ORIGINAL ARTICLE Maternal/neonatal vitamin D deficiency: a new risk factor for necrotizing enterocolitis in preterm infants? M Cetinkaya 1 , T Erener-Ercan 2 , T Kalayci-Oral 1 , A Babayiğit 1 , B Cebeci 1 , SY Semerci 1 and G Buyukkale 1 OBJECTIVE: The objective of the study was to investigate the possible association between maternal/neonatal 25-hydroxy vitamin D (25-OHD) levels and development of necrotizing enterocolitis (NEC). STUDY DESIGN: One hundred and forty-five preterm infants ⩽ 36 weeks of gestation were enrolled. 25-OHD levels were determined in maternal/neonatal blood samples that were obtained at the time of admission to the neonatal intensive care unit. RESULTS: Of the 145 enrolled patients, 26 (18%) developed NEC. Maternal/neonatal 25-OHD levels in the NEC group were significantly lower than those of the no-NEC group (P = 0.001 and 0.004, respectively). In univariate logistic regression analysis, both maternal/neonatal vitamin D levels were a significant predictor of NEC (odds ratio (OR): 0.92 and 0.89; P o0.001 and P o0.005, respectively). However, multivariate logistic regression analysis revealed that only maternal vitamin D level was a significant predictor of NEC ( OR: 0.86, P o0.0009). CONCLUSION: This is the first study to propose a possible association between maternal/neonatal 25-OHD levels and subsequent development of NEC in preterm infants. Journal of Perinatology advance online publication, 23 March 2017; doi:10.1038/jp.2017.18 INTRODUCTION Necrotizing enterocolitis (NEC) is primarily a disease of preterms, affecting ~ 10% of very-low-birth weight infants. 1,2 It is a major cause of morbidity and mortality among the preterm population with mortality rates ranging from 20 to 40%. 3,4 Despite advances in the care of preterm infants, NEC continues to impose a heavy burden on the neonatal population without a significant decline in overall morbidity and mortality rates. 5,6 The pathogenesis of NEC is complex and multifactorial with the primary end point of an inappropriate and exaggerated inflam- matory response to some type of insult. 2 It is now thought that the interaction among milk substrate, microbes and the immature host immunologic system is the key in initiating the pathogenesis of NEC leading to a hemorrhagic-ischemic necrosis as the terminal manifestation. 7,8 Therefore, it is currently hypothesized that NEC is created by bacterial invasion, immune activation, uncontrolled inflammation with production of reactive oxygen species (ROS) and nitrogen species, vasoconstriction followed by ischemia- reperfusion injury, gut barrier failure, intestinal necrosis, sepsis and shock. It has been postulated that transcription factors specifically nuclear factor κB (NFκB), proinflammatory mediators, chemokines (CXCL2), cytokines (tumor necrosis factor, interleukin (IL)), prostanoids, platelet-activating factor, nitric oxide, increased expression of toll-like receptor 4 (TLR-4) and decreased expression of TLR-9 participate in this vicious cycle of uncontrolled inflammation. 9 Recent studies show that vitamin D is a key modulator of immune function and inflammation with broad regulatory effects on cells of the adaptive and innate immune system. 10–12 Vitamin D exerts its biological effects through vitamin D receptor (VDR), which is expressed in various organs and tissues of the human body other than bone cells such as the kidney, the colonic mucosa and immune cells. 13,14 All cells of the immune system have been shown to express the VDR. 14 In the intestine, VDR has been suggested to play a role in regulating cell proliferation, differentiation and the induction of apoptosis. 13 Several studies have examined the role of vitamin D in immune-mediated diseases like inflammatory bowel disease (IBD). 15–17 Vitamin D deficiency was reported to be present in 60% of IBD patients. 18,19 Some of the probable effects of vitamin D deficiency on the gastrointestinal tract were postulated to be decreased colonic bacterial clearance, reduced expression of tight junctions (TJs) in the intestinal epithelium and elevated Th1-mediated inflammation at the gut level. 19–22 We have previously shown the possible association between maternal/neonatal vitamin D deficiency and neonatal sepsis in term infants. 23 We also found that maternal/neonatal vitamin D deficiency might be a risk factor for bronchopulmonary dysplasia in preterm infants. 24 However, to our knowledge, there is no prospective study that investigated the possible association between maternal/neonatal vitamin D levels and NEC develop- ment in premature infants. The aim of our study was to investigate whether there was an association between maternal/neonatal 25-hydroxy vitamin D (25-OHD) levels and NEC development in preterm infants. METHODS A total of 145 premature infants (⩽36 weeks' gestational age) who were admitted to the neonatal intensive care unit of Kanuni Sultan Suleyman Training and Research Hospital between March 2012 and December 2013, were enrolled in this prospective study. The exclusion criteria were refusal of parental consent, major congenital malformation and chromosomal anomalies. The infants with stage I NEC and/or infants who had diagnosis of spontaneous intestinal perforation were also excluded. The study 1 Department of Neonatology, Kanuni Sultan Suleyman Teaching and Research Hospital, Istanbul, Turkey and 2 Faculty of Medicine, Department of Neonatology, Maltepe University, Istanbul, Turkey. Correspondence: Dr M Çetinkaya, Department of Neonatology, Kanuni Sultan Suleyman Teaching and Research Hospital, Turgut Özal Bulvarı No:1, Halkalı/Küçükçekmece/İSTANBUL, Istanbul 34700, Turkey, E-mail: drmerih@yahoo.com Received 13 October 2016; revised 20 December 2016; accepted 12 January 2017 Journal of Perinatology (2017) 00, 1 – 6 © 2017 Nature America, Inc., part of Springer Nature. All rights reserved 0743-8346/17 www.nature.com/jp