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D-tech | Projects
Prenatal vitamin D exposure and the association with childhood obesity at Institute of Preventive Medicin

The overall hypothesis of the PhD-project is that indivduals exposured to abundant vitamin D prenantally will have a lower risk of developing obesity comapred to individuals with prenatal exposure to vitamin D.

The project will be based on data from Copenhagen School health Record Registry which comprises more than 350,000 records. For every child the register contains annual measures of height and weight starting at age 6 and ending at age 14.

The first subproject concerns vitamin D obtained through exposing skin to UVB-radiation from the sun. Our hypothesis is that prenatal vitamin D exposure from dermal synthesis of vitamin D will influence childhood BMI and we expect to see that children born in months with no or low sun-related UVB-exposure will have higher risk of becoming overweight or obese during childhood compared to children born in months wigh high or moderate sun-related UVB-exposure.

The other subprojects focus on dietary vitamin D and utilize the fact that in 1985 mandatory fortifying margarine with vitamin D in Denmark was canceled. We hypothesize that children born after fortification will have higher risks of developing obesity during childhood than children born during the period of vitamin D fortification.

Supervisors: Professor TIA Sørensen and Professor Berit L Heitmann
Associated researcher: PhD Student Camilla Bjørn Jensen

 Influence of vitamin D status in utero and at the time of birth on the risk of childhood fractures at Department of Clinical Research, University of Southern Denmark and Odense Patient data Explorative Network (OPEN), Odense University Hospital , Institute of Preventive Medicine & Parker Institute

The aim of the PhD project is to examine the influence of nutrition in early life on the risk of bone fractures during childhood and adolescence among the offspring. The PhD project is based on a systematic review of nutrient and food intakes in early life and risk of childhood fractures, as well as data from the Danish national registries, biobank from the National neonatal screening program and a comprehensive longitudinal birth cohort from the Southampton Women Survey.

The overall hypothesis is that individuals who are exposed to an insufficient diet during critical periods of growth are at higher risk of insufficient bone mineralization and hence have a higher risk of fractures compared to individuals with optimal nutritional status

The aim of the first subproject is to examine if exposure to vitamin D fortified food during prenatal life affects the risk of fractures in late childhood. The study design is based on termination of a mandatory vitamin D fortification program. The main study outcome is fracture of the forearm, wrist or scaphoid bone, clavicle and ankle in the period of vitamin D fortification. Using the civil registration numbers, individuals will be individually linked to the Danish National Patient Registry (Landspatientregisteret) for incident and recurrent diseases.

To validate the effect of fortification and for cases of fractures residual dried blood spots cards, stored in the Biological Specimen Bank for National Screening at State’s Serum Institute, will be used from individuals who had fractures entities and time and gender-matched controls. The aim is examine actual exposure differences at birth and we hypothesize that serum 25(OH)D3 levels at the time of birth is significantly lower among children who go on to sustain fractures in childhood.

The final subproject focus on the maternal antenatal serum vitamin A status and neonatal bone mineralization using the Southampton Women Survey mother-offspring cohort. We hypothesized that serum retinol concentrations during late pregnancy are negatively associated with offspring neonatal bone mineralization and serum β-carotene concentrations during late pregnancy are positively associated with offspring neonatal bone mineralization assessed by DXA.

Supervisors: Professor Bo Abrahamsen, Professor Berit L Heitmann and Professor Cyrus Cooper
Associated researcher: PhD Student Mina N.H. Händel

 Foetal vitamin D status and risk of preeclampsia later in life, at Institut of Preventive Medicine, Research Unit for Dietary Studies

Maternal vitamin D deficiency is common during pregnancy and a widespread public health problem. Vitamin D deficiency may have implications for both the healthy pregnant woman and for the child’s early development and health later in life due to the fact that the fetus’s and new-born child’s vitamin D status depend on the maternal vitamin D status.

Preeclampsia is a preganacy related disorder and affects 3 – 5 % of all pregnancies. Preeclampsia is characterised by hypertension and proteinuria after 20 weeks’ gestation and is associated with increased risk of preterm birth and intrauterine growth restriction. Compared with normal pregnancies, preeclampsia is charaterised by marked changes in vitamin D metabolism pointing toward an association between vitamin D status and the developing of preeclampsia. Several studies have suggested that maternal vitamin D deficiency may be an independent risk factor for preeclampsia. However, the findings are not consistent. A study, however with limted power, have reported that the risk of preeclampsia was lower among women who have received vitamin D supplementation regularly during their first years of life compared to women who only had received vitamin D supplementation irregularly, or not at all, supporting the hypothesis that vitamin D supplementation in infancy has long-term beneficial effects for the child later in life, in terms of an risk of developing preeclampsia when getting pregnant.

The aim of this PhD project is to investigate the influence of vitamin D status on the risk of developing preeclampsia both for the mother and later on for the female offspring during subsequent pregnancies. The hypothesis is that exposure to additional vitamin D via fortification has had a beneficial effect on the risk of developing preeclampsia.

Supervisors: Professor Berit L Heitmann and Dr. Med. Sci., Professor Peter Damm
Associated researcher: PhD Student Maria Stougaard

 Vitamin D during gestation and risk of type 1 diabetes later in life, at Institute of Preventive Medicine

Incidence of type 1 diabetes (T1D) has been increasing worldwide at alarming rates during the past decades, with the disease occurring earlier in life. Although it is generally accepted that the etiology of T1D arises from contributions of both genetics and environmental factors, the exact pathogenesis of human T1D remains essentially unknown. Vitamin D, however, was hypothesized to be involved in prevention of the disease.

