Assessing Health Consequences of Vitamin D Fortification Utilizing a Societal Experiment Design: Methodological Lessons Learned from the D-Tect Project

Mina Nicole Händel,Katrine Sidenius Duus,Ulrik Schiøler Kesmodel,Caroline Moos,Camilla Bjørn Jensen,Ramune Jacobsen,Fanney Thorsteinsdottir,Allan Jensen,Berit Lilienthal Heitmann,Maria Stougaard,Amélie Cléo Keller,Bo Abrahamsen

doi:10.3390/ijerph18158136

Abstract

By utilizing historical changes in Danish legislation related to mandatory vitamin D fortification of margarine, which was implemented in the mid 1930s and abruptly abandoned in June 1985, the studies in the D-tect project investigated the effects of vitamin D on health outcomes in individuals, who during gestation were exposed or unexposed to extra vitamin D from fortified margarine. This paper reviews and narratively summarizes the analytic approaches alongside the results of the societal fortification experiment studies from the D-tect project and addresses the challenges in designing societal experiment studies and evaluating their results. The latter are discussed as lessons learned that may be useful for designers of similar studies, expected to be extensively utilized while researching the health consequences of the COVID-19 pandemic by comparing individuals born before and after the epidemic. In the D-tect project, 16 articles based on the societal fortification experiment were published analyzing 10 different outcomes and using different statistical approaches. Lessons learned included the detail of the analysis of the historical information on the exposure, availability and validity of the outcome data, variety of analytical approaches, and specifics concerning vitamin D effect evaluation, such as consideration of the influence of sunshine or season. In conclusion, the D-tect project clearly demonstrated the cost-effectiveness and research potential of natural- or societal-experiment-based studies.

Highlights

Public and environmental health researchers often use societal or natural experiment design studies to explore how unplanned natural or societal events or national policy changes affect health outcomes, or when alternative study designs are not possible or not ethical [1]
Participants, data sources, and statistical methods used in the included studies of the D-tect project can be found in Table 1 and Table 2
To examine whether children born to women exposed to the margarine fortification policy with a small dose of extra vitamin D

Summary

Introduction

Public and environmental health researchers often use societal or natural experiment design studies to explore how unplanned natural or societal events (e.g., epidemics, famines, natural disasters, economic crises) or national policy changes affect health outcomes, or when alternative study designs are not possible or not ethical [1]. Among the most well-known examples of these studies are the Dutch famine studies that investigated the effects of extremely low macro- and micronutrient intake before or during gestation and early in life under famine on health outcomes later in life [2]. The Dutch famine studies later compared long-term health outcomes in individuals born in this part of the country before, during, or after the period of the famine. The studies utilized a life course approach to explore the role of early life factors on health throughout life. The Early Life Origins of Adult Disease hypothesis, known as the Developmental Origin of Health and Disease (DOHaD) hypothesis, proposed in the

Methods

Results

Discussion

Conclusion