage (n=59).
  • In 1684 serum samples collected before gestational age 22+0 weeks, the levels of 25(OH)D were compared between women who subsequently suffered spontaneous abortions (n=59) and the rest of the population, corrected for select covariates.

Study Type

Observational

Enrollment (Actual)

2874

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
      • Odense, Denmark, 5000
        • HCA Research, Odense University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Sampling Method

Non-Probability Sample

Study Population

The Odense Child Cohort Study (OCC) is a population-based cohort study, comprising pregnant women recruited between January 1st 2010 and December 31st 2012. All women who were pregnant in the municipality of Odense during this time were eligible for participation, and 6,707 women were approached directly with recruitment material.

The study complied with the Helsinki declaration and was approved by the Regional Scientific Ethical Committee for Southern Denmark, no. S-20090130. All participants gave informed consent. From a population base of 6,70 pregnant women, 2,874 (42.9%) enrolled in the OCC up to December 31st, 2012. The children will be followed until 18 years of age.

Description

Inclusion Criteria:

  • Pregnant and residing in the municipality of Odense during 2010-2012

Exclusion Criteria:

  • Not residing in Odense, leaving the municipality

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Spontaneous Abortion
Time Frame: Outcome is assessed in gestational weeks 5+0 to 22+0.
Occurrence of spontaneous abortion, as diagnosed by transvaginal ultrasound in medical files. The time from inclusion in cohort to occurrance of spontaneous abortion was on average 13 days.
Outcome is assessed in gestational weeks 5+0 to 22+0.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Odense University Hospital

Investigators

  • Principal Investigator: Henrik T Christesen, MD, PhD, project leader

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2010

Primary Completion (Anticipated)

December 1, 2031

Study Completion (Anticipated)

December 1, 2031

Study Registration Dates

First Submitted

November 20, 2014

First Submitted That Met QC Criteria

May 5, 2015

First Posted (Estimate)

May 6, 2015

Study Record Updates

Last Update Posted (Estimate)

May 6, 2015

Last Update Submitted That Met QC Criteria

May 5, 2015

Last Verified

April 1, 2015

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • VITAM1

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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