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PREDIN: Pregnancy and Vitamin D Intervention Study

Not Applicable
Active, not recruiting
Conditions
Pregnancy Complications
Vitamin D Deficiency
Vitamin D3 Deficiency
Interventions
Dietary Supplement: Vitamin D Supplementation 40 µg/day
Other: Usual Antenatal Care
Dietary Supplement: Vitamin D Supplementation 20 µg/day
Registration Number
NCT05329428
Lead Sponsor
Göteborg University
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.

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
Female
Target Recruitment
102
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Vitamin D Supplementation 40 µg/dayVitamin D Supplementation 40 µg/dayDietary supplements containing 40 µg of vitamin D per day will be provided to study subjects.
Usual Antenatal CareUsual Antenatal CareWomen randomized to usual antenatal care will receive advise about vitamin D supplementation according to usual antenatal care routines.
Vitamin D Supplementation 20 µg/dayVitamin D Supplementation 20 µg/dayDietary supplements containing 20 µg of vitamin D per day will be provided to study subjects.
Primary Outcome Measures
NameTimeMethod
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 routinesFrom 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

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 routinesFrom 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 routinesFrom 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 status (25OHD) between intake of vitamin D supplements (both 40 µg per day or 20 µg per day) during pregnancy and usual antenatal care routinesFrom 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 containing either 40 µg per day or 20 µg per day during pregnancyFrom 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

Secondary Outcome Measures
NameTimeMethod
Incidence of gestational diabetesUp to delivery (up to 9 months)

Diagnosis of gestational diabetes

C-reactive proteinFrom inclusion in first trimester to follow-up in third trimester, up to 9 months

Analyses of inflammation e.g. c-reactive protein

Incidence of small for gestational age (SGA)At delivery

SGA born infant

FerritinFrom inclusion in first trimester to follow-up in third trimester, up to 9 months

Analyses of ferritin

CytokinesFrom inclusion in first trimester to follow-up in third trimester, up to 9 months

Analyses of inflammation e.g. cytokines

Incidence of pre-eclampsiaUp to delivery

Diagnosis of pre-eclampsia

HemoglobinFrom inclusion in first trimester to follow-up in third trimester, up to 9 months

Analyses of hemoglobin

MetabolomicsFrom inclusion in first trimester to follow-up in third trimester, up to 9 months

Analyses of metabolomics in blood

Parathyroid hormoneFrom 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

Incidence of pregnancy-induced hypertensionUp to delivery

Diagnosis of pregnancy-induced hypertension

Apgar scoresAt 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.

Gene variant related to vitamin D metabolismAt inclusion in first trimester of pregnancy

Analyses of gene variants in blood sample drawn at inclusion in first trimester of pregnancy

Dietary intakeAt 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

Incidence of preterm deliveryUp to 37 completed weeks

Delivery before 37 weeks completed weeks of gestation

Incidence of large for gestational age (LGA)At delivery

LGA born infant

Incidence of Intrauterine fetal demise (IUFD)Any time during pregnancy after pregnancy week 22+0 (up to 9 months)

IUFD

InterleukinesFrom inclusion in first trimester to follow-up in third trimester, up to 9 months

Analyses of inflammation e.g. interleukines

Incidence of Intrauterine growth restriction (IUGR)At delivery

IUGR

Incidence of Caesarean sectionsAt delivery

Delivery by caesarean sections

CortisolFrom inclusion in first trimester to follow-up in third trimester, up to 9 months

Analyses of cortisol

EstrogenFrom inclusion in first trimester to follow-up in third trimester, up to 9 months

Analyses of estrogen, in sampled blood, at the routine laboratory

ProgesteroneFrom inclusion in first trimester to follow-up in third trimester, up to 9 months

Analyses of progesterone, in sampled blood, at the routine laboratory

Body weight developmentFrom 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 miscarriageDuring the first 21+6 weeks of pregnancy

Miscarriage

Trial Locations

Locations (1)

Antenatal Care

🇸🇪

Gothenburg, Sweden

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