Vitamin D and risk of preterm birth: Up‐to‐date meta‐analysis of randomized controlled trials and observational studies

Abstract

Aim: We performed a meta-analysis of randomized controlled trials (RCT) and observational studies to answer the two following questions: (i) whether low maternal circulating 25 hydroxyvitamin D (25-OHD) is associated with an increased risk of preterm birth (PTB) or spontaneous PTB (sPTB); and (ii) whether vitamin D supplementation alone during pregnancy can reduce the risk of PTB. Methods: Literature search was carried out using Pubmed, Web of Science and Embase databases up to June 2016. Pooled OR or relative risk (RR) with 95%CI were computed using fixed or random effects models depending on the size of heterogeneity. Subgroup analysis was used to explore potential sources of between-study heterogeneity. Publication bias was evaluated using Egger's test and Begg's test. Results: Twenty-four articles (six RCT and 18 observational studies) were identified. Maternal circulating 25-OHD deficiency (pooled OR, 1.25; 95%CI: 1.13-1.38) rather than insufficiency (pooled OR, 1.09; 95%CI: 0.89-1.35) was associated with an increased risk of PTB, and vitamin D supplementation alone during pregnancy could reduce the risk of PTB (pooled RR, 0.57; 95%CI: 0.36-0.91). This was also the case for the sPTB subgroup (circulating 25-OHD <50 vs >50 nmol/L; pooled OR, 1.45; 95%CI: 1.20-1.75). Conclusions: Maternal circulating 25-OHD deficiency could increase PTB risk and vitamin D supplementation alone during pregnancy could reduce PTB risk. Extrapolation of the results, however, must be done with caution, and there is urgent need for larger, better-designed RCT to confirm this effect.

Maternal 25(OH)D concentrations ≥40 ng/mL associated with 60% lower preterm birth risk among general obstetrical patients at an urban medical center

“…These findings support the inverse association between maternal 25(OH)D and PTB risk found in the Hollis and Wagner et al randomized clinical trials [12,14,15] as well as epidemiological studies [4–10]. Wagner et al found a 59% lower risk of PTB for women with serum 25(OH)D concentrations ≥40 ng/mL compared to those with concentrations ≤20 ng/mL (p = 0.02) [12].…”

“…A 70% lower risk of PTB was found for women ≥20 ng/mL vs. <20 ng/mL in a study by Perez-Ferre et al (p = 0.002) [5]. Two recent meta-analyses also found that higher 25(OH)D concentrations significantly decreased the risk of PTB [9,10]. Post-hoc analysis of the Hollis and Wagner et al trials [12] and the Bodnar et al study [4] assessed the non-linear relationship between 25(OH)D and PTB, both identifying a decreasing risk of PTB as 25(OH)D increased to approximately 40 ng/mL.…”

“…Multiple epidemiologic studies have found an association between higher maternal serum 25-hydroxyvitamin D [25(OH)D] concentration, the physiological measure of vitamin D status, and lower PTB risk [4–10]. Serum 25(OH)D concentration captures the effect of multiple vitamin D input sources (supplement, sun, and food) and makes provision for inter-individual variability in dose response [11].…”

Non-classical effects of vitamin D

“…Данные мета-анализов указывают на связь низких уровней 25(ОН)D во время беременности с повышен-ным риском преждевременных родов, который сни-жается при приеме препаратов витамина D [73], ге-стационного сахарного диабета [74], бактериального вагиноза, а также с низкой массой плода для данного гестационного возраста и более низкой массой ребен-ка при рождении [75,76]. При обследовании 800 бере-менных женщин, проживающих в г. Санкт-Петербург и Ленинградской области, недостаточность и дефицит витамина D встречался у 100% женщин с бесплодием, у пациенток с невынашиванием беременности дефи-цит и недостаточность витамина D наблюдался в 6 раз чаще, у беременных с преэклампсией в 5 раз чаще на-блюдался низкий уровень витамина D; при физиологи-ческой протекающей беременности недостаточность витамина D выявлена лишь у 18,5% женщин, дефицит витамина D выявлен не был [77].Результаты опубли-кованного недавно первого РКИ, в котором исследо-валось влияние приема витамина D во время бере-менности на массу костной ткани ребенка (MAVIDOS) показали, что при приеме 1000 МЕ колекальциферола во время беременности в целом не наблюдалось уве-личение массы костной ткани в сравнении с плацебо, но у родившихся в зимнее время детей было отмечено увеличение МПК почти на 10%; была также показана эффективность и безопасность приема 1000 МЕ коле-кальциферола для восполнения дефицита витамина D у беременных женщин [78].…”

Altered cord serum 25‐hydroxyvitamin D signaling and placental inflammation is associated with pre‐term birth

“…[9][10][11][12] The relationship of vitamin D and inflammation resembles hen and egg conundrum, whether inflammation reduces vitamin D concentration or vitamin D dampens inflammation still remains a puzzle. [21][22][23] Therefore, aforementioned observations instigated us to study if any alterations in vitamin D-mediated signals originating from fetal side modulate the maternal immune system in triggering the premature activation of labor as the information till date is fragmented and inconclusive, thus bestowing a major gap between two pathways. [13][14][15][16][17] In cancer and other immunological disorders, vitamin D has been extensively known to inhibit the expression and function of central transcription factor NF-κB.…”