PREDIN: Pregnancy and Vitamin D Intervention Study (PREDIN)

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.

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.

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

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.

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.

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.

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

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

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

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

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

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.

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