The objective of this sub-project is to examine if exposure to vitamin D fortified foods beneficially affects the development of T1D later in life, and to examine if low levels of vitamin D during gestation will have adverse effects on the long-term T1D risk of offspring.

The sub-study will test three hypotheses.

The first hypothesis focuses on dietary vitamin D and utilizes the fact that mandatory fortifying of margarine with vitamin D in Denmark was cancelled in 1985. We expect that individuals born during the periods of vitamin D fortification, and therefore exposed to greater amounts of vitamin D prenatally, will have a lower risk of developing T1D later in life than children born before or after vitamin D fortification.

The second hypothesis, additionally to food fortification, concerns also seasonal variation in vitamin D synthesis in the skin as a result of exposure to UVB-radiation from the sun. We expect to see that the vitamin D fortification during sun-deprived months will show greater effects in lowering the risk of T1D later in life, that the vitamin D fortification during sunny months.

The third hypothesis concerns neonatal vitamin D status in dried blood spots (DBS) from individuals who develop T1D later in life and a random cohort born during the same period, and examines association between actual vitamin D in newborn and the later risk of T1D. We expect that vitamin D levels at the time of birth is significantly lower in children who develop T1D later in life.

Associated researchers: Postdoc Ramune Jacobsen and Professor Berit L Heitmann

 Prenatal vitamin D deficiency and risk of schizophrenia in adulthood, at Institue of Preventive Medicine

Clinical studies have reported that perinatal vitamin D deficiency is associated with the development of schizophrenia in adulthood. However, research desings, methodologies and results have been ambigous.

We have utilized that mandatory fortification in Denmark of vitamin D to margarine was terminated June 1985. Two cohorts were selected for the study: an exposed cohort born 1983-85 and an unexposed cohort born 1986-88.. Due to the seasonal variation of vitamin D synthesis in the skin, we included month of birth as an interactive variable. All ID-numbers were screened in the Danish Psychiatric Research Register allowing us to estimate the hazard rate of schizophrenia in the first 25 years of life.

Associated researchers: Joachim Knop, M.D., Dr. Med. Sci, Peder Frederiksen, MSc and Professor Berit L Heitmann

 Prenatal exposure to vitamin D fortified food and risk of type 2 diabetes (T2D) later in life, at Institut of Preventive Medicine, Research Unit for Dietary Studies

Several studies suggested an association between prenatal vitamin D deficiency and risk of T2D later in life. The objective of this project is to examine if prenatal exposure to vitamin D fortified food affects the risk of developing T2D in adulthood.

Vitamin D fortification of margarine was mandatory in Denmark until 1985. Consequently, individuals born 1 – 2 years before 1985 were prenatally exposed to vitamin D fortified foods, while individuals born 1 – 2 years after 1985 were not. Moreover, in Denmark, every citizen receives a civil registration number (CPR), which can be individually linked to Danish administrative registries and large clinical database. Using CPR, the individuals from the above described birth cohorts will be linked to National Diabetes Registry to find out information on their diabetes outcomes. Statistical analyses will compare time to disease debut between exposed and unexposed cohorts, and will be conducted by Cox regression.

This project will be started up during 2014. We expect that individuals from birth cohorts exposed to vitamin D fortified foods prenatally will have lower T2D hazards compared to unexposed individuals.

Our results will provide evidence for the descisions on whether pregnant women should be supplemented with vitamin D to prevent T2D in their children.

Supervisors: Professor Berit L Heitmann, Dr. Med. Sci., Professor Allan Vaag & Postdoc Ramune Jacobsen
Associated researcher: PhD student Amélie C Keller

Influence of prenatal vitamin D on the development of asthma later in life, at The Parker Institute, Research Unit for Dietary Studies

A number of studies have indicated that vitamin D may be of importance for development of asthma. However, studies assessing the effect of Vitamin D status during prenatal life on childhood asthma development are few and conflicting. Some studies report an inverse association between maternal vitamin D intake during pregnancy and the development of asthma later in life and others report no association; it has even been proposed that high vitamin D status is associated with development of childhood asthma.

The aim of this project is to examine the association between extra prenatal vitamin D as a result of a national fortification program, and the risk of developing asthma later in life; as well as variations in vitamin D status at birth for children developing asthma and controls.

This project will use information from a Danish societal intervention, a mandatory vitamin D fortification of margarine, and data from dried blood spots stored in the Danish Neonatal Biological bank; and link the information at individual level to information on asthma from The National Patient Register, The Danish National Prescription Registry, and The Danish Health Examination Survey. The statistical analyses will be both longitudinal time to event using survival analysis, and case-control design using conditional logistic regression analysis.

Results from this project will show if extra vitamin D from fortification during fetal life impacts on risk of asthma; it will guide basic research examining the biological mechanism relating exposure to vitamin D and the development of asthma, and inform policy by providing new data on life course perspectives from vitamin D fortification.

Supervisors: Professor Berit L Heitmann, Postdoc Ekaterina Maslova, Postdoc Ramune Jacobsen
Associated researcher: PhD student Fanney Thorsteinsdottir