Next-generation Effects of Vitamin D Supplementation in Pregnancy

Study Overview
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Brief Summary
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Vitamin D deficiency is common among pregnant women, despite daily vitamin D supplements. This study aims to investigate if maternal vitamin D intake of 90 vs 10 µg affects the overall health, growth, and immune system of the offspring at birth and after 1 year. Blood samples at birth and after one year, questionnaires and clinical 1-year examination will be performed on the children.

Detailed Description
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Vitamin D deficiency is common among Danish pregnant women, although most pregnant women adhere to guidelines of a daily supplement of 10 µg vitamin D. Vitamin D deficiency increases the risk of complications in the pregnancy e.g., preeclampsia, gestational diabetes mellitus and fetal growth retardation. Several studies indicate that the offspring has an increased risk of immune diseases e.g., asthma and autoimmune related diseases e.g., multiple sclerosis if the mother had vitamin D deficiency during the pregnancy. It is well known that vitamin D affects the immune system, which raises the question of the effects of vitamin D supplements and which doses to give optimally. This study aims to investigate if maternal vitamin D intake of 90 vs 10 µg D3 affects the overall health, growth, and immune system of the offspring at birth and after 1 year. Blood samples at birth and after 1 year, questionnaires and clinical 1-year examination will be performed on the children. The hypothesis is that increased vitamin D supplementation in pregnancy improves fetal development including the offspring's immune system and the developing brain. The effects of vitamin D supplementation will strengthen the offspring's overall health at birth and during their first year of life. Hopefully, this can, in the future, be part of a guideline to which dose of vitamin D is recommended for Danish pregnant women.

Official Title
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Next-generation Effects of Vitamin D Supplementation in Pregnancy

Conditions
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Growth, Vitamin D Supplementation, Immune System Diseases, Child Development

Intervention / Treatment
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* Other: Intrauterine 90µg D-vitamin
* Other: Intrauterine 10µg D-vitamin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Born by mother from our previous RCT (NCT04291313) All with parental authority have given consent for inclusion Exclusion Criteria: Mother with compliance <80% to study drug Mother has denied further contact in this follow-up study

Ages Eligible for Study
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Maximum Age: 15 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| High-dose intrauterine D3-vitamin<br>Children of mothers who received 90 µg vitamin D3 daily during pregnancy from 12 weeks to delivery. | Other: Intrauterine 90µg D-vitamin<br>* Children of mothers who received 90 µg vitamin D3 daily during pregnancy:10 µg from a standard prenatal multivitamin + an additional supplement containing 80µg of vitamin D3<br>|
| Low-dose intrauterine D3-vitamin<br>Children of mothers who received 10 µg vitamin D3 daily during pregnancy from 12 weeks to delivery | Other: Intrauterine 10µg D-vitamin<br>* Children of mothers who received 10 µg vitamin D3 daily during pregnancy, which is the dose in a standard prenatal multivitamin and the dose currently recommended by the Danish Health Authorities to all pregnant women. They will receive a prenatal vitamin containing 10µg of vitamin D + a placebo supplement.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Growth of child | The growth from birth to the clinical examination at 11-13 month of age | From birth to 11-13 month of age | 
| Immune cell function | The immune cell function at birth and at 11-13 month of age. | From birth to 11-13 month of age | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Well-being and developmental scores | ASQ-3 scores and parent-reported well-being of the children at 11-13 month of age. | At birth and at 11-13 month of age | 
| Hospital contact | Number of hospital contacts during the first year | At birth to 11-13 month of age | 
| Parent reported infections | Number of infections during the first year of life | At birth to 11-13 month of age | 
| Colic | Does the child have colic | At birth to 11-13 month of age | 
| Medicine use | Parent reported use of medicine, incl. astma-medicine and movicol. | At birth to 11-13 month of age | 
| Scanning of the anterior fontanelle | Ultrasound-scan of the anterior fontanelle | At 11-13 month of age. |