Pregnancy Complications, Vitamin D3 Deficiency, Vitamin D Deficiency
Conditions
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.
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.
Interventions
DIETARY_SUPPLEMENTVitamin 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.
DIETARY_SUPPLEMENTVitamin 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.
OTHERUsual 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.
Sponsors
Göteborg University
Vastra Gotaland Region
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
No
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 µg/day * difficulties understanding the study information
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 24,25-Dihydroxyvitamin D | From inclusion in first trimester to follow-up in third trimester, up to 9 months | Analyses of 24,25(OH)2D (24,25(OH)2D3 and 24,25(OH)2D2) |
| 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 |
| Incidence of pre-eclampsia | Up to delivery | Diagnosis of pre-eclampsia |
| 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 |
Countries
Sweden
Contacts
PRINCIPAL_INVESTIGATORHanna Augustin, Ass Prof
Göteborg University
Outcome results
None listed