“Effect of Vitamin D replacement on maternal and neonatal outcomes: a randomized controlled trial in pregnant women with hypovitaminosis D”
About The Trial
Prescribing vitamin D, an over-the-counter and affordable supplement, has recently gained interest among obstetricians, due to the results from observational studies showing an association between low vitamin D levels and increased maternal and neonatal morbidity. Several scientific societies have issued guidelines on vitamin D replacement during pregnancy, but they recommended variable doses, ranging from none (World Health Organization Guidelines 2012
), to as little as 400 IU/day (NICE Guidelines 2008
) and as much as 2,000 IU/day (Endocrine Society Guidelines, Holick 2011
). The Institute Of Medicine (IOM) recommended 600 IU/day, with an upper limit of safe intake of 4,000 IU/day (IOM 2011). These guidelines targeted Western populations, characterized by more replete vitamin D levels, compared to non-Western countries. A recent Cochrane systematic review on vitamin D supplementation during pregnancy stated that there is no enough data on clinically important outcomes to allow definite conclusions. Noteworthy, most randomized controlled trials (RCTs) on vitamin D replacement in pregnancy are conducted in populations of Western origin, and thus their results cannot be generalized worldwide. To-date, only a single randomized vitamin D trial, by Dawodu et al, assessed the impact of vitamin D supplementation in pregnant mothers in the Middle East (United Arab Emirates). It was limited to measuring circulating maternal and neonatal vitamin D levels, and did not assess other outcomes. Therefore, the efficacy of vitamin D supplementation on pregnancy related outcomes needs to be demonstrated in high quality RCTs, targeting specifically vitamin D deficient/insufficient populations in regions such as the Middle East, where the needs may be higher.
Nowadays, interest in the impact of the “early environment” on the development of adulthood diseases is increasing, and evidence on the importance of intra-uterine and postnatal skeletal development on predicting fracture and osteoporosis risk later in life is accumulating.
Our study aims at defining the optimal vitamin D dose during pregnancy, dose that would translate into important maternal and neonatal outcomes. Given the scarcity of data from our region, this study will fill a large knowledge gap on the topic. Indeed, if vitamin D supplementation, started early during pregnancy, proves to be unequivocally beneficial in our populations, this will have a major impact on public health policy and practice guidelines in our country and region. Conversely, if study results are negative, our trial would put the lingering debate and controversy on this topic, in high risk populations such as ours, to final rest.
This is a randomized controlled trial that will be conducted over 3 years.
330 pregnant women from Lebanon and the Middle East region, with vitamin D deficiency/insufficiency will be randomized, early in their second trimester, to receive daily equivalent doses of cholecalciferol, 600 IU or 3,000 IU until delivery. Maternal 25(OH)D, chemistries, and fetal ultrasound will be assessed at study entry, during third trimester and at delivery. Neonatal anthropometric variables and venous umbilical cord 25(OH)D level will be measured at birth, and infants will also undergo DXA assessment, for bone and fat mass, at one month of age.
We will assess the effect of vitamin D supplementation on:
- Maternal 25-hydroxyviamin D [25(OH)D] level and the proportion of women who reach a 25(OH)D level ≥ 20 ng/ml.
- Neonatal 25(OH)D level
- Neonatal knee-heel length at birth
- Infant bone mineral content
- Infant fat mass
- Fetal and newborn anthropometrics
- Placental weight and other characteristics
- Maternal urine calcium
Trial Visits / Flow Chart
Trial Progress (monthly update on recruitment)
|Total expected number of participants|| Total number of participants enrolled*||Total number of participants Completed the Study |
|330|| 330 (Oct. 2018) ||309 (Oct. 2018)|
*Enrollment started in July 2015
Enrollment end date: June 5, 2018
Study Questions and Answers