PREDIN: Pregnancy and Vitamin D Intervention Study (PREDIN)

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Vitamin D Deficiency; Pregnancy Complications; Vitamin D3 Deficiency
• Intervention / Treatment: Dietary supplement: Vitamin D Supplementation 20 µg/day; Dietary supplement: Vitamin D Supplementation 40 µg/day; Other: Usual Antenatal Care

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 Type: Interventional
• Enrollment (Estimated): 102
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Sweden
  • Gothenburg, Sweden
    • Antenatal Care

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 43 years (Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Analyses of 25OHD (25OHD3 and 25OHD2) from blood samples drawn in first- and third trimester of pregnancy	From inclusion in first trimester to follow-up in third trimester, up to 9 months
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	Analyses of 25OHD (25OHD3 and 25OHD2) from blood samples drawn in first- and third trimester of pregnancy	From inclusion in first trimester to follow-up in third trimester, up to 9 months
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	Analyses of vitamin D metabolites 3-epi-25-Hydroxyvitamin D3 from blood samples drawn in first- and third trimester of pregnancy	From inclusion in first trimester to follow-up in third trimester, up to 9 months
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	Analyses of 1,25-dihydroxyvitamin D from blood samples drawn in first- and third trimester of pregnancy	From inclusion in first trimester to follow-up in third trimester, up to 9 months
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	Analyses of vitamin D binding proteins from blood samples drawn in first- and third trimester of pregnancy	From inclusion in first trimester to follow-up in third trimester, up to 9 months

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Göteborg University
• Collaborators: Vastra Gotaland Region
• Investigators: Principal Investigator: Hanna Augustin, Ass Prof, Göteborg University

Study record dates

Study Major Dates

• Study Start (Actual): April 14, 2022
• Primary Completion (Estimated): July 31, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: December 9, 2021
• First Submitted That Met QC Criteria: April 7, 2022
• First Posted (Actual): April 15, 2022

Study Record Updates

• Last Update Posted (Actual): March 15, 2024
• Last Update Submitted That Met QC Criteria: March 13, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nutrition Disorders; Avitaminosis; Deficiency Diseases; Malnutrition; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Vitamin D Deficiency; Pregnancy Complications; Physiological Effects of Drugs; Micronutrients; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol; Vitamins; Ergocalciferols
• Other Study ID Numbers: 2021-03871

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No