Vol.:(0123456789) 1 3 World Journal of Pediatrics https://doi.org/10.1007/s12519-019-00258-y ORIGINAL ARTICLE Cardiovascular dysfunction and vitamin D status in childhood acute lymphoblastic leukemia survivors Paola Muggeo 1  · Vito Michele Rosario Muggeo 2  · Paola Giordano 3  · Maurizio Delvecchio 4  · Maria Altomare 3  · Chiara Novielli 1  · Marco Matteo Ciccone 5  · Gabriele D’Amato 6  · Maria Felicia Faienza 3  · Nicola Santoro 1 Received: 21 November 2018 / Accepted: 12 April 2019 © Children’s Hospital, Zhejiang University School of Medicine 2019 Abstract Background Vitamin D (25-OHD) has a role in bone health after treatment for cancer. 25-OHD defciency has been associ- ated with risk factors for cardiovascular disease, but no data focusing on this topic in childhood cancer survivors have been published. We investigated the 25-OHD status in children treated for acute lymphoblastic leukemia (ALL), and evaluated its infuence on vascular function. Methods 25-OHD levels were evaluated in 52 ALL survivors and 40 matched healthy controls. Patients were grouped according to 25-OHD level (< 20 ng/m or ≥ 20 ng/ml). Auxological parameters, biochemical and hemostatic markers of endothelial function (AD, HMW-AD, ET-1, vWFAg, TAT, D-dimers, Fbg, and hs-CRP), ultrasound markers of vascular endothelial function (fow-mediated dilatation, FMD, common carotid intima-media thickness, C-IMT, and antero-posterior diameter of infra-renal abdominal aorta, APAO) were evaluated in the patients. Results Cases showed higher prevalence of 25-OHD defciency than controls (p = 0.002). In univariate analysis via mean comparisons, 25-OHD defcient (< 20 ng/ml) patients showed higher C-IMT values compared to the 25-OHD non-defcient (≥ 20 ng/ml) group (P = 0.023). Signifcant diferences were also found for ET-1 (P = 0.035) and AD-HMW (P = 0.015). In the multiple regression models controlling for some confounders, 25-OHD still was associated with C-IMT (P = 0.0163), ET-1 (P = 0.0077), and AD-HMW (P = 0.0008). Conclusions Childhood ALL survivors show higher prevalence of 25-OHD defciency as compared to controls. The 25-OHD levels appear to be linked to indicators of endothelial and vascular dysfunction. Careful monitoring of 25-OHD balance may help to prevent cardiovascular diseases in childhood ALL survivors, characterized by high cardiovascular risk. Keywords Acute lymphoblastic leukemia · Cardiovascular disease · C-IMT · Vascular ultrasound studies · Vitamin D Introduction Vitamin D is traditionally known for its role in bone metabo- lism, and has been widely investigated in cancer survivors [1–4]. Childhood cancer survivors have a higher risk of vita- min D defciency mainly due to their increased sedentary activities, more time spent indoors, poor diet and exposure to chemotherapy. Moreover, they are prone to dysbiosis due to extensive use of antibiotics during chemotherapy. Vitamin D is important to maintain gut microbiota in a state of eubio- sis [5], and to prevent metabolic syndrome and subsequent cardiovascular disease [6]. Recently, vitamin D defciency has been associated with various risk factors for cardiovascular disease, including obesity, hypertension, dyslipidaemia, insulin resistance, and metabolic syndrome [7–11]. Furthermore, vitamin D exerts * Paola Muggeo paola.muggeo@tiscali.it 1 Department of Pediatric Oncology and Hematology, University Hospital of Policlinico, Piazza G. Cesare 11, 70124 Bari, Italy 2 Department of Economical, Business and Statistical Sciences, University of Palermo, Palermo, Italy 3 Department of Biomedicine and Human Oncology, Pediatric Section, University “A. Moro”, Bari, Italy 4 Pediatric and Neonatology Unit, Mother and Children Health Care Department, “Madonna delle Grazie” Hospital, ASL Matera, Matera, Italy 5 Cardiovascular Diseases Section, Department of Emergency and Organ Transplantation, University “A. Moro”, Bari, Italy 6 Neonatal Intensive Care Unit, Di Venere Hospital, Bari, Italy