PREDIN: Pregnancy and Vitamin D Intervention Study

Sponsor

Göteborg University (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05329428

Collaborator

Vastra Gotaland Region (Other)

102

Enrollment

Location

Arms

28.3

Anticipated Duration (Months)

3.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Vitamin D deficiency is common among certain risk groups in Sweden, and occurs approximately in every tenth pregnant woman.The aim of the randomized double-blind controlled trial Pregnancy vitamin D intervention (PREDIN) is to investigate the dose of vitamin D supplementation required in achieving vitamin D sufficiency (25OHD ≥50 nmol/l) in pregnant women at risk of vitamin D deficiency. In addition, the investigators aim to examine if the overall vitamin D status and vitamin D intake have increased since the expanded vitamin D fortification program was initiated in year 2020.

Condition or Disease	Intervention/Treatment	Phase
Vitamin D Deficiency Vitamin D3 Deficiency Pregnancy Complications	Dietary Supplement: Vitamin D Supplementation 20 µg/day Dietary Supplement: Vitamin D Supplementation 40 µg/day Other: Usual Antenatal Care	N/A

Detailed Description

The effect of maternal vitamin D in pregnancy for maternal and offspring health needs to be clarified. In observational studies, the investigators and others show associations between poor maternal vitamin D status in pregnancy and an increased risk of pregnancy complications. Poor maternal vitamin D status is also linked to impaired growth in the first year of life, and potentially also to higher risk of developing obesity in childhood. Risk factors for vitamin D deficiency in Swedish pregnant women are related to lower intake of vitamin D and to less sun exposure.

Since the evidence for positive effects of maternal vitamin D status or intake is limited, vitamin D interventions in pregnancy are warranted to clarify the causal effects of vitamin D in pregnancy and the doses required to achieve sufficient vitamin D status in deficient women. In the first trimester, pregnant women will be screened at a routine visit in the antenatal care for the risk of vitamin D deficiency using a validated questionnaire. Women who are classified as having a high risk of vitamin D deficiency will be randomized to one of three study arms: usual antenatal care, 20 µg vitamin D per day or 40 µg vitamin D per day. The participants will be followed up until delivery. Blood will be collected for analysis of vitamin D status (25OHD) at screening and in the third trimester of pregnancy. Information regarding pregnancy, gestational complication and fetal growth will be retrieved from medical records after delivery. About 500 women will be screened and their vitamin D status and vitamin D intake will be compared to a previous population-based cohort study, to investigate if the status or intake of vitamin D has increased since the expanded food fortification program was introduced.

The study hypothesis is that vitamin D status and/or vitamin D intake is related to risk of developing complications during pregnancy or delivery and that maternal supplementation with vitamin D during pregnancy will be effective in achieving vitamin D sufficiency in pregnant women at risk of vitamin D deficiency. In addition, the investigators hypothesize that the expanded vitamin D food fortification program has increased the vitamin D status and vitamin D intake of pregnant women in Gothenburg since 2013-2014.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

102 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Care Provider)

Primary Purpose:

Treatment

Official Title:

PREDIN: Pregnancy and Vitamin D Intervention Study - A Randomized Controlled Trial

Anticipated Study Start Date :

Aug 22, 2022

Anticipated Primary Completion Date :

Dec 31, 2023

Anticipated Study Completion Date :

Dec 31, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Vitamin D Supplementation 20 µg/day Dietary supplements containing 20 µg of vitamin D per day will be provided to study subjects.	Dietary Supplement: Vitamin D Supplementation 20 µg/day At a routine visit at the antenatal care in early pregnancy (gestational week <15) women will be provided with with vitamin D3 (cholecalciferol) supplements. Two tablets, with a total content of 20 µg (800 IE), are taken daily throughout pregnancy.
Experimental: Vitamin D Supplementation 40 µg/day Dietary supplements containing 40 µg of vitamin D per day will be provided to study subjects.	Dietary Supplement: Vitamin D Supplementation 40 µg/day At a routine visit at the antenatal care in early pregnancy (gestational week <15) women will be provided with with vitamin D3 (cholecalciferol) supplements. Two tablets, with a total content of 40 µg (1600 IE), are taken daily throughout pregnancy.
Active Comparator: Usual Antenatal Care Women randomized to usual antenatal care will receive advise about vitamin D supplementation according to usual antenatal care routines.	Other: Usual Antenatal Care In early pregnancy (gestational week <15) women are advised by the regular midwife to take a daily supplement of Vitamin D throughout pregnancy, according to usual antenatal care routines.

Arm

Intervention/Treatment

Experimental: Vitamin D Supplementation 20 µg/day

Dietary supplements containing 20 µg of vitamin D per day will be provided to study subjects.

Dietary Supplement: Vitamin D Supplementation 20 µg/day

At a routine visit at the antenatal care in early pregnancy (gestational week <15) women will be provided with with vitamin D3 (cholecalciferol) supplements. Two tablets, with a total content of 20 µg (800 IE), are taken daily throughout pregnancy.

Experimental: Vitamin D Supplementation 40 µg/day

Dietary supplements containing 40 µg of vitamin D per day will be provided to study subjects.

Dietary Supplement: Vitamin D Supplementation 40 µg/day

At a routine visit at the antenatal care in early pregnancy (gestational week <15) women will be provided with with vitamin D3 (cholecalciferol) supplements. Two tablets, with a total content of 40 µg (1600 IE), are taken daily throughout pregnancy.

Active Comparator: Usual Antenatal Care

Women randomized to usual antenatal care will receive advise about vitamin D supplementation according to usual antenatal care routines.

