Clinical trial NCT04291313: Vitamin D in Pregnancy
Official title: Vitamin D Deficiency in Pregnancy - Identifying Associations and Mechanisms Linking Maternal Vitamin D Deficiency to Placental Dysfunction and Adverse Pregnancy Outcomes
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Vitamin D Deficiency
Pre-Eclampsia
Fetal Growth Retardation
Gestational Diabetes
Lead sponsor: University of Aarhus
Sponsor class: OTHER
First posted: 2020-03-02
Enrollment: 2000
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Danish pregnant women are recommended ad daily vitamin D supplement of 10 µg. Despite the fact that 9 out of 10 women take vitamin D supplements, more than 40% of pregnant women are vitamin D deficient, putting them at an increased risk of pregnancy complications like fetal growth restriction and pre-eclampsia. Our hypothesis is that pregnant women would benefit from an increased intake og vitamin D and that an intake of 90µg/day can reduce the prevalence of placenta-related pregnancy complications. Combining a double-blinded randomized trial (10µg vs.90µg) with collection of placental material, we want to test if the prevalence of pregnancy complications is reduced and explore how vitamin D affects placenta to improve our understanding of the disease pathology and risk factors.

Detailed description: As vitamin D (vit-D) is essential for growth and linked to placental function, health authorities recommend a daily 10µg vit-D supplement in pregnancy. Despite the fact that 9 out of 10 women take supplements, more than 40% of pregnant women are vit-D deficient, putting them at an increased risk of pregnancy complications like fetal growth restriction and pre-eclampsia. These conditions affect 6-10 % of all pregnancies, increasing the risk of preterm delivery, perinatal morbidity and mortality. In worse case, preeclampsia may also be fatal for the pregnant women herself. Around 20% of vit-D intake comes from the diet (e.g. fish, egg yolk) and the rest from sun-exposure. However, in Denmark, there is not enough sunlight from October to March to fuel vit-D synthesis underlining the need for supplementation. The high prevalence of vit-D deficiency indicates that current guidelines are not sufficient. Indeed, today´s recommendations date back to a small-scale 1986 Norwegian study not taking into account dietary differences such as the high intake of fish in Norway. Since then, accumulating evidence has linked exposure to pregnancy complications and vit-D deficiency per see to long-term health problems in the affected children. This include a higher risk of asthma, cardiovascular disease, diabetes, obesity schizophrenia, neurodevelopmental problems and multiple sclerosis. Notably, the affected women also suffer an increased risk of disease, e.g. heart disease in later life. Vitamin D supplements in the range of 90-100 µg are safe in pregnancy, but it is not yet known if and to what extent increased vitamin D supplementation prevents pregnancy-related diseases. Combining clinical testing of 90 µg vitamin D supplements, with identification of which placental pathways that are affected by vit-D would considerably improve our understanding of disease pathophysiology and the role of vit-D and improve the health of future generations in an easily implementable way.

Eligibility criteria: Inclusion Criteria:

* All pregnant women attending the nuchal translucency scan in week 11-13 of gestation as part of the national prenatal screening program

Exclusion Criteria:

* Age\< 18 years
* Women with calcium metabolism disorders,
* Women who gets doctor prescribed vitamin D treatment
* Women with chronic kidney disease

Primary outcomes:
measure: The prevalence of pre-eclampsia (PE)
timeFrame: From 20 weeks of gestation to delivery
measure: The prevalence of fetal growth retardation (FGR)
timeFrame: From 20 weeks of gestation to delivery
measure: The prevalence of gestational diabetes (GDM)
timeFrame: From 20 weeks of gestation to delivery
Secondary outcomes:
measure: Changes in the placental expression of genes- and proteins related to vitamin D, evaluated using Next Generation Sequencing (NGS), quantitative Polymerase Chain Reaction (qPCR), methylation (Bisulfite conversion) and western blotting.
timeFrame: At delivery
measure: Changes in the placental expression of genes- and proteins related to vitamin D and the pathogenesis of PE, FGR and GDM in placental tissue from complicated pregnancies compared to uncomplicated pregnancies, evaluated using NGS, qPCR and western blotting
timeFrame: At delivery
measure: Birthweight
timeFrame: At delivery
measure: Size related to gestational age
timeFrame: At delivery
measure: The prevalence of preterm birth
timeFrame: At delivery
measure: The prevalence of postterm birth
timeFrame: At delivery
measure: The prevalence of gestational hypertension
timeFrame: From 20 weeks of gestation to delivery
measure: Mode of delivery
timeFrame: At delivery
measure: The prevalence of infection during delivery
timeFrame: At delivery
measure: Admission to the neonatal ward
timeFrame: The first two weeks after birth
measure: Prevalence of post partum hemorrhage > 500 ml
timeFrame: The first 24 hours after delivery
Other outcomes:
Locations:
city: Aarhus
country: Denmark
facility: Department of Biomedicine, University of Aarhus
city: Randers
country: Denmark
facility: Randers Regional Hospital
Study officials:
References: