D-tecting Disease - From Exposure to Vitamin D During Critical Periods of Life (D-tect)

Vitamin D deficiency is common among otherwise healthy pregnant women and may have consequences for them as well as the early development and long-term health of their children. However, the importance of maternal vitamin D status has not been widely studied.

The present study is divided into a societal experiment (1) and a case-cohort study (2):

1. The present study includes an in-depth examination of the influence of exposure to vitamin D early in life and during critical periods of growth for development of type 1 diabetes (T1D), type 2 diabetes, gestational diabetes, pre-eclampsia, obesity, asthma, arthritis, cancer, mental and cognitive disorders, congenital disorders, dental caries and bone fractures during child- and adulthood. The study is based on the fact that mandatory fortification of margarine with vitamin D, which initiated in 1937, was terminated in 1985.

   Apart from determining the influences of exposure prior to conception and during pre- and postnatal life, the investigators examined the importance of vitamin D exposure during specific seasons and trimesters, by comparing disease incidence among individuals born before and after the fortification.

2. Additionally, a validated method was used to determine neonatal vitamin D status using stored dried blood spots (DBS) from individuals who develop the aforementioned disease entities as adults and their time and gender-matched controls.

Unparalleled, the study will help determine the effects of vitamin D exposure during critical periods in life. There are a sufficient number of individuals to verify any effects during different gestation phases and seasons of the year. The results, which will change our current understanding of the significance of vitamin D, will enable new research in related fields, including interventional research designed to assess supplementation needs for different subgroups of pregnant women. Also, other health outcomes can subsequently be studied to generate multiple new interdisciplinary health research opportunities involving vitamin D.

Study Overview

• Status: Completed
• Conditions: Obesity; Diabetes Mellitus; Cancer; Arthritis; Vitamin D Deficiency; Asthma; Pregnancy Complications; Tooth Diseases; Birth Weight; Pre-Eclampsia; Mental Disorder; Congenital Disorders; Bone Fracture; Birth Disorder
• Intervention / Treatment: Other: D-tect

• Study Type: Observational
• Enrollment (Actual): 222776

Contacts and Locations

Study Locations

• Denmark
  • Frederiksberg, Denmark, 2000
    • Parker Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Entire Danish population born between June1983-May1985 and September 1986-August 1988.

For the part of the study using vitamin D measurements from DBS:

The Danish Civil registration system was used to identify all live-born children during 1981-2002 (n = 1,360,466), and a random subcohort thereof was sampled for 25(OH)D analyses to be used across the D-tect studies (n = 3585)

Description

Inclusion Criteria:

1. Born in Denmark around the fortification period
2. Sufficient amount of blood from the DBS

Exclusion Criteria:

1.Born outside Denmark

1. Born outside the fortification period
2. Insufficient amount of blood from the DBS or DBS not found

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Exposed; Individuals born between June1983 and May1985 were exposed to the mandatory vitamin D margarine fortification during fetal life.; Cases: individuals defined as having one of the aforementioned diseases of interest from the registers	Other: D-tect; This study is based on a unique Danish social experiment that took place during a well-defined period between 1937 and December 1985, when it was mandatory to fortify all margarine with vitamin D (1.25 μg/100 g). This well-defined vitamin D fortification period makes it possible to investigate the impact of fetal exposure to extra vitamin D from food fortification on the risk of developing diseases later on. This study is possible due not only to the well-defined adjacent time window but also to the complete registration of every citizen via a civil registration number. This number can be linked, on an individual level, to Danish birth, patient and medical registries; social and ethnic registries; and clinical and other large databases; Case-cohort study: vitamin D measurements from dried blood spots and the risk of diseases later on
Non-exposed; Individuals born between September1986 and August 1988 were not exposed to the mandatory vitamin D margarine fortification during fetal life.; Controls: cohort of matched disease-free individuals	Other: D-tect; This study is based on a unique Danish social experiment that took place during a well-defined period between 1937 and December 1985, when it was mandatory to fortify all margarine with vitamin D (1.25 μg/100 g). This well-defined vitamin D fortification period makes it possible to investigate the impact of fetal exposure to extra vitamin D from food fortification on the risk of developing diseases later on. This study is possible due not only to the well-defined adjacent time window but also to the complete registration of every citizen via a civil registration number. This number can be linked, on an individual level, to Danish birth, patient and medical registries; social and ethnic registries; and clinical and other large databases; Case-cohort study: vitamin D measurements from dried blood spots and the risk of diseases later on

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Obesity	Register based	2012-2025
Type 1 diabetes	Register based	2012-2016
Pre-eclampsia	Register based	2012-2025
Bone facture	Register based	2012-2025

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Type 2 diabetes	Register based	2014-2025
Gestational diabetes	Register based	2014-2025
Asthma	Register based	2015-2025
Arthritis	Register based	2018-2025
Birth weight	Register based	2014-2019
Mental diseases	Register based	2012-2025

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cancers	Register based	2018-2025
Mental disorders	Register based	2018-2025
Dental caries	Register based	2018-2025
Congenital disorders	Register based	2018-2025

Collaborators and Investigators

• Sponsor: Bispebjerg Hospital
• Collaborators: The Danish Council for Strategic Research

Publications and helpful links

General Publications

• Keller A, Stougard M, Frederiksen P, Thorsteinsdottir F, Vaag A, Damm P, Jacobsen R, L Heitmann B. In utero exposure to extra vitamin D from food fortification and the risk of subsequent development of gestational diabetes: the D-tect study. Nutr J. 2018 Nov 2;17(1):100. doi: 10.1186/s12937-018-0403-5.

Helpful Links

• Study website

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2012
• Primary Completion (Actual): September 30, 2016
• Study Completion (Actual): September 30, 2016

Study Registration Dates

• First Submitted: October 31, 2017
• First Submitted That Met QC Criteria: October 31, 2017
• First Posted (Actual): November 6, 2017

Study Record Updates

• Last Update Posted (Actual): November 6, 2017
• Last Update Submitted That Met QC Criteria: November 2, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Wounds and Injuries; Nutrition Disorders; Body Weight; Stomatognathic Diseases; Avitaminosis; Deficiency Diseases; Malnutrition; Hypertension, Pregnancy-Induced; Disease; Vitamin D Deficiency; Mental Disorders; Birth Weight; Fractures, Bone; Eclampsia; Pre-Eclampsia; Pregnancy Complications; Tooth Diseases
• Other Study ID Numbers: 0603-00453B

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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