Other: Usual Antenatal Care

In early pregnancy (gestational week <15) women are advised by the regular midwife to take a daily supplement of Vitamin D throughout pregnancy, according to usual antenatal care routines.

Outcome Measures

Primary Outcome Measures

Difference in maternal vitamin D status (25OHD) between intake of vitamin D supplements containing either 40 µg per day or 20 µg per day during pregnancy [From inclusion in first trimester to follow-up in third trimester, up to 9 months]
Analyses of 25OHD (25OHD3 and 25OHD2) from blood samples drawn in first- and third trimester of pregnancy
Difference in maternal vitamin D status (25OHD) between intake of vitamin D supplements (both 40 µg per day or 20 µg per day) during pregnancy and usual antenatal care routines [From inclusion in first trimester to follow-up in third trimester, up to 9 months]
Analyses of 25OHD (25OHD3 and 25OHD2) from blood samples drawn in first- and third trimester of pregnancy
Difference in maternal 3-epi-25-Hydroxyvitamin D between the three groups; intakes of vitamin D supplements 40 µg/day or 20 µg/day or usual antenatal care routines [From inclusion in first trimester to follow-up in third trimester, up to 9 months]
Analyses of vitamin D metabolites 3-epi-25-Hydroxyvitamin D3 from blood samples drawn in first- and third trimester of pregnancy
Difference in maternal 1,25-dihydroxyvitamin D between the three groups; intakes of vitamin D supplements 40 µg/day or 20 µg/day or usual antenatal care routines [From inclusion in first trimester to follow-up in third trimester, up to 9 months]
Analyses of 1,25-dihydroxyvitamin D from blood samples drawn in first- and third trimester of pregnancy
Difference in maternal vitamin D binding proteins between the three groups; intakes of vitamin D supplements 40 µg/day or 20 µg/day or usual antenatal care routines [From inclusion in first trimester to follow-up in third trimester, up to 9 months]
Analyses of vitamin D binding proteins from blood samples drawn in first- and third trimester of pregnancy

Secondary Outcome Measures

Gene variant related to vitamin D metabolism [At inclusion in first trimester of pregnancy]
Analyses of gene variants in blood sample drawn at inclusion in first trimester of pregnancy
Ferritin [From inclusion in first trimester to follow-up in third trimester, up to 9 months]
Analyses of ferritin
Hemoglobin [From inclusion in first trimester to follow-up in third trimester, up to 9 months]
Analyses of hemoglobin
Metabolomics [From inclusion in first trimester to follow-up in third trimester, up to 9 months]
Analyses of metabolomics in blood
C-reactive protein [From inclusion in first trimester to follow-up in third trimester, up to 9 months]
Analyses of inflammation e.g. c-reactive protein
Interleukines [From inclusion in first trimester to follow-up in third trimester, up to 9 months]
Analyses of inflammation e.g. interleukines
Cytokines [From inclusion in first trimester to follow-up in third trimester, up to 9 months]
Analyses of inflammation e.g. cytokines
Cortisol [From inclusion in first trimester to follow-up in third trimester, up to 9 months]
Analyses of cortisol
Parathyroid hormone [From inclusion in first trimester to follow-up in third trimester, up to 9 months]
Analysis of parathyroid hormone in sampled blood at the routine laboratory
Estrogen [From inclusion in first trimester to follow-up in third trimester, up to 9 months]
Analyses of estrogen, in sampled blood, at the routine laboratory
Progesterone [From inclusion in first trimester to follow-up in third trimester, up to 9 months]
Analyses of progesterone, in sampled blood, at the routine laboratory
Dietary intake [At inclusion in first trimester and at follow-up in third trimester, up to 9 months]
Dietary intake of mother during pregnancy assessed by dietary record at two time points
Body weight development [From inclusion in first trimester to follow-up in third trimester, up to 9 months]
Self-reported weight (in kilograms) during pregnancy until delivery.
Incidence of pregnancy-induced hypertension [Up to delivery]
Diagnosis of pregnancy-induced hypertension, and gestational diabetes
Incidence of pre-eclampsia [Up to delivery]
Diagnosis of pre-eclampsia and gestational diabetes
Incidence of gestational diabetes [Up to delivery (up to 9 months)]
Diagnosis of gestational diabetes
Incidence of preterm delivery [Up to 37 completed weeks]
Delivery before 37 weeks completed weeks of gestation
Incidence of small for gestational age (SGA) [At delivery]
SGA born infant
Incidence of large for gestational age (LGA) [At delivery]
LGA born infant
Incidence of Intrauterine growth restriction (IUGR) [At delivery]
IUGR
Apgar scores [At 1, 5 and 10 minutes after delivery]
Vitality signs are estimated as Apgar scores at 1, 5 and 10 minutes after birth of the newborn. Apgar stands for Appearance, pulse, grimace, activity and respiration. The maximium score at each time point is 10 scores and a high score indicates high vitality, where as a low score indicates very low vitality.
Incidence of Caesarean sections [At delivery]
Delivery by caesarean sections
Incidence of miscarriage [During the first 21+6 weeks of pregnancy]
Miscarriage
Incidence of Intrauterine fetal demise (IUFD) [Any time during pregnancy after pregnancy week 22+0 (up to 9 months)]
IUFD

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 45 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

pregnant women in gestational week <15

Exclusion Criteria:

multi-fetal pregnancy
known disorder to the metabolism of vitamin D, calcium or phosphate (e.g. adrenal gland disorders, kidney disease)
ongoing treatment with vitamin D of ≥10/day
difficulties understanding the study information